Effect of pretreatment with coenzyme Q10 on isoproterenol-induced cardiotoxicity and cardiac hypertrophy in rats

AbstractBackground: Coenzyme Q10 (CoQ10) is a lipid-soluble, vitamin-like substance found in the hydrophobic interior of the phospholipid bilayer of most cellular membranes. It appears to be involved in the coordinated regulation between oxidative stress and antioxidant capacity of heart tissue when the heart is subjected to oxidative stress in various pathogenic conditions.Objective: The objective of the present study was to investigate the effect of pretreatment with CoQ10 (100 mg/kg) on isoproterenol (ISO)-induced cardiotoxicity and cardiac hypertrophy in rats.Methods: Albino male Wistar rats (250–300 g) were evenly divided by lottery method into 1 of the following 3 groups: the ISO group (olive oil 2 mL/kg orally for 18 days and ISO 1 mg/kg IP from days 9–18); the CoQ10 + ISO group (CoQ10 100 mg/kg orally for 18 days and ISO 1 mg/kg IP from days 9–18); and the control group (olive oil 2 mL/kg orally for 18 days and water IP from days 9–18). Twenty-four hours after the last dose of water or ISO, the rats were anesthetized and an ECG was recorded. Blood was withdrawn by retro-orbital puncture for estimation of serum creatine kinase-MB (CK-MB) isoenzyme levels, lactate dehydrogenase (LDH) levels, and aspartate aminotransferase activities. The animals were euthanized using an overdose of ether. The hearts of 6 animals from each group were used for estimation of superoxide dismutase (SOD) activity, reduced glutathione (GSH) concentration, lipid peroxidation (LPO), malondialdehyde (MDA), and total protein concentration. Histopathology of the 2 remaining hearts in each group was carried out by a blinded technician.Results: A total of 24 rats (8 in each group) were used in this study; all rats survived to study end. Compared with the control group, the ISO-treated rats had a significant change in heart to body weight ratio (P < 0.001); significant changes in the endogenous antioxidants (ie, significantly higher myocardial MDA concentration [P < 0.001]; significantly lower myocardial GSH concentration [P < 0.001] and SOD activity [P < 0.01]); and significantly higher serum activities of marker enzymes (eg, CK-MB [P < 0.001] and LDH [P < 0.001]). Compared with the ISO group, the CoQ10 + ISO group had a significant change in heart to body weight ratio (P < 0.001); significant changes in the endogenous antioxidants (ie, significantly lower MDA concentration [P < 0.05]; significantly higher myocardial GSH concentration [P < 0.001] and SOD activity [P < 0.05]); and significantly lower serum activities of marker enzymes (eg, CK-MB [P < 0.05] and LDH [P < 0.01]).Conclusion: Pretreatment with CoQ10 (100 mg/kg) for 18 days was associated with moderate protection against ISO-induced cardiotoxicity and cardiac hypertrophy, and with lower myocardial injury by preserving endogenous antioxidants and reducing LPO in rat heart

Rootstock affects stress relieving enzymatic activity during bud break in 'Red Globe' grapevine under semi-arid condition

       The role of stress relieving enzymes during bud sprouting in grapevines has already been established in different varieties. However, data on 'Red Globe' variety under tropical conditions are not reported. The present study was conducted to generate data on stress relieving enzymatic activities during bud sprout in 'Red Globe' on different rootstocks under arid conditions of India. Influence of different rootstocks on stress relieving enzymes (catalase, peroxidase, ascorbic acid oxidase and polyphenol oxidase) involved in bud sprouting under tropical conditions with double pruning and single cropping pattern was evidenced. Positive interactions were observed between enzymatic activities of stress relieving enzymes, increased bud break (64.25 %) and reduction in days taken to bud sprout (8.43 days). Among the rootstocks under study, vines on 110R and own rooted vines have strong impact on stress relieving enzymes that resulted into early and increased bud sprouting. Also, the dynamics of enzymatic activity can be used as biological indicators for forecasting the end of bud dormancy and recommencement of growth

Epigenetic control of cell cycle-dependent histone gene expression is a principal component of the abbreviated pluripotent cell cycle

