OBJECTIVE: To evaluate the relative bioavailibility and bioequivalence of paroxetine hydrochloride film-coated tablets. METHODS: In a randomized crossover study, 24 healthy Chinese male subjects received a single oral dose (20 mg) of either test or reference paroxetine hydrochloride tablets after an overnight fast. The plasma concentrations of paroxetine were determined by a validated LC-MS/MS method. The pharmacokinetic parameters, the relative bioavailability and bioequivalence of two formulations were evaluated by DAS 2.0 software. RESULTS: After a single oral dose of 20 mg test or reference paroxetine tablets, the pharmacokinetic parameters of paroxetine were as follows: ρmax(5.102 ± 2.955) and (5.396 ± 2.852) μg · L-1; tmax (5.22 ± 1.83) and (5.35 ± 0.78) h; t1/2(11.76 ± 2.91) and (11.98 ± 3.57) h; AUC0~96h(118.1 ± 90.2) and (118.9 ± 86.0) μg · h · L-1; AUC0-∞ (120.2 ± 91.0) and (121.5 ± 87.6) μg · h · L-1, respectively. CONCLUSION: The relative bioavailability of the test paroxetine hydrochloride film-coated tablets is (100.6 ± 22.0)%. The two preparations are bioequivalent. Copyright 2012 by the Chinese Pharmaceutical Association.

Hypoxic preconditioning with different simulated altitudes (3?000 m and 5?000 m) was performed on Wistar rats and the evoked population spikes were recorded from the hippocampal slices of these rats. The results showed that the appearance of hypoxic injury potential (HIP) and the disappearance of presynaptic volley (PV) were significantly delayed in response to acute lethal hypoxia. HIP and PV delay became more apparent when the hypoxic preconditioning altitude was increased from 3?000 m to 5?000 m. After reoxygenation, the recovery rate of PV in hypoxic preconditioning groups at 3?000 m and 5?000 m was apparently higher than that of control. The above results suggest that hypoxic preconditioning of animals in vivo increases hypoxic tolerance of hippocampal neurons.

This study was aimed to establish a stable animal model of left ventricular hypertrophy (LVH) to provide theoretical and experimental basis for understanding the development of LVH. The abdominal aorta of male Wistar rats (80-100 g) was constricted to a diameter of 0.55 mm between the branches of the celiac and anterior mesenteric arteries. Echocardiography using a linear phased array probe was performed as well as pathological examination and plasma B-type natriuretic peptide (BNP) measurement at 3, 4 and 6 weeks after abdominal aortic constriction (AAC). The results showed that the acute mortality rate (within 24 h) of this modified rat model was 8%. Animals who underwent AAC demonstrated significantly increased interventricular septal (IVS), LV posterior wall (LVPWd), LV mass index (LVMI), cross-sectional area (CSA) of myocytes, and perivascular fibrosis; the ejection fraction (EF), fractional shortening (FS), and cardiac output (CO) were consistently lower at each time point after AAC. Notably, differences in these parameters between AAC group and sham group were significant by 3 weeks and reached peaks at 4th week. Following AAC, the plasma BNP was gradually elevated compared with the sham group at 3rd and 6th week. It was concluded that this modified AAC model can develop LVH, both stably and safely, by week four post-surgery; echocardiography is able to assess changes in chamber dimensions and systolic properties accurately in rats with LVH.

There are multiple shared pathophysiological mechanisms between diabetes mellitus and cognitive impairment, and diabetic patients are at a significantly higher risk of developing cognitive impairment compared to the general population. It is thus crucial to accurately predict the onset of cognitive impairment in diabetic patients. This review summarizes the progress in research on risk prediction models for cognitive impairment in diabetes mellitus and analyzes and compares various models in terms of their basic types, development methods, and predictive performance. The aim is to provide a reference for the development and clinical application of risk prediction models for cognitive impairment in diabetic patients.

