Open Access Short Research Article

In Silico Analysis for DPYD Gene and the Effect of the Mutation on Dihydropyrimidine Dehydrogenase Enzyme

Asia M. Elrashid, Mohamed Y. Basher, Ali I. A. Gharib, Mohamed A. I. Alfaki, Nawarz M. Mohammed, Ahmed M. Elmoselhy, Sahar G. Elbager, Safinaz I. Khalil

Journal of Advances in Medical and Pharmaceutical Sciences, Page 1-10
DOI: 10.9734/JAMPS/2018/40300

Aim: The aim of this study was to implement an in silico bioinformatics analysis for clinically observed missense variants in human DPYD gene to investigate the effect these variants on Dihydropyrimidine dehydrogenase enzyme 's structure and function.

Methods: The human DPYD gene was investigated in dbSNP/NCBI, 273238 SNPs were found; 99645 SNPs were Homo sapins; of which 534 were missense SNPs. Missense SNPs were selected for in silico analysis; SIFT, Polyphen2, SNPs & GO, Imutant 2.0, Mutation 3D , UCSF Chimera and HOPE were used to investigate the effect of SNPs on DPD protein's structure and function.

Results: 69 SNPs were found to be highly damaging for the protein by SIFT and Polyphen, of which 4 SNPs were observed to be associated to clinical presentations (M166V, V335L, I560S, D949V). These 69 SNPs were further analyzed by SNPs & GO, one SNP (D949V) was observed to be associated to clinical presentations. The 4 nsSNPs that observed to be associated to clinical presentations were further analyzed by I-Mutant, HOPE and chimera tools to predict their stability index and visualize wide and mutant residues in their protein 3D structure

Conclusions: We observe a range of structural and functional changes caused by single amino acid differences, including changes in protein structural, stability and binding properties associated with the 4nsSNPs (M166V, V335L, I560S, D949V). This can explain the variability in drug response and toxicity in patients who acquire these nsSNPs and treated with 5-FU.

Open Access Original Research Article

Effect of an Angiotensin Converting Enzyme Inhibitor (Captopril) on Liver and Kidney Function Parameters in Plasmodium berghei-Infected Mice

R. K. Bala, A. M. Abdulazeez, A. I. Kiru, N. S. Abdullahi, B. A. Abubakar

Journal of Advances in Medical and Pharmaceutical Sciences, Page 1-8
DOI: 10.9734/JAMPS/2018/40599

Aim: This study was carried out to investigate the effect of captopril on serum liver enzymes (AST, ALT, and ALP), total serum protein and kidney function parameters such as electrolytes (HCO3-,  Cl-, Na+, and K+), urea and creatinine in Plasmodium berghei-infected mice.

Methodology: A total of 40 apparently healthy mice were randomly divided into five groups of 8 mice each; normal control group (not infected, not treated), malaria control (malaria-infected, not treated), standard control (malaria-infected, treated with 0.03 mg/kg of standard drug, Arthemeter 20 mg + Lumefantrine 120 mg), group 4 (malaria-infected, treated with 0.03 mg/kg of captopril) and group 5 (malaria-infected, treated with 0.09 mg/kg of captopril). The mice were treated for 14 days and parasitemia level monitored every other day. On the 15th day, mice were sacrificed and blood obtained to determine serum liver enzymes (AST, ALT, and ALP), total protein, serum electrolyte (HCO3-, Cl-, Na+, and K+), urea and creatinine levels.

Results: There was a significant increase (P<.05) in the % parasitemia, serum liver enzymes, urea, creatinine, and K+ after induction of malaria. This decreased significantly (P<.05) when mice were treated with 0.03 mg/kg of standard drug and 0.09 mg/kg of captopril compared to mice treated with 0.03 mg/kg of captopril and malaria control mice. However, serum total protein, Na+, K+, and Cl- decreased significantly (P<.05) in the malaria control group but increased significantly (P<.05) when treated with 0.03 mg/kg of standard drug and 0.09 mg/kg captopril compared to mice treated with 0.03 mg/kg of captopril.

Conclusion: This study has shown that captopril, at high concentration may be beneficial against malaria infection and renal disorders.

