Persulfidation of mitoKv7.4 channels contributes to the cardioprotective effects of the H2S-donor Erucin against ischemia/reperfusion injury.

BACKGROUND: Hydrogen sulfide (H2S) is a gasotransmitter deeply involved in cardiovascular homeostasis and implicated in the myocardial protection against ischemia/reperfusion. The post-translational persulfidation of cysteine residues has been identified as the mechanism through which H2S regulates a plethora of biological targets. Erucin (ERU) is an isothiocyanate produced upon hydrolysis of the glucosinolate glucoerucin, presents in edible plants of Brassicaceae family, such as Eruca sativa Mill., and it has emerged as a slow and long-lasting H2S-donor. AIM: In this study the cardioprotective profile of ERU has been investigated and the action mechanism explored, focusing on the possible role of the recently identified mitochondrial Kv7.4 (mitoKv7.4) potassium channels. RESULTS: Interestingly, ERU showed to release H2S and concentration-dependently protected H9c2 cells against H2O2-induced oxidative damage. Moreover, in in vivo model of myocardial infarct ERU showed protective effects, reducing the extension of ischemic area, the levels of troponin I and increasing the amount of total AnxA1, as well as co-related inflammatory outcomes. Conversely, the pre-treatment with XE991, a blocker of Kv7.4 channels, abolished them. In isolated cardiac mitochondria ERU exhibited the typical profile of a mitochondrial potassium channels opener, in particular, this isothiocyanate produced a mild depolarization of mitochondrial membrane potential, a reduction of calcium accumulation into the matrix and finally a flow of potassium ions. Finally, mitoKv7.4 channels were persulfidated in ERU-treated mitochondria. CONCLUSIONS: ERU modulates the cardiac mitoKv7.4 channels and this mechanism may be relevant for cardioprotective effects.

Genetic diversity and relationships among six local cattle populations in semi-arid areas assessed by a bovine medium-density single nucleotide polymorphism data.

The local cattle populations belonging to the 'Brune de l'Atlas' cattle in Algeria and Morocco are potential resources in terms of genetic diversity and socioeconomic prevalence and their characterization is an essential step in any program designed to conserve genetic diversity. Our objectives were to assess the genetic diversity, the population structure and relationships among four Algerian cattle breeds, the Biskra, Cheurfa, Chelifienne and Guelmoise and of two Moroccan, the Oulmès-Zaër and Tidili by genotyping 50 309 single nucleotide polymorphism in 203 unrelated animals. A low population structure was observed across breeds with pairwise F ST values ranging from 0.008 to 0.043, suggesting a high level of gene flow. These data were combined with the available data on cattle populations representative of Europe (EUT), West African taurine (WAT) and zebu (ZEB). Principle Components Analysis was carried out which revealed that the Maghrebin populations are closer to the EUT/ZEB population than to the WAT. Structure analysis confirmed this mixed origin of the Maghrebin cattle populations. We also detected the influence of zebu breeds in Cheurfa and Guelmoise populations. This study provides the first information about genetic diversity within and between Algerian and Moroccan cattle populations and gives a detailed description of their genetic structure and relationships according to their historical origins. This study revealed that several combined effects contributed to shape the genetic diversity of the six Maghrebin populations studied: (i) gene flow among local breeds, (ii) the recent introgression of European breeds in local Algerian breeds and (iii) the traditional management systems. The results of this study will primarily assist policy makers and livestock keepers to make useful decisions for improvement of genetic resources while ensuring the preservation and conservation of local breeds in Algeria and Morocco.

Effect of genetic European taurine ancestry on milk yield of Ankole-Holstein crossbred dairy cattle in mixed smallholders system of Burundi highlands.

Different breeding systems associated with specific bovine genetic resources have coexisted in Burundi. To prepare for the development of a national action plan for the improvement of bovine genetic resources in Burundi, we aimed at performing genetic characterization of Ankole and Ankole × European crossbred individuals and assessing the effect of European ancestry on milk productivity of cows kept under the mixed crops livestock system. To that end, we genotyped 37 Ankole and 138 crossbred individuals on 42 636 SNPs and combined these genotypes with those from 21 cattle breeds, representative of the bovine genetic diversity. We also measured milk yield not suckled and estimated suckled milk. Given the results, we confirmed the indicine × African taurine admixed origin of the Ankole in Burundi and showed that crossbred individuals present a high proportion of European ancestry (i.e. 57% on average). As the proportion of European ancestry increased, milk yield increased by 0.03 ± 0.01 l/day, at a lower extent than expected. We also observed that breeders were unable to correctly evaluate the European proportion in their livestock. Our results may provide useful information for objective dairy breeding in Burundi. As an example, an ex-situ conservation program of Ankole within the framework of value chains is proposed as an accompanying strategy to improve the sustainability of the crossbreeding program.

Transcription specificity of the class Ib genes SLA-6, SLA-7 and SLA-8 of the swine major histocompatibility complex and comparison with class Ia genes.

