Activation of Endogenous H2S Biosynthesis or Supplementation with Exogenous H2S Enhances Adipose Tissue Adipogenesis and Preserves Adipocyte Physiology in Humans.

Aims: To investigate the impact of exogenous hydrogen sulfide (H2S) and its endogenous biosynthesis on human adipocytes and adipose tissue in the context of obesity and insulin resistance. Results: Experiments in human adipose tissue explants and in isolated preadipocytes demonstrated that exogenous H2S or the activation of endogenous H2S biosynthesis resulted in increased adipogenesis, insulin action, sirtuin deacetylase, and PPARγ transcriptional activity, whereas chemical inhibition and gene knockdown of each enzyme generating H2S (CTH, CBS, MPST) led to altered adipocyte differentiation, cellular senescence, and increased inflammation. In agreement with these experimental data, visceral and subcutaneous adipose tissue expression of H2S-synthesising enzymes was significantly reduced in morbidly obese subjects in association with attenuated adipogenesis and increased markers of adipose tissue inflammation and senescence. Interestingly, weight-loss interventions (including bariatric surgery or diet/exercise) improved the expression of H2S biosynthesis-related genes. In human preadipocytes, the expression of CTH, CBS, and MPST genes and H2S production were dramatically increased during adipocyte differentiation. More importantly, the adipocyte proteome exhibiting persulfidation was characterized, disclosing that different proteins involved in fatty acid and lipid metabolism, the citrate cycle, insulin signaling, several adipokines, and PPAR, experienced the most dramatic persulfidation (85-98%). Innovation: No previous studies investigated the impact of H2S on human adipose tissue. This study suggests that the potentiation of adipose tissue H2S biosynthesis is a possible therapeutic approach to improve adipose tissue dysfunction in patients with obesity and insulin resistance. Conclusion: Altogether, these data supported the relevance of H2S biosynthesis in the modulation of human adipocyte physiology. Antioxid. Redox Signal. 35, 319-340.

Transcriptomic profile analysis of brain inferior colliculus following acute hydrogen sulfide exposure.

Hydrogen sulfide (H2S) is a gaseous molecule found naturally in the environment, and as an industrial byproduct, and is known to cause acute death and induces long-term neurological disorders following acute high dose exposures. Currently, there is no drug approved for treatment of acute H2S-induced neurotoxicity and/or neurological sequelae. Lack of a deep understanding of pathogenesis of H2S-induced neurotoxicity has delayed the development of appropriate therapeutic drugs that target H2S-induced neuropathology. RNA sequencing analysis was performed to elucidate the cellular and molecular mechanisms of H2S-induced neurodegeneration, and to identify key molecular elements and pathways that contribute to H2S-induced neurotoxicity. C57BL/6J mice were exposed by whole body inhalation to 700 ppm of H2S for either one day, two consecutive days or 4 consecutive days. Magnetic resonance imaging (MRI) scan analyses showed H2S exposure induced lesions in the inferior colliculus (IC) and thalamus (TH). This mechanistic study focused on the IC. RNA Sequencing analysis revealed that mice exposed once, twice, or 4 times had 283, 193 and 296 differentially expressed genes (DEG), respectively (q-value < 0.05, fold-change> 1.5). Hydrogen sulfide exposure modulated multiple biological pathways including unfolded protein response, neurotransmitters, oxidative stress, hypoxia, calcium signaling, and inflammatory response in the IC. Hydrogen sulfide exposure activated PI3K/Akt and MAPK signaling pathways. Pro-inflammatory cytokines were shown to be potential initiators of the modulated signaling pathways following H2S exposure. Furthermore, microglia were shown to release IL-18 and astrocytes released both IL-1ß and IL-18 in response to H2S. This transcriptomic analysis data revealed complex signaling pathways involved in H2S-induced neurotoxicity and may provide important associated mechanistic insights.

Hydrogen sulfide: a target to modulate oxidative stress and neuroplasticity for the treatment of pathological anxiety.

