Leucomycin A3, a new antibiotic from Streptomyces kitasatoensis.
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Biomedical subjects
Publications and source records attributed to T Hata.
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In a previous study, birth weight projections obtained with Rossavik growth models were systematically greater than actual birth weights in triplets but not in singletons. To investigate the cause of this overestimation, average mean percent deviations for head circumference (HC), abdominal circumference (AC), thigh circumference (ThC), and weight (WT) at different times in the third trimester were studied in 13 normal triplet and 20 normal singleton fetuses using individual growth curve standards. Average mean percent deviation values for HC in both singletons and triplets were close to zero throughout the third trimester. Average mean percent deviation values for AC in both singletons and triplets were similar, and remained relatively constant. Average mean percent deviation values for ThC in triplets decreased toward the end of the third trimester, but those for singletons increased. Average mean percent deviation values for estimated weight did not change during the third trimester in singletons whereas those in triplets decreased. The difference in average mean percent deviation values for estimated weight between singletons and triplets in the 32- to 36-week interval was statistically significant. There were no significant differences between actual and predicted measurements for HC in both singletons and triplets at birth. However, actual birth measurements were systematically less than predicted birth measurements for AC and ThC in singletons, and for AC, ThC, and WT for triplets. These systematic differences were significantly larger in triplets for ThC and WT. Nutrition Score values, direct measures of subcutaneous tissue, were significantly lower in triplets compared to singletons.(ABSTRACT TRUNCATED AT 250 WORDS)
This review article presents fetal organ measurements obtained with ultrasound. Data derived from measurements of the brain, heart, lung, thymus, liver, spleen, pancreas, stomach, gallbladder, kidney, adrenal glands, intestine, and bladder are summarized, compared and evaluated critically. The selection of optimal parameters, development of valid measurement procedures, and use of mathematical modeling and descriptive statistics are necessary for quantitative studies by ultrasound of fetal organ growth.
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Numerous studies suggest that the renin angiotensin system (RAS) is involved in the development of cardiac hypertrophy. In the present study we produced cardiac hypertrophy in rats subjected to abdominal aortic banding and also induced cardiac regression by the administration of an angiotensin converting enzyme (ACE) inhibitor, enalapril, at 3, 10 and 30 mg/kg/day. Each drug was administered to the rats for 6 weeks from 6 weeks after aortic banding. The left ventricular weight significantly decreased at 10 and 30 mg/kg/day of enalapril as well as the systolic blood pressure. Using the reverse transcriptase polymerase chain reaction, the increased levels of ACE and AT1 mRNA were significantly inhibited in the aortic banding rats treated with the above concentrations of enalapril. The ACE activity in both the plasma and heart tissue preparations was significantly inhibited by enalapril. Similar observations were also seen after the administration of angiotensin type 1 receptor blockade, E-4177, into the aortic banding rats. The treatment with enalapril at 3 mg/kg/day did not reduce the left ventricular weight or the systolic blood pressure in the aortic banding rats. However, this low-dose treatment did significantly decrease the left ventricle to body weight ratio in the aortic banding rats without a reduction of the systolic blood pressure. Therefore, using the low-dose enalapril, the ACE activity in plasma was in part inhibited and the levels of ACE mRNA also decreased in the heart tissue of aortic banding rats, while the level of AT1 mRNA showed no such decrease. These results thus indicate that chronic ACE inhibitor at low doses has a beneficial effect on the regression in the pressure-induced cardiac hypertrophy. It is thus assumed that this effect may also contribute to the presence of an alternate pathway for the conversion of angiotensin I to angiotensin II which might also act as a possible mechanism for cardiac regression.
The pharmacokinetics of droloxifene have been studied in female mice, rats, monkeys, and premenopausal and postmenopausal patients. Droloxifene was rapidly and almost completely absorbed after oral dosing. The bioavailability was 8% in mice, 18% in rats and 11% in monkeys due to extensive first-pass metabolism. Droloxifene is widely distributed as demonstrated by its large volume of distribution and the fact that radioactivity in most tissues and organs was higher than in the blood. After oral dosing, the serum and plasma concentrations of unchanged drug declined with terminal half-lives of 1.6 h in mice, 4.3 h in rats, 10.6 h in monkeys and 25 h in patients. The systemic clearance was in the order of mice > rats > monkeys, and nearly equalled the hepatic blood flow in each species. Most of the 14C from [14C]-droloxifene administered orally and i.v. to rats and monkeys was excreted in the faeces. Droloxifene was metabolized extensively by phase I and phase II metabolism. 3-methoxy-4-hydroxy droloxifene was the major metabolite in rat faeces. The metabolites in rat and monkey faeces were not so different qualitatively. Pharmacokinetic parameters were not significantly different between premenopausal and postmenopausal patients.
