Comparison of oral falecalcitriol and intravenous calcitriol in hemodialysis patients with secondary hyperparathyroidism: a randomized, crossover trial.

BACKGROUND: Falecalcitriol is a novel vitamin D analog, which has a greater potential to suppress parathyroid hormone (PTH) and a longer half-life. There are few studies to compare clinical effects of oral falecalcitriol treatment with those of intravenous calcitriol treatment. METHODS: Twenty-one patients with moderate to severe SHPT were included in a random 2 x 2 crossover trial with the two vitamin D analogs (12 weeks for each treatment). The primary endpoint measure was a decrease in serum intact PTH (iPTH) level, and the secondary outcome measures included changes in serum calcium (Ca), phosphate (P), and metabolic bone marker levels. RESULTS: Both treatments decreased iPTH and whole PTH (wPTH) levels by similar degrees (iPTH, -200.1 +/- 107.0 with falecalcitriol vs. -200.8 +/- 114.9 pg/ml with calcitriol, p = 0.9895; wPTH, -137.1 +/- 73.1 with falecalcitriol vs. -120.4 +/- 81.1 pg/ml with calcitriol, p = 0.5603). Serum Ca, P, and Ca x P product levels at the end of each treatment were comparable and the frequencies of hypercalcemia and hyperphosphatemia were also similar during each treatment period. Although intravenous calcitriol treatment significantly changed intact osteocalcin and cross-linked N-telopeptide of type I collagen after 12 weeks, oral falecalcitriol treatment did not change any bone metabolic marker level. CONCLUSION: The present study showed that oral falecalcitriol treatment is effective for PTH suppression, and Ca and P metabolism in hemodialysis patients with moderate to severe SHPT, as well as intravenous calcitriol administration.

Measurement of colonic mucosal concentrations of 5-aminosalicylic acid is useful for estimating its therapeutic efficacy in distal ulcerative colitis: comparison of orally administered mesalamine and sulfasalazine.

OBJECTIVES: Oral 5-aminosalicylic acid (5-ASA) preparations have been used frequently in the treatment of ulcerative colitis. However, there have been few reports investigating the relationship between colonic mucosal concentrations of 5-ASA and its clinical efficacy when oral sulfasalazine or 5-ASA compounds were administered. The aim of this study is to compare the mucosal concentrations of 5-ASA ensured by sulfasalazine or mesalamine, and to define the clinical significance of the measurement of 5-ASA concentrations in the treatment of distal ulcerative colitis. MATERIALS AND METHODS: Biopsies were taken from the rectum and sigmoid colon of the oral sulfasalazine group (n = 13) and the slow-release 5-ASA (mesalamine) group with (n = 5) or without (n = 11) rectal administration of 5-ASA. High-pressure liquid chromatography was used to measure the tissue concentrations of 5-ASA and its metabolites. We compared the 5-ASA concentrations of the sulfasalazine group with the mesalamine group. Furthermore, we analyzed the relationship between tissue 5-ASA concentrations and the Disease Activity Index (DAI). RESULTS: The concentrations of 5-ASA and acetyl-5-ASA in the sulfasalazine group were higher than those in the group taking oral mesalamine alone (p < 0.01). The concentration of 5-ASA was much higher in the patients who received oral and rectal mesalamine in an enema than in the patients who had oral mesalamine alone. There was a significant inverse correlation between the DAI and concentrations of 5-ASA in the rectum (r = 0.712, p < 0.001). CONCLUSIONS: We demonstrated that the colonic mucosal concentration of 5-ASA was significantly higher in the sulfasalazine group than in the mesalamine group. Furthermore, the concentrations of mucosal 5-ASA may be a good marker for the estimation of its efficacy in the treatment of ulcerative colitis.

The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation.

