Histone deacetylase inhibitors: pharmacotherapeutic implications as epigenetic modifier

Epigenetic modifications such as acetylation and deacetylation of histone proteins play a decisive role in transcriptional alteration and expression of genes. Acetylation is catalysed by the histone acetyl transferases enzymes and activates expression of genes by converting chromatin into a less compact, transcriptionally active state. Histone deacetylases enzymes catalyze deacetylation that condenses chromatin into a closed structure .Consequently transcriptional factors are unable to access DNA and gene expression is suppressed. Balanced activity of HATs and HDACS is essential for normal gene expression. Increased HDAC activity can lead to imbalance in protein acetylation resulting in hypoacetylation, tight chromatin structure and suppression of various genes. This aberrant suppression of genes is the hallmark of several malignant and other diseases including neurodegenerative disorders. Histone Deacetylase Inhibitors (HDACIs) have potential to restore the balance of histone acetylation that reverses the silencing of pathological genes. Thus HDACIs modify expression of genes without affecting sequence of DNA and act as epigenetic modifiers. Vorinostat and romidepsin are FDA approved HDACIs. Valproic acid, belinostat and many others are in different phases of clinical trials. This review article explores the target based epigenetic mechanisms as well as existing and potential therapeutic role of HDACIs in various malignant and non-malignant diseases. Data sources were articles published in medical journals and bibliographic database Medline

Assessment of Knowledge and Attitude Towards Hepatitis B Infection Among Health-Care Professionals in A North Indian City

Introduction: Hepatitis B is an infection which occurs frequently worldwide. Hepatitis B virus is a DNA virus and is etiologically related to family Hepadnaviridae.Most of the cases of Hepatitis B virus infection do not have any symptoms when they are newly or chronically infected due to which there is silent spread of the infection which later causes serious liver disease. Incidence of the Hepatitis B virus infection among health-care professionals has been estimated to be 2–4 times more as compared to the general population.Aims: to assess the knowledge and attitude towards Hepatitis B infection among medical, dental, and nursing students in Bareilly city.Settings and Design: A cross-sectional observational study was conducted among the medical and nursing students of Rohilkhand Medical College and Hospital and dental students of Institute of Dental Sciences, Bareilly.Method and Materials: A self-reported questionnaire was distributed among all the students of the study who were present at the day.Statistical analysis used: p-value was calculated using Kruskal Walli’s ANOVA test. A p-value of 0.05 or less was used as cut off level for statistical significance.Results: Total 222 students were selected out of which 60 were medical, 60 were dental and 102 were nursing. In our study medical students had better knowledge, attitude towards Hepatitis B infection than dental and nursing students.Conclusions: None of the students of medical, dental, and nursing were fully aware on all aspects of Hepatitis B Virus infection and the vaccination status was found to be unsatisfactory which increased the risk to acquire Hepatitis B infection

Surface sterilant effect on the regeneration efficiency from cotyledon explants of groundnut (Arachis hypogea L.) varieties adapted to eastern and Southern Africa

Five groundnut (Arachis hypogea L.) varieties - ICGV-12991, ICGV-99568, ICGV-90704, CG-2 and Chalimbana - that are adapted to Eastern and Southern Africa were compared to variety JL 24 for their regeneration response in tissue culture. Sodium hypochlorite and mercuric chloride were compared for efficiency as sterilizing agents and subsequent effect on regeneration. All five varieties formed shoot buds that elongated well on shoot elongation medium. ICGV-90704 and Chalimbana performed betterthan the other three varieties for shoot organogenesis although all varieties produced healthy rooted plants in vitro that were successfully transferred to the greenhouse where they exhibited normal growth, flowering and seed set. Both sterilizing agents were suitable, but mercuric chloride was lessharmful than sodium hypochlorite. This study established a basis for genetic engineering activities on African groundnuts in the future

αA-Crystallin Peptide 66SDRDKFVIFLDVKHF80 Accumulating in Aging Lens Impairs the Function of α-Crystallin and Induces Lens Protein Aggregation

