Low salt intake and changes in serum sodium levels in the combination therapy of low-dose hydrochlorothiazide and angiotensin II receptor blocker.

BACKGROUND: The present study was conducted to examine the association of dietary salt intake with changes in serum sodium (srNa) levels when angiotensin II receptor blocker (ARB) treatment is changed to the combination of ARB plus low-dose diuretic (hydrochlorothiazide [HCTZ]). METHODS AND RESULTS: In 88 patients (age 70 ± 12 years), ARB treatment was switched to the combination therapy (same dosage ARB+12.5mg/day HCTZ). The srNa level was measured before and 6 months after administration of the combination. The daily salt intake was estimated by the Kawasaki formula using second morning urine sample. The study subjects were divided into quintile ranges according to daily salt intake. The reduction in srNa levels by switching to the combination treatment was significant in subjects in the lowest quintile Q5 (≤ 8.9 g/day salt intake), but not in those in Q1-4 (28.1-9.3g/day salt intake). Increases in serum creatinine and uric acid levels were significantly larger in the former group than in the latter group. CONCLUSIONS: In elderly Japanese subjects with low salt intake (<8.9 g/day), the addition of a low-dose diuretic (12.5mg HCTZ) to ARB treatment causes significant reduction in srNa levels, which might affect blood osmolarity.

Effects of three Chinese herbal medicines on plasma and liver lipids in mice fed a high-fat diet.

Chinese herbal medicines, Inchinko-to, Bofu-tsusho-san and Dai-saiko-to, containing 3, 18 and 8 components, respectively, have since long been used as an anti-inflammatory, antipyretic, choleretic and diuretic agent for liver disorders and jaundice, as an anti-obesity agent, a hypocholesterolemic agent for liver disorders and a therapeutic and/or preventive agent for cholesterol gallstone disease with hypertriglycerid-emia in China and Japan, respectively. In the present study, we investigated the effects of these three herbal medicines in young male mice fed a high-fat diet. Plasma levels of lipids and the numbers of the fatty droplets in the liver cytoplasm were markedly lowered by the diets supplemented with three herbal medicines. The liver weights and the body growth were reduced by the diet supplemented with Dai-saiko-to, which slightly affected the concentrations of total protein, albumin, creatinine or calcium, and the activity of lactate dehydrogenase. Thus, Dai-saiko-to, besides Bofu-tsusho-san, seems effective in the activities of anti-obesity, anti-hyperlipidemia and anti-hyperlipids in liver cytoplasm, when used carefully.

Paradoxical effect of cytosine arabinoside on mouse leukemia cell line L1210 cells.

We investigated the effects of 1-beta-D-arabinofuranosylcytosine (ara-C) on the growth of murine leukemic L1210 cells, which were cultured with high (2.0 x 10(3) ng/ml), middle (100 ng/ml) and low doses (5.0 ng/ml) of ara-C. In the analysis by flow cytometry, high dose ara-C arrested the cell cycle in the G0/G1-phase. Middle and low doses ara-C induced a block in the S-phase, that was not completely blocked by the low dose. Analysis of DNA fragmentation revealed that ara-C dose-dependently induced apoptosis, which was only slightly induced by the low dose. We measured activities of cellular thymidylate synthase (TS) and thymidine kinase (TK) after 24-h culture. Low and middle doses, but not high dose ara-C markedly enhanced TS activity to 2.9- in low and 5.3-fold in middle doses ara-C, and TK activity to 1.3- in low and 2.2-fold in middle doses, respectively, compared with those of the control. The cells accumulated in the S-phase by 48-h culture with low dose ara-C and markedly proliferated compared to that of the control in ara-C-free medium. These results indicate that non-high dose ara-C enhances DNA-synthesizing enzyme activities in L1210 cells, and withdrawal of the non-high dose ara-C results in paradoxical cell proliferation. Thus, daily intramuscular injections with an insufficient dose of ara-C may induce cells into S-phase, resulting in the proliferation of leukemic cells.

Probucol, a hypocholesterolemic agent, prevents the development of uterine adenomyosis induced by pituitary grafting in mice.

This in vivo experimental study was designed to investigate the effects of probucol, a hypocholesterolemic agent, on uterine adenomyosis which is frequently induced by pituitary grafting in mice. SHN mice, which are known to develop uterine adenomyosis spontaneously, and much sooner after pituitary grafting, were used and histopathological study on the uteri in pituitary gland-implanted mice with or without probucol treatment was performed. Four out of 10 pituitary gland-implanted mice developed uterine adenomyosis with dilated blood vessels, but none of the probucol-treated mice. There were no differences between pituitary-grafted mice with or without probucol treatment in body weight and wet weights of uterus, ovaries, kidney and liver except spleen. Probucol markedly reduced the serum levels of total cholesterol, free cholesterol, free fatty acids, phospholipids and triglycerides and, thus, this agent inhibited the incidence of uterine adenomyosis induced by pituitary grafting in mice.

Early progression from dimethyl sulfoxide-induced G(0)/G(1) arrest in L(1210) cells.

Recently, dimethyl sulfoxide (DMSO) has been used as a convenient cryoprotectant for stem cells in stem cell transplantation using allogenic peripheral blood or umbilical cord blood. As the stem cells have a multipotency, clarification of the extent of cell proliferation after transplantation is difficult. In the present study, DMSO gradually induced G(0)/G(1) arrest in mouse leukemia L(1210) cells with good cell viability. After removal of DMSO, the cells proliferated appropriately, resulting in expression of the DNA-synthesizing enzymes thymidylate synthase and thymidine kinase within 6h, and the cells entering into S phase within 12h. The sequence was followed by the marked activation of both enzymes within 24h and the increase of bromodeoxyuridine (BrdU) immunoreactive (S phase) cells with rapid cell proliferation within 36 h. In conclusion, mouse leukemia L(1210) cells, which were treated with 1.5% DMSO for 96 h, tolerated the treatment and reversed the cell cycle arrest within 36 h.