New analysis of the toxic compounds from the Androctonus mauretanicus mauretanicus scorpion venom

Scorpion venoms are very complex mixtures of molecules, most of which are peptides displaying different kinds of biological activity. Indeed, these peptides specifically bind to a variety of pharmacological targets, in particular ionic channels located in prey tissues, resulting in neurotoxic effects. Toxins modulating Na+, K+, Ca2+ and Cl(-) currents have been described in scorpion venoms. In this work, we have used several specific antibodies raised against the most lethal scorpion toxins already described to screen the Moroccan scorpion Androctonus mauretanicus mauretanicus venom in order to characterize new compounds. This immunological screening was also implemented by toxicity tests in mice and with mass spectrometry study, providing new informations on the molecular composition of this venom. In fine, we were able to determine the molecular masses of 70-80 different compounds. According to the immunological data obtained, many toxins cross-react with three sera raised against the most lethal alpha-toxins found in North African scorpion venoms, but not at all with those raised against the main beta-toxins from South and North American venoms. Some of the previously described toxins from Androctonus mauretanicus mauretanicus venom could thus be detected by combining immunological tests, toxicity in mice and molecular masses. Among these toxins, one of them, which showed a mild cross-reaction with the serum raised against AaH I (a highly potent toxin from the venom of Androctonus australis), was identified as Amm III and fully sequenced.     

Interpretation of hypertransaminasemia

Raised serum level of transaminases aspartate (aminotransferase and alanine aminotransferase) is a frequent situation in medical practice. It is considered as moderate when the level is under 10 times normal and as chronic when it lasts for more than 6 months. The most common etiologies for chronically elevated transaminases are alcohol use, viral hepatitis, liver steatosis, diabetes, obesity and medications. Many non invasive tests, including history, physical examination, blood tests (markers for hepatitis A and B, muscular enzymes), and imaging procedures (abdominal ultrasonography) are usually done and lead to a correct diagnosis in 80% of patients. When the diagnosis cannot be determined non invasively a liver biopsy is recommended in order to make diagnosis, to evaluate the prognosis and to start an adapted treatment.     

Expressed isolated integrin beta1 subunit cytodomain induces endothelial cell death secondary to detachment

Expression of isolated beta integrin cytoplasmic domains in cultured endothelial cells was reported to induce cell detachment and death. To test whether cell death was the cause or the consequence of cell detachment, we expressed isolated integrin beta1 cytoplasmic and transmembrane domains (CH1) in cultured human umbilical vein endothelial cells (HUVEC), and monitored detachment, viability, caspase activation and signaling. CH1 expression induced dose-dependent cell detachment. At 24 h over 90% of CH1-expressing HUVEC were detached but largely viable (>85%). No evidence of pro-caspase-8,-3, and PARP cleavage or suppression of phosphorylation of ERK, PKB and Ikappa-B was observed. The caspase inhibitor z-VAD did not prevent cell detachment. At 48 h, however, CH1-expressing cells were over 50% dead. As a comparison trypsin-mediated detachment resulted in a time-dependent cell death, paralleled by caspase-3 activation and suppression of ERK, PKB and Ikappa-B phosphoyrylation at 24 h or later after detachment. HUVEC stimulation with agents that strengthen integrin-mediated adhesion (i.e. PMA, the Src inhibitor PP2 and COMP-Ang1) did not prevent CH1-induced detachment. Expression of CH1 in rat carotid artery endothelial cells in vivo caused endothelial cell detachment and increased nuclear DNA fragmentation among detached cells. A construct lacking the integrin cytoplasmic domain (CH2) had no effect on adhesion and cell viability in vitro and in vivo. These results demonstrate that isolated beta1 cytoplasmic domain expression induces caspase-independent detachment of viable endothelial cells and that death is secondary to detachment (i.e. anoikis). They also reveal an essential role for integrins in the adhesion and survival of quiescent endothelial cells in vivo.     

