Angiotensin II receptor antagonists in acute coronary syndromes.

Background: It is well known that inappropriate or exaggerated activity of the renin-angiotensin system might contribute to the development of systemic hypertension with consequent organ injury and associated increased risk of acute cardiovascular (CV) diseases. This review will discuss evidence form basic research and clinical studies, investigating the efficacy of angiotensin II receptor blockers (ARBs) in the management of acute coronary syndromes (ACS).

Materials And Methods: This narrative review is based on the material found on MEDLINE and PubMed up to June 2013.

A look at the upper heart chamber: the left atrium in chronic kidney disease.

Altered left ventricular (LV) mass and function are classical hallmarks of cardiomyopathy in chronic kidney disease (CKD). The left atrium (LA), a heart chamber exquisitely sensitive to volume overload and diastolic function, is an independent predictor of death and adverse cardiovascular (CV) events in high-risk patients such as those with hypertension and/or with heart failure. In this review we focus on the relationship of LA size with LV diastolic function, and the association between LA enlargement and CV and renal outcomes in patients with CKD, including patients with end-stage renal disease.

Androgen receptor activity is affected by both nuclear matrix localization and the phosphorylation status of the heterogeneous nuclear ribonucleoprotein K in anti-androgen-treated LNCaP cells.

The androgen receptor (AR) plays a central role in the development and progression of prostate cancer (PCa) and anti-androgen therapy is a standard treatment. Unfortunately, after a few years, the majority of patients progress, developing androgen-independent PCa. AR-driven gene transcription recruits a large number of co-activator/co-repressor complexes; among these, the heterogeneous nuclear ribonucleoprotein K (hnRNP K) directly interacts with and regulates the AR translational apparatus.

The treatment of melanoma brain metastases before the advent of targeted therapies: associations between therapeutic choice, clinical symptoms and outcome with survival.

The management of melanoma brain metastases (MBM) includes different therapeutic modalities, such as surgery, radiotherapy and chemotherapy. Despite the choice of treatments, survival remains poor, exceeding 1 year only in patients with solitary metastases and absence of extracranial disease. A total of 115 consecutive MBM patients observed between 1994 and 2010 were included in an historical cohort study.

Two ABCB4 point mutations of strategic NBD-motifs do not prevent protein targeting to the plasma membrane but promote MDR3 dysfunction.

The ABCB4 gene encodes for MDR3, a protein that translocates phosphatidylcholine from the inner to the outer leaflet of the hepatocanalicular membrane; its deficiency favors the formation of 'toxic bile'. Several forms of hepatobiliary diseases have been associated with ABCB4 mutations, but the detrimental effects of most mutations on the encoded protein needs to be clarified. Among subjects with cholangiopathies who were screened for mutations in ABCB4 by direct sequencing, we identified the new mutation p.

The effect of an artificial tear combining hyaluronic acid and tamarind seeds polysaccharide in patients with moderate dry eye syndrome: a new treatment for dry eye.

Purpose: Synergistic interactions between hyaluronic acid (HA) and tamarind seed polysaccharide (TS-polysaccharide) have been demonstrated by means of nuclear magnetic resonance spectroscopy. This study was designed to investigate the potential clinical benefit of a combination of HA and TS-polysaccharide in managing dry eye disease (DED).

Methods: A total of 49 subjects with moderate DED, confirmed by Ocular Surface Disease Index (OSDI) questionnaire score between 10 and 25, tear break-up time (BUT) <10 seconds, or Schirmer I test <5.

Management of early stage chronic myeloid leukemia: state-of-the-art approach and future perspectives.

Tyrosin kinase inhibitors (TKI), have dramatically changed the natural history of chronic myeloid leukemia (CML) leading to an impressive increase in overall survival rates and allowing many CML patients to achieve a close-to-normal life expectancy. Unfortunately, there is growing evidence that these drugs are not curative, about 30-35% of the patients who receive imatinib become resistant or discontinue the drug because of side effects; moreover, 15% of all patients become resistant to all TKIs, a condition which represents the biggest challenge in CML treatment. Recent progresses in CML stem cell biology have identified new agents and therapeutic strategies that can be used to target the CML stem cell compartment.

