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Antimalarial drug monocyte

Adriana A Marin Rodriguez, Leonardo J M Carvalho, Emilia A Kimura, Alejandro M Katzin
The development of new drugs is one of the strategies to control malaria. Isoprenoid biosynthesis in Plasmodium falciparum is an essential pathway for parasite survival, and is therefore a potential target for new antimalarial drugs. Indeed, plant-derived secondary metabolites, such as terpenes, exhibit antimalarial activity in vitro by inhibiting isoprenoid biosynthesis in P. falciparum. In this study, the in vitro antiplasmodial activity of perillyl alcohol (POH) was evaluated, along with its in vitro toxicity and its effect on the isoprenylation process...
March 2018: International Journal of Antimicrobial Agents
Anna C C Aguiar, Ananda C Cunha, Isabela Penna Ceravolo, Regina A Correia Gonçalves, Arildo J B Oliveira, Antoniana Ursine Krettli
Several species of Aspidosperma plants are used to treat diseases in the tropics, including Aspidosperma ramiflorum, which acts against leishmaniasis, an activity that is experimentally confirmed. The species, known as guatambu-yellow, yellow peroba, coffee-peroba and matiambu, grows in the Atlantic Forest of Brazil in the South to the Southeast regions. Through a guided biofractionation of A. ramiflorum extracts, the plant activity against Plasmodium falciparum was evaluated in vitro for toxicity towards human hepatoma G2 cells, normal monkey kidney cells and nonimmortalised human monocytes isolated from peripheral blood...
November 2015: Memórias do Instituto Oswaldo Cruz
Pedro Mejia, Monica Diez-Silva, Faustin Kamena, Fengxin Lu, Stacey M Fernandes, Peter H Seeberger, Alvin E Davis, James R Mitchell
Plasmodium falciparum-induced severe malaria remains a continuing problem in areas of endemicity, with elevated morbidity and mortality. Drugs targeting mechanisms involved in severe malaria pathology, including cytoadhesion of infected red blood cells (RBCs) to host receptors and production of proinflammatory cytokines, are still necessary. Human C1-inhibitor (C1INH) is a multifunctional protease inhibitor that regulates coagulation, vascular permeability, and inflammation, with beneficial effects in inflammatory disease models, including septic shock...
January 1, 2016: Journal of Infectious Diseases
André Said, Stephanie Bock, Trim Lajqi, Gerrit Müller, Günther Weindl
Recent studies suggest a role for autophagy in the secretion of IL-1 cytokines regulating the development of inflammatory diseases. The antimalarial drug and autophagy/lysosome inhibitor chloroquine (CHQ) is considered as potential trigger of drug-induced or drug-aggravated psoriasis, in which Th17 cells sustain a persistent inflammation. In this study, we investigated the effect of CHQ on human monocyte-derived Langerhans-like cells (MoLC) and dendritic cells (MoDC) in response to IL-1β. The presence of CHQ reduced IL-12p70 release in both subsets, but surprisingly increased IL-6 production in MoDC and IL-23 in MoLC...
December 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
W Armand Guiguemde, Nicholas H Hunt, Jintao Guo, Annael Marciano, Richard K Haynes, Julie Clark, R Kiplin Guy, Jacob Golenser
The decreasing effectiveness of antimalarial therapy due to drug resistance necessitates constant efforts to develop new drugs. Artemisinin derivatives are the most recent drugs that have been introduced and are considered the first line of treatment, but there are already indications of Plasmodium falciparum resistance to artemisinins. Consequently, drug combinations are recommended for prevention of the induction of resistance. The research here demonstrates the effects of novel combinations of the new artemisinin derivative, artemisone, a recently described 10-alkylamino artemisinin derivative with improved antimalarial activity and reduced neurotoxicity...
August 2014: Antimicrobial Agents and Chemotherapy
Patricia López, Javier Rodríguez-Carrio, Ana Suárez
OBJECTIVES: To analyse the influence of IFNα on TNFα production by human peripheral blood mononuclear cells (PBMCs), as well as the possible interference of this cytokine on the effect of antimalarial drugs, TNFα regulators widely used in the treatment of systemic lupus erythematosus (SLE). METHODS: PBMCs, monocytes or T cells were treated with IFNα alone or simultaneously to cellular stimuli as well as in the presence or absence of chloroquine. Supernatants from such cultures were collected to quantify TNFα by ELISA...
May 2014: Cytokine
Ifeoma C Ezenyi, Lalasoanirina Ranarivelo, Salawu A Oluwakanyinsola, Martins Emeje
BACKGROUND: Entada africana (EA) is a medicinal plant used in West Africa for the treatment of malaria fever, but its efficacy against malaria is yet to be scientifically validated. Our study explores the antimalarial potential of the ethanol leaf extract of EA. METHODS: The antiplasmodial activity of EA against chloroquine-sensitive (HB3) and chloroquine-resistant (FcM29) Plasmodium falciparum was determined as well as its peripheral antinociceptive and anti-inflammatory properties...