Introduction: Anxiety disorders result inhigh patient burden and utilization of healthcare resources. Evidence-based treatments for pathological anxiety include targeted psychotherapy and use of serotonin-augmenting agents. Limitations in access to cognitive behavioral therapy and potential disadvantages to the use of psychotropics make the need for novel approaches to therapeutics for pathological anxiety salient.Areas Covered: Neuroplasticity mechanisms, as well as managing oxidative stress and inflammatory cellular allostatic loads can decrease anxiety. The gasotransmitter hydrogen sulfide (H2S) can impact these mechanisms through a) maintaining intracellular reduced glutathione in the CNS to decrease oxidative stress; b) facilitating neuroplasticity in amygdalar regions via the 2B subunit of n-methyl-d-aspartate (NMDA) receptors, in conjunction with the cAMP messenger system and a CNS kinase, PKC-γ; and c) regulating intracellular Ca2+ homeostasis in neurons and glial cells, among others.Expert Opinion: Given the mounting evidence for the role of H2S in neuronal health and its potential to decrease pathological anxiety, the current challenge in H2S therapeutics remains finding an efficient delivery system of this gasotransmitter in a reliable, safe and nontoxic form to engage in clinical trials. Current efforts include H2S-delivering moieties attached to known drugs, natural sulfide-releasing compounds such as garlic, and the regulation of dysfunctional breathing through breathing retraining.

Hydrogen sulfide stimulates activation of hepatic stellate cells through increased cellular bio-energetics.

Hepatic fibrosis is caused by chronic inflammation and characterized as the excessive accumulation of extracellular matrix (ECM) by activated hepatic stellate cells (HSCs). Gasotransmitters like NO and CO are known to modulate inflammation and fibrosis, however, little is known about the role of the gasotransmitter hydrogen sulfide (H2S) in liver fibrogenesis and stellate cell activation. Endogenous H2S is produced by the enzymes cystathionine ß-synthase (CBS), cystathionine γ-lyase (CTH) and 3-mercaptopyruvate sulfur transferase (MPST) [1]. The aim of this study was to elucidate the role of endogenously produced and/or exogenously administered H2S on rat hepatic stellate cell activation and fibrogenesis. Primary rat HSCs were culture-activated for 7 days and treated with different H2S releasing donors (slow releasing donor GYY4137, fast releasing donor NaHS) or inhibitors of the H2S producing enzymes CTH and CBS (DL-PAG, AOAA). The main message of our study is that mRNA and protein expression level of H2S synthesizing enzymes are low in HSCs compared to hepatocytes and Kupffer cells. However, H2S promotes hepatic stellate cell activation. This conclusion is based on the fact that production of H2S and mRNA and protein expression of its producing enzyme CTH are increased during hepatic stellate cell activation. Furthermore, exogenous H2S increased HSC proliferation while inhibitors of endogenous H2S production reduce proliferation and fibrotic makers of HSCs. The effect of H2S on stellate cell activation correlated with increased cellular bioenergetics. Our results indicate that the H2S generation in hepatic stellate cells is a target for anti-fibrotic intervention and that systemic interventions with H2S should take into account cell-specific effects of H2S.

Hydrogen sulfide alleviates uranium-induced kidney cell apoptosis mediated by ER stress via 20S proteasome involving in Akt/GSK-3ß/Fyn-Nrf2 signaling.

