Metabolites in Conocarpus erectus leaves attenuate α-amylase activity by modulating amino acid residues of α-amylase: an in vitro and docking study / Los metabolitos en las hojas de Conocarpus erectus atenúan la actividad de la α-amilasa al modular los residuos de aminoácidos de la α-amilasa: un estudio in vitro y de acoplamiento

The antioxidant activity and the inhibitory potential of α-amylase of lyophilized hydroethanolic extracts of Conocarpus erectus leaves obtained by ultrasonication were determined. The most potent extract was subjected to ultra-high performance liquid chromatography system equipped with mass spectrometer for metabolite identification. The identified metabolites were docked in α-glucosidase to assess their binding mode. The results revealed that 60% ethanolic extract exhibited highest ferric reducing antioxidant power (4.08 ± 0.187 mg TE/g DE) and α-amylase inhibition (IC50 58.20 ± 1.25 µg/mL. The metabolites like ellagic acid, 3-O-methyl ellagic acid, ferujol, 5, 2 ́-dihydroxy-6,7,8-trimethyl flavone and kaempferol glucoside were identified in the extract and subjected to molecular docking studies regarding α-amylase inhibition. The comparison of binding affinities revealed 3-O-methyl ellagic acid as most effective inhibitor of α-amylase with binding energy of -14.5911 kcal/mol comparable to that of acarbose (-15.7815 kcal/mol). The secondary metabolites identified in the study may be extended further for functional food development with antidiabetic properties.

Se determinó la actividad antioxidante y el potencial inhibidor de la α-amilasa de extractos hidroetanólicos liofilizados de hojas de Conocarpus erectus obtenidos por ultrasónicación. El extracto más potente se sometió a un sistema de cromatografía líquida de ultra alto rendimiento equipado con un espectrómetro de masas para la identificación de metabolitos. Los metabolitos identificados se acoplaron en α-glucosidasa para evaluar su modo de unión. Los resultados revelaron que el extracto etanólico al 60% exhibió el mayor poder antioxidante reductor férrico (4.08 ± 0.187 mg TE/g DE) e inhibición de la α-amilasa (IC50 58.20 ± 1.25 µg/mL. Los metabolitos como el ácido elágico, 3-O-metil elágico ácido, ferujol, 5, 2 ́-dihidroxi-6,7,8-trimetil flavona y kaempferol glucósido se identificaron en el extracto y se sometieron a estudios de acoplamiento molecular con respecto a la inhibición de la α-amilasa. La comparación de las afinidades de unión reveló 3-O-metil El ácido elágico como inhibidor más eficaz de la α-amilasa con una energía de unión de -14,5911 kcal/mol comparable a la de la acarbosa (-15,7815 kcal/mol). Los metabolitos secundarios identificados en el estudio pueden ampliarse aún más para el desarrollo funcional de alimentos con propiedades antidiabéticas.

Ameliorating effect of Malva Neglecta on hyperglycemia and hyperlipidemia in diabetic rats

The plant, Malva neglecta wallr., is widely consumed for medicinal and nutritional purposes. The current study was carried out to assess the hypoglycemic and antihyperlipidemic potential of aqueous methanolic extract of M. neglecta. Chemical evaluation of the extract was performed by high pressure liquid chromatography. Oral glucose tolerance test (OGTT) was done in diabetic rats pre-exposed to 250, 500 and 750 mg/kg plant extract via the oral route. For hypoglycemic and biochemical study, the same therapy was administered to alloxan induced diabetic rats for 14 days. The standard control group received Glibenclamide (5 mg/kg). Ferulic acid, p-coumaric acid and other phenolic acids were detected and estimated in the extract. Administration of the plant extract significantly reduced blood glucose level in diabetic rats subjected to OGTT. The plant extract lowered the fasting blood glucose and alpha amylase, and prevented the damage to pancreas. It also corrected dyslipidemia in diabetic animals following 14 days therapy. Hence, this experimental study establishes the fact that M. neglecta exhibited significant antidiabetic and antihyperlipidemic activities in alloxan induced diabetic rats.

Evaluation of prevalence of different types of cancer and its chemotherapy in various ethnic groups of Pakistan: A retrospective study

The objective of the study was to evaluate different types of cancer and its chemotherapy in various ethnic groups of Pakistan. Ethnic groups includes, Pukhtoons, Punjabis, Sindhis, Muhajirs, Siraikis, Memoons, Hazaras, Hindkos, Baltis, Gilgitis, Kashmiris, and Afghanis. The data was collected from well reputed hospitals located in the different provinces of Pakistan. The collected data was taken from 15 hospitals where around 8500 patients visited during 2010 to 2017. From the visited patients, 8356 were analyzed for their ethnicity, age and sex while, 144 patients (male 77 and female 67) were excluded from analysis due to incomplete information or loss of follow-up. Among 8356 patients, 3762 were male (45%) whereas, 4594 were female (55%). The chemotherapy was carried out as per National Comprehensive Cancer Network guidelines (NCCN- guidelines). The most common five prevalent cancer among these ethnic groups were Head and Neck, Blood, Respiratory, Genito-urinary and Breast cancer. The most common cancer in female was breast cancer while, head and neck cancer was more prevalent in male. It can be concluded that the prevalence of cancer in Pakistan is very alarming, which may be due to lack of awareness, illiteracy, lack of national cancer control programs, and economics issues.

