The role of pulmonary vascular endothelium in chronic obstructive pulmonary disease (COPD): Does endothelium play a role in the onset and progression of COPD?

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung pathology characterized by persistent airflow limitation and is the third leading cause of death globally. COPD pathophysiology includes both environmental and host risk factors and the presence of comorbidities contributes to its harmful outcome. Cardiovascular disease (CVD) is closely related to COPD and their coexistence is associated with worse outcomes than either condition alone. COPD impairs the cardiovascular system favoring mostly endothelial dysfunction that is a significant COPD prognostic factor at different stages of the disease. The mechanisms promoting endothelial dysfunction in the systemic and/or pulmonary circulation of COPD patients are different and include systemic inflammation, alteration of adhesion and pro-inflammatory molecules, oxidative stress, cellular senescence, and apoptosis. Nevertheless, the role of endothelium in the onset and progression of COPD and CVD is not yet fully understood. Hence, the purpose of this narrative review is to analyze the literature and provide evidence supporting the importance of endothelial dysfunction in COPD

Low Adherence To Nutritional Recommendations In Patients With Cirrhosis: A Prospective Observational Study

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Fecal carriage of Escherichia coli O157:H7 and carcass contamination in cattle at slaughter in northern Italy

Feedlot cattle slaughtered at a large abattoir in northern Italy during 2002 were examined for intestinal carriage and carcass contamination with Escherichia coli O157:H7. Carcass samples were taken following the excision method described in the Decision 471/2001/EC, and fecal material was taken from the colon of the calves after evisceration. Bacteria were isolated and identified according to the MFLP-80 and MFLP-90 procedures (Food Directorate’s Health Canada’s). Eighty-eight non-sorbitol-fermenting E. coli O157:H7 isolates were obtained from 12 of the 45 calves examined. In particular, E. coli O157:H7 isolates were found in 11 (24%) fecal and five (11%) carcass samples. PCR analysis showed that all 11 fecal samples and five carcass samples carried eae-γ1-positive E. coli O157:H7 isolates. In addition, genes encoding Shigatoxins were detected in O157:H7 isolates from nine and two of those 11 fecal and five carcasses, respectively. A representative group of 32 E. coli O157:H7 isolates was analyzed by phage typing and DNA macrorestriction fragment analysis (PFGE). Five phage types (PT8, PT32v, PT32, PT54, and PT not typable) and seven (I–VII) distinct restriction patterns of similarity > 85% were detected. Up to three different O157:H7 strains in an individual fecal sample and up to four from the same animal could be isolated. These findings provide evidence of the epidemiological importance of subtyping more than one isolate from the same sample. Phage typing together with PFGE proved to be very useful tools to detect cross-contamination among carcasses and should therefore be included in HACCP programs at abattoirs. The results showed that the same PFGE-phage type E. coli O157:H7 profile was detected in the fecal and carcass samples from an animal, and also in two more carcasses corresponding to two animals slaughtered the same day. [Int Microbiol 2007; 10(2):109-116

Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia

Inflammatory proteases (mast cell tryptase and trypsins) cleave protease-activated receptor 2 (PAR2) on spinal afferent neurons and cause persistent inflammation and hyperalgesia by unknown mechanisms. We determined whether transient receptor potential vanilloid receptor 1 (TRPV1), a cation channel activated by capsaicin, protons, and noxious heat, mediates PAR2-induced hyperalgesia. PAR2 was coexpressed with TRPV1 in small- to medium-diameter neurons of the dorsal root ganglia (DRG), as determined by immunofluorescence. PAR2 agonists increased intracellular [Ca2+] ([Ca2+]i) in these neurons in culture, and PAR2-responsive neurons also responded to the TRPV1 agonist capsaicin, confirming coexpression of PAR2 and TRPV1. PAR2 agonists potentiated capsaicin-induced increases in [Ca2+]i in TRPV1-transfected human embryonic kidney (HEK) cells and DRG neurons and potentiated capsaicin-induced currents in DRG neurons. Inhibitors of phospholipase C and protein kinase C (PKC) suppressed PAR2-induced sensitization of TRPV1-mediated changes in [Ca2+]i and TRPV1 currents. Activation of PAR2 or PKC induced phosphorylation of TRPV1 in HEK cells, suggesting a direct regulation of the channel. Intraplantar injection of a PAR2 agonist caused persistent thermal hyperalgesia that was prevented by antagonism or deletion of TRPV1. Coinjection of nonhyperalgesic doses of PAR2 agonist and capsaicin induced hyperalgesia that was inhibited by deletion of TRPV1 or antagonism of PKC. PAR2 activation also potentiated capsaicin-induced release of substance P and calcitonin gene-related peptide from superfused segments of the dorsal horn of the spinal cord, where they mediate hyperalgesia. We have identified a novel mechanism by which proteases that activate PAR2 sensitize TRPV1 through PKC. Antagonism of PAR2, TRPV1, or PKC may abrogate protease-induced thermal hyperalgesia

