45 research outputs found

    Soluble TNF Mediates the Transition from Pulmonary Inflammation to Fibrosis

    Get PDF
    BACKGROUND: Fibrosis, the replacement of functional tissue with excessive fibrous tissue, can occur in all the main tissues and organ systems, resulting in various pathological disorders. Idiopathic Pulmonary Fibrosis is a prototype fibrotic disease involving abnormal wound healing in response to multiple sites of ongoing alveolar epithelial injury. METHODOLOGY/PRINCIPAL FINDINGS: To decipher the role of TNF and TNF-mediated inflammation in the development of fibrosis, we have utilized the bleomycin-induced animal model of Pulmonary Fibrosis and a series of genetically modified mice lacking components of TNF signaling. Transmembrane TNF expression is shown to be sufficient to elicit an inflammatory response, but inadequate for the transition to the fibrotic phase of the disease. Soluble TNF expression is shown to be crucial for lymphocyte recruitment, a prerequisite for TGF-b1 expression and the development of fibrotic lesions. Moreover, through a series of bone marrow transfers, the necessary TNF expression is shown to originate from the non-hematopoietic compartment further localized in apoptosing epithelial cells. CONCLUSIONS: These results suggest a primary detrimental role of soluble TNF in the pathologic cascade, separating it from the beneficial role of transmembrane TNF, and indicate the importance of assessing the efficacy of soluble TNF antagonists in the treatment of Idiopathic Pulmonary Fibrosis

    Preterm infants have significantly longer telomeres than their term born counterparts

    Get PDF
    There are well-established morbidities associated with preterm birth including respiratory, neurocognitive and developmental disorders. However several others have recently emerged that characterise an `aged' phenotype in the preterm infant by term-equivalent age. These include hypertension, insulin resistance and altered body fat distribution. Evidence shows that these morbidities persist into adult life, posing a significant public health concern. In this study, we measured relative telomere length in leukocytes as an indicator of biological ageing in 25 preterm infants at term equivalent age. Comparing our measurements with those from 22 preterm infants sampled at birth and from 31 term-born infants, we tested the hypothesis that by term equivalent age, preterm infants have significantly shorter telomeres (thus suggesting that they are prematurely aged). Our results demonstrate that relative telomere length is highly variable in newborn infants and is significantly negatively correlated with gestational age and birth weight in preterm infants. Further, longitudinal assessment in preterm infants who had telomere length measurements available at both birth and term age (n = 5) suggests that telomere attrition rate is negatively correlated with increasing gestational age. Contrary to our initial hypothesis however, relative telomere length was significantly shortest in the term born control group compared to both preterm groups and longest in the preterm at birth group. In addition, telomere lengths were not significantly different between preterm infants sampled at birth and those sampled at term equivalent age. These results indicate that other, as yet undetermined, factors may influence telomere length in the preterm born infant and raise the intriguing hypothesis that as preterm gestation declines, telomere attrition rate increases

    Is the meiofauna a good indicator for climate change and anthropogenic impacts?

    Get PDF
    Our planet is changing, and one of the most pressing challenges facing the scientific community revolves around understanding how ecological communities respond to global changes. From coastal to deep-sea ecosystems, ecologists are exploring new areas of research to find model organisms that help predict the future of life on our planet. Among the different categories of organisms, meiofauna offer several advantages for the study of marine benthic ecosystems. This paper reviews the advances in the study of meiofauna with regard to climate change and anthropogenic impacts. Four taxonomic groups are valuable for predicting global changes: foraminifers (especially calcareous forms), nematodes, copepods and ostracods. Environmental variables are fundamental in the interpretation of meiofaunal patterns and multistressor experiments are more informative than single stressor ones, revealing complex ecological and biological interactions. Global change has a general negative effect on meiofauna, with important consequences on benthic food webs. However, some meiofaunal species can be favoured by the extreme conditions induced by global change, as they can exhibit remarkable physiological adaptations. This review highlights the need to incorporate studies on taxonomy, genetics and function of meiofaunal taxa into global change impact research

    Pathogen reduction/inactivation of products for the treatment of bleeding disorders:what are the processes and what should we say to patients?

