Induction of light hydrocarbon nephropathy by p-dichlorobenzene

In order to clarify the etiology of a dose-related increase in the incidence of tubular cell adenocarcinomas of the kidney in male rats, the nephrotoxicity of p-dichlorobenzene (p-DCB) was investigated in a subchronic study. Groups of ten male and ten female Fischer 344 rats were dosed by gavage with 0 (controls), 75, 150, 300 or 600 mg p-DCB/kg/day in corn oil. Half of the animals were sacrificed after 4 weeks and the remainder after 13 weeks. Increased urinary LDH and epithelial cell excretion and exacerbation of hyaline droplet accumulation in the cytoplasm of renal cortical cells were observed in male rats over the entire dose range investigated. Tubular single cell necrosis, dilated tubules with granular cast formation in the outer zone of the medulla, were evident in male rats after 4 and 13 weeks of treatment with doses of 150–600 mg/kg/day. In female rats there was no indication of a nephrotoxic action of p-DCB. The effects on the kidney, both in their morphological characteristics and the fact that they occur exclusively in male animals, correspond to the light hydrocarbon nephropathy observed as a result of short-term treatment with a number of aliphatic and cyclic hydrocarbons. The development of cortical renal tumors seems to be associated with this kind of kidney damage which is unique to male rats. The literature on this subject generally regards these renal effects as not predictive for man.     

Thiol Reduction of 3′-Azidothymidine to 3′-Aminothymidine: Kinetics and Biomedical Implications

The ability of thiols to reduce 3-azidothymidine (AZT) to 3-aminothymidine has been investigated. Incubation with glutathione, dithiothreitol (DTT), or mercaptoethanol at pH 7.2 and 37°C leads to quantitative reduction of the azido moiety to an amine. The reaction is first order in AZT and first order in reducing agent (mono- or dithiol). The second-order rate constants are 2.77 × 10^–3, 6.55 × 10^–5, and 6.35 × 10^–6 M ^–l sec^–1 for the dithiothreitol, glutathione, and mercaptoethanol reductions, respectively. The thiol reduction of alkyl azide to amine under mild conditions is a synthetic method particularly suitable for water-soluble azido compounds that are sensitive to catalytic hydrogenation. The potential for the mono- or dithiol-mediated reduction of alkyl azides under biological conditions must be considered when conducting studies of azido drugs.     

民族药香青兰化学成分及药理作用研究进展

摘要：目的：对民族药香青兰进行化学成分及药理活性的研究,对该药材的综合应用和深入研究奠定基础。方法：通过查阅1995-2022年知网、PubMed中的中英文文献与相关文献对香青兰进行综述。结果：经过系统的研究,发现香青兰的组成主要包含总黄酮和黄酮苷类、挥发油、三萜类和蛋白质等。这些成分有着多种药理作用,如抗缺氧、抗血栓和降血压。结论：香青兰对于治疗高血压,心脏病等有一定疗效。香青兰在蒙医临床中应用广泛。研究表明,香青兰的化学成分和药理作用已经取得了一定的进展,其作用范围广泛,对心血管疾病有显著的疗效。     

呼吸道真菌感染核酸胶体金试纸条快速检测方法的建立和评价

目的 采用聚合酶链式反应（PCR）技术和胶体金技术建立一种呼吸道真菌感染核酸胶体金试纸条检测方法,并对其检测效果进行评价。 方法 根据GenBank数据库选择真菌内转录间隔区（ITS）基因片段作为靶基因,应用DNAMAN软件对真菌ITS基因片段进行分析,并分别在真菌通用引物5'端用生物素（Biotin）和异硫氰酸荧光素（FITC）进行修饰标记;建立PCR体系,进行体系的最佳条件优化;确定胶体金免疫层析试纸条标记链霉亲和素的最佳标记量和质控线及检测线最佳包被物浓度,组装核酸胶体金试纸条,对试纸条的特异度、灵敏度、重复性和稳定性进行验证。 结果 水煮法提取白假丝酵母菌、新生隐球菌和毛霉菌DNA,浓度为180 μg·L^－1以上,纯度为1.60~2.10;在pH 7.0条件下,每100 μL胶体金溶液中制备胶体金标记链霉亲和素最佳标记量为 3.3 μg,质控线包被Biotin化牛血清白蛋白（BSA-Biotin）浓度为2.00 g·L^－1,检测线包被抗FITC抗体浓度为1.00 g·L^－1。核酸试纸条的特异度与电泳结果一致,仅白假丝酵母菌、新生隐球菌和毛霉菌出现阳性结果,与金黄色葡萄球菌、肺炎链球菌、乙型溶血性链球菌、铜绿假单胞菌、肺炎克雷伯菌、鲍曼不动杆菌和大肠埃希菌等常见呼吸道感染细菌无交叉反应。灵敏度检测,白假丝酵母菌、新生隐球菌和毛霉菌的DNA浓度分别为10^－4、10^－2和10^－3 mg·L^－1时核酸试纸条仍可准确检出,而普通PCR电泳结果显示白假丝酵母菌、新生隐球菌和毛霉菌最低检测浓度分别为0.01、1.00和0.10 mg·L^－1;重复性检测,在不同实验室不同操作人员对核酸试纸条进行验证,结果一致,重复性良好;稳定性检测,核酸试纸条在第6、9和12个月进行检测,结果符合预期,稳定性良好。 结论 本研究建立的呼吸道真菌感染核酸胶体金试纸条可以检测白假丝酵母菌、新生隐球菌和毛霉菌等真菌,特异度和灵敏度均较高,操作简便且快速。     

