Acido solfidrico nella letteratura internazionale ottobre 2013 · Da Xue Xue Bao Yi Xue Ban 2013...

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Acido solfidrico nella letteratura internazionale ottobre 2013 (1) Zhang CZ, Zhang WJ, Xu J. Isolation and identification of methanethiol-utilizing bacterium CZ05 and its application in bio-trickling filter of biogas. Bioresour Technol 2013 Oct 14;150C:338-43. Abstract: A bacterium capable of methanethiol (MT) degradation was enriched and isolated by employing activated sewage sludge as the inoculum in a mineral medium containing MT. The isolate was identified as Paenibacillus polymyxa CZ05 through a Biolog test and 16S rDNA sequencing. This strain can utilize both organic and inorganic media and thrives at pH 4 to 9. The batch culture showed that the strain can degrade MT better in the No. 4 medium than in the No. 1 medium. A series-operating biotrickling filter with lava stone as the carrier was employed to test the application of P. polymyxa CZ05 in the removal of MT in simulated biogas. Long-term experiments showed that a high concentration of MT (60ppm) was efficiently removed (99.5%) by the biotrickling filters at EBRT 30s. The addition of hydrogen sulfide decreased the MT removal rate because the dissolved oxygen competed with MT (2) McKee RH, Nicolich M, Roy T, White R, Daughtrey WC. Use of a Statistical Model to Predict the Potential for Repeated Dose and Developmental Toxicity of Dermally Administered Crude Oil and Relation to Reproductive Toxicity. Int J Toxicol 2013 Oct 31. Abstract: Petroleum (commonly called crude oil) is a complex substance primarily composed of hydrocarbon constituents. Based on the results of previous toxicological studies as well as occupational experience, the principal acute toxicological hazards are those associated with exposure by inhalation to volatile hydrocarbon constituents and hydrogen sulfide, and chronic hazards are associated with inhalation exposure to benzene and dermal exposure to polycyclic aromatic compounds. The current assessment was an attempt to characterize the potential for repeated dose and/or developmental effects of crude oils following dermal exposures and to generalize the conclusions across a broad range of crude oils from different sources. Statistical models were used to predict the potential for repeated dose and developmental toxicity from compositional information. The model predictions indicated that the empirical data from previously tested crude oils approximated a "worst case" situation, and that the data from previously tested crude oils could be used as a reasonable basis for characterizing the repeated dose and developmental toxicological hazards of crude oils in general (3) Stipanicev M, Turcu F, Esnault L, Rosas O, Basseguy R, Sztyler M, et al. Corrosion of carbon steel by bacteria from North Sea offshore seawater injection systems: Laboratory investigation. Bioelectrochemistry 2013 Oct 9. Abstract: Influence of sulfidogenic bacteria, from a North Sea seawater injection system, on the corrosion of S235JR carbon steel was studied in a flow bioreactor; operating anaerobically for 100days with either inoculated or filtrated seawater. Deposits formed on steel placed in reactors contained magnesium and calcium minerals plus iron sulfide. The dominant biofilm-forming organism was an anaerobic bacterium, genus Caminicella, known to produce hydrogen sulfide and carbon dioxide. Open Circuit Potentials (OCP) of steel in the reactors was, for nearly the entire test duration, in the range -800<E(OCP)/mV (vs. SCE)<-700. Generally, the overall corrosion rate, expressed as 1/(Rp/ ohm), was lower in the inoculated seawater though they varied significantly on both reactors. Initial and final corrosion rates were virtually identical, namely initial 1/(Rp/ ohm)=2x10-6+/-5x10-7 and final 1/(Rp/ ohm)=1.1x10-5+/-2.5x10-6. Measured data, including electrochemical noise transients and statistical parameters (0.05<Localized

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Page 1: Acido solfidrico nella letteratura internazionale ottobre 2013 · Da Xue Xue Bao Yi Xue Ban 2013 Oct;38(10):977-83. Abstract: Objective: To investigate the effect of hydrogen sulfide

Acido solfidrico nella letteratura internazionale ottobre 2013

(1) Zhang CZ, Zhang WJ, Xu J. Isolation and identification of methanethiol-utilizing

bacterium CZ05 and its application in bio-trickling filter of biogas. Bioresour Technol 2013 Oct 14;150C:338-43. Abstract: A bacterium capable of methanethiol (MT) degradation was enriched and isolated by employing activated sewage sludge as the inoculum in a mineral medium containing MT. The isolate was identified as Paenibacillus polymyxa CZ05 through a Biolog test and 16S rDNA sequencing. This strain can utilize both organic and inorganic media and thrives at pH 4 to 9. The batch culture showed that the strain can degrade MT better in the No. 4 medium than in the No. 1 medium. A series-operating biotrickling filter with lava stone as the carrier was employed to test the application of P. polymyxa CZ05 in the removal of MT in simulated biogas. Long-term experiments showed that a high concentration of MT (60ppm) was efficiently removed (99.5%) by the biotrickling filters at EBRT 30s. The addition of hydrogen sulfide decreased the MT removal rate because the dissolved oxygen competed with MT

(2) McKee RH, Nicolich M, Roy T, White R, Daughtrey WC. Use of a Statistical Model to Predict the Potential for Repeated Dose and Developmental Toxicity of Dermally Administered Crude Oil and Relation to Reproductive Toxicity. Int J Toxicol 2013 Oct 31. Abstract: Petroleum (commonly called crude oil) is a complex substance primarily composed of hydrocarbon constituents. Based on the results of previous toxicological studies as well as occupational experience, the principal acute toxicological hazards are those associated with exposure by inhalation to volatile hydrocarbon constituents and hydrogen sulfide, and chronic hazards are associated with inhalation exposure to benzene and dermal exposure to polycyclic aromatic compounds. The current assessment was an attempt to characterize the potential for repeated dose and/or developmental effects of crude oils following dermal exposures and to generalize the conclusions across a broad range of crude oils from different sources. Statistical models were used to predict the potential for repeated dose and developmental toxicity from compositional information. The model predictions indicated that the empirical data from previously tested crude oils approximated a "worst case" situation, and that the data from previously tested crude oils could be used as a reasonable basis for characterizing the repeated dose and developmental toxicological hazards of crude oils in general

(3) Stipanicev M, Turcu F, Esnault L, Rosas O, Basseguy R, Sztyler M, et al. Corrosion of carbon steel by bacteria from North Sea offshore seawater injection systems: Laboratory investigation. Bioelectrochemistry 2013 Oct 9. Abstract: Influence of sulfidogenic bacteria, from a North Sea seawater injection system, on the corrosion of S235JR carbon steel was studied in a flow bioreactor; operating anaerobically for 100days with either inoculated or filtrated seawater. Deposits formed on steel placed in reactors contained magnesium and calcium minerals plus iron sulfide. The dominant biofilm-forming organism was an anaerobic bacterium, genus Caminicella, known to produce hydrogen sulfide and carbon dioxide. Open Circuit Potentials (OCP) of steel in the reactors was, for nearly the entire test duration, in the range -800<E(OCP)/mV (vs. SCE)<-700. Generally, the overall corrosion rate, expressed as 1/(Rp/ ohm), was lower in the inoculated seawater though they varied significantly on both reactors. Initial and final corrosion rates were virtually identical, namely initial 1/(Rp/ ohm)=2x10-6+/-5x10-7 and final 1/(Rp/ ohm)=1.1x10-5+/-2.5x10-6. Measured data, including electrochemical noise transients and statistical parameters (0.05<Localized

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Index<1; -5<Skewness<-5; Kurtosis>45), suggested pitting on steel samples within the inoculated environment. However, the actual degree of corrosion could neither be directly correlated with the electrochemical data and nor with the steel corrosion in the filtrated seawater environment. Further laboratory tests are thought to clarify the noticed apparent discrepancies

(4) Xu C, Wan Y, Guo T, Chen X. [Effect of hydrogen sulfide on the expression of CSE, NF-kappaB, and IL-8 mRNA in GES-1 cells with Helicobacter pylori infection]. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2013 Oct;38(10):977-83. Abstract: Objective: To investigate the effect of hydrogen sulfide (H2S) on the expression of CSE, NF-kappaB, and IL-8 mRNA in GES-1 cells with Helicobacter pylori (H. pylori) infection and to explore its mechanism on gastric mucosa inflammation caused by H. pylori. Methods: GES-1 cells were cultured for 24 h and divided into a control group (neither H. pylori nor NaHS), an H. pylori group, a NaHS group (which was further divided into 4 groups at 50, 100, 200, or 400 mumol/L NaHS), and H. pylori + NaHS group (which was further divided into 4 groups at 50, 100, 200, or 400 mumol/L NaHS). Each group was then cultured for 3, 6, or 12 h. The expression of CSE, NF-kappaB, and IL-8 mRNA was measured by RT-PCR, and their correlation was analyzed. Results: The expression of CSE, NF-kappaB, and IL-8 mRNA in GES-1 cells in the H. pylori group was higher than that in the control group. The expression of CSE in the 200 mumol/L NaHS group and 400 mumol/L NaHS group was lower than that of the control group (P<0.05), whereas the expression of NF-kappaB and IL-8 in all NaHS groups had no statistical differences compared with the control group (P>0.05). The expression of CSE, NF-kappaB, and IL-8 mRNA in all groups of NaHS, H. pylori + 200 mumol/L NaHS group, and H. pylori + 400 mumol/L NaHS group was lower than that in the H. pylori group (P<0.05). There was positive correlation among the expressions of CSE, NF-kappaB, and IL-8 mRNA in the H. pylori group, the H. pylori + 200 mumol/L NaHS group, and the H. pylori + 400 mumol/L NaHS group (P<0.05). Conclusion: H. pylori can induce NF-kappaB and IL-8 mRNA expression and upregulate CSE mRNA expression. At 200 and 400 mumol/L, NaHS can suppress H. pylori-induced NF-kappaB and IL-8 mRNA expression and ameliorate the morphology of H. pylori-induced GES-1 injury, which may protect gastric epithelial cells by H. pylori infection

(5) Huang X, Meng XM, Liu DH, Wu YS, Guo X, Lu HL, et al. Different regulatory effects of hydrogen sulfide and nitric oxide on gastric motility in mice. Eur J Pharmacol 2013 Oct 21. Abstract: NO and H2S are gaseous signaling molecules that modulate smooth muscle motility. We aimed to identify expressions of enzymes that catalyze H2S and NO generation in mouse gastric smooth muscle, and determine relationships between endogenous H2S and NO in regulation of smooth muscle motility. Western blotting and immunocytochemistry methods were used to track expressions of neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) in gastric smooth muscles. Smooth muscle motility was recorded by isometric force transducers. cGMP production was measured by a specific radioimmunoassay. We found that CBS, CSE, eNOS, and nNOS were all expressed in mice gastric antral smooth muscle tissues, and in cultured gastric antral smooth muscle cells. AOAA significantly inhibited smooth muscle contractions in the gastric antrum, which was significantly recovered by NaHS, while PAG had no significant effect. l-NAME enhanced contractions. NaHS at low concentrations increased basal tension but decreased it at high concentrations. SNP significantly inhibited the contractions, which could be recovered by NaHS both in the absence and presence of CuSO4. ODQ did not block NaHS-induced excitatory effect, while IBMX partially blocked this effect. cGMP production in smooth muscle was significantly increased by SNP but was not affected by NaHS. All these results suggest that endogenous H2S and NO appear to play opposite roles in regulating gastric motility and their effects may be via separate signal transduction pathways. Intracellular H2S/NO levels may be maintained in a state of balance to warrant normal smooth muscle motility

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(6) Peter EA, Shen X, Shah SH, Pardue S, Glawe JD, Zhang WW, et al. Plasma free H2S levels are elevated in patients with cardiovascular disease. J Am Heart Assoc 2013 Oct;2(5):e000387. Abstract: BACKGROUND: Hydrogen sulfide (H2S) has been implicated in regulating cardiovascular pathophysiology in experimental models. However, there is a paucity of information regarding the levels of H2S in health and cardiovascular disease. In this study we examine the levels of H2S in patients with cardiovascular disease as well as bioavailability of nitric oxide and inflammatory indicators. METHODS AND RESULTS: Patients over the age of 40 undergoing coronary or peripheral angiography were enrolled in the study. Ankle brachial index (ABI) measurement, measurement of plasma-free H2S and total nitric oxide (NO), thrombospondin-1 (TSP-1), Interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1 (sICAM-1) levels were performed. Patients with either coronary artery disease alone (n = 66), peripheral arterial disease (PAD) alone (n = 13), or any vascular disease (n = 140) had higher plasma-free H2S levels compared to patients without vascular disease (n = 53). Plasma-free H2S did not distinguish between disease in different vascular beds; however, total NO levels were significantly reduced in PAD patients and the ratio of plasma free H2S to NO was significantly greater in patients with PAD. Lastly, plasma IL-6, ICAM-1, and TSP-1 levels did not correlate with H2S or NO bioavailability in either vascular disease condition. CONCLUSIONS: Findings reported in this study reveal that plasma-free H2S levels are significantly elevated in vascular disease and identify a novel inverse relationship with NO bioavailability in patients with peripheral arterial disease

(7) Baltrusaitis J, de GC, Broer R, Patterson EV. H S-Mediated Thermal and Photochemical Methane Activation. Chemphyschem 2013 Oct 22. Abstract: Sustainable, low-temperature methods for natural gas activation are critical in addressing current and foreseeable energy and hydrocarbon feedstock needs. Large portions of natural gas resources are still too expensive to process due to their high content of hydrogen sulfide gas (H2 S) mixed with methane, deemed altogether as sub-quality or "sour" gas. We propose a unique method of activation to form a mixture of sulfur-containing hydrocarbon intermediates, CH3 SH and CH3 SCH3 , and an energy carrier such as H2 . For this purpose, we investigated the H2 S-mediated methane activation to form a reactive CH3 SH species by means of direct photolysis of sub-quality natural gas. Photoexcitation of hydrogen sulfide in the CH4 +H2 S complex resulted in a barrierless relaxation by a conical intersection to form a ground-state CH3 SH+H2 complex. The resulting CH3 SH could further be coupled over acidic catalysts to form higher hydrocarbons, and the resulting H2 used as a fuel. This process is very different from conventional thermal or radical-based processes and can be driven photolytically at low temperatures, with enhanced control over the conditions currently used in industrial oxidative natural gas activation. Finally, the proposed process is CO2 neutral, as opposed to the current industrial steam methane reforming (SMR)

(8) Zhuang J, Fu L, Lai W, Tang D, Chen G. Target-stimulated metallic HgS nanostructures on a DNA-based polyion complex membrane for highly efficient impedimetric detection of dissolved hydrogen sulfide. Chem Commun (Camb ) 2013 Oct 23. Abstract: Target-stimulated metallic HgS nanostructures formed on the DNA-based polyion complex (PIC) membrane were for the first time utilized as an efficient scheme for impedimetric detection of hydrogen sulfide (H2S) by coupling insoluble precipitation with sensitivity enhancement

(9) Kijjanapanich P, Annachhatre AP, Esposito G, van Hullebusch ED, Lens PN. Biological sulfate removal from gypsum contaminated construction and demolition debris. J Environ Manage 2013 Oct 19;131C:82-91. Abstract: Construction and demolition debris (CDD) contains high levels of sulfate that can cause detrimental environmental impacts when disposed without adequate treatment. In landfills, sulfate can be converted to hydrogen sulfide under anaerobic conditions.