Hydrogen sulfide (H2S) shows antioxidative, anti-inflammatory, antiapoptotic, and cytoprotective effects in kidneys. Recently, H2S has been reported to alleviate uranium-induced rat nephrotoxicity through oxidative stress and inflammatory response via Nrf2-NF-κB pathways. Here, the protective effect and molecular mechanism of H2S on uranium-induced apoptosis were examined in normal rat kidney proximal cells (NRK-52E) in vitro. The results indicate that NaHS (an H2S donor) administration in uranium-intoxicated kidney cells ameliorated uranium-induced reactive oxygen species generation, caspase-3-dependent apoptosis, and endoplasmic reticulum (ER) stress identified through several key markers including GRP78, C/EBP homologous protein (CHOP), and caspase-12. NaHS treatment in uranium-intoxicated kidney cells abolished the effects of uranium on Akt phosphorylation, GSK-3ß activation, increased Fyn nuclear expression, and concomitantly decreased Nrf2 nuclear expression. NaHS administration in uranium-treated kidney cells resorted uranium-decreased the expression of two key subunit PSMA6 and PSMB7 in 20S proteasome. But, DRB (an Nrf2 inhibitor) administration abrogated the effects of NaHS on PSMA6 and PSMB7 expression in uranium-contaminated kidney cells. Bortezomib (a proteasome inhibitor) treatment in NaHS pulsing uranium cotreated kidney cells reversed the effects of NaHS on not only PSMA6 and PSMB7 but also GRP78 and CHOP. Taken together, all data suggest that H2S can attenuate uranium-induced kidney cell apoptosis mediated by ER stress via 20S proteasome involving in Akt/GSK-3ß/Fyn-Nrf2 signaling axis.

A Review of Patents on Therapeutic Potential and Delivery of Hydroge n Sulfide.

BACKGROUND: Hydrogen sulfide (H2S) is a colorless gas with a characteristic smell of rotten eggs. Once only thought of as a toxic gas, evidence now shows that H2S plays major roles in pathological and physiological activities. These roles are being utilized to treat diseases and disorders ranging from hypertension, inflammation, edema, cardiovascular issues, chronic pain, cancer, and many more. Challenges facing the use of H2S currently involve achieving the optimum therapeutic concentrations, synthesizing chemically and physiologically stable donors, and developing clinically appropriate delivery systems. METHODS: We did an extensive literature search on therapeutic potentials and related issues of H2S which were presented in a systematic flow pattern in introduction. Patents accepted/filed on various aspects of hydrogen sulfide were searched using the United States Patent and Trademark Office database at http://patft.uspto.gov/ and google patents at https://patents.google.com/. The important search terms combined with H2S were therapeutic effect, pharmacological action, biochemistry, measurement, and delivery. We also incorporated our own experiences and publications while discussing the delivery approaches and associated challenges. RESULTS: In the process, researchers have discovered novel techniques in preparing the noxious gas by discovering and synthesizing H2S donors and developing controlled and predictable delivery systems. Donors utilized thus far include derivatives of anti-inflammatory drugs like H2S -aspirin, Allium sativum extracts, inorganic salts, phosphorodithioate derivatives, and thioaminoacid derivatives. Use of controlled delivery systems for H2S is critical to maintain its physiological stability, optimum therapeutic window, increase patient compliance, and make it easier to manufacture and administer. Numerous patents overcoming the challenges of using H2S therapeutically with various donors and delivery mechanisms have been reviewed. CONCLUSION: The scientific knowledge gained from the last decade researches has moved H2S from a foul smelling pungent gas to the status of a gasotransmitter with many potential therapeutic applications. However, developing a suitable donor and a delivery system using that donor for providing precise and sustained release of H2S for an extended period, is critically needed for any further development towards its translation into clinical practices.

Hydrogen sulfide (H2S) releasing agents: chemistry and biological applications.

Hydrogen sulfide (H2S) is a newly recognized signaling molecule with very potent cytoprotective actions. The fields of H2S physiology and pharmacology have been rapidly growing in recent years, but a number of fundamental issues must be addressed to advance our understanding of the biology and clinical potential of H2S in the future. Hydrogen sulfide releasing agents (also known as H2S donors) have been widely used in these fields. These compounds are not only useful research tools, but also potential therapeutic agents. It is therefore important to study the chemistry and pharmacology of exogenous H2S and to be aware of the limitations associated with the choice of donors used to generate H2S in vitro and in vivo. In this review we summarized the developments and limitations of currently available donors including H2S gas, sulfide salts, garlic-derived sulfur compounds, Lawesson's reagent/analogs, 1,2-dithiole-3-thiones, thiol-activated donors, photo-caged donors, and thioamino acids. Some biological applications of these donors were also discussed.

[Change in plasma H2S level and therapeutic effect of H2S supplementation in tubulointerstitial fibrosis among rats with unilateral ureteral obstruction].

