喷昔洛韦在大鼠体内的分布和排泄试验

目的：了解抗病毒药物喷昔洛韦静脉注射后在大鼠体内的分布和排泄情况。方法：喷昔洛韦在生物样品中的浓度用高效液相色谱法测定。结果：喷昔洛韦分布较快，15分钟后各组织中有较高浓度，分布广，以肝、肾、肺浓度较高，脑组织也有一定分布，2小时后主要脏器的药物浓度已明显减少。排泄试验表明：药物主要从肾脏清除，大鼠尾静脉注射喷昔洛韦24小时后，尿中排出给药量的59．61％；药物也可经胆汁排出，24小时内从胆汁中排出给药量的5．37％；72小时后粪中排出给药量4．96％。     

黄连素对T淋巴细胞活化和增殖的抑制作用

目的:研究黄连素(Ber)对T细胞体外活化和增殖的影响及作用机制。方法:正常人外周血全血培养,以植物血凝素(PHA)或佛波醇酯(PDB)加离子霉素(Ion)刺激活化淋巴细胞,双荧光染色及溶血获取有核细胞后,以流式细胞仪分析T细胞表达活化抗原CD69和CD25的水平,并以碘化丙锭染色分析细胞周期分布,7-AAD活染分析细胞死亡率。结果:浓度为100μmol/L和50μmol/L的Ber对PDB+Ion或PHA激活T细胞表达CD69有明显抑制,而25μmol/L的Ber抑制效应无显著性;随时间延长,对CD69表达的抑制程度下降;对于CD25表达,上述3个浓度的Ber抑制作用均有显著性,且呈剂量依赖性。同时,这3个浓度的Ber均能明显阻止淋巴细胞进入S期和G₂/M,对细胞周期的抑制作用没有时相特异性。活染分析显示Ber对淋巴细胞无明显细胞毒性。结论:Ber通过干扰早期活化信号转导通路而抑制T细胞活化和增殖,发挥其免疫抑制作用。     

11C-胆碱在线自动合成和生物体内分布

目的研究[11C-甲基]胆碱在线自动化合成的方法,并初步应用于临床试验.方法 11C-胆碱柱色层法在线制备.以Wistar大鼠研究动物体内生物学分布.结果柱色层制备的11C-胆碱放化纯度大于99%,合成效率为85%,合成时间11min.动物分布表明:放射性主要分布于肾、肝和肠道, 血液清除较快.结论柱色层法制备11C-胆碱时间短,效率高,操作简单.     

^11C-胆碱在线自动合成和生物体内分布

目的 研究[^11C-甲基]胆碱在线自动化合成的方法，并初步应用于临床试验．方法 ^11C-胆碱柱色层法在线制备，以Wistar大鼠研究动物体内生物学分布．结果 柱色层制备的^11C-胆碱放化纯度大于99％，合成效率为85％，合成时间11 min．动物分布表明：放射性主要分布于肾、肝和肠道，血液清除较快。结论 柱色层法制备^11C-胆碱时间短，效率高，操作简单。     

小檗碱对DNFB诱导的小鼠迟发型超敏反应的影响

目的:研究小檗碱(Ber)对二硝基氟苯(DNFB)诱导的小鼠迟发型超敏反应(DTH)的影响,探讨其免疫抑制作用的机制。方法:BALB/c小鼠分为对照组、DTH组与Ber处理的DTH组。对照组以不含DNFB的溶剂处理,DTH组以5g/LDNFB腹部致敏、耳廓激发的方法建立模型,Ber处理的DTH组每天腹腔注射(i.p)Ber,连续7d,总剂量为30mg/kg体质量。激发后48h,取小鼠双耳称重了解Ber对炎症抑制率的影响。镜下观察耳廓局部组织的变化;以结晶紫法检查Ber对脾脏T淋巴细胞与细胞外基质(ECM)黏附作用的影响;以膜联蛋白V(AnnexinV)染色检查淋巴结细胞的凋亡率。结果:双耳称重的结果显示,Ber处理的DTH组与DTH组具有显著的差异(P<0.05),能明显抑制DNFB引起的炎症反应;耳廓局部组织学检测也表明,Ber能够抑制DNFB诱导的DTH,明显减少淋巴细胞的浸润。Ber处理的DTH组的T细胞与ECM的黏附能力明显降低(P<0.05)。Ber处理的DTH组与DTH组和对照组的细胞凋亡率均无明显差异(P>0.05)。结论:Ber对DNFB诱导的小鼠DTH具有明显的抑制作用,降低小鼠T细胞与ECM的黏附能力可能是其抑制DTH的机制之一。     

