Decrease of glomerular filtration rate may be attributed to the microcirculation damage in renal artery stenosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The decrease of glomerular filtration rate has been theoretically supposed to be the result of low perfusion in renal artery stenosis (RAS). But the gap between artery stenosis and the glomerular filtration ability is still unclear.</p><p><b>METHODS</b>Patients with selective renal artery angiogram were divided by the degree of renal artery narrowing, level of estimated glomerular filtration rate (eGFR), respectively. The different levels of eGFR, renal microcirculation markers, and RAS severity were compared with each other, to determine the relationships among them.</p><p><b>RESULTS</b>A total of 215 consecutive patients were enrolled in the prospective cohort study. Concentrations of microcirculation markers had no significant difference between RAS group (RAS ≥ 50%) and no RAS group (RAS < 50%) or did not change correspondingly to RAS severity. The value of eGFR in RAS group was lower than that in the no RAS group, but it did not decline parallel to the progressive severity of RAS. The microcirculation markers presented integral difference if grouped by different eGFR level with negative tendency, especially that plasma cystatin C (cysC) and urinary microalbumin to creatinine ratio (mACR) increased with the deterioration of eGFR, with strong (r = -0.713, P < 0.001) and moderate (r = -0.580, P < 0.001) correlations. In the subgroup analysis of severe RAS (RAS ≥ 80%), the levels of plasma cysC and urinary mACR demonstrated stronger negative associations with eGFR, (r = -0.827, P < 0.001) and (r = -0.672, P < 0.001) correlations, respectively.</p><p><b>CONCLUSIONS</b>Severity of RAS could not accurately predict the value of eGFR, whereas microcirculation impairment may substantially contribute to the glomerular filtration loss in patients with RAS.</p>

Anti-tumor effects of a novel cyclophosphamide derivate 9b in vivo and in vitro / 药学学报

This study is to investigate the anti-tumor activities of a novel cyclophosphamide derivate 4, 6-diphenyl cyclophosphamide (9b) in vivo and in vitro, and its possible mechanism of action. The inhibitory effects of 9b on human hepatoma cell line HepG2, human breast carcinoma cell line MCF-7 and human myeloid leukemia cell line K562 were measured by MTT assay in vitro. Cell cycle distribution and apoptotic rate were evaluated by flow cytometry. To evaluate the anti-tumor effect of 9b in vivo, mouse model bearing inoculated H22 tumor was established. The results indicated that 9b could inhibit the proliferation of HepG2, MCF-7 and K562 cells in a dose and time dependent manner. The ICo50 values of 9b were 32.34 micromol.L-1 to HepG2 cells, 87.07 micromol.L-1 to MCF-7 cells and 149.10 micromol.L-1 to K562 cells after incubation for 48 h. The results of flow cytometry indicated that after being treated for 48 h with different concentrations of 9b, the ratios of HepG2, MCF-7 cells at the Go/G1 phase and K562 cells at the G0/Gl phase and G2/M phase increased significantly compared with control group, and the apoptotic rate increased with the increase of the concentration of 9b. 9b could significantly reduce tumor weight of H22 solid tumor mouse model in vivo. To summarize, 9b showed significantly anti-tumor activity in vivo and in vitro, of which the mechanism might be associated with the change of cell cycle distribution and induction of tumor cell apoptosis.