Efficacy and safety of sofosbuvir based antiviral therapy for chronic hepatitis C infection in patients with advanced chronic kidney disease

Background: Screening studies for hepatitis C have proved that it is more prevalent in patients with renal diseases. Chronic hepatitis C infection in patients with kidney disease not only accelerates renal deterioration but also adversely effects morbidity and mortality. Availability of direct acting antiviral drugs has revolutionized treatment of hepatitis C even in difficult patients. In advanced kidney diseases, selection of treatment is difficult. Aim of this study was to evaluate the efficacy and safety of Sofosbuvir based DAAs in patients with advanced CKD.Methods: In this Quasi experimental study, CHC patients with or without cirrhosis having advance CKD (eGFR <30 ml/min per 1.73 m2) and/or on dialysis were enrolled. End points of the study were documentation of SVR 12 or discontinuation of therapy. Different regimens of oral DAAs with or without Ribavirin were used.Results: 86 patients with a median age of 53 years were enrolled. 37 patients were on maintenance dialysis and 49 were not on dialysis with eGFR <30 ml/min per 1.73 m2. Virological response was 92.68% at the end of treatment and SVR was achieved by 90.2% twelve weeks after therapy. Insomnia 14%, headache 11% and anemia 7% were main dverse effects. Mean eGFR and creatinine before and after treatment remained the same. Only 2 patients relapsed, both were on dialysis thrice weekly.Conclusions: All Sofosbuvir based regimens used for the treatment of CHC in patients with end stage renal disease are effective and well tolerated. Close follow up is advised to monitor side effects.

A Case Report of Bardet Biedl Syndrome Presented to East Jeddah Hospital, Jeddah, Saudi Arabia

We would like to report a rare case of Bardet Biedl Syndrome of a women forty-three years, known case of Retinitis pigmentosa presented for medical report, after ocular and systemic assessment we found she is obese, moon face, and has extra toes of both feet and some other finding which was diagnosed later on Bardet Biedl Syndrome, We documented this rare case for its important in clinical practice for regular systemic follow up and therefore, subsequently requiring management accordingly.

Influence of different formulation variables on the performance of transdermal drug delivery system containing tizanidine hydrochloride: in vitro and ex vivo evaluations

The present study was aimed at preparation of transdermal patches of tizanidine HCl, evaluation of the effect of polymers on in vitro release pattern of the drug, and the effect of permeation enhancers on the penetration of the drug through the rabbit skin. Various proportions of hydrophilic (HPMC) and hydrophobic (Eudragit L-100) polymers were used with PEG 400 as film-forming agent, and Span 20 or DMSO as permeation enhancer. The formulations were assessed for physicochemical characteristics and in vitro drug release studies using USP paddle over disc method in phosphate buffered saline (pH 7.4) at 32.0±1°C. On the basis of in vitro studies and physicochemical evaluations, S03-A and S04-A were selected at Eudragit : HPMC ratios of 8 : 2 and 7 : 3, respectively, for further ex vivo analysis. The effects of different concentrations of Span 20 and DMSO were evaluated on excised rabbit skin using Franz diffusion cell. Cumulative drug permeation, flux, permeability coefficient, target flux, and enhancement ratio were calculated and compared with the control formulations. Kinetic models and Tukey's multiple comparison test were applied to evaluate the drug release patterns. Formulation SB03-PE containing Eudragit L-100:HPMC (7:3) with Span 20 (15% w/w) produced the highest enhancement in drug permeation, and followed zero order kinetic model with super case-II drug release mechanism.

Pre-Blood-Donation Screening of Volunteer Prisoners for Hepatitis B and C in Prisons of the Punjab, Pakistan.

