A novel calpain inhibitor for treatment of transient retinal ischemia in the rat

After an acute ischemia/reperfusion of the rat retina, the activation of cytotoxic proteases, including calpain, results in necrosis and apoptosis of retinal ganglion cells resulting in their degeneration. Using a systemically administered calpain inhibitor that crosses the blood-retinal barrier would provide for novel systemic intervention that protects the retina from acute injury and loss of function. Herein, we study a novel calpain peptide inhibitor, cysteic-leucyl-argininal (CYLA), in an in-vivo rat model of retinal ischemia to determine functional protection using electroretinography. The CYLA prodrug was administered intraperitoneally before and/or after ischemia-reperfusion at concentrations of 20-40 mg/kg. We found that administering 20 mg/kg of CYLA only after ischemia provides significant preservation of retinal function.     

SLC26A4 variations among Graves' hyper-functioning thyroid gland

Deleterious mutations of SLC26A4 cause Pendred syndrome (PS), an autosomal recessive disorder comprising goitre and deafness with enlarged vestibular aqueducts (EVA), and nonsyndromic hearing loss (NSHL). However, the SLC26A4 hyperactivity was recently associated with the emergence of autoimmune thyroid diseases (AITD) and asthma among human and mouse model. Here, by direct sequencing, we investigate the sequences of the 20 coding exons (2 to 21) of SLC26A4 and their flanking intron-exon junctions among patients affected with Graves' disease (GD) hyperthyroidism. Ten mono-allelic variants were identified, seven of which are intronic and previously unreported. Two, c.898A>C (p.I300L) and c.1061T>C (p.F354S), of the three exonic variants are non synonymous. The p.F354S variant is already described to be involved in PS or NSHL inheritances. The exploration by PCR-RFLP of p.I300L and p.F354S variants among 132 GD patients, 105 Hashimoto thyroiditis (HT), 206 Healthy subjects and 102 families with NSHL have shown the presence of both variants. The p.F354S variation was identified both among patients (1~HT and 3 GD) and healthy subjects (n=5). Whereas, the p.I300L variant was identified only in GD patients (n=3). Our studies provide evidence of the importance of systematic analysis of SLC26A4 gene sequences on models other than deafness. This approach allows the identification of new variants and the review of the pathogenic effects of certain mono-allelic variants reported responsible for PS and NSHL development.     

Bcl-2 expression and triple negative profile in breast carcinoma

Appearance of non-Hodgkin’s lymphomas (NHL) and renal cell carcinoma (RCC) in same person has been reported in the literature. There is a higher-than-expected incidence of co-occurrence of these neoplastic disorders. The cause for this association remains speculative. Two epidemiological studies have shown that the observed-to-expected ratio for occurrence of RCC in NHL patients were 1.86 to 2.67. We herein describe five patients with both RCC and lymphoid malignancies, and reviewed possible explanations for the association. In three of the five patients, RCC was diagnosed during lymphoproliferative disease work-up, and remaining two cases had been diagnosed with chronic lymphocytic leukemia 1 and 5 years prior to RCC. All RCC cases were detected during staging of the primary tumor, usually by CT scan and/or ultrasound. Our data are in correlation with the literature that there is an increased association of RCC and NHL more often among male patients, and that the lymphoproliferative disease often presents with extranodal involvement. The specialists should be alerted for this possibility when evaluating patients at diagnosis or during follow-up.     

Convulsions néonatales révélant une incontinentia pigmenti

Incontinentia pigmenti (IP) is a rare affection inherited as X-linked dominant disease. It is usually lethal in male infants. IP can affect ectodermal tissues such as the skin, teeth, eyes, bones, and the central nervous system. Skin lesions occur mostly during the neonatal period and are characterized by a classic progression in 4 stages leading to hyperpigmentation. We report on the case of a female neonate presenting on the 3rd day of life with seizures without obvious cause, in which the diagnosis of IP was made 1 week later when skin lesions appeared.     

