Tumour necrosis factor alpha upregulates platelet CD40L in patients with heart failure

AIMS: Patients with heart failure (HF) have elevated values of the pro-inflammatory protein CD40L but the underlying mechanism is unclear. This study was performed to evaluate the interplay between tumour necrosis factor alpha (TNFalpha) and CD40L in HF. METHODS AND RESULTS: In patients with HF (n=86) and healthy subjects (HS, n=43), plasma levels of soluble CD40L (sCD40L), TNFalpha, soluble receptors of TNFalpha such as soluble TNF receptors I and II (sTNFR1 and sTNFR2), and 8OH-dG, a marker of oxidative stress, were determined. Also, an in vitro study was performed by determining platelet CD40L regulation upon platelet stimulation with TNFalpha. Compared with HS, HF patients had higher plasma values of sCD40L, TNFalpha, sTNFR1 and sTNFR2, and higher platelet expression of TNFR1 and TNFR2 with a progressive increase from NYHA I to NYHA IV classification. sCD40L significantly correlated with TNFalpha, sTNFR1, and sTNFR2; plasma levels of TNFalpha significantly correlated with sCD40L. Incubation of platelets from HF patients with a TNFalpha receptor inhibitor significantly decreased platelet CD40L expression. The in vitro study demonstrated that TNFalpha significantly increased CD40L expression, an effect weakly influenced by aspirin but significantly reduced by AACOCF3, an inhibitor of PLA(2), apocynin, an inhibitor of NADPH oxidase, or staurosporine, an inhibitor of PKC. CONCLUSION: The study shows that in HF patients, platelet CD40L is upregulated by TNFalpha via a cyclooxygenase-1-independent, arachidonic acid-mediated oxidative stress mechanism.     

Hepatic apoptosis and proliferation in male and female rats fed alcohol: role of cytokines

Background: The female liver is more sensitive to the toxic effect of chronic alcohol intake than the male liver. The aim of the study was to compare the influence of gender and sex hormonal status on apoptosis and cell proliferation following chronic ethanol intake.
Methods: Male and female rats were pair fed for 8 weeks a liquid diet containing 36% of their total daily calories as ethanol (ETOH group) or sucrose (control group). Liver samples were analyzed for apoptosis and hepatocyte proliferation by immunohistochemistry. The hepatic production of factors able to influence cell death and proliferation, such as tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) were determined.
Results: In both male and female rats, ethanol intake promoted apoptosis in the liver. This effect of ethanol was more evident in female than male rat livers. Hepatic TNFα levels, which promote apoptosis, are significantly more elevated in female than in male livers. Hepatic IL-6 production, which promotes hepatocyte proliferation, was induced by ethanol only in males, but not female animals.
Conclusion: This observed difference in cytokine responses may contribute to the enhanced sensitivity of female liver to EtOH-induced injury.     

Pulmonary Aspergillosis: Spectrum of Disease

Aspergillus species are ubiquitous in the environment. Aspergillosis is acquired by inhalation of Aspergillus spores. In normal hosts, spore inhalation rarely causes lung disease. Pulmonary Aspergillosis covers a wide spectrum of clinical syndromes depending on the interaction between Aspergillus and the host (immune-status, prior bronchopulmonary disease). It runs the gamut from invasive Aspergillosis to Aspergillus bronchitis. Invasive Aspergillosis usually occurs in severely immunocompromised patients, typically in neutropenic but also in non-neutropenic patients. Chronic pulmonary Aspergillosis affects patients with chronic structural lung disease such as COPD or previous mycobacterial lung disease, but without other significant immunocompromise. Aspergillus bronchitis affects patients with bronchial disease such as bronchiectasis. Allergic bronchopulmonary Aspergillosis affects patients with bronchial asthma or cystic fibrosis, and is due to an allergic response to Aspergillus.     

