Isolated coronary artery ectasia: Clinical, angiographic, and follow up characteristics

Background: Isolated 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 methods: Coronary 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. Results: Of 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. Conclusion: The 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

Idiopathic dilatation of pulmonary artery: A review

The diagnosis of idiopathic dilatation of pulmonary artery is challenging because its clinical recognition is difficult and various other causes of dilated pulmonary artery need to be excluded. The clinical findings mimic various common cardiac disorders and both invasive and non-invasive investigations should be done to arrive at the diagnosis. It is a known clinical entity but etiology and pathophysiology are largely unknown. The current echocardiographic and catheterization based diagnostic criteria, may not be satisfied completely in a particular patient and need to be revisited in view of newer imaging modalities. There is paucity of information about the natural history of the disease with attendant lack of clarity in treatment guidelines. Certain cases may progress to huge dilatation and consequent serious implications. It is a rare disease and is the diagnosis of exclusion

An assessment of comprehensive knowledge of HIV/AIDS among slum and non-slum populations in Delhi, India

In order to design appropriate HIV prevention programs, it is important to examine the perception and knowledge of HIV/AIDS and methods of prevention. This article explores comprehensive knowledge of HIV/AIDS prevention methods among women and men in slum and non-slum areas in the National Capital Territory of Delhi, India. Data were drawn from the National Family Health Survey, 2005–06 (NFHS-3). The sample included 3096 women aged 15–49 years and 1321 men aged 15–54 years. Pearson Chi-square test and logistic regression analyses were conducted to examine the association between the study variables and the background characteristics of the slum and non-slum populations. Comprehensive knowledge of HIV/AIDS prevention methods was significantly lower among women and men in slum areas as compared with non-slum areas. Compared to men, women had less comprehensive knowledge of HIV/AIDS prevention methods in slum and non-slum areas, even after controlling for various demographic and socio-economic and exposure variables. Interventions are needed to build knowledge of HIV/AIDS transmission and prevention methods through mass media campaigns, and information, education and communication programs (IEC) on HIV/AIDS in slum areas

Oxidative Stress-Mediated Overexpression of Uracil DNA Glycosylase in Leishmania donovani

Leishmania donovani is an intracellular protozoan parasite that causes endemic tropical disease visceral leishmaniasis (VL). Present drugs used against this fatal disease are facing resistance and toxicity issues. Survival of leishmania inside the host cells depends on the parasite’s capacity to cope up with highly oxidative environment. Base excision repair (BER) pathway in L. donovani remains unexplored. We studied uracil DNA glycosylase (UNG), the key enzyme involved in BER pathway, and found that the glycosylase activity of recombinant LdUNG (Leishmania donovani UNG) expressed in E. coli is in sync with the activity of the parasite lysate under different reaction conditions. Overexpression of UNG in the parasite enhances its tolerance towards various agents which produce reactive oxygen species (ROS) and shows a higher infectivity in macrophages. Surprisingly, exposure of parasite to amphotericin B and sodium antimony gluconate upregulates the expression of UNG. Further, we found that the drug resistant parasites isolated from VL patients show higher expression of UNG. Mechanisms of action of some currently used drugs include accumulation of ROS. Our findings strongly suggest that targeting LdUNG would be an attractive therapeutic strategy as well as potential measure to tackle the problem of drug resistance in the treatment of leishmaniasis

HAT2 over-expression and activity analysis.

