scholarly journals Intravenous whole blood transfusion results in faster recovery of vascular integrity and increased survival in experimental cerebral malaria

2021 ◽  
Author(s):  
Saba Gul ◽  
Hans C. Ackerman ◽  
Cláudio Tadeu Daniel-Ribeiro ◽  
Leonardo Jose de Moura Carvalho
Keyword(s):  
Blood Transfusion ◽  
Cerebral Malaria ◽  
Late Stage ◽  
Whole Blood ◽  
Jugular Vein ◽  
Vascular Integrity ◽  
Experimental Cerebral Malaria ◽  
Intraperitoneal Route ◽  
The Right ◽  
Blood Brain Barrier Integrity

Transfusion of 10 mg/kg of whole blood via intraperitoneal route to mice with late-stage experimental cerebral malaria (ECM) along with artemether has been shown to result in markedly increased survival (75%) compared to artemether alone (51%). Intraperitoneal route was used to overcome the restrictions imposed by injection of large volumes of viscous fluid in small and deranged blood vessels of mice with ECM. In the present study, a method of intravenous transfusion was implemented by injecting 200mL of whole blood through the right jugular vein in mice with late-stage ECM, together with artemether given intraperitoneally, leading to a remarkable increase in survival, from 54% to 90%. On the contrary, mice receiving artemether plus plasma transfusion showed a worse outcome, with only 18% survival. Compared to the intraperitoneal route, intravascular transfusion led to faster and more pronounced recoveries of hematocrit, platelet counts, angiopoietins levels (ANG-1, ANG-2 and ANG-2/ANG-1) and blood brain barrier integrity. These findings indicate that whole blood transfusion when given intravenously show more efficacy over intraperitoneal transfusion, reinforcing evidence for benefit as an adjuvant therapy for cerebral malaria.

scholarly journals Whole blood transfusion improves vascular integrity and increases survival in artemether-treated experimental cerebral malaria

2021 ◽  
Author(s):  
Saba Gul ◽  
Flavia L. Ribeiro-Gomes ◽  
Aline S. Moreira ◽  
Guilherme S. Sanches ◽  
Fabiana G. Conceição ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Cerebral Malaria ◽  
Whole Blood ◽  
Plasmodium Berghei ◽  
Severe Thrombocytopenia ◽  
Blood Components ◽  
Vascular Integrity ◽  
Experimental Cerebral Malaria ◽  
Angiopoietin 2 ◽  
Lymphocyte Populations

Abstract Pathological features observed in both human and experimental cerebral malaria (ECM) are endothelial dysfunction and changes in blood components. Blood transfusion has been routinely used in patients with severe malarial anemia and can also benefit comatose and acidotic malaria patients. In present study Plasmodium berghei-infected mice were transfused intraperitoneally with 200 µL of whole blood along with 20 mg/kg of artemether. ECM mice showed severe thrombocytopenia and decreases in hematocrit. Artemether treatment markedly aggravated anemia within 24 hours. Whole blood administration significantly prevented further drop in hematocrit and partially restored the platelet count. Increased levels of plasma angiopoietin-2 (Ang-2) remained high 24 hours after artemether treatment but returned to normal levels 24 hours after blood transfusion, indicating reversal to quiescence. Ang-1 was depleted in ECM mice and levels were not restored by any treatment. Blood transfusion prevented the aggravation of the breakdown of blood brain barrier after artemether treatment and decreased spleen congestion without affecting splenic lymphocyte populations. Critically, blood transfusion resulted in markedly improved survival of mice with ECM (75.9% compared to 50.9% receiving artemether only). These findings indicate that whole blood transfusion can be an effective adjuvant therapy for cerebral malaria.

scholarly journals Whole blood transfusion improves vascular integrity and increases survival in artemether-treated experimental cerebral malaria

