Molecular epidemiology of malaria in Cameroon. XVIII. Polymorphisms of the Plasmodium falciparum merozoite surface antigen-2 gene in isolates from symptomatic patients

Merozoite surface antigen-2 (MSA-2) is a polymorphic genetic marker that is highly discriminatory for characterizing Plasmodium falciparum field isolates. Genetic diversity of isolates obtained from symptomatic patients residing in Yaounde, Cameroon was analyzed by an allele-specific polymerase chain reaction and direct sequencing of amplification products. Of 137 isolates, 25 (18%) had only FC27-type alleles, 40 (29%) had only 3D7-type alleles, and 72 (53%) had multiple parasite populations with both alleles. Of 295 fragments, 145 (49.2%) and 150 (50.8%) belonged to FC27 and 3D7 alleles, respectively. There were 23 different MSA-2 alleles (10 FC27-type and 13 3D7-type that yielded 44 different combinations in multiple infections). DNA sequencing showed distinct individual sequences. Sequences belonging to the FC27 allelic family were relatively conserved, with most of the polymorphism arising from differences in the number of repeat units. In contrast, the sequences within the GSA-rich region in 3D7 allelic family were less conserved, but many of the sequences in Cameroonian isolates have been identified in other isolates from geographically distant origins. Our results show an extensive diversity of the central region of MSA-2 in size, allelic family, combinations of these two features in multiple infections, and sequence variations underlying the complex population structure of P. falciparum clinical isolates in Yaounde, Cameroon.     

Sternal metastasis revealing hepatocarcinoma

INTRODUCTION: Bone metastasis from hepatocarcinoma are rare, their elective seats are the ribs, the vertebra and rarely the sternum. We report a case of a sternal metastasis which makes discovery of a hepatocarcinoma. EXEGESIS: A 64 year-old man, alcoholic with a previous history of jaundice who developed since 1999 an anterior chest tumor with excellent clinical condition. Laboratory examination showed cytolysis, cholestasis, positive antihepatitis C virus antibodies and elevated serum alphafetoprotein level. Standard radiography and computed tomography of the chest showed an osteolytic lesion of the sternum spread to the adjacent soft tissues and voluminous right hepatic lesion. Pathologic examination of the sternal tumor concluded to a differential adenocarcinoma. Etiologic investigations to find the primitive tumor were negative. Operative procedure was not possible in consideration of the infiltration of the tumor and its situation near the main blood vessels. Radiotherapy gives rise to partial regression of the tumor. A second reading of the tumor biopsy established the diagnosis of metastasis from a hepatocellular carcinoma. The patient died 22 months after the appearance of the sternal metastasis. CONCLUSION: Hepatocarcinoma is rarely disclosed by a sternal metastasis, our case-report is particular by its prolonged survival and the good clinical condition during its follow up.     

Influence of the three‐dimensional culture of human bone marrow mesenchymal stromal cells within a macroporous polysaccharides scaffold on Pannexin 1 and Pannexin 3

Because cell interactions play a fundamental role for cell differentiation, we investigated the expression of Pannexin 1 and Pannexin 3 in human bone marrow mesenchymal stromal cells (HBMSCs) in a three‐dimensional (3D) microenvironment provided by a polysaccharide‐based macroporous scaffold. The pannexin (Panx) family consists of three members, Panx1, Panx2, and Panx3. The roles of Panx large‐pore ion and metabolite channels are recognized in many physiological and pathophysiological scenarios, but the role of these proteins in human physiological processes is still under investigation. Our study demonstrates that HBMSCs cultured within 3D scaffolds have induced Panx1 and Panx3 expression, compared with two‐dimensional culture and that the Panx3 gene expression profile correlates with those of bone markers on mesenchymal stromal cells culture into the 3D scaffold. We showed that Panx1 is involved in the HBMSCs 3D cell–cell organization, as acting on the size of cellular aggregates, demonstrated by the use of Probenecid and the mimetic peptide 10panx1 as specific inhibitors. Inhibition of Panx3 using siRNA strategy shows to reduce the expression of osteocalcin as osteoblast‐specific marker by HBMSCs cultured in 3D conditions, suggesting a role of this Panx in osteogenesis. Moreover, we evaluated Panx1 and Panx3 expression within the cellularized scaffolds upon subcutaneous implantation in NOG (NOD/Shi‐scid/IL‐2Rγ^null) mice, where we could observe a more intense expression in the constructs than in the surrounding tissues in vivo. This study provides new insights on the expression of pannexins in HBMSCs on a 3D microenvironment during the osteogenic differentiation, in vitro and in vivo.     

