An isolated anterior mitral leaflet cleft: a case report

<p>Abstract</p> <p>Introduction</p> <p>The anterior mitral leaflet cleft is an unusual congenital lesion most often encountered in association with other congenital heart defects. The isolated anterior leaflet cleft is quite a rare anomaly and is usually cause of mitral valve regurgitation. The importance of the lesion is that it is often correctable. When feasible, cleft suture and, eventually, annuloplasty are preferable to valve replacement. Echocardiography is the first choice technique in the evaluation of mitral valve disease, providing useful information about valve anatomy and hemodynamic parameters.</p> <p>Case presentation</p> <p>We present a case of an isolated anterior mitral leaflet cleft producing moderate-severe mitral regurgitation correctly identified by echocardiography and successfully surgically corrected.</p> <p>Conclusion</p> <p>Isolated cleft is a rare aberration, that has to be known in order to be diagnosed. Transthoracic and transesophageal echocardiography is the most useful non invasive technique for cleft diagnosis and to indicate the right surgical correction.</p

The pharmacology and activity of non-steroidal anti-inflammatory drugs (NSAIDs): a review of their use as an adjuvant treatment in patients with HBV and HCV chronic hepatitis

Introduction: Different DNA and RNA viruses exploit common strategies to support their persistence and replication in infected individuals. In particular, the hepatitis B virus (HBV) and the hepatitis C virus (HCV) cause major health problems worldwide. These pathogens exert an immunosuppressive role by inducing the persistent activation of cyclooxygenase-2 (COX-2) and an increased synthesis of prostaglandin E2 (PGE2). The suppression of this proinflammatory network by non-steroidal anti-inflammatory drugs (NSAIDs) has been proposed as a therapeutic approach to decrease viral replication. Materials and methods: In this review, the role of inflammation in the support of viral replication and NSAIDs and ketoprofen pharmacology are briefly discussed. In addition, studies that have investigated the use of NSAIDs for the treatment of HBV and HCV chronic hepatitis, which were identified by a systematic literature search of PubMed and MEDLINE, are reported. Results: To date, pegylated-interferon (PEG-IFN) and/or nucleot(s)ide analogues and PEG-IFN and ribavirin remain the standard therapy for HBV and HCV chronic hepatitis, respectively. Discussion: The use of NSAIDs in patients with chronic viral hepatitis has only a ''historical'' interest. Nevertheless, the possible usefulness of ketoprofen with PEG-IFN and ribavirin for HCVinfected patients, non-responders to standard therapy or with genotype 1, should be evaluated in future clinical studies

The impact of active HIV-1 replication on the physiological age-related decline of immature-transitional B-cells in HIV-1 infected children

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Burkitt's lymphoma mimicking EBV disease as first sign of vertical HIV infection in an adolescent

Burkitt's Lymphoma (BL) rarely represents the first clinical manifestation of vertical HIV infection in adolescent in Western Europe. We report the case of a 17 year-old boy with two week history of fever and enlarged cervical lymph nodes firstly misdiagnosed as EBV infection, subsequently diagnosed as Burkitt's Lymphoma and vertical HIV infection

