Search results for: Fedil Jemal Ahmed
3 MCD-017: Potential Candidate from the Class of Nitroimidazoles to Treat Tuberculosis
Authors: Gurleen Kour, Mowkshi Khullar, B. K. Chandan, Parvinder Pal Singh, Kushalava Reddy Yumpalla, Gurunadham Munagala, Ram A. Vishwakarma, Zabeer Ahmed
Abstract:
New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). Apart from in-vitro potency against the target, physiochemical properties and pharmacokinetic properties play an imperative role in the process of drug discovery. We have identified novel nitroimidazole derivatives with potential activity against mycobacterium tuberculosis. One lead candidates, MCD-017, which showed potent activity against H37Rv strain (MIC=0.5µg/ml) and was further evaluated in the process of drug development. Methods: Basic physicochemical parameters like solubility and lipophilicity (LogP) were evaluated. Thermodynamic solubility was determined in PBS buffer (pH 7.4) using LC/MS-MS. The partition coefficient (Log P) of the compound was determined between octanol and phosphate buffered saline (PBS at pH 7.4) at 25°C by the microscale shake flask method. The compound followed Lipinski’s rule of five, which is predictive of good oral bioavailability and was further evaluated for metabolic stability. In-vitro metabolic stability was determined in rat liver microsomes. The hepatotoxicity of the compound was also determined in HepG2 cell line. In vivo pharmacokinetic profile of the compound after oral dosing was also obtained using balb/c mice. Results: The compound exhibited favorable solubility and lipophilicity. The physical and chemical properties of the compound were made use of as the first determination of drug-like properties. The compound obeyed Lipinski’s rule of five, with molecular weight < 500, number of hydrogen bond donors (HBD) < 5 and number of hydrogen bond acceptors(HBA) not more then 10. The log P of the compound was less than 5 and therefore the compound is predictive of exhibiting good absorption and permeation. Pooled rat liver microsomes were prepared from rat liver homogenate for measuring the metabolic stability. 99% of the compound was not metabolized and remained intact. The compound did not exhibit cytoxicity in hepG2 cells upto 40 µg/ml. The compound revealed good pharmacokinetic profile at a dose of 5mg/kg administered orally with a half life (t1/2) of 1.15 hours, Cmax of 642ng/ml, clearance of 4.84 ml/min/kg and a volume of distribution of 8.05 l/kg. Conclusion : The emergence of multi drug resistance (MDR) and extensively drug resistant (XDR) Tuberculosis emphasize the requirement of novel drugs active against tuberculosis. Thus, the need to evaluate physicochemical and pharmacokinetic properties in the early stages of drug discovery is required to reduce the attrition associated with poor drug exposure. In summary, it can be concluded that MCD-017 may be considered a good candidate for further preclinical and clinical evaluations.Keywords: mycobacterium tuberculosis, pharmacokinetics, physicochemical properties, hepatotoxicity
Procedia PDF Downloads 4512 Home-Based Care with Follow-Up at Outpatient Unit or Community-Follow-Up Center with/without Food Supplementation and/or Psychosocial Stimulation of Children with Moderate Acute Malnutrition in Bangladesh
Authors: Md Iqbal Hossain, Tahmeed Ahmed, Kenneth H. Brown
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Objective: To assess the effect of community-based follow up, with or without food-supplementation and/or psychosocial stimulation, as an alternative to current hospital-based follow-up of children with moderate-acute-malnutrition (WHZ < -2 to -3) (MAM). Design/methods: The study was conducted at the ICDDR,B Dhaka Hospital and in four urban primary health care centers of Dhaka, Bangladesh during 2005-2007. The efficacy of five different randomly assigned interventions was compared with respect to the rate of completion of follow-up, growth and morbidity in 227 MAM children aged 6-24 months who were initially treated at ICDDR,B for diarrhea and/or other morbidities. The interventions were: 1) Fortnightly follow-up care (FFC) at the ICDDR,B’s outpatient-unit, including growth monitoring, health education, and micro-nutrient supplementation (H-C, n=49). 2) FFC at community follow-up unit (CNFU) [established in the existing urban primary health-care centers close to the residence of the child] but received the same regimen as H-C (C-C, n=53). 3) As per C-C plus cereal-based supplementary food (SF) (C-SF, n=49). The SF packets were distributed on recruitment and at every visit in CNFU [@1 packet/day for 6–11 and 2 packets/day for 12-24 month old children. Each packet contained 20g toasted rice-powder, 10g toasted lentil-powder, 5g molasses, and 3g soy bean oil, to provide a total of ~ 150kcal with 11% energy from protein]. 4) As per C-C plus psychosocial stimulation (PS) (C-PS, n=43). PS consisted of child-stimulation and parental-counseling conducted by trained health workers. 