Role of the endothelium in modulating neointimal formation: vasculoprotective approaches to attenuate restenosis after percutaneous coronary interventions

Restenosis at the site of an endoluminal procedure remains a significant problem in the practice of interventional cardiology. We present current data on intimal hyperplasia, which identify the major role of endothelial cells (ECs) in the development of restenosis. Considering endothelial denudation as one of the most important mechanisms contributing to restenosis, we focus more attention on methods of accelerating restoration of endothelial continuity. Prevention of restenosis may be achieved by promoting endothelial regeneration through the use of growth factors, EC seeding, vessel reconstruction with autologous EC/fibrin matrix, and the use of estrogen-loaded stents and stents designed to capture progenitor ECs.     

Interaction between inflammation and thrombosis in acute coronary syndrome

BACKGROUND: Inflammation and thrombosis are important in the pathogenesis of acute coronary syndrome (ACS). Cytokines [interleukin-1beta (IL-1beta) and interleukin-6 (IL-6)] are inflammation markers which play a major role in the development of coronary heart disease. Experimental data documented that an increase of cytokine and von Willebrand factor (vWF) levels in unstable angina (UA) and non-Q wave myocardial infarction (MI) predicts an adverse outcome. AIM: To examine the correlation between the IL-1beta, IL-6 and vWF levels in patients with ACS. METHODS: We examined 92 patients (74 men, 18 women, aged from 43 to 76) divided into 3 groups. The first group included 43 patients with a Q-wave MI, the second group - 33 with a non-Q-wave MI, and the third group - 18 with UA. All patients were given 125-250 mg of aspirin and bolus of 5.000 units of unfractionated heparin, followed by heparin infusion titrated to maintain an activated partial thromboplastin time of 50-75 s. Patients with a Q-wave MI received thrombolytic therapy 1.5 million units of streptokinase. The IL-1b, IL-6 and vWF levels was measured on admission and 7 as well as 21 days later. Fifteen patients with stable angina served as the control group. RESULTS: The levels of cytokines and vWF were significantly higher in patients with ACS than in control subjects. A significant correlation between vWF and IL-6 levels, measured on admission and 7 days later, was found in patients with UA (r=+0.74 and r=+0.55, respectively). Also, a significant correlation was found between vWF and IL-1beta levels measured on admission in patients with either Q-wave or non-Q wave MI (r=+0.7 and r=+0.61, respectively). CONCLUSIONS: Our data suggest that there is a positive correlation between inflammation and thrombosis markers in patients with ACS.     

Effectiveness of inhaled hypertonic saline application for sputum induction to improve Mycobacterium tuberculosis identification in patients with pulmonary tuberculosis

Wiener Medizinische Wochenschrift - This study assessed the effectiveness and diagnostic significance of hypertonic saline sputum induction for improving Mycobacterium tuberculosis (MTB) detection....     

Modelling and Performance Analysis of MgB2 and Hybrid Magnetic Shields

Superconductors are strategic materials for the fabrication of magnetic shields, and within this class, MgB2 has been proven to be a very promising option. However, a successful approach to produce devices with high shielding ability also requires the availability of suitable simulation tools guiding the optimization process. In this paper, we report on a 3D numerical model based on a vector potential (A)-formulation, exploited to investigate the properties of superconducting (SC) shielding structures with cylindrical symmetry and an aspect ratio of height to diameter approaching one. To this aim, we first explored the viability of this model by solving a benchmark problem and comparing the computation outputs with those obtained with the most used approach based on the H-formulation. This comparison evidenced the full agreement of the computation outcomes as well as the much better performance of the model based on the A-formulation in terms of computation time. Relying on this result, the latter model was exploited to predict the shielding properties of open and single capped MgB2 tubes with and without the superimposition of a ferromagnetic (FM) shield. This investigation highlighted that the addition of the FM shell is very efficient in increasing the shielding factors of the SC screen when the applied magnetic field is tilted with respect to the shield axis. This effect is already significant at low tilt angles and allows compensating the strong decrease in the shielding ability that affects the short tubular SC screens when the external field is applied out of their axis.     