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Saba Gul ◽  
Flavia L. Ribeiro-Gomes ◽  
Aline S. Moreira ◽  
Guilherme S. Sanches ◽  
Fabiana G. Conceição ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Cerebral Malaria ◽  
Whole Blood ◽  
Plasmodium Berghei ◽  
Severe Thrombocytopenia ◽  
Blood Components ◽  
Vascular Integrity ◽  
Experimental Cerebral Malaria ◽  
Angiopoietin 2 ◽  
Lymphocyte Populations

AbstractPathological features observed in both human and experimental cerebral malaria (ECM) are endothelial dysfunction and changes in blood components. Blood transfusion has been routinely used in patients with severe malarial anemia and can also benefit comatose and acidotic malaria patients. In the present study Plasmodium berghei-infected mice were transfused intraperitoneally with 200 μL of whole blood along with 20 mg/kg of artemether. ECM mice showed severe thrombocytopenia and decreases in hematocrit. Artemether treatment markedly aggravated anemia within 24 h. Whole blood administration significantly prevented further drop in hematocrit and partially restored the platelet count. Increased levels of plasma angiopoietin-2 (Ang-2) remained high 24 h after artemether treatment but returned to normal levels 24 h after blood transfusion, indicating reversal to quiescence. Ang-1 was depleted in ECM mice and levels were not restored by any treatment. Blood transfusion prevented the aggravation of the breakdown of blood brain barrier after artemether treatment and decreased spleen congestion without affecting splenic lymphocyte populations. Critically, blood transfusion resulted in markedly improved survival of mice with ECM (75.9% compared to 50.9% receiving artemether only). These findings indicate that whole blood transfusion can be an effective adjuvant therapy for cerebral malaria.

scholarly journals THEMIS Is Required for Pathogenesis of Cerebral Malaria and Protection against Pulmonary Tuberculosis

2014 ◽  
Vol 83 (2) ◽  
pp. 759-768 ◽  
Author(s):  
Sabrina Torre ◽  
Sebastien P. Faucher ◽  
Nassima Fodil ◽  
Silayuv E. Bongfen ◽  
Joanne Berghout ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Cerebral Malaria ◽  
Functional Coupling ◽  
Experimental Cerebral Malaria ◽  
Content Type ◽  
Proinflammatory Responses ◽  
Inflammatory Bowel ◽  
Blood Brain Barrier Integrity

We identify anN-ethyl-N-nitrosourea (ENU)-induced I23N mutation in the THEMIS protein that causes protection against experimental cerebral malaria (ECM) caused by infection withPlasmodium bergheiANKA.ThemisI23Nhomozygous mice show reduced CD4+and CD8+T lymphocyte numbers. ECM resistance inP. bergheiANKA-infectedThemisI23Nmice is associated with decreased cerebral cellular infiltration, retention of blood-brain barrier integrity, and reduced proinflammatory cytokine production. THEMISI23Nprotein expression is absent from mutant mice, concurrent with the decreased THEMISI23Nstability observedin vitro. Biochemical studiesin vitroand functional complementationin vivoinThemisI23N/+:Lck−/+doubly heterozygous mice demonstrate that functional coupling of THEMIS to LCK tyrosine kinase is required for ECM pathogenesis. Damping of proinflammatory responses inThemisI23Nmice causes susceptibility to pulmonary tuberculosis. Thus, THEMIS is required for the development and ultimately the function of proinflammatory T cells.ThemisI23Nmice can be used to study the newly discovered association ofTHEMIS(6p22.33) with inflammatory bowel disease and multiple sclerosis.

scholarly journals A single rapamycin dose protects against late-stage experimental cerebral malaria via modulation of host immunity, endothelial activation and parasite sequestration

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Pedro Mejia ◽  
J. Humberto Treviño-Villarreal ◽  
Justin S. Reynolds ◽  
Mariana De Niz ◽  
Andrew Thompson ◽  
...  
Keyword(s):  
Cerebral Malaria ◽  
Late Stage ◽  
Endothelial Activation ◽  
Host Immunity ◽  
Experimental Cerebral Malaria

scholarly journals von Willebrand factor increases in experimental cerebral malaria but is not essential for late‐stage pathogenesis in mice