5) As per C-C plus both SF+PS (C-SF+PS, n=33). Results: A total of 227children (48.5% female), with a mean ± SD age of 12.6 ±3.8 months, and WHZ of - 2.53±0.28 enrolled. Baseline characteristics did not differ by treatment group. The rate of spontaneous attendance at scheduled follow-up visits gradually decreased in all groups. Follow-up attendance and gain in weight and length were greater in groups C-SF, C-SF+PS, and C-PS than C-C, and these indicators were observed least in H-C. Children in the H-C group more often suffered from diarrhea (25 % vs. 4-9%) and fever (28% vs. 8-11%) than other groups (p < 0.05). Children who attended at least five of the total six scheduled follow-up visits gained more in weight (median: 0.86 vs. 0.62 kg, p=0.002), length (median: 2.4 vs. 2.0 cm, p=0.009) than those who attended fewer. Conclusions: Community-based service delivery, especially including supplementary food with or without psychosocial stimulation, permits better rehabilitation of children with MAM compared to current hospital outpatients-based care. By scaling the community-based follow-up including food supplementation with or without psychosocial stimulation, it will be possible to rehabilitate a greater number of MAM children in a better way.Keywords: community-based management, moderate acute malnutrition, psychosocial stimulation, supplementary food
Procedia PDF Downloads 4291 The Impact of Developing an Educational Unit in the Light of Twenty-First Century Skills in Developing Language Skills for Non-Arabic Speakers: A Proposed Program for Application to Students of Educational Series in Regular Schools
Authors: Erfan Abdeldaim Mohamed Ahmed Abdalla
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The era of the knowledge explosion in which we live requires us to develop educational curricula quantitatively and qualitatively to adapt to the twenty-first-century skills of critical thinking, problem-solving, communication, cooperation, creativity, and innovation. The process of developing the curriculum is as significant as building it; in fact, the development of curricula may be more difficult than building them. And curriculum development includes analyzing needs, setting goals, designing the content and educational materials, creating language programs, developing teachers, applying for programmes in schools, monitoring and feedback, and then evaluating the language programme resulting from these processes. When we look back at the history of language teaching during the twentieth century, we find that developing the delivery method is the most crucial aspect of change in language teaching doctrines. The concept of delivery method in teaching is a systematic set of teaching practices based on a specific theory of language acquisition. This is a key consideration, as the process of development must include all the curriculum elements in its comprehensive sense: linguistically and non-linguistically. The various Arabic curricula provide the student with a set of units, each unit consisting of a set of linguistic elements. These elements are often not logically arranged, and more importantly, they neglect essential points and highlight other less important ones. Moreover, the educational curricula entail a great deal of monotony in the presentation of content, which makes it hard for the teacher to select adequate content; so that the teacher often navigates among diverse references to prepare a lesson and hardly finds the suitable one. Similarly, the student often gets bored when learning the Arabic language and fails to fulfill considerable progress in it. Therefore, the problem is not related to the lack of curricula, but the problem is the development of the curriculum with all its linguistic and non-linguistic elements in accordance with contemporary challenges and standards for teaching foreign languages. The Arabic library suffers from a lack of references for curriculum development. In this paper, the researcher investigates the elements of development, such as the teacher, content, methods, objectives, evaluation, and activities. Hence, a set of general guidelines in the field of educational development were reached. The paper highlights the need to identify weaknesses in educational curricula, decide the twenty-first-century skills that must be employed in Arabic education curricula, and the employment of foreign language teaching standards in current Arabic Curricula. The researcher assumes that the series of teaching Arabic to speakers of other languages in regular schools do not address the skills of the twenty-first century, which is what the researcher tries to apply in the proposed unit. The experimental method is the method of this study. It is based on two groups: experimental and control. The development of an educational unit will help build suitable educational series for students of the Arabic language in regular schools, in which twenty-first-century skills and standards for teaching foreign languages will be addressed and be more useful and attractive to students.Keywords: curriculum, development, Arabic language, non-native, skills
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