Synthesis of Hydrazide Derivative of Betulinic Acid, Its Organometallic Complexes, Characterization and Bioassay.

Betulinic acid and its derivatives comprehend an immense prospective toward the development of cytotoxic, antiviral, antimicrobial and antioxidant agents. Cisplatin (cytotoxic drug) divert the attentions to develop organometallic compounds with pronounced biological activities. The current study was aimed for the first time to synthesize, characterize and evaluate biologically a series of metal (Fe, Cu, Zn, Sn and Sb) complexes of betulinic acid hydrazide. First step involved the formation of hydrazide derivative of betulinic acid (ligand) by modification at C-28 carboxylic acid moiety of betulinic acid with hydrazine followed by the synthesis of its metal complexes using salts of different metals (Fe, Cu, Zn, Sn and Sb). Physical state, melting point, Fourier-transform infrared (FT-IR) and 1 H nuclear magnetic resonance (1 H-NMR) spectral techniques were used to characterized the ligand and its metal complexes. Agar well diffusion method and agar tube dilution assay were performed to evaluate its antibacterial and antifungal activities respectively. DPPH assay was carried out to develop antioxidant properties by the reported methods.

Preparation and comparison of binary and ternary inclusion complexes of aripiprazole using L-arginine/lysine and MßCD/HPßCD by using different molar ratios.

Aripiprazole (ARI), an antipsychotic having low solubility and stability. To overcome this, formation of binary and ternary using inclusion complexes of Methyl-ß-cyclodextrin (MßCD) /Hydroxy propyl beta cyclodextrin (HPßCD) and L-Arginine (ARG)/ Lysine (LYS) are analyzed by dissolution testing and phase stability study along with their complexation efficacy and solubility constants made by physical mixing. Inclusion complexes with ARG were better than LYS and prepared by solvent evaporation and lyophilization method as well. They are characterized by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (AT-FTIR), X-ray powder diffractometry (XRD), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM) and Thermal gravimetric analysis (TGA). The bond shifting in AT-FTIR confirmed the molecular interactions between host and guest molecules. The SEM images also confirmed a complete change of drug morphology in case of ternary inclusion complexes prepared by lyophilization method for both the polymers. ARI: MßCD: ARG when used in the specific molar ratio of 1:1:0.27 by prepared by lyophilization method has 18 times best solubility while ARI:HPßCD:ARG was 7 times best solubility than pure drug making MßCD a better choice than HPßCD. Change in the molar ratio will cause loss of stability or solubility. Solvent evaporation gave significant level of solubility but less stability.

Comparative studies of anticancer, antimicrobial, antidiabetic, antioxidant activities of Daphne oleoides and Berberis baluchistanica extracts native to Pakistan.

To investigate in vitro anticancer, antimicrobial, antioxidant and in vivo hypoglycaemic effects of crude methanolic extracts (CMEs) of Berberis baluchistanica and Daphne oleoides. MTT assay for cytotoxicity on HeLa and NIH cells, disc diffusion protocols for antimicrobial and DPPH assay for antioxidant potential were applied. In vivo hypoglycaemic effect was investigated on Alloxan-induced diabetic rabbits. D. oleoides CME exhibited moderate cytotoxic behaviour against HeLa cells (IC50 77.87µg/mL) whereas B. baluchistanica CME was found deficient (IC50 170.02µg/mL). P. aeruginosa was susceptible to both CMEs. M. luteus and B. subtilis was prone to the bactericidal effects of D. oleoides and B. baluchistanica CMEs respectively. D. oleoides CME inhibited more than 80% S. cerevisiae and 60% C. glabrata colonies. B. baluchistanica CME showed significant antioxidant activity (IC50 52.86µg/ml) than D. oleoides CME (IC50 87.30µg/ml) and standard resveratrol (IC50 109.46µg/ml). B. baluchistanica CME showed superior antidiabetic effect (135.75 mg/dl ±0.53) as compared to D. oleoides CME (191.50 mg/dl ± 0.48) but less antidiabetic effect than metformin hydrochloride (standard). All the above potentials exhibited by D. oleoides and B. baluchistanica CMEs propose further investigations to isolate and purify responsible biologically active lead molecule(s) with diverse capabilities.

In vitro cytotoxic, antioxidant, antibacterial and antifungal activity of Saussurea heteromalla indigenous to Pakistan.