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CDD can thus cause health impacts or odor problems to landfill employees and surrounding residents. Reduction of the sulfate content of CDD is an option to overcome these problems. This study aimed at developing a biological sulfate removal system to reduce the sulfate content of gypsum contaminated CDD in order to decrease the amount of solid waste, to improve the quality of CDD waste for recycling purposes and to recover sulfur from CDD. The treatment leached out the gypsum contained in CDD by water in a leaching column. The sulfate loaded leachate was then treated in a biological sulfate reducing Upflow Anaerobic Sludge Blanket (UASB) reactor to convert the sulfate to sulfide. The UASB reactor was operated at 23 +/- 3 degrees C with a hydraulic retention time and upflow velocity of 15.5 h and 0.1 m h-1, respectively while ethanol was added as electron donor at a final organic loading rate of 3.46 g COD L-1 reactor d-1. The CDD leachate had a pH of 8-9 and sulfate dissolution rates of 526.4 and 609.8 mg L-1 d-1 were achieved in CDD gypsum and CDD sand, respectively. Besides, it was observed that the gypsum dissolution was the rate limiting step for the biological treatment of CDD. The sulfate removal efficiency of the system stabilized at around 85%, enabling the reuse of the UASB effluent for the leaching step, proving the versatility of the bioreactor for practical applications

(10) Kovacs E, Wirth R, Maroti G, Bagi Z, Rakhely G, Kovacs KL. Biogas production from protein-rich biomass: fed-batch anaerobic fermentation of casein and of pig blood and associated changes in microbial community composition. PLoS One 2013;8(10):e77265. Abstract: It is generally accepted as a fact in the biogas technology that protein-rich biomass substrates should be avoided due to inevitable process inhibition. Substrate compositions with a low C/N ratio are considered difficult to handle and may lead to process failure, though protein-rich industrial waste products have outstanding biogas generation potential. This common belief has been challenged by using protein-rich substrates, i.e. casein and precipitated pig blood protein in laboratory scale continuously stirred mesophilic fed-batch biogas fermenters. Both substrates proved suitable for sustained biogas production (0.447 L CH4/g protein oDM, i.e. organic total solids) in high yield without any additives, following a period of adaptation of the microbial community. The apparent key limiting factors in the anaerobic degradation of these proteinaceous materials were the accumulation of ammonia and hydrogen sulfide. Changes in time in the composition of the microbiological community were determined by next-generation sequencing-based metagenomic analyses. Characteristic rearrangements of the biogas-producing community upon protein feeding and specific differences due to the individual protein substrates were recognized. The results clearly demonstrate that sustained biogas production is readily achievable, provided the system is well-characterized, understood and controlled. Biogas yields (0.45 L CH4/g oDM) significantly exceeding those of the commonly used agricultural substrates (0.25-0.28 L CH4/g oDM) were routinely obtained. The results amply reveal that these high-energy-content waste products can be converted to biogas, a renewable energy carrier with flexible uses that can replace fossil natural gas in its applications. Process control, with appropriate acclimation of the microbial community to the unusual substrate, is necessary. Metagenomic analysis of the microbial community by next-generation sequencing allows a precise determination of the alterations in the community composition in the course of the process

(11) Ning J, Mo L, Zhao H, Lu K, Wang L, Lai X, et al. Transient Regional Hypothermia Applied to a Traumatic Limb Attenuates Distant Lung Injury Following Blast Limb Trauma. Crit Care Med 2013 Oct 18. Abstract: OBJECTIVES:: Explosive traumatic injury to an extremity may lead to both local and distant organ injury. Regional traumatic tissue hypothermia has been reported to offer systemic protection; here we investigated the protective effects of regional limb hypothermia on local tissue trauma and the lungs. Furthermore, the optimal duration of regional traumatic limb hypothermic treatment was also evaluated. DESIGN:: Prospective, controlled, animal study. SETTING:: University research laboratory. SUBJECTS:: Adult

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male Sprague-Dawley rats. INTERVENTIONS:: Anesthetized rats were randomized to sham, blast limb trauma, sham and regional hypothermia for 30 minutes, and blast limb trauma and regional hypothermia for 30 minutes, 60 minutes, and 6 hours. Blast limb trauma was created using chartaceous electricity detonators. MEASUREMENTS AND MAIN RESULTS:: Distant lung and local tissue injury following blast limb trauma were attenuated by regional traumatic limb hypothermic treatment for 30 minutes, 60 minutes, and 6 hours reflected by reduced lung histopathological changes and water content. Regional traumatic limb hypothermic treatment for 60 minutes and 6 hours failed to further attenuate distant lung and local tissue injury compared with regional traumatic limb hypothermic treatment for 30 minutes. Inhibition of cystathionine gamma-lyase/hydrogen sulfide was reduced by regional traumatic limb hypothermic treatment for 30 minutes in blast limb trauma rats. A surrogate of neutrophil accumulation, myeloperoxidase activity, and release of tumor necrosis factor-alpha and interleukin-6 were also attenuated by regional traumatic limb hypothermic treatment for 30 minutes in blast limb trauma rats. Oxidative stress was alleviated by regional traumatic limb hypothermic treatment for 30 minutes evidenced by reduction of hydrogen peroxide and malondialdehyde and an increase of superoxide dismutase and glutathione in blast limb trauma rats. CONCLUSIONS:: Our data indicate that regional traumatic limb hypothermic treatment for 30 minutes offers both local protection for traumatic tissue and systemic protection for the lungs, which is likely associated with restoration of the cystathionine gamma-lyase/hydrogen sulfide pathway and inhibition of the inflammatory response and oxidative stress

(12) Chitnis MK, Njie-Mbye YF, Opere CA, Wood ME, Whiteman M, Ohia SE. Pharmacological actions of the slow release hydrogen sulfide donor GYY4137 on phenylephrine-induced tone in isolated bovine ciliary artery. Exp Eye Res 2013 Oct 18. Abstract: Hydrogen sulfide (H2S), a colorless gas characterized by its pungent odor of rotten eggs has been reported to elicit relaxation effects on basal and pre-contracted non-ocular smooth muscles of several mammalian species. In the present study, we investigated the pharmacological actions of a H2S donor, GYY4137 on isolated bovine posterior ciliary artery after contraction with the adrenergic receptor agonist, phenylephrine. Furthermore, we studied the underlying mechanism of inhibitory action of GYY4137 on the posterior ciliary arteries. Isolated bovine posterior ciliary arteries were mounted in oxygenated organ baths and changes in isometric tension were measured with a Grass FT03 transducer connected to a recorder using a Grass Polyview Software. The relaxant actions of GYY4137 on phenylephrine pre-contracted arteries were observed in the absence and presence of an inhibitor of cyclo-oxygenase, flurbiprofen. Furthermore, the inhibitory effects of GYY4137 were studied in the absence or presence of inhibitors/activators of biosynthetic enzymes for H2S and nitric oxide production, as well as specific ion channel blockers. In the concentration range, 100 nM to 100 muM, GYY4137 elicited a concentration-dependant relaxation of phenylephrine-induced tone in isolated posterior ciliary arteries, with IC50 value of 13.4 +/- 1.9 muM (n = 6). The cyclo-oxygenase inhibitor, flurbiprofen, significantly (p < 0.01) enhanced the relaxation induced by GYY4137 yielding IC50 value of 0.13 +/- 0.08 muM (n = 6). Both the inhibitors of cystathionine beta-synthase (aminooxyacetic acid, AOAA, 30 muM) and cystathionine gamma-lyase (propargylglycine, PAG, 1 mM) caused significant (p < 0.05) rightward shifts in the concentration-response curve to GYY4137. Furthermore, the KATP channel antagonist, glibenclamide (100 muM) significantly (p < 0.01) attenuated the relaxant action induced by GYY4137 on bovine ciliary artery. Conversely, the activator of cystathionine beta-synthase, SAM (100 muM) and an inhibitor of nitric oxide synthase, l-NAME (100 muM) had no significant effect on relaxations induced by GYY4137. We conclude that the inhibitory action of GYY4137 on isolated bovine ciliary artery is dependent upon the endogenous production of both prostanoids and H2S. Furthermore, the observed vascular smooth muscle relaxation induced by GYY4137 is mediated, at least in part, by KATP channels

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(13) Castro-Piedras I, Perez-Zoghbi JF. Hydrogen sulphide inhibits Ca2+ release through InsP3 receptors and relaxes airway smooth muscle. J Physiol 2013 Oct 21. Abstract: Hydrogen sulphide (H2S) is a signaling molecule that appears to regulate diverse cell physiological process in several organs and systems including vascular and airway smooth muscle cell (SMC) contraction. Decreases in endogenous H2S synthesis have been associated with the development of cardiovascular diseases and asthma. Here we investigated the mechanism of airway SMC relaxation induced by H2S in small intrapulmonary airways using mouse lung slices and confocal and phase-contrast video microscopy. Exogenous H2S donor Na2S (100 muM) reversibly inhibited Ca2+ release and airway contraction evoked by inositol-1,4,5-trisphosphate (InsP3) uncaging in airway SMCs. Similarly, InsP3-evoked Ca2+ release and contraction was inhibited by endogenous H2S precursor L-cysteine (10 mM) but not by L-serine (10 mM) or either amino acid in the presence of DL-propargylglycine (PPG). Consistent with the inhibition of Ca2+ release through InsP3 receptors (InsP3R), Na2S reversibly inhibited acetylcholine (ACh)-induced Ca2+ oscillations in airway SMCs. In addition, Na2S, H2S donor GYY-4137, and L-cysteine caused relaxation of airways pre-contracted with either ACh or 5-hydroxytriptamine (5-HT). Na2S-induced airway relaxation was resistant to a guanylyl cyclase inhibitor (ODQ) and a protein kinase G inhibitor (Rp-8-pCPT-cGMPS). The effects of H2S on InsP3-evoked Ca2+ release and contraction as well as on the relaxation of agonist-contracted airways were mimicked by the thiol-reducing agent dithiothreitol (DTT, 10 mM) and inhibited by the oxidizing agent diamide (30 muM). These studies indicate that H2S causes airway SMC relaxation by inhibiting Ca2+ release through InsP3R and consequent reduction of agonist-induced Ca2+ oscillations in SMCs. The results suggest a novel role for endogenously produced H2S that involves the modulation of InsP3-evoked Ca2+ release -a cell-signaling system of critical importance for many physiological and pathophysiological processes

(14) Hua W, Chen Q, Gong F, Xie C, Zhou S, Gao L. Cardioprotection of HS by downregulating iNOS and upregulating HO-1 expression in mice with CVB3-induced myocarditis. Life Sci 2013 Oct 18. Abstract: AIMS: To explore the effects and potential mechanisms of hydrogen sulfide (H2S) in CVB3-induced mice with myocarditis. MAIN METHODS: A total of 75 six-week-old inbred male Balb/c mice were divided randomly into four groups (N, C, P and S). Group N was the negative control. The others were inoculated intraperitoneally (i.p.) with CVB3. Subsequently, groups P and S were injected i.p. once a day with DL-Proparglygylcine (PAG) and NaHS respectively. Group C was the positive control. Inducible nitric oxide synthase (iNOS) and heme oxygenase-1(HO-1) expression on cardiac tissues were evaluated by histopathological examination, immunohistochemistry, RT-PCR and Western blot. KEY FINDINGS: The heart-weight to body-weight (HW/BW) ratio, the histologic scores and the iNOS mRNA and protein expression levels were higher, and the HO-1 mRNA and protein expression levels were lower in mice treated with PAG than those mice solely inoculated with CVB3. Mice in group S had a significant decreased in the HW/BW ratio, the histologic scores and the iNOS mRNA and protein expression levels, and had a significant increased in the HO-1 mRNA and protein expression levels compared to the mice in group C. H2S can attenuate inflammatory cell infiltration, alleviate cardiac edema, and limit myocardial lesions. SIGNIFICANCE: Our data support that H2S can inhibit iNOS overexpression and induce HO-1 expression, both of which contribute to the cardioprotection of H2S in CVB3-induced mice myocarditis

(15) Bergersen O, Haarstad K. Treating landfill gas hydrogen sulphide with mineral wool waste (MWW) and rod mill waste (RMW). Waste Manag 2013 Oct 17. Abstract: Hydrogen sulphide (H2S) gas is a major odorant at municipal landfills. The gas can be generated from different waste fractions, for example demolition waste containing gypsum based plaster board. The removal of H2S from landfill gas was investigated by filtering it through mineral wool waste products. The flow of gas varied from 0.3l/min to 3.0l/min. The gas was typical for landfill gas with a mean H2S concentration of ca.

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4500ppm. The results show that the sulphide gas can effectively be removed by mineral wool waste products. The ratios of the estimated potential for sulphide precipitation were 19:1 for rod mill waste (RMW) and mineral wool waste (MWW). A filter consisting of a mixture of MWW and RMW, with a vertical perforated gas tube through the center of filter material and with a downward gas flow, removed 98% of the sulfide gas over a period of 80days. A downward gas flow was more efficient in contacting the filter materials. Mineral wool waste products are effective in removing hydrogen sulphide from landfill gas given an adequate contact time and water content in the filter material. Based on the estimated sulphide removal potential of mineral wool and rod mill waste of 14g/kg and 261g/kg, and assuming an average sulphide gas concentration of 4500ppm, the removal capacity in the filter materials has been estimated to last between 11 and 308days. At the studied location the experimental gas flow was 100 times less than the actual gas flow. We believe that the system described here can be upscaled in order to treat this gas flow

(16) Moustafa A, Habara Y. Hydrogen Sulfide Regulates Ca Homeostasis Mediated by Concomitantly Produced Nitric Oxide via a Novel Synergistic Pathway in Exocrine Pancreas. Antioxid Redox Signal 2013 Oct 19. Abstract: Abstract Aim: The present study was designed to explore the effects of hydrogen sulfide (H2S) on Ca2+ homeostasis in rat pancreatic acini. Results: Sodium hydrosulfide (NaHS; an H2S donor) induced a biphasic increase in the intracellular Ca2+ concentration ([Ca2+]i) in a dose-dependent manner. The NaHS-induced [Ca2+]i elevation persisted with an EC50 of 73.3 muM in the absence of extracellular Ca2+ but was abolished by thapsigargin, indicating that both Ca2+ entry and Ca2+ release contributed to the increase. The [Ca2+]i increase was markedly inhibited in the presence of NG-monomethyl L-arginine or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), and diaminofluorescein-2/diaminofluorescein-2 triazole (DAF-2/DAF-2T) fluorometry demonstrated that nitric oxide (NO) was also produced by H2S in a dose-dependent manner with an EC50 of 64.8 muM, indicating that NO was involved in the H2S effect. The H2S-induced [Ca2+]i increase was inhibited by pretreatment with U73122, xestospongin C, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, KT5823, and GP2A, indicating that phospholipase C (PLC), the inositol 1,4,5-trisphosphate (IP3) receptor, soluble guanylate cyclase (sGC), protein kinase G (PKG), and Gq-protein play roles as intermediate components in the H2S-triggered intracellular signaling. Innovation: To our knowledge, our study is the first one highlighting the effect of H2S on intracellular Ca2+ dynamics in pancreatic acinar cells. Moreover, a novel cascade was presumed to function via the synergistic interaction between H2S and NO. Conclusion: We conclude that H2S affects [Ca2+]i homeostasis that is mediated by H2S-evoked NO production via an endothelial nitric oxide synthase (eNOS)-NO-sGC-cyclic guanosine monophosphate-PKG-Gq-protein-PLC-IP3 pathway to induce Ca2+ release, and this pathway is identical to the one we recently proposed for a sole effect of NO and the two gaseous molecules synergistically function to regulate Ca2+ homeostasis. Antioxid. Redox Signal. 00, 000-000

(17) Causey MW, Miller S, Singh N, Martin M. Pharmacologic attenuation of the hyperdynamic response to supraceliac aortic clamping. J Vasc Surg 2013 Oct 15. Abstract: BACKGROUND: Aortic occlusion is accompanied by a hyperdynamic cardiovascular response secondary to increased systemic vascular resistance and increased cardiac output. This study was designed primarily to determine the safety and cardiovascular response to hydrogen sulfide (H2S; HS) administration with supraceliac aortic cross-clamp and, secondarily, on short-duration resuscitation. METHODS: A validated porcine model (five sham swine compared with five controls) demonstrated a significant hyperdynamic cardiovascular response to 35% blood volume hemorrhage, 50-minute suprarenal aortic cross-clamping, and 6-hour resuscitation. Eight additional experimental swine were administered HS at 4 mg/min during aortic cross-clamping. RESULTS: During the cross-clamp period, hemodynamic curves of mean arterial