2020 ◽  
Vol 18 (9) ◽  
pp. 2377-2390
Author(s):  
Sirima Kraisin ◽  
Kimberly Martinod ◽  
Linda Desender ◽  
Inge Pareyn ◽  
Sebastien Verhenne ◽  
...  
Keyword(s):  
Cerebral Malaria ◽  
Von Willebrand Factor ◽  
Late Stage ◽  
Experimental Cerebral Malaria ◽  
Von Willebrand ◽  
Willebrand Factor

A role for Fas–Fas ligand interactions during the late-stage neuropathological processes of experimental cerebral malaria

2006 ◽  
Vol 173 (1-2) ◽  
pp. 96-107 ◽  
Author(s):  
Sarah M. Potter ◽  
Tailoi Chan-Ling ◽  
Emilia Rosinova ◽  
Helen J. Ball ◽  
Andrew J. Mitchell ◽  
...  
Keyword(s):  
Cerebral Malaria ◽  
Late Stage ◽  
Fas Ligand ◽  
Experimental Cerebral Malaria ◽  
Ligand Interactions

scholarly journals S-Nitrosoglutathione Reductase Deficiency Confers Improved Survival and Neurological Outcome in Experimental Cerebral Malaria

2017 ◽  
Vol 85 (9) ◽  
Author(s):  
Robyn E. Elphinstone ◽  
Rickvinder Besla ◽  
Eric A. Shikatani ◽  
Ziyue Lu ◽  
Alfred Hausladen ◽  
...  
Keyword(s):  
T Cell ◽  
Cerebral Malaria ◽  
Clinical Outcomes ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Experimental Cerebral Malaria ◽  
Content Type ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity

ABSTRACT Artesunate remains the mainstay of treatment for cerebral malaria, but it is less effective in later stages of disease when the host inflammatory response and blood-brain barrier integrity dictate clinical outcomes. Nitric oxide (NO) is an important regulator of inflammation and microvascular integrity, and impaired NO bioactivity is associated with fatal outcomes in malaria. Endogenous NO bioactivity in mammals is largely mediated by S-nitrosothiols (SNOs). Based on these observations, we hypothesized that animals deficient in the SNO-metabolizing enzyme, S-nitrosoglutathione reductase (GSNOR), which exhibit enhanced S-nitrosylation, would have improved outcomes in a preclinical model of cerebral malaria. GSNOR knockout (KO) mice infected with Plasmodium berghei ANKA had significantly delayed mortality compared to WT animals (P < 0.0001), despite higher parasite burdens (P < 0.01), and displayed markedly enhanced survival versus the wild type (WT) when treated with the antimalarial drug artesunate (77% versus 38%; P < 0.001). Improved survival was associated with higher levels of protein-bound NO, decreased levels of CD4+ and CD8+ T cells in the brain, improved blood-brain barrier integrity, and improved coma scores, as well as higher levels of gamma interferon. GSNOR KO animals receiving WT bone marrow had significantly reduced survival following P. berghei ANKA infection compared to those receiving KO bone barrow (P < 0.001). Reciprocal transplants established that survival benefits of GSNOR deletion were attributable primarily to the T cell compartment. These data indicate a role for GSNOR in the host response to malaria infection and suggest that strategies to disrupt its activity will improve clinical outcomes by enhancing microvascular integrity and modulating T cell tissue tropism.

scholarly journals Totally implantable venous catheters for chemotherapy: experience in 500 patients

2004 ◽  
Vol 122 (4) ◽  
pp. 147-151 ◽  
Author(s):  
Nelson Wolosker ◽  
Guilherme Yazbek ◽  
Kenji Nishinari ◽  
Luiz Caetano Malavolta ◽  
Marco Antonio Munia ◽  
...  
Keyword(s):  
Late Stage ◽  
Jugular Vein ◽  
Infectious Complications ◽  
External Jugular Vein ◽  
Distal Stump ◽  
Chemotherapy Treatment ◽  
Vein Thrombosis ◽  
Oncological Patients ◽  
The Right ◽  
Deep Vein