The HUMNxl scoring criteria for different cell types and nuclear anomalies in the buccal micronucleus cytome assay - an update and expanded photogallery.

The buccal micronucleus cytome assay is a minimally invasive cytological and interphase cytogenetic technique for measuring DNA damage and cell death biomarkers in the oral epithelium. In this report we provide an updated and more comprehensive version of the cellular and nuclear scoring criteria used in the assay accompanied with a photogallery of the various cell types and nuclear anomalies. These detailed scoring criteria complement previous published protocols of this assay and form the basis for guiding intra- and inter-laboratory slide scoring comparisons.

Serum uric acid and blood pressure in children at cardiovascular risk.

Objectives: Hyperuricemia has been shown to be a strong correlate of hypertension in children. However, the complex interaction between serum uric acid (UA), systemic blood pressure (BP), and possibly confounding factors has been elucidated only in part.

Methods: We evaluated office BP as well as clinical and biohumoral parameters in a cross-sectional cohort of 501 children (280 boys and 221 girls) aged between 6 and 18 years (mean = 10.

Blood pressure variability and multiple organ damage in primary hypertension.

Organ damage (OD) is an indicator of increased cardiovascular risk. Blood pressure variability (BPV) is related to greater incidence of events, regardless of the severity of hypertension. We investigated the relationship between ambulatory blood pressure monitoring (ABPM)-derived indices of BPV and the presence of multiple OD in primary hypertension (PH).

Free drugs in clinical trials and their potential cost saving impact on the National Health Service: a retrospective cost analysis in Italy.

Background: The cost of new anti-cancer drugs has dramatically increased in recent years, and countermeasures are required in order to limit pharmaceutical expenses. Sponsored clinical trials that provide drugs free of charge may be a useful tool in order to reduce drug costs. The aim of this analysis is to evaluate the effect of clinical trials on pharmaceutical expenditure savings.

Treatment of metastatic uveal melanoma with intravenous fotemustine.

The purpose of the present study was to retrospectively evaluate the safety and activity of intravenous fotemustine in patients with metastatic uveal melanoma. We report on a series of 25 consecutive patients diagnosed with metastatic uveal melanoma. Fotemustine was administered intravenously as a first-line treatment to all patients.

PRIMA-1 induces autophagy in cancer cells carrying mutant or wild type p53.

PRIMA-1 is a chemical compound identified as a growth suppressor of tumor cells expressing mutant p53. We previously found that in the MDA-MB-231 cell line expressing high level of the mutant p53-R280K protein, PRIMA-1 induced p53 ubiquitination and degradation associated to cell death. In this study, we investigated the ability of PRIMA-1 to induce autophagy in cancer cells.

Development of therapeutics for high grade gliomas using orthotopic rodent models.

To study novel treatments for high grade gliomas (WHO grade III and IV) we need animal models of those disorders. Orthotopic tumors in mouse or rats seem at present the most reliable in vivo glioma model in order to develop specific therapies. The orthotopic tumor characteristics should yet closely mimic the human glioma features (in particular infiltrating growth and neovascularization).

Structure and evolution of human sirtuins.

Sirtuins form a large homology family of enzymes found almost ubiquitously in living organisms and involved in numerous biological processes. The human genome encodes for seven paralog sirtuins, identified as SIRT1-7. In this review the major structural features of the sirtuin catalytic domain are illustrated and the relevant sources of biological information indicated.

Left-ventricular hypertrophy and renal outcome in hypertensive patients in primary-care.

Background: Subclinical cardiac damage has recently emerged as a potential predictor of adverse renal outcome. We therefore retrospectively evaluated the effect of left-ventricular hypertrophy (LVH), diagnosed electrocardiographically, on the renal outcome of hypertensive patients managed in primary care.

