Search results for "Malaria."
showing 10 items of 155 documents
¿Pueden la malaria y el dengue reaparecer en España?
2010
ResumenEl aumento de la inmigración durante los últimos años en España ha facilitado la importación de numerosas enfermedades tropicales. Entre ellas, las de transmisión vectorial son algunas de las más complicadas de estudiar por la complejidad que conlleva la participación de diversos hospedadores en los ciclos de transmisión, así como por la necesidad de conocer todos los parámetros fisiológicos, bioecológicos y biogeográficos relacionados con el organismo vector para poder inferir las posibilidades reales de la emergencia o la reemergencia de las enfermedades pertinentes. En estas circunstancias, el presente trabajo aporta información acerca de enfermedades importadas de incuestionable …
¿Pueden la malaria y el dengue reaparecer en España? Could malaria and dengue reappear in Spain?
2010
El aumento de la inmigración durante los últimos años en España ha facilitado la importación de numerosas enfermedades tropicales. Entre ellas, las de transmisión vectorial son algunas de las más complicadas de estudiar por la complejidad que conlleva la participación de diversos hospedadores en los ciclos de transmisión, así como por la necesidad de conocer todos los parámetros fisiológicos, bioecológicos y biogeográficos relacionados con el organismo vector para poder inferir las posibilidades reales de la emergencia o la reemergencia de las enfermedades pertinentes. En estas circunstancias, el presente trabajo aporta información acerca de enfermedades importadas de incuestionable interés…
Total Synthesis and Biological Investigation of (−)‐Artemisinin: The Antimalarial Activity of Artemisinin Is not Stereospecific
2018
Here, we describe an efficient and diversity-oriented entry to both (-)-artemisinin (1) and its natural antipode (+)-artemisinin, starting from commercially and readily available S-(+)- and R-(-)-citronellene, respectively. Subsequently, we answered the still open question regarding the specificity of artemisinins action. By using a drug-sensitive Plasmodium falciparum NF54 strain, we showed that the antimalarial activity of artemisinin is not stereospecific. Our straightforward and biomimetic approach to this natural endoperoxide enables the synthesis of artemisinin derivatives that are not accessible through applying current methods and may help to address the problem of emerging resistan…
Oxidative stress response of tumor cells: microarray-based comparison between artemisinins and anthracyclines
2004
The antimalarial artemisinins also reveal profound cytotoxic activity against tumor cells. Artemisinins harbor an endoperoxide bridge whose cleavage results in the generation of reactive oxygen species (ROS) and/or artemisinin carbon-centered free radicals. Established cancer drugs such as anthracyclines also form ROS and free radicals that are responsible for the cardiotoxicity of anthracyclines. In contrast, artemisinins do not reveal cardiotoxicity. In the present investigation, we compared the cytotoxic activities of different artemisinins (artemisinin, artesunate, arteether, artemether, artemisitene, dihydroartemisinylester stereoisomers) in 60 cell lines of the National Cancer Institu…
Toxicity of the antimalarial artemisinin and its dervatives.
2010
As long as no effective malaria vaccine is available, chemotherapy belongs to the most important weapons fighting malaria. One of the most promising new drug developments is the sesquiterpene artemisinin (ARS) and its derivatives, e.g., artemether, arteether, and sodium artesunate. Large clinical studies and meta-analyses did not show serious side effects, although proper monitoring of adverse effects in developing countries might not be a trivial task. There is a paucity of large-scale clinical trials suitable to detect rare but significant toxicity. Therefore, a final and definitive statement on the safety of artemisinins still cannot be made. In contrast, animal experiments show consider…
Cutaneous Lupus Erythematosus
2008
Lupus erythematosus (LE) is an inflammatory autoimmune disease, characterized by a heterogeneous clinical presentation. The skin lesions are one of the most frequent symptoms of the disease and present with a broad spectrum of LE-nonspecific and LE-specific cutaneous manifestations. Therefore, the development of a classification for skin lesions in the disease has proven difficult. For example, the LE-nonspecific cutaneous manifestations include livedo racemosa, thrombophlebitis, and leukocytoclastic vasculitis and can be associated with high disease activity and systemic organ involvement. The LE-specific cutaneous manifestations encompass the subtypes of cutaneous lupus erythematosus (CLE…
Artesunate Activates Mitochondrial Apoptosis in Breast Cancer Cells via Iron-catalyzed Lysosomal Reactive Oxygen Species Production
2011
The antimalarial agent artesunate (ART) activates programmed cell death (PCD) in cancer cells in a manner dependent on the presence of iron and the generation of reactive oxygen species. In malaria parasites, ART cytotoxicity originates from interactions with heme-derived iron within the food vacuole. The analogous digestive compartment of mammalian cells, the lysosome, similarly contains high levels of redox-active iron and in response to specific stimuli can initiate mitochondrial apoptosis. We thus investigated the role of lysosomes in ART-induced PCD and determined that in MCF-7 breast cancer cells ART activates lysosome-dependent mitochondrial outer membrane permeabilization. ART impac…
GSK-3? Can Regulate the Sensitivity of MIA-PaCa-2 Pancreatic and MCF-7 Breast Cancer Cells to Chemotherapeutic Drugs, Targeted Therapeutics and Nutra…
2021
Glycogen synthase kinase-3 (GSK-3) is a regulator of signaling pathways. KRas is frequently mutated in pancreatic cancers. The growth of certain pancreatic cancers is KRas-dependent and can be suppressed by GSK-3 inhibitors, documenting a link between KRas and GSK-3. To further elucidate the roles of GSK-3β in drug-resistance, we transfected KRas-dependent MIA-PaCa-2 pancreatic cells with wild-type (WT) and kinase-dead (KD) forms of GSK-3β. Transfection of MIA-PaCa-2 cells with WT-GSK-3β increased their resistance to various chemotherapeutic drugs and certain small molecule inhibitors. Transfection of cells with KD-GSK-3β often increased therapeutic sensitivity. An exception was observed wi…
Factors determining sensitivity or resistance of tumor cell lines towards artesunate.
2009
Clinical oncology is still challenged by the development of drug resistance of tumors that result in poor prognosis for patients. There is an urgent necessity to understand the molecular mechanisms of resistance and to develop novel therapy strategies. Artesunate (ART) is an anti-malarial drug, which also exerts profound cytotoxic activity towards cancer cells. We first applied a gene-hunting approach using cluster and COMPARE analyses of microarray-based transcriptome-wide mRNA expression profiles. Among the genes identified by this approach were genes from diverse functional groups such as structural constituents of ribosomes (RPL6, RPL7, RPS12, RPS15A), kinases (CABC1, CCT2, RPL41), tran…
Solid-State Electrochemical Assay of Heme-Binding Molecules for Screening of Drugs with Antimalarial Potential
2013
The interaction between heme and ligands is the basis for a variety of tests aimed at the discovery of antiplasmodial molecules. Two electrochemical methods for the screening of molecules with potential antimalarial activity through heme-binding mechanism are described. The first method is applicable to lipophilic environment, by using solution phase electrochemistry in DMSO solutions of Fe(III)-heme plus the tested compounds at carbon electrodes. This method provides well-defined voltammetric signals, characteristic of the heme-ligand (L) interaction. The second method involves aqueous media at biological pH and the use of voltammetry of immobilized particles, by means of microparticulate …