Use of a physiologically based pharmacokinetic model to simulate drug-drug interactions between antineoplastic and antiretroviral drugs.

Background: Co-administration of antineoplastics with ART is challenging due to potential drug-drug interactions (DDIs). However, trials specifically assessing such DDIs are lacking. Our objective was to simulate DDIs between the antineoplastics erlotinib and gefitinib with key antiretroviral drugs and to predict dose adjustments using a physiologically based pharmacokinetic (PBPK) model.

Impact of Chiral Bioanalytical Methods on the Bioequivalence of Ibuprofen Products Containing Ibuprofen Lysinate and Ibuprofen Base.

The purpose was to assess the impact of the use of a chiral bioanalytical method on the conclusions of a bioequivalence study that compared two ibuprofen suspensions with different rates of absorption. A comparison of the conclusion of bioequivalence between a chiral method and an achiral approach was made. Plasma concentrations of R-ibuprofen and S-ibuprofen were determined using a chiral bioanalytical method; bioequivalence was tested for R-ibuprofen and for S-ibuprofen separately and for the sum of both enantiomers as an approach for an achiral bioanalytical method.

Genome-wide association analysis of self-reported events in 6135 individuals and 252 827 controls identifies 8 loci associated with thrombosis.

Thrombotic diseases are among the leading causes of morbidity and mortality in the world. To add insights into the genetic regulation of thrombotic disease, we conducted a genome-wide association study (GWAS) of 6135 self-reported blood clots events and 252 827 controls of European ancestry belonging to the 23andMe cohort of research participants. Eight loci exceeded genome-wide significance.

Beliefs, Barriers, and Preferences of European Overweight Women to Adopt a Healthier Lifestyle in Pregnancy to Minimize Risk of Developing Gestational Diabetes Mellitus: An Explorative Study.

Introduction: We explored beliefs, perceived barriers, and preferences regarding lifestyle changes among overweight European pregnant women to help inform the development of future lifestyle interventions in the prevention of gestational diabetes mellitus.

Methods: An explorative mixed methods, two-staged study was conducted to gather information from pregnant European women (BMI ≥ 25 kg/m2). In three European countries 21 interviews were conducted, followed by 71 questionnaires in six other European countries.

Inducible and Acquired Clarithromycin Resistance in the Mycobacterium abscessus Complex.

Purpose: Clarithromycin was considered the cornerstone for the treatment of Mycobacterium abscessus complex infections. Genetic resistance mechanisms have been described and many experts propose amikacin as an alternative. Nevertheless, clarithromycin has several advantages; therefore, it is necessary to identify the non-functional erm(41) allele to determine the most suitable treatment.

Quantification of In Vitro Macrophage Cholesterol Efflux and In Vivo Macrophage-Specific Reverse Cholesterol Transport.

Promotion of reverse cholesterol transport (RCT) is thought to be a major HDL-mediated mechanism for protecting against atherosclerosis. Preclinical studies support the concept that increasing cholesterol efflux from macrophages may confer atheroprotective benefits independently of the plasma HDL-cholesterol concentration. The application of the macrophage-to-feces RCT method in genetically engineered mice has provided evidence that this major HDL property correlates closely with changes in atherosclerosis susceptibility.

Two unusual hepatitis C virus subtypes, 2j and 2q, in Spain: Identification by nested-PCR and sequencing of a NS5B region.

Many studies have reported the use of the NS5B gene to subtype hepatitis C virus (HCV). Other HCV genes, such as HCV-5' UTR, Core (C) and E1, have also been used. In some studies, NS5B have been used together with 5'-UTR or C genes to improve genotyping results obtained using commercial procedures.

Physical activity, depressed mood and pregnancy worries in European obese pregnant women: results from the DALI study.

Background: The purpose of this study was to examine the association between mental health status (i.e. depressed mood and pregnancy-related worries) and objectively measured physical activity levels in obese pregnant women from seven European countries.

Hypoxia worsens the impact of intracellular triglyceride accumulation promoted by electronegative low-density lipoprotein in cardiomyocytes by impairing perilipin 5 upregulation.

Plasma lipoproteins are a source of lipids for the heart, and the proportion of electronegative low density lipoprotein [LDL(-)] is elevated in cardiometabolic diseases. Perilipin 5 (Plin5) is a crucial protein for lipid droplet management in the heart. Our aim was to assess the effect of LDL(-) on intracellular lipid content and Plin5 levels in cardiomyocytes and to determine whether these effects were influenced by hypoxia.

Bariatric surgery in morbidly obese patients improves the atherogenic qualitative properties of the plasma lipoproteins.

Objective: The purpose of this study was to evaluate the effect of weight loss induced in morbidly obese subjects by Roux-en-Y gastric bypass bariatric surgery on the atherogenic features of their plasma lipoproteins.

Methods: Twenty-one morbidly obese subjects undergoing bariatric surgery were followed up for up to 1 year after surgery. Plasma and lipoproteins were assayed for chemical composition and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity.

[Hypovitaminosis D and metabolic syndrome].

Metabolic syndrome and hypovitaminosis D are 2 diseases with high prevalence that share several risk factors, while epidemiological evidence shows they are associated. Although the mechanisms involved in this association are not well established, hypovitaminosis D is associated with insulin resistance, decreased insulin secretion and activation of the renin-angiotensin system, mechanisms involved in the pathophysiology of metabolic syndrome. However, the apparent ineffectiveness of vitamin D supplementation on metabolic syndrome components, as well as the limited information about the effect of improving metabolic syndrome components on vitamin D concentrations, does not clarify the direction and the mechanisms involved in the causal relationship between these 2 pathologies.