<p>(2A) RE double digestion of HAT2 cloned in pLPneo2. Clone was digested with HindIII and XhoI. Two fragments (~1800 base pairs for HAT2 and ~5500 base pairs for vector pLPneo2) were resolved in 1% agarose gel. (2B) WT and HAT2 over-expressing <i>L</i>. <i>donovani</i> cells were counted every eight hours for seven days and plotted. P <0.0001 was observed in two-way analysis of variance showing statistical significance. (2C) Relative histone acetylation activity assay for <i>L</i>. <i>donovani</i> cells over-expressing HAT1, HAT2, HAT3 and HAT4. The activities were compared to WT cells and vector (pLPneo2) alone transfected cells. Nuclear extract supplied with kit was taken as experimental control. Total histone acetylation was measured at 2 hours 30 minutes and 3 hours after start of reaction and relative activities were calculated per minute and per gram of total cell extract. The data shown represent average of three independent experiments. The p values < 0.0001 compared with control values is shown as ***.</p

Acetylation of Histones H3 and H4 in over-expressing <i>Leishmania donovani</i>.

<p>(3A) Western blot analysis of HAT2 over-expressing <i>L</i>. <i>donovani</i> (Lane 3) using Anti-acetyl-Histone H4 (Millipore, Cat. 06–866) antibody. WT (Lane 1) and vector (pLPneo2) transfected <i>L</i>. <i>donovani</i> (Lane 2) were used as controls. M indicates molecular weight marker. For nuclear loading control, blot was reprobed with anti H3 antibody. (3B) H4K4 acetylation assay using histones isolated from HATs over-expressing cells by colorimetric method. Histones of WT cells and pLPneo2 transfected cells were used as control. Relative levels of acetylation of H4K4 are shown in percentage assuming that of WT cells as 100%. The p values < 0.0001 compared with WT cells are shown as ***. (3C) Total histone H3 acetylation assay by fluorimetric method for HATs over-expressing cells. Histones isolated from WT cells and vector (pLPneo2) only transfected cell were taken as controls. H3 acetylation was presented in percentage considering 100% for WT cells. *** represents p values < 0.0001 compared to WT cells.</p

Sequence analysis of Histone H4 and HAT2 of <i>L</i>. <i>donovani</i>.

<p>(1A) Comparison of N-terminus region of histone H4 of <i>L</i>. <i>donovani</i> (LdH4) with that of <i>L</i>. <i>infantum</i> (LiH4), <i>L</i>. <i>major</i> (LmH4), <i>L</i>. <i>mexicana</i> (LmxH4), <i>Trypanosoma brucei</i> (TbH4), <i>T</i>. <i>cruzi</i> (TcH4) and human (HuH4). Boxes represent conserved lysine residues. The arrow represents K16 of human histone H4 which is replaced by arginine (R14) in <i>L</i>. <i>donovani</i>. (1B) Zinc finger motif present in the sequence of HAT2 formed by two cysteine and two histidine residues (C₂H₂ type).</p

In-vitro anti-lithiatic activity study of Meyna laxiflora seeds and Tectona grandis bark

This study involves the evaluation of Meyna laxiflora seeds and Tectona grandis bark for antiurolithatic activity. Homogeneous precipitation method was used for In-vitro anti-lithiatic activity on generated calcium oxalate crystals. Extracts were compared with synthetic drug Spironolactone, polyherbal formulation Cystone, other extracts and furosemide. Extracts like aqueous extract, pet ether extract, chloroform extract, methanol extract and aqueous extract were used for study at different concentrations

HAT2 mediates histone H4K4 acetylation and affects micrococcal nuclease sensitivity of chromatin in <i>Leishmania donovani</i>

<div><p>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 <i>Leishmania donovani</i> have been partially characterized. However, there is no report about HAT2 of <i>Leishmania donovani</i>. Lysine residues present on the N-terminal tail of <i>Leishmania donovani</i> 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 <i>L</i>. <i>donovani</i> 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 <i>L</i>. <i>donovani</i> 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 <i>L</i>. <i>donovani</i> resulted in highly accessible chromatin suggesting chromatin decondensation. HAT2 may have an important role to play in global regulation of transcription in <i>L</i>. <i>donovani</i>. Better understanding of these epigenetic determinants of parasite would help in designing novel therapeutic strategies.</p></div

Religionens varp och trasor

En festskrift till Åke Sande