Drenaje Biliar Percutáneo: Técnica, indicaciones y resultados

Antecedentes: La descompresión de la vía biliarpuede lograrse empleando métodos quirúrgicos,endoscópicos o percutáneos; los procedimientos dedrenaje percutáneo (DP) aplicados a la ictericia obstructivabrindan resultados muy alentadores.Pacientes y método: Diez y nueve pacientescon ictericia obstructiva tratados con DP fueron seleccionadospara este estudio retrospectivo que tienepor objetivo estudiar las indicaciones, técnica yresultados. El procedimiento fue realizado con guíaimagenológica (ecografía, radioscopía y tomografíaaxial computarizada) y se colocó un catéter pigtailcon técnica de Seldinger.Resultados: La ictericia se debía a una enfermedadneoplásica inoperable en 18 casos; el restante correspondea una estenosis benigna postoperatoria. En 12 casoslas lesiones afectaban la vía biliar proximal (arribadel cístico) y en los 7 restantes en la porción distal (infracística).En el 84% de los casos el drenaje fue exitoso(16% resultó fallido en el primer intento). Se comprobaron4 complicaciones, relacionadas al mal estado delos paciente. La mortalidad fue del 21%.Conclusión: los pacientes con obstrucción biliarneoplásica inoperable pueden ser tratados medianteun DP; los resultados preliminares son buenos, peropueden ser mejorados

Atorvastatin prevents Plasmodium falciparum cytoadherence and endothelial damage

<p>Abstract</p> <p>Background</p> <p>The adhesion of <it>Plasmodium falciparum </it>parasitized red blood cell (PRBC) to human endothelial cells (EC) induces inflammatory processes, coagulation cascades, oxidative stress and apoptosis. These pathological processes are suspected to be responsible for the blood-brain-barrier and other organs' endothelial dysfunctions observed in fatal cases of malaria. Atorvastatin, a drug that belongs to the lowering cholesterol molecule family of statins, has been shown to ameliorate endothelial functions and is widely used in patients with cardiovascular disorders.</p> <p>Methods</p> <p>The effect of this compound on PRBC induced endothelial impairments was assessed using endothelial co-culture models.</p> <p>Results</p> <p>Atorvastatin pre-treatment of EC was found to reduce the expression of adhesion molecules and <it>P. falciparum </it>cytoadherence, to protect cells against PRBC-induced apoptosis and to enhance endothelial monolayer integrity during co-incubation with parasites.</p> <p>Conclusions</p> <p>These results might suggest a potential interest use of atorvastatin as a protective treatment to interfere with the pathophysiological cascades leading to severe malaria.</p

Antimalarial Activity of Potential Inhibitors of Plasmodium falciparum Lactate Dehydrogenase Enzyme Selected by Docking Studies

The Plasmodium falciparum lactate dehydrogenase enzyme (PfLDH) has been considered as a potential molecular target for antimalarials due to this parasite's dependence on glycolysis for energy production. Because the LDH enzymes found in P. vivax, P. malariae and P. ovale (pLDH) all exhibit ∼90% identity to PfLDH, it would be desirable to have new anti-pLDH drugs, particularly ones that are effective against P. falciparum, the most virulent species of human malaria. Our present work used docking studies to select potential inhibitors of pLDH, which were then tested for antimalarial activity against P. falciparum in vitro and P. berghei malaria in mice. A virtual screening in DrugBank for analogs of NADH (an essential cofactor to pLDH) and computational studies were undertaken, and the potential binding of the selected compounds to the PfLDH active site was analyzed using Molegro Virtual Docker software. Fifty compounds were selected based on their similarity to NADH. The compounds with the best binding energies (itraconazole, atorvastatin and posaconazole) were tested against P. falciparum chloroquine-resistant blood parasites. All three compounds proved to be active in two immunoenzymatic assays performed in parallel using monoclonals specific to PfLDH or a histidine rich protein (HRP2). The IC50 values for each drug in both tests were similar, were lowest for posaconazole (<5 µM) and were 40- and 100-fold less active than chloroquine. The compounds reduced P. berghei parasitemia in treated mice, in comparison to untreated controls; itraconazole was the least active compound. The results of these activity trials confirmed that molecular docking studies are an important strategy for discovering new antimalarial drugs. This approach is more practical and less expensive than discovering novel compounds that require studies on human toxicology, since these compounds are already commercially available and thus approved for human use

Novel Polymorphisms in Plasmodium falciparum ABC Transporter Genes Are Associated with Major ACT Antimalarial Drug Resistance