The eye lens is composed of fiber cells that are filled with α-, β- and γ-crystallins. The primary function of crystallins is to maintain the clarity of the lens through ordered interactions as well as through the chaperone-like function of α-crystallin. With aging, the chaperone function of α-crystallin decreases, with the concomitant accumulation of water-insoluble, light-scattering oligomers and crystallin-derived peptides. The role of crystallin-derived peptides in age-related lens protein aggregation and insolubilization is not understood.We found that αA-crystallin-derived peptide, (66)SDRDKFVIFLDVKHF(80), which accumulates in the aging lens, can inhibit the chaperone activity of α-crystallin and cause aggregation and precipitation of lens crystallins. Age-related change in the concentration of αA-(66-80) peptide was estimated by mass spectrometry. The interaction of the peptide with native crystallin was studied by multi-angle light scattering and fluorescence methods. High molar ratios of peptide-to-crystallin were favourable for aggregation and precipitation. Time-lapse recordings showed that, in the presence of αA-(66-80) peptide, α-crystallin aggregates and functions as a nucleus for protein aggregation, attracting aggregation of additional α-, β- and γ-crystallins. Additionally, the αA-(66-80) peptide shares the principal properties of amyloid peptides, such as β-sheet structure and fibril formation.These results suggest that crystallin-derived peptides such as αA-(66-80), generated in vivo, can induce age-related lens changes by disrupting the structure and organization of crystallins, leading to their insolubilization. The accumulation of such peptides in aging lenses may explain a novel mechanism for age-related crystallin aggregation and cataractogenesis

Cardiac rehabilitation versus standard care after aortic aneurysm repair (Aneurysm CaRe): study protocol for a randomised controlled trial.

BACKGROUND: Abdominal and thoracic aortic aneurysms (A/TAA) are an important cause of mortality amongst the older population. Although A/TAA repair can be performed with low peri-operative risk, overall life expectancy remains poor in the years that follow surgery. The majority of deaths are caused by heart attack or stroke, which can both be prevented by cardiac rehabilitation (CR) in patients with clinically-manifest coronary artery disease. A Cochrane review has urged researchers to widen the use of CR to other populations with severe cardiovascular risk, and patients surviving A/TAA repair appear ideal candidates. However, it is unknown whether CR is feasible or acceptable to A/TAA patients, who are a decade older than those currently enrolling in CR. Aneurysm-CaRe is a feasibility randomised controlled trial (RCT) that will address these issues. METHODS AND DESIGN: Aneurysm-CaRe is a pilot RCT of CR versus standard care after A/TAA repair, with the primary objectives of estimating enrolment to a trial of CR after A/TAA repair and estimating compliance with CR amongst patients with A/TAA. Aneurysm-CaRe will randomise 84 patients at two sites. Patients discharged from hospital after elective A/TAA repair will be randomised to standard care or enrolment in their local CR programme with a protocolised approach to medical cardiovascular risk reduction. The primary outcome measures are enrolment in the RCT and compliance with CR. Secondary outcomes will include phenotypic markers of cardiovascular risk and smoking cessation, alongside disease-specific and generic quality-of-life measures. TRIAL REGISTRATION: ISRCTN 65746249 5 June 2014