AIMTo study the protective effect of Quinacrine(QA) on rat striatum neurons from the injury caused by heat environment treatment, to probe the relationship between cell membrane injury and cellular injury protection, and to seek the possibility of QA as a preventive agent to heat injury.

METHODSPrimary cultured striatum neurons from newborn rats were pretreated with QA at different concentration for 1 h, and then heat-treated at 43 degrees C for another 1 h. Cell necrosis was detected by Trypan blue staining, and apoptosis was evaluated through Activated Caspase-3 dye and TdT dye.

RESULTSHeat treatment effected the survival of striatum neurons and resulted in great number of cell death, which was mainly mediated by cell necrosis process. It was shown that treatment of QA itself had little effect on the survival of striatum neurons, while QA pretreatment decreased cellular necrosis caused by following heat treatment.

CONCLUSIONQA protects striatum neurons from heat environment injury at about 20 pmol/L, and the protection may mediated by reduction of necrosis.

Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Death ; drug effects ; Cells, Cultured ; Corpus Striatum ; cytology ; Heat-Shock Response ; Neurons ; drug effects ; Quinacrine ; pharmacology ; Rats ; Rats, Wistar

AIMTo investigate protective effects of ginkgolide B (GB) in different administration modes on glutamate-induced neuronal damage.

METHODSEssential GB were obtained by supercritical CO2 fluid extraction. Glutamate excitotoxicity were examined in primary cultures from neonatal Wistar rat, by using of Trypan blue dye staining, testing the lactate dehydrogenase leakage from cultured neurons and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) method. The protective effects of GB in different administration modes (pre-treatment and post-treatment) were adopted and compared with the NMDA receptor uncompetitive antagonist-MK-801 in acute-treatment.

RESULTSTreatment with GB in two administration modes both could increase ratio of surviving neuron, decrease LDH efflux and reduce ratio of neuron apoptosis in different degree, depended on dose in certain range. The protective effect of pre-treatment was superior to post-treatment, but inferior to MK-801.

CONCLUSIONGB can protect neurons against glutamate damage, and preventive using has more efficiency. The potential mechanism of its neural protection may be not only related to PAF receptor. If the predominant protection effect of GB in pretreatment is considered, precautionary intervention to high-risk population could have more value.

Animals ; Cells, Cultured ; Dizocilpine Maleate ; pharmacology ; Ginkgolides ; administration & dosage ; pharmacology ; Glutamic Acid ; adverse effects ; Hippocampus ; drug effects ; metabolism ; Lactones ; administration & dosage ; pharmacology ; Neurons ; drug effects ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo construct the sodium channel gene SCN5A-delQKP1507-1509 mutation associated with congenital long QT syndrome, and its eukaryotic expression vector, and to examine the expression of mutation protein in human embryonic kidney (HEK) 293 cells.

METHODSEukaryotic expression vector PEGFP-delQKP-hH1 for SCN5A-delQKP1507-1509 mutation was constructed by rapid site-directed mutagenesis. HEK293 cells were transfected with the wild or mutant vector using lipofectamine, and then subjected to confocal microscopy. The transfected cells were immunostained to visualize intracellular expression of the mutant molecules.

RESULTSDirect sequence and electrophoresis analysis revealed 9 basic group absences at position 1507-1509. The delQKP1507-1509 mutation eukaryotic expression vector was expressed in HEK293 cells. Immunostaining of transfected cells showed the expression of both wild type and mutant molecules on the plasma membrane and there was no difference in the amount of protein, which suggested that the mutant delQKP1507-1509 did not impair normal protein expression in HEK293 cells.

CONCLUSIONSSuccessful construction of mutant SCN5AdelQKP1507-1509 eukaryotic expression vector and expression of SCN5A protein in HEK293 cells provides a basis for further study on the functional effects of congenital long QT syndrome as a cause of SCN5A mutation.