小檗碱对人骨髓增生异常综合征细胞MUTZ-1自噬活性的影响及机制

为探讨小檗碱(Berberine, Ber)对人骨髓增生异常综合征(myelodysplastic syndrome, MDS)细胞MUTZ-1自噬活性的影响及机制,以MTT法检测Ber对MUTZ-1细胞的增殖抑制率、半数抑制浓度(half inhibitory concentration, IC_(50)),并绘制增殖抑制率曲线;免疫荧光法测定细胞中LAMP1表达;Western blotting测定LC3-Ⅰ、LC3-Ⅱ、p-mTOR、Beclin-1、p-Akt、p-ERK、ATG3、ATG4、ATG5、ATG7蛋白表达。结果显示,Ber作用后MUTZ-1细胞增殖抑制水平随时间而增强,Ber对MUTZ-1细胞24、48 h的IC_(50)分别为265.1μmol/L和143.2μmol/L;LAMP1、LC3-Ⅱ蛋白表达水平、LC3-Ⅱ/LC3-Ⅰ比值随时间而增加;Beclin-1、ATG3、ATG5表达水平增加,p-mTOR、p-Akt表达水平降低,p-ERK、ATG4、ATG7表达水平无明显变化。由此说明Ber可抑制MUTZ-1细胞增殖并诱导其自噬,自噬的诱导与Beclin-1、ATG3、ATG5表达上调和mTOR活性受抑制有关。     

小檗碱增强丝裂霉素C诱导的膀胱癌T24细胞周期阻滞及凋亡

目的:研究小檗碱(berberine,Ber)增强丝裂霉素C(mitomycin C,MMC)诱导的人类膀胱癌T24细胞周期阻滞和细胞凋亡的作用及其相关机制。方法:将T24细胞分为4组:对照组、MMC组、MMC+Ber组和Ber组;采用CCK-8法检测不同药物处理后T24细胞的活力;采用流式细胞术分析不同药物处理后T24细胞周期的情况;Western blot检测细胞周期调控相关蛋白及凋亡相关蛋白的表达;Annexin V-FITC/PI双染后用流式细胞术检测各组细胞凋亡率。结果:CCK-8实验表明Ber能增强MMC抑制T24细胞活力的作用;流式细胞术检测细胞周期结果显示,MMC+Ber组T24细胞滞于G_0/G_1期(P0.05);与MMC组相比,MMC+Ber组p21和p27的蛋白表达上调(P0.05),cyclin D1、CDK2和CDK4的蛋白表达下调(P0.05),同时Ber促进MMC下调survivin的蛋白表达(P0.05);Annexin V-FITC/PI双染结果显示,Ber能促进MMC诱导的T24细胞凋亡(P0.05)。结论:Ber能显著增强MMC抑制T24细胞活力的作用,其机制可能是通过上调p21和p27,进而抑制cyclin D1、CDK2和CDK4表达;同时通过抑制survivin蛋白的表达,最终导致细胞被阻滞在G_0/G_1期,并促进细胞凋亡。     