Diesel exhaust particulates affect cell signaling,mucin profiles,and apoptosis in trachea explants of Balb/C mice

Particulate matter from diesel exhaust (DEP) has toxic properties and can activate intracellular signaling pathways and induce metabolic changes. This study was conducted to evaluate the activation of extracellular signal‐regulated kinase (ERK) and c‐Jun N‐terminal kinase (JNK) and to analyze the mucin profile (acid (AB⁺), neutral (PAS⁺), or mixed (AB/PAS⁺) mucus) and vacuolization (V) of tracheal explants after treatment with 50 or 100 μg/mL DEP for 30 or 60 min. Western blot analyses showed small increases in ERK1/2 and JNK phosphorylation after 30 min of 100 μg/mL DEP treatment compared with the control. An increase in JNK phosphorylation was observed after 60 min of treatment with 50 μg/mL DEP compared with the control. We did not observe any change in the level of ERK1/2 phosphorylation after treatment with 50 μg/mL DEP. Other groups of tracheas were subjected to histological sectioning and stained with periodic acid‐Schiff (PAS) reagent and Alcian Blue (AB). The stained tissue sections were then subjected to morphometric analysis. The results obtained were compared using ANOVA. Treatment with 50 μg/mL DEP for 30 min or 60 min showed a significant increase (p < 0.001) in the amount of acid mucus, a reduction in neutral mucus, a significant reduction in mixed mucus, and greater vacuolization. Our results suggest that compounds found in DEPs are able to activate acid mucus production and enhance vacuolization and cell signaling pathways, which can lead to airway diseases. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1297–1308, 2015.     

The Research Board of the European Dialysis and Transplantation Nurses Association/European Renal Care Association (EDTNA/ERCA)

The Research Board (RB) of EDTNA/ERCA is a multidisciplinary group, established by the participation of renal care centres all around Europe. The RB also works with the association's Special Interest Groups (SIGs) on developing guidelines for implementing safe renal clinical practice. It is composed of six permanent members, with co-opted experts from specific fields. This article describes how the RB works and the projects implemented since 1996.     

Relationships between leisure-time physical activity, obesity and disability in elderly men

BACKGROUND AND AIMS: Relationships have already been shown between leisure-time physical activity, obesity and body composition in young adults. However, this association needs to be confirmed in the elderly. The aim of this study was to investigate the relationship between leisure-time physical activity, obesity, preservation of muscle mass and disability in elderly men. METHODS: Cross-sectional analysis of a sample of 85 community-dwelling men, 68 to 79 years of age. Body mass index (BMI) was used to quantify obesity. Body composition was evaluated using Dual Energy X-ray Absorptiometry. Disability was measured using a modified version of the Activities of Daily Living scale. Leisure-time physical activity was evaluated by a validated self-administered questionnaire. RESULTS: A negative relation between obesity and weekly walking was observed. Walking less than 30 minutes per day was associated with a 2.7 greater probability of being obese (95% CI 1.1-6.7). High-intensity exercise, such as brisk walking or gardening, was inversely correlated with body fat (R = -0.296, p < 0.01) and directly correlated with appendicular skeletal mass (R = 0.238, p < 0.05). The prevalence of disability was the highest (58%) among overweight elderly subjects at the lowest tertile of exercise. Multiple logistic regression selected BMI as a positive predictor and high-intensity exercise as a negative predictor of disability. CONCLUSIONS: Our study shows that, in elderly men, leisure-time physical activity is inversely associated with body fat, BMI, and reported disability, but positively associated with appendicular fat-free mass. The highest prevalence of reported disability was observed in sedentary subjects with BMI higher than 25 kg/m2.     

European study on epidemiology and the management of HCV in the haemodialysis population--Part 1: centre policy

Haemodialysis patients are known to be at risk of infection of Hepatitis C Virus (HCV) through nosocomial spread. This paper presents the first part of a study on epidemiology and management of HCV, in a haemodialysis population, conducted by the EDTNA/ERCA Research Board. Data on HCV management and infection control procedures was collected from 136 European centres using an electronic questionnaire. The study identifies a number of possible risk factors for transmission of the virus: failing to disinfect devices between patients, sharing of single-use vials to prepare drugs or infusions for different patients, inadequate sterilisation or cleaning of machines between dialysis sessions, unsatisfactory environmental cleaning and distance less than one metre between chairs.