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pressure and heart rate demonstrated a blunting effect with HS administration, with a significant decrease being seen with mean arterial pressure at the end of the cross-clamp period (120 vs 149 mm Hg; P = .04). Resuscitation requirements were significantly reduced at 6 hours because the HS cohort received 8 L less crystalloid (P = .001) and 10.4 mg less epinephrine (P < .001). There was not a significant change in cardiac output, systemic vascular resistance, pulmonary vascular resistance, or pathologic liver analysis. CONCLUSIONS: The administration of HS during the 50 minutes of supraceliac aortic cross-clamp significantly reduced stress of the left heart. On clamp release, HS significantly reduced the need for volume and pressors. HS has positive benefits during cross-clamp and subsequent resuscitation, demonstrating that targeted pharmacologic therapy is possible to minimize adverse physiologic changes with aortic occlusion

(18) Jung HY, Kim YL, Park S, Datar A, Lee HJ, Huang J, et al. High-performance H2S detection by redox reactions in semiconducting carbon nanotube-based devices. Analyst 2013 Dec 7;138(23):7206-11. Abstract: Here we report the highly effective detection of hydrogen sulfide (H2S) gas by redox reactions based on single-walled carbon nanotubes (SWCNTs) functionalized with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) as a catalyst and we also discuss the important role of water vapor in the electrical conductivity of SWCNTs during the sensing of H2S molecules. To explore the H2S sensing mechanism, we investigate the adsorption properties of H2S on carbon nanotubes (CNTs) and the effects of the TEMPO functionalization using first-principles density functional theory (DFT) and we summarize current changes of devices resulting from the redox reactions in the presence of H2S. The semiconducting-SWCNT (s-SWCNT) device functionalized with TEMPO shows a very high sensitivity of 420% at 60% humidity, which is 17 times higher than a bare s-SWCNT device under dry conditions. Our results offer promising prospects for personal safety and real-time monitoring of H2S gases with the highest sensitivity and low power consumption and potentially at a low cost

(19) Zhao DA, Liu J, Huang Q, Han ZM. [Change in plasma H2S level and therapeutic effect of H2S supplementation in tubulointerstitial fibrosis among rats with unilateral ureteral obstruction]. Zhongguo Dang Dai Er Ke Za Zhi 2013 Oct;15(10):903-8. Abstract: OBJECTIVE: To observe the level in plasma hydrogen sulfide (H2S) and the expression of cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) (two key synthetases for endogenous H2S generation in the kidney) in obstructed kidney tissue among rats with tubulointerstitial fibrosis (TIF) induced by unilateral ureteral obstruction (UUO), and to explore the role of H2S in TIF. METHODS: Ninety-six male Sprague-Dawley rats were randomly divided into sham-operated, model, low-dose NaHS and high-dose NaHS groups (n=24 each). TIF was induced by UUO in the model, low-dose NaHS and high-dose NaHS groups. The low-dose and high-dose NaHS groups were intraperitoneally injected with NaHS (1.4 and 7.0 mumol/kg respectively) twice daily immediately after operation, and the sham-operated and model groups were intraperitoneally injected with an identical volume of normal saline. In each group, 8 rats were randomly selected and sacrificed at 7, 14 or 21 days after operation. Plasma H2S concentration was measured by deproteinization. The obstructed kidney tissue was subjected to hematoxylin and eosin staining and Masson staining, and the renal tubulointerstitial injury was evaluated under a microscope. mRNA and protein expression of CBS and CSE in the obstructed kidney tissue was measured by RT-PCR and immunohistochemistry respectively. RESULTS: The degree of UUO-induced renal tubulointerstitial injury was negatively correlated with plasma H2S concentration in (r=-0.891, P<0.01). With H2S supplementation, renal tubulointerstitial injury was reduced (P<0.01), the expression of mRNA and protein of CBS and CSE in the kidney tissue and plasma H2S level were upregulated (P<0.01), and the degree of TIF was reduced (P<0.01). There were no significant differences in plasma H2S level and mRNA and protein expression of CBS and CSE between the low-dose and high-dose NaHS groups (P>0.05). CONCLUSIONS: H2S is involved in the development of UUO-induced TIF, and

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the CBS/H2S and CSE/H2S systems play key roles in this process. H2S supplementation can delay the progression of TIF

(20) Xu DQ, Gao C, Niu W, Li Y, Wang YX, Gao CJ, et al. Sodium hydrosulfide alleviates lung inflammation and cell apoptosis following resuscitated hemorrhagic shock in rats. Acta Pharmacol Sin 2013 Oct 14. Abstract: Aim:To investigate the protective effects of hydrogen sulfide (H2S) against inflammation, oxidative stress and apoptosis in a rat model of resuscitated hemorrhagic shock.Methods:Hemorrhagic shock was induced in adult male SD rats by drawing blood from the femoral artery for 10 min. The mean arterial pressure was maintained at 35-40 mmHg for 1.5 h. After resuscitation the animals were observed for 200 min, and then killed. The lungs were harvested and bronchoalveolar lavage fluid was prepared. The levels of relevant proteins were examined using Western blotting and immunohistochemical analyses. NaHS (28 mumol/kg, ip) was injected before the resuscitation.Results:Resuscitated hemorrhagic shock induced lung inflammatory responses and significantly increased the levels of inflammatory cytokines IL-6, TNF-alpha, and HMGB1 in bronchoalveolar lavage fluid. Furthermore, resuscitated hemorrhagic shock caused marked oxidative stress in lung tissue as shown by significant increases in the production of reactive oxygen species H2O2 and .OH, the translocation of Nrf2, an important regulator of antioxidant expression, into nucleus, and the decrease of thioredoxin 1 expression. Moreover, resuscitated hemorrhagic shock markedly increased the expression of death receptor Fas and Fas-ligand and the number apoptotic cells in lung tissue, as well as the expression of pro-apoptotic proteins FADD, active-caspase 3, active-caspase 8, Bax, and decreased the expression of Bcl-2. Injection with NaHS significantly attenuated these pathophysiological abnormalities induced by the resuscitated hemorrhagic shock.Conclusion:NaHS administration protects rat lungs against inflammatory responses induced by resuscitated hemorrhagic shock via suppressing oxidative stress and the Fas/FasL apoptotic signaling pathway

(21) Feng Z, Fan C, Huang W, Ding S. Microorganisms and typical organic matter responsible for lacustrine "black bloom". Sci Total Environ 2013 Oct 8;470-471C:1-8. Abstract: Identifying the causation of the black substance in lacustrine "black bloom" is of great significance for forecasting and preventing black bloom in many waters of the world. In this research, an array of black bloom was simulated in a laboratory to investigate how microorganisms and organic matter affect black bloom. Sulphate-reducing bacteria (SRB) are the main biological factor, and protein is the key organic factor contributing to lacustrine black bloom. The black colour of black bloom is strongly associated with a relatively high SRB population density. Hydrogen sulphide concentration can serve as a predictor of black bloom

(22) Kwiatkoski M, Soriano RN, da Silva GS, Francescato HD, Coimbra TM, Glass ML, et al. Endogenous preoptic hydrogen sulphide attenuates hypoxia-induced hyperventilation. Acta Physiol (Oxf) 2013 Oct 1. Abstract: AIM: We hypothesized that hydrogen sulphide (H2 S), acting specifically in the anteroventral preoptic region (A

(23) Kim KI, Kang JY, Park JY, Joh SJ, Lee HS, Kwon YK. Phenotypic traits, virulence-associated gene profile and genetic relatedness of Edwardsiella tarda isolates from Japanese eel Anguilla japonica in Korea. Lett Appl Microbiol 2013 Oct 7. Abstract: Edwardsiella tarda is the predominant bacterium in farm-cultured eel in Korea. Here, we evaluated the heterogeneity of 37 E. tarda isolates derived from Japanese eel with various origins (olive flounder, common carp and ornamental fish) between 2003 and 2010. Regardless of origins, the biochemical characteristics of E. tarda isolates were homogenous except hydrogen sulfide production, citrate utilization and mannitol fermentation. Based on the phylogenetic analysis of 16S rRNA, E. tarda isolates could be classified into two subgroups and displayed a close relation with Edwardsiella ictaluri and

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Edwardsiella hosinae lineages, suggesting that the subgroup I has been a predominant type in the Jeonnam and Jeonbuk provinces. I-CeuI-based pulsed-field gel electrophoresis (PFGE) typing showed that the isolates from Japanese eels belonged to 11 pulsotypes, indicating that the presence of highly genomic diversity. Additionally, two isolates, ET-060 and ET-191, showed a high frequency of virulence genes (100%) and caused 90% and 60% mortality in Japanese eel, respectively. This finding suggests a substantial congruence of virulence gene profiles and pathogenicity. Our results demonstrate that the intraspecific diversity within E. tarda strains from Japanese eel has been in prior existence. SIGNIFICANCE AND IMPACT OF THE STUDY: Based on the biochemical characteristics, the phylogenetic property of the 16S rRNA gene and PFGE types of Edwardsiella tarda, we could identify the intraspecific diversity of isolates from Japanese eel, Anguilla japonica in Korea. In addition, this study describes the strong congruence of virulence-related genes and pathogenicity, suggesting that the virulence profile may be useful tool for prediction of pathogenicity

(24) Luo ZL, Tang LJ, Wang T, Dai RW, Ren JD, Cheng L, et al. Treatment with hydrogen sulfide prevents methionine-choline deficient diet-induced non-alcoholic steatohepatitis in rats. J Gastroenterol Hepatol 2013 Oct 3. Abstract: BACKGROUND AND AIM: Oxidative stress and inflammation play important roles in the progression from simple fatty liver to nonalcoholic steatohepatitis (NASH). The aim of this work was to investigate whether treatment with hydrogen sulfide (H2 S) prevented NASH in rats through abating oxidative stress and suppressing inflammation. METHODS: A methionine-choline-deficient (MCD) diet rat model was prepared. Rats were divided into three experimental groups and fed for 8 weeks as follows: (1) control rats; (2) MCD-diet-fed rats; (3) MCD-diet-fed rats treated with NaHS (intraperitoneal injection of 0.1 ml/kg/d of 0.28 mol/l NaHS, a donor of H2 S). RESULTS: MCD diet impaired hepatic H2 S biosynthesis in rats. Treatment with H2 S prevented MCD-diet-induced NASH, as evidenced by hematoxylin and eosin staining, reduced apoptosis and activities of ALT and AST, and attenuated hepatic fat accumulation in rats. Treatment with H2 S abated MCD-diet-induced oxidative stress through reducing CYP2E1 expression, enhancing HO-1 expression and suppressing mitochondrial ROS formation, and suppressed MCD-diet-induced inflammation through suppressing activated NFkappaB signaling and reducing IL-6 and TNFalpha expression. In addition, Treatment of MCD-diet fed rats with H2 S had a beneficial modulation on expression profiles of fatty acid metabolism genes in livers. CONCLUSIONS: Treatment with H2 S prevented NASH induced by MCD diet in rats possibly through abating oxidative stress and suppressing inflammation

(25) Roger T, Raynaud F, Bouillaud F, Ransy C, Simonet S, Crespo C, et al. New Biologically Active Hydrogen Sulfide Donors. Chembiochem 2013 Oct 2. Abstract: Generous donors: The dithioperoxyanhydrides (CH3 COS)2 , (PhCOS)2 , CH3 COSSCO2 Me and PhCOSSCO2 Me act as thiol-activated hydrogen sulfide donors in aqueous buffer solution. The most efficient donor (CH3 COS)2 can induce a biological response in cells, and advantageously replace hydrogen sulfide in ex vivo vascular studies

(26) Markova J, Hudecova S, Soltysova A, Sirova M, Csaderova L, Lencesova L, et al. Sodium/calcium exchanger is upregulated by sulfide signaling, forms complex with the beta1 and beta3 but not beta2 adrenergic receptors, and induces apoptosis. Pflugers Arch 2013 Oct 10. Abstract: Hydrogen sulfide (H2S) as a novel gasotransmitter regulates variety of processes, including calcium transport systems. Sodium calcium exchanger (NCX) is one of the key players in a regulation calcium homeostasis. Thus, the aims of our work were to determine effect of sulfide signaling on the NCX type 1 (NCX1) expression and function in HeLa cells, to investigate the relationship of beta-adrenergic receptors with the NCX1 in the presence and/or absence of H2S, and to determine physiological importance

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of this potential communication. As a H2S donor, we used morpholin-4-ium-4-methoxyphenyl(morpholino) phosphinodithioate-GYY4137. We observed increased levels of the NCX1 mRNA, protein, and activity after 24 h of GYY4137 treatment. This increase was accompanied by elevated cAMP due to the GYY4137 treatment, which was completely abolished, when NCX1 was silenced. Increased cAMP levels would point to upregulation of beta-adrenergic receptors. Indeed, GYY4137 increased expression of beta1 and beta3 (but not beta2) adrenergic receptors. These receptors co-precipitated, co-localized with the NCX1, and induced apoptosis in the presence of H2S. Our results suggest that sulfide signaling plays a role in regulation of the NCX1, beta1 and beta3 adrenergic receptors, their co-localization, and stimulation of apoptosis, which might be of a potential importance in cancer treatment

(27) Frijhoff J, Dagnell M, Godfrey R, Ostman A. Regulation of Protein Tyrosine Phosphatase Oxidation in Cell Adhesion and Migration. Antioxid Redox Signal 2013 Oct 10. Abstract: Significance: Redox-regulated control of protein tyrosine phosphatases through inhibitory reversible oxidation of their active site is emerging as a novel and general mechanism for control of cell surface receptor-activated signalling. This mechanism allows for a previously unrecognized crosstalk between redox regulators and signalling pathways, governed by e.g. receptor tyrosine kinases and integrins, which control cell proliferation and migration. Recent Advances: A large number of different molecules, in addition to hydrogen peroxide, have been found to induce PTP inactivation, including lipid peroxides, reactive nitrogen species and hydrogen sulfide. Characterization of oxidized PTPs has identified different types of oxidative modifications which are likely to display differential sensitivity to various reducing systems. Accumulating evidence demonstrates that PTP oxidation occurs in a temporally and spatially restricted manner. Studies in cell and animal models indicate altered PTP oxidation in models of common diseases such as cancer and metabolic/cardiovascular disease. Novel methods have appeared allowing characterization of global PTP oxidation. Critical Issues: As the understanding of the molecular and cellular biology of PTP oxidation is developing it will be important to establish experimental procedures allowing analyses of PTP oxidation, and its regulation, in physiological and pathophysiological settings. Future studies should also aim to establish specific connections between various oxidants, specific PTPs and defined signalling contexts. Future directions: Modulation of PTP activity still appears as a valid strategy for correction or inhibition of dys-regulated cell signalling. Continued studies on PTP oxidation might present yet un-recognized means to exploit this regulatory mechanism for pharmacological purposes

(28) Yang F, Huang S, He T, Catrenich C, Teng F, Bo C, et al. Microbial Basis of Oral Malodor Development in Humans. J Dent Res 2013 Oct 7. Abstract: To better understand the microbial basis of oral malodor development in humans, we used a cross-sectional and longitudinal study design and the pyrosequencing approach to track and compare the tongue microbiota associated with oral malodor in 29 Chinese adults who underwent a consecutive three-day evaluation for the amount of H2S excreted orally. Three levels of the oral malodor state (healthy, oral malodor, and severe oral malodor) were defined based on the H2S level. Community structure of the tongue plaques was more sensitive to changes of malodor state than to interpersonal variations or differences in sampling times. Within each individual, the structure of microbiota was relatively stable, while their variations were correlated with the change in the H2S level. Severe oral malodor microbiota were the most conserved in community structure, whereas the healthy ones were relatively varied. Oral-malodor-associated bacteria were identified. The relative abundance of Leptotrichia and Prevotella was positively correlated with oral malodor severity, whereas Hemophilus and Gemella exhibited a negative relationship with oral malodor severity. Our study provides one of the first landscapes of oral microbiota changes associated with oral malodor development and reveals microbes potentially useful to the evaluation and control of oral malodor