Comparative study of human and mouse postsynaptic proteomes finds high compositional conservation and abundance differences for key synaptic proteins.

Direct comparison of protein components from human and mouse excitatory synapses is important for determining the suitability of mice as models of human brain disease and to understand the evolution of the mammalian brain. The postsynaptic density is a highly complex set of proteins organized into molecular networks that play a central role in behavior and disease. We report the first direct comparison of the proteome of triplicate isolates of mouse and human cortical postsynaptic densities.

Ritonavir boosting dose reduction from 100 to 50 mg does not change the atazanavir steady-state exposure in healthy volunteers.

Objectives: To evaluate the pharmacokinetics, tolerability and safety of 300 mg of atazanavir boosted with 100 or 50 mg of ritonavir, both once daily, at steady state.

Methods: This was a single-blind, multiple-dose, crossover, sequence-randomized trial. Thirteen healthy HIV-1-negative men received witnessed once-daily doses of atazanavir (300 mg) and 100 or 50 mg of ritonavir for 10 days (15 day washout).

Associations of Body Mass Index (Maternal BMI) and Gestational Diabetes Mellitus with Neonatal and Maternal Pregnancy Outcomes in a Multicentre European Database (Diabetes and Pregnancy Vitamin D and Lifestyle Intervention for Gestational Diabetes Mellitus Prevention).

Objective. Assess the impact of Gestational Diabetes Mellitus (GDM) and obesity on neonatal and maternal pregnancy outcomes. Methods.

A new gene-based association test for genome-wide association studies.

Genome-wide association studies are widely used today to discover genetic factors that modify the risk of complex diseases. Usually, these methods work in a SNP-by-SNP fashion. We present a gene-based test that can be applied in the context of genome-wide association studies.

Combined cis-regulator elements as important mechanism affecting FXII plasma levels.

Introduction: Factor XII (FXII) deficiency is a recessive Mendelian trait due to mutations in the F12 gene. There is no bleeding associated with FXII deficiency, but FXII deficiency has been reported to be associated with risk of thrombosis in some studies.

Material And Methods: We examined the functional effect of two naturally-occurring mutations in two Spanish FXII deficient families: a C/G substitution at position -8, and a C/T substitution at position -13.

In vivo macrophage-specific RCT and antioxidant and antiinflammatory HDL activity measurements: New tools for predicting HDL atheroprotection.

The beneficial therapeutic effects of raising HDL cholesterol are proving difficult to confirm in humans. The evaluation of antiatherogenic functions of HDL is an important area of research which includes the role of HDL in reverse cholesterol transport (RCT), especially macrophage-specific RCT, and its antioxidant and antiinflammatory roles. The antioxidant and antiinflammatory functions of HDL can be assessed using cell-free and cell-based assays.

Bobel-24 and derivatives induce caspase-independent death in pancreatic cancer regardless of apoptotic resistance.

The poor prognosis of pancreatic cancer and poor sensitivity to current therapeutics, associated with resistance to apoptosis, urge the search for new drugs. We previously described the induction of caspase-independent mithochondrial death in leukemia cells by Bobel-24 (AM-24) and derivatives. Here, we explored whether these compounds induce a similar cytotoxicity in human pancreatic carcinoma cell lines (NP18, NP9, NP31, and NP29).

Searching for master regulators of transcription in a human gene expression data set.

Microarray technologies allow the measurement of the expression levels of thousands of transcripts at the same time. As part of Genetic Analysis Workshop 15 (GAW15), we analyzed a data set that measured the expression of more than 3000 genes in 14 families. Our goal was to identify genomic regions that regulate the expression of several genes at the same time.

Evidence for convergent evolution of CTX-M-14 ESBL in Escherichia coli and its prevalence.

A total of 2440 Escherichia coli strains isolated in 2003 at the Hospital de la Santa Creu i Sant Pau were evaluated for the presence of extended-spectrum beta-lactamases. Two different nucleotide sequences that encode the same beta-lactamase, CTX-M-14, were detected when the bla(CTX-M-14)-genes of 35 E. coli isolates were analysed.

Effects of olanzapine, risperidone and haloperidol on sleep after a single oral morning dose in healthy volunteers.

Objectives: To compare the effects of typical and atypical antipsychotic drugs on sleep activity and subjective sleep quality.

Design: Randomised, double-blind, placebo-controlled, four-period cross-over, clinical trial was used to evaluate the effects of active treatments on objective and subjective sleep variables.

Setting: Sleep laboratory evaluation.

Antiatherogenic role of high-density lipoproteins: insights from genetically engineered-mice.

Plasma levels of high-density lipoprotein (HDL) cholesterol are inversely correlated with the incidence of atherosclerotic cardiovascular disease. The cardioprotective effects of HDL have been attributed to its role in reverse cholesterol transport (RCT) and especially the macrophage-dependent RCT, and also to the antioxidant properties of HDL as well as its direct effects on endothelial function. However, few of these effects have been verified in vivo in humans.

Surveillance of extended-spectrum beta-lactamases from clinical samples and faecal carriers in Barcelona, Spain.

Objectives: The aim of the present study was to characterize and compare the extended-spectrum beta-lactamase (ESBL)-producing organisms isolated from clinical samples and faecal carriers in 2001 and 2002.

Methods: A total of 5251 Enterobacteriaceae isolated from clinical samples and 1321 stool samples were evaluated for the presence of ESBLs. The stool samples were spread onto plates of MacConkey agar containing 2 mg/L cefotaxime for selection of ESBL-producing strains.