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A microfluidic model for single-cell capillary obstruction by Plasmodium falciparum-infected erythrocytes

Shelby, J. Patrick; White, John; Ganesan, Karthikeyan; Rathod, Pradipsinh K.; Chiu, Daniel T.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
25.75%
Severe malaria by Plasmodium falciparum is a potentially fatal disease, frequently unresponsive to even the most aggressive treatments. Host organ failure is associated with acquired rigidity of infected red blood cells and capillary blockage. In vitro techniques have played an important role in modeling cell deformability. Although, historically they have either been applied to bulk cell populations or to measure single physical parameters of individual cells. In this article, we demonstrate the unique abilities and benefits of elastomeric microchannels to characterize complex behaviors of single cells, under flow, in multicellular capillary blockages. Channels of 8-, 6-, 4-, and 2-μm widths were readily traversed by the 8 μm-wide, highly elastic, uninfected red blood cells, as well as by infected cells in the early ring stages. Trophozoite stages failed to freely traverse 2- to 4-μm channels; some that passed through the 4-μm channels emerged from constricted space with deformations whose shape-recovery could be observed in real time. In 2-μm channels, trophozoites mimicked “pitting,” a normal process in the body where spleen beds remove parasites without destroying the red cell. Schizont forms failed to traverse even 6-μm channels and rapidly formed a capillary blockage. Interestingly...

Plasmodium falciparum Malaria: Reduction of Endothelial Cell Apoptosis In Vitro

Hemmer, Christoph Josef; Lehr, Hans Anton; Westphal, Kathi; Unverricht, Marcus; Kratzius, Manja; Reisinger, Emil Christian
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /03/2005 EN
Relevância na Pesquisa
35.91%
Organ failure in Plasmodium falciparum malaria is associated with neutrophil activation and endothelial damage. This study investigates whether neutrophil-induced endothelial damage involves apoptosis and whether it can be prevented by neutralization of neutrophil secretory products. Endothelial cells from human umbilical veins were coincubated with neutrophils from healthy donors and with sera from eight patients with P. falciparum malaria, three patients with P. vivax malaria, and three healthy controls. Endothelial apoptosis was demonstrated by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) and annexin V staining. The rate of apoptosis of cells was markedly increased after incubation with patient serum compared to that with control serum. Apoptosis was most pronounced after incubation with sera from two patients with fatal cases of P. falciparum malaria, followed by sera of survivors with severe P. falciparum malaria and, finally, by sera of patients with mild P. falciparum and P. vivax malaria. Ascorbic acid, tocopherol, and ulinastatin reduced the apoptosis rate, but gabexate mesilate and pentoxifylline did not. Furthermore, in fatal P. falciparum malaria, apoptotic endothelial cells were identified in renal and pulmonary tissue by TUNEL staining. These findings show that apoptosis caused by neutrophil secretory products plays a major role in endothelial cell damage in malaria. The antioxidants ascorbic acid and tocopherol and the protease inhibitor ulinastatin can reduce malaria-associated endothelial apoptosis in vitro.

Translational Systems Approaches to the Biology of Inflammation and Healing

Vodovotz, Yoram; Constantine, Gregory; Faeder, James; Mi, Qi; Rubin, Jonathan; Bartels, John; Sarkar, Joydeep; Squires, Robert H.; Okonkwo, David O.; Gerlach, Jörg; Zamora, Ruben; Luckhart, Shirley; Ermentrout, Bard; An, Gary
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/2010 EN
Relevância na Pesquisa
15.67%
Inflammation is a complex, non-linear process central to many of the diseases that affect both developed and emerging nations. A systems-based understanding of inflammation, coupled to translational applications, is therefore necessary for efficient development of drugs and devices, for streamlining analyses at the level of populations, and for the implementation of personalized medicine. We have carried out an iterative and ongoing program of literature analysis, generation of prospective data, data analysis, and computational modeling in various experimental and clinical inflammatory disease settings. These simulations have been used to gain basic insights into the inflammatory response under baseline, gene-knockout, and drug-treated experimental animals for in silico studies associated with the clinical settings of sepsis, trauma, acute liver failure, and wound healing to create patient-specific simulations in polytrauma, traumatic brain injury, and vocal fold inflammation; and to gain insight into host-pathogen interactions in malaria, necrotizing enterocolitis, and sepsis. These simulations have converged with other systems biology approaches (e.g., functional genomics) to aid in the design of new drugs or devices geared towards modulating inflammation. Since they include both circulating and tissue-level inflammatory mediators...