Self-renewal of human pluripotent embryonic stem cells proceeds via an abbreviated cell cycle with a shortened G(1) phase. We examined which genes are modulated in this abbreviated period and the epigenetic mechanisms that control their expression. Accelerated upregulation of genes encoding histone proteins that support DNA replication is the most prominent gene regulatory program at the G(1)/S-phase transition in pluripotent cells. Expedited expression of histone genes is mediated by a unique chromatin architecture reflected by major nuclease hypersensitive sites, atypical distribution of epigenetic histone marks, and a region devoid of histone octamers. We observed remarkable differences in chromatin structure--hypersensitivity and histone protein modifications--between human embryonic stem (hES) and normal diploid cells. Cell cycle-dependent transcription factor binding permits dynamic three-dimensional interactions between transcript initiating and processing factors at 5\u27 and 3\u27 regions of the gene. Thus, progression through the abbreviated G(1) phase involves cell cycle stage-specific chromatin-remodeling events and rapid assembly of subnuclear microenvironments that activate histone gene transcription to promote nucleosomal packaging of newly replicated DNA during stem cell renewal

FORMULATION AND DEVELOPMENT OF SUSTAINED RELEASE MATRIX TABLETS OF LORNOXICAM

Lornoxicam is a NSAID having oxicam class mainly prescribed in the treatment of osteoarthritis and rheumatoid arthritis. NSAID have the potential to relieve the pain and inflammation without the immunosuppressive and metabolic side effects associated with corticosteroids. Generally the classification of NSAID is applied to drugs that inhibit one or more steps in the metabolism of Arachidonic Acid (AA). In general, NSAID do not inhibit lipoxygenase formation or the formation of other inflammatory mediators. Due to its more biological half-life i.e. 3-5 hrs. in India, the dosage form is available in 8-16 mg, it can be increased upto 24 mg/day if necessary. The main objectives of present investigation are to confirm the drug by various analytical techniques, to study the drug excipients compatibility, to avoid the dose as well as the frequency of the dosage form and to perform the stability. The tablet can be developed with the combination of HPMC K 100M and Ethyl Cellulose as a matrix former. Lornoxicam is NSAID that has numerous functions in the body. It can be absorbed rapidly and completely from gastrointestinal track after the oral administration. Absolute bioavailability of Lornoxicam is 90-100%. No first pass effect is observed. It is found in the plasma in the unchanged form and as its hydroxylated metabolite. The hydroxylated metabolite exhibits no pharmacological activity. CYP2C3 has been shown to be the primary enzyme responsible for the biotransformation of Lornoxicam. Approximately 2/3 part of Lornoxicam is eliminated via the liver and 1/3 via the kidneys as inactive substance. Lornoxicam inhibits the production of prostaglandins by inhibiting the action of cyclooxygenase, which regulates the conversion of Arachidonic Acid to Prostaglandins. Lornoxicam mainly prescribed in the treatment of osteoarthritis and rheumatoid arthritis, and also in the management of ankylosing spondylitis, acute sciatica and low back pain.Keywords: Lornoxicam, Sustained release, matrix

In vitro Evaluation of Novel Sustained Release Microspheres of Glipizide Prepared by the Emulsion Solvent Diffusion-Evaporation Method

The objective of the current investigation is to reduce dosing frequency and improve patient compliance by designing and systematically evaluating sustained release microspheres of Glipizide. An anti-diabetic drug, Glipizide, is delivered through the microparticulate system using ethyl cellulose as the controlled release polymer. Microspheres were developed by the emulsion solvent diffusion-evaporation technique by using the modified ethanol,-dichloromethane co-solvent system. The polymer mixture of ethyl cellulose and Eudragit® S100 was used in different ratios (1:0, 1:1, 2:3, 1:4 and 0:1) to formulate batches F1 to F5. The resulting microspheres were evaluated for particle size, densities, flow properties, morphology, recovery yield, drug content, and in vitro drug release behavior. The formulated microspheres were discrete, spherical with relatively smooth surface, and with good flow properties. Among different formulations, the fabricated microspheres of batch F3 had shown the optimum percent drug encapsulation of microspheres and the sustained release of the Glipizide for about 12 h. Release pattern of Glipizide from microspheres of batch F3 followed Korsmeyers-peppas model and zero-order release kinetic model. The value of ‘n’ was found to be 0.960, which indicates that the drug release was followed by anomalous (non-fickian) diffusion. The data obtained thus suggest that a microparticulate system can be successfully designed for sustained delivery of Glipizide and to improve dosage form characteristics for easy formulation

Intimate partner violence and condom versus other modern contraception use among married women in rural India