小檗碱和育亨宾对LPS诱导的小鼠肠道损伤和肠上皮细胞增殖抑制的影响

目的:观察小檗碱(Ber)和育亨宾(Y)对LPS诱导的小鼠肠道损伤和肠上皮细胞增殖抑制的影响。方法:雄性BALB/c小鼠随机分为对照组(control)、脂多糖组(LPS)、小檗碱组(Ber+LPS)、小檗碱与育亨宾合剂组(Ber+Y+LPS)、育亨宾组(Y+LPS)、小檗碱组(Ber)、小檗碱和育亨宾合剂组(Ber+Y)及育亨宾组(Y)。分别予以双蒸水、Ber(50mg/kg)、Ber(50mg/kg)+Y(2mg/kg)、Y(2mg/kg)灌胃,1time/d,连续3d,于实验第3d灌胃后1h,腹腔注射生理盐水或LPS(18mg/kg,0.2mL/10g)。观察各组小鼠肠组织形态学、肠黏膜重量和绒毛高度的改变;酶联免疫吸附实验(ELISA)测定肠组织二胺氧化酶(DAO)含量;免疫组化染色方法分析各组肠组织增殖细胞核抗原(PCNA)的表达。结果:LPS组小鼠肠腔显示炎性渗出、出血;肠损伤评分明显高于对照组;LPS组肠黏膜重量、肠绒毛高度、肠组织DAO含量、肠上皮细胞PCNA表达明显低于对照组。与LPS组比较,Ber组、Ber+Y组上述改变明显减轻,但两组间未见明显差异;育亨宾对LPS引起的上述指标变化无明显抑制作用。结论:Ber通过非α2肾上腺素能受体依赖的途径减轻LPS引起的肠上皮细胞增殖抑制和肠道损伤。     

人参总皂苷和小檗碱对肺癌PG细胞"Fas反击"的影响

目的：探讨人参总皂苷（Ginsenosirde，Gs）和小檗碱（Berberine，Ber）对肿瘤“Fas反击”免疫逃逸机制的影响。方法：首先建立肺癌PG细胞与Jurkat细胞的共培养体系；Giemsa染色和流式细胞仪观察和检测共培养后的Jurkat细胞的凋亡；SABC免疫细胞化学法检测Gs和Ber处理后的PG细胞FasL、Fas分子的表达。结果：Jurkat细胞与PG细胞共培养后产生凋亡，Gs和Ber处理的PG细胞诱导的Jurkat细胞凋亡更为显著；Gs和Ber可以上调PG细胞FasL、Fas分子的表达。结论：Gs和Ber可以促进PG细胞诱导Jurkat细胞凋亡的作用，其机制可能与Gs和Ber上调PG细胞FasL分子的表达有关。     

川芎嗪对器官微循环的影响

川芎嗪是中药伞形科植物川芎的有效成分,化学结构为四甲基吡嗪（Ｔｅｔｒａｍｅｔｈｙｌｐｙｒａｚｉｎｅ）。１９７０年代初,由北京制药工业研究所从川芎提取物中析出单体川芎嗪［１］,现在已由人工合成。川芎嗪在动物体内主要分布在消化系统如肝、胃、肠,还大量分布于肺脏、心脏,并可透过血脑屏障稳定而持久地存在于大脑组织中［２］。静脉用药后,在机体内含量和保留时间上,各靶器官之间存在差异,血液中半衰期为３０ｍｉｎ［２,３］。动物实验和临床研究均证实：川芎嗪有活血化瘀、抗血小板凝聚、扩张小动脉、改善微循环障碍的药…     

Testing of 24 food, drug, cosmetic, and fabric dyes in the in vitro and the in vivo/in vitro rat hepatocyte primary culture/DNA repair assays