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(29) Vozdek R, Hnizda A, Krijt J, Sera L, Kozich V. Biochemical properties of nematode O-acetylserine(thiol)lyase paralogs imply their distinct roles in hydrogen sulfide homeostasis. Biochim Biophys Acta 2013 Oct 4;1834(12):2691-701. Abstract: O-Acetylserine(thiol)lyases (OAS-TLs) play a pivotal role in a sulfur assimilation pathway incorporating sulfide into amino acids in microorganisms and plants, however, these enzymes have not been found in the animal kingdom. Interestingly, the genome of the roundworm Caenorhabditis elegans contains three expressed genes predicted to encode OAS-TL orthologs (cysl-1-cysl-3), and a related pseudogene (cysl-4); these genes play different roles in resistance to hypoxia, hydrogen sulfide and cyanide. To get an insight into the underlying molecular mechanisms we purified the three recombinant worm OAS-TL proteins, and we determined their enzymatic activities, substrate binding affinities, quaternary structures and the conformations of their active site shapes. We show that the nematode OAS-TL orthologs can bind O-acetylserine and catalyze the canonical reaction although this ligand may more likely serve as a competitive inhibitor to natural substrates instead of being a substrate for sulfur assimilation. In addition, we propose that S-sulfocysteine may be a novel endogenous substrate for these proteins. However, we observed that the three OAS-TL proteins are conformationally different and exhibit distinct substrate specificity. Based on the available evidences we propose the following model: CYSL-1 interacts with EGL-9 and activates HIF-1 that upregulates expression of genes detoxifying sulfide and cyanide, the CYSL-2 acts as a cyanoalanine synthase in the cyanide detoxification pathway and simultaneously produces hydrogen sulfide, while the role of CYSL-3 remains unclear although it exhibits sulfhydrylase activity in vitro. All these data indicate that C. elegans OAS-TL paralogs have distinct cellular functions and may play different roles in maintaining hydrogen sulfide homeostasis

(30) Biddle AS, Black SJ, Blanchard JL. An in vitro model of the horse gut microbiome enables identification of lactate-utilizing bacteria that differentially respond to starch induction. PLoS One 2013;8(10):e77599. Abstract: Laminitis is a chronic, crippling disease triggered by the sudden influx of dietary starch. Starch reaches the hindgut resulting in enrichment of lactic acid bacteria, lactate accumulation, and acidification of the gut contents. Bacterial products enter the bloodstream and precipitate systemic inflammation. Hindgut lactate levels are normally low because specific bacterial groups convert lactate to short chain fatty acids. Why this mechanism fails when lactate levels rapidly rise, and why some hindgut communities can recover is unknown. Fecal samples from three adult horses eating identical diets provided bacterial communities for this in vitro study. Triplicate microcosms of fecal slurries were enriched with lactate and/or starch. Metabolic products (short chain fatty acids, headspace gases, and hydrogen sulfide) were measured and microbial community compositions determined using Illumina 16S rRNA sequencing over 12-hour intervals. We report that patterns of change in short chain fatty acid levels and pH in our in vitro system are similar to those seen in in vivo laminitis induction models. Community differences between microcosms with disparate abilities to clear excess lactate suggest profiles conferring resistance of starch-induction conditions. Where lactate levels recover following starch induction conditions, propionate and acetate levels rise correspondingly and taxa related to Megasphaeraelsdenii reach levels exceeding 70% relative abundance. In lactate and control cultures, taxa related to Veillonellamontpellierensis are enriched as lactate levels fall. Understanding these community differences and factors promoting the growth of specific lactate utilizing taxa may be useful to prevent acidosis under starch-induction conditions

(31) Guo W, Cheng ZY, Zhu YZ. Hydrogen sulfide and translational medicine. Acta Pharmacol Sin 2013 Oct 7;34(10):1284-91. Abstract: Hydrogen sulfide (H2S) along with carbon monoxide and nitric oxide is an important signaling molecule that has undergone large numbers of fundamental investigations. H2S is involved in various physiological activities associated with the

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regulation of homeostasis, vascular contractility, pro- and anti-inflammatory activities, as well as pro- and anti-apoptotic activities etc. However, the actions of H2S are influenced by its concentration, reaction time, and cell/disease types. Therefore, H2S is a signaling molecule without definite effect. The use of existing H2S donors is limited because of the instant release and short lifetime of H2S. Thus, translational medicine involving the sustained and controlled release of H2S is of great value for both scientific and clinical uses. H2S donation can be manipulated by different ways, including where H2S is given, how H2S is donated, or the specific structures of H2S-releasing drugs and H2S donor molecules. This review briefly summarizes recent progress in research on the physiological and pathological functions of H2S and H2S-releasing drugs, and suggests hope for future investigations

(32) Wang Z, Zhan J, Wang X, Gu J, Xie K, Zhang Q, et al. Sodium hydrosulfide prevents hypoxia-induced behavioral impairment in neonatal mice. Brain Res 2013 Nov 13;1538:126-34. Abstract: Hypoxic encephalopathy is a common cause of neonatal seizures and long-term neurological abnormalities. Endogenous hydrogen sulfide (H2S) may have multiple functions in brain. The aim of this study is to investigate whether sodium hydrosulfide (NaHS), a H2S donor, provides protection against neonatal hypoxia-induced neurobehavioral deficits. Neonatal mice were subjected to hypoxia (5% oxygen for 120min) at postnatal day 1 and received NaHS (5.6mg/kg) once daily for 3d. Neurobehavioral toxicity was examined at 3-30d after hypoxia. Treatment with NaHS significantly attenuated the delayed development of sensory and motor reflexes induced by hypoxia up to two weeks after the insult. Moreover, NaHS improved the learning and memory performance of hypoxic animals as indicated in Morris water maze test at 30d after hypoxia. In mice exposed to hypoxia, treatment with NaHS enhanced expression of brain derived neurotrophic factor (BDNF) in the hippocampus. Furthermore, the protective effects of NaHS were associated with its ability to repress the hypoxia-induced nitric oxide synthase (NOS) activity and nitric oxide production in the hippocampus of mice brain. Taken together, these results suggest that the long-lasting beneficial effects of NaHS on hypoxia-induced neurobehavioral deficits are mediated, at least in part, by inducing BDNF expression and suppressing NOS activity in the brain of mice

(33) Bailey TS, Pluth MD. Chemiluminescent Detection of Enzymatically Produced Hydrogen Sulfide: Substrate Hydrogen Bonding Influences Selectivity for HS over Biological Thiols. J Am Chem Soc 2013 Oct 23. Abstract: Hydrogen sulfide (H2S) is now recognized as an important biological regulator and signaling agent that is active in many physiological processes and diseases. Understanding the important roles of this emerging signaling molecule has remained challenging, in part due to the limited methods available for detecting endogenous H2S. Here we report two reaction-based ChemiLuminescent Sulfide Sensors, CLSS-1 and CLSS-2, with strong luminescence responses toward H2S (128- and 48-fold, respectively) and H2S detection limits (0.7 +/- 0.3, 4.6 +/- 2.0 muM, respectively) compatible with biological H2S levels. CLSS-2 is highly selective for H2S over other reactive sulfur, nitrogen, and oxygen species (RSONS) including GSH, Cys, Hcy, S2O32-, NO2-, HNO, ONOO-, and NO. Despite its similar chemical structure, CLSS-1 displays lower selectivity toward amino acid-derived thiols than CLSS-2. The origin of this differential selectivity was investigated using both computational DFT studies and NMR experiments. Our results suggest a model in which amino acid binding to the hydrazide moiety of the luminol-derived probes provides differential access to the reactive azide in CLSS-1 and CLSS-2, thus eroding the selectivity of CLSS-1 for H2S over Cys and GSH. On the basis of its high selectivity for H2S, we used CLSS-2 to detect enzymatically produced H2S from isolated cystathionine gamma-lyase (CSE) enzymes (p < 0.001) and also from C6 cells expressing CSE (p < 0.001). CLSS-2 can readily differentiate between H2S production in active CSE and CSE inhibited with beta-cyanoalanine (BCA) in both isolated CSE enzymes (p < 0.005) and in C6 cells (p < 0.005). In addition to providing a

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highly sensitive and selective reaction-based tool for chemiluminescent H2S detection and quantification, the insights into substrate-probe interactions controlling the selectivity for H2S over biologically relevant thiols may guide the design of other selective H2S detection scaffolds

(34) Moore PK, Qabazard B, Li L, Gruber J, Ng LF, Srinivasan DK, et al. Hydrogen sulfide is an endogenous regulator of ageing in Caenorhabditis elegans. Antioxid Redox Signal 2013 Oct 5. Abstract: Aims: To investigate the role of endogenous hydrogen sulfide (H2S) in the control of ageing and healthspan of Caenorhabditis elegans. Results: We show that the model organism, C. elegans, synthesizes H2S. Three H2S synthesizing enzymes are present in C. elegans namely cystathionine lyase (CSE), cystathionine synthetase (CBS) and 3-mercaptopyruvate transferase (MPST or 3-MST). Genetic deficiency of mpst-1 (3-MST orthologue 1), but not cth-2 (CSE orthologue) reduced lifespan of C. elegans. This effect was reversed by a pharmacological H2S donor (GYY4137). GYY4137 also reduced detrimental age-dependent changes in a range of physiological indices including pharyngeal contraction and defecation. Treatment of C. elegans with GYY4137 increased the expression of several age-related, stress response and anti-oxidant genes whilst MitoSOX Red fluorescence, indicative of reactive oxygen species generation, was increased in mpst-1 knockouts and decreased by GYY4137 treatment. GYY4137 additionally increased lifespan in short-lived mev-1 mutants with elevated oxidative stress and protected wild type C. elegans against paraquat poisoning. The lifespan-prolonging and health-promoting effects of H2S in C. elegans are likely due to the anti-oxidant action of this highly cell-permeable gas. Conclusion: Our results show that H2S is an endogenous regulator of oxidative damage, metabolism and ageing in C. elegans and provide new insight into the mechanisms which control ageing in this model organism. The possibility that novel pharmacological agents based on the principle of H2S donation may be able to retard the onset of age-related disease by slowing the ageing process warrants further study

(35) Wang K, Peng H, Ni N, Dai C, Wang B. 2,6-Dansyl Azide as a Fluorescent Probe for Hydrogen Sulfide. J Fluoresc 2013 Oct 1. Abstract: A second-generation sulfonyl azide-based fluorescent probe, 2,6-DNS-Az, has been developed for the quantitative detection of H2S in aqueous media such as phosphate buffer and bovine serum. Compare to the first-generation 1,5-DNS-Az probe, this probe shows both high sensitivity in phosphate buffer without the need for addition of surfactant and selectivity for sulfide over other anions and biomolecules, and thus can be used as a useful tool for detection of H2S in the biological system

(36) Nicholls P, Marshall DC, Cooper CE, Wilson MT. Sulfide inhibition of and metabolism by cytochrome c oxidase. Biochem Soc Trans 2013 Oct;41(5):1312-6. Abstract: Hydrogen sulfide (H2S), a classic cytochrome c oxidase inhibitor, is also an in vitro oxidase substrate and an in vivo candidate hormonal ('gasotransmitter') species affecting sleep and hibernation. H2S, nitric oxide (NO) and carbon monoxide (CO) share some common features. All are low-molecular-mass physiological effectors and also oxidase inhibitors, capable of binding more than one enzyme site, and each is an oxidizable 'substrate'. The oxidase oxidizes CO to CO2, NO to nitrite and sulfide to probable persulfide species. Mitochondrial cytochrome c oxidase in an aerobic steady state with ascorbate and cytochrome c is rapidly inhibited by sulfide in a biphasic manner. At least two successive inhibited species are involved, probably partially reduced. The oxidized enzyme, in the absence of turnover, occurs in at least two forms: the 'pulsed' and 'resting' states. The pulsed form reacts aerobically with sulfide to form two intermediates, 'P' and 'F', otherwise involved in the reaction of oxygen with reduced enzyme. Sulfide can directly reduce the oxygen-reactive a3CuB binuclear centre in the pulsed state. The resting enzyme does not undergo such a step, but only a very slow one-electron reduction of the electron-transferring haem a. In final reactivation phases,

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both the steady-state inhibition of catalysis and the accumulation of P and F states are reversed by slow sulfide oxidation. A model for this complex reaction pattern is presented

(37) Pikaar I, Rozendal RA, Rabaey K, Yuan Z. In-situ caustic generation from sewage: the impact of caustic strength and sewage composition. Water Res 2013 Oct 1;47(15):5828-35. Abstract: Periodic caustic dosage is a commonly used method by the water industry to elevate pH levels and deactivate sewer biofilms responsible for hydrogen sulfide generation. Caustic (NaOH) can be generated in-situ from sewage using a divided electrochemical cell, which avoids the need for transport, handling and storage of concentrated caustic solutions. In this study, we investigated the impact of caustic strength in the cathode compartment and the impact of sodium concentration in sewage on the Coulombic efficiency (CE) for caustic generation. The CE was found to be independent of the caustic strength produced in the range of up to ~3 wt%. Results showed that a caustic solution of ~3 wt% could be produced directly from sewage at a CE of up to 75 +/- 0.5%. The sodium concentration in sewage had a significant impact on the CE for caustic generation as well as on the energy requirements of the system, with a higher sodium concentration leading to a higher CE and lower energy consumption. The proton, calcium, magnesium and ammonium concentrations in sewage affected the CE for caustic generation, especially at low sodium concentrations. Economical assessment based on the experimental results indicated that sulfide control in sewers using electrochemically-generated caustic from sewage is an economically attractive strategy

(38) Chen J, Xie Z. Removal of H2S in a novel dielectric barrier discharge reactor with photocatalytic electrode and activated carbon fiber. J Hazard Mater 2013 Oct 15;261:38-43. Abstract: A novel dielectric barrier discharge (DBD) reactor was applied for removal of H2S. Activated carbon fiber (ACF) and a photocatalytic electrode prepared from sintered metal fibers (SMF) were introduced into the novel reactor. H2S removal rate was enhanced dramatically due to the synergism between DBD and ACF. Peak voltage, initial concentration, resident time and humidity were important factors that influenced the H2S removal rate. 75mg/m(3) H2S removal rate reached 99.9% at a peak voltage of 25kV and with a resident time of 2s in the novel reactor. Humidity had an inhibition to H2S decomposition at low peak voltages. And the inhibition became slight at high peak voltages (>20kV). The novel reactor exhibited better by-products (SO2 and O3) control than other reactors did. And it also had excellent performance stabilization in a long-term operation (30 d)

(39) Chattopadhyay M, Nath N, Kodela R, Sobocki T, Metkar S, Gan ZY, et al. Hydrogen sulfide-releasing aspirin inhibits the growth of leukemic Jurkat cells and modulates beta-catenin expression. Leuk Res 2013 Oct;37(10):1302-8. Abstract: Hydrogen sulfide-releasing aspirin (HS-ASA) is a novel compound with potential against cancer. It inhibited the growth of Jurkat T-leukemia cells with an IC(5)(0) of 1.9 +/- 0.2 muM whereas that of ASA was >5000 muM. It dose-dependently inhibited proliferation and induced apoptosis in these cells, causing a G(0)/G(1) cell cycle arrest. HS-ASA down-regulated beta-catenin protein levels and reduced mRNA and protein expression of beta-catenin/TCF downstream target genes cyclinD1 and c-myc. Aspirin up to 5 mM had no effect on beta-catenin expression. HS-ASA also increased caspase-3 protein levels and dose-dependently increased its activity. These effects were substantially blocked by z-VAD-fmk, a pan-caspase inhibitor

(40) Anet B, Lemasle M, Couriol C, Lendormi T, Amrane A, Le CP, et al. Characterization of gaseous odorous emissions from a rendering plant by GC/MS and treatment by biofiltration. J Environ Manage 2013 Oct 15;128:981-7. Abstract: This research focuses on the identification and quantification of odorous components in rendering plant emissions by GC/MS and other analytical methods, as

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well as the description of phenomena occurring in biofilter in order to improve the removal efficiency of industrial biofilters. Among the 36 compounds quantified in the process air stream, methanethiol, isopentanal and hydrogen sulfide, presented the major odorous contributions according to their high concentrations, generally higher than 10 mg m(-3), and their low odorous detection thresholds. The elimination of such component mixtures by biofiltration (Peat packing material, EBRT: 113 s) was investigated and revealed that more than 83% of hydrogen sulfide and isopentanal were removed by biofilter. Nevertheless, the incomplete degradation of such easily degradable pollutants suggested inappropriate conditions as lack of nutrients and acidic pH. These inadequate conditions could explain the lack of performance, especially observed on methanethiol (53% of RE) and the production of oxygenated and sulfur by-products by the biofilter itself