The relationship between plasma concentrations and inhibitory effects on gastric acid secretion by proton pump inhibitors (PPIs) omeprazole (OPZ), lansoprazole (LPZ) and pantoprazole (PPZ), was analyzed using a pharmacokinetic/pharmacodynamic (PK/PD) model in humans. The estimated values of apparent reaction rate constant of PPI and H+,K+-ATPase (K) were 1.34 +/- 0.17 (microM(-1) x h(-1)), 0.339 +/- 0.002 and 0.134 +/- 0.006 for OPZ, LPZ and PPZ, respectively. The estimated values of apparent turn-over rate constant of H+,K+-ATPase (k) were 0.0252 +/- 0.0019 (h(-1)), 0.0537 +/- 0.0006 and 0.0151 +/- 0.0002 for OPZ, LPZ and PPZ, respectively. The apparent dissociation constants of the H+,K+-ATPase-PPI complex (k/K x fp) corrected with plasma free fraction (fp) were about 1 nM for OPZ and LPZ and 2.3 nM for PPZ. Therefore, the potency of the inhibitory effect of PPZ on acid secretion may be slightly weaker than that of OPZ or LPZ. The apparent half lives (ln2/k) of the inhibitory effect on acid secretion were 12.9 h for LPZ, < 27.5 h for OPZ, and < 45.9 h for PPZ, the recovery rate of the inhibitory effect of PPZ on acid secretion was slowest among these PPIs. In conclusion, the relationship between plasma concentrations and inhibitory effects of PPIs on gastric acid secretion could be analyzed by the PK/PD model.
The effects of long-term monotherapy with cilazapril, an angiotensin-converting enzyme inhibitor, on blood pressure, glucose tolerance, and serum lipid profiles were prospectively investigated in 66 patients with hypertension: 23 with normal glucose tolerance and 43 with glucose intolerance (including 9 patients with non-insulin-dependent diabetes mellitus). The levels of plasma glucose, serum insulin, serum lipids, glycated hemoglobin A(lc) (Hb A(lc)), and fructosamine were determined before and during long-term (mean +/- SD, 26.2 +/- 1.2 weeks) therapy with cilazapril. A 75-g oral glucose tolerance test was performed before and during treatment. Significant reductions in both systolic and diastolic blood pressures in both patient groups were maintained during the study. Neither fasting nor post-glucose load venous plasma glucose levels were altered in either group of patients, and no patient with normal glucose tolerance developed diabetes mellitus during the study. There was no significant change in the insulinogenic index (delta serum insulin/delta venous plasma glucose at 30 minutes post-glucose load) in either group, and glucose intolerance was slightly improved with significant reductions (P < 0.01) in Hb A(lc) and fructosamine in the patient group with impaired glucose tolerance. Serum total cholesterol (TC), low-density lipoprotein cholesterol, and triglyceride levels were significantly (P < 0.01) decreased and high-density lipoprotein cholesterol levels increased in patients with hypercholesterolemia (TC levels > or = 5.69 mmol/L). These results suggest that long-term cilazapril therapy may improve glucose and lipid metabolism in hypertensive patients with impaired glucose tolerance. Cilazapril also appears to be useful as an antihypertensive agent for hypertensive patients with either impaired glucose tolerance or hypercholesterolemia.
Transport of iron from the mother to the fetus is essential for the normal development of the fetus and abnormalities in the transferrin receptor (TFR) on the placental trophoblasts might have some crucial effects on the fetal iron metabolism. The present study was undertaken to determine whether there are any changes in the expression of the transferrin receptor in the placenta from pre-eclamptic mothers. An immunohistochemical study using antibodies specific for C-terminus and N-terminus regions of the TFR revealed that TFR expression by syncytiotrophoblasts around chorionic villi is markedly reduced in placentae from pre-eclamptic pregnancies compared to those from normal pregnancies and pregnancies at early gestational age that terminated by abortion. The same result, although to a lesser extent, was obtained even in trophoblasts which were located around atrophic villi with fibrotic changes in the interstitium, or which invaded into the deciduas. The expression of human chorionic gonadotropin (HCG) on those cells was observed to the same extent in the normal and pre-eclamptic pregnancy groups. The concentration of TFR in the peripheral blood also decreased in pre-eclampsia. These results suggest that TFR synthesis in the pre-eclampsia, especially in the placental trophoblasts, is decreased.
