PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-8 (8)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
Document Types
1.  The complex effects of the slow-releasing hydrogen sulfide donor GYY4137 in a model of acute joint inflammation and in human cartilage cells 
The role of hydrogen sulfide (H2S) in inflammation remains unclear with both pro- and anti-inflammatory actions of this gas described. We have now assessed the effect of GYY4137 (a slow-releasing H2S donor) on lipopolysaccharide (LPS)-evoked release of inflammatory mediators from human synoviocytes (HFLS) and articular chondrocytes (HAC) in vitro. We have also examined the effect of GYY4137 in a complete Freund’s adjuvant (CFA) model of acute joint inflammation in the mouse. GYY4137 (0.1–0.5 mM) decreased LPS-induced production of nitrite (NO2−), PGE2, TNF-α and IL-6 from HFLS and HAC, reduced the levels and catalytic activity of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and reduced LPS-induced NF-κB activation in vitro. Using recombinant human enzymes, GYY4137 inhibited the activity of COX-2, iNOS and TNF-α converting enzyme (TACE). In the CFA-treated mouse, GYY4137 (50 mg/kg, i.p.) injected 1 hr prior to CFA increased knee joint swelling while an anti-inflammatory effect, as demonstrated by reduced synovial fluid myeloperoxidase (MPO) and N-acetyl-β-D-glucosa-minidase (NAG) activity and decreased TNF-α, IL-1β, IL-6 and IL-8 concentration, was apparent when GYY4137 was injected 6 hrs after CFA. GYY4137 was also anti-inflammatory when given 18 hrs after CFA. Thus, although GYY4137 consistently reduced the generation of pro-inflammatory mediators from human joint cells in vitro, its effect on acute joint inflammation in vivo depended on the timing of administration.
doi:10.1111/jcmm.12016
PMCID: PMC3823018  PMID: 23356870
hydrogen sulfide; GYY4137; inflammation; synoviocyte; cytokines; myeloperoxidase; lipopolysaccharide; Freund’s adjuvant; COX-2; TNF-alpha converting enzyme
2.  C. elegans Aging Is Modulated by Hydrogen Sulfide and the sulfhydrylase/cysteine Synthase cysl-2 
PLoS ONE  2013;8(11):e80135.
Exogenous hydrogen sulfide (H2S) administration and endogenous H2S metabolism were explored in the nematode C. elegans. Chronic treatment with a slow-releasing H2S donor, GYY4137, extended median survival by 17-23% and increased tolerance towards oxidative and endoplasmic reticulum (ER) stress. Also, cysl-2, a sulfhydrylase/cysteine synthase in C. elegans, was transcriptionally upregulated by GYY4137 treatment and the deletion of cysl-2 resulted in a significant reduction in lifespan which was partially recovered by the supplementation of GYY4137. Likewise, a mammalian cell culture system, GYY4137 was able to protect bovine aortic endothelial cells (BAECs) from oxidative stress and (H2O2)-induced cell death. Taken together, this provides further support that H2S exerts a protective function which is consistent with the longevity dividend theory. Overall, this study underlines the therapeutic potential of a slow-releasing H2S donor as regulators of the aging and cellular stress pathways.
doi:10.1371/journal.pone.0080135
PMCID: PMC3832670  PMID: 24260346
3.  The complex effects of the slow-releasing hydrogen sulfide donor GYY4137 in a model of acute joint inflammation and in human cartilage cells 
The role of hydrogen sulfide (H2S) in inflammation remains unclear with both pro- and anti-inflammatory actions of this gas described. We have now assessed the effect of GYY4137 (a slow-releasing H2S donor) on lipopolysaccharide (LPS)-evoked release of inflammatory mediators from human synoviocytes (HFLS) and articular chondrocytes (HAC) in vitro. We have also examined the effect of GYY4137 in a complete Freund's adjuvant (CFA) model of acute joint inflammation in the mouse. GYY4137 (0.1–0.5 mM) decreased LPS-induced production of nitrite (NO2−), PGE2, TNF-α and IL-6 from HFLS and HAC, reduced the levels and catalytic activity of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and reduced LPS-induced NF-κB activation in vitro. Using recombinant human enzymes, GYY4137 inhibited the activity of COX-2, iNOS and TNF-α converting enzyme (TACE). In the CFA-treated mouse, GYY4137 (50 mg/kg, i.p.) injected 1 hr prior to CFA increased knee joint swelling while an anti-inflammatory effect, as demonstrated by reduced synovial fluid myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAG) activity and decreased TNF-α, IL-1β, IL-6 and IL-8 concentration, was apparent when GYY4137 was injected 6 hrs after CFA. GYY4137 was also anti-inflammatory when given 18 hrs after CFA. Thus, although GYY4137 consistently reduced the generation of pro-inflammatory mediators from human joint cells in vitro, its effect on acute joint inflammation in vivo depended on the timing of administration.
doi:10.1111/jcmm.12016
PMCID: PMC3823018  PMID: 23356870
hydrogen sulfide; GYY4137; inflammation; synoviocyte; cytokines; myeloperoxidase; lipopolysaccharide; Freund's adjuvant; COX-2; TNF-alpha converting enzyme
4.  The Slow-Releasing Hydrogen Sulfide Donor, GYY4137, Exhibits Novel Anti-Cancer Effects In Vitro and In Vivo 
PLoS ONE  2011;6(6):e21077.