May 1, 2014: Journal of Basic and Clinical Physiology and Pharmacology
Minghua Yang, Lizhi Cao, Min Xie, Yan Yu, Rui Kang, Liangchun Yang, Mingyi Zhao, Daolin Tang
Sepsis is caused by an overwhelming immune response to bacterial infection. The discovery of high mobility group box 1 (HMGB1) as a late mediator of lethal sepsis has prompted investigation into the development of new therapeutics which specifically target this protein. Here, we show that chloroquine, an anti-malarial drug, prevents lethality in mice with established endotoxemia or sepsis. This effect is still observed even if administration of chloroquine is delayed. The protective effects of chloroquine were mediated through inhibition of HMGB1 release in macrophages, monocytes, and endothelial cells, thereby preventing its cytokine-like activities...
August 1, 2013: Biochemical Pharmacology
Tonia Woodberry, Gabriela Minigo, Kim A Piera, Fiona H Amante, Alberto Pinzon-Charry, Michael F Good, J Alejandro Lopez, Christian R Engwerda, James S McCarthy, Nicholas M Anstey
BACKGROUND: Dendritic cells (DCs) are highly specialized antigen-presenting cells that are crucial for initiation of immune responses. During naturally acquired malaria, DC number and function is reduced. METHODS: The timing of, parasitemia threshold of, and contribution of apoptosis to DC loss were prospectively evaluated in 10 men after experimental challenge with approximately 1800 Plasmodium falciparum-parasitized red blood cells (pRBCs) and after drug cure initiated at a parasite level of ≥ 1000 parasites/mL...
August 1, 2012: Journal of Infectious Diseases
Patrice N Mimche, Eloise Thompson, Donatella Taramelli, Livia Vivas
OBJECTIVES: Curcumin is a natural plant product with antimalarial activity and immunomodulatory properties. In this study we aimed to investigate its effects on CD36 expression and CD36-mediated Plasmodium falciparum phagocytosis as well as the role played by reactive oxygen species (ROS) and the peroxisome proliferator-activated receptor γ retinoid X receptor (PPARγ-RXR) in these processes. METHODS: In vitro antimalarial activity was evaluated by the [³H]hypoxanthine assay...
August 2012: Journal of Antimicrobial Chemotherapy
Bridgette M Cumming, Gregory M F Watson, J P Dean Goldring
In interferon-γ activated human macrophages, GTP-cyclohydrolase 1 catalyses the conversion of guanosine triphosphate to 7,8-dihydroneopterin triphosphate, which is dephosphorylated and oxidized to form neopterin. Elevated levels of neopterin have been detected in the urine and serum of malaria-infected patients. In this study, U937 cells were treated with interferon-γ and one of the following antimalarial drugs: amodiaquine, artemisinin, chloroquine, doxycycline, primaquine, pyrimethamine or quinine. The effects of treating the U937 cells with malaria pigment (β-haematin), latex beads, or Plasmodium falciparum-infected-red blood cell lysates were also investigated...
November 2011: Experimental Parasitology
Rosangela Frita, Maria Rebelo, Ana Pamplona, Ana M Vigario, Maria M Mota, Martin P Grobusch, Thomas Hänscheid
BACKGROUND: Malaria pigment (haemozoin, Hz) has been the focus of diverse research efforts. However, identification of Hz-containing leukocytes or parasitized erythrocytes is usually based on microscopy, with inherent limitations. Flow cytometric detection of depolarized Side-Scatter is more accurate and its adaptation to common bench top flow cytometers might allow several applications. These can range from the ex-vivo and in-vitro detection and functional analysis of Hz-containing leukocytes to the detection of parasitized Red-Blood-Cells (pRBCs) to assess antimalarial activity...
2011: Malaria Journal
Cong Han, Yahui Lin, Guangliang Shan, Zaixing Zhang, Xiaodong Sun, Zhensheng Wang, Chunyan Wei, Yan Deng, Lianhui Zhang, Lingyi Bu, Dingding Shao, Heng Wang
Host macrophage migration inhibitory factor (MIF) has been implicated in the pathogenesis of malaria infections. Several Plasmodium parasite-derived MIFs were identified to have the potential to regulate host immune response. However, the role of Plasmodium MIFs in the immunopathogenesis of malaria infection and the relationships between these mediators and inflammatory cytokines remained unclear. In this study, we have investigated two Plasmodium MIFs in peripheral blood of uncomplicated malaria patients and analyzed their correlations with several major factors during malaria infection...
