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 the effects of hypoxia on the proliferation of mouse embryonic stem cells (mouse ES cells) in vitro.

METHODSWe observed the proliferation of ES cells by hematometery and BrdU-labeled flow cytometry (FCM), and we also detected the expression of hypoxia inducible factor-1a (HIF-1a) by RT-PCR.

RESULTS(1) The number of ES cells after culturing in the hypoxia environment (3% O2 and 10% O2) for 24 hours were lesser than those in normoxia (20% O2). (2) The number of ES cells significantly increased after intermittent hypoxia (3% O2) stimulus for 10 minutes per day for 4 days. (3) We also observed the relation between the expression of HIF-1a and the proliferation of ES cells by RT-PCR. The results showed that the expression of HIF-1a had no significant change after ES cells were culturing in hypoxia environment (3% O2 and 10% O2) for 24 hours or in intermittent hypoxia (3% O2 and 10% O2) for 4 days.

CONCLUSIONThese results suggest that intermittent hypoxia (3% O2) can significantly promote the proliferation of ES cells in vitro, while persistent hypoxia inhibits those, and the mechanism of these should be addressed in further.

Animals ; Cell Hypoxia ; Cell Proliferation ; Cells, Cultured ; Embryonic Stem Cells ; cytology ; Mice

OBJECTIVETo investigate the effect of Shuganlipi decoction on Th1/Th2 cytokines, liver function and HBV replication in patients with chronic hepatitis B (CHB).

METHODSEighty-six confirmed CHB cases were randomly divided into control group (n=42) and experimental group (n=44) for treatment with routine western medication and additional treatment with Shuganlipi decoction, respectively. The production of IFN-γ, IL-2, IL-6, IL-10 and liver function, HBV DNA, and HBeAg were detected in all the patients.

RESULTSThe total response rate to the treatment was significantly higher in the experimental group than in the control group (78.13% vs 57.14%, P<0.01). ALT, AST, TBIL and ALB were all improved obviously in the two groups after the treatments (P<0.01). In terms of ALT and ALB, the experimental group showed more obvious improvement than the control group(P<0.05). The treatments also resulted in significant increases of IFN-γ and IL-2 levels and reductions of IL-6 and IL-10 levels in the two groups (P<0.01).

CONCLUSIONShuganlipi decoction can improve the liver function and activity of Th1/Th2 cytokines to promote the clearance of liver cell HBV infection.

Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; Hepatitis B, Chronic ; drug therapy ; immunology ; virology ; Humans ; Interleukin-10 ; immunology ; Interleukin-2 ; immunology ; Interleukin-6 ; immunology ; Male ; Middle Aged ; Phytotherapy

The aim of present study was to investigate the effect of chronic intermittent hypobaric hypoxia (CIHH) on collagen-induced arthritis (CIA) in rat. Fifty male adult Sprague-Dawley rats were randomly divided into 5 groups: CIHH pre-treatment group (Pre-T), pre-control group (Pre-C), CIHH post-treatment group (Post-T), post-control group (Post-C) and blank control group (Con). The rats in Pre-T and Post-T groups were exposed to 28 d of hypobaric hypoxia (simulated 3 000 m altitude, 5 h per day, pO2 = 108.8 mmHg, 14% O2) in a hypobaric chamber before and 12 days after CIA induction, respectively. The rats in Pre-C and Post-C groups were only experienced CIA induction, being control groups for Pre-T and Post-T groups, respectively. The rats in Con group were not given any treatment. The thickness of two-hind paw of rat was measured with spiral micrometer and the degree of arthritis was evaluated by arthritis index (AI). Morphological changes of ankle joint were observed through HE staining. The apoptotic rate in synovial tissue was measured by terminal dUTP nick end labeling (TUNEL) and the apoptotic rate of CD3(+) T lymphocyte in spleen was measured by flow cytometry technique. The protein expressions of Bcl-2 and Bax were measured using immunohistochemistry SP method. The results showed that incidence rate of CIA in Pre-T rats was lower than that in Pre-C rats (P < 0.05). AI in Pre-T and Post-T rats were smaller than those in Pre-C and Post-C, respectively (P < 0.05). In Pre-C and Post-C rats, there were hyperplasia of synovial cell, pannus forming, infiltration with inflammatory cell, and destroyed cartilage and bone in ankle joint. On the contrary, pathological changes of ankle joint were alleviated significantly in Pre-T and Post-T rats. Compared with Pre-C and Post-C rats, apoptotic rates of synovial cell and T lymphocyte in Pre-T and Post-T rats were increased (P < 0.05). As to the possible anti-apoptosis mechanism, CIHH, no matter before and after CIA induction, decreased Bcl-2 expression and increased Bax expression in joint synovial cells and spleen T lymphocytes (P < 0.05), respectively. In conclusion, CIHH possesses a protective effect against CIA in rat by enhancing apoptosis of synovial cells and T lymphocytes, which may be related to the inhibition of Bcl-2 protein expression and the promotion of Bax protein expression.
Animals ; Apoptosis ; physiology ; Arthritis, Experimental ; pathology ; physiopathology ; prevention & control ; Hypoxia ; physiopathology ; Ischemic Postconditioning ; methods ; Ischemic Preconditioning ; methods ; Joints ; pathology ; Male ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spleen ; cytology ; Synovial Membrane ; pathology ; T-Lymphocytes ; pathology ; bcl-2-Associated X Protein

AIMTo establish the model of oxygen-glucose deprivation in vitro rat hippocampal neurons.

METHODSThe hippocampal neurons cultured for 12 d were exposed to combined oxygen-glucose deprivation for 0.5-4 h and then cultured with original medium in normoxia for 24 h. Auto-biochemical analyzer determined LDH activity. The change of neuronal morphology and neuron survival were observed by converted contrast microscope and assessed by photography analysis system. Neuron apoptosis was detected by using the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nickel end labeling (TUNEL) method.

RESULTSThe neurons swelled, LDH release increased and neuron survival decreased after gradually oxygen-glucose deprivation. The percentage of apoptosis increased obviously 24 h after recovering the supply of oxygen and glucose.

CONCLUSIONThe model of oxygen-glucose deprivation in vitro rat hippocampal neurons is established successfully by using the modified ACSF (artificial cerebral spinal fluid) with serum and glucose free.

Animals ; Animals, Newborn ; Cell Hypoxia ; Cells, Cultured ; Glucose ; deficiency ; Hippocampus ; cytology ; Neurons ; cytology ; Oxygen ; physiology ; Rats ; Rats, Wistar