Inhibition of ecto-ATPase activity by curcumin in hepatocellular carcinoma HepG2 cells

Effects of curcumin, a major constituent of turmeric, on ecto-nucleotidases have not been clarified. Here, we investigated whether curcumin affects ecto-nucleotidase activities in human hepatocellular carcinoma HepG2 cells. In the cells, high levels of Mg²⁺-dependent activity of ecto-nucleotidases were observed in the presence of 1 mM adenosine triphosphate (ATP). The activity was inhibited by ecto-ATPase inhibitors such as suramin, ZnCl₂ and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid. On the other hand, the activity was significantly decreased at alkaline pH (pH 9) and was not inhibited by levamisole, an inhibitor of alkaline phosphatase. In the presence of ATP, curcumin inhibited the activity in a concentration-dependent manner (IC₅₀ = 6.2 μM). In contrast, curcumin had no effects on ecto-nucleotidase activity in the presence of ADP (1 mM) or AMP (1 mM). The K _m value for ATP hydrolysis of curcumin-sensitive ecto-ATPase was similar to the value of NTPDase2, an isoform of ecto-nucleoside triphosphate diphosphohydrolase. These results suggest that curcumin is a potent inhibitor of ecto-ATPase and may affect extracellular ATP-dependent responses.     

Pseudorenal failure due to intraperitoneal bladder rupture after blunt trauma: usefulness of examining ascitic fluid sediment

A 42-year-old man noted decreased urine output and visited our emergency department. He said that 3 days previously, he had gotten drunk and fallen down a set of stairs. Blood tests and abdominal contrast-enhanced computed tomography revealed no abnormalities. A serum creatinine level of 5.89 mg/dL led to a diagnosis of acute renal failure and his hospitalization. After admission, his ascitic fluid level gradually increased, suggesting urine leakage into the peritoneal cavity. Microscopic examination of his ascitic fluid sediment revealed the presence of hyaline casts enclosing renal tubular epithelial cells. Cystography demonstrated contrast medium leakage into the peritoneal cavity, which led to a diagnosis of bladder rupture. Examination of ascitic fluid sediment is simple and very useful for diagnosing bladder rupture.     

Neonatal herpes simplex type II virus infection complicated with meningitis and virus-associated hemophagocytic syndrome

A 14-day-old neonate was transferred to our university hospital because of respiratory distress and mild disturbance of consciousness. He had no history of abnormal pregnancy or delivery, but had developed apnea at 6 days old. Thereafter, respiratory distress progressed and his condition deteriorated. On admission to our hospital, several vesicles were found on the left upper arm, and moderate hepatomegaly was also present. Herpes simplex virus (HSV) type II genome was detected from serum, spinal fluid, and bone marrow. Laboratory examinations revealed typical abnormalities of disseminated intravascular coagulation, increased levels of serum ferritin, aspartate aminotransferase, and lactate dehydrogenase. Bone marrow aspiration demonstrated activated macrophages and hemophagocytosis. Spinal tap revealed numerous mononuclear cells. Meningitis and virus-associated hemophagocytic syndrome (VAHS) due to systemic HSV type II infection were thus diagnosed. Acyclovir (60 mg/kg/day) and vidarabine were promptly administered. Dexamethasone palmitate and intravenous cyclosporine were also administered for systemic inflammation due to VAHS. Finally, these aggressive therapies rescued the patient without any sequelae. In general, neonatal systemic HSV infection is life-threatening and results in poor intact survival. Our case report suggests that not only antiviral treatment for HSV, but also anti-inflammatory treatment including steroid and cyclosporine should be considered from the early phase of neonatal systemic HSV infection.     

The effects of clonidine on arterial baroreflex sensitivity and cardiopulmonary baroreflex control of sympathetic nerve activity in patients with left ventricular dysfunction

Background: Clonidine is a potent sympatholytic drug with central neural effects. The aim of this study was to evaluate the effects of clonidine on arterial baroreflex sensitivity (BRS) and cardiopulmonary (CP) baroreflex control of muscle sympathetic nerve activity (MSNA) in patients with left ventricular (LV) dysfunction. Method: Twenty patients were randomly assigned to either clonidine or placebo groups (10 in each group). BRS (by phenylephrine method) and CP baroreflex (by lower body negative pressure) effects on sympathetic nerve activity (circulating norepinephrine and MSNA recordings) were measured before and after a 4‐week treatment period. Results: Clonidine lowered blood pressure and heart rate. Clonidine was accompanied not only by a decrease in plasma noradrenaline (from 444 ± 196 to 260 ± 144 pg ml^?1) but also by a reduction in directly measured MSNA (from 47 ± 16 to 36 ± 16 bursts min^?1). BRS increased significantly from 3·01 ± 1·19 to 6·86 ± 2·84 ms mmHg^?1 after clonidine. When expressed as per cent change in MSNA during CP baroreceptor stimulation, CP baroreflex control of MSNA was significantly increased from 9·26 ± 8·93% to 28·83 ± 11·96% after clonidine. However, there were no significant changes in the measured variables in the control group. Conclusion: Clonidine enhanced BRS and CP baroreflex control of MSNA while reducing baseline sympathetic activity in patients with LV dysfunction.