Profile of antimicrobial resistance of agents causing urinary tract infections in children

OBJECTIVE: The management of urinary tract infection in children faces the problem of the emergence of resistant strains to antibiotics. The aim of this study is to precise the frequency of the different germs and their susceptibility to antibiotics. METHODS: We report a retrospective study concerning 200 cases of urinary tract infection hospitalised in the paediatric department of Monastir between January 1995 and December 2000. There were 58 boys and 142 girls aged between two months and 14 years with a mean age of 5 years. The frequency of urinary tract infection is 1.85%. RESULTS: The most common causative agent is Escherichia coli in 75.5% of cases, followed by Proteus mirabilis (10%) then by Klebsiella pneumoniae (6%). Escherichia coli is predominant in girls, whereas Proteus mirabilis and Klebsiella pneumoniae are likely encountred in boys. Of all the strains, 96% are resistant to ampicillin, amoxicillin and cefalotin, 67% to amoxicillin + clavulanic acid and 34% to cotrimoxazole. A resistance to ampicillin, amoxicillin and cefalotin is noted in 96% of the germs. The resistance is of 67% for amoxicillin + clavulanic-acid and of 34% for cotrimoxazole. However, third generation cephalosporins and aminoglycosides remain usually active on the majority of strains incriminated in these infections a part from Pseudomonas.     

The impact of out‐of‐pocket health expenditure on household impoverishment: Evidence from Morocco

Health financing in Morocco relies mainly on out‐of‐pocket (OoP) payments. World Health Organization (WHO) has shown that these payments can expose households to catastrophic health expenditure (hereinafter CHE) and impoverish them. The study examines the financial burden of OoP health payments on Moroccan households. Two approaches—that developed by Wagstaff and Doeslear and the one advocated by WHO—are adopted to estimate the extent of CHE. These show that 1.77% of households incurred CHE at the 40% threshold for nonfood expenditure. At the 10% threshold for total consumption expenditure, 12.8% of households incurred CHE. We find that these OoP payments have made 1.11% of Moroccan households poorer. In analyzing the determinants of CHE, we estimated an ordered probit model. It appears that any of (a) hospitalization, (b) presence of an elderly person in the household, or (c) the level of poverty increases significantly the likelihood of health expenditure becoming catastrophic. On the other hand, we find that coverage by health insurance protects against CHE.     

Effect of donor CTLA-4 alleles and haplotypes on graft-versus-host disease occurrence in Tunisian patients receiving a human leukocyte antigen-identical sibling hematopoietic stem cell transplant

The CTLA-4 genetic variation, such as single nucleotide polymorphisms (SNPs) may be critical and can affect the functional activity of cells that initiate the graft-versus-host disease (GVHD) effects. The aim of this study is to examine the effect of donor CTLA-4 alleles and haplotypes for the -318C>T and the 49A>G polymorphisms on the occurrence of GVHD in Tunisians recipients of HSCs. A total of 112 patients and their 112 respective sibling donors of HSCs were enrolled in this study. All patients had either grades 0-I or grades II-IV acute GVHD, or chronic GVHD. The SNPs genotyping assay was performed using sets of sequence specific primers (SSP-PCR). The single marker association analysis showed that the 49G allele, in a genetic recessive model, may be a potential risk factor only for the chronic GVHD (p = 0.032, odds ratio [OR] = 2.58, 95% confidence interval = 1.05-6.32). The haplotypes analyses showed that the CTLA-4 -318C49G nucleotide combination is significantly associated with the incidence of chronic GVHD (p = 0.043, χ2 = 3.27). Donor CTLA-4 -318C49G haplotype may be a significant risk factor for developing chronic GVHD after allo-stem cell transplantation. We suppose that donor T cells expressing this haplotype in a homozygous state have higher proliferation than those expressing other haplotypes, especially after recognition of the recipient's minor histocompatibility antigens.     

Chromosomal segregation in spermatozoa of five Robertsonian translocation carriers t(13;14)

Purpose  

To analyse the segregation of a Robertsonian translocation t(13;14) in five male carriers, and to verify a possible inter-chromosomal effect (ICE) of the Robertsonian translocation on chromosomes 18, X, and Y.