Background: Data from India document that spousal intimate partner violence (IPV) is associated with both unintended pregnancy and spacing contraceptive use. Analysis of IPV by type of contraception is lacking. Condom use may be less likely than other spacing contraception in the context of IPV, as it is under male control. This study aims to assess associations of physical and sexual IPV with condom and other contraception use among married women in rural India. We hypothesize that women reporting physical and sexual IPV victimization are significantly less likely to report condom use but not other contraception use, relative to women reporting no such victimization. Methods: Study participants were from the randomized control trial evaluation of CHARM, a male-centered family planning intervention for young married couples in rural Maharashtra, India. Baseline data from women (age 18-30, residing with husbands) were used for analyses; data were restricted to those who were not pregnant at interview (n¼867). Surveys assessed socio-demographics, husband’s physical and sexual IPV perpetration, and an item on primary form of contraception used by women in the past 3 months (subsequently categorized as none, condom, other modern spacing contraception). Multinomial logistic regression analyses assessed associations between past 6 month physical and sexual IPV and contraceptive use, adjusting for age, education, length of marriage, caste, parity, and husband’s alcohol use. All participants provided written informed consent; all study procedures were approved by Institutional Review Boards at UCSD, and ICMR. Findings: Participants were aged 18-30 (SD: 2.5), and 17% reported no formal education.12% and 4% of women reported past 6 month physical 218 Social and Environmental Determinants of Health and sexual IPV, respectively. The majority (72%) reported not using any modern spacing method of contraceptive in the past 3 months; 14% reported condom use and other modern spacing contraception, respectively. Physical IPV was significantly associated with condom use (AOR: 1.89, 95% CI: 1.04, 3.28) but not other contraception use. Sexual violence was associated with other modern contraceptive use (AOR: 2.78, 95% CI: 1.11, 7.00), but not condom use. Interpretation: Women contending with sexual violence were more likely to engage in other modern contraceptive use but not condom use. This finding may indicate that women contending with sexual violence may depend on forms of contraception more within their control. To our knowledge, this study is the first of its kind to examine such associations between IPV and contraception use by type of method. These findings are limited due to the cross-sectional nature of the data, and are not generalizable to the larger population of women in India. Further research is needed to explain the association between recent physical IPV and condom use, a finding inconsistent with prior research

Dimensionality of Carbon Nanomaterials Determines the Binding and Dynamics of Amyloidogenic Peptides: Multiscale Theoretical Simulations

Experimental studies have demonstrated that nanoparticles can affect the rate of protein self-assembly, possibly interfering with the development of protein misfolding diseases such as Alzheimer's, Parkinson's and prion disease caused by aggregation and fibril formation of amyloid-prone proteins. We employ classical molecular dynamics simulations and large-scale density functional theory calculations to investigate the effects of nanomaterials on the structure, dynamics and binding of an amyloidogenic peptide apoC-II(60-70). We show that the binding affinity of this peptide to carbonaceous nanomaterials such as C60, nanotubes and graphene decreases with increasing nanoparticle curvature. Strong binding is facilitated by the large contact area available for π-stacking between the aromatic residues of the peptide and the extended surfaces of graphene and the nanotube. The highly curved fullerene surface exhibits reduced efficiency for π-stacking but promotes increased peptide dynamics. We postulate that the increase in conformational dynamics of the amyloid peptide can be unfavorable for the formation of fibril competent structures. In contrast, extended fibril forming peptide conformations are promoted by the nanotube and graphene surfaces which can provide a template for fibril-growth

The PROMISES study: A mixed methods approach to explore the acceptability of salivary progesterone testing for preterm birth risk among pregnant women and trained frontline healthcare workers in rural India

Introduction India has an overall neonatal mortality rate of 28/1000 live births, with higher rates in rural India. Approximately 3.5 million pregnancies in India are affected by preterm birth (PTB) annually and contribute to approximately a quarter of PTBs globally. Embedded within the PROMISES study (which aims to validate a low-cost salivary progesterone test for early detection of PTB risk), we present a mixed methods explanatory sequential feasibility substudy of the salivary progesterone test. Methods A pretraining and post-training questionnaire to assess Accredited Social Health Activists (ASHAs) (n=201) knowledge and experience of PTB and salivary progesterone sampling was analysed using the McNemar test. Descriptive statistics for a cross-sectional survey of pregnant women (n=400) are presented in which the acceptability of this test for pregnant women is assessed. Structured interviews were undertaken with ASHAs (n=10) and pregnant women (n=9), and were analysed using thematic framework analysis to explore the barriers and facilitators influencing the use of this test in rural India. Results Before training, ASHAs' knowledge of PTB (including risk factors, causes, postnatal support and testing) was very limited. After the training programme, there was a significant improvement in the ASHAs' knowledge of PTB. All 400 women reported the salivary test was acceptable with the majority finding it easy but not quick or better than drawing blood. For the qualitative aspects of the study, analysis of interview data with ASHAs and women, our thematic framework comprised of three main areas: implementation of intervention; networks of influence and access to healthcare. Qualitative data were stratified and presented as barriers and facilitators. Conclusion This study suggests support for ongoing investigations validating PTB testing using salivary progesterone in rural settings