Open Access Original Research Article

Theoretical Investigation of Correlations Between Molecular and Electronic Structure and Antifungal Activity in Coumarin Derivatives: Combining Qsar and Dft Studies

Abduljelil Ajala, Adamu Uzairu, Idris O. Suleiman, Ahmed Jibrin Uttu

Journal of Advances in Medical and Pharmaceutical Sciences, Page 1-18
DOI: 10.9734/JAMPS/2018/22801

Quantitative structure-activity relationship (QSAR) models were combined with density functional computations and used to predict anti-fungi activities in a series of coumarin derivatives. Essential descriptors employed in this study were chosen based on the use of the Genetic Function Approximation (GFA) method.  Leave-N-Out (LNO) and Y-randomization techniques affirmed the model’s robustness and validity. Computed pMIC values were found to be in good agreement (+/- XX%) with experimentally determined values.  The proposed model may be a superior predictor of the counter-parasitic action of coumarin analogs and can be utilized for recommendation of new chemopreventive species.

Open Access Original Research Article

Antityrosinase Activities of Thespesia populnea Bark and Phyllanthus emblica Fruit

H. K. I. Perera, A. P. C. Pradeep, K. D. U. Devinda, R. M. U. K. Ratnayake, D. K. L. R. Gunawardhana, J. A. V. P. Jayasinghe

Journal of Advances in Medical and Pharmaceutical Sciences, Page 1-8
DOI: 10.9734/JAMPS/2018/40775

Aims: Currently there is enormous demand for skin-lightening agents, creating a quest for identification of new substances. Tyrosinase has become the main drug target for reducing skin pigmentation. The objective of this study was to detect tyrosinase inhibitory effects of eight medicinal plants that are used to treat skin conditions.

Study Design:  In vitro assay.

Place and Duration of Study: Department of Biochemistry, Faculty of Medicine, University of Peradeniya, Sri Lanka, from June 2016 to December 2017.

Methodology: Tyrosinase inhibitory effects of methanol extracts of eight plant species that are used to treat various skin conditions were measured using 3,4-Dihydroxy-L-phenylalanine (L-DOPA) as the substrate. Kojic acid was used as the positive control. IC50 values of extracts with high activity were measured using a range of concentrations. Statistical significance of the differences between the inhibitory effects was calculated using ANOVA.

Results: Thespesia populnea bark showed the highest inhibition among the tested, with an IC50 of 190 µg/mL. Phyllanthus emblica fruit also showed higher inhibitory effect with IC50 value of 251 µg/mL. IC50 value of kojic acid (3.4 µg/mL) against tyrosinase was significantly lower than that of P. emblica and T. populnea. Even though Santalum album bark and Vernonia cinerea plant showed 36.3 and 32.8% inhibitions respectively at 0.5 mg/mL, these effects did not show a dose-dependent increase. Extracts of Coscinium fenestratum, Persea Americana, Vigna radiata and Vigna unguiculata demonstrated only lower inhibitory effects on tyrosinase.

Conclusion: Current study reveals higher antityrosinase activities in methanol extracts of P. emblica fruit and T. populnea bark.

Open Access Original Research Article

Comparative Study of Cardiopulmonary Functions in Trained Male Athletes and Singers– A Pilot Study

O. O. Omodara, P. P. Mshelia, A. A. Madaki, M. I. A. Saleh

Journal of Advances in Medical and Pharmaceutical Sciences, Page 1-8
DOI: 10.9734/JAMPS/2018/40220

Objectives: Studies have shown that both physical exercise and singing have beneficial medical effects on the cardiopulmonary functions of humans in health and disease conditions, but it is not yet known whether physical exercise or singing is more effective in producing these benefits. The aim of this pilot study was to investigate if there is difference between the cardiopulmonary functions in trained male athletes and singers.

Study Design: A total of 20 male human subjects, consisting of 10 trained athletes and 10 trained singers, participated in this study. The ages of the subjects ranged from 20 to 35 years. The trained athletes were individuals who have been engaging in physical exercise under the supervision of a trainer not less than 3 times in a week for 5 years or more. While the trained singers were individuals who are members of singing groups and have been singing at least 3 times in a week in the last 5 years or more.

Methods: Each subject was allowed to rest for about 15minutes in order to allow cardiorespiratory parameters return to basal resting levels. Thereafter, pressor, cardiac and pulmonary function parameters of each subject were measured.

Results: Results showed that conduction of impulses within the ventricle (QRS amplitude) and rate of conduction of impulses from the atrium to the ventricle (PR interval) were higher (P<0.02 and P<0.001 respectively) in trained athletes, while voltage supply during ventricular repolarization (T-wave amplitude) was significantly higher (P<0.001) in trained singers. Forced expiratory volume in one second (FEV1) was higher (P<0.05) in trained athletes. Also, there was notable difference (P<0.001) in the FEV1% of trained athletes and trained singers.

Conclusion: The results of this study suggest that there is no significant difference in the cardiovascular functions of trained male athletes and singers, but the effects of physical exercise could be more beneficial than that of singing on the pulmonary function.