One-pot synthesis and negative ion mass spectrometric investigation of a densely functionalized cinnoline, 3-amino-5,7,8-trichloro-6-hydroxycinnoline-4-carbonitrile

Known densely substituted 3-amino-5,7,8-trichloro-6-hydroxycinnoline-4-carbonitrile was synthesized using a new synthetic protocol involving chloranil and malonitrile via quinone methide formation. This one-pot synthesis occurs under base mediated conditions in a polar medium. The method involves condensation of excess malononitrile with chloranil in ethanol at reflux to 2-(2,4,5-trichloro-3-hydroxy-6-oxocyclohexa-2,4-dien-1-ylidene) malononitrile. This is an atom efficient, simple and effective procedure for the preparation of a highly substituted cinnoline that can serve as a relay to antimalarial prototypes

Antibiotic usage in pediatric respiratory tract infection

Respiratory tract infections are the worldwide main cause of death in children aging less than 5 years. In developed countries; respiratory tract infections are the leading cause of morbidity, accounted for 20% of medical consultation, 30% of work absenteeism and 75 % of all antibiotic prescription. Upper respiratory tract infections in children, which often associated with viral infection, and in average about 40 – 60 % of children with upper respiratory tract infections were prescribed with antibiotics. The type of antibiotics also varies from hospital to another.The objectives of this study are to describe the pattern, outcome, and cost of antibiotic usage in pediatric respiratory tract infections. A prospective study of pediatrics admitted to Pediatric Ward, Penang Hospital for respiratory tract infections was carried out. Appropriate descriptive analysiswas used. The results showed that penicillin, erythromycin; amoxicillinclavulanate were the most commonly prescribed antibiotics for respiratory tract infections. The average duration of antibiotic therapy 3.0 ± 3.2 days, fever clearance time 2.2 ± 2.4 days, improvement of sign and symptoms 3.7 ± 2.5 days and mean length of stay in the ward was 4.9 ± 2.8 days. The average cost of antibiotics was RM 14.83 ± 83.13, and total cost of respiratory tract infections treatment was RM 98.88 ± 65.87.Key words: antibiotic, respiratory tract infection, pediatric, hospita

Liquid chromatography mass spectrometry analysis and cytotoxicity of Asparagus adscendens roots against human cancer cell lines

Background: Asparagus adscendens Roxb. (Asparagaceae), is native to the Himalayas. This plant has been used in the prevention and effective treatment of various forms of cancers. Objective: This paper reports, for the first time, on the cytotoxicity of the methanol (MeOH) extract of the roots of A. adscendens and its solid‑phase extraction (SPE) fractions against four human carcinoma cell lines and LC‑ESI‑QTOF‑MS analysis of the SPE fractions. Materials and Methods: Finely powdered roots of A. adscendens were macerated in methanol and extracted through SPE using gradient solvent system (water: methanol) proceeded for analysis on LC‑ESI‑QTOF‑MS and cytotoxicity against four human carcinoma cell lines: breast (MCF7), liver (HEPG2), lung (A549), and urinary bladder (EJ138), using the 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazoliumbromide assay. Results: The MeOH extract and four SPE fractions exhibited cytotoxicity against all cell lines with the IC50 values ranging from 6 to 79 μg/mL. As observedin other Asparagus species, the presence of saponins and sapogenins in the SPE fractions was evident in the liquid chromatography‑mass spectrometry data. Conclusion: It is reasonable to assume that the cytotoxicity of the MeOH extract of the roots of A. adscendens and its SPE fractions, at least partly, due to the presence of saponins and their aglycones. This suggests that A. adscendens could be exploited as a potential source of cytotoxic compounds with putative anticancer potential

A cost effectiveness and capacity analysis for the introduction of universal rotavirus vaccination in Kenya : comparison between Rotarix and RotaTeq vaccines

Background Diarrhoea is an important cause of death in the developing world, and rotavirus is the single most important cause of diarrhoea associated mortality. Two vaccines (Rotarix and RotaTeq) are available to prevent rotavirus disease. This analysis was undertaken to aid the decision in Kenya as to which vaccine to choose when introducing rotavirus vaccination. Methods Cost-effectiveness modelling, using national and sentinel surveillance data, and an impact assessment on the cold chain. Results The median estimated incidence of rotavirus disease in Kenya was 3015 outpatient visits, 279 hospitalisations and 65 deaths per 100,000 children under five years of age per year. Cumulated over the first five years of life vaccination was predicted to prevent 34% of the outpatient visits, 31% of the hospitalizations and 42% of the deaths. The estimated prevented costs accumulated over five years totalled US$1,782,761 (direct and indirect costs) with an associated 48,585 DALYs. From a societal perspective Rotarix had a cost-effectiveness ratio of US$142 per DALY (US$5 for the full course of two doses) and RotaTeq US$288 per DALY ($10.5 for the full course of three doses). RotaTeq will have a bigger impact on the cold chain compared to Rotarix. Conclusion Vaccination against rotavirus disease is cost-effective for Kenya irrespective of the vaccine. Of the two vaccines Rotarix was the preferred choice due to a better cost-effectiveness ratio, the presence of a vaccine vial monitor, the requirement of fewer doses and less storage space, and proven thermo-stability