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

Inhalation gases or gaseous mediators as neuroprotectants for cerebral ischaemia.

Ischaemic stroke is one of the leading causes of morbidity and mortality worldwide. While recombinant tissue plasminogen activator can be administered to produce thrombolysis and restore blood flow to the ischaemic brain, therapeutic benefit is only achieved in a fraction of the subset of patients eligible for fibrinolytic intervention. Neuroprotective therapies attempting to restrict the extent of brain injury following cerebral ischaemia have not been successfully translated into the clinic despite overwhelming pre-clinical evidence of neuroprotection. Therefore, an adequate treatment for the majority of acute ischaemic stroke patients remains elusive. In the stroke literature, the use of therapeutic gases has received relatively little attention. Gases such as hyperbaric and normobaric oxygen, xenon, hydrogen, helium and argon all possess biological effects that have shown to be neuroprotective in pre-clinical models of ischaemic stroke. There are significant advantages to using gases including their relative abundance, low cost and feasibility for administration, all of which make them ideal candidates for a translational therapy for stroke. In addition, modulating cellular gaseous mediators including nitric oxide, carbon monoxide, and hydrogen sulphide may be an attractive option for ischaemic stroke therapy. Inhalation of these gaseous mediators can also produce neuroprotection, but this strategy remains to be confirmed as a viable therapy for ischaemic stroke. This review highlights the neuroprotective potential of therapeutic gas therapy and modulation of gaseous mediators for ischaemic stroke. The therapeutic advantages of gaseous therapy offer new promising directions in breaking the translational barrier for ischaemic stroke.

Supplemental hydrogen sulphide protects transplant kidney function and prolongs recipient survival after prolonged cold ischaemia-reperfusion injury by mitigating renal graft apoptosis and inflammation.

UNLABELLED: What's known on the subject? and What does the study add? Hydrogen sulphide (H(2) S) has recently been classified as a member of the family of small gaseous molecules called gasotransmitters and has been found to have many important physiological functions. Several recent studies have elucidated the protective effects of H(2) S in many models of tissue ischaemia-reperfusion injury (IRI), including hepatic, myocardial, pulmonary, cerebral and renal IRI. It has previously been shown that H(2) S has a number of properties that may contribute to its protection against IRI, including vasodilatory, anti-apoptotic, anti-inflammatory and anti-oxidant effects, although the specific actions appear to vary between tissues. The few studies investigating the effects of H(2) S against renal IRI have only involved clamping of the renal pedicle to induce warm IRI. This study investigated the protective effects of H(2) S in the context of renal transplantation (RTx), which generally involves a more severe period of prolonged cold IRI. A previous study investigated the actions of H(2) S in RTx, but it was performed ex vivo and did not involve actual transplantation of donor kidneys. To our knowledge, this is the first study using a clinically relevant model of RTx to show that treatment of donor kidneys with H(2) S during preservation is protective against prolonged cold IRI. These findings suggest that H(2) S has potential utility in improving clinical organ preservation techniques and increasing the overall success of organ transplantation. OBJECTIVE: • To characterize the effects of hydrogen sulphide (H(2) S), an endogenously produced molecule recently described to have protective effects against warm ischaemic tissue injury, in mitigating transplantation-associated prolonged cold ischaemia-reperfusion injury (IRI) in a clinically applicable in vivo model of renal transplantation (RTx). MATERIALS AND METHODS: • After undergoing bilateral native nephrectomy, Lewis rats underwent RTx with kidneys that were flushed with either cold (4 °C) standard University of Wisconsin preservation solution (UW) or cold UW + 150 µM NaHS (H(2) S) solution and stored for 24 h at 4 °C in the same solution. • Recipient rats were monitored for a 14-day time course using metabolic cages to assess various characteristics of renal graft function. • Renal grafts were removed at time of death or after the rats were killed for histological, immunohistochemical and quantitative PCR analysis. RESULTS: • H(2) S-treated rats exhibited immediate and significant (P < 0.05) decreases in serum creatinine levels, increased urine output and increased survival compared with UW-treated rats. • H(2) S-treated grafts showed significantly reduced glomerular and tubular necrosis and apoptosis, diminished graft neutrophil and macrophage infiltrates and a trend towards improved inflammatory and anti-apoptotic cytokine profiles. CONCLUSION: • Our results provide the first evidence that supplemental H(2) S can mitigate renal graft IRI incurred during transplantation and prolonged cold storage, improving early graft function and recipient survival in a clinically applicable model of RTx.

