Pharmacokinetics and pharmacodynamics of intravenous trasemide in mutant Nagase analbuminemic rats

The importance of plasma protein binding of intravenous furosemide in circulating blood for its urinary excretion and hence its diuretic effects in mutant Nagase analbuminemic rats (NARs, an animal model for human familial analbuminemia) was reported. Based on the furosemide report, the diuretic effects of another loop diuretic, torasemide, could be expected in NARs if plasma protein binding of torasemide is considerable in the rats. This was proven by this study. After intravenous administration of torasemide, 10 mg/kg, to NARs, the plasma protein binding of torasemide was 23.3% in the rats due to binding to alpha- and beta-globulins (this value, 23.3%, was greater than only 12% for furosemide), and hence the percentages of intravenous dose of torasemide excreted in 8-h urine as unchanged drug was 14.9% in the rat (this value was considerably greater than only 7% for furosemide). After intravenous administration of torasemide to NARs, the AUC (301 versus 2680 microg/min/ml) was significantly smaller [due to significantly faster both Cl(r) (4.81 versus 0.386 ml/min/kg) and Cl(nr) (28.3 versus 3.33 ml/min/kg)], terminal half-life (18.3 versus 73.5 min) and mean residence time (6.97 versus 61.8 min) were significantly shorter (due to faster Cl, 33.2 versus 3.74 ml/min/kg), and amount of 8-h urinary excretion of unchanged torasemide (446 versus 323 microg, due to increase in intrinsic renal excretion) was significantly greater than those in control rats. The 8-h urine output and 8-h urinary excretions of sodium and chloride were comparable between two groups of rats although the 8-h urinary excretion of torasemide was significantly greater in NARs. This could be explained by the following. The amount of urinary excretion of torasemide was significantly greater in NARs than that in control rats only between 0 and 30 min urine collection. In both groups of rats, the urinary excretion rate of torasemide during 0-30 min reached an upper plateau with respect to urine flow rate as well urinary excretion rates of sodium and chloride. Therefore, the diuretic effects (8-h urine output and 8-h urinary excretions of sodium and chloride) were not significantly different between the two groups of rats.     

A new acylglycosyl sterol from quisqualis fructus

A new acylglycosyl sterol (4) was isolated from the MeOH extract of Quisqualis Fructus together with four known compounds. On the basis of spectroscopic data, their structures were elucidated as clerosterol (1), betulinic acid (2), methylursolate (3), 3-O-[6'-O-(8Z-octadecenoyl)-beta-D-glucopyranosyl]-clerosterol (4) and alpha-xylofuranosyluracil (5).     

Efficacy and Safety of Omija (Schisandra chinensis) Extract Mixture on the Improvement of Hyperglycemia: A Randomized,Double-Blind,and Placebo-Controlled Clinical Trial

A previous animal study demonstrated that the administration of Omija extract and soybean mixture (OSM) improved glycemic control in the type 2 diabetes model. In this study, we conducted a 12-week, randomized, double-blinded, and placebo-controlled clinical trial to determine the effects of OSM in humans with hyperglycemia. Participants with fasting plasma concentrations of 100–140 mg/dL were enrolled (n = 80) and administered either OSM or placebo products for 12 weeks. The outcomes included measurements of efficacy (fasting plasma glucose (FPG), postprandial glucose (PPG), fasting plasma insulin (FPI), postprandial insulin (PPI), hemoglobin A1c (HbA1c), C-peptide, fructosamine, and lipid parameters) and safety at baseline and at 12 weeks. After the intervention, the OSM group showed significantly decreased levels of FPG, PPG (30, 60 min), PPI (60 min), insulin area under the curve (AUC), fructosamine, and low-density-lipoprotein (LDL) cholesterol compared to the placebo group. No clinically significant changes in any safety parameter were observed. Therefore, it is hypothesized that OSM supplementation is an effective and safe functional food supplement for humans with hyperglycemia.     

Down syndrome biochemical markers and screening for preeclampsia at first and second trimester: correlation with the week of onset and the severity

OBJECTIVES: To estimate the combined screening performance of first and early second trimester prenatal serum markers for Down syndrome, in screening for the development of preeclampsia, and analyze the correlation among marker levels, week of onset, and severity of the disease. METHODS: A retrospective cohort study was carried out on 32 women with preeclampsia and 3044 controls. Serum samples from these pregnancies were assayed for pregnancy-associated plasma protein-A (PAPP-A), alpha-fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotrophin (hCG), and inhibin-A. A likelihood ratio and the odds of being affected given a positive result (OAPR) of various combinations of markers were calculated and receiver operating characteristic (ROC) curves analysis was performed. RESULTS: In the pregnancies that subsequently developed preeclampsia, first trimester PAPP-A concentration was significantly lower and concentrations of early second trimester inhibin-A and hCG significantly elevated. Levels of early second trimester uE3 and AFP were not significantly altered. We also found that inhibin-A correlates with both onset of the disease and the severity. CONCLUSION: Down syndrome biochemical markers levels are altered in those patients who subsequently developed preeclampsia and may be a useful screening test for preeclampsia. Inhibin-A is the most predictive marker and correlates with the severity of subsequent preeclampsia and inversely with the week of occurrence of preeclampsia.     

Three-vessel view of the fetal heart: in utero development of the great vessels

OBJECTIVES: The purpose of our study is to provide reference values for the great vessels obtained from images of the three-vessel view of the fetal heart, with an emphasis on the size discrepancy of the great vessels. METHODS: From February 2003 to May 2003, the main pulmonary artery (MPA), ascending aorta (AA), and SVC were measured in well-dated, nonanomalous fetuses scanned at 14-38 weeks of gestation. RESULTS: The size of each great vessel had a significant positive relationship with advance in gestation (P < 0.001); MPA (mm) = -2.76 + 0.34 x GA, ascending aorta (AA) (mm) = -1.73 + 0.26 x GA - 1.18E - 05 x GA(3), and SVC (mm) = 0.33 + 0.01 x GA(2) - 4.12E - 05 x GA(3). The AA/MPA ratio was significantly decreased with advance in gestation, while the SVC/AA ratio was significantly increased; AA/MPA ratio = -1.24 - 0.03 x GA + 3.88E - 04 x GA(2); P < 0.001, SVC/AA ratio = 0.63 - 5.43E - 03 x GA + 1.96E - 04 x GA(2); P < 0.001. CONCLUSION: On the three-vessel view of the fetal heart, the interpretation of the size discrepancy of the great vessels needs to be adjusted according to fetal growth.