抗消化性溃疡病药物杂环甲醛缩N4-取代苯基氨(硫)脲的合成和定量构效分析

按类型衍化出的先导物结构,经逐步调整苯环上取代基的电性和疏水性,合成了45个呋喃、吡咯和N-甲基吡咯-α-甲醛缩N⁴-3-,或4-取代的苯基氨脲和氨硫脲。对抗溃疡作用和毒性作用的定量评价及构效分析表明,活性与疏水性呈抛物线关系;引入推电子基团,有利于抗溃疡活性。化合物17和30的活性与毒性的分离较大,其药理作用在深入研究中。     

Patterns of 8-hydroxydeoxyguanosine formation in DNA and indications of oxidative stress in rat and human pleural mesothelial cells after exposure to crocidolite asbestos

Oxidative damage is a proposed mechanism of asbestos-induced carcinogenesis, but the detection of oxidative DNA lesions in target cells of asbestos-induced mesothelioma has not been examined. In studies here, DNA was isolated from both rat pleural mesothelial (RPM) cells and a human mesothelial cell line (MET5A) after exposure in vitro to crocidolite asbestos at various concentrations. DNA was then examined for formation of 8-hydroxydeoxyguanosine (8-OHdG) at 24, 48 and 72 h using HPLC with electrochemical detection. In addition, steady- state mRNA levels of manganese-containing superoxide dismutase (MnSOD) were assessed as an indication of oxidative stress. Whereas RPM cells showed dose-dependent and significant increases in 8-OHdG formation in response to crocidolite asbestos or iron-chelated crocidolite fibers (but not after exposure to glass beads), MET5A cells showed decreases in 8-OHdG. Both cell types exhibited elevations in message levels of MnSOD. In comparison with human MET5A cells, RPM cells exhibited increased cytotoxicity and apoptosis in response to asbestos, as documented by cell viability assays and flow cytometry analysis using propidium iodide. Results in RPM cells indicate that asbestos causes oxidative damage that may result in potentially mutagenic lesions in DNA and/or apoptosis, despite compensatory increases in expression of an antioxidant enzyme.      

柱前衍生化的人血浆中(+),(-)棉酚的HPLC测定法

本文报道分别定量检测人血浆中(+),(-)棉酚含量的高效液相色谱测定法。棉酚人血浆样品经乙腈沉淀蛋白后,上清液加手性试剂——(+)-2-氨基-1-丁醇,75℃加热45min。反应液加NaCl进行溶剂反混合处理后,取乙腈层50～100μl进样。选用ODS固定相,紫外254nm检测,以甲醇—异丙醇—水—磷酸(80:20:20:0.1 V/V)为流动相,流速1.2ml/min时,(+),(-) 棉酚衍生物的保留时间分别为4.2,7.7 min。检测人血浆中(+),(-)棉酚在0.125～2.0μg/ml范围内呈线性关系。棉酚回收率达94～98%,此法已用于棉酚的临床血药浓度监测和动物实验研究。     

成人脑电图中的阵发性过度换气反应的意义

０　引言　儿童在过度换气（ＨＶ）后可出现阵发性慢波,有时混有尖波成分,目前一般认为是正常变异．成人有代谢紊乱（特别是有低血糖等）在ＨＶ后也可出现阵发性慢波,有人认为是“脑功能不稳定”或“阵发趋势”的一个依据;在临床上对癫痫诊断不能肯定时,它又可能被错误地当作支持诊断的依据．我们观察ＨＶ后的阵发性慢波在非低血糖成年人ＥＥＧ上的意义如下．１　临床资料　作者在工作中有意识地收集病例,对１００例ＥＥＧ,其中男５８例,女４２例,年龄２１岁～７５岁,平均４８岁,仅在ＨＶ诱发的阵发性慢波外余均正常患者进行分析…     

新型输送型球囊扩张导管在颅内动脉狭窄治疗中的临床应用研究

目的：探讨新型输送型球囊扩张导管(Fastunnel)在颅内动脉粥样硬化狭窄介入治疗中的应用效果。方法：2021年11月至2022年2月,我们使用新型输送型球囊扩张导管对10例颅内动脉粥样硬化狭窄的患者进行了球囊扩张+支架成形术。收集并分析了患者的基线情况、影像学特点、治疗情况及围手术期情况。结果：男6例,女性4例,平均年龄(62.7±6.7)岁。10例患者均成功接受手术治疗,手术时长为16~65(37.3±18.2)min,治疗过程所受辐射剂量为1381~4901(2643.7±1131.7)mGy,剂量面积乘积(DAP)值为5707~38112(17526.8±10809.5)μGym₂^。围手术期无出血及缺血相关并发症。结论：输送型球囊扩张导管具有较好的安全性,能有效地简化手术步骤、缩短手术时间,对减少患者及医生所受射线剂量。     

