Transporter associated with antigen processing (TAP) 1 gene polymorphisms in patients with hypersensitivity pneumonitis

Hypersensitivity pneumonitis (HP) is a lung inflammatory disease caused by the inhalation of a variety of antigens. Previous studies support the role of the major histocompatibility complex (MHC) class II genes in the susceptibility to develop HP. However, the putative role of other MHC loci has not been elucidated. Transporters associated with antigen processing (TAP) genes are located within the MHC class II region and play an important role transporting peptides across the endoplasmic reticulum membrane for MHC class I molecules assembly. The distribution of single nucleotide polymorphisms (SNPs) in TAP1 genes was analyzed in 73 hypersensitivity pneumonitis (HP) patients and 58 normal subjects. We found a significant association of the allele Gly-637 (GGC) (p=0.00004, OR=27.30, CI=3.87-548.04) and the genotypes Asp-637/Gly-637 (p=0.01, OR=16.0, CI=2.19-631.21), Pro-661/Pro-661 (p=0.006, OR=11.30, CI=2.28-75.77) with HP. A significant decrease in the frequency of the allele Pro-661 (CCA) (p=0.008, OR=0.06, CI=0-0.45), the genotype Asp-637/Asp-637 (p=0.01, OR=0.17, 95% CI=0.05-0.58) and the haplotype [Val-333 (GTC), Val-458 (GTG), Gly-637 (GGC), Pro-661 (CCA)] was detected in HP patients compared with controls (p=0.002, OR=0.07, CI=0.0-0.57). These findings suggest that TAP1 gene polymorphisms are related to HP risk, and highlight the importance of the MHC in the development of this disease.     

Anti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a p38 MAPK inhibitor, in an experimental model of acute lung inflammation

We investigated the effects of LASSBio-998 (L-998), a compound designed to be a p38 MAPK (mitogen-activated protein kinase) inhibitor, on lipopolysaccharide (LPS)-induced acute lung inflammation in vivo. BALB/c mice were challenged with aerosolized LPS inhalation (0.5 mg/ml) 4 h after oral administration of L-998. Three hours after LPS inhalation, bronchoalveolar lavage fluid was obtained to measure the levels of the proinflammatory cytokines TNF-α (tumor necrosis factor-α) and IL-1 (interleukin-1) and the chemokines MCP-1 (monocyte chemoattractant protein-1) and KC (keratinocyte chemoattractant). In addition, neutrophil infiltration and p38 MAPK phosphorylation was measured. L-998 inhibited LPS-induced production of TNF-α and IL-1β and did not alter KC and MCP-1 levels. Furthermore, L-998 also significantly decreased neutrophil accumulation in lung tissues. As expected, L-998 diminished p38 MAPK phosphorylation and reduced acute lung inflammation. Inhibition of p38 MAPK phosphorylation by L-998 was also demonstrated in LPS-challenged murine C57BL/6 peritoneal macrophages in vitro, with concentration-dependent effects. L-998 suppressed LPS-induced lung inflammation, most likely by inhibition of the cytokine-p38 MAPK pathway, and we postulate that L-998 could be a clinically relevant anti-inflammatory drug candidate.     

Emerging drugs for idiopathic pulmonary fibrosis

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and usually lethal lung disorder of unknown etiology. The disease is characterized by alveolar epithelial cell injury, formation of activated fibroblasts/myofibroblasts foci and finally by the exaggerated accumulation of extracellular matrix with the subsequent destruction of the lung architecture. The long-term survival is distinctly poor, with only a 20-30% survival 5 years after the time of diagnosis. Actually, regardless of extensive research, no current therapy has been shown to either reverse or stop the progression of this disease. AREAS COVERED: The authors searched the Medline database from January 1990 to December 2010 using search terms 'pulmonary fibrosis', 'fibrosing alveolitis' and 'usual interstitial pneumonia'. Several subsets were included: definition and epidemiology, risk factors, clinical behavior, pathogenesis and therapy. For the section of IPF treatment, the authors examined all relevant studies including randomized controlled trials, cohort studies, case-control studies and cross-sectional studies. In this review, the authors describe the current therapeutic approaches, the ongoing clinical trials and some future options based on stem cells, lung bioengineering and microRNAs. EXPERT OPINION: The treatment of IPF represents one of the greatest challenges confronting respiratory medicine and, currently, there is no effective therapeutic option for IPF. Perhaps some of the drugs that are under evaluation in clinical trials will slow the decline of the pulmonary function tests or hopefully stabilize some patients. Nonetheless, it appears clear that new therapeutic approaches are urgently needed.     

