Hydrogen sulfide regulates homocysteine-mediated glomerulosclerosis.

BACKGROUND/AIMS: In this study we tested the hypothesis that H(2)S regulates collagen deposition, matrix metalloproteinases (MMP) and inflammatory molecules during hyperhomocysteinemia (HHcy) resulting in attenuation of glomerulosclerosis and improved renal function. MATERIALS AND METHODS: A genetic model of HHcy, cystathionine beta-synthase heterozygous (CBS+/-) and wild-type (WT) 2-kidney (2K) mice were used in this study and supplemented with or without NaHS (30 micromol/l, H(2)S donor) in drinking water for 8 weeks. To expedite the renal damage associated with HHcy, uninephrectomized (1K) mice of similar groups were also used. RESULTS: Results demonstrated that NAD(P)H oxidase (p47(phox)subunit) and blood pressure were upregulated in WT 1K, CBS+/- 2K and CBS+/- 1K mice with downregulation of H(2)S production and reduced glomerular filtration rate. These changes were normalized with H(2)S supplementation. Both pro- and active MMP-2 and -9 and collagen protein expressions and glomerular depositions were also upregulated in WT 1K, CBS+/- 2K and CBS+/- 1K mice. Increased expressions of inflammatory molecules, intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1, as well as increased macrophage infiltration, were detected in WT 1K, CBS+/- 2K and CBS+/- 1K mice. These changes were ameliorated with H(2)S supplementation. CONCLUSION: Together, these results suggest that increased oxidative stress and decreased H(2)S in HHcy causes matrix remodeling and inflammation resulting in glomerulosclerosis and reduced renal function.

Sports participation and radiographic findings of adolescents treated nonoperatively for displaced clavicle fractures.

BACKGROUND: There is a relative paucity of high-level evidence that guides the treatment of displaced midshaft clavicle fractures in adolescents. Some use overhead sports or significant shortening as relative indications for surgical treatment, while others rarely consider operative intervention for these patients. The purpose of this study is to determine the effect of overhead sports participation and fracture shortening on subjective and objective outcomes after nonoperative treatment of displaced midshaft clavicle fractures in those aged 10-17 years. METHODS: Using a radiographic database, adolescents with displaced clavicle fractures were identified and contacted over the phone. These subjects were invited to take part in the study in return for compensation. Radiographic measurements of dedicated clavicle films around the time of injury were performed, and a custom survey aimed at elucidating participation in overhead or contact sports was given. The Nottingham Clavicle Score (NCS) and the Constant Shoulder Score were obtained for each patient to provide both subjective and objective outcome data. Statistical Package for Social Science (SPSS) software (version 22, IBM) was used to compare radiographic and sports data to the outcome measures. RESULTS: Gender, age at the time of fracture, time since fracture, relative and absolute radiographic shortening, and hand dominance were all not significantly correlated with subjective or objective outcomes. Five patients (23%) reported not feeling happy with the appearance of their shoulder at the beach or at the pool. This group had statistically lower NCS results. Eleven of 22 participated in ≥6 months per year of overhead or contact sports; they did not have worse subjective or objective outcomes. CONCLUSIONS: Fracture shortening and sports participation do not have a significant impact in adolescents on outcomes after displaced midshaft clavicle fracture.

Hydrogen sulfide mitigates transition from compensatory hypertrophy to heart failure.

We reported previously that although there is disruption of coordinated cardiac hypertrophy and angiogenesis in transition to heart failure, matrix metalloproteinase (MMP)-9 induced antiangiogenic factors play a vital role in this process. Previous studies have shown the cardioprotective role of hydrogen sulfide (H2S) in various cardiac diseases, but its role during transition from compensatory hypertrophy to heart failure is yet to be unveiled. We hypothesize that H2S induces MMP-2 activation and inhibits MMP-9 activation, thus promoting angiogenesis, and mitigates transition from compensatory cardiac hypertrophy to heart failure. To verify this, aortic banding (AB) was created to mimic pressure overload in wild-type (WT) mice, which were treated with sodium hydrosulfide (NaHS, H2S donor) in drinking water and compared with untreated control mice. Mice were studied at 3 and 8 wk. In the NaHS-treated AB 8 wk group, the expression of MMP-2, CD31, and VEGF was increased while the expression of MMP-9, endostatin, angiostatin, and tissue inhibitor of matrix metalloproteinase (TIMP)-3 was decreased compared with untreated control mice. There was significant reduction in fibrosis in NaHS-treated groups. Echocardiograph and pressure-volume data revealed improvement of cardiac function in NaHS-treated groups over untreated controls. These results show that H2S by inducing MMP-2 promotes VEGF synthesis and angiogenesis while it suppresses MMP-9 and TIMP-3 levels, inhibits antiangiogenic factors, reduces intracardiac fibrosis, and mitigates transition from compensatory hypertrophy to heart failure.