(41) Sarturi JO, Erickson GE, Klopfenstein TJ, Vasconcelos JT, Griffin WA, Rolfe KM, et al. Effect of sulfur content in wet or dry distillers grains fed at several inclusions on cattle growth performance, ruminal parameters, and hydrogen sulfide. J Anim Sci 2013 Oct;91(10):4849-60. Abstract: Effects of S from wet or dry distillers grains with solubles (DGS) containing 0.82 or 1.16% S on animal growth performance, carcass characteristics, apparent total tract digestibility, and ruminal parameters were evaluated. In Exp. 1, crossbred beef steers (n = 120; 345 +/- 34 kg BW) were individually fed ad libitum using Calan gates. Treatments were applied as a 2 x 2 x 3 + 1 factorial treatment arrangement with factors of DGS type (wet or dry), S content in DGS (0.82 or 1.16% DM basis), and DGS inclusion (20, 30, and 40%, DM basis), as well as a corn control diet (no DGS). In Exp. 2, ruminally cannulated crossbred beef steers (n = 6; 381 +/- 31 kg BW) were assigned to 1 of 5 diets in a 5 x 6 unbalanced Latin Square design and fed ad libitum through five 14-d periods. A 2 x 2 + 1 factorial treatment arrangement was used with the factors of DGS type and S content in DGS (similar to Exp. 1). Inclusion of DGS was 40%, except for a MATCH diet containing wet 1.16% S DGS included at 31.4% (DM basis). Intake of DM decreased linearly (P < 0.01) and quadratically (P < 0.01) for steers fed wet and dry DGS that was 1.16% S, respectively. In addition, steers fed dry DGS consumed 9% more DM (P < 0.01) than those fed wet. Gain decreased linearly (P = 0.02) when wet 1.16% S DGS increased in the diet, representing a 12% drop in ADG between the Control and 40% DGS inclusion. A quadratic (P = 0.02) improvement in G:F was observed for steers fed wet DGS compared with dry, regardless of S content (P = 0.52). Feeding diets with wet 1.16% S DGS linearly decreased (P = 0.03) HCW. In Exp. 2, molar proportion of propionate declined (P = 0.01) 9% and A:P ratio tended (P = 0.13) to be greater when 1.16 compared with 0.82% S DGS was fed. Apparent total tract DMD was not affected (P > 0.16) and only subtle changes (P < 0.01) in ruminal pH parameters were observed. Greater (P = 0.02) ruminal H2S concentration for steers fed wet compared with dry DGS was observed, while 1.16% S DGS tended (P = 0.12) to produce greater ruminal H2S than 0.82% S. Sulfur in wet DGS appears to be more prone to be converted to ruminal H2S, because feeding 1.16% S as wet DGS had a greater impact on ADG, DMI, and ruminal H2S compared with dry DGS

(42) Zheng Y, Luo N, Mu D, Jiang P, Liu R, Sun H, et al. Lipopolysaccharide regulates biosynthesis of cystathionine gamma-lyase and hydrogen sulfide through toll-like receptor-4/p38 and toll-like receptor-4/NF-kappaB pathways in macrophages. In Vitro Cell Dev Biol Anim 2013 Oct;49(9):679-88. Abstract: Hydrogen sulfide (H2S), formed mainly by the enzyme cystathionine gamma-lyase (CSE) in macrophages, is emerging as a novel regulator in inflammation. Although elevated production of H2S has been shown in inflammatory processes, the underlying molecular mechanism remains to be further elucidated. In this study, we compared parallel TLR4 knockout (TLR4(-/-)) mice with their wild-type counterparts following lipopolysaccharide (LPS) treatment. It showed that LPS increased the expressions of CSE and biosynthesis of H2S in C57BL/6 mice both in vivo and in vitro. However, the effects of LPS were not present in TLR4(-/-) mice, indicating the crucial role

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of TLR4 in LPS-induced expression of CSE and biosynthesis of H2S. We subsequently used JNK inhibitor, P38 inhibitor, and ERK inhibitor to block the downstream MAPK pathways of TLR4 in macrophages, and found that LPS-induced CSE expression and H2S synthesizing activity were inhibited by pretreatment with the p38 inhibitor. Similarly, the NF-kappaB inhibitor (BAY 11-7082) reversed the effects of LPS. These results suggest that LPS increases the biosynthesis of CSE and H2S in macrophages mainly in a TLR4-p38-dependent and TLR-4-NF-kappaB-dependent manner. These findings expand our knowledge of H2S biosynthesis during inflammation and provide a foundation for the development of novel H2S-based therapies

(43) Takahashi K, Ohta T. Inflammatory acidic pH enhances hydrogen sulfide-induced transient receptor potential ankyrin 1 activation in RIN-14B cells. J Neurosci Res 2013 Oct;91(10):1322-7. Abstract: Hydrogen sulfide (H2 S), a toxic volcanic gas, functions as a gaseous physiological and pathophysiological molecule. Recently we have shown that H2 S elicits acute pain through the activation of transient receptor potential ankyrin 1 (TRPA1), which is expressed mainly in primary nociceptive neurons. We also demonstrated enhancement of H2 S-induced TRPA1 activation and pain under inflammatory acidic conditions, but the underlying mechanism has not been elucidated. Here, we attempted to clarify this mechanism by using endogenously TRPA1-expressing RIN-14B, a rat pancreatic islet cell line. For this purpose, the intracellular Ca(2+) concentration ([Ca(2+) ]i )], reactive oxygen species (ROS), and intracellular pH (pHi ) were measured with fluorescent imaging techniques. The intracellular H2 S concentration was assayed by the methylene blue method. To clarify the cellular function of H2 S, 5-hydroxytryptamine (5-HT) secretion was analyzed. In RIN-14B, the increase of [Ca(2+) ]i and the release of 5-HT induced by NaHS, an H2 S donor, were enhanced under inflammatory acidic conditions. Transition of H2 S into cells was enhanced at pH 6.8. H2 S failed to increase the intracellular ROS level and only slightly decreased pHi . These results suggest that H2 S directly activates TRPA1 and that its increment of diffusion into cells may be involved in the potentiation of TRPA1 activation under external acidic conditions. Thus, our study supports the pathophysiological functions of H2 S in inflammatory pain

(44) Chan MV, Wallace JL. Hydrogen sulfide-based therapeutics and gastrointestinal diseases: translating physiology to treatments. Am J Physiol Gastrointest Liver Physiol 2013 Oct;305(7):G467-G473. Abstract: Hydrogen sulfide (H2S) is a gaseous meditator that has various physiological and pathophysiological roles in the body. It has been shown to be an important mediator of gastrointestinal (GI) mucosal defense and contributes significantly to repair of damage and resolution of inflammation. Synthesis of H2S increases markedly after mucosal injury, and inhibition of H2S in such circumstances leads to delayed healing and exacerbated inflammation. The beneficial effects of H2S may be attributable to its ability to elevate mucosal blood flow, prevent leukocyte-endothelial adhesion, reduce oxidative stress, and stimulate angiogenesis. The use of H2S-donating agents and inhibitors of the key enzymes contributing to H2S synthesis have provided strong evidence for the importance of H2S in enhancing mucosal resistance to damage, as well as modulating inflammation and repair. In recent years, significant evidence has been generated to support the notion that these positive aspects of H2S can be exploited in drug design, particularly for arthritis, inflammatory bowel disease, and colon cancer chemoprevention. Thus novel H2S-based therapies have been shown to be effective anti-inflammatories that can promote the resolution of inflammation and accelerate the healing of GI ulcers. Encouraging results have already been seen experimentally with a mesalamine derivative and with H2S-releasing derivatives of nonsteroidal anti-inflammatory drugs

(45) Wang K, Zhu D, Yu X, Sun J, Yao W. Differences in the H2S-induced quantal release of catecholamine in adrenal chromaffin cells of neonatal and adult rats. Toxicology 2013 Oct 4;312:12-7.

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Abstract: Both catecholamine (CA) released from adrenal chromaffin cells and hydrogen sulfide (H2S) have been shown to play critical roles in the regulation of hypoxic stress response. Our previous study has demonstrated that exogenous H2S directly induced quantal CA released from adult rat adrenal chromaffin cells (ARACCs) by inhibiting Ca(2+)-activated K(+) current [IK(Ca) current]. However, it is not clear now whether H2S can also directly induce quantal CA released from neonatal rat adrenal chromaffin cells (NRACCs). In the present study, we investigated whether exogenous H2S can stimulate quantal CA released from NRACCs, and whether there were differences in the kinetics of H2S-induced quantal CA released between ARACCs and NRACCs. Using carbon-fiber amperometry and whole-cell patch clamping techniques, our experimental results showed: (1) H2S can directly induce quantal CA released from NRACCs; (2) H2S induced the depolarization of membrane potential and inhibited IK(Ca) current; (3) compared with ARACCs, much smaller quantal size and faster quantal release were showed in NRACCs through the kinetic analysis of the single-vesicle secretion induced by H2S. Our results may not only help to further understand the H2S-induced CA released from adrenal chromaffin cells in the aspect of development, but also provide the insights for the clinical prevention and therapy for hypoxic stress-induced injury in neonates at birth

(46) Hsu CC, Lin RL, Lee LY, Lin YS. Hydrogen sulfide induces hypersensitivity of rat capsaicin-sensitive lung vagal neurons: role of TRPA1 receptors. Am J Physiol Regul Integr Comp Physiol 2013 Oct;305(7):R769-R779. Abstract: The sensitization of capsaicin-sensitive lung vagal (CSLV) afferents by inflammatory mediators is important in the development of airway hypersensitivity. Hydrogen sulfide (H2S) is an endogenous mediator inducing hyperalgesia through transient receptor potential ankyrin 1 (TRPA1) receptors located on nociceptors. We conducted this study to determine whether H2S elevates the sensitivity of rat CSLV afferents. In anesthetized, artificially ventilated rats, the inhalation of aerosolized sodium hydrosulfide (NaHS, a H2S donor) caused no significant changes in the baseline activity of CSLV afferents. However, the afferent responses to right atrial injection of capsaicin or phenylbiguanide and to lung inflation were all markedly potentiated after NaHS inhalation. By contrast, the inhalation of its vehicle or NaOH (with a similar pH to NaHS) failed to enhance the afferent responses. Additionally, the potentiating effect on the afferent responses was found in rats inhaling l-cysteine (a substrate of H2S synthase) that slowly releases H2S. The potentiating effect of NaHS on the sensitivity of CSLV afferents was completely blocked by pretreatment of HC-030031 (a TRPA1 receptor antagonist) but was unaffected by its vehicle. In isolated rat CSLV neurons, the perfusion of NaHS alone did not influence the intracellular Ca(2+) concentration but markedly potentiated the Ca(2+) transients evoked by capsaicin. The NaHS-caused effect was totally abolished by HC-030031 pretreatment. These results suggest that H2S induces a nonspecific sensitizing effect on CSLV fibers to both chemical and mechanical stimulation in rat lungs, which appears mediated through an action on the TRPA1 receptors expressed on the nerve endings of CSLV afferents

(47) Soldavini J, Kaunitz JD. Pathobiology and potential therapeutic value of intestinal short-chain fatty acids in gut inflammation and obesity. Dig Dis Sci 2013 Oct;58(10):2756-66. Abstract: BACKGROUND: The lumen of the gastrointestinal tract contains many substances produced from the breakdown of foodstuffs, from salivary, esophageal, intestinal, hepatic, and pancreatic secretions, and from sloughed cells present in the gastrointestinal lumen. Although these substances were traditionally regarded as waste products, there is increasing realization that many can be biologically active, either as signalling compounds or as nutrients. For example, proteins are broken down into amino acids, which are then sensed by nutrient receptors. The gut microbiome, which is at highest abundance in the ileocecum, has powerful metabolic activity, digesting and breaking down unabsorbed carbohydrates, proteins, and other ingested nutrients into

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phenols, amines, volatile organic compounds, methane, carbon dioxide, hydrogen, and hydrogen sulfide into volatile fatty acids, also called short-chain fatty acids (SCFAs). CONCLUSION: These latter substances are the topic of this review. In this review, we will briefly discuss recent advances in the understanding SCFA production, signalling, and absorption, followed by a detailed description and discussion of trials of SCFAs, probiotics, and prebiotics in the treatment of gastrointestinal disease, in particular ulcerative colitis (UC), pouchitis, short bowel syndrome, and obesity

(48) Hu S, Xu W, Miao X, Gao Y, Zhu L, Zhou Y, et al. Sensitization of sodium channels by cystathionine beta-synthetase activation in colon sensory neurons in adult rats with neonatal maternal deprivation. Exp Neurol 2013 Oct;248:275-85. Abstract: BACKGROUND: The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood and treatment remains difficult. We have previously reported that TTX-resistant (TTX-R) sodium channels in colon-specific dorsal root ganglion (DRG) neurons were sensitized and the expression of the endogenous hydrogen sulfide producing enzyme cystathionine beta-synthetase (CBS) was upregulated in a rat model of visceral hypersensitivity induced by neonatal maternal deprivation (NMD). However, the detailed molecular mechanism for activation of sodium channels remains unknown. This study was designed to examine roles for CBS-H(2)S signaling in sensitization of sodium channels in a previously validated rat model of IBS. METHODS: Neonatal male rats (postnatal days 2-15) were exposed to a 3 hour period of daily maternal separation with temperature maintained at ~33 degrees C. Colon-specific dorsal root ganglion (DRG) neurons were labeled with DiI and acutely dissociated for measuring excitability and sodium channel current under whole-cell patch clamp configurations. The expression of Na(V)1.8 was analyzed by Western blot and Immunofluorescence study. The endogenous H(2)S producing enzyme CBS antagonist was injected intraperitoneally. RESULTS: We showed that CBS was colocalized with Na(V)1.8 in colon-specific DRG neurons pre-labeled with DiI. Pretreatment of O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA), an inhibitor of CBS, significantly reduced expression of Na(V)1.8 in NMD rats. AOAA treatment also inhibited the TTX-R sodium current density, right-shifted the V(1)/(2) of activation curve, and reversed hyperexcitability of colon-specific DRG neurons in NMD rats. Conversely, addition of NaHS, a donor of H(2)S, greatly enhanced TTX-R sodium current density, left shifted the activation curve and enhanced excitability of colon DRG neurons in age-matched healthy rats. Furthermore, application of H-89, an inhibitor of protein kinase A, markedly attenuated the potentiation of TTX-R sodium current density by NaHS. CONCLUSION: These data suggest that sensitization of sodium channels of colon DRG neurons in NMD rats is most likely mediated by CBS-H(2)S signaling, thus identifying a potential target for treatment for chronic visceral pain in patients with IBS

(49) Velasco-Xolalpa ME, Barragan-Iglesias P, Roa-Coria JE, Godinez-Chaparro B, Flores-Murrieta FJ, Torres-Lopez JE, et al. Role of hydrogen sulfide in the pain processing of non-diabetic and diabetic rats. Neuroscience 2013 Oct 10;250:786-97. Abstract: Hydrogen sulfide (H2S) is a gasotransmitter endogenously generated from the metabolism of L-cysteine by action of two main enzymes called cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE). This gas has been involved in the pain processing and insulin resistance produced during diabetes development. However, there is no evidence about its participation in the peripheral neuropathy induced by this metabolic disorder. Experimental diabetes was induced by streptozotocin (50mg/kg, i.p.) in female Wistar rats. Streptozotocin injection increased formalin-evoked flinching in diabetic rats as compared to non-diabetic rats after 2 weeks. Peripheral administration of NaHS (an exogenous donor of H2S) and L-cysteine (an endogenous donor of H2S) dose-dependently increased flinching behavior in diabetic and non-diabetic rats. Contrariwise, hydroxylamine (HA, a CBS inhibitor) and DL-propargylglycine (PPG, a CSE inhibitor) decreased formalin-induced nociceptive behavior in both experimental groups. In addition, an ineffective dose of HA and PPG partially prevented the