Chemotherapy is a critical component of malaria control. However, the most deadly malaria pathogen, Plasmodium falciparum, has repeatedly mounted resistance against a series of antimalarial drugs used in the last decades. Southeast Asia is an epicenter of emerging antimalarial drug resistance, including recent resistance to the artemisinins, the core component of all recommended antimalarial combination therapies. Alterations in the parasitic membrane proteins Pgh-1, PfCRT and PfMRP1 are believed to be major contributors to resistance through decreasing intracellular drug accumulation. The pfcrt, pfmdr1 and pfmrp1 genes were sequenced from a set of P.falciparum field isolates from the Thai-Myanmar border. In vitro drug susceptibility to artemisinin, dihydroartemisinin, mefloquine and lumefantrine were assessed. Positive correlations were seen between the in vitro susceptibility responses to artemisinin and dihydroartemisinin and the responses to the arylamino-alcohol quinolines lumefantrine and mefloquine. The previously unstudied pfmdr1 F1226Y and pfmrp1 F1390I SNPs were associated significantly with artemisinin, mefloquine and lumefantrine in vitro susceptibility. A variation in pfmdr1 gene copy number was also associated with parasite drug susceptibility of artemisinin, mefloquine and lumefantrine. Our work unveils new candidate markers of P. falciparum multidrug resistance in vitro, while contributing to the understanding of subjacent genetic complexity, essential for future evidence-based drug policy decisions

Cinétique entérohépatique et métabolisme hépatique de l'acide murocholique chez le hamster

International audienc

Adiponectin receptors are expressed in hypothalamus and colocalized with proopiomelanocortin and neuropeptide Y in rodent arcuate neurons

1479-6805 (Electronic) Journal ArticleAdiponectin is involved in the control of energy homeostasis in peripheral tissues through Adipor1 and Adipor2 receptors. An increasing amount of evidence suggests that this adipocyte-secreted hormone may also act at the hypothalamic level to control energy homeostasis. In the present study, we observed the gene and protein expressions of Adipor1 and Adipor2 in rat hypothalamus using different approaches. By immunohistochemistry, Adipor1 expression was ubiquitous in the rat brain. By contrast, Adipor2 expression was more limited to specific brain areas such as hypothalamus, cortex, and hippocampus. In arcuate and paraventricular hypothalamic nuclei, Adipor1, and Adipor2 were expressed by neurons and astrocytes. Furthermore, using transgenic green fluorescent protein mice, we showed that Adipor1 and Adipor2 were present in pro-opiomelanocortin (POMC) and neuropeptide Y (NPY) neurons in the arcuate nucleus. Finally, adiponectin treatment by intracerebroventricular injection induced AMP-activated protein kinase (AMPK) phosphorylation in the rat hypothalamus. This was confirmed by in vitro studies using hypothalamic membrane fractions. In conclusion, Adipor1 and Adipor2 are both expressed by neurons (including POMC and NPY neurons) and astrocytes in the rat hypothalamic nuclei. Adiponectin is able to increase AMPK phosphorylation in the rat hypothalamus. These data reinforced a potential role of adiponectin and its hypothalamic receptors in the control of energy homeostasis

Trasplante experimental de hígado en cerdos. Aplicación de Protocolos quirúrgicos

Este proyecto de investigación, fue  llevado a cabo entre los meses de Octubre 2004 – Enero 2005, buscando consolidar a un equipo multidisciplinario de trasplante de hígado, a fin de encontrar una solución a la problemática de la insuficiencia hepática en fase terminal. Se han aplicado protocolos de ablación, Back Table, hepatectomías e implante, a mas de un protocolo de anestesia, respetando los preceptos de Bioética, para el manejo de animales de experimentación. Utilizamos 8 cerdos de raza Landrace , White Large o cruzas, el peso promedio fue de31.25 kg. Tres animales fueron usados como donantes de hígado y sangre ( promedio 1066 cc/ animal) y tres fueron receptores; los otros dos fueron utilizados como banco de sangre .El tiempo operatorio de ablación utilizado fue en promedio de 1 hora y 23 minutos. Usamos 3000 cc de suero para el enfriado. Empleamos en promedio 3 horas y 12 minutos de cirugía en la hepatectomía y el implante. El tiempo de isquemia fría para el órgano donado fue en promedio de 3 horas y 7 minutos; las anastomosis vasculares las hicimos respetando estrictamente los protocolos, y la anastomosis biliodigestiva del tercer cerdo  la realizamos mediante una colédocoyeyunoanastomosis en Omega. Concluimos que, es posible realizar cirugía experimental en el ámbito Universitario y debe ser realizado enla Facultadde Medicina