October 2010: Clinical and Vaccine Immunology: CVI
Rolf Fendel, Christian Brandts, Annika Rudat, Andrea Kreidenweiss, Claudia Steur, Iris Appelmann, Bettina Ruehe, Paul Schröder, Wolfgang E Berdel, Peter G Kremsner, Benjamin Mordmüller
BACKGROUND: Falciparum Malaria, an infectious disease caused by the apicomplexan parasite Plasmodium falciparum, is among the leading causes of death and morbidity attributable to infectious diseases worldwide. In Gabon, Central Africa, one out of four inpatients have severe malarial anemia (SMA), a life-threatening complication if left untreated. Emerging drug resistant parasites might aggravate the situation. This case control study investigates biomarkers of enhanced hemolysis in hospitalized children with either SMA or mild malaria (MM)...
2010: PloS One
Andreas Pospischil, Paul Walther, Jasper Dingemanse
Lipid storage disorders and phospholipidosis share similar morphologic characteristics displayed as lamellar bodies at ultrastructural level. More than 50 cationic amphiphilic drugs (CADs), including antidepressants, antianginal, antimalarial, and cholesterol-lowering agents, have been reported to induce phospholipidosis, however, the mechanism by which this occurs has not been extensively studied and is not well understood. Both the Food and Drug Administration (FDA) and the pharmaceutical industry recognized drug-induced phospholipidosis as a significant challenge for drug development...
September 2010: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
Andrea K Boggild, Srivicha Krudsood, Samir N Patel, Lena Serghides, Noppadon Tangpukdee, Kevin Katz, Polrat Wilairatana, W Conrad Liles, Sornchai Looareesuwan, Kevin C Kain
BACKGROUND: Despite the use of potent antimalarial drugs, the fatality rate associated with severe malaria remains high. Adjunctive therapies that target the immunopathological responses to infection may decrease mortality associated with severe malaria. We hypothesized that peroxisome proliferator-activated receptor gamma agonists (eg, rosiglitazone) would modulate the host's innate immune response to malaria and improve outcome. METHODS: In a randomized, double-blind, placebo-controlled, phase I/II trial of treatment for malaria acquired in Thailand, we investigated the safety, tolerability, and efficacy of rosiglitazone use for parasite clearance and for reducing malaria-induced inflammation...
September 15, 2009: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Judith Hannah Waknine-Grinberg, Joseph El-On, Vivian Barak, Yechezkel Barenholz, Jacob Golenser
A nontoxic dose of Sambucol, an immunomodulator commercially sold as an immune stimulator, was examined in murine models of leishmaniasis and malaria. Sambucol causes a shift in the immune response, as demonstrated in human monocyte cultures, to Th1 (inflammation-associated) responses. Treatment of leishmania-infected mice with Sambucol delayed the development of the disease. As there was no direct IN VITRO anti-leishmanial effect, the observed partial protection IN VIVO is most likely related to immune modulation...
May 2009: Planta Medica
Jacob H Rand, Xiao-Xuan Wu, Anthony S Quinn, Pojen P Chen, James J Hathcock, Douglas J Taatjes
Treatment with the antimalarial drug hydroxychloroquine (HCQ) has been associated with reduced risk of thrombosis in the antiphospholipid (aPL) syndrome (APS) and, in an animal model of APS, with reduction of experimentally induced thrombosis. Recognition of beta2-glycoprotein I (beta2GPI) by aPL antibodies appears to play a major role in the disease process. We therefore used the techniques of ellipsometry and atomic force microscopy (AFM) to investigate whether HCQ directly affects the formation of aPL IgG-beta2GPI complexes on phospholipid bilayers...
September 1, 2008: Blood
Thomas Hänscheid, Timothy J Egan, Martin P Grobusch
Plasmodium spp produce a pigment (haemozoin) to detoxify the free haem that is generated by haemoglobin degradation. Haemozoin was originally thought to be an inert waste byproduct of the parasite. However, recent research has led to the recognition that haemozoin is possibly of great importance in various aspects of malaria. Haemozoin is the target of many antimalarial drugs, and the unravelling of the exact modes of action may allow the design of novel antimalarial compounds. The detection of haemozoin in erythrocytes or leucocytes facilitates the diagnosis of malaria...
October 2007: Lancet Infectious Diseases
Aun Chea, Sotheara Hout, Sok-Siya Bun, Nino Tabatadze, Monique Gasquet, Nadine Azas, Riad Elias, Guy Balansard
Stephania rotunda (Menispermaceae) is used in traditional medicine for the treatment of fever. Four major alkaloids: dehydroroemerine, tetrahydropalmatine, xylopinine, cepharanthine as well as aqueous extract (SA), dichloromethane extracts (SD1 and SD2) from this plant were tested against Plasmodium falciparum W2 in vitro. Dehydroroemerine, cepharanthine and SD1 were the most active against W2 with IC(50) of 0.36, 0.61microM and 0.7microg/mL, respectively. Their IC(50) on human monocytic THP1 cells were 10...
May 30, 2007: Journal of Ethnopharmacology
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