小儿肺炎痰热闭肺证中舌象与肺部啰音变化的关系

目的:探讨小儿肺炎痰热闭肺证中舌象与肺部啰音变化的关系.方法:观察93例痰热闭肺证肺炎患儿舌象及肺部啰音在治疗前后及治疗期间的变化,并分析两者之间的关系.结果:痰热闭肺证中第1 d舌象大多数为舌红、苔黄,占89.2%;至第3 d,逐步转变为舌质红、苔白,占23.7%;第5 d,舌苔颜色多由黄转白,转变为舌质红、苔白者占39.8%,少数由于痰热凝集日久耗伤气阴,或致气虚血瘀,出现舌质暗红有瘀斑或舌红苔剥脱,占7.5%;第7 d舌质暗红或淡、苔少或苔剥脱者增多,占18.3%.肺部啰音的变化为第1 d肺部听诊固定湿啰音的占88%,至第3 d消失5%,第5 d消失37%,第7 d消失69%.结论:痰热闭肺证肺炎患儿随着舌象转为正常而啰音相应逐步消失.     

Effects of imidazoline I(2) receptor agonists and morphine on schedule-controlled responding in rats

Accumulating evidence indicates that imidazoline I₂ receptor agonists enhance the antinociceptive effects of opioids and therefore may be suitable for combination therapy with opioids for pain treatment. However, little is known of the effects of I₂ receptor agonists on other behavioral effects of opioids. This study used schedule-controlled responding and dose-addition analyses to examine interactions between the μ opioid receptor agonist morphine and two imidazoline I₂ receptor agonists, 2-BFI and BU224. In 8 rats responding under a fixed ratio 10 schedule of food presentation, morphine (3.2-17.8 mg/kg), 2-BFI (3.2-17.8 mg/kg), and BU224 (5.6-17.8 mg/kg) each dose-dependently decreased responding. The addition of fixed proportions of 2-BFI or BU224 shifted the morphine dose-effect curves leftward. The interactions between morphine and 2-BFI or BU224 were infra-additive when the same proportions of morphine and I₂ receptor agonists were mixed; however, the interaction between morphine and I₂ receptor agonists was additive when the drugs were mixed at other proportions. These results provide quantitative evidence that I₂ receptor agonists do not enhance the response rate-decreasing effect of morphine and suggest that the enhancement of morphine antinociception is selective. Together, these results further support the therapeutic potential of combining I₂ receptor agonists and opioids for pain control.     

Melamine induced cognitive impairment associated with oxidative damage in rat's hippocampus

Previous studies reported that melamine could affect hippocampal function and cause spatial cognition impairment. Moreover, some evidences implied that there might be an oxidative damage pathway linking melamine to the function of hippocampus in vitro, but there was a paucity of data about this adverse effect in vivo. The aim of this study was to investigate the toxicology of melamine induced by oxidative damage in hippocampus in vivo. Male Wistar rats were randomly divided into two groups: control group (n = 8) and melamine group (n = 8). The animals were treated with melamine at a dose of 300 mg/kg/day in 1% carboxymethylcellulose (CMC) solution as a suspension by oral administration, while rats received the same dose of solution of 1% CMC in control group. Melamine was given once a day and for 28 consecutive days. The MWM experiment and histopathological examination were performed. MWM results showed that there were significant deficits of spatial learning and memory in melamine group. The levels of superoxide anion radical, hydroxyl free radical and malonaldehyde (MDA) were significantly increased by melamine, which also reduced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). The analysis of hippocampal energy metabolism showed that melamine caused significant decrease in the content of adenosine-triphosphate (ATP), implying the reduction of energy synthesis in hippocampal neurocytes. The results suggest that the selective neurotoxicity of melamine in hippocampus may be in part associated with oxidative damage.     