Twenty-four dyes currently or previously used in the food, drug, cosmetic, and textile industries were tested in the in vitro rat hepatocyte primary culture/DNA repair (HPC/DR) assay and, to a limited extent, in the in vivo/in vitro HPC/DR assay. The positive control, Solvent Yellow 3 (o-aminoazotoluene), and five other dyes (4-dimethylaminobenzeneazo-1-naphthalene, 4-dimethylaminobenzeneazo-2-naphthalene, Direct Blue 53, Acid Blue 9, and 4-dimethylaminostilbene) induced DNA repair in rat hepatocytes both in vitro and in vivo, while 13 of the dyes (Food Red 1, Food Red 5, Food Orange 4, Food Red 7, Acid Red 14, Acid Red 27, Pigment Red 53, Acid Yellow 23, Food Black 1, Food Green 3, Acid Red 51, Acid Blue 74, and Natural Red 4) did not produce any detectable DNA repair in either the in vitro or in vivo/in vitro assays. Direct Blue 14 had weak activity in vitro but none was detected in vivo. In contrast, Solvent Yellow 5 was not active in vitro, but produced a weak positive response in vivo. Negative responses were also obtained for Solvent Yellow 14 and Acid Green 5 in the in vitro assay, whereas the responses produced by these dyes in the in vivo/in vitro assay were judged to be equivocal. An equivocal response was also obtained for Direct Red 28 in the in vivo/in vitro assay as well as in the in vitro assay. These findings provide information about the potential genotoxicity of a number of dyes for which previous genotoxicity data has been inconsistent or inadequate. For some dyes (eg, Solvent Yellow 5), discrepancies between the results obtained in the in vitro and in vivo/in vitro assays may implicate a role for intestinal microflora in their metabolic activation.     

Histopathology and etiology of childhood pneumonia: an autopsy study of 93 patients in Bangladesh

The causes and pathogenesis of severe childhood pneumonia in a developing country were studied in lungs removed at autopsy from 119 Bangladeshi children who presented with pneumonia and/or diarrhea. Pneumonia was observed in 93 patients. Morphologic features included acute alveolar exudate in 51% (of the 93 patients), necrotizing pneumonia in 31%, interstitial pneumonia in 22%, and caseating granulomas in 4%, while a mixed pattern occurred in 16% of patients. Causes of pneumonia were Gram-negative bacteria in 27%, pneumococcus in 8%, cytomegalovirus (CMV) in 8%, Pneumocystis carinii (PC) in 4%, mycobacteria in 3%, aspergillus in 3%, mixed anaerobes in 3%, viral (not CMV) in 2%, Staphylococcus aureus in 1% and ascaris in 1%. Two causative agents were identified in 7% of patients. In 46% of the cases, no etiologic agent was identified. Our data suggest that most pneumonias had a bacterial etiology; however, viruses, including CMV, and other opportunistic organisms such as PC, were also important pathogens. Gram-negative pneumonia was partially attributed to concomitant intestinal infections. Opportunistic infections resulted from malnutrition and debilitated host defenses during prolonged fatal illnesses.     

Involvement of clusterin and the aggresome in abnormal protein deposits in myofibrillar myopathies and inclusion body myositis

Myofibrillar myopathies (MM) are characterized morphologically by the presence of non-hyaline structures corresponding to foci of dissolution of myofibrils, and hyaline lesions composed of aggregates of compacted and degraded myofibrillar elements. Inclusion body myositis (IBM) is characterized by the presence of rimmed vacuoles, eosinophilic inclusions in the cytoplasm, rare intranuclear inclusions, and by the accumulation of several abnormal proteins. Recent studies have demonstrated impaired proteasomal expression and activity in MM and IBM, thus accounting, in part, for the abnormal protein accumulation in these diseases. The present study examines other factors involved in protein aggregation in MM and IBM. Clusterin is a multiple-function protein which participates in Abeta-amyloid, PrP(res) and a-synuclein aggregation in Alzheimer disease, prionopathies and a-synucleinopathies, respectively. gamma-Tubulin is present in the centrosome and is an intracellular marker of the aggresome. Moderate or strong clusterin immunoreactivity has been found in association with abnormal protein deposits, as revealed by immunohistochemistry, single and double-labeling immunofluorescence and confocal microscopy, in MM and IBM, and in target structures in denervation atrophy. Gamma-Tubulin has also been observed in association with abnormal protein deposits in MM, IBM, and in target fibers in denervation atrophy. These morphological findings are accompanied by increased expression of clusterin and gamma-tubulin in muscle homogenates of MM and IBM cases, as revealed by gel electrophoresis and Western blots. Together, these observations demonstrate involvement of clusterin in protein aggregates, and increased expression of aggresome markers in association with abnormal protein inclusions in MM and IBM and in targets, as crucial events related to the pathogenesis of abnormal protein accumulation and degradation in these muscular diseases.     