术前右美托咪定滴鼻对扁桃体腺样体切除术患儿围术期的影响

探讨术前应用右美托咪定滴鼻对扁桃体腺样体切除术患儿围术期呼吸系统不良事件的影响。方法 选取2020年10月—2021年6月徐州医科大学附属医院收治的择期扁桃体腺样体切除术的患儿120例,采用随机数字表法将患儿分为右美托咪定组（D组）和生理盐水组（N组）,每组60例。D组在术前30 min经鼻给予右美托咪定2.0 μg/kg（容量配置1 mL）,N组术前30 min经鼻给予1 mL生理盐水。比较两组围术期呼吸系统不良事件发生率,镇静水平,术后疼痛评分,术后躁动谵妄水平,恶心、呕吐等其他不良事件。结果D组围术期呼吸系统不良事件发生率明显低于N组（P＜0.05）,且镇静水平高于N组（P＜0.05）,D组术后需求补救镇静的人数低于N组（P＜0.05）,D组苏醒期躁动发生率低于N组（P＜0.05）。结论 右美托咪定术前滴鼻可能与降低呼吸系统不良事件的发生率相关,并可取得较为满意的镇静效果,能减轻术后疼痛,降低苏醒期躁动的发生率     

低频脉冲电刺激联合摄食-吞咽训练在AIS后吞咽障碍的应用及疗效

探讨低频脉冲电刺激联合摄食-吞咽训练在急性缺血性脑卒中（AIS）后吞咽障碍的应用及对呼吸能力、吞咽功能、营养指标的影响。方法 选取本院2019年6月—2021年8月107例AIS后吞咽功能障碍患者,随机分为观察组（n=54）和对照组（n=53）,对照组给予摄食-吞咽训练,观察组在对照组的基础上使用低频脉冲电刺激治疗,两组均持续治疗1个月,比较两组治疗前后吞咽功能、舌骨喉复合体动度、喉镜吞咽功能(FEES)评估结果、呼吸功能、营养指标以及并发症发生情况。结果 观察组治疗后洼田饮水试验评定、标准吞咽功能评价量表（SSA）评分、吞咽功能初筛量表（EAT-10）评分低于对照组（P＜0.05）;观察组治疗后舌骨喉复合体动度包括舌骨向前、上移以及喉向前、喉上移最大幅度均大于对照组（P＜0.05）;观察组治疗后FEES评价中声带麻痹、食物渗漏、食物潴留、误吸比例低于对照组（P＜0.05）;观察组治疗后肺功能指标最长呼气时间、第一秒用力呼气容积（FEV1）、用力肺活量（FVC）以及最大吸气压（PImax）均大于对照组（P＜0.05）;观察组治疗后营养指标BMI指数、血清总蛋白（TP）、白蛋白（ALB）、转铁蛋白（TRF）、前白蛋白（PALB）水平均高于对照组（P＜0.05）;观察组吸入性肺炎发生率低于对照组,营养不良发生率为低于对照组（均P＜0.05）。结论 低频脉冲电刺激联合摄食-吞咽训练治疗AIS后吞咽障碍,可有效促进吞咽功能恢复,改善舌骨喉复合体动度,增强呼吸功能,提高营养状态,降低并发症发生风险     

Changes in ultrastructure of hepatocytes and liver test results before,during, and after treatment with interferon-β in patients with HBeAg-positive chronic active hepatitis