以泼尼松为主联合治疗多发性肌炎和皮肌炎32例

目的：比较泼尼松联合疗法和单用治疗多发性肌炎 (PM) 和皮肌炎 (DM)的疗效。方法：PM和DM患者67例分为对照组(单用糖皮质激素)35例，给予泼尼松1 mg·kg 1·d 1，qd。治疗组 32例，给予泼尼松1 mg·kg 1·d 1， qd，加甲氨蝶呤片 7.5～10.0 mg，po，每周1次；加火把花根片3片，tid。疗程4周。主要观察指标有肌力变化，皮疹，血清 ALT、AST、LDH、CK的水平及药物副作用发生率。结果∶治疗后两组患者的肌力均有不同程度改善，肌力改善幅度≥2级患者在对照组中占54.3%，在治疗组中占62.5%，二者差异无显著性(P＞0.05)。两组患者在治疗后血清 ALT、AST、LDH、CK水平均比治疗前有明显下降，差异有极显著性(P＜0.01)。治疗组患者的血清ALT、AST、LDH、CK下降的幅度明显大于对照组，差异有显著性(P＜0.05)。结论：与单用糖皮质激素的疗法相比，联合治疗方法能够使血清肌酶更快地下降，对PM和DM有更好的近期疗效。     

Ulinastatin inhibits unilateral ureteral obstruction-induced renal interstitial fibrosis in rats via transforming growth factor β (TGF-β)/Smad signalling pathways

This study aims to explore the protective effects and mechanisms of ulinastatin (UTI), which is a urinary trypsin inhibitor, of the renal interstitial fibrosis of rats subjected to unilateral ureteral obstruction (UUO). A total of 36 male Wistar rats were divided in random into three groups, namely, the sham operation (SOR) group (n = 12), the UUO group (n = 12), and the UTI treatment group (n = 12). Six rats from each group were euthanised after unilateral ureteral obstruction operation on the seventh and fourteenth days, respectively. Blood samples were harvested for blood urea nitrogen (BUN) and serum creatinine (Scr) measurement. The interstitial pathological changes of the tissue from the obstructed kidneys were observed using haematoxylin–eosin (H&E) and Masson staining. The expression of the transforming growth factor β type 1 (TGF-β1), α-smooth muscle actin (α-SMA), type I collagen (Col-I), and phosphorylated Smad2/3 (p-Smad2/3) was determined using immunohistochemistry. The protein expression levels of TGF-β1, α-SMA, and p-Smad2/3 were examined using Western blot analysis. The results show that ulinastatin has no statistically significant effect on the BUN and Scr levels (P > 0.05), but it can significantly reduce renal interstitial injury and suppress interstitial collagen deposits. The renoprotective effect of ulinastatin is likely realised through the TGF-β/Smad signalling pathways.     

2010年我院160例药品不良反应报告分析

目的 了解医院药品不良反应(ADR)发生的规律和特点,促进临床合理用药,提高药物治疗安全性.方法 采用回顾性调查方法,对2010年上报的167例药品不良反应报告,按患者年龄、性别,给药途径,涉及药品种类,累及器官和临床表现、转归与评价等进行分析.结果 167例报告中,7例为皮肤过敏试验阳性,有效报告160例.其中患者女47.50%(76/160),男52.50%(84/160),平均年龄54.37岁;静脉给药145例(90.63%),口服给药ll例(6.88%),皮下注射给药4例(25.00%);涉及药品12类73种,列前3位的药品是抗感染药物83例(51.88%),中药制剂40例(25.00%),消化系统用药9例(5.63%);以皮肤及其附件损害为主;药品不良反应多为一般性的(97.50%),严重的4例(2.50%),并且转归良好,无死亡病例.结论 药品不良反应发生无明显年龄和性别差异.抗感染药物、中药制剂及静脉给药途径是引发药品不良反应的主要因素.应加强合理用药监管,保障患者用药安全.     

Ile118Val genetic polymorphism of CYP3A4 and its effects on lipid-lowering efficacy of simvastatin in Chinese hyperlipidemic patients

