Hydrogen sulfide (H2S) has been shown recently to function as an important gasotransmitter. The present study investigated the vascular effects of H2S, both exogenously applied and endogenously generated, on resistance mesenteric arteries of rats and the underlying mechanisms. Both H2S and NaHS evoked concentration-dependent relaxation of in vitro perfused rat mesenteric artery beds (MAB). The sensitivity of MAB to H2S (EC50, 25.2 +/- 3.6 microM) was about fivefold higher than that of rat aortic tissues. Removal of endothelium or coapplication of charybdotoxin and apamin to endothelium-intact MAB significantly reduced the vasorelaxation effects of H2S. The H2S-induced relaxation of MAB was partially mediated by ATP-sensitive K+ (KATP) channel activity in vascular smooth muscle cells. Pinacidil (EC50, 1.7 +/- 0.1 microM, n=6) mimicked, but glibenclamide (10 microM, n=6) suppressed, the vasorelaxant effect of H2S. KATP channel currents in isolated mesenteric artery smooth muscle cells were significantly augmented by H2S. L-cysteine, a substrate of cystathionine-gamma-lyase (CSE), at 1 mM increased endogenous H2S production by sixfold in rat mesenteric artery tissues and decreased contractility of MAB. DL-propargylglycine (a blocker of CSE) at 10 microM abolished L-cysteine-dependent increase in H2S production and relaxation of MAB. Our results demonstrated a tissue-specific relaxant response of resistance arteries to H2S. The stimulation of KATP channels in vascular smooth muscle cells and charybdotoxin/apamin-sensitive K+ channels in vascular endothelium by H2S represents important cellular mechanisms for H2S effect on MAB. Our study also demonstrated that endogenous CSE can generate sufficient H2S from exogenous L-cysteine to cause vasodilation. Future studies are merited to investigate direct contribution of endogenous H2S to regulation of vascular tone.
In summary, dysfunction of the vascular H2S synthase/H2S pathway was found in l-NAME-induced hypertensive rats. Exogenous H2S effectively prevented the development of hypertension induced by l-NAME. These findings suggest that the H2S synthase/H2S pathway participates in hypertension.
A full list of the Investigators is given in the Acknowledgements section Measurement of D-dimer as aid in risk evaluation of VTE in elderly patients hospitalized for acute illness: A prospective, multicenter study in China Abstract Purpose: Advanced age and hospitalization are associated with increasing risk of venous thromboembolic (VTE) events. e aim of this study was to investigate whether elevated D-dimer levels could predict VTE events in elderly patients hospitalized for acute illness.Methods: 458 consecutive patients (65% men; mean age, 77 ± 7 years) who were older than 60 years, immobilized for ≥ 3 days, and hospitalized for heart failure, respiratory failure, acute ischemic stroke, or acute infectious disease without pharmacological prophylaxis or recent major surgery, were enrolled. Elevated D-dimer levels were de ned as > 500 ng/ ml. VTE events included symptomatic VTE within 90 days or asymptomatic deep venous thrombosis screened by compression ultrasonography at enrollment and 3-week follow-up. e association between baseline D-dimer levels and subsequent VTE events, adjusted for age, sex, ethnicity, body mass index, co-morbidities, and acute disease status, was assessed using multivariate Cox proportional hazard models.Results: 49.1% (n = 225) of patients had elevated baseline D-dimer levels, and of these patients, 14.2% (n = 32) developed VTE during the 90-day follow-up. In contrast,only 5.6% (n = 13) of patients with normal D-dimer levels developed VTE. Multivariate analysis showed that patients with elevated D-dimer levels had a 3.2-fold increased risk of developing VTE (95% con dence interval, 1.5-6.5; P = 0.002) in comparison with patients with normal levels. Conclusions:In elderly patients who were hospitalized for acute medical illness, elevated D-dimer levels are associated with subsequent VTE events. Our data suggest that measurement of D-dimer, a widely-performed objective test, may help clinicians address highrisk individuals for VTE.
Background contextPedicle screw loosening is a common complication after spine surgeries. Traditionally, it was assessed by radiological approaches, both X-ray and CT (computed tomography) scan, while reports using mechanical method to study screw loosening after spine surgery are rare. The primary objective was to study the prevalent of pedicle screw loosening according to extraction torque during screw removal surgery and access the sensitivity and specificity of both X-ray and CT scan for diagnosing screw loosening. The second objective was to identify the risk factors for low extraction torque of pedicle screw that might lead to loosening.MethodsThirty-three patients who underwent pedicle screw removal surgery after at least 2 years from primary surgery were evaluated preoperatively for fixation stability by X-ray and CT scan. In total, 236 screws were taken out, and the extraction torque data was recorded and analyzed to identify the sensitivity and specificity of both imaging studies for screw loosening. Furthermore, risk factors that might contribute to low extraction torque were also studied.ResultsThe mean extraction torque of removed screws was 1.55 ± 1.00 Nm; a torque force of less than 1.02 Nm was used to define a screw as loosened. According to such criterion, the loosening rate was found to be 33%. X-ray had a sensitivity of 24% and a specificity of 98%, while CT scan had a sensitivity of 22% and a specificity of 96%. Extraction torque of pedicle screws inserted in fractured vertebrae was significantly lower than those in non-fractured vertebrae (p = 0.009); meanwhile, screws of non-fusion surgery had lower extraction torque when compared to those in fusion surgery (p = 0.001). BMD (bone mineral density) and age had low but significant linear relationship with screw extraction torque (p = 0.01, R2 = 0.304; p = 0.045, R2 = 0.123).ConclusionsOur findings showed that both X-ray and CT scan had high specificity for screw loosening detection, but their sensitivities were relatively low. Surgeons needed to be more cautious when assessing screw loosening merely according to radiological examination, and aware of that screws in fractured vertebrae or non-fusion surgery were vulnerable to loosening.
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