Role of the chemokine receptor CXCR2 in bleomycin-induced pulmonary inflammation and fibrosis

Pulmonary fibrosis is characterized by chronic inflammation and excessive collagen deposition. Neutrophils are thought to be involved in the pathogenesis of lung fibrosis. We hypothesized that CXCR2-mediated neutrophil recruitment is essential for the cascade of events leading to bleomycin-induced pulmonary fibrosis. CXCL1/KC was detected as early as 6 hours after bleomycin instillation and returned to basal levels after Day 8. Neutrophils were detected in bronchoalveolar lavage and interstitium from 12 hours and peaked at Day 8 after instillation. Treatment with the CXCR2 receptor antagonist, DF2162, reduced airway neutrophil transmigration but led to an increase of neutrophils in lung parenchyma. There was a significant reduction in IL-13, IL-10, CCL5/RANTES, and active transforming growth factor (TGF)-beta(1) levels, but not on IFN-gamma and total TGF-beta(1,) and enhanced granulocyte macrophage-colony-stimulating factor production in DF2162-treated animals. Notably, treatment with the CXCR2 antagonist led to an improvement of the lung pathology and reduced collagen deposition. Using a therapeutic schedule, DF2162 administered from Days 8 to 16 after bleomycin reduced pulmonary fibrosis and levels of active TGF-beta(1) and IL-13. DF2162 treatment reduced bleomycin-induced expression of von Willebrand Factor, a marker of angiogenesis, in the lung. In vitro, DF2162 reduced the angiogenic activity of IL-8 on human umbilical vein endothelial cells. In conclusion, we show that CXCR2 plays an important role in mediating fibrosis after bleomycin instillation. The compound blocks angiogenesis and the production of pro-angiogenic cytokines, and decreases IL-8-induced endothelial cell activation. An effect on neutrophils does not appear to account for the major effects of the blockade of CXCR2 in the system.     

Possible influence of spiritual and religious beliefs on hypertension

Religious and spiritual beliefs are beneficial in stroke patients as coping strategies. This work has investigated the feeling of people about it by proposing to 174 volunteers aged 54.0 +/- 16.9 years the Royal Free Interview (RFI). Interviewed subjects considered the beliefs beneficial for health independently of their form. Ascertaining the pre-morbid understanding of life in subjects at risk of hypertension may be useful to verify self-confidence and coping possibilities against anger, fear, and stress, factors that may exert a negative effect.     

Magnetic resonance spectroscopy in Parkinson's disease and parkinsonian syndromes

This paper looks at the use of magnetic resonance spectroscopy (MRS) for diagnostic and research purposes in Parkinson's disease and parkinsonian syndromes. The review considers both proton MRS (1H MRS) and phosphorus MRS (31 P MRS) studies. MRS is useful for diagnostic purposes, helping to differentiate Parkinson's disease from other parkinsonian syndromes. Even more usefully, MRS can be used for non invasive in vivo human research.     

Age and target organ damage in essential hypertension: role of the metabolic syndrome

OBJECTIVE: We sought to investigate the association of the metabolic syndrome (MS) with cardiovascular alterations in essential hypertensives in relation to age. METHODS: A total of 3266 untreated and treated hypertensive patients categorized in three age groups (I: 17 to 40 years; II: 41 to 64 years; III: >64 years) were considered for this analysis. All patients underwent extensive investigations searching for target organ damage (TOD). The MS was defined according to Advanced Technology Laboratories (ATP) III criteria. RESULTS: In the entire population, the risk of left ventricular hypertrophy (LVH), carotid abnormalities, and microalbuminuria increased by 2.5 (P = .003), 2.2 (P = .005), and 1.5 times (P = .01), respectively, in the presence of MS after adjusting for several confounders. Prevalence of LVH (group I: 39% v 22%; group II: 53% v 35%; group III: 69% v 52%, P < .01 for all), carotid thickening (group I: 8% v 2%; group II 29% v 19%; group III: 69% v 52%, P < .05 for all) and microalbuminuria (group I: 20% v 11%; group II: 16% v 8%; group III: 18% v 11%, P 相似文献   

Body Composition Alterations,Energy Expenditure and Fat Oxidation in Elderly Males Suffering from Prostate Cancer,Pre and Post Orchiectomy

INTRODUCTION

Testosterone is needed for normal male development, muscle strength, bone mineralization, hematopoietic function, and sexual and reproductive functions. The main purpose of androgen deprivation therapy in prostate cancer is to reduce tumor progression, but therapy is often accompanied by significant adverse effects.

OBJECTIVE

This study aimed to determine the effects of androgen deprivation therapy on body composition and resting metabolic rate in patients with prostate cancer.

PATIENTS AND METHODS

A prospective study was performed to evaluate the body composition of 16 elderly males (aged 63–96; median age 71) with prostate cancer scheduled for orchiectomy, one year before and after surgery. Body composition was measured by DEXA, and energy expenditure, fat and carbohydrate oxidation were measured by indirect calorimetry.

RESULTS

Body weight (p=0.01), lean mass (p=0.004), and lipid oxidation (p=0.001) decreased significantly. Carbohydrate oxidation (p=0.02), FSH (p=0.0001) and LH (p=0.0001) levels increased significantly. Changes in fat mass (p=0.06) and bone mineral density (p=0.48) were not significant.

CONCLUSIONS

After 12 months of androgen deprivation therapy, elderly men with metastatic prostate cancer exhibit a decline in lean body mass and lipid oxidation, together with increased carbohydrate oxidation.     

Naturally Acquired Antibodies to Plasmodium vivax Duffy Binding Protein (DBP) in Rural Brazilian Amazon

Duffy binding protein (DBP), a leading malaria vaccine candidate, plays a critical role in Plasmodium vivax erythrocyte invasion. Sixty-eight of 366 (18.6%) subjects had IgG anti-DBP antibodies by enzyme-linked immunosorbent assay (ELISA) in a community-based cross-sectional survey in the Brazilian Amazon Basin. Despite continuous exposure to low-level malaria transmission, the overall seroprevalence decreased to 9.0% when the population was reexamined 12 months later. Antibodies from 16 of 50 (36.0%) subjects who were ELISA-positive at the baseline were able to inhibit erythrocyte binding to at least one of two DBP variants tested. Most (13 of 16) of these subjects still had inhibitory antibodies when reevaluated 12 months later. Cumulative exposure to malaria was the strongest predictor of DBP seropositivity identified by multiple logistic regression models in this population. The poor antibody recognition of DBP elicited by natural exposure to P. vivax in Amazonian populations represents a challenge to be addressed by vaccine development strategies.