The Brazilian Football Association (CBF) model for epidemiological studies on professional soccer player injuries

OBJECTIVE:

This study aims to establish a national methodological model for epidemiological studies on professional soccer player injuries and to describe the numerous relevant studies previously published on this topic.

INTRODUCTION:

The risk of injury in professional soccer is high. However, previous studies of injury risk in Brazil and other countries have been characterized by large variations in study design and data collection methods as well as definitions of injury, standardized diagnostic criteria, and recovery times.

METHODS:

A system developed by the Union of European Football for epidemiological studies on professional soccer players is being used as a starting point to create a methodological model for the Brazilian Football Association. To describe the existing studies on professional soccer player injuries, we developed a search strategy to identify relevant epidemiological studies. We included the Latin American and Caribbean Center on Health Sciences and Medline databases in our study.

RESULTS:

We considered 60 studies from Medline and 16 studies from the Latin American and Caribbean Center on Health Sciences in the final analysis. Twelve studies were selected for final inclusion in this review: seven from the Latin American and Caribbean Center on Health Sciences and five from Medline. We identified a lack of uniformity in the study design, data collection methods, injury definitions, standardized diagnostic criteria, and the definition of recovery time. Based on the information contained within these articles, we developed a model for epidemiological studies for the Brazilian Football Association.

CONCLUSIONS:

There is no uniform model for epidemiological studies of professional soccer injuries. Here, we propose a novel model to be applied for epidemiological studies of professional soccer player injuries in Brazil and throughout the world.     

Effectiveness of low-frequency vibration recovery method on blood lactate removal,muscle contractile properties and on time to exhaustion during cycling at <Emphasis Type="Italic">V</Emphasis>O<Subscript>2max</Subscript> power output

The aim of the study was to determine the effectiveness of low-frequency vibration recovery (LFV-rec) on blood lactate removal, muscle contractile properties, and on time to exhaustion during cycling at maximal oxygen uptake power output (pVO_2max). Twelve active males carried out three experimental sessions. In session 1, participant’s maximal oxygen uptake (VO_2max) and pVO_2max were determined, and in sessions 2 and 3, the participants performed a fatiguing exercise (2 min of cycling at pVO_2max) and then a 15 min recovery period using one of two different methods: LFV-rec which consisted on sitting with feet on the vibratory platform (20 Hz; 4 mm) and passive recovery (P-rec), sitting without vibration stimulus. After that, participants performed an all-out exercise test on cycle ergometer at pVO_2max. In the recovery period, variables such as heart rate (HR), blood lactate concentration [Lac], and tensiomyographic parameters (D _m: maximal radial displacement; T _s: time of contraction maintenance, and T _r: relaxation time) were measured. In an all-out exercise test, mean time to exhaustion (TTE), total distance covered (TD), mean cycling velocity (V _m), and maximal HR (HR_max) were also assessed. The results showed no effect of recovery strategy on any of the assessed variables; nevertheless, higher values, although not significant, were observed in TTE, TD, and V _m after LFV-rec intervention. In conclusion, LFV-rec strategy applied during 15 min after short and intense exercise does not seem to be effective on blood lactate removal, muscle contractile properties, and on time to exhaustion during cycling at pVO_2max.     

Increase in dopaminergic, but not serotoninergic, receptors in T-cells as a marker for schizophrenia severity

Schizophrenia is characterized by a slow deteriorating mental illness. Although the pathophysiology mechanisms are not fully understood, different studies have suggested a role for the immune system in the pathogenesis of schizophrenia. To date, an altered expression or signaling of neurotransmitters receptors is observed in immune cells during psychiatric disorders. In the present study, we investigated the expression of different serotonin and dopamine receptors in T-cells of schizophrenic and control patients. We used flow cytometry to determine the pattern of expression of dopamine (D2 and D4) and serotonine receptors (SR1A, SR1C, SR2A, SR2B), as well as serotonin transporter (ST), in T-cell subsets (CD4 and CD8). Expression of serotonin receptors and ST in T-cells of schizophrenic patients were not different from controls. However, the percentages of CD4+D4+ and CD8+D4+ were increased in schizophrenic patients as compared to controls. In addition, increased percentages of CD8+D2+ cells were also observed in schizophrenic patients, albeit this population revealed lower CD4+D2+ cells in comparison to controls. Interestingly, a relationship between clinical symptoms and immunological parameters was also observed. We showed that the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS) and the Abnormal Involuntary Movement Scale (AIMS) were positively related to CD8+D2+ cells, though AIMS was inversely related to CD4+D4+ cells. In conclusion, the alteration in the pattern of cell population and molecules expressed by them might serve as a promising biomarker for diagnosis of schizophrenia.