CONTEXT: Totally implantable devices are increasingly being utilized for chemotherapy treatment of oncological patients, although few studies have been done in our environment to analyze the results obtained from the implantation and utilization of such catheters. OBJECTIVE: To study the results obtained from the implantation of totally implantable catheters in patients submitted to chemotherapy. TYPE OF STUDY: Prospective. SETTING: Hospital do Câncer A.C. Camargo, São Paulo, Brazil. METHODS: 519 totally implantable catheters were placed in 500 patients submitted to chemotherapy, with preference for the use of the right external jugular vein. Evaluations were made of the early and late-stage complications and patient evolution until removal of the device, death or the end of the treatment. RESULTS: The prospective analysis showed an average duration of 353 days for the catheters. There were 427 (82.2%) catheters with no complications. Among the early complications observed, there were 15 pathway hematomas, 8 cases of thrombophlebitis of the distal stump of the external jugular vein and one case of pocket infection. Among the late-stage complications observed, there were 43 infectious complications (0.23/1000 days of catheter use), 11 obstructions (0.06/1000 days of catheter use) and 14 cases of deep vein thrombosis (0.07/1000 days of catheter use). Removal of 101 catheters was performed: 35 due to complications and 66 upon terminating the treatment. A total of 240 patients died while the catheter was functioning and 178 patients are still making use of the catheter. CONCLUSION: The low rate of complications obtained in this study confirms the safety and convenience of the use of totally implantable accesses in patients undergoing prolonged chemotherapy regimes.

scholarly journals Molecular Correlates of Experimental Cerebral Malaria Detectable in Whole Blood

2010 ◽  
Vol 79 (3) ◽  
pp. 1244-1253 ◽  
Author(s):  
Miranda S. Oakley ◽  
Vivek Anantharaman ◽  
Thiago M. Venancio ◽  
Hong Zheng ◽  
Babita Mahajan ◽  
...  
Keyword(s):  
Cerebral Malaria ◽  
Whole Blood ◽  
Cell Receptor ◽  
Sub Saharan Africa ◽  
Molecular Signature ◽  
Receptor Protein ◽  
Pcr Analysis ◽  
Data Set ◽  
Experimental Cerebral Malaria ◽  
Sub Saharan

ABSTRACTCerebral malaria (CM) is a primary cause of deaths caused byPlasmodium falciparumin young children in sub-Saharan Africa. Laboratory tests based on early detection of host biomarkers in patient blood would help in the prognosis and differential diagnosis of CM. Using thePlasmodium bergheiANKA murine model of experimental cerebral malaria (ECM), we have identified over 300 putative diagnostic biomarkers of ECM in the circulation by comparing the whole-blood transcriptional profiles of resistant mice (BALB/c) to those of two susceptible strains (C57BL/6 and CBA/CaJ). Our results suggest that the transcriptional profile of whole blood captures the molecular and immunological events associated with the pathogenesis of disease. We find that during ECM, erythropoiesis is dysfunctional, thrombocytopenia is evident, and glycosylation of cell surface components may be modified. Furthermore, analysis of immunity-related genes suggests that slightly distinct mechanisms of immunopathogenesis may operate in susceptible C57BL/6 and CBA/CaJ mice. Furthermore, our data set has allowed us to create a molecular signature of ECM composed of a subset of circulatory markers. Complement component C1q, β-chain, nonspecific cytotoxic cell receptor protein 1, prostate stem cell antigen, DnaJC, member 15, glutathioneS-transferase omega-1, and thymidine kinase 1 were overexpressed in blood during the symptomatic phase of ECM, as measured by quantitative real-time PCR analysis. These studies provide the first host transcriptome database that is uniquely altered during the pathogenesis of ECM in blood. A subset of these mediators of ECM warrant validation inP. falciparum-infected young African children as diagnostic markers of CM.

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