Synthesis and anthelmintic activity of some hybrid Benzimidazolyl-chalcone derivatives

Purpose: To synthesize hybrid benzimidazolyl-chalcone derivatives, evaluate their anthelmintic activity, and establish some structural elements which could lead to induction and enhancement of this activity.Methods: A series of 1-(1H-benzimidazol-2-yl)-3-aryl-2-propen-1-one compounds (6a-z) was synthesized by condensation reaction of 2-acetylbenzimidazole with aryl and heteroaryl aldehyde derivatives. The physicochemical characterization of these benzimidazolyl-chalcones was carried out by nuclear magnetic resonance spectroscopy (1H and 13C NMR) and mass spectroscopy (MS). All compounds were screened in vitro for their nematicidal activity against Haemonchus contortus in larval development assay. The anthelmintic activities obtained were compared with those of anthelmintic reference drugs (fenbendazole and ivermectin); 1,3-diphenyl-2-propen-1-one also used as reference for chalcone.Results: Compounds 6a, 6g, 6w and 6y showed good nematicidal activity (LC100) at 0.002 and 0.0092 μg/ml. The activity of these four benzimidazolyl-chalcones is nearly equal to that of fenbendazole. It is also interesting to know that these compounds have anti-haemonchus activity which is equal or more efficient than ivermectin. Four other compounds (6d, 6h, 6o and 6t) possess interesting anthelmintic activities at 0.68 and 0.16 μg/ml.Conclusion: Preliminary structure-activity relationship studies revealed that arylpropenone group in position 2 of the benzimidazole ring can be considered as new pharmacophore for nematicidal activity.Keywords: Benzimidazole, Chalcone, Anthelmintic activity, Haemonchus contortu

Ostéo-arthrites tuberculeuses inhabituelles multifocales chez une patiente immunocompétente

Les formes multifocales de la tuberculose, surviennent habituellement chez des sujets immunodéprimés. Dans les formes multifocales, certaines localisations osseuses sont rares. Les auteurs rapportent le cas d'une patiente de 58 ans, immunocompétente qui présentait une tuberculose multifocale associant une atteinte pulmonaire et des localisations osseuses et articulaires inhabituelles (l'épaule, la cheville et le pied homolatéral, la branche illio-pubienne). Le diagnostic a été histologique (biopsie ostéo-articulaire) et bactériologique (mise en évidence des BAAR dans les crachats). Le traitement a été médico-chirurgical

Potential impact of host immunity on malaria treatment outcome in Tanzanian children infected with Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>In malaria endemic areas children may recover from malaria after chemotherapy in spite of harbouring genotypically drug-resistant <it>Plasmodium falciparum</it>. This phenomenon suggests that there is a synergy between drug treatment and acquired immunity. This hypothesis was examined in an area of moderately intense transmission of <it>P. falciparum </it>in Tanzania during a drug trail with sulphadoxine-pyrimethamine (SP) or amodiaquine (AQ).</p> <p>Methods</p> <p>One hundred children with uncomplicated malaria were treated with either SP or AQ and followed for 28 days. Mutations in parasite genes related to SP and AQ-resistance as well as human sickle cell trait and alpha-thalassaemia were determined using PCR and sequence-specific oligonucleotide probes and enzyme-linked immunosorbent assay (SSOP-ELISA), and IgG antibody responses to a panel of <it>P. falciparum </it>antigens were assessed and related to treatment outcome.</p> <p>Results</p> <p>Parasitological or clinical treatment failure (TF) was observed in 68% and 38% of children receiving SP or AQ, respectively. In those with adequate clinical and parasitological response (ACPR) compared to children with TF, and for both treatment regimens, prevalence and levels of anti-Glutamate-rich Protein (GLURP)-specific IgG antibodies were significantly higher (P < 0.001), while prevalence of parasite haplotypes associated with SP and AQ resistance was lower (P = 0.02 and P = 0.07, respectively). Interestingly, anti-GLURP-IgG antibodies were more strongly associated with treatment outcome than parasite resistant haplotypes, while the IgG responses to none of the other 11 malaria antigens were not significantly associated with ACPR.</p> <p>Conclusion</p> <p>These findings suggest that GLURP-specific IgG antibodies in this setting contribute to clearance of drug-resistant infections and support the hypothesis that acquired immunity enhances the clinical efficacy of drug therapy. The results should be confirmed in larger scale with greater sample size and with variation in transmission intensity.</p

Mosquito behavior and vector control.

Effective indoor residual spraying against malaria vectors depends on whether mosquitoes rest indoors (i.e., endophilic behavior). This varies among species and is affected by insecticidal irritancy. Exophilic behavior has evolved in certain populations exposed to prolonged spraying programs. Optimum effectiveness of insecticide-treated nets presumably depends on vectors biting at hours when most people are in bed. Time of biting varies among different malaria vector species, but so far there is inconclusive evidence for these evolving so as to avoid bednets. Use of an untreated net diverts extra biting to someone in the same room who is without a net. Understanding choice of oviposition sites and dispersal behavior is important for the design of successful larval control programs including those using predatory mosquito larvae. Prospects for genetic control by sterile males or genes rendering mosquitoes harmless to humans will depend on competitive mating behavior. These methods are hampered by the immigration of monogamous, already-mated females

613 cases of splenic rupture without risk factors or previously diagnosed disease: a systematic review

Background Rupture of the spleen in the absence of trauma or previously diagnosed disease is largely ignored in the emergency literature and is often not documented as such in journals from other fields. We have conducted a systematic review of the literature to highlight the surprisingly frequent occurrence of this phenomenon and to document the diversity of diseases that can present in this fashion. Methods Systematic review of English and French language publications catalogued in Pubmed, Embase and CINAHL between 1950 and 2011. Results We found 613 cases of splenic rupture meeting the criteria above, 327 of which occurred as the presenting complaint of an underlying disease and 112 of which occurred following a medical procedure. Rupture appeared to occur spontaneously in histologically normal (but not necessarily normal size) spleens in 35 cases and after minor trauma in 23 cases. Medications were implicated in 47 cases, a splenic or adjacent anatomical abnormality in 31 cases and pregnancy or its complications in 38 cases. The most common associated diseases were infectious (n = 143), haematologic (n = 84) and non-haematologic neoplasms (n = 48). Amyloidosis (n = 24), internal trauma such as cough or vomiting (n = 17) and rheumatologic diseases (n = 10) are less frequently reported. Colonoscopy (n = 87) was the procedure reported most frequently as a cause of rupture. The anatomic abnormalities associated with rupture include splenic cysts (n = 6), infarction (n = 6) and hamartomata (n = 5). Medications associated with rupture include anticoagulants (n = 21), thrombolytics (n = 13) and recombinant G-CSF (n = 10). Other causes or associations reported very infrequently include other endoscopy, pulmonary, cardiac or abdominal surgery, hysterectomy, peliosis, empyema, remote pancreato-renal transplant, thrombosed splenic vein, hemangiomata, pancreatic pseudocysts, splenic artery aneurysm, cholesterol embolism, splenic granuloma, congenital diaphragmatic hernia, rib exostosis, pancreatitis, Gaucher's disease, Wilson's disease, pheochromocytoma, afibrinogenemia and ruptured ectopic pregnancy. Conclusions Emergency physicians should be attuned to the fact that rupture of the spleen can occur in the absence of major trauma or previously diagnosed splenic disease. The occurrence of such a rupture is likely to be the manifesting complaint of an underlying disease. Furthermore, colonoscopy should be more widely documented as a cause of splenic rupture