Blotting, Western ; HEK293 Cells ; Humans ; Long QT Syndrome ; congenital ; genetics ; Mutagenesis, Site-Directed ; NAV1.5 Voltage-Gated Sodium Channel ; analysis ; genetics ; physiology

The chitosan/PHEA-blended hydrogels were prepared from PHEA and chitosan in various blend ratios. The water contents of the hydrogels were in the range of 50%-80% (wt). The attachment and growth of fibroblast cells(L929) on the hydrogels were studied. The results indicated the PHEA content in hydrogels has great effect on cell attachment but has little effect on the growth of L929 cells.
Animals ; Biocompatible Materials ; chemistry ; Cell Adhesion ; physiology ; Cell Division ; physiology ; Cells, Cultured ; Chitin ; analogs & derivatives ; chemistry ; Chitosan ; Fibroblasts ; cytology ; physiology ; Hydrogel, Polyethylene Glycol Dimethacrylate ; chemistry ; Mice ; Peptides ; chemistry ; Water ; chemistry

OBJECTIVETo examine the effect of multiple micronutrients supplementation on anti-oxidative activity and decreasing oxidized DNA damage of lymphocytes in Chinese children.

METHODS82 healthy children in a rural areas, aged 9-11 years, were selected and randomized allocated into group receiving supplements and control group with each of them 41. 24-hour dietary recall was used to collect data on daily nutrient intakes of the research subjects. The subjects in the supplement group were given vitamin A (VA) 600 microg, beta-carotene (beta-C) 1.0 mg, vitamin E (VE) 100 mg, vitamin C (VC) 300 mg and Na2SeO3(Se) 200 microg in a tablet on daily base while those in the control group took a same-sized color placebo tablet. The trial lasted 8 weeks. 5 ml blood samples from each subject were taken during 7 to 9 o'clock in the morning. DNA damage of lymphocytes and levels of plasma VA, VE, VC, beta-C, Se, malondialdehyde (MDA), activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were then analyzed twice before and after the 8-week of trial.

RESULTSThe low intakes of VA, VC and Se only accounted for 50.6%, 65.6% and 67.3% of their recommended nutrient intake (RNI) respectively. After the trial, levels of plasma beta-C, VA, VE, VC and Se in the supplemented group increased by 13.4%, 32.8%, 11.5%, 46.9% and 24.6% respectively, compared with the control group, indicating that nutritional status regarding antioxidant nutrients had largely been improved. GSH-Px activity had a significant increase in the supplement group than before the supplement and in the control group (P < 0.01). GSH-Px before the trial (the 100.4 U/ml) also showed significant increase after the trial (161.7 U/ml) (P < 0.01). However, the values of SOD and MDA significantly decreased after the trial. Analysis of DNA damage indicated that there was no significant difference in the intrinsic damage of DNA (P > 0.05). Significant decreases of oxidized DNA damage induced by 5 micromol/L, 10 micromol/L and 25 micromol/L H2O2 were found more in peripheral lymphocytes of the supplemented group, than in pre-supplement and the control group after the trial (P < 0.01).

CONCLUSIONSupplementation of multiple micronutrients could effectively increase the levels of beta-C, VA, VE, VC and Se in plasma, and GSH-Px activity. In the meantime, MDA and oxidized DNA damage induced by a low level H2O2 decreased significantly after the trial. The reason accounted for the decrease of SOD activity after the trial needs to be further studied.

Antioxidants ; administration & dosage ; Ascorbic Acid ; administration & dosage ; Child ; China ; DNA Damage ; drug effects ; Dietary Supplements ; Female ; Humans ; Lymphocytes ; metabolism ; Male ; Malondialdehyde ; blood ; Nutrition Surveys ; Oxidative Stress ; drug effects ; genetics ; Rural Health ; Selenium ; administration & dosage ; Superoxide Dismutase ; blood ; Vitamin A ; administration & dosage ; Vitamin E ; administration & dosage ; Vitamins ; administration & dosage