Antithrombotics in heart failure

Heart failure is a common clinical condition associated with high morbidity and mortality rate despite significant improvements in pharmacotherapy and implementation of medical procedures. Patients with heart failure are at an increased risk of developing arterial and venous thrombosis, which contribute to the high rate of adverse events and fatal outcomes. Many heart failure patients routinely receive antithrombotic therapy due to the presence of a specific indication for its use, like ischemic heart disease or atrial fibrillation. However, there is no solid evidence to support the routine use of antithrombotic agents in all heart failure patients. This article reviews the evidence for using antithrombotic therapy in heart failure patients.Heart failure (HF) is a complex clinical syndrome caused by a number of different disorders that impair the heart muscle’s ability to maintain adequate blood flow to meet the body''s metabolic needs. Research and advances in managing HF so far have been mainly focused on improving the neurohormonal imbalance and assisting the myocardium to increase the cardiac output with different types of devices. Over the last couple of decades there have been considerable improvements in pharmacotherapy and medical procedures for treating HF, such as the introduction of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta blockers, aldosterone antagonists, I_f channel blocker ivabradine, cardiac resynchronization therapy (CRT), and ventricular assist devices (VADs). However, HF is still a major public health issue associated with increased morbidity and mortality (1). Because of the broad spectrum of its clinical presentations, aging of the population, and different comorbidities and treatment options, HF treatment represents a considerable challenge. Patients with HF are at an increased risk of developing arterial and venous thrombosis, which contribute to the high rate of adverse events and fatal outcomes (2-5). Further research should clarify whether routine use of antithrombotic agents brings clinical benefit to all HF patients.     

New Drugs on the Block—Emerging Treatments for Nonalcoholic Steatohepatitis

Patients with nonalcoholic steatohepatitis (NASH) are at higher risk of progression to advanced stages of fibrosis, cirrhosis, hepatocellular carcinoma and othe...     

Radiological Impact of An Active Quarry in The Papuk Nature Park,Croatia

Papuk Nature Park, unlike most similar parks and preserves in the world, contains active quarries. Quarries dig stone from the ground, creating dust and exposing deeper, potentially more radioactive layers. Since the forest trails in the Park lead right up to the quarries, we believed it was important to determine the radiological impact of the quarries on the Park environment. We measured ambient dose rate equivalent H*(10) and sampled moss at 26 Park locations along two of four quarries, along the road between them, and near Lake Orahovac, a very popular tourist destination close to the quarries. Moss is a standard bioindicator of exposure to heavy metals, including radionuclides. Using-gamma ray spectrometry we determined the activity concentration of ¹³⁷Cs and of representative naturally occurring radionuclides – ²³⁸U, ²²⁶Ra, ²¹⁰Pb, ²³²Th, and ⁴⁰K – in sampled moss. H*(10) at selected locations was similar to the background H*(10) measured continuously all over Croatia. The ranges of measured activity concentrations of ¹³⁷Cs and naturally occurring radionuclides in moss did not differ significantly from other parts of Croatia and nearby countries.Key words: ¹³⁷Cs, ambient dose rate equivalent H*(10), gamma ray spectrometry, moss, naturally occurring radionuclides     

The lack of influence of IVS5-91 G>A polymorphism of the SCN1A gene on efficacy of lamotrigine in patients with focal epilepsy

ABSTRACT

Background: IVS5-91G>A (rs3812718) polymorphism of the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene has been associated with inadequate responsiveness to common antiepileptic drugs which act as sodium channel blockers. This study was performed to investigate the effect of IVS5-91G>A (rs3812718) polymorphism on lamotrigine (LTG) efficacy in a cohort of patients with non-lesional focal epilepsy taking LTG as monotherapy.

Methods: A total of 100 of patients with non-lesional focal epilepsy on LTG monotherapy was included in this prospective interventional study. After reaching a stable dose of LTG patients were followed-up for 12 consecutive months. LTG responsiveness was defined as a 75% or more reduction in seizure frequency on a stable dose of LTG. Genotyping was performed at the end of the study using standard procedures and data were correlated with clinical data.