    Get PDF
    Patients with blood disorders (including leukaemia, platelet function disorders and coagulation factor deficiencies) or acute bleeding receive blood-derived products, such as red blood cells, platelet concentrates and plasma-derived products. Although the risk of pathogen contamination of blood products has fallen considerably over the past three decades, contamination is still a topic of concern. In order to counsel patients and obtain informed consent before transfusion, physicians are required to keep up to date with current knowledge on residual risk of pathogen transmission and methods of pathogen removal/inactivation. Here, we describe pathogens relevant to transfusion of blood products and discuss contemporary pathogen removal/inactivation procedures, as well as the potential risks associated with these products: the risk of contamination by infectious agents varies according to blood product/region, and there is a fine line between adequate inactivation and functional impairment of the product. The cost implications of implementing pathogen inactivation technology are also considered

    Discovery of the first Hippocratic cranial trepanation from the Greek colony of Himera, Sicily (6th-5th century B.C.)

    No full text
    The cranium of the young woman from HimPT2004 has been trepanated during life for unknown reasons. Survival after trepanation, if any, was minimal and radiologically not detectable. It is the first Italian case of trepanation of classical Greek age and culture. The form of the trepanation is consistent with the utilisation of a cylindrical crown wheel drill, the prion or Hippocratic drill. This type of drill is mentioned in Hippocratic texts and it has been found in archeological excavations but the trepanated skull from Himera is the first direct evidence of its utilization. Moreover, the dating of the tomb (between 525 and 480 B.C.) proves that the instrument was invented before the birth of Hippocrates himself (460-355 B.C.). This find sheds new light on Greek pre-Hippocratic medicine and proves that sophisticated surgical techniques and surgical instruments already existed at least by the beginning of the 5th century B.C. This knowledge was later improved and formalized by Hippocrates, but not entirely discovered by him

    Partial cranial trephination by means of Hippocrates' trypanon from 5th century BC Himera (Sicily, Italy)

    No full text
    The paper deals with a new case of partial cranial trephination found in one of the necropolises of the Greek colony of Himera in Sicily. It is one of the very few cases of cranial trephination of Greek classical age. Macroscopic as well as radiological investigations prove that the operation was perimortal as no growth of new bone could be detected, SEM-EDS microanalysis of the piece revealed the traces left by the tool used during trephination. The review of ancient Greek and Latin medical and surgical texts permitted us to establish that the tool used in Himera was a (trypanon) mentioned by Hippocrates and named terebra by Latin authors. Copyright (c) 2010 John Wiley & Sons, Ltd

    Dental health in patients affected by alcohol use disorders: a cross-sectional study

    No full text
    OBJECTIVE: Chronic alcohol abuse represents a risk factor for oral diseases, in particular, oral cancer. Periodontal disease has been showed to be involved in the pathophysiology of cardiovascular and metabolic diseases, such as atherosclerosis and liver steatosis. The role of chronic alcohol consumption on periodontitis is still controversial. The aim of the study was to evaluate the effect of chronic alcohol abuse on oral health. PATIENTS AND METHODS: Twenty-three alcohol use disorders (AUD) patients and twenty-three healthy social drinkers underwent an oral examination by trained oral clinicians in order to evaluate oral and dental health. A questionnaire assessing oral hygiene was administered together with the evaluation of DMFT (decayed, missing, flled teeth), SLI (Silness-Loë plaque index) and CPI (community periodontal index of treatment needs) scores. RESULTS: Alcoholic patients showed significantly lower oral hygiene scores compared to controls. Alcoholic patients showed significantly poorer scores at DMFT, SLI and CPI tests. Moreover, among alcoholics, smokers showed a significantly poorer oral health than non-smokers. CONCLUSIONS: Chronic alcohol abuse increases the risk of dental and periodontal diseases. Smoking represents a significant co-factor. The practice of basic oral hygiene and the access to professional dental care should be encouraged among AUD patients in order to reduce oral diseases
    corecore