Objectives To determine the frequencies of CYP3A4 alleles (CYP3A4*4,*5 and *6) in Chinese hyperlipidemic patients and to observe the impact of CYP3A4*4 (Ile118Val) genetic polymorphism on the lipid-lowering effects of simvastatin and on the activity of CYP3A4.Methods From hospitalized and non-hospitalized patients, 211 unrelated hyperlipidemic patients were recruited for genotyping. CYP3A4 genotypes were determined by means of polymerase chain reaction and restriction fragment length polymorphism analysis. Of the non-hospitalized hyperlipidemic patients, 8 with CYP3A4*1/*1 and 8 with CYP3A4*1/*4 genotypes were selected to be treated with 20 mg simvastatin daily for 4 weeks. Serum triglycerides (TG), cholesterol (CHO) and low-density lipoprotein (LDL) levels were determined using an automated analyzer (Hitachi 747, Boehringer Mannheim, Mannheim, Germany). CYP3A4 activity was determined by the ratio of 6-hydroxycortisol to free cortisol (6-OHC/FC) in the morning spot urine with a high-throughput liquid chromatography–tandem mass spectrometry method.Results Of 211 subjects, 14 (allele frequency 3.32%) were heterozygous for CYP3A4*4 (Ile118Val). Nevertheless, no subjects with a CYP3A4*5 or CYP3A4*6 allele or homozygous for CYP3A4*4 were identified. The ratio of 6-OHC/FC was 9.9±13.7 and 56.6±35.7 in subjects with the Ile118Val variant (n=8) and in CYP3A4 wild-type subjects (n=8), respectively (P=0.0039). After oral intake of simvastatin 20 mg daily for 4 weeks, the change of serum lipids in CYP3A4*1/*1 and CYP3A4*1/*4 groups showed a significant difference, with a mean decrease in triglycerides and total cholesterol of 38.1±7.6% versus 25.1±8.3% (P=0.034) and of 35.8±9.6% versus 22.0±20.4% (P=0.0015) (means ± SD), respectively. We found no statistically significant difference in the reductions of LDL between subjects carrying the *1 and *4 genotypes (29.0±7.4% versus 36.8±8.8%, P=0.0721).Conclusions The allele frequency of CYP3A4*4 was 3.32% among the hyperlipidemic patients from the Chinese mainland. CYP3A4*4 was an allelic variant related to a functional decrease of CYP3A4 activity, and *4 expression seemed to increase the lipid-lowering effects of simvastatin.     

Improved mitochondrial bioenergetics by anesthetic preconditioning during and after 2 hours of 27 degrees C ischemia in isolated hearts

We examined if sevoflurane given before cold ischemia of intact hearts (anesthetic preconditioning, APC) affords additional protection by further improving mitochondrial energy balance and if this is abolished by a mitochondrial KATP blocker. NADH and FAD fluorescence was measured within the left ventricular wall of 5 groups of isolated guinea pig hearts: (1) hypothermia alone; (2) hypothermia+ischemia; (3) APC (4.1% sevoflurane)+cold ischemia; (4) 5-HD+cold ischemia, and (5) APC+5-HD+cold ischemia. Hearts were exposed to sevoflurane for 15 minutes followed by 15 minutes of washout at 37 degrees C before cooling, 2 hours of 27 degrees C ischemia, and 2 hours of 37 degrees C reperfusion. The KATP channel inhibitor 5-HD was perfused before and after sevoflurane. Ischemia caused a rapid increase in NADH and a decrease in FAD that waned over 2 hours. Warm reperfusion led to a decrease in NADH and an increase in FAD. APC attenuated the changes in NADH and FAD and further improved postischemic function and reduced infarct size. 5-HD blocked the cardioprotective effects of APC but not APC-induced alterations of NADH and FAD. Thus, APC improves redox balance and has additive cardioprotective effects with mild hypothermic ischemia. 5-HD blocks APC-induced cardioprotective effects but not improvements in mitochondrial bioenergetics. This suggests that mediation of protection by KATP channel opening during cold ischemia and reperfusion is downstream from the APC-induced improvement in redox state or that these changes in redox state are not attenuated by KATP channel antagonism.     

Evaluation of interaction between intrathecal adenosine and MK801 or NBQX in a rat formalin pain model

Adenosine and excitatory amino acids have been known to be involved in modulating nociceptive transmission at the spinal level. The authors assessed the characteristics of the interaction of the adenosine-excitatory amino acid antagonist combinations in the spinal cord of rats on the formalin-induced nociception. Intrathecal NMDA antagonist ((5R, 10S)-(+)-5-methyl-10,11-dihydro-(5)H-dibenzo[a[,]d]cyclohepten-5,10-imine hydrogen maleate, MK801, 30 microg) and AMPA antagonist (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[F]quinoxaline-7-sulfonamide, NBQX, 3 microg) decreased the total number of flinches during both phases in the formalin test. Intrathecal adenosine (300 microg) had little effect on the phase 1 flinching response, but decreased the phase 2 response. The fixed dose analysis and the isobolographic analysis revealed that adenosine interacts additively with MK801 and NBQX in the spinal cord.