Effects of individual terphenyls and polychlorinated terphenyls on rat hepatic microsomal cytochrome P-450-dependent monooxygenases: structure-activity relationships

The effects of o-, m- and p-terphenyl, 2,4-dichloro-, 2,4,6-trichloro-, 2,3,5,6-tetrachloro-, 2,3,4,6-tetrachloro-, 2,4,4'",6- tetrachloro- and 2,3,4,5-tetrachloro-p-terphenyl, 2,3,4,5-tetrachloro-m- and o-terphenyl as inducers of hepatic drug-metabolizing enzymes were determined in immature male Wistar rats. o-Terphenyl, 2,4-dichloro-, 2,4,6-trichloro-p-terphenyl and 2,3,4,5-tetrachloro-o-terphenyl induced 4,4-dimethylamino antipyrine N-demethylase at total dose levels of 300 mol/kg and the 2,3,4,5-tetrachloro-p-terphenyl induced ethoxyresorufin O-deethylase (EROD). In contrast, none of the other terphenyls or polychlorinated terphenyls (PCTs) induced these enzyme activities. Previous studies have demonstrated that 2,3,4,5-tetrachloro-p-terphenyl did not exhibit a high affinity for the 2,3,7,8-tetrachlorodibenzo-p-trachlorodibenzo-p-dioxin (TCDD) receptor protein (EC₅₀= 6.6×10^–6M). In contrast, this study showed that 2,3,4,5-tetrachloro-p-terphenyl was more active than either 2,3,4,5-tetrachloro-o- or m-terphenyl as an inducer of EROD. Moreover, the competitive receptor binding EC₅₀ values for the latter two isomers were > 10^–5 M and this result was also consistent with their lack of EROD induction activity. Previous studies showed that analysis of the data for a series of 4-substituted-2,3,4,5-tetrachlorobiphenyls indicated that the p-terphenyl structural moiety (i.e. 4-substituent = phenyl) did not interact with high affinity with the receptor protein binding site. Since the 2,3,4,5-tetrachloro o- and m-terphenyls are also poor ligands for the receptor protein, this data and results from other studies indicate that PCT congeners (and commercial mixtures) are therefore unlikely to elicit significant 2,3,7,8-TCDD-like biologic or toxic effects in target species.     

Influence of age on serum protein binding of propranolol

Summary The extent of propranolol protein binding was determined in three different age groups of healthy drug-free caucasian males. Volunteers selected for study were 6–15 years old, 25–36 years old and 68–76 years old. Ten milliliters of blood were obtained via venipuncture and collected in glass tubes from the subjects after an overnight fast. Binding determinations were performed by equilibrium dialysis using radiolabelled propranolol. Serum albumin and ₁-acid glycoprotein concentrations were determined in all subjects by radial immunodiffusion. The results obtained showed wide intersubject variability in the binding ratio of propranolol and serum concentrations of ₁-acid glycoprotein. Mean albumin serum concentration was found to be significantly lower in the elderly group as compared to the adult and pediatric groups (p<0.02). A positive correlation was found between the binding ratio of propranolol and the serum concentration of ₁-acid glycoprotein in all the subjects (r=+0.66,p<0.005). No significant correlation was found between the binding ratio of propranolol and the serum concentration of albumin (r=–0.03,p<0.88). These data suggest that the extent of propranolol binding is influenced primarily by serum concentrations of ₁-acid glycoprotein and not by differences in age.     

Effect of vibration on red cell metabolism

Summary In investigating the influence of vibrational energy on the metabolism of the erythrocyte, it was hypothesized that under conditions of normal PaO₂ and SaO₂ in arterial blood, vibration induced vasoconstriction would decrease local blood flow and induce hypokinetic hypoxia. This decreased blood flow and therefore decreased delivery of oxygen to the tissue would markedly lower tissue PO₂ (hypokinetic hypoxia), which would influence the energetics and metabolism of the erythrocyte. The metabolism of the red blood cell (RBC) was evaluated by measuring the enzymatic activities of PFK (2.7.1.11), PGI (5.3.1.9), PK (2.7.1.40), and aldolase (4.1.3.13) from the anaerobic glycolytic cycle and D-G-6-P (1.1.1.49) from the pentose cycle. Also measured were the levels of ATP and 2,3 DPG and the in-vitro production of lactic acid. In the group of workers showing early changes (vibration angioneurosis) associated with the vibration syndrome, changes in RBC metabolism were demonstrated. Statistically significant were increases of PFK, PK and the production of lactic acid, indicating the activation of anaerobic glycolysis. Furthermore statistically significant were the increased 2,3 DPG and decreased ATP levels.     