石蜡包埋胰腺癌组织中DPC4基因改变的检测

目的 研究石蜡包埋胰腺癌组织中ＤＰＣ４基因的改变。方法 用聚合酶链反应－单链构象多态性分析（ＰＣＲ－ＳＳＣＰ）银染技术检测４６例石蜡包埋胰腺癌组织中ＤＰＣ４基因的缺失和突变。结果 ＤＰＣ４基因第１、２、３、４、８和１１外显子的纯合性缺失率为１３／４６（２８．３％）,具体分布为１例在第１１外显子;１例在第１、２、３、４、８和１１外显子的纯合性缺失率为１３／４６（２８．３％）,具体分布为１例在第１１外     

Alterations in bronchoalveolar lavage constituents, oxidant/antioxidant status, and lung histology following intratracheal instillation of respirable suspended particulate matter.

Urban suspended particulate pollutants differ with place of occurrence, meteorological conditions, physicochemical compositions, and the response of the bronchopulmonary apparatus. Lung injury following intratracheal instillation of respirable suspended particulate matter (RSPM) collected in an urban setting in India was investigated in rats. The animals were killed 15 days after exposure to 2.5, 5.0, and 10.0 mg of RSPM. We examined the changes in lung histology, enzymatic activity in the bronchoalveolar lavage (BAL), and the oxidant/ antioxidant status in lung homogenates.The alterations in these parameters were compared with those in rats instilled with quartz particulates, which were used as positive controls. Exposure to RSPM resulted in an increase in the relative weight of lungs and inflammatory changes evidenced by an increase in the total cellularity of the lungs, predominantly polymorphonuclear cells, demonstrable both in the lungs sections and in the bronchoalveolar lavage of the exposed animals. An increase in the protein content and in the lactate dehydrogenase activity in the BAL was found in the RSPM-exposed rats. A marked increase in the output of lipid peroxides and a dose-dependent increase in the formation of reactive nitrogen species (NO) in lung homogenates and BAL, respectively, was found in the RSPM-exposed rats. A significant decrease in the enzymatic lung antioxidants, superoxide dismutase, and catalase was observed. However, the alterations in the levels of glutathione in the lungs of the RSPM-exposed animals were not significant. The inflammatory reaction, oxidative changes, and enzyme release, were more marked in quartz-exposed animals in comparison to the RSPM-exposed rats.     

Immunohistochemical localization of galectin-3 in the reproductive organs of the cow

The protein levels and immunohistochemical localization of galectin-3, which is a beta-galactoside-binding protein, were studied in the cow reproductive organs. Using Western blot analysis, galectin-3 was detected at low levels in the ovary and oviduct, at moderate levels in the uterus, and at high levels in the cervix. Using immunohistochemistry, galectin-3 was immunolocalized in macrophages in the interstitium, in cells in the atretic follicles, and in luteal cells in the regressing corpus luteum, but not in the growing follicles in the ovary. In the oviduct, galectin-3 was detected in some macrophages in the lamina propria, submucosa and muscle layers, as well as in some cells in the covering epithelium. In the uterus, galectin-3 was immunolocalized in some epithelial cells and in some macrophages in the submucosa, but not in the endometrial glands at the non-pregnant stage. In the cervix, galectin-3 was immunolocalized in many mucus-secreting cells in the mucosa and in a few macrophages in the submucosa and muscle layers. Based on its localization, we postulate that galectin-3 in the covering epithelium is involved in the mucosal defense system, and that galectin-3-positive macrophages in all tissues are involved in either cell survival or death. In addition, galectin-3 plays an important role in the regression of follicles and the corpus luteum.     

