BACKGROUND: Food restriction has been reported to ameliorate diabetes and obesity. In this study, we examined the effects of the food restriction on phenotypes of TALLYHO/JngJ (TH) mouse, a recently developed diabetic model animal. METHODS: 3 week-old TH mice were divided into 2 groups (n = 20 each for food-restricted (THR) and free-fed (THF)) and THR mice were fed the same amount of food as normal control mice (C57BL/6, n = 20). Body weight was weekly monitored till 14 weeks of age. The half of animals were sacrificed at 8 weeks of age, and liver, kidney, and fat weight were measured. The histopathology of liver and brown fat tissues and mRNA expression of leptin in adipose tissue were analyzed. The oral glucose tolerance test and insulin resistance test was done at 14 weeks of age. The plasma concentrations of glucose, free fatty acid, triglyceride, cholesterol and leptin were analyzed. RESULTS: The THR mice had lower body weights than the THF mice, similar to C57BL/6 mice, with reduced fat deposition in liver and brown fat tissue. The plasma levels of glucose, triglyceride and free fatty acid were decreased in the THR group. The THR mice, however, carried more fat than normal mice, with increased plasma leptin concentration and leptin mRNA expression in fats and no alteration in plasma cholesterol levels. Furthermore, the THR mice revealed glucose intolerance with impaired after-meal insulin secretion and slight insulin resistance CONCLUSION: The food restriction apparently ameliorated the obesity and diabetic phenotypes of TH mice. However, plasma concentration of cholesterol were not improved in THR mice with increased adiposity index and glucose intolerance, suggesting the genetically prone tendency of obesity and diabetes development in TH mice possibly with an impairment in cholesterol metabolism.
Adipose Tissue ; Adipose Tissue, Brown ; Adiposity ; Animals ; Body Weight ; Cholesterol ; Diabetes Mellitus ; Fats ; Glucose ; Glucose Intolerance ; Glucose Tolerance Test ; Insulin ; Insulin Resistance ; Kidney ; Leptin ; Liver ; Mice ; Obesity ; Phenotype ; Plasma ; RNA, Messenger

OBJECTIVE: The study aims were to demonstrate apoptosis in the placenta of normal pregnancy, and to identify its change and quantify its incidence by gestational age. METHODS: Placenta samples were collected from 25 normal full-term pregnancies and 20 second trimester pregnancies undergoing termination due to medical and social reasons. Hematoxylin and eosin staining and TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) staining were used to quantify the incidence of apoptosis and the electron microscopy was used to confirm it. Mann-Whitney U test and ANOVA test were used for statistical analysis. RESULTS: 1. Apoptosis was demonstrated by variable cytopathologic methods, and especially TUNEL staining and electron microscopy are found to be confirmatory methods. 2. In TUNEL staining, quantification of apoptosis was as follows: 2nd trimester (n=20) 1.05+/-0.69, full- term (n=25) 1.92+/-1.00. The incidence of apoptosis was significantly higher in full-term than in 2nd trimester (p<0.05, Mann-Whitney U test). 3. In hematoxylin and eosin staining, quantification of apoptosis was as follows: 2nd trimester (n=20) 0.40+/-0.50, full-term trimester (n=25) 0.72+/-0.61. The incidence of apoptosis was not significantly higher in full- term trimester than in 2nd trimester (p>0.05, Mann-Whitney U test). 4. There was no statistical significance in the incidence of apoptosis by maternal age, parity, cause of termination during 2nd trimester, and mode of delivery in each group. 5. In the electron microscopy, apoptotic cells were observed to have membrane blebbing, loss of microvilli, chromatin condensation and localization in the border of nuclear membrane, and cell shrinkage and increase in granularity. This method was conformatory in identifying apoptosis. CONCLUSION: Placental apoptosis increased significantly with increased gestational age, and this result suggests that it may play a role in the normal development and aging of the placenta.
Aging ; Apoptosis ; Blister ; Chromatin ; Deoxyuridine ; Eosine Yellowish-(YS) ; Female ; Gestational Age ; Hematoxylin ; Humans ; In Situ Nick-End Labeling ; Incidence ; Maternal Age ; Membranes ; Microscopy, Electron ; Microvilli ; Nuclear Envelope ; Parity ; Placenta ; Pregnancy Trimester, Second ; Pregnancy*

