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1.
Hend Kothayer Samy M. Ibrahim Moustafa K. Soltan Samar Rezq Shireen S. Mahmoud 《Drug development research》2019,80(3):343-352
In light of the pharmacophoric structural requirements for achieving anticonvulsant activity, a series of N-(1-methyl-4-oxo-2-un/substituted-1,2-dihydroquinazolin-3[4H]-yl)benzamide (4a-g) and N-(1-methyl-4-oxo-2-un/substituted-1,2-dihydroquinazolin-3[4H]-yl)-2-phenylacetamide (4h-n) derivatives were synthesized in two steps starting from the reaction of N-methyl isatoic anhydride with the appropriate hydrazide and followed by condensation with the appropriate aldehyde. The anticonvulsant activities of the synthesized compounds were evaluated according to the anticonvulsant drug development (ADD) programme protocol. Among the synthesized compounds, 4n showed promising activity in both the maximal electroshock (MES) and pentylenetetrazole (PTZ) tests with median effective dose (ED50) values of 40.7 and 6 mg/kg, respectively. The six most promising derivatives, 4b , 4a , 4c , 4f , 4j , and 4i , showed very low ED50 values in the PTZ test (3.1, 4.96, 8.68, 9.89, 12, and 13.53 mg/kg, respectively). All the tested compounds showed no to low neurotoxicity in the rotarod test with a wide therapeutic index. Docking studies of compound 4n suggested that GABAA binding could be the mechanism of action of these derivatives. The in silico drug likeliness parameters indicated that none of the designed compounds violate Lipinski's rule of five and that they are able to cross the blood–brain barrier.
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Hit, Lead & Candidate Discovery |
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Fawzi S. AlKhawari Gerry V. Stimson Anthony N. Warrens 《American journal of transplantation》2005,5(6):1326-1331
The worldwide shortage of organs for transplantation makes it important to understand why some oppose donation. Attitudes vary with religion and ethnicity. Accordingly, we undertook a qualitative study of the attitudes of 141 U.K. Muslim Indo-Asians to organ donation. Participants were observed, focus group discussions held and in-depth individual interviews conducted. We identified a high level of alienation from the health care system in general. With respect to organ donation in particular, its importance was generally discounted, often in deference to authority figures within the community who appeared negatively disposed. The culture-specific issues arguing against donation included a sense of the sacredness of the body, a fatalistic approach to illness, a belief that organs took on an independent role as 'witnesses' to an individual's life on Judgement Day and an anxiety that the donor would have no control of the probity of the recipient of an organ. We believe these data suggest a need to improve in a culturally sensitive fashion the provision of health information provided to this community. 相似文献
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A case is reported of right atrial myxoma presenting clinically as ascites and fever of unknown origin. An extensive work-up, including laboratory investigations, X-ray imaging, laparoscopy and laparotomy, failed to explain the clinical picture which was manifested post partum. Echocardiography was diagnostic and led to the curative treatment of surgical resection. 相似文献
5.
El-Darouti M. A. Fawzi S. A. Marzook S. A. 《世界核心医学期刊文摘》2006,2(3):58-59
背景:家族性巨大黑色素细胞增生症(FGM)是一种罕见疾病,于1984年首次描述并命名为“家族性巨大黑色素细胞黑变病”。其病因尚不清楚。色素增多或减少处皮肤中的黑色素细胞似乎无法向周围的角质形成细胞输送黑色素。目的:作者报道4例新发FGM患者。实施电镜检查以便进一步阐明本病的潜在缺陷。患者和方法:对患者进行临床检查,并在色素沉着处和减退处皮损切取活检标本,将标本分成两份;一份经苏木素伊红和马松丰塔纳染色后行常规显微镜检查, 相似文献
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A review of the literature suggested that prolonged treatment time may lessen the probability of cure for patients with advanced squamous cell carcinoma of the upper aerodigestive tract. To shorten treatment time, rapid sequence treatment (RST) was devised in which chemotherapy, surgery, and irrada-tion were administered in a total treatment time of 8 weeks. Twelve patients were treated and followed 3 years or longer. Medical complications were minor. Osteonecrosis occurred in each of the first five patients and was the only major complication of the protocol. Surgical techniques were modified, and no additional patient developed osteonecrosis. No patient developed local or regional recurrence. Two patients developed distant metastases and three other patients developed second primaries. Absolute survival was 50%. Rapid sequence treatment is an aggressive and potentially hazardous protocol that yielded encouraging results in this pilot study. 相似文献
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Mary Arevian Samar Noureddine Tamar Kabakian-Khasholian 《Journal of transcultural nursing》2006,17(4):357-364
Women need to practice cervical screening regularly to reduce morbidity and mortality. The purpose of this study was to examine the impact of an intervention program on knowledge, attitude, and practice of cervical screening in the population of Lebanese/Armenian women. The design was a cross-sectional, quasi-experimental posttest survey following a year long intervention program. The sample included 176 women, who were members of the Armenian Relief Cross in Lebanon. Interventions consisted of educational classes, media messages, and free screening. The instrument was a self-administered questionnaire. Knowledge of women with intervention was higher (p > .05) and practice rate increased between intervention and comparison groups. No difference in attitude was noted. The study was successful in raising awareness and increasing screening in the sample. It is recommended to continue helping women to overcome barriers for cervical screening. 相似文献
9.