Modulation of Antimalarial Activity at a Putative Bisquinoline Receptor in vivo Using Fluorinated Bisquinolines

Antimalarials can interact with heme covalently, by - interactions or hydrogen bonding. Consequently, the prototropy of 4-aminoquinolines and quinoline methanols was investigated using quantum mechanics. Calculations showed mefloquine protonated preferentially at the piperidine and was impeded at the endocyclic nitrogen due to electronic rather than steric factors. In gas phase calculations, 7-substituted mono- and bis-4-aminoquinolines were preferentially protonated at the endocyclic quinoline nitrogen. By contrast, compounds with a trifluoromethyl substituent on both the 2- and 8-positions, reversed the order of protonation which now favored the exocyclic secondary amine nitrogen at the 4-position. Loss of antimalarial efficacy by CF3 groups simultaneously occupying the 2- and 8-positions was recovered if the CF3 group occupied the 7-position. Hence, trifluromethyl groups buttressing quinolinyl nitrogen shifted binding of antimalarials to hematin, enabling switching from endocyclic to the exocyclic N. Both theoretical calculations (DFT calculations: B3LYP/6- 31+G*) and crystal structure of (±)-trans-N1,N2-bis-(2,8-ditrifluoromethylquinolin-4- yl)cyclohexane-1,2-diamine were used to reveal preferred mode(s) of interaction with hematin. The order of antimalarial activity in vivo followed the capacity for a redox change of the iron(III)state which has important implications for the future rational design of 4- aminoquinoline antimalarials

Purpurogallin-A heme binding component of oak galls

Recently, it has been shown that Purpurogallin (PPG), an orange benztropolone constituent of oak galls and its derivative, CU-CPT22, can compete with the binding of the specific lipoprotein ligand to toll-like receptors (TLRs), which are type I transmembrane proteins. These recognize pathogen-derived macromolecules that play a key role in the innate immune system. This system provides an attractive target for the treatment of various immune disorders. Notably, PPG also interacts with various metals and its mode of action against HIV in vitro may involve inhibition of metal containing integrases. In the current study, an optimised synthesis of PPG is presented together with its gas phase behaviour (probed by mass spectrometry) as well as its redox behaviour with porphyrins such as heme. This interaction may also explain its effects at metal containing integrases within HIV in vitro as well as its action during processing of iron complexes within Plasmodia. This compound could serve as a novel prototype for the synthesis of novel redox active antimalarials

Integration of Islamic Input in Medical Curriculum – Universiti Sains Islam Malaysia (USIM) Experience

Muslim doctors are those qualified doctors who practise their professional knowledge and skills in line with Islam and upholds the highest standards of ethical and professional behaviour. The medical curriculum of the Faculty of Medicine and Health Sciences of Universiti Sains Islam Malaysia (USIM) was designed with the integration of Islamic input which aims at producing doctors who are able to practise medicine that is integrated with Islamic, moral and ethical values. Halaqah Studies and Fundamental Islamic Knowledge (FIK) courses such as History of Medicine in Islam, Science and Medicine in Quran and Sunnah, Akhlak and Tasawuf, Islamic Jurisprudence and Medical Ethics and Fiqh Issues are taught to students during the pre-clinical and clinical phases. Memorization of selected Quranic verses throughout the programme aim to get the students to apply the verses of the al-Quran into practice in everyday life and especially in their clinical practice. Islamic values are emphasised during doctor-patient interactions in all clinical postings. Islamic knowledge and values integrated in the curriculum are assessed in written and clinical examinations. The outcome of the integration of the Naqli component in the medical curriculum has been demonstrated positively by the students in the patient management problems and clinical consultations. Studies on the outcome of the integrated Islamic input in the medical curriculum among the clinical students and graduates are being carried out

Randomized Clinical Trial Between Fluoxetine and Dapoxetine for Premature Ejaculation and Its Effect on Marital Relationship