The inhibition of RasGRF2, but not RasGRF1, alters cocaine reward in mice

Ras/Raf/MEK/ERK(Ras-ERK) signaling has been implicated in the effects of drugs of abuse. Inhibitors of MEK1/2, the kinases upstream of ERK1/2, have been critical in defining the role of the Ras-ERK cascade in drug-dependent alterations in behavioral plasticity, but the Ras family of small GTPases has not been extensively examined in drug-related behaviors. We examined the role of Ras Guanine Nucleotide Releasing Factor 1(RasGRF1) and 2(RasGRF2), upstream regulators of the Ras-ERK signaling cascade, on cocaine self-administration(SA) in male mice. We first established a role for Ras-ERK signaling in cocaine SA, demonstrating that pERK1/2 is upregulated following SA in C57Bl/6N mice in striatum. We then compared RasGRF1 and RasGRF2 knock-out(KO) mouse lines, demonstrating that cocaine SA in RasGRF2 KO mice was increased relative to wild-type(WT) controls, while RasGRF1 KO and WT mice did not differ. This effect in RasGRF2 mice is likely mediated by the Ras-ERK signaling pathway, as pERK1/2 upregulation following cocaine SA was absent in RasGRF2 KO mice. Interestingly, the lentiviral knockdown of RasGRF2 in the NAc had the opposite effect to that in RasGRF2 KO mice, reducing cocaine SA. We subsequently demonstrated that the MEK inhibitor PD325901 administered peripherally prior to cocaine SA increased cocaine intake, replicating the increase seen in RasGRF2 KO mice, while PD325901 administered into the NAc decreased cocaine intake, similar to the effect seen following lentiviral knockdown of RasGRF2. These data indicate a role for RasGRF2 in cocaine SA in mice that is ERK-dependent, and suggest a differential effect of global versus site-specific RasGRF2 inhibition

Evaluation of human gene variant detection in amplicon pools by the GS-FLX parallel Pyrosequencer

<p>Abstract</p> <p>Background</p> <p>A new priority in genome research is large-scale resequencing of genes to understand the molecular basis of hereditary disease and cancer. We assessed the ability of massively parallel pyrosequencing to identify sequence variants in pools. From a large collection of human PCR samples we selected 343 PCR products belonging to 16 disease genes and including a large spectrum of sequence variations previously identified by Sanger sequencing. The sequence variants included SNPs and small deletions and insertions (up to 44 bp), in homozygous or heterozygous state.</p> <p>Results</p> <p>The DNA was combined in 4 pools containing from 27 to 164 amplicons and from 8,9 to 50,8 Kb to sequence for a total of 110 Kb. Pyrosequencing generated over 80 million base pairs of data. Blind searching for sequence variations with a specifically designed bioinformatics procedure identified 465 putative sequence variants, including 412 true variants, 53 false positives (in or adjacent to homopolymeric tracts), no false negatives. All known variants in positions covered with at least 30× depth were correctly recognized.</p> <p>Conclusion</p> <p>Massively parallel pyrosequencing may be used to simplify and speed the search for DNA variations in PCR products. Our results encourage further studies to evaluate molecular diagnostics applications.</p

TRAIL reduces impaired glucose tolerance and NAFLD in the high-fat diet-fed mouse

Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis inducing ligand) may have an important role in the treatment of type 2 diabetes. It has been shown that TRAIL deficiency worsens diabetes and that TRAIL delivery, when it is given before disease onset, slows down its development. The present study aimed at evaluating whether TRAIL had the potential not only to prevent, but also to treat type 2 diabetes. Thirty male C57BL/6J mice were randomized to a standard or a high-fat diet (HFD). After 4 weeks of HFD, mice were further randomized to receive either placebo or TRAIL, which was delivered weekly for 8 weeks. Body weight, food intake, fasting glucose, and insulin were measured at baseline and every 4 weeks. Tolerance tests were performed before drug randomization and at the end of the study. Tissues were collected for further analyses. Parallel in vitro studies were conducted on HepG2 cells and mouse primary hepatocytes. TRAIL significantly reduced body weight, adipocyte hypertrophy, free fatty acid levels, and inflammation. Moreover, it significantly improved impaired glucose tolerance, and ameliorated non-alcoholic fatty liver disease (NAFLD). TRAIL treatment reduced liver fat content by 47% in vivo as well as by 45% in HepG2 cells and by 39% in primary hepatocytes. This was associated with a significant increase in liver peroxisome proliferator-activated receptor (PPAR) \u3b3 (PPAR\u3b3) co-activator-1 \u3b1 (PGC-1\u3b1) expression both in vivo and in vitro, pointing to a direct protective effect of TRAIL on the liver. The present study confirms the ability of TRAIL to significantly attenuate diet-induced metabolic abnormalities, and it shows for the first time that TRAIL is effective also when administered after disease onset. In addition, our data shed light on TRAIL therapeutic potential not only against impaired glucose tolerance, but also against NAFLD