Association of β-adrenergic receptor genes polymorphisms with incidence of subsequent cardiovascular events in Han Chinese patients with coronary artery disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Sequence variants in the β-adrenergic receptor (ADRB) genes have a close relationship with the development of coronary artery disease (CAD) and the patient's prognosis. However, there is a lack of data on the role of the variants in ADRBs genes in Han Chinese patients with CAD. We aimed to investigate the association of genetic variants in the ADRB1 and ADRB2 genes with the incidence of major adverse cardiac event (MACE) in Han Chinese patients with CAD.</p><p><b>METHODS</b>A total of 545 Han Chinese patients with CAD undergoing percutaneous coronary intervention (PCI) were recruited to the study and followed for one year. Three variant sites in ADRB1 (rs1801253) and ADRB2 (rs1042713 and rs1042714) were genotyped. The effect of the ADRB1 and ADRB2 genotypes on MACE within one year was assessed.</p><p><b>RESULTS</b>There were 47 cases of MACE during follow-up. There was no significant difference in the incidence of MACE among patients carrying different genotypes of the three variants in ADRB1 and ADRB2 (Log-rank, all P > 0.05). Cox regression analysis showed no association between three variants in ADRB1 and ADRB2 genes and the incidence of MACE during one-year follow-up, the adjusted hazard ratios (95% confidence interval) for rs1801253, rs1042713 and rs1042714 were 1.05 (0.54-2.02), 1.24 (0.58-2.64) and 1.66 (0.81-3.42), respectively.</p><p><b>CONCLUSION</b>Our data did not support a relationship between the three polymorphisms of ADRB1 (rs1801253) and ADRB2 (rs1042713 and rs1042714) genes and risk of subsequent cardiovascular events after PCI in Han Chinese patients with CAD.</p>

Research and practice of permeating the humanity quality education into pharmacology teaching / 中华医学教育探索杂志

Enhancing medical students' humane quality education is an urgent requirement for modem medical mode transformation for medical education.The pharmacology teachers of Chongqing Medical University follow the modem education concepts and fully search the human spirit materials hidden in pharmacology,then actively explore how to integrate the humanity spirit education into the pharmacology teaching to achieve the changes of from exam-oriented education to quality education.

Berberine and total base from rhizoma coptis chinensis attenuate brain injury in an aluminum-induced rat model of neurodegenerative disease

To investigate the protective effects of the total base from rhizoma coptis chinensis [CTB] and berberine [Ber] on neurodegeneration induced by aluminum overload in rats. The study took place in the Department of Pharmacology, Chongqing Medical University, Chongqing, China, between February 2005 and May 2007. Wistar rats were divided into control group, model group, Ber-treated group, CTB [55 mg/kg and 110 mg/kg]-treated group, and nimodipine-treated group [n=20]. A rat brain damage model was established via intragastric administration of 400 mg/kg element aluminum once a day, 5 days a week for 12 weeks. The CTB, Ber, and nimodipine were intragastrically administered 4 hours after each aluminum administration for 12 weeks. The morphological changes of the neurons of the rat hippocampus and the changes of rat learning and memory functions were observed. The superoxide dismutase [SOD], choline acetyltransferase [ChAT], acetylcholinesterase [AchE], and monoamine oxidase-B [MAO-B] activities and malondialdehyde [MDA] content, as well as the MAO-B expression in the rat brain were examined. The CTB, Ber, and nimodipine significantly improved the learning and memory ability impairment and hippocampal neuronal death. The CTB, Ber, and nimodipine also significantly blunted the decrease of SOD and ChAT activities, and the increase of MDA content, AchE activities, and MAO-B expressions and activity in the aluminum-overload rats. The CTB and Ber have protective effects on neurodegeneration induced by aluminum overload. The CTB [110 mg/kg] has more powerful neuroprotection than Ber

Effect of ketoconazole on the activity of CYP4503A4 and CYP450 1A2 of hepatic microsomes in healthy adults / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of ketoconazole on the activity of cytochrome P450 (CYP) 1A2 and 3A4 in hepatic microsomes of healthy adults.</p><p><b>METHODS</b>Human hepatic microsomes obtained from healthy adults were randomly divided into control group and ketoconazole-treatment groups at different concentrations. After 15 min of culture, the substrates (testosterone for CYP3A4 and phenacetin for CYP1A2) were added and incubated for another 20 min. The metabolites (6-testosterone and acetaminophen) were then measured with high-performance liquid chromatography (HPLC) to assess the activities of CYP3A4 and 1A2.</p><p><b>RESULTS</b>Significant difference was found between the groups in the quantity of 6-testosterone and the relative activity of CYP3A4 (P<0.05). The IC(50) of ketoconazole for CYP3A4 was 0. 16 mg/L. Both the quantity of 6-testosterone and the relative activity of CYP3A4 were reduced gradually with the increment of ketoconazole concentration. Significant differences were found between the ketoconazole groups and the control group in both the quantity of acetaminophen and the relative activity of CYP1A2 (P<0.05). Ketoconazole at low doses reduced CYP1A2 activity and but increased the activities at high doses (P<0.05).</p><p><b>CONCLUSION</b>In the range of maximum clinical blood concentration, ketoconazole can inhibit the activity of CYP3A4, but not that of CYP1A2, in the hepatic microsomes in healthy adults.</p>