Immunohistochemistry of folliculo-stellate cells in normal human adenohypophyses and in pituitary adenomas

Summary Presence and distribution of S-100 protein (S-100), neuron-specific enolase (NSE), cytokeratin polypeptides, glial fibrillary acidic protein (GFAP), vimentin, actin, lysozyme and pituitary hormones (prolactin, hGH, ACTH, -FSH, -LH, -TSH, alpha subunit) in folliculo-stellate cells (FSC) were studied in seven normal human pituitary glands and 28 pituitary adenomas using peroxidase-antiperoxidase and the avidin-biotin immunohistochemical techniques. Approximately 5% of the cells of the adenohypophysis were agranular, non-hormon-producing FSC most of which showed a conspicuous and strong reaction with S-100 antibodies but some were, in addition, GFAP- and vimentin-positive. In contrast to endocrine cells (EC), FSC were not decorated by antibodies to NSE or cytokeratins. In addition to supportive functions, these cells, due to their close special relationship to EC, seem to have transport and other metabolic functions yet to be elucidated. By their S-100 reactivity and their distribution FSC are comparable to glial cells of the central and schwann and satellite cells of the peripheral nervous system (PNS) as well as to supportive cells in neuroendocrine organs and related tumors (e.g., pheochromocytomas, paragangliomas, carcinoids). With one exception, S-100 reactive FSC were not found in pituitary adenomas. The immunohistochemical demonstration of S-100 protein in pituitary tissue is, therefore, a reliable aid in the discrimination between adenomas and normal pituitary tissue, particularly in small and poorly preserved specimens. In one adenoma FSC were found in addition to ACTH-producing tumor cells. This seems to be an extremely rare event suggesting a combination tumor.Supported in part by Fonds zur Förderung der wissenschaftlichen Forschung (no. 4708) to H. Denk     

泽漆水提物对香烟烟雾诱导小鼠慢性阻塞性肺病及肺组织癌前病变相关蛋白的影响

目的：探究泽漆水提物对香烟烟雾(CS)所致的慢性阻塞性肺病(COPD)的保护作用及肺组织癌前病变相关蛋白的影响。方法：通过建立CS所致的COPD小鼠模型(60只),随机分为正常组、模型组、阳性药组(地塞米松2 mg·kg^-1)及泽漆水提物低、中、高剂量组(1.875、3.75、7.5 g·kg^-1)。采用高效液相色谱法(HPLC)测定泽漆水提物中相关成分;动物肺功能仪检测小鼠呼气末期暂停(EEP)、气道阻力(Penh)、50%肺活量呼吸时的呼气流量(EF50)等肺功能指标变化;高通量液相蛋白芯片技术检测小鼠肺泡灌洗液(BALF)中白细胞介素(IL)-2、IL-5、IL-18、IL-17A、IL-27等炎性因子水平变化;苏木素-伊红(HE)染色检测小鼠肺组织的病理变化;比色法测定小鼠肺组织中的丙二醛(MDA)、髓过氧化物酶(MPO)及谷胱甘肽过氧化物酶(GSH-Px)含量变化;实时荧光定量聚合酶链式反应(Real-time PCR)检测肿瘤坏死因子-α(TNF-α)、转化生长因子-β(TGF-β)、基质金属蛋白酶(MMP)-2、MMP-9及MM...     

枳实-白术调节PINK1/Parkin信号通路介导的线粒体自噬改善慢传输型便秘大鼠结肠动力障碍

目的：基于线粒体自噬及磷酸酶及张力蛋白同源物诱导的蛋白激酶1(PINK1)/帕金蛋白(Parkin)通路观察枳实、白术及其配伍对慢传输型便秘大鼠结肠动力障碍的改善作用,为临床精准用药提供理论参考。方法：将56只雄性SD大鼠按体质量随机分成正常组、模型组、自然恢复组、枳实组、白术组、枳实-白术组和莫沙必利组,每组各8只。除正常组外,采用洛哌丁胺连续14 d灌胃(3 mg·kg^-1·d^-1)构建慢传输型便秘大鼠模型。造模成功后,除模型组继续洛哌丁胺诱导外,正常组和自然恢复组采用0.9%生理盐水灌胃,枳实组(1.35 g·kg^-1·d^-1)、白术组(2.7 g·kg^-1·d^-1)、枳实-白术组(4.05 g·kg^-1·d^-1)和莫沙必利组(1.56 mg·kg^-1·d^-1)大鼠分别给予相应的药物灌胃,连续7 d。观察药物对大鼠粪便数量、粪便含水率及小肠推进率的影响;苏木素-伊...     