Detrimental effects of prolonged warm renal ischaemia-reperfusion injury are abrogated by supplemental hydrogen sulphide: an analysis using real-time intravital microscopy and polymerase chain reaction.

UNLABELLED: What's known on the subject? and What does the study add? Hydrogen sulphide (H(2) S) has recently been classified as a member of the gasotransmitter family. Its physiological and pathophysiological effects are rapidly expanding with numerous studies highlighting the protective effects of H(2) S on ischaemia-reperfusion injury (IRI) in various organ systems, e.g. heart, liver, CNS and lungs. The mechanisms behind its protective effects reside in its vasodilatory, anti-inflammatory and anti-oxidant characteristics. These specific mechanistic profiles appear to be different across different tissues and models of IRI. We recently showed that supplementation of preservation solutions with H(2) S during periods of prolonged cold renal storage and subsequent renal transplantation leads to a massive and significant survival, functional and tissue protective advantage compared with storage in standard preservation solution alone. However, there have only been a few studies that have evaluated the effects of H(2) S against warm renal IRI; although these studies have focused primarily upon shorter periods of warm renal pedicle clamping, they have shown a clear survival benefit to H(2) S supplementation. The present study adds to the existing literature by evaluating the effects of H(2) S in a model of warm IRI with clinically relevant, prolonged warm ischaemia-reperfusion times (1 h ischaemia, 2 h reperfusion). We show an unprecedented view into real-time renal and hepatic perfusion with intravital microscopy throughout the reperfusion period. We show, for the first time, that supplemental H(2) S has multiple protective functions against the warm IRI-induced tissue damage, which may be clinically applicable to both donation after cardiac death models of renal transplantation, as well as to uro-oncological practices requiring surgical clamping of the renal pedicle, e.g. during a partial nephrectomy. OBJECTIVE: • To determine the protective role of supplemental hydrogen sulphide (H(2) S) in prolonged warm renal ischaemia-reperfusion injury (IRI) using real-time intravital microscopy (IVM). MATERIALS AND METHODS: • Uninephrectomised Lewis rats underwent 1 h of warm ischaemia and 2 h of reperfusion during intraperitoneal treatment with phosphate buffer saline (IRI, n = 10) or 150 µmol/L NaHS (IRI+H(2) S, n = 12) and were compared with sham-operated rats (n = 9). • Blood was collected for measurement of serum creatinine (Cr), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). • IVM was performed to assess renal and hepatic microcirculation. • Kidneys were sectioned for histology and real-time quantitative polymerase chain reaction for markers of inflammation. RESULTS: • The mean (sd) Cr concentration raised to 72.8(2.5) µmol/L after IRI from 11.0 (0.7) µmol/L (sham) but was partially inhibited with H(2) S to 62.8 (0.9) µmol/L (P < 0.05). • H(2) S supplementation during IRI increased renal capillary perfusion on IVM, and improved acute tubular necrosis and apoptotic scores on histology (P < 0.05). • Supplemental H(2) S decreased expression of the pro-inflammatory markers toll-like receptor 4, tumour necrosis factor α, interleukin 8, C-C chemokine receptor type 5, interferon γ and interleukin 2 (P < 0.05). • Distant organ (liver) dysfunction after renal IRI was limited with H(2) S supplementation: blunting of the ALT and AST surge, decreased hepatic sinusoidal vasodilation, and decreased leukocyte infiltration in post-sinusoidal venules (P < 0.05). • H(2) S supplementation directly inhibited interleukin 8-induced neutrophil chemotaxis in vitro (P < 0.05). CONCLUSIONS: • These findings are the first to show the real-time protective role of supplemental H(2) S in prolonged periods of warm renal IRI, perhaps acting by decreasing leukocyte migration and limiting inflammatory responses. • The protective effects of H(2) S suggest potential clinical applications in both donors after cardiac death models of renal transplantation and oncological practices requiring vascular clamping.