Methods: From a historical cohort of 39,525 hypertensive individuals evaluated in 2005, we retrieved 5-year data of the 18,510 surviving subjects for whom renal follow-up was available.

Effects of ACE inhibitors on long-term outcome of renal transplant recipients: a randomized controlled trial.

Background: Available data on the role of renin-angiotensin system blockade in renal transplantation are inconclusive. Herein, we report the long-term results of a randomized controlled trial planned to evaluate the impact of angiotensin-converting enzyme inhibitors (ACE-i) on the cardiovascular outcome of renal transplant recipients (RTRs) receiving calcineurin inhibitors, steroids, and mycophenolate mofetil.

Methods: Thirty-six RTRs were allocated to receive ACE-i and 34 served as controls.

PLI: a web-based tool for the comparison of protein-ligand interactions observed on PDB structures.

Motivation: A large fraction of the entries contained in the Protein Data Bank describe proteins in complex with low molecular weight molecules such as physiological compounds or synthetic drugs. In many cases, the same molecule is found in distinct protein-ligand complexes. There is an increasing interest in Medicinal Chemistry in comparing protein binding sites to get insight on interactions that modulate the binding specificity, as this structural information can be correlated with other experimental data of biochemical or physiological nature and may help in rational drug design.

Socio-economic inequalities: a review of methodological issues and the relationships with cancer survival.

During the past few decades, many studies on socio-economic factors and health outcomes have been developed using various methodologies with differing approaches. A bibliographic research in MEDLINE/PubMed and SCOPUS was carried out for the period 2000-2011 to describe the influence of socio-economic status (SES) on cancer survival, in particular with reference to the outcome of European research results and the results of some cases of other Western studies. This review is divided into two sections: the first describing the different approaches of the study on individuals and populations of the concept of "social class" as well as methods used to measure the association between deprivation and health (i.

Hematopoietic stem cell transplantation for systemic lupus erythematosus.

Two streams of research are at the origin of the utilization of hematopoietic stem cell transplantation (HSCT) for severe autoimmune diseases (SADs). The allogeneic approach came from experimental studies on lupus mice, besides clinical results in coincidental diseases. The autologous procedure was encouraged by researches on experimental neurological and rheumatic disorders.

Therapeutic implications of adding the psychotropic drug escitalopram in the treatment of patients suffering from moderate-severe psoriasis and psychiatric comorbidity: a retrospective study.

Background: It is known that stress and/or psychiatric diseases can play an important role in determining psoriasis, including the well-known negative somato-psychiatric rebound that comes with the disease.

Methods: Samples of 38 subjects suffering from both moderate-severe psoriasis treated with anti-TNFα, and depressive and/or anxious mood disorders were studied. Part of them were additionally treated with escitalopram, whereas the other group only consulted to a dermatological and psychiatric follow-up.

Use of SERTS (Socio-Economic, health Resources and Technologic Supplies) models to estimate cancer survival at provincial geographical level.

Aim: The main aim of this work is to compute expected cancer survival for Italian provinces by Socio-Economic and health Resources and Technologic Supplies (SERTS) models, based on demographic, socioeconomic variables and information describing the health care system (SEH).

Methods: Five-year age-standardised relative survival rates by gender for 11 cancer sites and all cancers combined of patients diagnosed in 1995-1999, were obtained from the Italian Association of Cancer Registries (CRs) database. The SEH variables describe at provincial level macro-economy, demography, labour market, health resources in 1995-2005.

Identification of a novel set of genes reflecting different in vivo invasive patterns of human GBM cells.

Background: Most patients affected by Glioblastoma multiforme (GBM, grade IV glioma) experience a recurrence of the disease because of the spreading of tumor cells beyond surgical boundaries. Unveiling mechanisms causing this process is a logic goal to impair the killing capacity of GBM cells by molecular targeting.We noticed that our long-term GBM cultures, established from different patients, may display two categories/types of growth behavior in an orthotopic xenograft model: expansion of the tumor mass and formation of tumor branches/nodules (nodular like, NL-type) or highly diffuse single tumor cell infiltration (HD-type).