Mitochondrial response to controlled nutrition in health and disease

Mitochondria exert crucial physiological functions that create complex links among nutrition, health, and disease. While mitochondrial dysfunction with subsequent impairment of oxidative phosphorylation (OXPHOS) is the hallmark of the rare inherited OXPHOS diseases, OXPHOS dysfunction also plays a central role in the pathophysiology of common conditions such as type 2 diabetes and various neurodegenerative disorders. Dietary interventions, especially calorie restriction, have been shown to improve the course of these diseases and to extend the lifespan. Few data are available on the impact of nutraceuticals (macronutrients, vitamins, and cofactors) on primary inherited OXPHOS diseases. This review presents recent knowledge about the impact of nutritional modulation on mitochondria and lifespan regulation and about the development of potential treatments for mitochondrial dysfunction diseases.     

Synthesis of New N,N’-Bis(5-arylidene-4-oxo-4,5-dihydrothiazolin-2-yl)piperazine Derivatives Under Microwave Irradiation and Preliminary Biological Evaluation

New N,N’-bis(5-arylidene-4-oxo-4,5-dihydrothiazoline-2-yl)diamine derivatives 5 were prepared in two steps from rhodanine and piperazine, or 1,4-bis(3-amino-propyl)piperazine, under microwave reaction conditions with retention of configuration. Some of these compounds were tested for in vitro antiproliferative activities and for their kinase inhibitory potencies towards six kinases (CDK5/p25, GSK3α/β, DYRK1A, DYRK2, CLK1, and CLK2). The compound 5d showed nanomolar activity towards DYRK1A kinase (IC₅₀ = 0.041 μM).     

Traumatismes de la rate dans le service de chirurgie générale du CHU Gabriel Touré

We have carried out a retrospective survey from January 1999 to December 2010, it has included all operated patients or not hospitalized for spleen traumatism at the general surgery service of training hospital Gabriel Toure. Our objectives were to determine the hospital frequency of spleen traumatism, describe the clinical and paraclinical signs and to analyze the treatment outcome. So, we have recorded 107 cases of splenic traumatisms, making 15.3% of abdominal traumatisms and 1.1% of abdominal emergencies, the average age was 23 year ±4–85, the sex ratio at 2.68. The etiology was dominated by road accidents with 80 (74.8%), followed by the fall off trees 12 (11.2%) The scuffles 10 (9.3%), the sport accidents 4 (3.7%) and one case from animal horns; the traumatism was closed 99% of cases, and located at left hypocondrium in 89.7% of cases. The average admission delay was 1.68 H, and the abdominal pain was diffuse in 80.3%. 86 (80.3%) patients were haemodynamically unstable, 44 (41.1%) had anemia. The splenic lesion was identified in 77.5%. According to Moore 58 (54.2%) were classified grade IV. The treatment was non-surgical in 21(19, 7%) of patients, the splenoraphy in 20 (18.6%) and the splenectomy in 63 patients (58.9%); the blood transfusion has been done in 44.9% of patients. We have noticed 4 (3.7%) parietal abscess. One evisceration, 5 (4.7%) fatalities. The average hospitalization duration was 8.7 days. Conclusion: spleen traumatisms are frequent in youth; the non-surgical treatment is the gold standard.     

Genotype diversity of group A rotavirus strains in children with acute diarrhea in urban Burkina Faso, 2008-2010

In this study, the diversity of G and P genotypes of rotavirus strains in Burkinabe children were examined. Between November 2008 and February 2010, 447 stool samples were collected from children <5 years of age with acute diarrhea visiting hospital in Ouagadougou. Group A rotavirus was previously detected in 151/447 (33.8%) of the samples tested by an immunochromatographic test and these samples were now tested further for rotavirus G and P genotypes by RT-PCR. Of these, the rotavirus type genes were amplified by RT-PCR for 140/151 (92.7%) samples and G and P genotypes were successfully determined for 81 (57.9%) and 130 (92.9%) samples, respectively. The most prevalent G genotypes were G1, 34/140 (24.3%), and G9, 21/140 (15%), while the predominant P genotypes were P[6], 56/140 (40%), and P[8], 54/140 (38.6%). Among the single infections, 63/140 (45%), the predominant G/P combinations were: G1P[8] (33%), G9P[8] (29%), and G2P[6] (14%). The unusual strains G1P[9] (3%), G12P[6] (3%), G10P[6] (2%), and G2P[8] (2%) were also detected. In a high number of strains 61/140 (43.6%), the G genotype could not be determined and mixed infections were determined in 17/140 (12.1%) of strains identified. This study highlights the high diversity and presence of unusual rotavirus strains in children in Burkina Faso.     

Unexpected high frequency of P46L TNFRSF1A allele in sub-Saharan West African populations

TNF receptor-associated periodic syndrome (TRAPS) is an autosomal dominant disorder characterized by recurrent attacks of fever and serositis. To date, more than 30 mutations have been reported in TNFRSF1A, the responsible gene. In Caucasian populations, the P46L (c.224C>T) TNFRSF1A sequence variation is considered as a low-penetrance mutation because its allele frequency is similar in patients and controls ( approximately 1%). Whereas the spectrum of TNFRSF1A gene mutations has been well established in Caucasian and several Mediterranean populations, it remains unknown in sub-Saharan African populations. In this study, we found an unexpected high P46L allele frequency ( approximately 10%) in two groups from West Africa - a group of 145 patients with sickle cell anaemia and a group of 349 healthy controls. These data suggest that the P46L variant is rather a polymorphism than a TRAPS causative mutation. We propose that the P46L high frequency in West African populations could be explained by some biological advantage conferred to carriers.     