Villamor E Msamanga G Spiegelman D Peterson KE Antelman G Fawzi WW 《Journal of acquired immune deficiency syndromes (1999)》2003,32(5):560-569
Progression of HIV disease is often accompanied by weight loss and wasting. Gestational weight gain is a strong determinant of maternal and neonatal outcomes; however, the pattern and predictors of weight gain during pregnancy among HIV-positive women are unknown. We obtained monthly anthropometric measurements in a cohort of 957 pregnant women from Tanzania who were HIV infected. We estimated the weekly rate of weight gain at various points during the second and third trimesters of pregnancy and computed rate differences between levels of sociodemographic, nutritional, immunologic, and parasitic variables at the first prenatal visit. The change in mid-upper arm circumference (MUAC) from baseline to delivery was also examined. The rate of weight gain decreased progressively during pregnancy. There was an average decline of 1 cm in MUAC between weeks 12 and 38. Lower level of education and helminthic infections at first visit were associated with decreased adjusted rates of weight gain during the third trimester. High baseline MUAC, not contributing to household income, lower serum retinol and selenium concentrations, advanced clinical stage of HIV disease, and malaria infection were related to decreased rates of weight gain during the second trimester. Low baseline CD4 T-cell counts were related to a poorer pattern of weight gain throughout pregnancy. Prevention and treatment of parasitic infections and improvement of nutritional status are likely to enhance the pattern of gestational weight gain among HIV-infected women. 相似文献
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Villamor E Saathoff E Msamanga G O'Brien ME Manji K Fawzi WW 《Journal of acquired immune deficiency syndromes (1999)》2005,38(5):622-626
OBJECTIVES: To examine whether wasting during pregnancy, as measured by weight loss and low weight gain, is associated with increased mother-to-child transmission (MTCT) of HIV-1. METHODS: This was a cohort study in Dar es Salaam, Tanzania, among 957 HIV-1-infected pregnant women. Weight was measured at the first prenatal visit and every month thereafter until delivery. Weight loss was defined as a weekly rate of weight gain =0 and low weight gain as a weekly rate >0 and =166 g/wk. The incidences of presumptive intrauterine transmission (HIV status at birth) and presumptive intrapartum and early breast-feeding transmission (HIV status at 6 weeks) were examined in relation to baseline anthropometric characteristics and weight change during pregnancy using 2xn tables and multivariable binomial regression. RESULTS: Compared with women who gained >/=167 g/wk, weight loss during pregnancy was related to higher risk of intrauterine MTCT (adjusted relative risk [RR] = 2.32, 95% CI = 1.23-4.36, P = 0.009), HIV positive at birth or fetal death (RR = 2.13, 95% CI = 1.40-3.24, P = 0.0004), and HIV positive at birth or early neonatal death (RR = 1.96, 95% CI = 1.26-3.07, P = 0.003). The rate of weight gain during the 3rd trimester was inversely related to the risk of intrapartum/early breast-feeding transmission (adjusted P value, test for trend = 0.05). CONCLUSIONS: Weight loss during pregnancy increases the risk of early MTCT. Identifying causes of wasting during pregnancy may provide clues for new strategies to prevent MTCT. 相似文献