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Introduction sur le plan génétique, Plasmodium falciparum(P. falciparum) est une espèce extrêmement polymorphe. Il existe une diversité de souches parasitaires qui infestent les individus vivant en zone d´endémie palustre. La présente étude vise à étudier la relation entre le polymorphisme de P. falciparum et les mutations au niveau des gènes Pfcrt et Pfmdr1 dans la zone de Nanoro au Burkina Faso. Méthodes les échantillons sanguins de porteurs de plasmodiums résidant dans le district sanitaire de Nanoro ont fait l´objet d´un génotypage par PCR nichée. Les mutations au niveau des gènes de résistance du parasite aux antipaludiques ont été détectées par la technique PCR-RFLP. Résultats les échantillons de 672 patients ont été génotypés avec succès. Aucune famille allélique des gènes msp1et msp2n´avaient une susceptibilité accrue à développer des mutations au niveau des gènes de résistance. Par contre, les souches mutantes de ces gènes étaient significativement plus importantes dans les infections monoclonales que dans les infections multi clonales. Conclusion cette étude fournit un aperçu global de la relation entre le polymorphisme de P. falciparum et les mutations au niveau des gènes de résistance. Ces données contribueront sans doute à améliorer les connaissances sur la biologie du parasite et de ses mécanismes de résistance aux antipaludiques.

Objectif. Evaluation comparative de l’efficacite et de la tolerance des associations artemether-lumefantrine (A-L), amodiaquine-sulfadoxine-pyrimethamine (AQ-SP) et amodiaquine-artesunate (AQ-AS) dans le traitement du paludisme simple chez les enfants de moins de 5 ans a Bangui, Centrafrique. Methodologie. Cent quatre-vingt-six enfants âges de 6 a 59 mois atteints du paludisme simple a Plasmodium falciparum ont ete inclus a Bede-Combattant de juillet a octobre 2010. Parmi ces enfants, soixante-trois ont ete randomises pour recevoir A-L, soixante-trois AQ-SP et soixante-trois AQ-AS. Les reponses cliniques ont ete classees selon de criteres de l’OMS, en echec therapeutique precoce (ETP), echec clinique tardif (ECT), echec parasitologique tardif (EPT) et reponse clinique et parasitologique adequate (RCPA). Les genes pfcrt, pfmdr-1, dhfr et dhps ont ete analyses par la technique de PCR-RFLP. Resultats. Apres correction par PCR, le RCPA pour A-L, AQ-SP et AQ-AS, a ete respectivement de 100 %, 96,55 % et 100 %, sans difference significative entre les trois combinaisons (p = 0,36). Les cas d’echec observes avec AQ-SP ont ete associes a une mutation pfcrt 76T, pfmdr-1 86Y, dhfr 108N et dhps A437G. Il n’y avait pas de difference significative dans la reduction de l’anemie, de la fievre (p = 0,87) et de la parasitemie (p = 0,63) entre les trois combinaisons. Conclusion. Cette etude demontre que les combinaisons a base d’artemisinine sont efficaces et tolerees dans le traitement du paludisme simple a Bangui. Les cas d’echecs etaient dus a des infections nouvelles et a des mutations de resistance.

The identification of biliary tranporters has enhanced our understanding of bile formation and some liver diseases. In this review, we first describe the main hepatobiliary transporters and their function. Then, some liver diseases related to mutations of biliary tranporters (FIC1/ATP8B1, BSEP/ABCB11, MDR3 /ABCB4 and MRP2/ABCC2) will be described with a focus on the pathological aspects. These diseases include progressive familial intrahepatic cholestasis (PFIC), benign recurrent intrahepatic cholestasis (BRIC), intrahepatic cholestasis of pregnancy, Dubin-Johnson's syndrome and low phospholipid associated cholelithiasis (LPAC).

Pseudoxanthoma elasticum (PXE) is an inherited connective tissue disease characterized by skin, eye, cardiovascular, and, less often, cerebrovascular manifestations. We report the case of a 32-year-old woman who presented with fortuitously discovered cerebral white matter lesions. The pattern of the lesions was compatible with vascular leucopathy. Neurological examination, CSF and biological assessment were normal. Physical examination demonstrated cutaneous lesions characterized by yellowish papules in the neck and axilla with calcification of elastic fibres showed on the skin biopsy and retinal angioid streaks, which made PXE a plausible diagnosis. Sequencing of the ABCC6 gene confirmed PXE. Thus, PXE must be considered when confronted with cerebral microangiopathy of undetermined origin.

