JC Virus T-Antigen DNA in Gastrointestinal Mucosa of Immunosuppressed Patients: A Prospective,Controlled Study

Background  

JC virus (JCV), a polyoma virus, is the etiological agent of progressive multifocal leukoencephalopathy in immunosuppressed patients. JCV T-Ag has proven oncogenic potential and is expressed in colonic polyps and carcinomas. We proposed that the prevalence of JCV T-Ag DNA is higher in the normal gastrointestinal (GI) mucosa of immunosuppressed patients compared with their immunocompetent counterparts.     

Corynebacterium striatum—A classic pathogen eluding diagnosis

We report one case of infective endocarditis and two cases of arthritis due to Corynebacterium striatum. After reviewing all previously reported cases, we illustrate the clinical features typical of infection, including nosocomial risk factors and prominent embolic phenomena in the cases of endocarditis. Our cases underscore the importance of prompt diagnosis when confronted with positive blood and synovial cultures. This ubiquitous organism and common contaminant is a rare yet deadly pathogen.     

Passive and Carrier-Mediated Intestinal Absorption Components of Two Angiotensin Converting Enzyme (ACE) Inhibitor Prodrugs in Rats: Enalapril and Fosinopril

The intestinal absorption mechanism of two ACE inhibitor prodrugs, enalapril and fosinopril, was investigated in rats using a single-pass perfusion method. A modified boundary layer solution was applied to determine the apparent intestinal wall permeability. The prodrug enalapril is well absorbed from rat jejunum, whereas the parent drug, enalaprilat, is poorly absorbed. The permeability of enalapril is concentration dependent and is decreased by the dipeptide Tyr-Gly and by cephradine but not by the amino acids L-leucine or L-phenylalanine, indicating a nonpassive absorption mechanism via the small peptide carrier-mediated transport system. In contrast, fosinopril is readily absorbed by a concentration-independent mechanism without the involvement of the peptide carrier.     

Oral Absorption of Peptides: Influence of pH and Inhibitors on the Intestinal Hydrolysis of Leu-Enkephalin and Analogues

Leu-enkephalin (YGGFL) and several analogues were chosen as model peptides for the study of peptide absorption and hydrolysis in the rat jejunum. An HPLC assay was adapted to detect YGGFL or the analogues and metabolites. Peptide hydrolysis was studied in the rat jejunum using a single-pass perfusion method. Extensive hydrolysis of YGGFL was observed in the rat jejunum and approaches to reduce its metabolism were studied. The brush border enzymes are a major site of enkephalin hydrolysis. Lumenal peptidases were secondary to the brush border enzymes in hydrolyzing the enkephalins in this system. In the in situ perfusion system, YGGFL is hydrolyzed primarily to Tyr and GGFL by the brush border aminopeptidase and to YGG and FL by brush border endopeptidase. Lowering the jejunal pH below 5.0 significantly reduces aminopeptidase activity and, to a lesser extent, endopeptidase activity. An aminopeptidase inhibitor, amastatin, produced more pronounced inhibitory effects at higher pH and the endopeptidase inhibitors, tripeptides YGG and GGF, are effective even below pH 5.0. Coperfusion of YGGFL with a combination of aminopeptidase and endopeptidase inhibitors, e.g., amastatin and YGG, is more effective in inhibiting hydrolysis since both metabolic pathways are inhibited. Leu-D(Ala)²-enkephalin, while showing enhanced stability against aminopeptidase hydrolysis, is hydrolyzed at the Gly–Phe bond by the endopeptidase. Its hydrolysis is not affected by pH changes or amastatin but is decreased by YGG. The YGGFL wall permeability was estimated and is not a limiting factor for oral absorption.     

The challenge of using the low back pain guidelines: a qualitative research

PURPOSE: Current low back pain (LBP) clinical guidelines have helped to summarize the scientific evidence and research, but have failed to provide tools and guide family physicians (FPs). The purpose of this study is to identify barriers and facilitators for the implementation of LBP guidelines from family FPs' perspective. METHODS: A qualitative focus group study of FPs in the north of Israel. Purposeful sampling was used to recruit participants, all of them board-certified FPs. Four focus groups were created, and discussions were taped, transcribed and analysed for major themes. RESULTS: Focus groups findings have expanded the understanding of the intellectual and mental challenges faced by Israeli FPs caring for LBP patients and highlighted the many obstacles to implementing LBP guidelines. Physicians' decision-making, pertaining to LBP, functions on three levels simultaneously: the physicians' agenda based on familiarity with the guidelines; their need to remain grounded in the context of the specific patient-doctor relationship; and the constraints and demands of the physician's workplace, medical system and environment. CONCLUSIONS: Despite an overall positive attitude towards LBP guideline implementation, FPs found it hard to come to terms with the conflicting dimensions of LBP patient care. The patient-doctor interaction determined the outcome of the encounter, whether it complied with the guidelines and whether the encounter leads to a healing process or to a vicious circle of unnecessary utilization of services.     

The role of the individual TOM subunits in the association of PINK1 with depolarized mitochondria

Journal of Molecular Medicine - Mitochondria dysfunction is involved in the pathomechanism of many illnesses including Parkinson’s disease. PINK1, which is mutated in some cases of familial...     

HIV-1 fusion peptide targets the TCR and inhibits antigen-specific T cell activation

The fusion peptide (FP) in the N terminus of the HIV envelope glycoprotein, gp41, functions together with other gp41 domains to fuse the virion with the host cell membrane. We now report that FP colocalizes with CD4 and TCR molecules, coprecipitates with the TCR, and inhibits antigen-specific T cell proliferation and proinflammatory cytokine secretion in vitro. These effects are specific: T cell activation by PMA/ionomycin or mitogenic antibodies is not affected by FPs, and FPs do not interfere with antigen-presenting cell function. In vivo, FPs inhibit the activation of arthritogenic T cells in the autoimmune disease model of adjuvant arthritis and reduce the disease-associated IFN-gamma response. Hence, FPs might play 2 roles in HIV infection: mediating membrane fusion while downregulating T cell responses to itself that could block infection. Disassociated from HIV, however, the FP molecule provides a novel reagent for downregulating undesirable immune responses, exemplified here by adjuvant arthritis.