The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Daniel J. Wallace - One of the best experts on this subject based on the ideXlab platform.
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New insights into mechanisms of therapeutic effects of Antimalarial Agents in SLE
Nature Reviews Rheumatology, 2012Co-Authors: Daniel J. Wallace, Vineet S. Gudsoorkar, Michael H. Weisman, Swamy R. VenuturupalliAbstract:Antimalarial Agents are the cornerstone Agents in the clinical management of systemic lupus erythematosus Toll-like receptor (TLR)-antagonism has emerged as an important mechanism of action of Antimalarial Agents The antilipidaemic, photoprotective and antiproliferative effects of chloroquine, hydroxychloroquine and quinacrine are in part explained by TLR antagonism Antimalarial Agents also act by several additional molecular mechanisms, the understanding of which continues to evolve Antimalarial Agents are generally safe, effective and clinically useful in almost all patients with systemic lupus erythematosus These drugs offer considerable promise for treating a variety of immune-mediated as well as nonimmune diseases, and have exciting potential Antimalarial Agents are mainstays in the clinical management of systemic lupus erythematosus, and have been in routine use for more than 50 years. This Review summarizes recent insights into the mechanisms of action of these Agents and their clinical implications. Antimalarial Agents have routinely been used for the treatment of systemic lupus erythematosus (SLE) for over 50 years. These Agents continue to enjoy success as the initial pharmacotherapy for SLE even in the era of targeted therapies. Antimalarial Agents have numerous biological effects that are responsible for their immunomodulatory actions in SLE. Their inhibitory effect on Toll-like receptor-mediated activation of the innate immune response is perhaps the most important discovery regarding their putative mechanism of action, but some other, previously known properties, such as antithrombotic and antilipidaemic effects, are now explained by new research. In the 1980s and 1990s, these antihyperlipidaemic and antithrombotic effects were demonstrated in retrospective clinical studies, and over the past few years prospective studies have confirmed those findings. Knowledge about the risk–benefit profile of Antimalarial Agents during pregnancy and lactation has evolved, as has the concept of retinal toxicity. Antimalarial Agents have unique disease-modifying properties in SLE and newer iterations of this class of anti-inflammatory Agents will have a profound effect upon the treatment of autoimmune disease.
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new insights into mechanisms of therapeutic effects of Antimalarial Agents in sle
Nature Reviews Rheumatology, 2012Co-Authors: Daniel J. Wallace, Vineet S. Gudsoorkar, Michael H. Weisman, Swamy R. VenuturupalliAbstract:Antimalarial Agents are mainstays in the clinical management of systemic lupus erythematosus, and have been in routine use for more than 50 years. This Review summarizes recent insights into the mechanisms of action of these Agents and their clinical implications.
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Antimalarial Agents and lupus.
Rheumatic diseases clinics of North America, 1994Co-Authors: Daniel J. WallaceAbstract:Antimalarials are under-utilized, disease-modifying Agents that are useful in the management of lupus erythematosus. Antimalarials can promote a remission in non-organ-threatening lupus and decrease its risk of dissemination. They are especially useful for cutaneous and inflammatory joint disease and have modest actions in improving serositis, fatigue, and cognitive dysfunction. As Agents that do not depress the bone marrow or promote opportunistic infections, Antimalarials have potential applications in combination with other antilupus medications and with each other.
Swamy R. Venuturupalli - One of the best experts on this subject based on the ideXlab platform.
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New insights into mechanisms of therapeutic effects of Antimalarial Agents in SLE
Nature Reviews Rheumatology, 2012Co-Authors: Daniel J. Wallace, Vineet S. Gudsoorkar, Michael H. Weisman, Swamy R. VenuturupalliAbstract:Antimalarial Agents are the cornerstone Agents in the clinical management of systemic lupus erythematosus Toll-like receptor (TLR)-antagonism has emerged as an important mechanism of action of Antimalarial Agents The antilipidaemic, photoprotective and antiproliferative effects of chloroquine, hydroxychloroquine and quinacrine are in part explained by TLR antagonism Antimalarial Agents also act by several additional molecular mechanisms, the understanding of which continues to evolve Antimalarial Agents are generally safe, effective and clinically useful in almost all patients with systemic lupus erythematosus These drugs offer considerable promise for treating a variety of immune-mediated as well as nonimmune diseases, and have exciting potential Antimalarial Agents are mainstays in the clinical management of systemic lupus erythematosus, and have been in routine use for more than 50 years. This Review summarizes recent insights into the mechanisms of action of these Agents and their clinical implications. Antimalarial Agents have routinely been used for the treatment of systemic lupus erythematosus (SLE) for over 50 years. These Agents continue to enjoy success as the initial pharmacotherapy for SLE even in the era of targeted therapies. Antimalarial Agents have numerous biological effects that are responsible for their immunomodulatory actions in SLE. Their inhibitory effect on Toll-like receptor-mediated activation of the innate immune response is perhaps the most important discovery regarding their putative mechanism of action, but some other, previously known properties, such as antithrombotic and antilipidaemic effects, are now explained by new research. In the 1980s and 1990s, these antihyperlipidaemic and antithrombotic effects were demonstrated in retrospective clinical studies, and over the past few years prospective studies have confirmed those findings. Knowledge about the risk–benefit profile of Antimalarial Agents during pregnancy and lactation has evolved, as has the concept of retinal toxicity. Antimalarial Agents have unique disease-modifying properties in SLE and newer iterations of this class of anti-inflammatory Agents will have a profound effect upon the treatment of autoimmune disease.