Our aim was to analyse the transcription levels of the three non-classical class Ib genes SLA-6, SLA-7 and SLA-8 of the swine major histocompatibility complex in various tissues and conditions and to compare them to the transcription levels of classical class Ia genes. Twenty-five adult tissues from two pig breeds, pig renal PK15 cells infected with the Pseudorabies virus, and peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide or a mixture of phorbol myristate acetate and ionomycin were included in our study. Relative transcription was quantified by quantitative real-time PCR. On average, in adult tissues and PBMCs and compared to SLA-6, the transcription level of SLA-Ia genes was 100-1000 times higher, the level of SLA-8 was 10-20 times higher, and that of SLA-7 was five times higher. Thus, SLA-8 is the most transcribed SLA-Ib gene, followed by the SLA-7 and SLA-6 genes. The highest transcription levels of SLA-Ib transcripts were found in the lymphoid organs, followed by the lung and the digestive tract. The tissue variability of expression levels was widest for the SLA-6 gene, with a 1:32 ratio between the lowest and highest levels in contrast to a 1:12 ratio for the SLA-7 and SLA-8 genes and a 1:16 ratio for the SLA-Ia genes. During PK-15 infection and PBMC stimulation, SLA-Ia and SLA-8 genes were downregulated, whereas SLA-6 and SLA-7 were upregulated, downregulated or not significantly modified. Our overall results confirm the tissue-wide transcription of the three SLA-Ib genes and suggest that they have complementary roles.

Clinical outcome evaluation following cyclosporine a treatment in moderate to severe psoriasis: a retrospective study.

This retrospective study was conducted on 193 patients treated in three Italian Psoriasis Units with the aim of evaluating the evolution of psoriasis severity and the safety of cyclosporin A (Sandimmun Neoral) in moderate to severe psoriasis, at the regimens usually employed in common clinical practice. Cyclosporin A (CyA) was administered for a mean period of 14 months, the mean number of treatment courses was 1.6 (range 1-4), and the mean dosage ranged from 1.5 to 3.1 mg/kg/die. Ninety percent of patients obtained complete therapeutic success or clinical remission, defined as complete clearance of lesions or clearance of lesions with residual minor pigmentations respectively, when treated with CyA in monotherapy. The mean Psoriasis Area and Severity Index (PASI) decreased from 23.31 before CyA administration to 5.64 at the end of treatment. The clinicians judgement on CyA tolerability was good/very good in 90 percent of cases. Adverse events occurred in 36 percent of patients, with hypertension being the most commonly reported (17.6 percent). The results of this study indicate that in the common clinical practice CyA in moderate to severe psoriasis is usually employed at low doses, resulting both safe and effective.

A combined transcriptomic approach to analyse the dialogue between pseudorabies virus and porcine cells.

The pseudorabies virus (PrV), a porcine Alphaherpesvirus, is a good model for the study of virus-host cell dialog. As PrV has a strong tropism for mucous epithelial cells, we chose to follow in vitro the PrV time course-infection of porcine PK15 cells. The viral and cellular transcriptome modifications were simultaneously analysed using a combined SLA/PrV cDNA microarray, the porcine Qiagen-NRSP8 oligonucleotides microarray and real time quantitative PCR.Ahigh increase in viral gene expression was found from 4 h post-infection (PI), concomitantly to the first viral progeny and most viral genes were differentially expressed 12 h PI. No early global cellular shutoff was observed but many cellular genes were downregulated between 8 and 12 h PI, when UL41 transcripts encoding the virion shutoff protein, were first detected. Several genes involved in the MHC class I mediated antigenic pathway were downregulated including SLA-la, TAP1, TAP2, PSMB8 and PSMB9 genes. These results suggested that PrV prevents the viral antigen presentation by epithelial cells to cytotoxic T lymphocytes by decreasing transcription levels of SLA Ia mediated antigenic pathway genes. Other genes involved in the immune response, the apoptosis pathway, nucleic acid metabolism and cytoskeleton also appeared to be regulated during PrV infection. The combined approach will help to decipher host response evasion strategies developed by PrV and to study early cellular modifications.

TNF as a malaria candidate gene: polymorphism-screening and family-based association analysis of mild malaria attack and parasitemia in Burkina Faso.

We have previously obtained strong evidence for linkage of mild malaria attack to the MHC region, with a peak close to the tumor necrosis factor (TNF) gene. We screened, for polymorphisms, the entire TNF gene in the same sample of 34 families comprising 197 individuals living in a Plasmodium falciparum endemic area and we found 17 polymorphisms. In a longitudinal study, we investigated whether the 11 most frequent and informative polymorphisms were associated with mild malaria attack and maximum parasitemia, which was the highest parasitemia in each individual over 2 years. Mild malaria attack and maximum parasitemia were positively correlated. Transmission disequilibrium tests showed nominal evidence for association between TNF-1031, TNF-308, TNF851 and TNF1304 polymorphisms, and mild malaria attack on the one hand, and between TNF-238, TNF851 and TNF1304 polymorphisms, and maximum parasitemia on the other hand. After accounting for multiple tests, we confirmed the association of TNF-238 with maximum parasitemia and the association of TNF1304 and TNF851 with maximum parasitemia and mild malaria attack. The association tests with mild malaria attack suggest a moderate effect of TNF-308 polymorphism. In conclusion, our study suggests that several TNF variants may be part of the genetic determinants for maximum parasitemia and/or mild malaria attack.