INTRODUCTION: Premature ejaculation(PE) decreases sexual pleasure and quality of life, and both Fluoxetine and Dapoxetine were used in PE therapy. Dapoxetine is the first SSRI with a short half-life and fewer side effects, primarily designed for PE therapy. The aim is to evaluate and compare the effects of Fluoxetine and Dapoxetine on PE symptoms and marital satisfaction. MATERIALS AND METHODS: 44 participants aged between 18 and 64 with a PEDT score of ≥9 from Hospital USM's Primary-Care-Clinic, Kelantan Malaysia were selected and randomized into two groups: Fluoxetine(FG) and Dapoxetine Group(DG), and administered for 8 weeks with either regular Fluoxetine(20mg) or Dapoxetine (30mg) on-demand at least once a week. Premature Ejaculation Diagnostics Tool(PEDT) score was used to assess PE symptoms and Dyadic Satisfaction-Dyadic Adjustment Scale (DS-DAS) used to evaluate marital satisfaction at baseline and the 8th week. RESULT: 22 and 21 participants in FG and DG completed the study. For both groups, PEDT scores decreased substantially [from 11.41 to 5.45(P< 0.001) among FG, from 13.43 to 3.10(P<0.001) among DG]. After adjustment of the baseline PEDT score, PEDT scores in DG(6.03 vs 2.49, P><0.001) were lower at the 8th week. All groups showed significantly improved DS-DAS scores [from 34.50 to 40.68(P><0.001) in FG, from 36.57 to 44.33(P><0.001) in DG]. No marked difference in DS-DAS was scored after adjustment of the baseline DS-DAS score(41.13 vs 43.86, P=0.055) at the end of the assessment. CONCLUSION: Treatment of PE with either Fluoxetine or Dapoxetine decreases PE symptoms and increases marital satisfaction. ><0.001) among DG]. After adjustment of the baseline PEDT score, PEDT scores in DG (6.03 vs 2.49, P< 0.001) were lower at the 8th week. All groups showed significantly improved DS-DAS scores [from 34.50 to 40.68(P< 0.001) in FG, from 36.57 to 44.33(P< 0.001) in DG]. No marked difference in DS-DAS was scored after adjustment of the baseline DS-DAS score (41.13 vs 43.86, P=0.055) at the end of the assessment. CONCLUSION: Treatment of PE with either Fluoxetine or Dapoxetine decreases PE symptoms and increases marital satisfaction

Personal And Professional Characteristics Of A Good Muslim Doctor: Perception Of Newly Graduated Doctors

Introduction: The Medical Faculty of Universiti Sains Islam Malaysia (USIM) aims to produce good Muslim doctors (GMD) who are able to practise medicine that is integrated with Islamic values. Islamic courses and Medical Ethics are integrated into the curriculum in its effort to provide adequate Islamic knowledge and nurturing professionalism as a process of personal and professional development (PPD) within the framework of Islamic teaching. The objective of the study was to evaluate the perception of graduates and students of characteristics of a GMD. Method: A self-administered questionnaire was distributed to the participants. The respondents were asked to rate their level of agreement or disagreement on the statements that represent the characteristics of a GMD. Statistical analysis of the data was carried out using SPSS version 18.0. The mean, median and inter quartile ranges of the characteristics were determined and differences between the groups were analysed using Mann-Whitney U test. Results: Results showed significant difference between gender for the item “Conscious of professional ethics” (p=0.021). Significant differences were seen in the median scores between the graduates and the final year students in four out of six items for personal characteristic. Conclusion: Islamic input in the medical curriculum and the teaching of professionalism has an impact on graduate perception of characteristics of a GMD. Further improvement in the teaching of professionalism among undergraduates is necessary in order to promote greater impact on the understanding and internalization of characteristics of a GMD. The Islamic input in the medical curriculum can thus be regarded as the blueprint for PPD of medical undergraduates to become a GMD

The development and psychometric properties of the Arabic version of the child oral health impact profile-short form (COHIP- SF 19)

BACKGROUND: This study aims to cross-culturally adapt the original English-language COHIP-SF 19 to Arabic culture and to test its psychometric properties in a community sample. METHODS: The Arabic COHIP-SF 19 was developed and its psychometric properties were examined in a population-based sample of 876 schoolchildren who were aged 12 years of age, in Benghazi, Libya. The Arabic COHIP-SF 19 was tested for its internal consistency, reproducibility, construct validity, factorial validity and floor as well as ceiling effects. A Mann-Whitney U test was used to compare the mean scores of COHIP-SF 19 by participants' caries status and self-reported oral health rating, satisfaction and treatment need. RESULTS: The Arabic COHIP-SF 19 was successfully and smoothly developed. It showed an acceptable level of equivalence to the original version. Overall, the internal consistency and reproducibility were acceptable to excellent, with a Cronbach's alpha of 0.84 and an intra-class correlation coefficient (ICC) of 0.76. All hypotheses predefined to test construct validity were confirmed. That is, children who had active dental caries, and who rated their oral health as poor, were not satisfied with their oral health or indicated the need of treatment had lower COHIP-SF 19 scores (P < 0.05). Floor or ceiling effects were not observed. The exploratory Factorial analysis suggested a 4-component solution and deletion of one item. CONCLUSION: The Arabic COHIP-SF 19 was successfully developed. The measure demonstrated satisfactory reliability and validity to estimate OHRQoL in a representative sample of 12-year-old schoolchildren