Profile of HIV infected patients among blood donors in Abidjan, Côte d'Ivoire (1992-1999)

The FonSIDA is a private clinic created in 1992 within the premises of the National Blood Transfusion Center of Abidjan (CNTS), the largest city in C?te d'Ivoire. It provides medical and psychological follow-up for blood donors which are diagnosed as HIV-infected. This Centre provides blood for transfusions in Abidjan and the surrounding area, which from 1992 to 1999 collected 263,398 blood units. In this period, 5574 subjects were detected HIV-positive. Among those, 1766 (32%) HIV infected blood donors came back to be tested for confirmation of HIV diagnosis. Since then, only 9% of the 5574 donors have been seen at least twice a year for medical and psychological follow-up. Women were more compliant than men in the FonSIDA Clinic: they constituted 62% of the 409 patients who were followed-up (p < 0.001). 53% of men had sex with prostitutes the year before HIV diagnosis. 67% of women stated voluntary abortion at least once. In the same period the systematic use of condoms was reported by only 7% of women and 5% of men. 22% of women and 28% of men reported having two or more sexual partners in the year before HIV diagnosis. The main aim of every blood center is to improve blood safety, particularly in developing countries. The appropriate counseling towards blood donors and especially those detected HIV positive can contribute to reduce new HIV infections in high HIV prevalence cities. Rate of compliance of HIV-infected patients to follow-up has risen to 11% in 1992-1994 to 60% in 1997-1999 and will contribute to reach this aim.     

Antibacterial activity of Thonningia sanguinea against some multi-drug resistant strains of Salmonella enterica

Background: The emergence of strains of S.enterica with multiple drug resistance (MDR) is of great concern worldwide.The extracts of flowers of Thonningia sanguinea are used in traditional medicine in Ivory Coast to treat diarrhoeal diseases including salmonellosis. Previous studies had shown inhibition of the MDR strain Salmonella Enteritidis lysotype 6. Objectives: The present study focused to investigate the effect of the extract of the flowers of Thonningia sanguinea on some clinical MDR strains of Salmonella namely S. Tyhpi, S. Typhimurium, S. Hadar and a sensitive strain (S. Enteritidis). Methods: The antimicrobial parameters were determined by double dilution with agar slant method. This method led us to determine MIC, IC(50) and MBC. Results: The MDR strain of S.Typhimurium presented the highest MIC (2.5 mg/ml) whereas the other two MDR strains (S. Hadar, S. Typhi) and the sensitive one (S. Enteritidis) had the same MIC (1.25 mg/ml). The four strains presented the same MBC (2.5 mg/ml). The MDR strain of S. Typhi is the most susceptible strain to the aqueous extract of the flowers of Thonningia sanguinea according to The IC(50) values. Conclusions: The aqueous extract of Thonningia sanguinea can provide an alternative therapy for the treatment of salmonellosis, mainly for typhoid fever caused by MDR strains of S Typhi. The extract also inhibits S.Hadar a MDR emerging strain in Ivory Coast.     

Analysis of antibodies directed against merozoite surface protein 1 of the human malaria parasite Plasmodium falciparum

The 190-kDa merozoite surface protein 1 (MSP-1) of Plasmodium falciparum, an essential component in the parasite's life cycle, is a primary candidate for a malaria vaccine. Rabbit antibodies elicited by the heterologously produced MSP-1 processing products p83, p30, p38, and p42, derived from strain 3D7, were analyzed for the potential to inhibit in vitro erythrocyte invasion by the parasite and parasite growth. Our data show that (i) epitopes recognized by antibodies, which inhibit parasite replication, are distributed throughout the entire MSP-1 molecule; (ii) when combined, antibodies specific for different regions of MSP-1 inhibit in a strictly additive manner; (iii) anti-MSP-1 antibodies interfere with erythrocyte invasion as well as with the intraerythrocytic growth of the parasite; and (iv) antibodies raised against MSP-1 of strain 3D7 strongly cross-inhibit replication of the heterologous strain FCB-1. Accordingly, anti-MSP-1 antibodies appear to be capable of interfering with parasite multiplication at more than one level. Since the overall immunogenicity profile of MSP-1 in rabbits closely resembles that found in sera of Aotus monkeys immunized with parasite-derived MSP-1 and of humans semi-immune to malaria from whom highly inhibiting antigen-specific antibodies were recovered, we consider the findings reported here to be relevant for the development of MSP-1-based vaccines against malaria.     

Identification of three mutations and associated haplotypes in the protoporphyrinogen oxidase gene in South African families with variegate porphyria

Mutation analysis of genomic DNA samples obtained from 17 unrelated South African patients with variegate porphyria (VP) revealed three novel missense mutations in the protoporphyrinogen oxidase (PPOX) gene. A common C to T transition at nucleotide position 452 (R59W) was identified in 15 of the patients analysed, while base changes at positions 336 (H20P) and 779 (R168C) were identified in the remaining two patients. Using protein analysis software we were able to predict that all three mutations have a similar biophysical effect on the protein, being the disturbance of amphiphatic regions within the protein, which might result in misfolding of the protein. Mutation R59W, identified in the majority of South African VP families, was shown to create a Styl restriction site, while mutation R168C would abolish a Dsal restriction site in genomic DNA of affected individuals. As 100% of the index patients analysed were molecularly characterized, the combined use of restriction enzyme and single-strand conformation polymorphism (SSCP) analysis now allows a rapid and accurate diagnosis of VP in South Africa. Mutation R59W was furthermore shown to be in association with one of four potential haplotypes defined by two newly described polymorphisms in exon 1 of the PPOX gene. Our molecular data thus strongly support the founder hypothesis for VP in South Africa.