Results: There were no significant differences in the prevalence of responsiveness to LTG between carriers of different genotypes. Average maintenance LTG doses in the responder group differed by genotype in the order AA>GA>GG, but these differences did not reach statistical significance.

Conclusion: Our data suggest lack of association between SCN1A IVS5-91G>A (rs3812718) polymorphism and response to LTG.     

Frequency of loss of heterozygosity of the NF2 gene in schwannomas from Croatian patients

Aim. To identify gross deletions in the NF2 gene in a panel of schwannomas from Croatian patients in order to establish their frequencies in Croatian population. Methods. Changes of the NF2 gene were tested by polymerase chain reaction/loss of heterozygosity (LOH) using two microsatellite markers, D22S444 and D22S929. Results. The analysis with both markers demonstrated that 43.75% of schwannomas exhibited LOH of the NF2 gene. The D22S444 region exhibited 45.5% of LOHs and the D22S929 region exhibited 14.3% of LOHs. Four LOHs were found in Antoni B, 2 in Antoni A, and 1 in Antoni A and B type tumors. Conclusion. The frequency of changes observed in Croatian patients is broadly similar to that reported in other populations and thus confirms the existing hypothesis regarding the tumorigenesis of schwannomas and contributes to schwannoma genetic profile helping us to better understand its etiology and treatment.     

Sexual dimorphism of the extraorbital lacrimal glands in SF-1 knockout mice

Sexual dimorphism (SD) represents all the differences between males and females of the same species. SD of the murine lacrimal gland and the major effect of testosterone on its formation are well documented. Steroidogenic factor-1 (SF-1, NR5a1) is a nuclear receptor essential for the fetal development of steroid hormones producing organs and SF-1 knockout mice (Sf-1 KO) are therefore born without gonads and adrenal glands. The aim of this study was to investigate whether SD in lacrimal glands is present in the absence of exposure to sex hormones during development. Lacrimal glands from adult Sf-1 KO male and female mice without hormonal exposure, and from males that were treated with testosterone propionate (TP) prior to sacrifice, were examined. After sacrifice, glandular tissue was processed using standard histological procedures. Paraffin sections were analysed by stereology and immunostained against the androgen receptor (AR). Our results showed that there were no statistically significant differences in the mean volumes of acini, connective tissue or ductal system between males, females, and males on TP. The same pertains to the mean length of the ducts in all three groups. In the absence of sex hormones, sex chromosomes proved to be insufficient in inducing sexual dimorphism in LG. However, nuclei of the acinar cells in males on TP were positive for AR, whereas in males without TP no expression of AR was detected. Administration of TP induced the expression of AR in the nuclei of acinar cells of males but did not affect the morphology of LG. We conclude that SD in the lacrimal gland is not present in Sf-1 KO mice and this suggests that sex hormones have a major role in the development of SD in the lacrimal gland.     

Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A

Classical Hutchinson-Gilford progeria syndrome (HGPS) is caused by LMNA mutations that generate an alternatively spliced form of lamin A, termed progerin. HGPS patients present in early childhood with atherosclerosis and striking features of accelerated aging. We report on two pedigrees of adult-onset coronary artery disease with progeroid features, who were referred to our International Registry of Werner Syndrome (WS) because of clinical features consistent with the diagnosis. No mutations were identified in the WRN gene that is responsible for WS, among these patients. Instead, we found two novel heterozygous mutations at the junction of exon 10 and intron 11 of the LMNA gene. These mutations resulted in the production of progerin at a level substantially lower than that of HGPS. Our findings indicate that LMNA mutations may result in coronary artery disease presenting in the fourth to sixth decades along with short stature and a progeroid appearance resembling WS. The absence of early-onset cataracts in this setting should suggest the diagnosis of progeroid laminopathy. This study illustrates the evolving genotype-phenotype relationship between the amount of progerin produced and the age of onset among the spectrum of restrictive dermopathy, HGPS, and atypical forms of WS.