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L-cysteine-induced hyperalgesia in diabetic and non-diabetic rats. Interestingly, HA and PPG were three order of magnitude more potent in diabetic rats respect to non-diabetic rats, whereas NaHS was ten times more potent in the streptozotocin-diabetic group. Nine to 11 weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. On this condition, subcutaneous administration of PPG or HA reduced tactile allodynia in diabetic rats. Paradoxically, H2S levels were decreased in nerve sciatic, dorsal root ganglion and spinal cord, but not paw nor blood plasma, during diabetes-associated peripheral neuropathy development. Collectively, results suggest that H2S synthesized by CBS and CSE participate in formalin-induced nociception in diabetic and non-diabetic rats, as well as; in tactile allodynia in streptozotocin-injected rats. In addition, data seems to indicate that diabetic rats are more sensible to H2S-induced hyperalgesia than normoglycemic rats

(50) Pan LL, Liu XH, Shen YQ, Wang NZ, Xu J, Wu D, et al. Inhibition of NADPH oxidase 4-related signaling by sodium hydrosulfide attenuates myocardial fibrotic response. Int J Cardiol 2013 Oct 9;168(4):3770-8. Abstract: BACKGROUND: Myocardial fibrosis plays a pivotal role in the development of heart failure. Hydrogen sulfide (H2S) is an endogenous gasotransmitter with potent cardioprotective properties; however, whether H2S is involved in fibrotic process remains unknown. This study aimed to explore the role of H2S in the process of cardiac fibrosis and the underlying mechanisms. METHODS: Myocardial infarction (MI) was established in rats by ligation of coronary artery. Activation of rat neonatal cardiac fibroblasts was induced by angiotensin II (Ang II). Fibrotic responses in ischemic myocardium and in Ang II-stimulated cardiac fibroblasts were examined. The effects of sodium hydrosulfide (NaHS, an exogenous H2S donor) on NADPH oxidase 4 (Nox4), reactive oxygen species (ROS) production, extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, heme oxygenase-1 (HO-1), and cystathionine gamma-lyase (CSE) were tested to elucidate the protective mechanisms of H2S on fibrotic response. RESULTS: NaHS treatment inhibited Ang II-induced expression of alpha-smooth muscle actin, connective tissue growth factor (CTGF), and type I collagen and upregulated expression of HO-1 in cardiac fibroblasts. Ang II-induced Nox4 expression in cardiac fibroblasts was quenched by NaHS and this was associated with a decreased ROS production and reduced ERK1/2 phosphorylation and CTGF expression. In vivo studies using MI model indicated that NaHS administration attenuated Nox4 expression and fibrotic response. Moreover, NaHS therapy also prevented cardiac inflammatory response accompanied by increases in HO-1 and CSE expression. CONCLUSIONS: The beneficial effect of H2S, at least in part, was associated with a decrease of Nox4-ROS-ERK1/2 signaling axis and an increase in HO-1 expression

(51) Wang J, Lin W, Li W. Three-channel fluorescent sensing via organic white light-emitting dyes for detection of hydrogen sulfide in living cells. Biomaterials 2013 Oct;34(30):7429-36. Abstract: To demonstrate the feasibility of development of three-channel based fluorescent sensors based on organic white light-emitting dyes, in this work, for proof-of-principle, we initially judiciously designed an organic white light-emitting dye, which was further used as a robust platform to engineer a new fluorescent sensor for monitoring H2S with turn-on fluorescence signals in blue, green, and red emission channels in both solution and living cells. This work should open a new avenue for design of three- and multiple-channel based fluorescent sensors for various analytes

(52) Zeng T, Zhang CL, Song FY, Zhao XL, Yu LH, Zhu ZP, et al. The activation of HO-1/Nrf-2 contributes to the protective effects of diallyl disulfide (DADS) against ethanol-induced oxidative stress. Biochim Biophys Acta 2013 Oct;1830(10):4848-59. Abstract: BACKGROUND: Diallyl disulfide (DADS) is a garlic-derived organosulfur compound. The current study is designed to evaluate the protective effects of DADS against ethanol-induced oxidative stress, and to explore the underlying mechanisms by

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examining the HO-1/Nrf-2 pathway. METHODS: We investigated whether or not DADS could activate the HO-1 in normal human liver cell LO2, and then evaluated the protective effects of DADS against ethanol-induced damage in LO2 cells and in acute ethanol-intoxicated mice. The biochemical parameters were measured using commercial kits. HO-1 mRNA level was determined by RT-PCR. Histopathology and immunofluorescence assay were performed with routine methods. Protein levels were measured by western blot. RESULTS: DADS significantly increased the mRNA and protein levels of HO-1, stimulated the nuclear translocation of Nrf-2 and increased the phosphorylation of MAPK in LO2 cells. The nuclear translocation of Nrf-2 was abrogated by MAPK inhibitors. DADS significantly suppressed ethanol-induced elevation of lactate dehydrogenase (LDH) and aspartate transaminase (AST) activities, decrease of glutathione (GSH) level, increase of malondialdehyde (MDA) levels, and apoptosis of LO2 cells, which were all blocked by ZnPPIX. In mice, DADS effectively suppressed acute ethanol-induced elevation of aminotransferase activities, and improved liver histopathological changes, which might be associated with HO-1 activation. CONCLUSION: These results demonstrate that DADS could induce the activation of HO-1/Nrf-2 pathway, which may contribute to the protective effects of DADS against ethanol-induced liver injury. GENERAL SIGNIFICANCE: DADS may be beneficial for the prevention and treatment of ALD due to significant activation of HO-1/Nrf-2 pathway

(53) Camarillo MK, Stringfellow WT, Spier CL, Hanlon JS, Domen JK. Impact of co-digestion on existing salt and nutrient mass balances for a full-scale dairy energy project. J Environ Manage 2013 Oct 15;128:233-42. Abstract: Anaerobic digestion of manure and other agricultural waste streams with subsequent energy production can result in more sustainable dairy operations; however, importation of digester feedstocks onto dairy farms alters previously established carbon, nutrient, and salinity mass balances. Salt and nutrient mass balance must be maintained to avoid groundwater contamination and salination. To better understand salt and nutrient contributions of imported methane-producing substrates, a mass balance for a full-scale dairy biomass energy project was developed for solids, carbon, nitrogen, sulfur, phosphorus, chloride, and potassium. Digester feedstocks, consisting of thickened manure flush-water slurry, screened manure solids, sudan grass silage, and feed-waste, were tracked separately in the mass balance. The error in mass balance closure for most elements was less than 5%. Manure contributed 69.2% of influent dry matter while contributing 77.7% of nitrogen, 90.9% of sulfur, and 73.4% of phosphorus. Sudan grass silage contributed high quantities of chloride and potassium, 33.3% and 43.4%, respectively, relative to the dry matter contribution of 22.3%. Five potential off-site co-digestates (egg waste, grape pomace, milk waste, pasta waste, whey wastewater) were evaluated for anaerobic digestion based on salt and nutrient content in addition to bio-methane potential. Egg waste and wine grape pomace appeared the most promising co-digestates due to their high methane potentials relative to bulk volume. Increasing power production from the current rate of 369 kW to the design value of 710 kW would require co-digestion with either 26800 L d(-1) egg waste or 60900 kg d(-1) grape pomace. However, importation of egg waste would more than double nitrogen loading, resulting in an increase of 172% above the baseline while co-digestion with grape pomace would increase potassium by 279%. Careful selection of imported co-digestates and management of digester effluent is required to manage salt and nutrient mass loadings and reduce groundwater impacts

(54) Du Y, Liu G, Yan Y, Huang D, Luo W, Martinkova M, et al. Conversion of a heme-based oxygen sensor to a heme oxygenase by hydrogen sulfide: effects of mutations in the heme distal side of a heme-based oxygen sensor phosphodiesterase (Ec DOS). Biometals 2013 Oct;26(5):839-52. Abstract: The heme-based oxygen-sensor phosphodiesterase from Escherichia coli (Ec DOS), is composed of an N-terminal heme-bound oxygen sensing domain and a C-terminal catalytic domain. Oxygen (O2) binding to the heme Fe(II) complex in Ec DOS

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substantially enhances catalysis. Addition of hydrogen sulfide (H2S) to the heme Fe(III) complex in Ec DOS also remarkably stimulates catalysis in part due to the heme Fe(III)-SH and heme Fe(II)-O2 complexes formed by H2S. In this study, we examined the roles of the heme distal amino acids, M95 (the axial ligand of the heme Fe(II) complex) and R97 (the O2 binding site in the heme Fe(II)-O2 complex) of the isolated heme-binding domain of Ec DOS (Ec DOS-PAS) in the binding of H2S under aerobic conditions. Interestingly, R97A and R97I mutant proteins formed an oxygen-incorporated modified heme, verdoheme, following addition of H2S combined with H2O2 generated by the reactions. Time-dependent mass spectroscopic data corroborated the findings. In contrast, H2S did not interact with the heme Fe(III) complex of M95H and R97E mutants. Thus, M95 and/or R97 on the heme distal side in Ec DOS-PAS significantly contribute to the interaction of H2S with the Fe(III) heme complex and also to the modification of the heme Fe(III) complex with reactive oxygen species. Importantly, mutations of the O2 binding site of the heme protein converted its function from oxygen sensor to that of a heme oxygenase. This study establishes the novel role of H2S in modifying the heme iron complex to form verdoheme with the aid of reactive oxygen species

(55) Manna P, Jain SK. L-cysteine and hydrogen sulfide increase PIP3 and AMPK/PPARgamma expression and decrease ROS and vascular inflammation markers in high glucose treated human U937 monocytes. J Cell Biochem 2013 Oct;114(10):2334-45. Abstract: Diabetic patients have lower blood levels of L-cysteine (LC) and hydrogen sulfide (H2 S) and a higher incidence of vascular inflammation. This study examined whether impaired LC or H2S levels affect vascular inflammation markers in diabetes. Human U937 monocytic cells were treated with high-glucose (HG, 25 mM, 20 h) in the presence or absence of LC (100, 500, or 1,000 microM, an endogenous precursor of H2 S) or Na2S (5 or 25 microM, an exogenous source of H2S). Both LC and Na2 S supplementation decreased intracellular ROS production and increased cellular PIP3 (phosphatidylinositol-3,4,5-trisphosphate) in HG-exposed cells. The effect of LC on PIP3 was prevented by propargylglycine, an inhibitor of cystathionine-gamma-lyase (CSE) that catalyzes H2S formation from LC. Signal silencing studies with CSE siRNA also showed the inhibition of H2S formation and PIP3 upregulation in LC-supplemented CSE knockdown cells exposed to HG. This demonstrates that H2S plays a role in mediating the effect of LC on increased PIP3. Using the PI3K specific inhibitor LY294002, this study demonstrated that PI3K activation mediates the effect of LC and Na2S on PIP3 upregulation. Results showed that supplementation with LC and Na2S reduced NF-kappaB phosphorylation and the secretion of TNF-alpha, MCP-1, IL-8, IL-1beta, and IP-10. Treatment with LC (500 microM), Na2S (25 microM), and PIP3 (5 nM) increased the AMPK phosphorylation and PPARgamma expression in cells exposed to HG. This study reports for the first time a novel molecular mechanism by which Na2S or LC supplementation can lower oxidative stress and various markers of vascular inflammation in diabetes

(56) Yang J, Zhao J, Du S, Liu D, Fu C, Li X, et al. Postural orthostatic tachycardia syndrome with increased erythrocytic hydrogen sulfide and response to midodrine hydrochloride. J Pediatr 2013 Oct;163(4):1169-73. Abstract: OBJECTIVES: To evaluate the use of erythrocytic hydrogen sulfide (H2S) in predicting the therapeutic efficacy of midodrine hydrochloride for children with postural orthostatic tachycardia syndrome (POTS). STUDY DESIGN: Fifty-five children were included in this study, involving 28 children with POTS (POTS group) and 27 healthy children (control group). Children in the POTS group received midodrine hydrochloride treatment. Erythrocytic H2S production was measured; a receiver operating characteristic curve was used to assess if erythrocytic H2S could predict the therapeutic response to midodrine hydrochloride treatment. RESULTS: H2S production from erythrocytes was significantly higher in the POTS group than in the control group (P < .01). H2S production was also significantly higher in responders to midodrine hydrochloride than in

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non-responders (P < .05). The change in symptom score and baseline erythrocytic H2S production had a positive linear relationship (P < .01). There was also a positive correlation with the change in heart rate (P < .05). The receiver operating characteristic curve showed an area under curve value of 0.813. Erythrocytic H2S production yielded a sensitivity of 78.9% and a specificity of 77.8% in predicting the efficacy of midodrine hydrochloride therapy for children with POTS. CONCLUSION: Erythrocytic H2S could serve as a useful predictor of therapeutic response to midodrine hydrochloride in children with POTS

(57) Swaminathan K, Kumar SM, Clemens DL, Dey A. Inhibition of CYP2E1 leads to decreased advanced glycated end product formation in high glucose treated ADH and CYP2E1 over-expressing VL-17A cells. Biochim Biophys Acta 2013 Oct;1830(10):4407-16. Abstract: BACKGROUND: In recent years, there has been a growing interest to explore the association between liver injury and diabetes. Advanced glycated end product (AGE) formation which characterizes diabetic complications is formed through hyperglycemia mediated oxidative stress and is itself a source for ROS. Further, in VL-17A cells over-expressing ADH and CYP2E1, greatly increased oxidative stress and decreased viability have been observed with high glucose exposure. METHODS: In VL-17A cells treated with high glucose and pretreated with the different inhibitors of ADH and CYP2E1, the changes in cell viability, oxidative stress parameters and formation of AGE, were studied. RESULTS: Inhibition of CYP2E1 with 10muM diallyl sulfide most effectively led to decreases in the oxidative stress and toxicity as compared with ADH inhibition with 2mM pyrazole or the combined inhibition of ADH and CYP2E1 with 5mM 4-methyl pyrazole. AGE formation was decreased in VL-17A cells when compared with HepG2 cells devoid of the enzymes. Further, AGE formation was decreased to the greatest extent with the inhibitor for CYP2E1 suggesting that high glucose inducible CYP2E1 and the consequent ROS aid AGE formation. CONCLUSIONS: Thus, CYP2E1 plays a pivotal role in the high glucose induced oxidative stress and toxicity in liver cells as observed through direct evidences obtained utilizing the different inhibitors for ADH and CYP2E1. GENERAL SIGNIFICANCE: The study demonstrates the role of CYP2E1 mediated oxidative stress in aggravating hyperglycemic insult and suggests that CYP2E1 may be a vital component of hyperglycemia mediated oxidative injury in liver

(58) Jiang X, Huang Y, Lin W, Gao D, Fei Z. Protective effects of hydrogen sulfide in a rat model of traumatic brain injury via activation of mitochondrial adenosine triphosphate-sensitive potassium channels and reduction of oxidative stress. J Surg Res 2013 Oct;184(2):e27-e35. Abstract: BACKGROUND: Hydrogen sulfide (H2S) is considered an important neuromodulator in the central nervous system. We designed the present study to investigate the effects of exogenous H2S in a rat model of traumatic brain injury (TBI) and the mechanism(s) that underlie this effect. METHODS: We induced a TBI model by controlled cortical impact injury. We intraperitoneally administered sodium hydrosulfide (NaHS) (an H2S donor) (3 mg/kg) or vehicle alone at 5 min after a TBI operation. We then measured the H2S level, brain edema, blood-brain barrier integrity, neurologic dysfunction, and lesion volume in all animals. Moreover, we assessed the role of mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP)channels by intraperitoneal injection of the selective blocker 5-hydroxydecanoate before NaHS administration. In addition, we detected the levels of oxidative products and the activities of antioxidant enzymes in brain tissue. RESULTS: Administration of NaHS significantly increased the H2S level of brain tissue in TBI-challenged rats. The TBI-challenged animals exhibited significant brain injuries, characterized by an increase of blood-brain barrier permeability, brain edema, and lesion volume, as well as neurologic dysfunction, which were significantly ameliorated by NaHS treatment. However, the protective effects of H2S in TBI could be abolished by the mitoK(ATP) channel blocker 5-hydroxydecanoate. Moreover, we found that NaHS treatment increased endogenous