In order to characterize the expression of adrenomedullin during pregnancy, we measured the mature and total concentrations in maternal plasma and amniotic fluid, and examined its expression in fetoplacental tissues. Plasma samples were obtained from 13 normal normotensive non-pregnant women and 14 normal normotensive post partum women. Maternal plasma and amniotic fluid samples were obtained from 37 normal pregnant women (10 in the first trimester, 13 in the second trimester and 14 in the third trimester). Fetoplacental tissues were obtained from first and third-trimester pregnancies. Mature and total adrenomedullin concentrations in plasma and amniotic fluid were determined by using specific radioimmunoassay. The distribution and expression of adrenomedullin were determined using immunohistochemistry, reverse-transcriptase polymerase chain reaction, and in situ hybridization. Plasma total adrenomedullin concentrations were increasing with advancing gestation. The mature/total adrenomedullin ratio in the second trimester was the highest during pregnancy. Mature and total adrenomedullin concentrations in the amniotic fluid were significantly higher than those in the maternal plasma throughout gestation (P< 0.05). Mature adrenomedullin concentrations and the mature/total adrenomedullin ratio in the amniotic fluid increased with advancing gestation. There was a significant linear correlation between amniotic fluid and maternal plasma mature/total adrenomedullin ratio in the first or second trimester of pregnancy. Adrenomedullin mRNA was identified in the amniotic membrane and chorionic villi, and within the endothelial layers of villous blood vessels. These results suggest that the mature/total adrenomedullin ratio is modified in maternal plasma and amniotic fluid with advancing gestation.
To assess the growth and function of the fetal spleen, ultrasonographic examinations were performed on 229 normal fetuses, ranging from 20 to 41 weeks, menstrual age. Curvilinear relationships were found between the menstrual age and splenic length (R2 = 92.7%), circumference (R2 = 93.9%), and area (R2 = 95.2%). A normal range of splenic length, circumference, and area measurements for estimating the growth of the fetal spleen during normal pregnancy was generated. Splenic parameter values just after delivery were significantly lower than those measured within 7 days before delivery, and returned to former sizes 24 hours later, in both vaginal delivery and cesarean section groups. Splenic parameter values in the vaginal delivery group were also significantly lower than those in the cesarean section group, just after delivery. Moreover, neonatal splenic length showed negative correlations with lactate dehydrogenase (p < 0.001) and glutamic oxaloacetic transaminase (p < 0.05) in the umbilical venous blood, respectively. These results provide a foundation for the evaluation of fetal splenic growth and function during pregnancy and the early neonatal period.
The purpose of this study was to evaluate the long-term efficacy and tolerability of pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in elderly patients with hypercholesterolemia. Pravastatin was administered for 12 months at a mean final dose of 9.9 mg/d to 208 elderly patients (mean [+/- SD] age, 70 +/- 7 years) with levels of total serum cholesterol greater than 5.69 mmol/L. The mean total cholesterol level was significantly decreased from 6.85 +/- 0.80 mmol/L to 5.59 +/- 0.70 mmol/L after 3 months, and this decrease was maintained thereafter. A similar change was observed in the mean serum level of low-density lipoprotein cholesterol. Although the mean serum level of high-density lipoprotein cholesterol in all the patients did not change significantly, the level in 34 patients with a value lower than 1.03 mmol/L was significantly increased after 3 months and thereafter. The serum level of triglycerides in all patients was significantly decreased after 3 months and thereafter and the decrease was more marked in 101 patients with levels greater than 1.73 mmol/L. In 168 elderly patients receiving 10 mg/d of pravastatin, there were significant negative correlations between the percent decrease in total cholesterol and both baseline total serum cholesterol level (r = -.354, P < 0.001) and age (r = -.208, P = 0.007). No serious side effects were observed. These results indicate that long-term administration of pravastatin is beneficial in the treatment of hypercholesterolemia in elderly patients.