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Background:The optimal sampling points and thresholds for initial serum vancomycin (VCM) concentrations have not been determined in hemodialysis (HD) patients. To clarify this, multiple blood tests were performed, and the correlations between VCM concentrations at several sampling points and the area under the concentration-time curve for 24 hours (AUC24h) were analyzed., Methods:A single-center, prospective observational study was conducted. Patients with end-stage renal failure who received VCM treatment while undergoing chronic maintenance HD were enrolled in this study. HD was performed using a high-flux membrane as the dialyzer. After VCM administration, 7 points were sampled between the first and second HD. The AUC24h after the end of the first HD (AUC0-24) and that before the end of the second HD (AUC24-48) were calculated using the linear trapezoidal method. Correlation analysis and simple regression analysis between AUC24h and serum concentrations were performed at each sampling point., Results:Nine patients were evaluated. Strong correlations were found between AUC24-48 and serum concentrations at 24 hours after the initiation of VCM treatment following the first HD (C24h, R = 0.983 and P < 0.001), between AUC0-24 and C24h (R = 0.967 and P < 0.001), and between AUC24-48 and serum concentration just before the second HD (Cpre(HD2), R = 0.965 and P < 0.001). Regression equations with high coefficients of determination (R2 > 0.9) were obtained, and a C24h of ≥18.0 mg/L and a Cpre(HD2) of ≥16.5 mg/L were required to achieve an AUC24-48 value of ≥400 mg·h/L. In addition, a C24h of ≤23.3 mg/L was estimated to satisfy the AUC0-24 range of ≤600 mg·h/L., Conclusions:C24h and Cpre(HD2) are optimal sampling points for predicting VCM-AUC24h in HD patients.

We treated a patient with neurosarcoidosis, which caused the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), in whom diagnosis was performed using neuroendoscopy. The patient was a 56-year-old female who was hospitalized for hyponatremia and diagnosed with SIADH based on a detailed examination. During the course, she developed impaired consciousness due to acute hydrocephalus, which improved after ventricular drainage. Head magnetic resonance imaging (MRI) confirmed nodular lesions at the floor of the third ventricle and the cerebral aqueduct. Neuroendoscopic biopsy led to the diagnosis of neurosarcoidosis. Her hyponatremia improved after steroid therapy. Neurosarcoidosis can cause SIADH, and complication of hydrocephalus may lead to a poor prognosis. Neuroendoscopy appears to be effective for the diagnosis of neurosarcoidosis with hydrocephalus and helps in deciding the treatment modality.

Lithocholic acid (LCA), one of the major components in secondary bile acids, promotes carcinogenesis in rat colon epithelial cells induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), which methylates DNA. Base-excision repair of DNA lesions caused by the DNA methylating agents requires DNA polymerase beta (pol beta). In the present study, we examined 17 kinds of bile acids with respect to inhibition of mammalian DNA polymerases in vitro. Among them, only LCA and its derivatives inhibited DNA polymerases, while other bile acids were not inhibitory. Among eukaryotic DNA polymerases alpha, beta, delta, epsilon, and gamma, pol beta was the most sensitive to inhibition by LCA. The inhibition mode of pol beta was non-competitive with respect to the DNA template-primer and was competitive with the substrate, dTTP, with the Ki value of 10 microM. Chemical structures at the C-7 and C-12 positions in the sterol skeleton are important for the inhibitory activity of LCA. This inhibition could contribute to the tumor-promoting activity of LCA.

Effect of simvastatin on the lipid profile of hemodialysis patients. Background Simvastatin, a 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is used widely for treatment of hypercholesterolemia. Simvastatin may be a suitable treatment for dyslipidemia in hemodialysis (HD) patients. However, investigation of the side-effects and safety of long-term administration of simvastatin to HD patients has been limited. In this study, we investigated the effects and safety of simvastatin and its effects on lipoprotein metabolism in hypercholesterolemic patients on HD. Methods Simvastatin was administered at a dosage of 5 mg/day for 24 weeks to 38 HD patients with high serum total cholesterol (TC) levels (200 mg/dl) or low high-density lipoprotein cholesterol (HDL-C) levels (35 mg/dl). Every four weeks, serum lipids, apolipoprotein, lipoprotein(a) [Lp(a)] and malondialdehyde (MDA) levels were measured. In addition, lipid levels were determined in each lipoprotein fraction separated by ultracentrifugation. Results After 24 weeks of simvastatin administration, TC significantly decreased by 25.7%, and low-density lipoprotein cholesterol (LDL-C) was significantly decreased by 33.6%. Triglyceride (TG) and HDL-C showed no significant changes. Apolipoprotein (apo) B significantly decreased by 24.5% and apo E by 30.0%. No significant changes were observed in the other apolipoproteins. MDA was also significantly decreased, whereas Lp(a) was not significantly altered. In the lipoprotein fractions, very LDL cholesterol (VLDL-C), intermediate-density lipoprotein cholesterol (IDL-C), LDL1 cholesterol (LDL1-C), and LDL2 cholesterol (LDL2-C) showed significant decreases. No particular side-effects were observed during the 12 months of simvastatin administration. Conclusions These results suggest that simvastatin appears to be safe and effective in HD patients with hypercholesterolemia.