Epidemiological, therapeutic and evolutionary profiles in patients with lymph node tuberculosis

Tuberculosis remains a public health concern worldwide particularly in Third World countries. Lymph node (LN) tuberculosis is the most frequent extra lung localization. Because of modern transport and mass migration from the developing to the developed world, it is important for all clinicians to keep this diagnostic possibility in mind. Evaluate demographic characteristics, diagnosis approaches, therapeutic strategies and evolutionary aspects while treatment in patients with confirmed LN tuberculosis. Data were retrospectively analyzed in 69 patients collected in 2 health centers in Rabat over a period of 4 years. There was a female (70%) and a young age predominance of patients (31.4 year +/-13.1). The median duration between the onset of symptoms and diagnosis was long: 115 days (interquartile range 34-150 days) explicated by low Socioeconomic conditions (p< 0.05). The cervical LN were most frequently involved (85.5%). The confirmation was histological in 98.5%, bacterial in the liquid from puncture LN in 1.5% of cases. 48% of patients had received treatment according to the national guide of tuberculosis. Half of the patients had received prolonged treatment on average of 7 months and a half (7.3 month +/-1.3) because of the paradoxical response (PR) (p< 0.05). At the end of treatment, LN had returned to their normal size in 80% of patients, we noted residual nodes in 11.6%, and a scrofula in 8.6%. The delay of diagnosis of LN tuberculosis is still important, and the treatment is prolonged because of PR.     

Botanicus and phytotox: data base of plant toxicology. Interest in emergency toxicology and in phytovigilance

The purposes of this project were to summarize more than 279 standard botanical names and their 2294 vernacular ones (French common names, Arabic common names and Moroccan common names) for the first part of database named "Botanicus". The second part of this data base named "Phytotox", concerns relevant toxic data of 120 plants available in Mediterranean region. The database will be useful for emergency physicians, particularly of Maghreb and French- speaking countries. Botanicus and Phytotox permit to assist them in providing fast and appropriate answers to questions concerning adverse effects associated with plant use.     

Distinct effects of amlodipine treatment on vascular elastocalcinosis and stiffness in a rat model of isolated systolic hypertension

OBJECTIVE: Medial elastocalcinosis (MEC) contributes to the development of large artery stiffness and isolated systolic hypertension. Since endothelin receptor antagonists can prevent and regress elastocalcinosis, our aim was to determine whether amlodipine, a calcium channel blocker that inhibits endothelin signaling, could likewise influence MEC, or reduce pressure mainly through its vasorelaxing properties. METHODS: Control male Wistar rats were compared with rats receiving warfarin (20 mg/kg per day) with vitamin K1 (15 mg/kg per day) alone (WVK) or in association with amlodipine (15 mg/kg per day) for 4 weeks or during the last week or last 4 weeks of an 8-week WVK treatment (two regression groups). RESULTS: Inactivation of matrix Gla protein by WVK for 4 or 8 weeks increased the calcium content 10-fold in the aorta, inducing a significant elevation of pulse wave velocity and pulse pressure by selective augmentation of systolic blood pressure. Amlodipine prevented aortic MEC, pulse wave velocity and pulse pressure elevation, but reversed only MEC and pulse pressure when administered for 4 weeks. One week of amlodipine administered after 7 weeks of WVK partially decreased pulse pressure without modifying aortic MEC. Amlodipine did not reduce the fibrosis associated with calcified areas in the WVK model during the regression protocols. CONCLUSION: The clinical efficacy of amlodipine in improving hemodynamic variables and reducing cardiovascular events in isolated systolic hypertension could be explained by its beneficial effect on vascular calcification. Amlodipine's lack of effect on pulse wave velocity and collagen deposition, however, suggests that it may reduce pulse pressure by means other than improving arterial stiffness.     

Comparative characterization of cellular and molecular anti-restenotic profiles of paclitaxel and sirolimus. Implications for local drug delivery

Pleiotropic anti-restenotic properties of drugs that are eluted from coated stents are critical for efficacy and safety. Little is known about comparative drug properties in appropriate human coronary target cell lines for the two compounds that are utilized on FDA-approved drug-eluting stent (DES) platforms, paclitaxel (PTX) and sirolimus (SRL). Target cell lines that play a pivotal role for the pathogenesis of restenosis and vascular healing include human coronary artery smooth muscle (CASMC) and endothelial cells (CAEC). PTX and SRL inhibited CASMC and CAEC proliferation and migration efficiently. However, there was a differential effect on proliferation and migration in CAEC with a more profound inhibition of both parameters by PTX, even at low dosages. Induction of cytotoxicity and apoptosis was pronounced in PTX- and very modest in SRL-treated CASMC and CAEC. PTX increased eNOS activity and nitric oxide (NO) release from CAEC. Neutrophilic leukocyte activation and transmigration, which should be avoided since it may precipitate adverse coronary events such as restenosis and stent thrombosis, was suppressed by SRL, whereas PTX tended to increase neutrophilic leucocyte activity. Therefore, although the primary drug target, inhibition of mitogen-mediated CASMC proliferation, is effectively accomplished by both drugs, auxiliary pharmacological properties that are crucial for the anti-restenotic drug effect and vascular healing are considerably different between PTX and SRL. In comparison with PTX, SRL shows minor interference with endothelial cell proliferation and migration, lower levels of cytotoxicity and apoptosis, a broader therapeutic range and distinctive immunosuppressive properties.