Recent reports have revealed that hydrogen sulfide (HS) exerts critical actions to promote cardiovascular homeostasis and health. Thiosulfate is one of the products formed during oxidative HS metabolism, and thiosulfate has been used extensively and safely to treat calcific uremic arteriopathy in dialysis patients. Yet despite its significance, fundamental questions regarding how thiosulfate and HS interact during redox signaling remain unanswered. In the present study, we examined the effect of exogenous thiosulfate on hypoxia-induced HS metabolite bioavailability in human umbilical vein endothelial cells (HUVECs). Under hypoxic conditions, we observed a decrease of GSH and GSSG levels in HUVECs at 0.5 and 4 h as well as decreased free HS and acid-labile sulfide and increased bound sulfide at all time points. Treatment with exogenous thiosulfate significantly decreased the ratio of GSH/GSSG to total sulfide of HUVECs under 0.5 h of hypoxia but significantly increased this ratio in HUVECs under 4 h of hypoxia. These responses reveal that thiosulfate has different effects at low and high doses and under different O tensions. In addition, treatment with thiosulfate also diminished VEGF-induced cystathionine-γ-lyase expression and reduced VEGF-induced HUVEC proliferation under both normoxic and hypoxic conditions. These results indicate that thiosulfate can modulate HS metabolites and signaling under various culture conditions that impact angiogenic activity. Thus, thiosulfate may serve as a unique sulfide donor to modulate endothelial responses under pathophysiological conditions involving angiogenesis. This report provides new evidence that different levels of exogenous thiosulfate dynamically change discrete sulfide biochemical metabolite bioavailability in endothelial cells under normoxia or hypoxia, acting in a slow manner to modulate sulfide metabolites. Moreover, our findings also reveal that thiosulfate surprisingly inhibits VEGF-dependent endothelial cell proliferation associated with a reduction in cystathionine-γ-lyase protein levels.
The emergency department (ED) at Louisiana State University-Health Science Center in Shreveport (LSUHSC-S) serves an urban population with a large rural catchment area. This study focuses on demographic variables in substance abuse trends in this region based on urine drug screen (UDS) results. A database of de-identified UDSs ordered in the ED at LSUHSC-S between 1998 and 2011 was analyzed. Samples were tested for the presence of amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, 3,4-methylenedioxymethamphetamine (MDMA), methadone, methamphetamine, opiates, phencyclidine, and propoxyphene. The patient population was categorized by age group, gender, and race. The majority of tests were performed on African-American and Caucasian patients ages 18 to 54 followed by the 0 to 11-year-old group. Of the drugs tested, cannabinoids represented the highest percentage of positive results in both the African-American and Caucasian populations. Opiates returned the highest percent of positive results among all prescription drugs. The Caucasian population predominated in positive tests for prescription drugs (opiates and benzodiazepines), while the African-American population predominated in results positive for illicit drugs (cannabinoids and cocaine). The increasing presence of opiates and cannabinoids, particularly in very young patients, should prompt policy makers and healthcare providers to develop intervention strategies to protect the most vulnerable populations.
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