The slow-releasing hydrogen sulfide (H2S) donor, GYY4137, caused concentration-dependent killing of seven different human cancer cell lines (HeLa, HCT-116, Hep G2, HL-60, MCF-7, MV4-11 and U2OS) but did not affect survival of normal human lung fibroblasts (IMR90, WI-38) as determined by trypan blue exclusion. Sodium hydrosulfide (NaHS) was less potent and not active in all cell lines. A structural analogue of GYY4137 (ZYJ1122) lacking sulfur and thence not able to release H2S was inactive. Similar results were obtained using a clonogenic assay. Incubation of GYY4137 (400 µM) in culture medium led to the generation of low (<20 µM) concentrations of H2S sustained over 7 days. In contrast, incubation of NaHS (400 µM) in the same way led to much higher (up to 400 µM) concentrations of H2S which persisted for only 1 hour. Mechanistic studies revealed that GYY4137 (400 µM) incubated for 5 days with MCF-7 but not IMR90 cells caused the generation of cleaved PARP and cleaved caspase 9, indicative of a pro-apoptotic effect. GYY4137 (but not ZYJ1122) also caused partial G2/M arrest of these cells. Mice xenograft studies using HL-60 and MV4-11 cells showed that GYY4137 (100–300 mg/kg/day for 14 days) significantly reduced tumor growth. We conclude that GYY4137 exhibits anti-cancer activity by releasing H2S over a period of days. We also propose that a combination of apoptosis and cell cycle arrest contributes to this effect and that H2S donors should be investigated further as potential anti-cancer agents.
doi:10.1371/journal.pone.0021077
PMCID: PMC3119065  PMID: 21701688
5.  The Effect of Hydrogen Sulfide Donors on Lipopolysaccharide-Induced Formation of Inflammatory Mediators in Macrophages 
Antioxidants & Redox Signaling  2010;12(10):1147-1154.
Abstract
The role of hydrogen sulfide (H2S) in inflammation is controversial, with both pro- and antiinflammatory effects documented. Many studies have used simple sulfide salts as the source of H2S, which give a rapid bolus of H2S in aqueous solutions and thus do not accurately reflect the enzymatic generation of H2S. We therefore compared the effects of sodium hydrosulfide and a novel slow-releasing H2S donor (GYY4137) on the release of pro- and antiinflammatory mediators in lipopolysaccharide (LPS)-treated murine RAW264.7 macrophages. For the first time, we show that GYY4137 significantly and concentration-dependently inhibits LPS-induced release of proinflammatory mediators such as IL-1β, IL-6, TNF-α, nitric oxide (•NO), and PGE2 but increased the synthesis of the antiinflammatory chemokine IL-10 through NF-κB/ATF-2/HSP-27–dependent pathways. In contrast, NaHS elicited a biphasic effect on proinflammatory mediators and, at high concentrations, increased the synthesis of IL-1β, IL-6, NO, PGE2 and TNF-α. This study clearly shows that the effects of H2S on the inflammatory process are complex and dependent not only on H2S concentration but also on the rate of H2S generation. This study may also explain some of the apparent discrepancies in the literature regarding the pro- versus antiinflammatory role of H2S. Antioxid. Redox Signal. 12, 1147–1154.
doi:10.1089/ars.2009.2899
PMCID: PMC2875982  PMID: 19769459
6.  Medical malpractice 
Western Journal of Medicine  2000;173(4):244-250.
Objective To examine the causal effects of doctor-patient relations and the severity of a medical outcome on medical patient perceptions and malpractice intentions in the event of an adverse medical outcome. Design Randomized between-subjects experimental design. Patients were given scenarios depicting interactions between an obstetric patient and her physician throughout the patient's pregnancy, labor, and delivery. Participants One hundred twenty-eight postpartum obstetric patients were approached for participation, of whom 104 completed the study. Main outcome measures Patients' perceptions of physician competence and intentions to file a malpractice claim. Results Positive physician communication behaviors increased patients' perceptions of physician competence and decreased malpractice claim intentions toward both the physician and the hospital. A more severe outcome increased only patients' intentions to sue the hospital. Conclusion These results provide empiric evidence for a direct, causal effect of the doctor-patient relationship on medical patients' treatment perceptions and malpractice claim intentions in the event of an adverse medical outcome.
PMCID: PMC1071103  PMID: 11017984
7.  Patients' knowledge of heart disease in general practice 
Interviews with 400 consecutive patients attending a general practice sought their knowledge of the signs and symptoms of an acute heart attack, what action they would take for such an event, and their understanding of the predisposing factors contributing to heart disease. The survey revealed poor recognition of the relevant signs and symptoms of an acute heart attack and lack of knowledge of some of the main predisposing factors associated with heart disease.
PMCID: PMC2157977  PMID: 618352

Results 1-8 (8)