黄芪桂枝五物汤加减对糖尿病大鼠坐骨神经细胞凋亡相关Bax和Caspase-12的影响

目的 研究黄芪桂枝五物汤加减对糖尿病大鼠坐骨神经细胞凋亡相关B细胞淋巴瘤-2相关X蛋白（Bax）和胱天蛋白酶-12（Caspase-12）蛋白与mRNA表达的影响,以探究黄芪桂枝五物汤加减治疗糖尿病周围神经病变的作用机制。方法 选用动物实验方法进行研究,将60只雄性SD大鼠通过高糖高脂饲料喂养联合链尿佐菌素（STZ）腹腔注射诱导成糖尿病大鼠动物模型,连续3 d随机血糖≥16.7 mmol·L^-1者为糖尿病大鼠造模成功,将48只造模成功的糖尿病大鼠随机分为模型组、α-硫辛酸组（0.026 8 g·kg^-1·d^-1）、中药高、低剂量组（2.5、1.25 g·kg^-1·d^-1）,每组各12只,并设正常组10只。监测大鼠体质量和随机血糖水平;干预16周末通过Key point肌电采集系统检测大鼠坐骨神经传导速度;分别通过蛋白免疫印迹法（Western blot）和实时荧光定量聚合酶链式反应（Real-time PCR）检测大鼠坐骨神经中Bax和Caspase-12蛋白与mRNA的表达。结果 与正常组比较,模型组大鼠体质量显著下降（P<0.01）,随机血糖水平显著升高（P<0.01）;干预16周,与模型组比较,中药高剂量组大鼠体质量明显升高（P<0.05）,其他给药组体质量变化差异无统计学意义;各给药组随机血糖水平均显著降低（P<0.01）。与正常组比较,干预16周,模型组大鼠运动和感觉神经传导速度显著降低（P<0.01）;与模型组比较,各给药组大鼠运动和感觉神经传导速度均明显升高（P<0.05,P<0.01）。与正常组比较,模型组大鼠坐骨神经Bax和Caspase-12蛋白表达显著升高（P<0.01）;与模型组比较,各给药组大鼠坐骨神经Bax和Caspase-12蛋白表达均显著降低（P<0.01）。与正常组比较,模型组大鼠坐骨神经Bax和Caspase-12 mRNA表达显著升高（P<0.01）;与模型组比较,α-硫辛酸组、中药高剂量组大鼠坐骨神经Bax mRNA表达明显降低（P<0.05,P<0.01）,中药低剂量组坐骨神经Bax mRNA表达降低有下降趋势;各给药组大鼠坐骨神经Caspase-12 mRNA表达显著降低（P<0.01）。结论 黄芪桂枝五物汤加减可能通过抑制坐骨神经细胞凋亡来改善和修复糖尿病大鼠坐骨神经损伤。     

血清脂联素、骨桥蛋白和HE4在子宫内膜癌患者中的表达及意义

目的：探讨血清脂联素（APN）、骨桥蛋白（OPN）和人附睾分泌蛋白4(HE4)在子宫内膜癌患者中的表达及意义。方法：选取2019年11月至2022年9月郴州市第一人民医院收治的子宫内膜癌患者62例（子宫内膜癌组）,另选取同期50例子宫内膜不典型增生患者（内膜增生组）和50例健康志愿者（正常内膜组）。检测并比较三组血清APN、OPN、HE4水平,采用受试者工作特征（ROC）曲线分析血清APN、OPN、HE4对子宫内膜癌的诊断效能,并采用Spearman相关性分析探讨血清APN、OPN、HE4与临床病理特征的相关性。结果：子宫内膜癌组患者血清APN水平低于内膜增生组和正常内膜组,OPN、HE4水平高于内膜增生组和正常内膜组。国际妇产科联盟（FIGO）分期为Ⅲ期患者血清APN水平低于Ⅱ期和Ⅰ期患者,OPN、HE4水平高于Ⅱ期和Ⅰ期患者;肌层浸润深度≥1/2肌层患者血清APN水平低于<1/2肌层患者,OPN、HE4水平高于<1/2肌层患者;淋巴结转移患者血清APN水平低于无淋巴结转移患者,OPN、HE4水平高于无淋巴结转移患者,差异均具有统计学意义（P <0.05）。ROC曲...     

错配修复蛋白表达缺失在子宫内膜癌中的临床病理意义

目的:探究错配修复(MMR)蛋白表达缺失在子宫内膜癌(EC)中的临床病理意义。方法:选取惠州市第一人民医院2019年3月至2022年12月收集的EC患者术后石蜡包埋子宫内膜组织标本50例,采用免疫组织化学检测法检测MMR蛋白表达,包含MLH1、MSH2、MSH6及PMS2,观察MMR蛋白表达缺失率,对不同年龄及EC病理特征的MMR蛋白表达缺失情况进行比较。结果:(1)50例EC患者MMR蛋白表达缺失发生率为36.00%。MMR蛋白MLH1、MSH2、PMS2、MSH6表达缺失率分别为22.00%、6.00%、30.00%、6.00%,其中单项缺失4例(8.00%),两项表达缺失14例(18.00%)。(2)≤50岁EC患者MMR蛋白缺失表达率(56.00%)高于> 50岁EC患者(16.00%),差异具有统计学意义(P <0.05)。(3)不同细胞分化程度、肌层浸润程度及淋巴结转移情况患者MMR蛋白表达缺失情况比较,差异均无统计学意义(P> 0.05)。结论:MMR蛋白在EC中表达缺失率较高,以PMS2表达缺失为主,且MMR蛋白表达缺失率在≤50岁EC患者中更高,故需...