Objectives: To identify the potential benefits of pre-donation screening of blood. Study design: Retrospective. Place and Duration: Prisons in the Punjab province. From January 2011 t0 September 2013. Background: Prisoners, as a high risk group, are not recommended for blood donations. In Pakistan, however, prisoners are legally allowed to donate blood and get thirty days remission. Methodology: Volunteer prisoners, after examination and verification by a physician for their physical fitness, were tested for Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) by Rapid Test Kit before bleeding. Data was analyzed by Epi-Info. Results: A total of 5894 male volunteer prisoner donors were screened and 1038 (17.6%) were rejected because of hepatitis infection. The mean age was 28 years (range; 17 - 70 years). Of 5894 prisoners, 857 (14.5%) were HCV positive and 222 (3.8%) were HBV positive. Co-infection of HCV and HBV was present among 41 (0.7%). Hepatitis infection, among convicted- prisoner blood donor, is significantly associated with higher seroprevalence for HCV (OR 1.35, 95% C.I. 1.17-1.57) while under-trial- prisoner is significantly associated with higher seroprevalence for HBV (OR 1.40, 95% C.I. 1.06-1.85). Conclusion: Hepatitis B and C viruses were responsible for almost 18% prisoner blood donor rejection. Pre-donation screening of blood donors is an effective intervention to improve the safety and limit the cost of blood. Treatment of identified infected prisoners may contribute to public health. In the international scenario this study findings necessitate the amendments in the relevant prison rules.

Convergent synthesis of new N -substituted 2-{[5-(1H -indol-3-ylmethyl)-1, 3, 4-oxadiazol-2-yl]sulfanyl}acetamides as suitable therapeutic agents

abstract A series of N-substituted 2-{[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides (8a-w) was synthesized in three steps. The first step involved the sequential conversion of 2-(1H-indol-3-yl)acetic acid (1) to ester (2) followed by hydrazide (3) formation and finally cyclization in the presence of CS2 and alcoholic KOH yielded 5-(1H-indole-3-yl-methyl)-1,3,4-oxadiazole-2-thiol (4). In the second step, aryl/aralkyl amines (5a-w) were reacted with 2-bromoacetyl bromide (6) in basic medium to yield 2-bromo-N-substituted acetamides (7a-w). In the third step, these electrophiles (7a-w) were reacted with 4 to afford the target compounds (8a-w). Structural elucidation of all the synthesized derivatives was done by 1H-NMR, IR and EI-MS spectral techniques. Moreover, they were screened for antibacterial and hemolytic activity. Enzyme inhibition activity was well supported by molecular docking results, for example, compound 8q exhibited better inhibitory potential against α-glucosidase, while 8g and 8b exhibited comparatively better inhibition against butyrylcholinesterase and lipoxygenase, respectively. Similarly, compounds 8b and 8c showed very good antibacterial activity against Salmonella typhi, which was very close to that of ciprofloxacin, a standard antibiotic used in this study. 8c and 8l also showed very good antibacterial activity against Staphylococcus aureus as well. Almost all compounds showed very slight hemolytic activity, where 8p exhibited the least. Therefore, the molecules synthesized may have utility as suitable therapeutic agents.

resumo Uma série de acetamidas 2-{[5-(1H-indol-3-ilmetil)-1,3,4-oxadiazol-2-il]sulfanila} N-substituídas (8a-w) foi sintetizada em três fases. A primeira etapa envolveu a conversão sequencial de ácido 2-(1H-indol-3-il)acético (1) a éster (2), seguido por hidrazida (3) e, finalmente, a e ciclização na presença de CS2 e KOH alcoólico produziu 5-(1H-indol-3-il- metil)-1,3,4-oxadiazole-2-tiol (4). Na segunda etapa, aminas arílicas/aralquílicas(5a-w) reagiram com brometo de 2-bromoacetila (6​​), em meio básico, para se obter acetamidas 2-bromo-N-substituídas (7a-w). Na terceira etapa, estes eletrófilos (7a- w) reagiram com 4, para se obter os compostos alvo (8a-w). A elucidação estrutural de todos os derivados sintetizados foi realizada por 1H-NMR, IR e técnicas de espectrometria de EI-MS. Além disso, eles foram submetidos a triagem de atividade antibacteriana e hemolítica. Análise da inibição enzimática foi bem apoiada pelos resultados de docking molecular. Por exemplo, o composto 8q exibiu melhor potencial inibitório contra α-glicosidase, e os compostos 8g e 8b exibiram, comparativamente, melhor inibição contra butirilcolinesterase (BChE) elipoxigenase (LOX), respectivamente. Do mesmo modo os compostos 8b e 8c mostraram excelente potencial antibacteriano contra SalmonellaTyphi, semelhante ao do ciprofloxacino, antibiótico padrão usado neste estudo. Os compostos 8c e 8l também mostraram excelente potencial antibacteriano contra Staphylococcus aureus . Quase todos os compostos mostraram pequena atividade hemolítica, sendo que o composto 8p apresentou menor atividade. Assim, as moléculas sintetizadas podem ter a sua utilidade como agentes terapêuticos adequados.