Medicinal plants are proven to reveal vast promising potential providing novel drug candidates to combat health-related problems. The aim of current study is to discover new drug compounds with anti-anticancer, antioxidant, antibacterial and antifungal potential, to serve the purpose Saussurea heteromalla (Family: Asteraceae) indigenous to Pakistan was screened for the in vitro cytotoxicity against HeLa cells (Human cervical cancer cell line) compared to the NIH / 3T3 cells (mouse normal fibroblast cells) by performing the MTT colorimetric assay and antifungal, antibacterial and antioxidant potential by adopting standard protocols. S. heteromalla crude methanolic extract (CME) demonstrated strong cytotoxic potential against HeLa cells at 200µg/mL; (77.28 ±1.53% kill; IC50: 62.13µg/mL) compared to standard doxorubicin (95.90% kill; IC50: 0.2µg/mL). Inhibitory Zone of the extract at concentrations (30, 60, 90µg/mL) against Bacillus subtilis, Serratia marecescens, Staphylococcus aureus, Micrococcus luteus, Pseudomonas aeruginosa, Strptotropomonas maltophilia, Escherichia coli, Salmonella typhi, and Saccharomyces cerevisiae, Candida albicans, Candida glabrata was measured. Manifestation of intensified results against Gram-negative Serratia marecescens qualifies the S. heteromalla extract as a considerable source of narrow spectrum antibiotic. However, antifungal activity against C. albicans was found to be logical. Antioxidant potential was determined through DPPH assay which declared no notable antioxidant effects. To the best of our knowledge this is first research and report on above mentioned biological studies of S. heteromalla.

Acute toxicity appraisal of Saussurea heteromalla extract and development of its chemotherapeutic herbal dosage form.

Ethnopharmacological relevance of Saussurea species for anti-cancer compounds instigated us to develop chemotherapeutic herbal tablets. This study was an ongoing part of our previous research based on the scientific evaluation of Saussurea heteromalla (S. heteromalla) for anti-cancer lead compounds. In the current study, S. heteromalla herbal tablets (500 /800 mg) were designed and evaluated for anti-cancer activity. Arctigenin was found as a bioactive lead molecule with anti-cancer potential for cervical cancer. The in vitro results on the HeLa cell line supported the ethnopharmacological relevance and traditional utilization of S. heteromalla and provided the scientific basis for the management of cervical cancer as proclaimed by traditional practitioners in China. LD50 of the crude extract was established trough oral acute toxicity profiling in mice, wherein the minimum lethal dose was noticed as higher than 1000 mg/kg body weight orally. Chromatographic fingerprint analysis ensured the identity and consistency of S. heteromalla in herbal tablets in terms of standardization of the herbal drug. About 99.15% of the drug (S. heteromalla crude extract) was recovered in herbal tablets (RSD: 0.45%). In vitro drug release profile was found to be more than 87% within 1 h, which was also correlated with different mathematical kinetic models of drug release (r2 = 0.992), indicating that drug release from matrix tablets into the blood is constant throughout the delivery. The dosage form was found stable after an accelerated stability parameters study which may be used for anti-cervical cancer therapy in the future, if it qualifies successful preclinical investigation parameters.

Effect of multiple micronutrient supplementation during pregnancy on maternal and birth outcomes.