Apoptosis in human chorionic villi and decidua in normal and ectopic pregnancy

To investigate possible effects of implantation on apoptosis, we examined the cleavage of DNA in human chorionic villi and decidua in intrauterine and ectopic pregnancy. Very limited but detectable cleavage of DNA was recognized in the chorionic villi and decidua in normal pregnancy. A ladder pattern, characteristic of the apoptotic breakdown of DNA, was present in the villi in tubal pregnancy. High molecular weight DNA was predominant in the decidua in tubal pregnancy. Quantitative analysis of low molecular weight fragments of DNA revealed a significant increase in the villous tissue, together with a significant decrease in the decidual tissue, in tubal pregnancy as compared to those in normal pregnancy. An analysis in situ revealed that apoptotic cells were predominant in the syncytiotrophoblast in tubal pregnancy. In decidual tissue, labelled cells were occasionally seen in normal pregnancy, and their numbers decreased in tubal pregnancy. The present study demonstrates that apoptosis occurs in the villi, but not in the decidua in tubal pregnancy, unlike the situation in normal pregnancy. Our results suggest that the implantation site might affect the occurrence of apoptotic changes in early pregnancy of humans.      

Magnesium distribution in rats after maximal exercise in air and under hypoxic conditions.

Variations in serum levels and distribution of Mg in the heart, gastrocnemius, liver and kidney in rats were studied after exercise to exhaustion in air (normoxia) and during hypoxia (FIO2 = 0.10). After exercise serum Mg concentrations increased significantly in air, but not during hypoxia. At rest, they increased significantly during hypoxia. In air, increases in Mg in the gastrocnemius and liver were found after exercise. At rest in hypoxia, Mg was reduced in heart, liver and kidney. After exercise in hypoxia, Mg was decreased in heart, gastrocnemius and liver, the greatest decrease occurring in the gastrocnemius, with a relative increase in kidney. Exercise and hypoxia both affect magnesium homeostasis.     

Comparative neurochemical and physiological characteristics of catalepsy-type rest and sleep

With the exception of mammals, rest in vertebrates can also be a special catalepsy-type state. For hens, the total duration of this state is longer in daytime than in twilight, and it is completely absent at night. This natural state in hens is similar to photogenic catalepsy, which they develop in response to rhythmical light stimulation. A cytospectrophotometrical investigation of individual cells from the supraoptic nucleus showed that catalepsy-type rest in hens did not differ from sleep in rats, in that there was no change in the absolute content (per cell) of proteins in neurons. However, in contrast with sleep, this state of immobility is accompanied by a decrease in the RNA content of neurons and by an absence of the RNA and protein accumulation in gliocytes, which is significant during sleep. During catalepsy-type rest in hens, there were no statistically reliable changes in protein and RNA contents in cells from the ectomammilar nucleus of the supplementary optical system and from the round thalamic nucleus. Cataleptiform (photogenic) immobility in hens is apparently a metabolically passive form of rest in comparison with sleep in rats, which is characterized by anabolic processes in the brain.Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 13, No. 1, pp. 56–61, January–February, 1977.     

Acute renal failure amongst children in a tropical environment

The pathogenetic factors leading to acute renal failure (ARF) in 223 children between the ages of 20 days and 14 years were studied. Diarrhoeal diseases were responsible for ARF in 49.8%, acute glomerulonephritis in 34.1%, drug induced intravascular hemolysis in glucose -6-phosphate dehydrogenase deficiency in 4.5%, snake bite in 4%, hemolytic uremic syndrome in 2.2%, and miscellaneous causes in 5.4%. Dialysis was instituted in 178 children and the others were treated conservatively. Renal histology in 39 out of 76 children who presented with an acute nephritic illness revealed acute endocapillary proliferative glomerulonephritis in 27 and crescentic glomerulonephritis in 12. The histology in 79 out of 147 remaining patients showed acute tubular necrosis in 64, acute cortical necrosis in 13, and acute interstitial nephritis in 2. Overall mortality was 27.4%. This high incidence of ARF due to infective diarrhoeas and dysentery reflects poor socio-economic and hygienic conditions, inadequate facilities in rural areas, delays in seeking medical advice, and lack of knowledge about fluid and electrolyte therapy amongst the staff.