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new insights into mechanisms of therapeutic effects of Antimalarial Agents in sle
Nature Reviews Rheumatology, 2012Co-Authors: Daniel J. Wallace, Vineet S. Gudsoorkar, Michael H. Weisman, Swamy R. VenuturupalliAbstract:Antimalarial Agents are mainstays in the clinical management of systemic lupus erythematosus, and have been in routine use for more than 50 years. This Review summarizes recent insights into the mechanisms of action of these Agents and their clinical implications.
Michael K. Riscoe - One of the best experts on this subject based on the ideXlab platform.
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Xanthones as Antimalarial Agents: discovery, mode of action, and optimization.
Current medicinal chemistry, 2005Co-Authors: Michael K. Riscoe, Jane X. Kelly, R. W. WinterAbstract:It is believed that at no time in the history of the human race malaria has been absent. This disease, which is caused by protozoa of the genus Plasmodium, in all likelihood has been responsible for the death of about half of all people who ever lived. Even today, after attempts at intervention on a worldwide scale, malaria remains the most significant parasitic disease in the tropics and sub-tropics, where it causes at least 500 million clinical episodes and claims 1.5 million lives each year, mostly young children and pregnant women. Widespread resistance to the best and least expensive Antimalarials, chloroquine and S/P (i.e., a combination of sulfadoxine and pyrimethamine), combined with an increasing tolerance to insecticides in the mosquito vector, threaten a global malaria tragedy unless new countermeasures are developed. For malaria therapy, the great panacea would be the development of a long-lasting vaccine, but until this becomes a reality, people living in and traveling to endemic regions must rely on a dwindling cache of more expensive drugs; many beyond the economic reach of impoverished people living in malarious regions of the world. Our course to recognition of xanthones as potential Antimalarial Agents took a rather circuitous route, involving both serendipity and empiricism, and is described together with mechanistic details of drug action. From a chance encounter with a sea urchin collected near the city of Cannon Beach on the Oregon coast to naturally occurring and functionalized xanthones, it is revealed how these compounds target the Plasmodium parasites most vulnerable feature - the digestive vacuole.
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Xanthones as Antimalarial Agents: stage specificity.
The American journal of tropical medicine and hygiene, 2000Co-Authors: Marina Ignatushchenko, R. W. Winter, Michael K. RiscoeAbstract:The erythrocytic development of Plasmodium falciparum is divided into the ring, trophozoite, and schizont stages based on morphologic assessment. Using highly synchronous ring and trophozoite cultures of P. falciparum, we observed considerable differences in their sensitivity to hydroxyxanthones: trophozoites were much more sensitive to the drugs than ring-stage parasites. Trophozoites treated with a prototypic xanthone, the 2,3,4,5,6-pentahydroxy derivative (X5), were arrested in their development and became degenerate in appearance within 24 hr of drug exposure. These morphologic changes appeared to reflect the cytotoxic nature of the action of the drug against the parasite, since daughter ring-stage forms were not observed following addition of the drug. That X5 was more active against parasites in the later stages of intraerythrocytic development is consistent with the proposed mode of action, inhibition of heme polymerization. Knowledge of the structure-activity relationships for xanthones as Antimalarial Agents has also been expanded. Xanthones with a hydroxyl group in the peri-position exhibited decreased Antimalarial activity, possibly due to intramolecular hydrogen bonding with the carbonyl and consequent reduced affinity for heme. Paired hydroxyls attached to the lower half of the xanthone greatly enhanced drug potency.
R. W. Winter - One of the best experts on this subject based on the ideXlab platform.
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Xanthones as Antimalarial Agents: discovery, mode of action, and optimization.
Current medicinal chemistry, 2005Co-Authors: Michael K. Riscoe, Jane X. Kelly, R. W. WinterAbstract:It is believed that at no time in the history of the human race malaria has been absent. This disease, which is caused by protozoa of the genus Plasmodium, in all likelihood has been responsible for the death of about half of all people who ever lived. Even today, after attempts at intervention on a worldwide scale, malaria remains the most significant parasitic disease in the tropics and sub-tropics, where it causes at least 500 million clinical episodes and claims 1.5 million lives each year, mostly young children and pregnant women. Widespread resistance to the best and least expensive Antimalarials, chloroquine and S/P (i.e., a combination of sulfadoxine and pyrimethamine), combined with an increasing tolerance to insecticides in the mosquito vector, threaten a global malaria tragedy unless new countermeasures are developed. For malaria therapy, the great panacea would be the development of a long-lasting vaccine, but until this becomes a reality, people living in and traveling to endemic regions must rely on a dwindling cache of more expensive drugs; many beyond the economic reach of impoverished people living in malarious regions of the world. Our course to recognition of xanthones as potential Antimalarial Agents took a rather circuitous route, involving both serendipity and empiricism, and is described together with mechanistic details of drug action. From a chance encounter with a sea urchin collected near the city of Cannon Beach on the Oregon coast to naturally occurring and functionalized xanthones, it is revealed how these compounds target the Plasmodium parasites most vulnerable feature - the digestive vacuole.