麝香酮在大鼠、家兔和狗体内的药代动力学

麝香酮在大鼠体内的药时过程符合二室开放模型,在家兔和狗体内的药时过程则符合三室开放模型。大鼠、家兔和狗之间的药代动力学过程存在着显著的种属差异,大鼠iv麝香酮12,18和24 mg/kg三种剂量间的药代动力学主要参数无显著性差异。iv给药大鼠的T_1/2B为118.1～131.2min。家兔和狗的T_1/2B分别为24.9和30.0 min,T_1/2γ分别为331.9和366.4 min。大鼠、家兔和狗三b种动物的V_ss分别为23.0,51.7和7.3 L/kg.V_c分别为2.33,2.13和0.38 L/kg。     

Intestinal microsporidiosis in diarrheal patients infected with human immunodeficiency virus-1 in Addis Ababa, Ethiopia

Intestinal microsporidiosis is most commonly associated with persistent diarrhea in advanced AIDS cases. To determine the prevalence and clinical manifestations of this infection in HIV/AIDS patients, a single fresh stool sample and blood were collected from 243 (214 HIV-positive and 29 HIV-negative) diarrheal patients. The presence of intestinal microsporidiosis in the stool was determined by Uvitex-2B staining and a PCR-based detection method. HIV screening was done by using ELISA, and reactive samples were confirmed by Western blotting. The CD4+ cell count was analyzed using FACScan. Out of 243 diarrheal patients, 39 (16.0%) cases were positive for intestinal microsporidial infection by either of the methods used. Of the 39, only 18 cases positive by microscopy were also positive by PCR. Based on PCR and microscopic analyses the microsporidial parasites were identified as Enterocytozoon bieneusi (30), Ecephalitozoon intestinalis (6), and double infections (3). All microsporidia-positive cases were HIV-positive, and 92.3% had diarrhea for over 4 weeks. The diarrhea was watery in 79.5% of the patients. Weight loss >10% was recorded in 37 (94.9%) cases. The CD4+ cell count was <100 cells/mm(3) in 84.4% of subjects, and 59.4% of the patients had a CD4+ cell count of < or =50 cells/mm(3), with a mean of 22.8 cells/mm(3). This study revealed that intestinal microsporidiosis is a common cause of chronic diarrhea and severe weight loss in advanced AIDS patients in Ethiopia. This condition is attributable mainly to E. bieneusi. Thus, early diagnosis of intestinal microsporidiosis in HIV/AIDS patients would certainly be helpful in the understanding and management of diarrheal illness.     

Clinical characteristics of obstructive sleep apnea in community-dwelling older adults

OBJECTIVES: To examine whether traditional risk factors are common in older adults with obstructive sleep apnea (OSA). DESIGN: Cross-sectional study. SETTING: Atlanta, Georgia. PARTICIPANTS: A convenience sample of 94 community-dwelling adults aged 62 to 91. MEASUREMENTS: Demographic, medical, and sleep-related information obtained using questionnaires. Epworth Sleepiness Scale (ESS) and 72-hour voiding diary were used to determine daytime sleepiness and nocturia frequency, respectively. Overnight ambulatory sleep recording device was used to screen for OSA. RESULTS: Fifteen female and 15 male subjects had an apnea-hypopnea index (AHI) of 15 or more per hour of sleep (moderate to severe OSA). Traditional risk factors such as snoring, body mass index, and neck circumference were not significantly associated with OSA. An AHI of 15 or more per hour was independently associated with not feeling well rested in the morning, higher ESS score, and greater frequency of nocturia. CONCLUSION: Traditional risk factors for OSA were not common presenting symptoms and signs in study subjects with an AHI of 15 or more per hour of sleep; this may contribute to underdiagnosis of OSA in this population. Subjects with an AHI of 15 or more per hour had more sleep-related complaints and excessive daytime sleepiness. Although occult, this suggests that OSA may contribute to disease burden in this group of people.     

Hb Bart's level in cord blood and deletions of alpha-globin genes

The white blood cell DNA of 36 cord blood samples with Hb Bart's in the red blood cells was studied for alpha-globin gene deletions by hybridization of DNA fragments digested by the restriction endonucleases Eco RI, Hpa I, Bam HI, and Bgl II. All 16 DNA samples from cord blood with Hb Bart's below 3% and no other abnormal hemoglobin had one alpha-globin gene deletion (alpha thal2), except one which had two alpha-globin gene deletions (alpha thal1). Most of the alpha thal2 were of the rightward deletion alpha thal2 genotype. Two new types of alpha thal2 variation was found, probably due to a polymorphism somewhere in an area outside the alpha-globin gene. All 14 cases with Hb Bart's between 3.5% and 8.5% and no other abnormal hemoglobin had two alpha-globin gene deletions (alpha thal1), except one that did not have any alpha-globin gene deletion and one that had one alpha-globin gene deletion. Three DNA samples of cord blood with Hb Bart's accompanied by Hb CoSp did not have any alpha-globin gene deletion. Sixty-five DNA samples from cord blood without Hb Bart's or other abnormal hemoglobin had no alpha-globin gene deletions, except one that had one alpha-globin gene deletion (alpha thal2). Two of the 65 DNA samples were found to have triplicated alpha-globin gene loci.