Low prevalence of BRAF mutations in radiation-induced thyroid tumors in contrast to sporadic papillary carcinomas

Point mutations of the BRAF gene have been recently described with high prevalence in papillary thyroid carcinomas. However, this molecular alteration has not been studied in radiation-induced thyroid tumors. We analyzed the prevalence of BRAF point mutations and RET/PTC rearrangements in 55 post-Chernobyl papillary carcinomas, compared with 82 sporadic papillary carcinomas. Radiation-induced tumors demonstrated a low prevalence (4%) of BRAF point mutations and high prevalence (58%) of RET/PTC rearrangements. Sporadic papillary carcinomas revealed a clearly distinct pattern, with 37% of tumors harboring BRAF mutations and 20% RET/PTC rearrangements. These results demonstrate a significant difference in the molecular genetic profile of sporadic and radiation-induced thyroid tumors.     

Poly(ADP-ribosyl)ation enhancement in brain cell nuclei is associated with diabetic neuropathy

The study has been undertaken to evaluate the effect of streptozotocin (STZ)-induced diabetes on rat brain poly(ADP-ribose)polymerase (Parp) activity and assess whether and how a Parp inhibitor, nicotinamide (NAm), may potentially regulate the diabetes-induced changes. Experiments were carried out after 4 weeks of diabetes duration in rats treated with or without NAm (100 or 200 mg kg(-1) day(-1), injected intraperitonally for 2 weeks). Assays were performed in purified brain cell nuclei to determine Parp activity by incorporation of radiolabeled ADP-ribose moieties from nicotinamide adenine dinucleotide (NAD+) into nuclear proteins. NAD+ and ATP levels were measured by enzymatic procedures. DNA damage was detected spectrophotometrically. RESULTS: Parp activity but not NAD-glycohydrolase (NADase) was stimulated by 21% in diabetes vs. control while lowering effects of diabetes on NAD+ and ATP levels were observed. Increase in Parp activity was accompanied by accumulation of malondialdehyde (MDA) and increase in DNA breakage. Treatment with either 100 or 200 mg/kg NAm dose diminished both DNA damage and Parp activity and partially restored the NAD+ and ATP contents, which is probably associated with direct competitive inhibition of Parp as well as with NAm's ability to block diabetes induced oxidative stress. CONCLUSION: Poly(ADP-ribosyl)polymerase overactivation is involved in the development of brain dysfunction in diabetic neuropathy. The mechanism of brain disorders seems to be at least partially connected with a decrease in cellular content and altered subcellular distribution of Parp substrate, NAD+, which, in turn, results in a reduction of ATP level that leads to a total failure of oxidative metabolism. NAm in both doses is effective for the inhibition of poly(ADP-ribosyl)ation.     

Systematics meanders of microsporidia

Meanders of systematics of Microsporidia. Taxonomical questions of Microsporidia, its systematic position and evolutionary relationship with other Eukaryota are discussed. Utilizations of modern methods of investigations of microsporidians cause new taxonomical troubles. At the present time it is difficult to create a clear hypothesis concerning the phylogeny and evolution of Microsporidia. Most likely they are representatives of a new kingdom of Eukaryota. Existing problems will not be dissolved until new detailed data concerning the new and common species are obtained.     

Histopathological features of papillary thyroid carcinomas detected during four screening examinations of a Ukrainian-American cohort

Background:

There are limited data on the histopathology of papillary thyroid carcinomas (PTCs) diagnosed in irradiated populations. We evaluated the associations between iodine-131 dose and the histopathological characteristics of post-Chernobyl PTCs, the changes in these characteristics over time, and their associations with selected somatic mutations.

Methods:

This study included 115 PTCs diagnosed in a Ukrainian-American cohort (n=13 243) during prescreening and four successive thyroid screenings. Of these PTCs, 65 were subjected to somatic mutation profiling. All individuals were <18 years at the time of the Chernobyl accident and had direct thyroid radioactivity measurements. Statistical analyses included multivariate linear and logistic regression.

Results:

We identified a borderline significant linear-quadratic association (P=0.063) between iodine-131 dose and overall tumour invasiveness (presence of extrathyroidal extension, lymphatic/vascular invasion, and regional or distant metastases). Irrespective of dose, tumours with chromosomal rearrangements were more likely to have lymphatic/vascular invasion than tumours without chromosomal rearrangements (P=0.020) or tumours with BRAF or RAS point mutations (P=0.008). Controlling for age, there were significant time trends in decreasing tumour size (P<0.001), the extent of lymphatic/vascular invasion (P=0.005), and overall invasiveness (P=0.026).

Conclusions:

We determined that the invasive properties of PTCs that develop in iodine-131-exposed children may be associated with radiation dose. In addition, based on a subset of cases, tumours with chromosomal rearrangements appear to have a more invasive phenotype. The increase in small, less invasive PTCs over time is a consequence of repeated screening examinations.