BRCA1-BARD1 constitutes a heterodimeric RING finger complex associated through its N-terminal regions. Here we demonstrate that the BRCA1-BARD1 heterodimeric RING finger complex contains significant ubiquitin ligase activity that can be disrupted by a breast cancer-derived RING finger mutation in BRCA1. Whereas individually BRCA1 and BARD1 have very low ubiquitin ligase activities in vitro, BRCA1 combined with BARD1 exhibits dramatically higher activity. Bacterially purified RING finger domains comprising residues 1-304 of BRCA1 and residues 25-189 of BARD1 are capable of polymerizing ubiquitin. The steady-state level of transfected BRCA1 in vivo was increased by co-transfection of BARD1, and reciprocally that of transfected BARD1 was increased by BRCA1 in a dose-dependent manner. The breast cancer-derived BARD1-interaction-deficient mutant, BRCA1(C61G), does not exhibit ubiquitin ligase activity in vitro. These results suggest that the BRCA1-BARD1 complex contains a ubiquitin ligase activity that is important in prevention of breast and ovarian cancer development.

[Efficacy of mesalamine enema in the treatment of steroid-resistant or dependent distal ulcerative colitis].

The efficacy and safety of mesalamine enema were examined in 20 patients with steroid-resistant or dependent, distal ulcerative colitis. Rectal bleeding disappeared in 3 (18%). 8 (50%) of 16 patients within 2 weeks and 4 weeks after the start of mesalamine enema treatment, respectively. Mean clinical activity index (CAI) score after the treatment was significantly reduced (8.1-->3.6, p < 0.001). Furthermore, Mean doses of oral corticosteroid after the treatment (7.3 mg) were also significantly lower than those before the treatment (12.8 mg) (p < 0.01). Four patients dropped out. Three patients could not retain the enemas because of abdominal discomfort and one patient had fever and rash. There were no significant differences in age, gender, disease duration, disease type, and mean doses of oral corticosteroid before the treatment between the response group (n = 8) and the non-response group (n = 8). However, clinical and endoscopic activities before mesalamine enema treatment in the non-response group (CAI 9.8, Matts score 8.0) were higher than those in the response group (CAI 6.4, Matts score 5.5). These results suggest that mesalamine enema is useful for mildly to moderately active distal ulcerative colitis by improving clinical symptoms and reducing corticosteroid.

Active oxygen species generation and cellular damage by additives of parenteral preparations: selenium and sulfhydryl compounds.

We investigated the relationship between active oxygen species (AOS) generation and cultured vascular endothelial cellular damage caused by simultaneous exposure to selenium compounds and sulfhydryl compounds such as cysteine (Cys) or reduced glutathione (GSH). Selenium compounds, selenite, selenate or selenomethionine (SeMet), are added to total parenteral nutrition (TPN) and intravenously administered. We confirmed by luminol dependent chemiluminescence, an indicator of AOS generation, that selenite generates AOS in the presence of clinical concentrations of sulfhydryl compounds, 0.5 mM Cys or 0.5 mM GSH, and that the amount of AOS generated reaches the maximum when their mole ratio is 1:50. However, AOS generation was not observed after simultaneous administration of various concentrations of selenate or SeMet with sulfhydryl compounds. Moreover, simultaneous exposure to 10 microM selenite and sulfhydryl compounds was found to result in significant increases in the [3H]-adenine and lactate dehydrogenase (LDH) release rates from cells, a significant decrease in the amount of cellular protein, and enhancement of cellular damage as compared with after exposure to selenite alone. However, simultaneous exposure to 10 microM selenate or 10 microM SeMet together with sulfhydryl compounds did not induce cellular damage. These findings revealed that selenite generates AOS and causes cellular damage in the presence of sulfhydryl compounds. Accordingly, it seems better to choose selenate or SeMet instead of selenite when a selenium compound is to be added to TPN.

[Serum immunoglobulin concentrations and autoantibodies in patients with Yusho].

To evaluate chronic immune effects of polychlorinated biphenyl (PCB), serum immunoglobulin concentrations and autoantibodies were studied in 79 patients with Yusho in 1997. Serum levels of immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) were elevated in 10 cases (12.7%), 19 cases (24.1%) and 7 cases (8.9%), respectively. Autoatibodies were present in some patients of Yusho; 10 cases (12.7%) for rheumatoid factor and 36 cases (45.6%) for antinuclear antibody. LE factor was not detected. There were no significant correlations between blood PCB concentrations and serum immunoglobulin concentrations, or presence of autoantibodies. We conclude that antinuclear antibody in patients with Yusho is frequent, although it may not be associated with blood PCB concentration.

A case of bilateral reversible thalamic lesions.