Outcome and prognostic factors of malaria-associated acute kidney injury requiring hemodialysis: A single center experience

Kute, V. B.; Shah, P. R.; Munjappa, B. C.; Gumber, M. R.; Patel, H. V.; Jain, S. H.; Engineer, D. P.; Naresh, V. V. Sai; Vanikar, A. V.; Trivedi, H. L.
Fonte: Medknow Publications & Media Pvt Ltd Publicador: Medknow Publications & Media Pvt Ltd
Tipo: Artigo de Revista Científica
Publicado em //2012 EN
Relevância na Pesquisa
45.97%
Acute kidney injury (AKI) is one of the most dreaded complications of severe malaria. We carried out prospective study in 2010, to describe clinical characteristics, laboratory parameters, prognostic factors, and outcome in 59 (44 males, 15 females) smear-positive malaria patients with AKI. The severity of illness was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA) score, Multiple Organ Dysfunction Score (MODS), and Glasgow Coma Scale (GCS) scores. All patients received artesunate and hemodialysis (HD). Mean age of patients was 33.63 ± 14 years. Plasmodium falciparum malaria was seen in 76.3% (n = 45), Plasmodium vivax in 16.9% (n = 10), and mixed infection in 6.8% (n = 4) patients. Presenting clinical features were fever (100%), nausea-vomiting (85%), oliguria (61%), abdominal pain/tenderness (50.8%), and jaundice (74.5%). Mean APACHE II, SOFA, MODS, and GCS scores were 18.1 ± 3, 10.16 ± 3.09, 9.71 ± 2.69, and 14.15 ± 1.67, respectively, all were higher among patients who died than among those who survived. APACHE II ≥20, SOFA and MODS scores ≥12 were associated with higher mortality (P < 0.05). 34% patients received blood component transfusion and exchange transfusion was done in 15%. Mean number of HD sessions required was 4.59 ± 3.03. Renal biopsies were performed in five patients (three with patchy cortical necrosis and two with acute tubular necrosis). 81.3% of patients had complete renal recovery and 11.8% succumbed to malaria. Prompt diagnosis...

Severe Imported Malaria in Critical Care Patients; Malária Grave Importada em Doentes Críticos

Palma dos Reis, Inês; Serviço de Medicina 4.Hospital São Francisco Xavier, Centro Hospitalar de Lisboa Ocidental. Lisboa. Portugal.; Serafim, Catarina; Serviço de Medicina Interna. Hospital de Beja. Beja. Portugal.; Valério, Bernardino; Unidade de Cu
Fonte: Ordem dos Médicos Publicador: Ordem dos Médicos
Tipo: info:eu-repo/semantics/article; article; info:eu-repo/semantics/publishedVersion Formato: application/x-pdf
Publicado em 12/11/2012 POR
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36.02%
Introduction: Imported malaria is a frequent diagnosis in Portugal, and in the most severe clinical forms it may present a high mortality rate. Material and Methods: We present seven cases of severe imported malaria, admitted to an intensive care unit between 2000 and 2010, with particular focus on risk factors, clinical presentation, treatment and results. Results: All patients had a history of recent travel to African endemic areas for malaria. Plasmodium falciparum was the agent isolated in all cases. Most patients had an inadequate prophylaxis. High parasitaemia in non-immune patients and treatment delay were associated with more severe clinical presentation. All the cases were complicated by organ failure, and three patients needed organ support and in two exchange blood transfusions were performed. There was one single death that was associated with marked delay in the initiation of therapy. Conclusion: In these patients, early and aggressive treatment, with a organ support in a critical care setting, allowed a good outcome with low mortality and no significant sequelae, despite the severity of presentation.; Introdução: A malária importada é um diagnóstico frequente em Portugal, podendo apresentar nas suas formas mais graves...

Evidence of IL-17, IP-10, and IL-10 involvement in multiple-organ dysfunction and IL-17 pathway in acute renal failure associated to Plasmodium falciparum malaria

Herbert, Fabien; Tchitchek, Nicolas; Bansal, Devendra; Jacques, Julien; Pathak, Sulabha; Bécavin, Christophe; Fesel, Constantin; Dalko, Esther; Cazenave, Pierre-André; Preda, Cristian; Ravindran, Balachandran; Sharma, Shobhona; Das, Bidyut; Pied, Sylvia
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 24/11/2015 EN
Relevância na Pesquisa
15.67%

Evidence of IL-17, IP-10, and IL-10 involvement in multiple-organ dysfunction and IL-17 pathway in acute renal failure associated to Plasmodium falciparum malaria

Herbert, Fabien; Tchitchek, Nicolas; Bansal, Devendra; Jacques, Julien; Pathak, Sulabha; Bécavin, Christophe; Fesel, Constantin; Dalko, Esther; Cazenave, Pierre-André; Preda, Cristian; Ravindran, Balachandran; Sharma, Shobhona; Das, Bidyut; Pied, Sylvia
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 24/11/2015 ENG
Relevância na Pesquisa
66.17%
Plasmodium falciparum malaria in India is characterized by high rates of severe disease, with multiple organ dysfunction (MOD)-mainly associated with acute renal failure (ARF)-and increased mortality. The objective of this study is to identify cytokine signatures differentiating severe malaria patients with MOD, cerebral malaria (CM), and cerebral malaria with MOD (CM-MOD) in India. We have previously shown that two cytokines clusters differentiated CM from mild malaria in Maharashtra. Hence, we also aimed to determine if these cytokines could discriminate malaria subphenotypes in Odisha.; Indo-French Centre for the Promotion of Advanced Research (IFCPAR project No 3703), International Associated Laboratory Systems Immunology and Genetics of Infectious Diseases (LIA SIGID, CNRS, Lille University and the Department of Biotechnology (DBT), Ministry of Science and Technology of India and the ANR LAbEx Parafrap).