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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.
相似文献
Hit, Lead & Candidate Discovery |
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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
5.
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
6.
Hashaam Akhtar Maham Afridi Samar Akhtar Hamaad Ahmad Sabahat Ali Sundas Khalid Sajid Mahmood Awan Shahzaib Jahangiri Yousef Saleh Khader 《JMIR Public Health and Surveillance》2021,7(5)
The COVID-19 outbreak started as pneumonia in December 2019 in Wuhan, China. The subsequent pandemic was declared as the sixth public health emergency of international concern on January 30, 2020, by the World Health Organization. Pakistan could be a potential hotspot for COVID-19 owing to its high population of 204.65 million and its struggling health care and economic systems. Pakistan was able to tackle the challenge with relatively mild repercussions. The present analysis has been conducted to highlight the situation of the disease in Pakistan in 2020 and the measures taken by various stakeholders coupled with support from the community to abate the risk of catastrophic spread of the virus. 相似文献
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Hashaam Akhtar Samar Akhtar Fazal-Ul Rahman Maham Afridi Sundas Khalid Sabahat Ali Nasim Akhtar Yousef S Khader Hamaad Ahmad Muhammad Mujeeb Khan 《JMIR Public Health and Surveillance》2021,7(5)
BackgroundSince the first reports of COVID-19 infection, the foremost requirement has been to identify a treatment regimen that not only fights the causative agent but also controls the associated complications of the infection. Due to the time-consuming process of drug discovery, physicians have used readily available drugs and therapies for treatment of infections to minimize the death toll.ObjectiveThe aim of this study is to provide a snapshot analysis of the major drugs used in a cohort of 1562 Pakistani patients during the period from May to July 2020, when the first wave of COVID-19 peaked in Pakistan.MethodsA retrospective observational study was performed to provide an overview of the major drugs used in a cohort of 1562 patients with COVID-19 admitted to the four major tertiary-care hospitals in the Rawalpindi-Islamabad region of Pakistan during the peak of the first wave of COVID-19 in the country (May-July 2020).ResultsAntibiotics were the most common choice out of all the therapies employed, and they were used as first line of treatment for COVID-19. Azithromycin was the most prescribed drug for treatment. No monthly trend was observed in the choice of antibiotics, and these drugs appeared to be a random but favored choice throughout the months of the study. It was also noted that even antibiotics used for multidrug resistant infections were prescribed irrespective of the severity or progression of the infection. The results of the analysis are alarming, as this approach may lead to antibiotic resistance and complications in immunocompromised patients with COVID-19. A total of 1562 patients (1064 male, 68.1%, and 498 female, 31.9%) with a mean age of 47.35 years (SD 17.03) were included in the study. The highest frequency of patient hospitalizations occurred in June (846/1562, 54.2%).ConclusionsGuidelines for a targeted treatment regime are needed to control related complications and to limit the misuse of antibiotics in the management of COVID-19. 相似文献
8.
Ferraris ME Samar ME Busso C Avila RE Ferraris RV de Fabro SP 《Acta odontológica latinoamericana : AOL》1993,7(1):23-29
The histogenesis of the salivary glands was structurally and cytochemically studied in human embryos and fetuses during the period of 8 to 32 weeks of intrauterine life. Glandular buds appeared at about 12 weeks of embryonic development. The rounded distal ends of the epithelial cords and neighbouring mesenchyma showed small and abundant PAS positive and alcianophilic granules. At age 14 weeks the secretory end pieces and the duct system were seen at different morphologic and structural stages of a differentiation. Mucous acini with scanty mixed acini predominated and serous acini appeared occasionally. From 20 to 24 weeks the mucous acini stained with toluidine blue featured different degrees of metachromasia even in the case of cells of the same acinus. In the ducts it was also possible to identify metachromatic cells intermingled with basophilic cells in the epithelial coat. These findings suggest that the palatine glands present typical histophysiological material from 14 to 20 weeks. The presence of PAS positive, alcianophilic and metachromatic secretory substance in the acinar lumen and the luminal content of ducts suggests that mucin secretion begins during intrauterine life. 相似文献
9.
Hala U Gali-Muhtasib Makhluf J Haddadin Musa Z Nazer Nicole M Sodir Samar W Maalouf 《Medical oncology (Northwood, London, England)》1998,15(4):262-269
2-benzoyl-3-phenylquinoxaline 1,4-dioxide (BPQ) and other substituted quinoxaline 1,4-dioxides (QdO) were tested for their
ability to inhibit the stimulations of ornithine decarboxylase (ODC) enzyme activity and DNA synthesis, two biochemical markers
linked to skin tumour promotion by ultraviolet B (UVB) radiation. Topical application of BPQ on the dorsal skin of hairless
mice was found to inhibit in a dose-dependent manner UVB-induced ODC activity and DNA synthesis. When applied 20 min before
UVB radiation, a dose of 17 mg BPQ applied in 0.4 ml of vehicle inhibited UVB-induced ODC activity and DNA synthesis by 95%
and 85%, respectively. This inhibitory effect is dependent on the time of administration of BPQ relative to UVB radiation,
with a generally greater inhibition observed when this compound is applied before rather than after UVB treatment. The inhibitory
abilities of the other QdO on the ODC and DNA responses induced by UVB radiation greatly varied and appear to be dependent
on the structure of the compounds and their metabolic activation in the skin following irradiation. The remarkable effectiveness
of BPQ against the ODC and DNA markers of UVB promotion is also observed following multiple applications of this agent. These
results suggest that QdO, in particular BPQ and certain derivatives of it, may be useful in protecting the skin against UVB-induced
skin damage. 相似文献
10.
Sándor Drabant Katalin Balogh Nemes Viola Horváth Antal Tolokán Gyula Grézal Markku Anttila Béla Gachályi Harri Kanerva Samar Al-Behaisi George Horvai Imre Klebovich 《European journal of pharmaceutics and biopharmaceutics》2004,58(3):689-695
The effect of a high-fat meal on the oral bioavailability of deramciclane 30 mg tablet was evaluated in 18 healthy male volunteers in a randomised, single dose, two-way crossover study. The drug was administered following an overnight fast or a standardised high-fat breakfast. The plasma concentrations of deramciclane and N-desmethylderamciclane were determined by using a validated HPLC-MS -MS/MS method. An effect of food on the bioavailability was indicated if the 90% confidence interval (CI) for the ratio of geometric means of fed and fasted treatments was not contained in the equivalence limit of 0.8-1.25 for AUC and C(max). The ratios of the mean C(max) and AUC(0-infinity) values of deramciclane were 1.24 (90% CI 1.12-1.38) and 1.31 (90% CI 1.21-1.41) in fed versus fasted subjects, which overlapped but exceeded the equivalence limit. In contrast to the parent compound, the 90% CI of the mean ratios for AUC(0-infinity) and C(max) of N-desmethylderamciclane were within the predefined range. The 24 and 31% increase in C(max) and AUC(0-infinity) of deramciclane, respectively, under fed condition is modest and probably has no clinical significance since it is relatively small compared to the inter-individual variability of these parameters. 相似文献