Medical radiation from x-rays and nuclear medicine is the largest man-made source of radiation exposure in Western countries, accounting for a mean effective dose of 3.0 mSv per capita per year, comparable to the radiologic risk of 150 chest x-rays, and in many cases gonads fall in the imaging field, with > 20 millions examinations per year in US being abdominal and pelvic CT, and > 0.5 million barium enema. Of the over 7 million workers exposed to medical radiation, special attention has been paid to those working in the interventional cardiology and radiology labs, with high and increasing professional exposures, two-to three times higher than diagnostic radiologists. Thus, adverse effects of radiation exposure are well worth of the scientific community's interest. Aims of this review are: 1) to assess gonad dose to patients undergoing diagnostic testing or interventional fluoroscopy therapy and in professionally exposed interventional fluoroscopists; and 2) to evaluate the evidence linking radiation exposure in the low-to-moderate range (besides the radiotherapy high dose range) to adverse reproductive effects. In patients, the gonad radiation exposure can reach 5 mSv for a lower limb angiography, 20 mSv for a CT pelvis and hips, and 36 (in females) to 90 mSv (for males) for a lower gastrointestinal series. For interventional cardiologists, the gonad dose (below lead apron) is in the same order of magnitude of the shielded thyroid dose, with a median of 50 to 100 microSievert per cine-angiography procedure. The dose can be ten-fold higher for a complex interventional procedure. This leads to a cumulative exposure in the 0.5-1 Sv range over a professional lifetime of 30 years. At present, the epidemiological approach provided inconclusive results, inadequate for a robust evidence-based advice to exposed subjects, since large groups followed-up for decades would be required to detect a small increase in risk. A molecular epidemiology approach and/or the use of integrated biomarkers of reproductive health (e.h., reproductive hormone balance, sperm quality, sperm DNA damage) might be more fruitful in future research focused in the low-to-moderate dose range (< 1000 mSv) of greatest interest for diagnostic and professional exposures.
PTX3 is a long pentraxin of the innate immune system produced by different cell types (mononuclear phagocytes, dendritic cells, fibroblasts and endothelial cells) at the inflammatory site. It appears to have a cardiovascular protective function by acting on the immune-inflammatory balance in the cardiovascular system. PTX3 plasma concentration is an independent predictor of mortality in patients with acute myocardial infarction (AMI) but the influence of PTX3 genetic variants on PTX3 plasma concentration has been investigated very little and there is no information on the association between PTX3 variations and AMI. Subjects of European origin (3245, 1751 AMI survivors and 1494 controls) were genotyped for three common PTX3 polymorphisms (SNPs) (rs2305619, rs3816527, rs1840680). Genotype and allele frequencies of the three SNPs and the haplotype frequencies were compared for the two groups. None of the genotypes, alleles or haplotypes were significantly associated with the risk of AMI. However, analysis adjusted for age and sex indicated that the three PTX3 SNPs and the corresponding haplotypes were significantly associated with different PTX3 plasma levels. There was also a significant association between PTX3 plasma concentrations and the risk of all-cause mortality at three years in AMI patients (OR 1.10, 95% CI: 1.01-1.20, p = 0.02). Our study showed that PTX3 plasma levels are influenced by three PTX3 polymorphisms. Genetically determined high PTX3 levels do not influence the risk of AMI, suggesting that the PTX3 concentration itself is unlikely to be even a modest causal factor for AMI. Analysis also confirmed that PTX3 is a prognostic marker after AMI.
A hexanucleotide repeat expansion within the <i>C9orf72</i> gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and its discovery has revolutionized our understanding of this devastating disease. Model systems are a valuable tool for studying ALS pathobiology and potential therapies. The zebrafish (<i>Danio rerio</i>) has particularly become a useful model organism to study neurological diseases, including ALS, due to high genetic and physiological homology to mammals, and sensitivity to various genetic and pharmacological manipulations. In this review we summarize the zebrafish models that have been used to study the pathology of <i>C9orf72</i>-related ALS. We discuss their value in providing mechanistic insights and their potential use for drug discovery.
Read moreAn entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Read morePTX3, a marker of vascular inflammation and cardiovascular damage, is a predictor of short-term functional recovery and 1-year MACE in patients undergoing rehabilitation after cardiac surgery, regardless of clinical and instrumental parameters.
Read moreOM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®, Paxoral®, Vaxoral®), a product made of the water soluble fractions of 21 inactivated bacterial strain patterns responsible for respiratory tract infections, is used for the prevention of recurrent upper respiratory tract infections and acute exacerbations in chronic obstructive pulmonary disease patients. OM-85 is able to potentiate both innate and adaptive immune responses. However, the molecular mechanisms responsible for OM-85 activation are still largely unknown. Purpose of this study was to investigate the impact of OM-85 stimulation on human dendritic cell functions. We show that OM-85 selectively induced NF-kB and MAPK activation in human DC with no detectable action on the interferon regulatory factor (IRF) pathway. As a consequence, chemokines (i.e. CXCL8, CXCL6, CCL3, CCL20, CCL22) and B-cell activating cytokines (i.e. IL-6, BAFF and IL-10) were strongly upregulated. OM-85 also synergized with the action of classical pro-inflammatory stimuli used at suboptimal concentrations. Peripheral blood mononuclear cells from patients with COPD, a pathological condition often associated with altered PRR expression pattern, fully retained the capability to respond to OM-85. These results provide new insights on the molecular mechanisms of OM-85 activation of the immune response and strengthen the rational for its use in clinical settings.
Read moreEctopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21+ follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.
Read moreAwareness of a bidirectional relationship between depression and RA through a biopsychosocial framework may assist clinicians in maintaining an appropriate index of suspicion about the co-occurrence of these conditions. This review also suggests an important need for integration of rheumatologic and mental health services and generates hypotheses for future research towards a better understanding of both depression and RA.
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