The long noncoding RNA SUMO1P3 as urinary biomarker for monitoring bladder cancer progression

IntroductionUrothelial Bladder Cancer (BC) is the ninth most common cancer worldwide. It is classified into Non Muscle Invasive (NMIBC) and Muscle Invasive Bladder Cancer (MIBC), which are characterized by frequent recurrences and progression rate, respectively. The diagnosis and monitoring are obtained through invasive methods as cystoscopy and post-surgery biopsies. Thus, a panel of biomarkers able to discriminate BC based on grading or staging represents a significant step forward in the patients’ workup. In this perspective, long non-coding RNAs (lncRNAs) are emerged as reliable candidates as potential biomarker given their specific and regulated expression. In the present work we propose two lncRNAs, the Small Ubiquitin Modifier 1 pseudogene 3 (SUMO1P3), a poorly characterized pseudogene, and the Urothelial Carcinoma Associated 1 (UCA1) as candidates to monitor the BC progression.MethodsThis study was a retrospective trial enrolling NMIBC and MIBC patients undergoing surgical intervention: the expression of the lncRNA SUMO1P3 and UCA1 was evaluated in urine from 113 subjects (cases and controls). The receiver operating characteristic curve analysis was used to evaluate the performance of single or combined biomarkers in discriminating cases from controls.ResultsSUMO1P3 and UCA1 expression in urine was able to significantly discriminate low grade NMIBC, healthy control and benign prostatic hyperplasia subjects versus high grade NMIBC and MIBC patients. We also demonstrated that miR-320a, which binds SUMO1P3, was reduced in high grade NMIBC and MIBC patients and the SUMO1P3/miR-320a ratio was used to differentiate cases versus controls, showing a statistically significant power. Finally, we provided an automated method of RNA extraction coupled to ddPCR analysis in a perspective of clinical application.DiscussionWe have shown that the lncRNA SUMO1P3 is increased in urine from patients with high grade NMIBC and MIBC and that it is likely to be good candidate to predict bladder cancer progression if used alone or in combination with UCA1 or with miRNA320a

Nomenclature for renal replacement therapy in acute kidney injury: basic principles

Abstract This article reports the conclusions of a consensus expert conference on the basic principles and nomenclature of renal replacement therapy (RRT) currently utilized to manage acute kidney injury (AKI). This multidisciplinary consensus conference discusses common definitions, components, techniques, and operations of the machines and platforms used to deliver extracorporeal therapies, utilizing a “machine-centric” rather than a “patient-centric” approach. We provide a detailed description of the performance characteristics of membranes, filters, transmembrane transport of solutes and fluid, flows, and methods of measurement of delivered treatment, focusing on continuous renal replacement therapies (CRRT) which are utilized in the management of critically ill patients with AKI. This is a consensus report on nomenclature harmonization for principles of extracorporeal renal replacement therapies. Devices and operations are classified and defined in detail to serve as guidelines for future use of terminology in papers and research

Antidromic vasodilatation and the migraine mechanism

Despite the fact that an unprecedented series of new discoveries in neurochemistry, neuroimaging, genetics and clinical pharmacology accumulated over the last 20 years has significantly increased our current knowledge, the underlying mechanism of the migraine headache remains elusive. The present review article addresses, from early evidence that emerged at the end of the nineteenth century, the role of ‘antidromic vasodilatation’ as part of the more general phenomenon, currently defined as neurogenic inflammation, in the unique type of pain reported by patients suffering from migraine headaches. The present paper describes distinctive orthodromic and antidromic properties of a subset of somatosensory neurons, the vascular- and neurobiology of peptides contained in these neurons, and the clinical–pharmacological data obtained in recent investigations using provocation tests in experimental animals and human beings. Altogether, previous and recent data underscore that antidromic vasodilatation, originating from the activation of peptidergic somatosensory neurons, cannot yet be discarded as a major contributing mechanism of the throbbing head pain and hyperalgesia of migraine