We describe a case of bilateral reversible thalamic lesions with no neurological deficits and a good prognosis. The lesions appeared as low-density areas on CT and high-intensity areas on T2-weighted MR imaging, and resolved within 1 month, suggesting that the cause was edema.

Comparison of effects of margarite extract and recombinant human superoxide dismutase on paraquat-induced superoxide anion radicals in rat lung.

The effects of medicinal margarite extract and recombinant human superoxide dismutase (r-h SOD) on acute paraquat intoxication were examined in the rat lung. Forty-eight Sprague-Dawley rats under pentobarbital anesthesia were randomly assigned to one of four groups receiving i.v. injection of physiological saline (control), i.v. injection of 70 mg/kg paraquat, or i.v. injection of either 50 mg/kg of margarite extract or 50,000 unit/kg of r-h SOD 10 minutes before and 1 and 2 hours after an equivalent paraquat administration. Examination of lung superoxide anion radicals (O2-.), lipid peroxides, and histopathological changes showed that paraquat significantly increased superoxide anion radicals (383% of control) reacted with CLA-phenyl. Both margarite extract and r-h SOD decreased superoxide anion radicals to 119% and 83% of control, respectively. Margarite extract, rather than r-h SOD, significantly alleviated the paraquat-induced infiltration of polymorphonuclear leukocytes and macrophages into the alveolar walls. There were no significant inter-group differences in lipid peroxides in the lung. Component analysis showed that margarite extract was rich in L- and D-arginine. The scavenging mechanism of margarite extract may be related to L-arginine but needs to be further verified in the future study.

Effect of phospholipid emulsifiers on physicochemical properties of intravenous fat emulsions and/or drug carrier emulsions.

The physicochemical properties of soy bean oil emulsions stabilized with purified egg lecithins (phosphatides) of various concentrations have been examined. The zeta potential of the emulsion droplets and the mean particle size of oil droplets in 10% (w/w) o/w-type emulsion decreased with increasing emulsifier concentration and then levelled off at more than 1.2% (w/w). In rheological measurements, at the initial stage, the viscosity of 10% (w/w) o/w-type emulsion gradually increased with increasing purified egg lecithin concentration, at the next stage, a plateau was reached at about 1.0-1.4% (w/w), and at the final stage, the viscosity curve showed a dramatic increase. These results indicate that emulsions stabilized by purified egg lecithin at more than 1.2% (w/w) are likely to be sufficiently stable.

Electrical skin resistance changes in meridians during ophthalmic surgery with local anesthesia.

Electrical skin resistance on Accumulation points in twelve meridians was measured during operation of cataract under local anesthesia. Electrical skin resistance increased an average of 15 percent in bladder, kidney, liver, stomach, gall bladder meridians, and decreased an average of 18 percent in lung, small intestine, heart, spleen-pancreas, heart constrictor, triple heater, large intestine meridians. When comparing the skin resistance values with those under acupuncture anesthesia during ophthalmic surgery, the skin resistance value under acupuncture anesthesia exhibited a marked decrease in all meridians (average 23 percent decrease) except the kidney meridian. On the other hand, the skin resistance under local anesthesia was only a 7.4 percent decrease in all meridians except the kidney meridian. It was speculated as one of the reasons for less changes of skin resistance under local anesthesia that sympathetic nervous activity did not occur so much because of pain relief due to local anesthesia.

Changes in the electrical skin resistance on meridians during gastric surgery under general anesthesia.

The purpose of this experiment was to investigate how the skin resistance on accumulation points is modified by general anesthesia in gastric surgery and whether the stomach meridian shows particular changes or not. Ten patients were inducted with 5 mg/kg of thiopental and maintained with nitrous oxide-oxygen-halothane. The skin resistance on 12 meridians decreased gradually from an average of 432 K alpha before anesthesia to an average of 266 K alpha at the end of surgery. However, the kidney and the bladder meridians showed a trend to exceptional increase by a maximum of 100 and 73 percent, respectively. The skin resistance on the stomach meridian showed only a 23 percent decrease and no particular changes. No significant difference was noted in the change rate of meridians between the Yin and Yang groups. Comparison of these changes with those under acupuncture or local anesthesia during ophthalmic surgery was discussed.