We studied the histological and ultrastructural changes in the liver and alterations in the liver test results before, during, and after treatment with human interferon- from five patients with hepatitis B e antigen-positive chronic active hepatitis. A daily dose of 3×10⁶ to 6×10⁶ units of interferon- was given intravenously for four weeks. The total index of periportal and portal inflammation, intralobular degeneration, and focal necrosis before treatment was decreased significantly six months after treatment (P<0.05). Ultrastructurally, the structure of endoplasmic reticulum was irregularly shaped or fragmentally decreased during treatment, but these disappeared six or 12 months after treatment. Glycogen particles diminished greatly during treatment. The alanine aminotransferase concentrations in these patients increased during treatment. Serum albumin and cholinesterase levels decreased significantly at the fourth week of treatment (P<0.01) and at the third day (P<0.01) to the second week (P<0.05) of treatment, respectively. These results suggest that interferon- injures endoplasmic reticulum and glycogen areas and damages the cholinesterase activity in the early stage of treatment and protein synthesis in patients with hepatitis B e antigen-positive chronic active hepatitis.     

Histochemical study of pituitary adenomas with Ki-67 and anti-DNA polymerase α monoclonal antibodies,bromodeoxyuridine labeling,and nucleolar organizer region counts

Summary The growth potential of 65 pituitary adenomas was determined by histochemical analysis with Ki-67 and anti-DNA polymerase monoclonal antibodies, bromodeoxyuridine (BrdUdR) labeling, and counts of argyrophilic nucleolar organizer regions (Ag-NORs). The mean proliferating cell indices (PCIs) determined by Ki-67 and anti-DNA polymerase and the BrdUdR labeling index (LI) were generally very low [1.0±0.2%, 1.1±0.2%, and 0.5±0.1% (±SE), respectively]. Apart from adrenocorticotropic hormone-positive adenomas, which had significantly higher indices, there were no statistically significant differences in the indices among the other subtypes of pituitary adenomas. Recurrent tumors had higher Ki-67 and DNA polymerase PCIs and BrdUdR LIs (3.6%, 4.2%, 1.4%) than primary tumors (0.8%, 0.8%, 0.3%; P<0.005). The number of Ag-NORs did not correlated significantly with any of the three indices. The mean number of Ag-NORs was higher in nonfunctioning adenomas than in functioning adenomas (2.04 vs 1.66, P<0.005); among prolactin-positive adenomas, those treated preoperatively with bromocriptine had more Ag-NORs than untreated tumors (1.75 vs 1.57, P<0.005). These results suggest that the Ki-67 and DNA polymerase PCIs and the BrdUdR LI predict the growth potential of individual pituitary adenomas, whereas the number of Ag-NORs appears to correlate with hormone production rather than with the proliferative potential.Supported by grants CA-13525 and CA-50210 from the National Cancer Institute, by a grant from the Phi Beta Psi Sorority, and by Grant-in-Aid A 63771083 from the Ministry of Education, Science, and Culture of Japan     

Regional brain kinetics of 6-fluoro-(β-11C)-L-dopa and (β-11C)-L-dopa following COMT inhibition. A study in vivo using positron emission tomography

Summary The regional brain kinetics of (-11C)-L-dopa and 6-fluoro-(-11C)-L-dopa was measured in six Rhesus monkeys using positron emission tomography (PET). Radioactivity accumulated specifically in the striatal region and the increase in L-dopa-derived radioactivity utilization with time was calculated using surrounding brain as a reference area, this being devoid of dopaminergic activity. The rate constant for selective striatal utilization i.e. grossly decarboxylation was 0.0110 ± 0.0007 (S.D) and 0.0057 ± 0.0006 min1 for (-11C)-L-dopa and 6-fluoro-(-11C)-L-dopa, respectively. After pre-treatment of the monkeys with the peripherally and centrally active catecholamine-O-methyl transferase (COMT) inhibitor Ro 40-7592 10 mg/kg, the decarboxylation rate remained unchanged (0.0112 ± 0.0015 min-1) for (11C)-L-dopa, whereas an increase in rate was measured for 6-fluoro-(-11C)L-dopa (0.0092 ± 0.0015 min–1). Differences in the distribution of radiolabelled metabolites i.e. the corresponding O-methyl-L-dopa in the reference area is most probably the reason for the difference in calculated decarboxylation rate seen between the radiotracers. The higher decarboxylation rate measured for 6-fluoro-(-11C)-L-dopa after blockade of COMT shows that the radiolabelled metabolites i.e. 6-fluoro-O-methyl-(-11C)-L-dopa significantly contributes to background radioactivity.