Remote sensing of spectral signatures of tropospheric aerosols

With the launch of the German Aerospace Agency's (DLR) Modular Opto-electronic Scanner (MOS) sensor on board the Indian Remote Sensing satellite (IRS-P3) launched by the Indian Space Research Organization (ISRO) in March 1996, 13 channel multi-spectral data in the range of 408 to 1010nm at high radiometric resolution, precision, and with narrow spectral bands have been available for a variety of land, atmospheric and oceanic studies. We found that these data are best for validation of radiative transfer model and the corresponding code developed by one of the authors at Space Applications Centre, and called ATMRAD (abbreviated for ATMospheric RADiation). Once this model/code is validated, it can be used for retrieving information on tropospheric aerosols over ocean or land. This paper deals with two clear objectives, viz., (1) Validation of ATMRAD model/code using MOS data and synchronously measured atmospheric data, and if found performing well, then to (2) derive relationship between MOS radiances and Aerosol Optical Thickness (AOT). The data validation procedure essentially involves near-synchronous measurements of columnar aerosol optical thickness and altitude profiles of aerosol concentration using ground-based multi-filter solar radiometers and Argon-ion Lidar, respectively and computation of the top-of-the-atmosphere (TOA) radiances from a low reflecting target (near clear water reservoir in the present study) using the ATMRAD model. The results show that the model performance is satisfactory and a relationship between the spectral parameters of MOS radiances and aerosol optical thickness can be established. In this communication, we present the details of the experiments conducted, database, validation of the ATMRAD model and development of the relationship between AOT and MOS radiance

RAPID DETECTION OF MULTI DRUG RESISTANCE AMONG MULTI DRUG RESISTANT TUBERCULOSIS SUSPECTS USING LINE PROBE ASSAY

Objective: GenoType MTBDRplus line probe assay (LPA) is developed for performing drug susceptibility testing (DST) for Rifampicin (RIF) and isoniazid in sputum specimens from smear-positive pulmonary tuberculosis (TB) patients and revised national TB control Programme (RNTCP) has endorsed LPA for the diagnosis of multi drug resistant TB (MDR-TB). This study was conducted to assess the potential utility of LPA for MDR-TB patient management.Methods: MDR-TB suspects under RNTCP PMDT criteria C referred from different districts in Delhi state were included in the study January 2013 toDecember 2014. Sputum specimens found acid-fast bacilli positive by fluorescent microscopy were processed for LPA.Results: Out of 3062 specimens, 2055 (67.1%) MDR-TB suspects were read as positive and specimens from 1007 (32.9%) suspects were read as negative in sputum smear microscopy. Out of 2019 specimens valid LPA results, 1427 were found to be pan-sensitive, 280 were MDR-TB, 40 were RIF monoresistant, 183 were Isoniazid (INH) monoresistant, and 89 specimens were found negative for Mycobacterium tuberculosis.Conclusion: Routine use of LPA can substantially reduce the time to diagnosis of RIF and/or INH-resistant TB and can hence potentially enable earlier commencement of appropriate drug therapy and thereby facilitate prevention of further transmission of drug resistant strains.Keywords: Multi drug resistant tuberculosis, Line probe assay, Rifampicin, Isoniazid

Unusual acquired gastric outlet obstruction during infancy: a case report

Acquired gastric outlet obstruction (GOO) during infancy beyond the neonatal period is a very rare condition when other congenital causes like infantile hypertrophic pyloric stenosis, antral diaphragm, pyloric atresia etc are excluded. We report an unusual case of 6 month old male child who presented with recurrent episode of vomiting not relieved by medication. On gastrograffin study there was pre pyloric stricture of unknown etiology and was managed by stricturoplasty. We are reporting this case because of its rarity and with excellent outcome if diagnosed and managed properly. Even on extensive search of English literature we are not able to find a single report of this lesion in infants

Prevalence and risk factors associated with chronic kidney disease in Nepal: evidence from a nationally representative population-based cross-sectional study.