Efflux pumps located in the bacterial membranes are responsible for low level resistance to antibiotics, considered not to be relevant in the clinic and thus often neglected. However, these pumps contribute to the emergence of high level antibiotic resistance mechanisms, which are responsible for severe complications during the treatment of infectious diseases. Therefore it is necessary to take into account these pumps while developing novel antibacterial agents. Among these new research strategies, the development of efflux pump inhibitors seems to be an attractive approach to restore the activity of some "classical" antibiotics and to limit the emergence of multiresistant strains associated with hospital-acquired infections. In this review, we focalise on Staphylococcus aureus efflux pumps and their potential inhibitors.

Adefovir is transported by the organic anion transporter (OAT1) and the multidrug resistant protein (MRP2, 4 and 5). We studied adefovir clearance in rat after inhibition of transporters by probenecid and in TR- rats, in which MRP2 is lacking. After treatment by probenecid or placebo, pharmacokinetics of adefovir 10 mg/kg was studied via population modeling (NONMEM). The fraction of drug excreted in the urine was low. Renal clearance of adefovir was significantly lower (P0.05) in probenecid TR- rats (0.03 +/- 0.02 l/hour) than in normal control (0.09 +/- 0.05 l/hour), in normal probenecid (0.10 +/- 0.07 l/hour) and in TR- control rats (0.13 +/- 0.07 l/hour). In vivo in rats MRP2 mutation alone did not affect adefovir clearance suggesting that MRP2 does not play a critical role in the secretion of adefovir. Additional pharmacological inhibition of transporters decreased renal clearance, which may reflect inhibition of compensating transport mechanisms activated when MRP2 is lacking.

DEFINITION OF HYPOURICEMIA: Hypouricemia (serum uric acid less than 120 micro mol/l) is a biological abnormality often discovered accidentally and with a low prevalence depending on its permanent or transitory nature ranging from 0.15 to 3.38%. NEW PHYSIOLOGICAL CONCEPTS OF ITS PATHOGENESIS: Recently, our knowledge of the physiopathological mechanisms of hypouricemia has been emphasized by the identification of three systems of renal and extra-renal uric acid transport: a Cl/urate (URAT1) transporter, a multispecific organic anion transporter (OAT) and a urate transporter/channel. ETIOLOGY AND COMPLICATIONS OF HYPOURICEMIA: Through questioning, drugs and toxics (allopurinol.) are generally rapidly recognized as responsible for half of the hypouricemia encountered. It can be concomitant to a known disease: severe liver disease, neoplasia, diabetes, AIDS, syndrome of inappropriate antidiuretic hormone secretion. Hypouricemia can also be isolated and justifies the measurement of uric acid clearance, the normality or reduction of which orients towards a deficiency in xanthine-oxydase, the increase in which suggests an abnormality in uric acid transport in the proximal tubule (Fanconi syndrome, primary hereditary anomaly of tubular uric acid transport). Hypouricemia does not appear to expose the patient to any danger, but the onset of nephrolithiasis or acute renal failure secondary to the combination of severe hypouricemia and oxidant stress is always possible.

Understanding the features of the various hereditary vascular pathologies allows consideration and confirmation of the diagnosis, and a search for treatable hidden disorders, avoiding harmful investigations, initiating follow up, performing family investigations and providing genetic counselling. Pseudoxanthoma elasticum must be considered in the presence of calcified distal arteriopathy of the lower limbs in a young subject without any other aetiological aspects. Cutaneous or mucosal lesions confirmed on histological examination, angioid streaks at the back of the eye and a family history support the diagnosis, which is confirmed by showing pathogenic mutations of the ABCC6 gene. It is then important to search for a peripheral disorder in other arterial territory, a low grade coronaropathy, hypertension and an endocardial disorder. Prescription of antithrombotics must be made carefully because of the risk of gastro-intestinal haemorrhage. Vascular Ehlers-Danlos syndrome is suspected in a subject less than 30 years old with diffuse aneurysmal disease, spontaneous arterial rupture or dissection, a carotido-cavernous fistula or early onset varices. Demonstrating an ecchymotic tendency or an acrogeric morphology, especially in a familial context, warrants cutaneous biopsy for anatomopathological examination and fibroblast culture for a study of the C0L3A1 gene. When the diagnosis is suggested, it is advisable to prohibit any arterial puncture, cold surgery or gastro-intestinal endoscopy. The search for aneurysmal lesions must be performed by non-invasive imaging. The therapeutic management requires specialised teams. The combination of repeated epistaxis, muco-cutaneous telangectasia and similar characteristics in a family suggests the diagnosis of Osler-Weber-Rendu disease. The search for iron deficiency, gastro-intestinal bleeds and pulmonary, hepatic or cerebral arterio-venous malformations is then necessary. Besides skilled endovascular management when indicated, it is important to advise every patient with a pulmonary arterio-venous malformation to take antibiotic prophylaxis against cerebral abscess in situations at risk of bacteraemia.