BACKGROUND: Cefcapene pivoxil hydrochloride (CFPN-PI) is an oral ester cephalosporin antibiotic with a broad spectrum. In this study, we investigated the pharmacokinetics (PK) and tolerability of CFPN-PI following single oral administration in healthy Korean subjects. METHODS: An open label, dose escalation, parallel group study was conducted in 18 healthy male volunteers. A single dose of CFPN-PI was administered to 6 subjects in each treatment group of 100, 150 and 200 mg. Serial blood and urine samples were collected up to 12 h and 24 h after dosing, respectively. Plasma and urine concentrations of cefcapene were measured by HPLC-UV. PK parameters were estimated using non-compartmental analysis. For the safety evaluation, adverse event monitoring, clinical laboratory tests and physical examination were performed throughout the study. RESULTS: Median values of time to peak plasma concentration were observed around 1.5 to 2.0 h. Maximum plasma concentrations (Cmax) were 1.04 +/- 0.22, 1.24 +/- 0.46 and 1.56 +/- 0.43 mg/L (mean +/- SD), and area under the plasma concentration time curve (AUCinf) were 2.94 +/- 0.46, 3.97 +/- 1.28 and 4.70 +/- 1.19 h*mg/L in 100, 150 and 200 mg dose groups, respectively. The differences of dose normalized Cmax and AUCinf among three groups were not statistically significant. The fractions of drug excreted in urine unchanged were 31.5 % - 42.9 %. There were no serious adverse events or clinically significant abnormalities related to CFPN-PI. CONCLUSION: CFPN-PI was well tolerated with single oral administration and showed a linear PK property within 100 - 200 mg in healthy Korean male subjects.
Administration, Oral* ; Humans ; Male ; Pharmacokinetics ; Physical Examination ; Plasma

BACKGROUND AND OBJECTIVES: Wall shear stress contributes to atherosclerosis progression and plaque rupture. There are limited studies for statin as a major contributing factor on whole blood viscosity (WBV) in patients with acute coronary syndrome (ACS). This study investigates the effect of statin on WBV in ACS patients. SUBJECTS AND METHODS: We prospectively enrolled 189 consecutive patients (mean age, 61.3±10.9 years; 132 males; ST-segment elevation myocardial infarction, n=52; non-ST-segment elevation myocardial infarction, n=84; unstable angina n=53). Patients were divided into two groups (group I: previous use of statins for at least 3 months, n=51; group II: statin-naïve patients, n=138). Blood viscosities at shear rates of 1 s-1 (diastolic blood viscosity; DBV) and 300 s-1 (systolic blood viscosity; SBV) were measured at baseline and one month after statin treatment. Rosuvastatin was administered to patients after enrollment (mean daily dose, 16.2±4.9 mg). RESULTS: Baseline WBV was significantly higher in group II ([SBV: group I vs group II, 40.8±5.9 mP vs. 44.2±7.4 mP, p=0.003], [DBV: 262.2±67.8 mP vs. 296.9±76.0 mP, p=0.002]). WBV in group II was significantly lower one month after statin treatment ([SBV: 42.0±4.7 mP, p=0.012, DBV: 281.4±52.6 mP, p=0.044]). However, low-density lipoprotein cholesterol level was not associated with WBV in both baseline (SBV: R2=0.074, p=0.326; DBV: R2=0.073, p=0.337) and after one month follow up (SBV: R2=0.104, p=0.265; DBV: R2=0.112, p=0.232). CONCLUSION: Previous statin medication is an important determinant in lowering WBV in patients with ACS. However, one month of rosuvastatin decreased WBV in statin-naïve ACS patients.
Acute Coronary Syndrome* ; Angina, Unstable ; Atherosclerosis ; Blood Viscosity* ; Cholesterol ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Lipoproteins ; Male ; Myocardial Infarction ; Prospective Studies ; Rheology ; Rupture ; Rosuvastatin Calcium