The in vitro effects of zearalenone and T-2 toxins on Vero cells

The aim of the present study was to investigate in vitro, whether cytolethality and oxidative damage is enhanced by combination of both mycotoxins as compared to their individual effect. In our paper, we applied a tiered in vitro experimental approach in order to predict the possible health risk effects of two interactive fusarial toxins. Considering the concomitant production of zearalenone (ZEN) and T-2 toxin, it is very likely that humans and animals are always exposed to the mixture rather than to individual compounds.Our results clearly showed that cultured renal cells respond to individual (ZEN) or T-2 toxin exposure by a moderate inhibition of cell proliferation, respectively. However, when combined, they exert a more significant decrease in cell viability. Similar results were found for the investigated oxidative status endpoints. When combined, ZEN and T-2 toxin increased ROS production and heat shock protein (Hsp) 70 expression as compared to the effect of each mycotoxin taken alone.We can conclude that the mixture of ZEN and T-2 toxin increased their toxic effects. The health risk is heightened by the interactions between co-occurring mycotoxins.     

UDP-glucuronosyltransferase genetic variation in North African populations: a comparison with African and European data

Background: Genetic variation in glucuronosyltransferases (UGT) is crucial in drug metabolism and risk of some diseases.

Aim: To examine genetic variation in UGT in North African populations.

Subjects and methods: Allele frequencies of SNPs UGT1A4^24Thr, UGT1A4^48Val, UGT2B15^85Tyr, UGT2B15^523Thr and UGT2B17 CNV deletion from Morocco, Algeria, Tunisia and Libya were compared to European and Sub-Saharan populations.

Results: North Africans are the group with the highest genetic heterogeneity given by internal differences in the occurrence of UGT2B17 deletion, UGT1A4^48Val and UGT1A4 haplotypes. UGT2B15 SNPs differentiate Sub-Saharans from the rest of the populations.

Conclusion: North African populations show a high frequency of carriers of UGT2B15^523Thr, a variant linked to an increased risk of prostate cancer. High Atlas Moroccans and Algerians show low frequency of UGT2B17^del, a variant associated with high concentrations of testosterone and oestradiol.     

Epidemiological profile of methicillin resistant Staphylococcus epidermidis with diminished sensitivity to teicoplanin and isolated from neutropenic patients at the National Center of Bone Marrow Transplantation in Tunis]

Fifty-seven methicillin resistant S. epidermidis with decreased susceptibility to teicoplanin were obtained from 14 neutropenic patients on a period of 11 months (19 February-31 December 1998) from essentially blood culture (30 strains) and ORL specimens (21 strains). The MIC90 of methicillin, gentamicin, ofloxacin and telcoplanin were respectively 1024, 1024, 512 and 32 mg/l. We applied pulsed field gel electrophoresis (PFGE) after Smal digestion to 21 isolates choosed between eight patients with multiple isolates (> two strains). For epidemiological control, a MetiR and TeicoR S. epidermidis isolated from blood culture taken from Caen CHU was include in study. Twenty-one isolates were separated by PFGE into eight group, from I to VIII. The control strain was classed in group IX. Group I include 14 strains which can be subdivised on three sub-types (differed by a single to three bands): seven strains have the pulsotype Ia and obtained respectively from five strains in transplantation unit and two strains in hematology unit. Two strains have the pulsotype Ib and isolated in the two units. Five strains have the pulsotype Ic and obtained also from transplantation unit (four strains) and hematology unit (one strain). All the other pulsotypes were identified in only one strain, frequently in association with the pulsotype I. Until recently, infections due to coagulase negative staphylococci have been regarded as endogenous in origin, these results with some pulsotype of S. epidermidis MetiR and TeicoR in the two separate units suggered a nosocomial origin, probably by medical staff transmission because no S. epidermidis TeicoR was isolated from environmental control during all the period.     

Intraspecific 16S rRNA gene diversity among clinical isolates of Neisseria species

In the present work, nearly the entire 16S rRNA gene sequences of 46 clinical samples of Neisseria spp. were determined, and the aligned sequences were analyzed to investigate the diversity of 16S rRNA genes in each commensal Neisseria species. Two 16S rRNA types were identified in two Neisseria sicca strains, three 16S rRNA types in five Neisseria macacae strains, fourteen 16S rRNA types in twenty Neisseria flavescens isolates, and fourteen 16S rRNA types in nineteen Neisseria mucosa isolates. The number of nucleotides that were different between 16S rRNA sequences within specie ranged from 1 to 15. We found high intraspecific sequence variation in 16S rRNA genes of Neisseria spp. strains.