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antioxidant enzymatic activities and decreased oxidative product levels in brain tissue of TBI-challenged rats. CONCLUSIONS: Exogenous H2S administered at an appropriate dose can exert a protective effect against TBI via activation of mitoK(ATP) channels and reduction of oxidative stress

(59) Zhu X, Tang Z, Cong B, Du J, Wang C, Wang L, et al. Estrogens increase cystathionine-gamma-lyase expression and decrease inflammation and oxidative stress in the myocardium of ovariectomized rats. Menopause 2013 Oct;20(10):1084-91. Abstract: OBJECTIVE: Hydrogen sulfide (H2S), generated in the myocardium predominantly via cystathionine-gamma-lyase (CSE), is cardioprotective. The objectives of the present study were to investigate the effects of estrogens on CSE expression and H2S generation in the myocardium and to examine whether serum 17beta-estradiol (E2) level is associated with CSE activity and H2S generation and whether H2S or E2 level is associated with proinflammatory cytokines and oxidative stress status. METHODS: Ovariectomized Sprague-Dawley rats received subcutaneous E2 (30 mug/kg/d) or vehicle for 12 weeks. At the end of the 12-week treatment, CSE expression, H2S generation, reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity, interleukin (IL)-6 concentration, and tumor necrosis factor-alpha (TNF-alpha) concentration in the left ventricle were determined. RESULTS: E2 increased CSE expression and H2S generation in the myocardium of ovariectomized rats. H2S production rate and serum E2 were positively correlated. E2 increased GSH/GSSG ratio, T-AOC, CAT, and SOD activity but decreased IL-6 and TNF-alpha levels. Serum E2 level was positively correlated with GSH/GSSG ratio, T-AOC, CAT, and SOD activity, and inversely correlated with IL-6 and TNF-alpha levels. H2S generation rate was positively correlated with T-AOC and GSH/GSSG ratio, and inversely correlated with IL-6 and TNF-alpha levels. CONCLUSIONS: E2 increases CSE expression and endogenous H2S generation in the myocardium. The effects of E2 are associated with decreased oxidative stress and inflammatory status. Our data suggest that estrogens might exert cardioprotective effects through up-regulation of CSE expression and H2S generation

(60) Chakraborty S, Jackson TL, Ahmed M, Thiemens MH. Sulfur isotopic fractionation in vacuum UV photodissociation of hydrogen sulfide and its potential relevance to meteorite analysis. Proc Natl Acad Sci U S A 2013 Oct 29;110(44):17650-5. Abstract: Select meteoritic classes possess mass-independent sulfur isotopic compositions in sulfide and organic phases. Photochemistry in the solar nebula has been attributed as a source of these anomalies. Hydrogen sulfide (H2S) is the most abundant gas-phase species in the solar nebula, and hence, photodissociation of H2S by solar vacuum UV (VUV) photons (especially by Lyman-alpha radiation) is a relevant process. Because of experimental difficulties associated with accessing VUV radiation, there is a paucity of data and a lack of theoretical basis to test the hypothesis of a photochemical origin of mass-independent sulfur. Here, we present multiisotopic measurements of elemental sulfur produced during the VUV photolysis of H2S. Mass-independent sulfur isotopic compositions are observed. The observed isotopic fractionation patterns are wavelength-dependent. VUV photodissociation of H2S takes place through several predissociative channels, and the measured mass-independent fractionation is most likely a manifestation of these processes. Meteorite sulfur data are discussed in light of the present experiments, and suggestions are made to guide future experiments and models

(61) Farquhar J, Cliff J, Zerkle AL, Kamyshny A, Poulton SW, Claire M, et al. Pathways for Neoarchean pyrite formation constrained by mass-independent sulfur isotopes. Proc Natl Acad Sci U S A 2013 Oct 29;110(44):17638-43. Abstract: It is generally thought that the sulfate reduction metabolism is ancient and would have been established well before the Neoarchean. It is puzzling, therefore, that the sulfur isotope record of the Neoarchean is characterized by a signal of atmospheric

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mass-independent chemistry rather than a strong overprint by sulfate reducers. Here, we present a study of the four sulfur isotopes obtained using secondary ion MS that seeks to reconcile a number of features seen in the Neoarchean sulfur isotope record. We suggest that Neoarchean ocean basins had two coexisting, significantly sized sulfur pools and that the pathways forming pyrite precursors played an important role in establishing how the isotopic characteristics of each of these pools was transferred to the sedimentary rock record. One of these pools is suggested to be a soluble (sulfate) pool, and the other pool (atmospherically derived elemental sulfur) is suggested to be largely insoluble and unreactive until it reacts with hydrogen sulfide. We suggest that the relative contributions of these pools to the formation of pyrite depend on both the accumulation of the insoluble pool and the rate of sulfide production in the pyrite-forming environments. We also suggest that the existence of a significant nonsulfate pool of reactive sulfur has masked isotopic evidence for the widespread activity of sulfate reducers in the rock record

(62) Roman HB, Hirschberger LL, Krijt J, Valli A, Kozich V, Stipanuk MH. The Cysteine Dioxgenase Knockout Mouse: Altered Cysteine Metabolism in Nonhepatic Tissues Leads to Excess H2S/HS(-) Production and Evidence of Pancreatic and Lung Toxicity. Antioxid Redox Signal 2013 Oct 20;19(12):1321-36. Abstract: Abstract Aims: To define the consequences of loss of cysteine dioxygenase (CDO) on cysteine metabolism at the tissue level, we determined levels of relevant metabolites and enzymes and evidence of H2S/HS(-) (gaseous hydrogen sulfide and its conjugate base) toxicity in liver, pancreas, kidney, and lung of CDO(-/-) mice that were fed either a taurine-free or taurine-supplemented diet. Results: CDO(-/-) mice had low tissue and serum taurine and hypotaurine levels and high tissue levels of cysteine, consistent with the loss of CDO. CDO(-/-) mice had elevated urinary excretion of thiosulfate, high tissue and serum cystathionine and lanthionine levels, and evidence of inhibition and destabilization of cytochrome c oxidase, which is consistent with excess production of H2S/HS(-). Accumulation of cystathionine and lanthionine appeared to result from cystathionine beta-synthase (CBS)-mediated cysteine desulfhydration. Very high levels of hypotaurine in pancreas of wild-type mice and very high levels of cystathionine and lanthionine in pancreas of CDO(-/-) mice were observed, suggesting a unique cysteine metabolism in the pancreas. Innovation: The CDO(-/-) mouse model provides new insights into tissue-specific cysteine metabolism, particularly the role of pancreas in metabolism of excess cysteine by CBS-catalyzed reactions, and will be a useful model for studying the effects of excess endogenous production of H2S/HS(-). Conclusion: The CDO(-/-) mouse clearly demonstrates that H2S/HS(-) production in tissues can exceed the capacity of the animal to oxidize sulfide to sulfate and demonstrates that pancreas and lung are more susceptible to toxicity from endogenous H2S/HS(-)production than are liver and kidney. Antioxid. Redox Signal. 19, 1321-1336

(63) Eaktasang N, Min HS, Kang C, Kim HS. Control of malodorous hydrogen sulfide compounds using microbial fuel cell. Bioprocess Biosyst Eng 2013 Oct;36(10):1417-25. Abstract: In this study, a microbial fuel cell (MFC) was used to control malodorous hydrogen sulfide compounds generated from domestic wastewaters. The electricity production demonstrated a distinct pattern of a two-step increase during 170 h of system run: the first maximum current density was 118.6 +/- 7.2 mA m(-)(2) followed by a rebound of current density increase, reaching the second maximum of 176.8 +/- 9.4 mA m(-)(2). The behaviors of the redox potential and the sulfate level in the anode compartment indicated that the microbial production of hydrogen sulfide compounds was suppressed in the first stage, and the hydrogen sulfide compounds generated from the system were removed effectively as a result of their electrochemical oxidation, which contributed to the additional electricity production in the second stage. This was also directly supported by sulfur deposits formed on the anode surface, which was confirmed by analyses on those solids using a scanning electron microscope equipped with energy dispersive X-ray spectroscopy as well as an elemental analyzer. To this end, the overall reduction efficiencies for HS(-) and H(2)S(g) were as high as 67.5 and 96.4 %,

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respectively. The correlations among current density, redox potential, and sulfate level supported the idea that the electricity signal generated in the MFC can be utilized as a potential indicator of malodor control for the domestic wastewater system

(64) Fujii S, Akaike T. Redox Signaling by 8-Nitro-cyclic Guanosine Monophosphate: Nitric Oxide- and Reactive Oxygen Species-Derived Electrophilic Messenger. Antioxid Redox Signal 2013 Oct 10;19(11):1236-46. Abstract: Abstract Significance: Emerging evidence has revealed that nitric oxide (NO)- and reactive oxygen species (ROS)-derived electrophiles formed in cells mediate signal transduction for responses to oxidative stress. Recent Advances: The cyclic nucleotide with a nitrated guanine moiety-8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP)-first identified in 2007 as a second messenger for NO and ROS-has certain unique properties that its parental cGMP lacks. For example, it can react with particular protein Cys thiols because of its electrophilicity and can cause unique post-translational modifications of redox-sensor proteins such as Keap1 and H-Ras. Critical Issues: Site-specific S-guanylation of Keap1 at Cys434 induced NO- and ROS-mediated adaptive responses to oxidative stress. H-Ras Cys184 S-guanylation was recently found to be involved in activation of mitogen-activated protein kinase cascades as manifested by cellular senescence and heart failure in mouse cardiac hypertrophy models. The latest finding related to the concept of electrophile-based redox signaling is a potent regulatory function of endogenously produced hydrogen sulfide for redox signaling via 8-nitro-cGMP. Future Directions: Electrophile modification of 8-nitro-cGMP, as a second messenger for NO and ROS, by hydrogen sulfide (i.e., electrophile sulfhydration) can most likely effect physiological regulation of cellular redox signaling. Continued investigation of the precise function of cellular hydrogen sulfide that may control electrophile-dependent redox cellular signaling, most typically via 8-nitro-cGMP formation, may provide novel insights into the molecular mechanisms of oxidative stress responses, oxidative stress-related pathology and disease control, and development of therapeutics for various diseases. Antioxid. Redox Signal. 19, 1236-1246

(65) Tan T, Liu C, Liu L, Zhang K, Zou S, Hong J, et al. Hydrogen sulfide formation as well as ethanol production in different media by cysND- and/or cysIJ-inactivated mutant strains of Zymomonas mobilis ZM4. Bioprocess Biosyst Eng 2013 Oct;36(10):1363-73. Abstract: Many bacteria reduce inorganic sulfate to sulfide to satisfy their need for sulfur, one of the most important elements for biological life. But little is known about the metabolic pathways involving hydrogen sulfide (H(2)S) in mesophilic bacteria. By genomic sequence analysis, a complete set of genes for the assimilatory sulfate reduction pathway has been identified in the ethanologen Zymomonas mobilis. In this study, the first ATP sulfurylase- and final sulfite reductase-encoding genes cysND and cysIJ, respectively, in the putative pathway from sulfate to sulfite in Z. mobilis ZM4 was singly or doubly inactivated by homologous recombination and a site-specific FLP-FRT recombination. The resultant mutants, cysND, cysIJ and cysND-catcysIJ, were unable to produce detectable H(2)S in glucose or sucrose-containing rich medium and sweet sorghum juice, in which the wild-type ZM4 produced detectable H(2)S. While adding sulfite (SO(3)(2)(-)) into media impaired the growth of the mutants and ZM4 to varying degrees, the sulfite restored the H(2)S formation in the cysND in the above media, but not in the cysIJ and cysND-catcysIJ mutants. Although it seemed that the inactivation of cysND and cysIJ did not exert a significant negative effect on the cell growth at least in glucose or sucrose medium, the ethanol production of all mutants was inferior to that of ZM4 in sucrose medium and sweet sorghum juice. In addition, adding L-cysteine to glucose-containing rich media restored H(2)S formation of all mutants, indicating the existence of another pathway for producing H(2)S in Z. mobilis. All these results would help to further elucidate the metabolic pathways involving H(2)S in Z. mobilis and exploit the biotechnological applications of this industrially important bacterium

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(66) Cazzoli G, Puzzarini C. Sub-Doppler Resolution in the THz Frequency Domain: 1 kHz Accuracy at 1 THz by Exploiting the Lamb-Dip Technique. J Phys Chem A 2013 Oct 4. Abstract: We report the first thorough investigation of the Lamb-dip effect in the THz region, which in turn allows sub-Doppler resolution to be exploited in this frequency region. It is demonstrated that an accuracy of 1 kHz, or even better (i.e., an accuracy better than 1 part in 109), and a frequency resolution of 50 kHz (i.e., a resolution better than 5 parts in 108) can be routinely obtained in our laboratory. It has also shown that Lamb-dip spectra can be recorded using either a Fabry-Perot interferometric cell or a free-space cell. Hydrogen sulfide (H2S), sulfur dioxide (SO2), deuterated water (D2O), and methyl fluoride (CH3F) have been selected as examples for demonstrating the accuracy and resolution reachable, thus providing the most accurate frequency values in the 1.0-1.2 THz frequency range for these molecules. Measurements for SO2 have also been employed in a global fit, thus improving its spectroscopic parameters for the vibrational ground state

(67) Tabase RK, Liu D, Feilberg A. Chemisorption of hydrogen sulphide and methanethiol by light expanded clay aggregates (Leca). Chemosphere 2013 Oct;93(7):1345-51. Abstract: Removal of volatile sulphur compounds from livestock waste air by biological air filtration may be enhanced by application of packing materials with reactive properties. In this study, light expanded clay aggregates (Leca(R)) was tested with respect to sorption and potential chemical degradation of H2S, Methanethiol (MT) and Dimethyl sulphide (DMS). Leca was selected due to its content of minerals, including iron, and due to its high specific surface area. The performance of Leca was evaluated based on breakthrough curves and by comparing the difference between the inlet and outlet gas concentrations. Whereas DMS did not appear to be removed by Leca, both H2S and MT were removed with variable efficiency depending on the specific conditions. Dimethyl disulphide (DMDS) and dimethyl trisulphide (DMTS) were demonstrated to be produced during the degradation process in relatively high yields. A comparison between ambient air and nitrogen gas conditions showed that the chemisorption of H2S and MT did not necessarily need oxygen to be present. X-ray analysis of Leca showed an abundance of Fe2O3. It is therefore hypothesized that Fe2O3 in Leca can remove H2S and MT by chemisorption. Both air velocity and moisture content clearly affected the capacity of Leca for removal of H2S and MT. Lower removal is seen at higher air velocities, whereas higher moisture content enhances removal. However, chemisorption of MT by Leca appears to be limited above a threshold moisture level. Potential reaction mechanisms are discussed in relation to the observed effects. The results implicate that Leca can be used as a filter material with reactive properties provided that moisture content is controlled and that an adequate air velocity is used

(68) Lim CS, Das SK, Yang SY, Kim ES, Chun HJ, Cho BR. Quantitative estimation of the total sulfide concentration in live tissues by two-photon microscopy. Anal Chem 2013 Oct 1;85(19):9288-95. Abstract: Hydrogen sulfide (H2S) is a newly recognized transmitter, which protects various organs from oxidative stress. In this article, we report a ratiometric two-photon probe, TFCA, which can be excited by 750 nm femtosecond pulses, shows a 110-fold increase in the intensity ratio upon reaction with HS(-) and high selectivity for HS(-) and can visualize the total sulfide ([H2S] + [HS(-)]) distribution in live tissue by two-photon microscopy (TPM). We also developed a kinetic method to quantitatively estimate the total sulfide concentration ([H2S] + [HS(-)]) in live tissues. The kinetic method allowed us to measure the observed rate constants (kobs) for the sulfide-induced deazidation reaction of TFCA in live cells and tissues using TPM. The total sulfide concentration was calculated by using kobs = k2[HS(-)], with the k2 value determined in HEPES/EtOH (1/1, pH = 7.2), and [H2S]/[HS(-)] = [H(+)]/Ka. The total sulfide concentration was found to be nearly zero in HeLa cells and 4-7 muM in rat colon tissues