Inhaled hydrogen sulfide improves graft function in an experimental model of lung transplantation.

OBJECTIVES: Ischemia/reperfusion injury (IRI) is a common complication of lung transplantation (LTx). Hydrogen sulfide (H(2)S) is a novel agent previously shown to slow metabolism and scavenge reactive oxygen species, potentially mitigating IRI. We hypothesized that pretreatment with inhaled H(2)S would improve graft function in an ex vivo model of LTx. METHODS: Rabbits (n = 10) were ventilated for 2 h prior to heart-lung bloc procurement. The treatment group (n = 5) inhaled room air (21% O(2)) supplemented with 150 ppm H(2)S while the control group (n = 5) inhaled room air alone. Both groups were gradually cooled to 34°C. All heart-lung blocs were then recovered and cold-stored in low-potassium dextran solution for 18 h. Following storage, the blocs were reperfused with donor rabbit blood in an ex vivo apparatus. Serial clinical parameters were assessed and serial tissue biochemistry was examined. RESULTS: Prior to heart-lung bloc procurement, rabbits pretreated with H(2)S exhibited similar oxygenation (P = 0.1), ventilation (P = 0.7), and heart rate (P = 0.5); however, treated rabbits exhibited consistently higher mean arterial blood pressures (P = 0.01). During reperfusion, lungs pretreated with H(2)S had better oxygenation (P < 0.01) and ventilation (P = 0.02), as well as lower pulmonary artery pressures (P < 0.01). Reactive oxygen species levels were lower in treated lungs during reperfusion (P = 0.01). Additionally, prior to reperfusion, treated lungs demonstrated more preserved mitochondrial cytochrome c oxidase activity (P = 0.01). CONCLUSIONS: To our knowledge, this study represents the first reported therapeutic use of inhaled H(2)S in an experimental model of LTx. After prolonged ischemia, lungs pretreated with inhaled H(2)S exhibited improved graft function during reperfusion. Donor pretreatment with inhaled H(2)S represents a potentially novel adjunct to conventional preservation techniques and merits further exploration.

[Magneto-peloidotherapy and hydrogen sulfide baths for the correction of dyslipidemia and immune inflammation in patients with ischemic heart disease during resort treatment].

A total of 55 patients with angina of effort (functional classes I-II) were treated by magneto-peloidotherapy and hydrogen sulfide baths. Effectiveness of he treatment was evaluated based on the lipid profile (total cholesterol, triglycerides, high and low density lipoproteides), atherogenicity index, lipid peroxidation, reactivity of the antioxidative defense system, and immune characteristics. Results of the study indicate that combination of magneto-peloidotherapy and hydrogen sulfide baths has hypolipidemic effect and reduces lipid peroxidation in the absence of activation of the antioxidative defense system and correction of the disbalanced immune system. Taken together, these effects decrease severity of the systemic inflammatory reaction and facilitate remission of the atherosclerotic process.

[The inhalation use of hydrogen sulfide water in the health resort rehabilitation of osteoarthrosis patients living in areas with radionuclide contamination]. / Ingaliatsionnoe primenenie serovodorodnoi vody v kurortnoi reabilitatsii bol'nykh osteoartrozom, prozhivaiushchikh na territoriiakh radionuklidnogo zagriazneniia.

A randomized trial of 77 patients with polyosteoarthrosis of stage I-II was made in two groups which received hydrogen sulfide balneotherapy according to conventional regimen (controls) and inhalations of hydrogen sulfide water. Ultrasonic hydrogen sulfide inhalations are not inferior in efficacy to conventional treatment, but balneoreaction occurred less frequently. High bioavailability of hydrogen sulfide in inhalations provides antiinflammatory, analgetic, trophic effects, stimulates general and immune reactivity of the body.