[Skin and respiratory allergic disease caused by polyfunctional aziridine]. / Allergopatie cutanee e respiratorie da aziridina polifunzionale.

BACKGROUND: Polyfunctional aziridine (PFA) hardener is increasingly used in water-based paints and inks as a replacement for organic solvents. Allergic contact dermatitis, contact urticaria, respiratory allergy in occupationally exposed patients with hypersensitivity to PFA are reported. OBJECTIVES: The aim was to study a population of adhesive tape printers for occupational respiratory and skin sensitisation to PFA hardener. Also 2 cases of occupational asthma in workers exposed to PFA in tanneries are reported. METHODS: A standard series prick and patch tests was carried out on 15 workers with skin symptoms out of 36 adhesive tape printers exposed to PFA. Prick tests with a 1% PFA water solution and patch tests with a dilution series (0.1-0.32-0.5-1%) of PFA in petrolatum were performed. Lung and nasal provocation tests with PFA hardener were also carried out on 4 subjects with skin and respiratory symptoms. RESULTS: Skin sensitivity to PFA prick tests was demonstrated in 8.3% of the exposed population; 22.2% of the exposed workers suffered from allergic contact dermatitis due to PFA with positive patch tests for this compound. One case of occupational rhinitis due to PFA was diagnosed. CONCLUSIONS: PFA is a strong sensitizer and the use of gloves and protective clothing appears to be insufficient to prevent occupational allergic diseases. Elimination of PFA from production processes is desirable.

Linkage and association between Plasmodium falciparum blood infection levels and chromosome 5q31-q33.

We have previously mapped a locus controlling Plasmodium falciparum blood infection levels (PFBI) to chromosome 5q31-q33. We genotyped 19 microsatellite markers on chromosome 5q31-q33 in a new sample of 44 pedigrees comprising 84 nuclear families and 292 individuals living in a P. falciparum endemic area. Using a nonparametric multipoint variance-component approach (by GENEHUNTER), we evidenced a peak of linkage close to D5S636 (P=0.0069), with a heritability of 0.46. Using a variance-component method for linkage-disequilibrium mapping of quantitative traits (by QTDT) and the Bonferroni correction for multiple testing, we further detected allelic association in the presence of linkage between blood infection levels and D5S487 (P=6 x 10(-5); P(c)=0.0011), which is located on the distal part of the peak. These results confirm the importance of chromosome 5q31-q33 in the genetic control of PFBI levels.

Practical applications of cutaneous colorimetry.

Dermatologists have long tried to quantify skin color and had few results until the advent of tristimulus colorimetry. With the Minolta colorimeter, quantification of skin color has become a simple matter: skin color can be measured rapidly, noninvasively, and reproducibly. The instrument, which can be used by paramedical staff, provides data that lend themselves for comparison, irrespective of where they are collected. The instrument has enabled definition of the range of physiologic values of skin color, and has revealed marked variations between exposed and nonexposed skin. Constitutional skin color characterizes an individual's phenotype better than facultative skin color and is highly indicative of vulnerability to sunlight. It is therefore a parameter for predicting the immediate and delayed response to light stimulation. On the practical level, colorimetric skin color values can be used to study pigmentation capacity, to program photochemotherapy, and to predict the risk of, and prevent, actinic cancer. Colorimetry can be used to quantify the intensity of erythema of spontaneous and experimental lesions. It has been used to monitor the efficacy of anti-inflammatory treatment of psoriasis and atopic dermatitis. It has also been used in the study of reactions induced by physical and allergic stimuli. Finally, colorimetry is useful in cosmetology for choosing appropriate sunscreens, for studying the effect of depigmentation products, and for determining the delicacy of detergents, and in any other situation that requires the measurement of parameters correlated with skin color that cannot be appreciated by visual observation.

Analysis by BrUdR-labelling technique of induced aneuploidy in mammalian cells in culture.

To study the origin of induced aneuploid cells, the BrUdR-labelling technique was applied to V79/AP4 Chinese hamster cells treated with colcemid or benomyl. In this way we were able to recognize the cells which had undergone one cellular division after the treatment since their chromosomes exhibited sister-chromatid differentiation. The results showed that the induced aneuploid cells can have either a few or numerous additional chromosomes depending on the concentrations of the drug. Moreover, it could be established that aneuploid cells with numerous additional chromosomes were obtained mainly when polyploid cells were also present in the treated population. This strongly suggests that the excess of additional chromosomes found in the aneuploid cells induced by the highest concentrations may be derived by disturbances of the whole mitotic apparatus rather than by a multiplicity of errors affecting individual chromosomes.