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(69) Zhang CY, Li XH, Zhang T, Fu J, Cui XD. Hydrogen sulfide suppresses the expression of MMP-8, MMP-13, and TIMP-1 in left ventricles of rats with cardiac volume overload. Acta Pharmacol Sin 2013 Oct 7;34(10):1301-9. Abstract: Aim:To study the effects of hydrogen sulfide (H2S) on the left ventricular expression of MMP-8, MMP-13, and TIMP-1 in a rat model of congenital heart disease.Methods:Male SD rats underwent abdominal aorta-inferior vena cava shunt operation. H2S donor NaHS (56 mumol.kg(-1).d(-1), ip) was injected from the next day for 8 weeks. At 8 weeks, the hemodynamic parameters, including the left ventricular systolic pressure (LVSP), the left ventricular peak rate of contraction and relaxation (LV+/-dp/dtmax) and the left ventricular end diastolic pressure (LVEDP) were measured. The left ventricular tissues were dissected out, and hydroxyproline and collagen I contents were detected with ELISA. The expression of MMP-8, MMP-13, and a tissue inhibitor of metalloproteinase-1 (TIMP-1) in the tissues was measured using real-time PCR, Western blotting, and immunohistochemistry, respectively.Results:The shunt operation markedly reduced LVSP and LV+/-dp/dtmax, increased LVEDP, hydroxyproline and collagen I contents, as well as the mRNA and protein levels of MMP-8, MMP-13, and TIMP-1 in the left ventricles. Chronic treatment of the shunt operation rats with NaHS effectively prevented the abnormalities in the hemodynamic parameters, hydroxyproline and collagen I contents, and the mRNA and protein levels of MMP-13 and TIMP-1 in the left ventricles. NaHS also prevented the increase of MMP-8 protein expression, but did not affect the increase of mRNA level of MMP-8 in the shunt operation rats.Conclusion:H2S suppresses protein and mRNA expression of MMP-8, MMP-13, and TIMP-1 in rats with cardiac volume overload, which may be contributed to the amelioration of ventricular structural remodeling and cardiac function

(70) Shi H, Ye T, Chan Z. Exogenous application of hydrogen sulfide donor sodium hydrosulfide enhanced multiple abiotic stress tolerance in bermudagrass (Cynodon dactylon (L). Pers.). Plant Physiol Biochem 2013 Oct;71:226-34. Abstract: As a gaseous molecule, hydrogen sulfide (H2S) has been recently found to be involved in plant responses to multiple abiotic stress. In this study, salt (150 and 300 mM NaCl), osmotic (15% and 30% PEG6000) and cold (4 degrees C) stress treatments induced accumulation of endogenous H2S level, indicating that H2S might play a role in bermudagrass responses to salt, osmotic and cold stresses. Exogenous application of H2S donor (sodium hydrosulfide, NaHS) conferred improved salt, osmotic and freezing stress tolerances in bermudagrass, which were evidenced by decreased electrolyte leakage and increased survival rate under stress conditions. Additionally, NaHS treatment alleviated the reactive oxygen species (ROS) burst and cell damage induced by abiotic stress, via modulating metabolisms of several antioxidant enzymes [catalase (CAT), peroxidase (POD) and GR (glutathione reductase)] and non-enzymatic glutathione antioxidant pool and redox state. Moreover, exogenous NaHS treatment led to accumulation of osmolytes (proline, sucrose and soluble total sugars) in stressed bermudagrass plants. Taken together, all these data indicated the protective roles of H2S in bermudagrass responses to salt, osmotic and freezing stresses, via activation of the antioxidant response and osmolyte accumulation. These findings might be applicable to grass and crop engineering to improve abiotic stress tolerance

(71) Chen X, Wu S, Han J, Han S. Rhodamine-propargylic esters for detection of mitochondrial hydrogen sulfide in living cells. Bioorg Med Chem Lett 2013 Oct 1;23(19):5295-9. Abstract: Flow cytometric detection of mitochondrial H2S was achieved with propargylic esters of rhodamine B which selectively react with H2S via cationic rhodamine-moiety directed thiolysis of the propargylic esters to give nonfluorescent rhodamine thio-spirolactone

(72) Iha K, Suzuki N, Yoneda M, Takeshita T, Hirofuji T. Effect of mouth cleaning with hinokitiol-containing gel on oral malodor: a randomized, open-label pilot study. Oral Surg

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Oral Med Oral Pathol Oral Radiol 2013 Oct;116(4):433-9. Abstract: AIM: The aim of the study was to evaluate the effect of mouth cleaning with hinokitiol-containing gel on oral malodor. METHODS: An open-label, randomized, controlled trial was conducted to assess oral malodor and clinical parameters related to oral malodor before and after mouth cleaning with hinokitiol-containing gel (n = 9) or with gel not including hinokitiol (n = 9). Mouth cleaning included the teeth, gingiva, and tongue and was carried out 3 times per day for 4 weeks. RESULTS: Organoleptic test (OLT) scores (P = .021), levels of hydrogen sulfide (P = .008) and methyl mercaptan (P = .020), frequency of bleeding on probing, average probing pocket depth, and plaque index significantly improved in the group using hinokitiol. In contrast, only the OLT score (P = .031) significantly improved in the control group after the treatment regimen. CONCLUSION: Mouth cleaning with hinokitiol-containing gel may be effective for reduction of oral malodor

(73) Monti M, Terzuoli E, Ziche M, Morbidelli L. The sulphydryl containing ACE inhibitor Zofenoprilat protects coronary endothelium from Doxorubicin-induced apoptosis. Pharmacol Res 2013 Oct;76:171-81. Abstract: Pediatric and adult cancer patients, following the use of the antitumor drug Doxorubicin develop cardiotoxicity. Pharmacological protection of microvascular endothelium might produce a double benefit: (i) reduction of myocardial toxicity (the primary target of Doxorubicin action) and (ii) maintenance of the vascular functionality for the adequate delivery of chemotherapeutics to tumor cells. This study was aimed to evaluate the mechanisms responsible of the protective effects of the angiotensin converting enzyme inhibitor (ACEI) Zofenoprilat against the toxic effects exerted by Doxorubicin on coronary microvascular endothelium. We found that exposure of endothelial cells to Doxorubicin (0.1-1muM range) impaired cell survival by promoting their apoptosis. ERK1/2 related p53 activation, but not reactive oxygen species, was responsible for Doxorubicin induced caspase-3 cleavage. P53 mediated-apoptosis and impairment of survival were reverted by treatment with Zofenoprilat. The previously described PI-3K/eNOS/endogenous fibroblast growth factor signaling was not involved in the protective effect, which, instead, could be ascribed to cystathionine gamma lyase dependent availability of H2S from Zofenoprilat. Furthermore, considering the tumor environment, the treatment of endothelial/tumor co-cultures with Zofenoprilat did not affect the antitumor efficacy of Doxorubicin. In conclusion the ACEI Zofenoprilat exerts a protective effect on Doxorubicin induced endothelial damage, without affecting its antitumor efficacy. Thus, sulfhydryl containing ACEI may be a useful therapy for Doxorubicin-induced cardiotoxicity

(74) Sharma K, Ganigue R, Yuan Z. pH dynamics in sewers and its modeling. Water Res 2013 Oct 15;47(16):6086-96. Abstract: pH variation in sewers has a significant effect on hydrogen sulfide production and emissions, and hence its accurate prediction is critical for the optimization of mitigation strategies. In this study, the nature and dynamics of pH variation in a sewer system is examined. Three sewer systems collecting domestic wastewater were monitored, with pH in all cases showing large diurnal variations. pH in fresh sewage in all three cases had a very similar trend with maximum pH in the range of 8.5-8.7. pH variation in fresh sewage followed the same pattern as the sewage flow rate, suggesting that sewage pH is influenced by household water use. Nitrogen content of the wastewater was found to be the most influential factor causing pH variation in fresh sewage, with the total ammonium concentration variation well correlated with the pH variation. A methodology for predicting pH variation in sewers is developed and calibration protocols proposed. The methodology, which is based on the concept of charge balance, was validated using titration curves and field pH data. Measurement of the total ammonium concentration in fresh sewage was found necessary and adequate for the calibration of the charge balance-based pH model

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(75) Li X, Zhang S, Cao J, Xie N, Liu T, Yang B, et al. An ICT-based fluorescent switch-on probe for hydrogen sulfide in living cells. Chem Commun (Camb ) 2013 Oct 7;49(77):8656-8. Abstract: An ICT-based fluorescent turn-on probe for hydrogen sulfide with high selectivity has been designed and synthesized. It exhibits up to 62-fold switch-on response toward H2S at given concentrations and can detect H2S in living cells with high sensitivity

(76) Lee M, McGeer E, Kodela R, Kashfi K, McGeer PL. NOSH-aspirin (NBS-1120), a novel nitric oxide and hydrogen sulfide releasing hybrid, attenuates neuroinflammation induced by microglial and astrocytic activation: a new candidate for treatment of neurodegenerative disorders. Glia 2013 Oct;61(10):1724-34. Abstract: Hydrogen sulfide (H2 S) and nitric oxide (NO) have been described as gasotransmitters. Anti-inflammatory activity in the central and peripheral nervous systems may be one of their functions. Previously we demonstrated that several SH(-) donors including H2 S-releasing aspirin (S-ASA) exhibited anti-inflammatory and neuroprotective activity in vitro against toxins released by activated microglia and astrocytes. Here we report that NOSH-ASA, an NO- and H2 S-releasing hybrid of aspirin, has a significantly greater anti-inflammatory and neuroprotective effect than S-ASA or NO-ASA. When activated by LPS/IFNgamma, human microglia and THP-1 cells release materials that are toxic to differentiated SH-SY5Y cells. These phenomena also occur with IFNgamma-stimulated human astroglia and U373 cells. When the cells were treated with the S-ASA or NO-ASA, there was a significant enhancement of neuroprotection. However, NOSH-ASA had significantly more potent protection properties than NO-ASA or S-ASA. The effect was concentration-dependent, as well as incubation time-dependent. Such treatment not only reduced the release of the TNFalpha and IL-6, but also attenuated activation of P38 MAPK and NFkappaB proteins. All the compounds tested were not harmful when applied directly to SH-SY5Y cells. These data suggest that NOSH-ASA has significant anti-inflammatory properties and may be a new candidate for treating neurodegenerative disorders that have a prominent neuroinflammatory component such as Alzheimer disease and Parkinson disease

(77) Park CM, Zhao Y, Zhu Z, Pacheco A, Peng B, varie-Baez NO, et al. Synthesis and evaluation of phosphorodithioate-based hydrogen sulfide donors. Mol Biosyst 2013 Oct;9(10):2430-4. Abstract: A series of O-aryl- and alkyl-substituted phosphorodithioates were designed and synthesized as hydrogen sulfide (H2S) donors. H2S releasing capability of these compounds was evaluated using fluorescence methods. O-aryl substituted donors showed slow and sustained H2S release while O-alkylated compounds showed very weak H2S releasing capability. We also evaluated donors' protective effects against hydrogen peroxide (H2O2)-induced oxidative damage in myocytes and donors' toxicity toward B16BL6 mouse melanoma cells

(78) Xu W, Wu W, Chen J, Guo R, Lin J, Liao X, et al. Exogenous hydrogen sulfide protects H9c2 cardiac cells against high glucose-induced injury by inhibiting the activities of the p38 MAPK and ERK1/2 pathways. Int J Mol Med 2013 Oct;32(4):917-25. Abstract: Hyperglycemia is a risk factor for the development of diabetic cardiovascular complications, which are associated with the activation of the mitogen-activated protein kinase (MAPK) signaling pathway. In this study, we demonstrate the inhibitory effects of exogenous hydrogen sulfide (H(2)S) on the activation of the MAPK pathway. The aim of the present study was to determine whether exogenous H(2)S prevents high glucose (HG)-induced injury by inhibiting the activation of the p38 MAPK and extracellular signal-regulated kinase (ERK)1/2 (members of MAPK) pathways in cardiomyoblasts (H9c2 cells). The findings of the present study demonstrated that the treatment of H9c2 cells with HG (35 mM glucose) for 24 h not only significantly induced injury, including cytotoxicity, apoptosis, overproduction of reactive oxygen species (ROS) and the loss of

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mitochondrial membrane potential (MMP), but also upregulated the expression levels of phosphorylated (p)-p38 MAPK and p-ERK1/2. The increased expression levels of p-p38 MAPK and p-ERK1/2 were markedly reduced by pre-treatment of the H9c2 cells with 400 microM sodium hydrogen sulfide (NaHS; a donor of H2S) prior to exposure to 35 mM glucose. Importantly, pre-treatment of the cells with 400 microM NaHS or 3 microM SB203580 (a selective inhibitor of p38 MAPK) or 15 microM U0126 (a selective inhibitor of ERK1/2) attenuated the HG-induced cardiomyocyte injury, leading to an increase in cell viability and a decrease in the number of apoptotic cells, preventing ROS generation, as well as the loss of MMP. In addition, pre-treatment of the cells with 1,000 microM NacetylLcysteine (a ROS scavenger) prior to exposure to HG ameliorated the HG-induced cytotoxicity. Taken together, the data from the present study demonstrate for the first time, to our knowledge, that exogenous H2S exerts a protective effect against HGinduced injury by inhibiting the activation of the p38 MAPK and ERK1/2 pathways and preventing oxidative stress in H9c2 cells

(79) Zeng J, Lin X, Fan H, Li C. Hydrogen sulfide attenuates the inflammatory response in a mouse burn injury model. Mol Med Rep 2013 Oct;8(4):1204-8. Abstract: Hydrogen sulfide (H2S) is a naturally occurring gaseous transmitter, which is important in normal physiology and disease. In the present study, the involvement of H2S in the regulation of the immune response induced by burn injury was investigated in mice. Adult male C57BL/6 mice were subjected to burn injuries and treated with vehicle (0.9% sodium chloride, NaCl; 100 ml/kg body weight; subcutaneously, s.c.) or the H2S donor (sodium hydrosulfide, NaHS; 2 mg/kg body weight; s.c.). Compared with the controls, mice which received burn injuries exhibited a significant decrease in plasma H2S levels. Moreover, the levels of tumor necrosis factor (TNF)alpha, interleukin (IL)6 and IL8 significantly increased, while IL10 levels were decreased, compared with that of the controls in the plasma of mice subjected to burn injuries. Myeloperoxidase (MPO) activity in the liver tissue of injured mice was also markedly higher compared with that of the control group. However, the administration of NaHS significantly decreased the levels of TNFalpha, IL6 and IL8 but increased the levels of IL10 in the plasma of mice subjected to burn injuries. In addition, the MPO activity was decreased by NaHS. These results suggested that H2S regulates the inflammatory response induced by burn injury by modulating the levels of TNFalpha, IL6, IL8 and IL10. Thus, it was proposed that the administration of the H2S donor, NaHS, may be a useful therapy against the exaggerated immune response that is associated with burn injury

(80) Ali S, Farooq MA, Hussain S, Yasmeen T, Abbasi GH, Zhang G. Alleviation of chromium toxicity by hydrogen sulfide in barley. Environ Toxicol Chem 2013 Oct;32(10):2234-9. Abstract: A hydroponic experiment was carried out to examine the effect of hydrogen sulfide (H2 S) in alleviating chromium (Cr) stress in barley. A 2-factorial design with 6 replications was selected, including 3 levels of NaHS (0 muM, 100 muM, and 200 muM) and 2 levels of Cr (0 muM and 100 muM) as treatments. The results showed that NaHS addition enhances plant growth and photosynthesis slightly compared with the control. Moreover, NaHS alleviated the inhibition in plant growth and photosynthesis by Cr stress. Higher levels of NaHS exhibited more pronounced effects in reducing Cr concentrations in roots, shoots, and leaves. Ultrastructural examination of plant cells supported the facts by indication of visible alleviation of cell disorders in both root and leaf with exogenous application of NaHS. An increased number of plastoglobuli, disintegration, and disappearance of thylakoid membranes and starch granules were visualized inside the chloroplast of Cr-stressed plants. Starch accumulation in the chloroplasts was also noticed in the Cr-treated cells, with the effect being much less in Cr + NaHS-treated plants. Hence, it is concluded that H2 S produced from NaHS can improve plant tolerance under Cr stress