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Xanthones as Antimalarial Agents: stage specificity.
The American journal of tropical medicine and hygiene, 2000Co-Authors: Marina Ignatushchenko, R. W. Winter, Michael K. RiscoeAbstract:The erythrocytic development of Plasmodium falciparum is divided into the ring, trophozoite, and schizont stages based on morphologic assessment. Using highly synchronous ring and trophozoite cultures of P. falciparum, we observed considerable differences in their sensitivity to hydroxyxanthones: trophozoites were much more sensitive to the drugs than ring-stage parasites. Trophozoites treated with a prototypic xanthone, the 2,3,4,5,6-pentahydroxy derivative (X5), were arrested in their development and became degenerate in appearance within 24 hr of drug exposure. These morphologic changes appeared to reflect the cytotoxic nature of the action of the drug against the parasite, since daughter ring-stage forms were not observed following addition of the drug. That X5 was more active against parasites in the later stages of intraerythrocytic development is consistent with the proposed mode of action, inhibition of heme polymerization. Knowledge of the structure-activity relationships for xanthones as Antimalarial Agents has also been expanded. Xanthones with a hydroxyl group in the peri-position exhibited decreased Antimalarial activity, possibly due to intramolecular hydrogen bonding with the carbonyl and consequent reduced affinity for heme. Paired hydroxyls attached to the lower half of the xanthone greatly enhanced drug potency.
David Greenwood - One of the best experts on this subject based on the ideXlab platform.
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eLS - History of Antimalarial Agents
Encyclopedia of Life Sciences, 2009Co-Authors: David GreenwoodAbstract:Malaria is a debilitating and, in its most severe form, falciparum malaria, a potentially fatal disease. Treatment in the form of powdered bark of the cinchona tree from South America has been available from at least the seventeenth century. Synthetic Antimalarial Agents were not developed until the twentieth century, stimulated by serious shortages of supply during the two World Wars. The first advances were made in Germany in the interwar period. During and after World War II, further progress was made in Britain and the United States. Inevitably resistance to these Agents emerged and became a major problem after the 1960s. Other active chemicals have since been developed, but many have serious side effects and much hope is now pinned on derivatives of a natural product, artemisinin, obtained from sweet wormwood (Artemisia annua) and used for centuries (though not at first for malaria) in traditional Chinese medicine. Key Concepts Malaria is a potentially fatal disease affecting millions of people, chiefly in tropical countries. A treatment in the form of powdered bark of the cinchona tree from northern South America has been available since the seventeenth century. Cinchona bark contains several Antimalarial alkaloids, most importantly quinine. Synthetic Antimalarial Agents were first developed in Germany in the 1920s and 1930s. The first antifolate compound active against malaria, proguanil, was developed in England during World War II. After World War II, several important synthetic Antimalarial compounds, notably chloroquine and pyrimethamine became available for prophylaxis and treatment. From the 1960s resistance emerged as a major issue and quinine once again became the treatment of choice for serious falciparum malaria. Derivatives of artemisinin, a natural product used in traditional Chinese medicine, is being now being successfully used in treatment. Keywords: Antimalarial Agents; quinine; cinchona bark; chloroquine; artemisinin
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Conflicts of interest: the genesis of synthetic Antimalarial Agents in peace and war
The Journal of antimicrobial chemotherapy, 1995Co-Authors: David GreenwoodAbstract:Malaria has had an enormous impact on human history, not least in times of war. The disease has been treatable by a natural remedy, quinine, since the 17th century, but the production of synthetic Antimalarial Agents was first achieved in Germany in the wake of the Great War of 1914-1918, in which malaria had caused immense problems. In the 1920s research workers in the Bayer laboratories of the IG Farbenindustrie consortium developed the 8-aminoquinoline plasmoquine (the forerunner of primaquine). They went on to develop the acridine dye, atebrin (mepacrine) and the 4-aminoquinolines, Resochin (developed at the end of the Second World War in America as chloroquine) and Sontochin. British attempts to match the advances achieved by the Germans were at first unproductive, partly because collaboration between academic and industrial organizations in the UK was beset by concerns over patent rights. However, with the outbreak of World War II, when supplies of Antimalarials were scarce, ICI succeeded in the large-scale production of mepacrine (essential to prosecution of the war, particularly in the Far East) and also initiated a programme of collaborative research that eventually led to the discovery of proguanil (Paludrine); this, in its turn led to the diaminopyrimidine, pyrimethamine. A massive cooperative screening programme in the USA during World War II eventually bore fruit in the realization of the therapeutic potential of chloroquine, and in the later development of amodiaquine and primaquine. Some of this work also influenced the subsequent discovery of mefloquine and halofantrine at the Walter Reed Army Institute of Research.