BackgroundIsolated Coronary artery ectasia (CAE) is considered an uncommon angiographic finding with varying patterns of presentation and carries significant morbidity burden to the patient. Our objective was to evaluate the prevalence of this condition, to analyse its clinical, angiographic, and follow up characteristics.Patients and methodsCoronary angiography was performed in 4950 patients from January 2009 to August 2014. The epidemiological, clinical, angiographic, and follow up characteristics of 52 patients with isolated CAE were examined.ResultsOf the 4950 angiograms analysed, isolated CAE was found in 52 patients, a prevalence of 1.05 %. The mean age of patients was 53.4 years. A predominance of the male sex was observed (71.1%). Angina on exertion was the most common presenting symptom (61.5%). Single vessel was involved in 61.5%. Left anterior descending artery was the most commonly involved vessel followed by right coronary artery, left circumflex and left main coronary artery. Type IV CAE as per Markis classification was the most common involvement. The median follow-up was 28 ± 20 months, during which 10 patients (19.2%) had recurrent chest pain, and four patients were re-hospitalised, three for unstable angina, one for myocardial infarction.ConclusionThe prevalence of isolated coronary ectasia was 1.05%. The majority of patients had single vessel involvement, and left anterior descending branch was the most common involved vessel. This condition may not be considered completely benign, as it is associated with atherosclerotic risk factors and occurrence of coronary events including angina and myocardial infarction.

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l-Asparaginases belong to a family of amidohydrolases that catalyze the conversion of l-asparagine into l-aspartic acid and ammonia. Although bacterial l-asparaginases have been used extensively as anti-leukemic agents, their possible role as potential drug targets for pathogenic organisms has not been explored. The presence of genes coding for putative l-asparaginase enzymes in the Leishmania donovani genome hinted towards the specific role of these enzymes in extending survival benefit to the organism. To investigate whether this enzyme can serve as a potential drug target against the Leishmania pathogen, we obtained structural models of one of the putative Leishmania l-asparaginase I (LdAI). Using an integrated computational approach involving molecular modelling, docking and molecular dynamics simulations, we found crucial differences between catalytic residues of LdAI as compared to bacterial l-asparaginases. The deviation from the canonical acid-base pair at triad I, along with the structural reorganization of a β-hairpin loop in the presence of a substrate, indicated an altogether new mechanism of action of the LdAI enzyme. Moreover, the finding of compositional and functional differences between LdAI and human asparaginase was used as a criterion to identify specific small molecule inhibitors. Through virtual screening of a library of 11 438 compounds, we report five compounds that showed favorable interactions with the active pocket of LdAI, without adversely affecting human asparaginase. One of these compounds when tested on cultured Leishmania promastigotes displayed a promising leishmanicidal effect. Overall, our work not only provides first hand mechanistic insights of LdAI but also proposes five strongly active compounds which may prove as effective anti-leishmaniasis molecules.

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BackgroundPrevious studies have shown that microalbuminuria (MAU) is an independent risk factor for cardiovascular diseases in diabetics, hypertensive patients and in the general population. However, the correlation of MAU with the severity of coronary artery disease (CAD) in non-diabetic patients has not been addressed in detail. This study aimed to investigate the relationship between MAU and severity of angiographically confirmed CAD in non-diabetic patients.MethodsThis was a cross-sectional study, which included 90 non-diabetic patients with documented CAD by coronary angiography. The ratio of urine albumin to creatinine was used to define MAU and severity of CAD was estimated using SYNTAX score. Patients were divided into two groups: group I that included patients without MAU and group II that included patients with MAU.ResultsOut of 90 non-diabetic CAD patients, 62 (68.9%) were in group I (MAU negative) and 28 (31.1%) were in group II (MAU positive). There was statistically significant difference in the median SYNTAX score between the groups (21 vs. 28, P < 0.001). The prevalences of double vessel CAD and triple vessel CAD were significantly higher in MAU positive group. There was a strong relationship between the presence of MAU and the extent and complexity of CAD (r = 0.094; P < 0.001).ConclusionThus, we conclude that patients with MAU have more severe angiographically detected CAD than those without MAU, and MAU exhibits a significant association with the presence and severity of CAD.

Histone post-translational modifications (PTMs) such as acetylation and methylation are known to affect chromatin higher order structures. Primary targets of these modifications include basic residues present at N-terminus tail region of core histones. Four histone acetyltransferase (HAT) genes have been identified in trypanosomatids. HAT1, HAT3 and HAT4 of Leishmania donovani have been partially characterized. However, there is no report about HAT2 of Leishmania donovani. Lysine residues present on the N-terminal tail of Leishmania donovani histone H4 are conserved in other trypanosomatids and humans. PTMs of lysines modulate various functions at chromatin level. The four histone acetyltransferases encoded in Leishmania genome were over-expressed to analyse their functional activity. All four HATs were found actively acetylating core histones H3/H4. Similar to L. donovani HAT3 and HAT4, HAT2 was found to be a member of MYST family protein and have SAS2 type domain. Over-expression of HAT2 significantly increases acetylation of H4K4. To analyse the effect of HAT2 over-expression on chromatin accessibility, micrococcal nuclease digestion assay was performed. MNase digestion resulted in a higher proportion of the mononucleosomes and dinucleosomes in HAT2 over-expressing cells as compared to WT L. donovani cells. Acetylation of lysine-4 neutralizes the amino terminal region of histone H4. This weakens its interaction with neighbouring nucleosomes and the linker DNA. HAT2 over-expression in L. donovani resulted in highly accessible chromatin suggesting chromatin decondensation. HAT2 may have an important role to play in global regulation of transcription in L. donovani. Better understanding of these epigenetic determinants of parasite would help in designing novel therapeutic strategies.

A prototype DNA assembled quantum dot-photosensitizer (PS) nanodevice for targeted delivery of PS drug.

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