OBJECTIVE: This study aimed to determine population-based prevalence of chronic kidney disease (CKD) and its associated factors in Nepal. STUDY DESIGN: The study was a nationwide population-based cross-sectional study. SETTING AND PARTICIPANTS: Cross-sectional survey conducted in a nationally representative sample of 12 109 Nepalese adult from 2016 to 2018 on selected chronic non-communicable diseases was examined. Multistage cluster sampling with a mix of probability proportionate to size and systematic random sampling was used for the selection of individuals aged 20 years and above. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome in this study was population-based prevalence of CKD in Nepal. A participant was considered to have CKD if the urine albumin-to-creatinine ratio was greater than or equal to 30 mg/g and/or estimated glomerular filtration rate is less than 60 mL/min/1.73 m2 at baseline and in follow-up using modification of diet in renal disease study equations. The secondary outcome measure was factors associated with CKD in Nepal. The covariate adjusted association of risk factors and CKD was calculated using multivariable binary logistic regression. RESULTS: The overall prevalence of CKD in Nepal was 6.0% (95% CI 5.5 to 6.6). Factors independently associated with CKD included older age (adjusted OR (AOR) 2.6, 95% CI 1.9 to 3.6), Dalit caste (AOR 1.6, 95% CI 1.1 to 2.3), hypertension (AOR 2.4, 95% CI 2.0 to 3.0), diabetes mellitus (AOR 3.2, 95% CI 2.5 to 4.1), raised total cholesterol (AOR 1.3, 95% CI 1.0 to 1.6) and increased waist-to-hip ratio (AOR 1.6, 95% CI 1.2 to 2.3). CONCLUSION: This nationally representative study shows that the prevalence of CKD in the adult population of Nepal is substantial, and it is independently associated with several cardiometabolic traits. These findings warrant longitudinal studies to identify the causes of CKD in Nepal and effective strategies to prevent it

MAK-4 and -5 supplemented diet inhibits liver carcinogenesis in mice

<p>Abstract</p> <p>Background</p> <p>Maharishi Amrit Kalash (MAK) is an herbal formulation composed of two herbal mixtures, MAK-4 and MAK-5. These preparations are part of a natural health care system from India, known as Maharishi Ayur-Veda. MAK-4 and MAK-5 are each composed of different herbs and are said to have maximum benefit when used in combination. This investigation evaluated the cancer inhibiting effects of MAK-4 and MAK-5, <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p><it>In vitro </it>assays: Aqueous extracts of MAK-4 and MAK-5 were tested for effects on <it>ras </it>induced cell transformation in the Rat 6 cell line assessed by focus formation assay. <it>In vivo </it>assays: Urethane-treated mice were put on a standard pellet diet or a diet supplemented with MAK-4, MAK-5 or both. At 36 weeks, livers were examined for tumors, sera for oxygen radical absorbance capacity (ORAC), and liver homogenates for enzyme activities of glutathione peroxidase (GPX), glutathione-S-transferase (GST), and NAD(P)H: quinone reductase (QR). Liver fragments of MAK-fed mice were analyzed for connexin (cx) protein expression.</p> <p>Results</p> <p>MAK-5 and a combination of MAK-5 plus MAK-4, inhibited <it>ras</it>-induced cell transformation. In MAK-4, MAK-5 and MAK4+5-treated mice we observed a 35%, 27% and 46% reduction in the development of urethane-induced liver nodules respectively. MAK-4 and MAK4+5-treated mice had a significantly higher ORAC value (<it>P </it>< 0.05) compared to controls (200.2 ± 33.7 and 191.6 ± 32.2 <it>vs. </it>152.2 ± 15.7 ORAC units, respectively). The urethane-treated MAK-4, MAK-5 and MAK4+5-fed mice had significantly higher activities of liver cytosolic enzymes compared to the urethane-treated controls and to untreated mice: GPX(0.23 ± 0.08, 0.21 ± 0.05, 0.25 ± 0.04, 0.20 ± 0.05, 0.21 ± 0.03 U/mg protein, respectively), GST (2.0 ± 0.4, 2.0 ± 0.6, 2.1 ± 0.3, 1.7 ± 0.2, 1.7 ± 0.2 U/mg protein, respectively) and QR (0.13 ± 0.02, 0.12 ± 0.06, 0.15 ± 0.03, 0.1 ± 0.04, 0.11 ± 0.03 U/mg protein, respectively). Livers of MAK-treated mice showed a time-dependent increased expression of cx32.</p> <p>Conclusion</p> <p>Our results show that a MAK-supplemented diet inhibits liver carcinogenesis in urethane-treated mice. The prevention of excessive oxidative damage and the up-regulation of connexin expression are two of the possible effects of these products.</p