Protective effects and mechanism of total coptis alkaloids on a beta 25-35 induced learning and memory dysfunction in rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of total coptis alkaloids (TCA) on beta -amyloid peptide (A beta 25-35) induced learning and memory dysfunction in rats, and to explore its mechanism.</p><p><b>METHODS</b>Forty male Wistar rats were randomly divided into four groups: the control group, the model group, the TCA low dose (60 mg/kg) group and the TCA high dose (120 mg/kg) group, 10 in each. A beta 25-35 (5microl, 2 microg/microl) was injected into bilateral hippocampi of each rat to induce learning and memory dysfunction. TCA were administered through intragavage for consecutive 15 days. Morris Water Maze test was used to assess the impairment of learning and memory; concentration of malondialdehyde (MDA) in cerebral cortex was determined by thiobarbituric acid reactive substance to indicate the level of lipid peroxidation in brain tissues; activity of manganese-superoxide dismutase (Mn-SOD) in cerebral cortex was determined by xanthine-oxidase to indicate the activity of the enzyme; and NF- kappa B protein expression in cerebral cortex was measured by SP immunohistochemistry.</p><p><b>RESULTS</b>(1) Morris Water Maze test showed that, during the 4 consecutive days of acquisition trials, the rats in the model group took longer latency and searching distance than those in the control group (P<0.01), which could be shortened by high dose TCA (P<0.05); during the spatial probe trial on the fifth day, the rats in the model group took shorter searching time and distance on the previous flat area than those in the control group (P<0.01), which could be prolonged after TCA treatment (for low dose group, P<0.05; for high dose group, P<0.01). (2) Analysis of cerebral cortical tissues showed that, compared with the control group, MDA level got significantly increased and Mn-SOD activity decreased in the model group (both P<0.01). After having been treated with TCA, the MDA level got significantly decreased (P<0.05 and P<0.01 respectively for low and high dose group), while relative increase of Mn-SOD activity only appeared in high dose group (P<0.05). (3) Immunohistochemistry analysis showed the protein expression of NF- kappa B got significantly increased after modeling, while high dose TCA can significantly inhibit it.</p><p><b>CONCLUSION</b>TCA could improve A beta 25-35 induced dysfunction of learning and memory in rats, and its protective mechanism is associated with its actions in decreasing MDA level, increasing Mn-SOD activity and inhibiting the expression of NF-kappa B in cerebral cortex.</p>

Protective effects of total alkaloids from rhizoma Coptis chinensis on alcohol-induced gastric lesion in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of total alkaloids(TA) from rhizoma Coptis chinensis on alcohol-induced gastric lesion in rats and the possible mechanisms.</p><p><b>METHOD</b>The experimental gastric damges were established by intragastric(ig) absolute ethanol, and possible protective effects of TA given orally previously were evaluated by following parameters: gastric damage indexes, gastric juice volume, acidity, and mucus quantity. The contents of NO, MDA, *OH, and SOD activity were also measured in gastric mucosa.</p><p><b>RESULT</b>TA showed significantly inhibitive effects on gastric damages induced by ig ethanol in a dose dependent manner. The effects of TA (120 mg x kg(-1)) were stronger than that of both cimitidine(70 mg x kg(-1)) and berberine(100 mg x kg(-1)), the quantity of later was equal to TA as calculated with berberine. TA significantly suppressed secretion of gastric acid caused by ethanol without clear influences on gastric juice volume and mucus secretion. TA obviously blunted ethanol-induced elevation of MDA and *OH, as well as decrease of NO level and SOD activity from gastric mucosa.</p><p><b>CONCLUSION</b>It is suggested that the TA is a potent protective agent against ethanol-induced gastric damages. The mechanism of actions may be related with inhibiting the secretion of gastric acid and blunting the increase of MDA and *OH, as well as the decrease of NO level and SOD activity from gastric mucus.</p>