OBJECTIVES/BACKGROUND: Given the widespread prevalence of micronutrient deficiencies in developing countries, supplementation with multiple micronutrients rather than iron-folate alone, could be of potential benefit to the mother and the fetus. These benefits could relate to prevention of maternal complications and reduction in other adverse pregnancy outcomes such as small-for-gestational age (SGA) births, low birth weight, stillbirths, perinatal and neonatal mortality. This review evaluates the evidence of the impact of multiple micronutrient supplements during pregnancy, in comparison with standard iron-folate supplements, on specific maternal and pregnancy outcomes of relevance to the Lives Saved Tool (LiST). DATA SOURCES/REVIEW METHODS: A systematic review of randomized controlled trials was conducted. Search engines used were PubMed, the Cochrane Library, the WHO regional databases and hand search of bibliographies. A standardized data abstraction and Child Health Epidemiology Reference (CHERG) adaptation of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) technique were used for data abstraction and overall quality of evidence. Meta-analyses were performed to calculate summary estimates of utility to the LiST model for the specified outcome of incidence of SGA births. We also evaluated the potential impact of multiple micronutrients on neonatal mortality according to the proportion of deliveries occurring in facilities (using a threshold of 60% to indicate functionality of health systems for skilled births). RESULTS: We included 17 studies for detailed data abstraction. There was no significant benefit of multiple micronutrients as compared to iron folate on maternal anemia in third trimester [Relative risk (RR) = 1.03; 95% confidence interval (CI): 0.87 - 1.22 (random model)]. Our analysis, however, showed a significant reduction in SGA by 9% [RR = 0.91; 95% CI: 0.86 - 0.96 (fixed model)]. In the fixed model, the SGA outcome remained significant only in women with mean body mass index (BMI) ≥ 22 kg/m2. There was an increased risk of neonatal mortality in studies with majority of births at home [RR = 1.47, 95% CI: 1.13-1.92]; such an effect was not evident where ≥ 60% of births occurred in facility settings [RR = 0.94, 95% CI: 0.81-1.09]. Overall there was no increase in the risk of neonatal mortality [RR = 1.05, 95% CI: 0.92 - 1.19 (fixed model)]. CONCLUSION: This review provides evidence of a significant benefit of MMN supplementation during pregnancy on reducing SGA births as compared to iron-folate, with no significant increase in the risk of neonatal mortality in populations where skilled birth care is available and majority of births take place in facilities. Given comparability of impacts on maternal anemia, the decision to replace iron-folate with multiple micronutrients during pregnancy may be taken in the context of available services in health systems and birth outcomes monitored.

Alma-Ata: Rebirth and Revision 6 Interventions to address maternal, newborn, and child survival: what difference can integrated primary health care strategies make?

Several recent reviews of maternal, newborn, and child health (MNCH) and mortality have emphasised that a large range of interventions are available with the potential to reduce deaths and disability. The emphasis within MNCH varies, with skilled care at facility levels recommended for saving maternal lives and scale-up of community and household care for improving newborn and child survival. Systematic review of new evidence on potentially useful interventions and delivery strategies identifies 37 key promotional, preventive, and treatment interventions and strategies for delivery in primary health care. Some are especially suitable for delivery through community support groups and health workers, whereas others can only be delivered by linking community-based strategies with functional first-level referral facilities. Case studies of MNCH indicators in Pakistan and Uganda show how primary health-care interventions can be used effectively. Inclusion of evidence-based interventions in MNCH programmes in primary health care at pragmatic coverage in these two countries could prevent 20-30% of all maternal deaths (up to 32% with capability for caesarean section at first-level facilities), 20-21% of newborn deaths, and 29-40% of all postneonatal deaths in children aged less than 5 years. Strengthening MNCH at the primary health-care level should be a priority for countries to reach their Millennium Development Goal targets for reducing maternal and child mortality.

Relationship between resilience and quality of life in diabetics.

OBJECTIVE: To determine the relationship between resilience and quality of life of diabetes patients controlling the effect of personal level (i.e., gender, age, and income) and disease-specific (i.e., duration of disease, and current glucose level) demographics. STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: Outpatient Departments of various hospitals in Islamabad and Rawalpindi, from October to November 2012. METHODOLOGY: Patients diagnosed with diabetes taking treatment in an outdoor patients' facility were included. Patients with a major diabetes complications causing or coexistent with a physical disability, medical condition or psychiatric comorbidity were excluded. Informed consent was taken from patients before administration of questionnaires. The patients were asked to respond to a demographic sheet, State-Trait resilience inventory, and WHO-Quality of Life BREF. Statistical testing was conducting using bivariate correlation, Mann-Whitney U-test, and multiple linear regression analysis for moderation testing. RESULTS: There were 242 patients including (n=108, 44% females; and n=134, 56% males) aged 17 - 85 years with mean of 44.56 ± 16.56 years. Trait resilience predicted all aspects of quality of life of diabetic patients (b range = 0.30 to 0.42, p < .01) and explained 17% variance in physical functioning, 29% in psychological functioning, 17% in environmental functioning, 30% in social dimension, and 29% in overall quality of life. Duration of diabetes moderated effect of state resilience on all aspects of quality of life (b interaction range = 0.20 to 0.26, p < .05) and explained an additional 4% variance in physical functioning, 5% in psychological functioning, 3% in environmental functioning, 5% in social dimension, and 4% in overall quality of life of diabetics. CONCLUSION: Trait resilience has unconditional positive effect on all aspect of quality of life. Long standing diabetics may benefit from intervention addressing state resilience.