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Artemisinin and its semi-synthetic derivatives are a group of drugs used against Plasmodium falciparum malaria. Artemisinin is isolated from the plant Artemisia annua , sweet wormwood, a herb employed in Chinese traditional medicine. A precursor compound can be produced using genetically engineered yeast. Chemically, artemisinin is a sesquiterpene lactone containing an unusual peroxide bridge.

This peroxide is believed to be responsible for the drug's mechanism of action. Few other natural compounds with such a peroxide bridge are known. Artemisinin and its endoperoxide derivatives have been used for the treatment of P. Therapies that combine artemisinin or its derivatives with some other antimalarial drug are the preferred treatment for malaria and are both effective and well tolerated in patients. The drug is also increasingly being used in Plasmodium vivax malaria.

Artemisinins can be used alone, but this leads to a high rate of recrudescence return of parasites and other drugs are required to clear the body of all parasites and prevent recurrence. The World Health Organization WHO is pressuring manufacturers to stop making the uncompounded drug available to the medical community at large, aware of the catastrophe that would result if the malaria parasite developed resistance to artemisinins. Increasingly, these combinations are being made to GMP standard.

A separate issue concerns the quality of some artemisinin-containing products being sold in Africa and Southeast Asia. Artemisinins are not used for malaria prophylaxis prevention because of the extremely short activity half-life of the drug. To be effective, it would have to be administered multiple times each day. Artesunate administered by intravenous or intramuscular injection has proven superior to quinine in large, randomised controlled trials in both adults [13] and children. Artesunate is now recommended by the WHO for treatment of all cases of severe malaria.

A serendipitous discovery was made in China in the early s while searching for novel anthelmintics for schistosomiasis that artemisinin was effective against schistosomes , [16] [17] [18] the human blood flukes, which are the second-most prevalent parasitic infections, after malaria. Artemisinin and its derivatives are all potent anthelmintics. Clinical trials were also successfully conducted in Africa among patients with schistosomiasis.

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Artemisinins are generally well tolerated at the doses used to treat malaria. Mild blood abnormalities have also been noted. A rare but serious adverse effect is allergic reaction.

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Adverse effects in patients with acute P. Clinical evidence for artemisinin resistance in southeast Asia was first reported in , [25] and was subsequently confirmed by a detailed study from western Cambodia. In April , the WHO stated that resistance to the most effective antimalarial drug, artemisinin, could unravel national Indian malaria control programs, which have achieved significant progress in the last decade.

WHO advocates the rational use of antimalarial drugs and acknowledges the crucial role of community health workers in reducing malaria in the region. Two main mechanisms of resistance drive Plasmodium resistance to antimalarial drugs. The first one is an efflux of the drug away from its action site due to mutations in different transporter genes like pfcrt in chloroquine resistance or an increased number of the gene copies like pfmdr1 copy number in mefloquine resistance.

The second is a change in the parasite target due to mutations in corresponding genes like, at the cytosol level, dhfr and dhps in sulfadoxine - pyrimethamine resistance or, at the mitochondrion level, cytochrome b in atovaquone resistance.

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Resistance of Plasmodium falciparum to the new artemisinin compounds involves a novel mechanism corresponding to a quiescence phenomenon. As of , the mechanism of action of arteminisins was not known, but the most widely accepted theory was that they are first activated through cleavage after reacting with haem and iron II oxide , which results in the generation of free radicals that in turn damage susceptible proteins, resulting in the death of the parasite.

Seedlings are grown in nurseries and then transplanted into fields. It takes about 8 months for them to reach full size. The plants are harvested, the leaves are dried and sent to facilities where the artemisinin is extracted using solvent, typically hexane. Alternative extraction methods have been proposed. The Chinese company Artepharm created a combination artimisinin and piperaquine drug marketed as Artequick. In addition to clinical studies performed in China and southeast Asia, Artequick was used in large scale malaria eradication efforts in the Comoros Islands.

After negotiation with the WHO, Novartis and Sanofi-Aventis provide ACT drugs at cost on a nonprofit basis; however, these drugs are still more expensive than other malaria treatments. In April , Sanofi announced the launch [42] of a production facility in Garessio, Italy, to manufacture the anti-plasmodial drug on a large scale. The reaction is followed by a photochemical process creating singlet oxygen to obtain the end product.

Sanofi expects to produce 25 tons of artemisinin in , ramping up the production to 55—60 tons in In August , Sanofi announced the release of the first batch of semisynthetic artemisinin. A systematic review of four studies from East Africa concluded that subsidizing artemisinin-based combination therapy ACT in the private retail sector in combination with training and marketing led to increased availability of ACTs in stores, increased use of ACTs for febrile children under five years of age, and decrease in the use of older, less effective antimalarials among children under five years of age; the underlying studies did not determine if the children had malaria nor determine if there were health benefits.

The biosynthesis of artemisinin is believed to involve the mevalonate pathway MVA and the cyclization of farnesyl diphosphate FDP. The routes from artemisinic alcohol to artemisinin remain controversial, and they differ mainly in when the reduction step takes place. Both routes suggested dihydroartemisinic acid as the final precursor to artemisinin. Dihydroartemisinic acid then undergoes photo-oxidation to produce dihydroartemisinic acid hydroperoxide. Ring expansion by the cleavage of hydroperoxide and a second oxygen-mediated hydroperoxidation finish the biosynthesis of artemisinin.

The total synthesis of artemisinin has been performed from available organic starting materials, using basic organic reagents, many times.

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The first two total syntheses were a "remarkable The project began in , and initial project partners included the University of California, Berkeley which provided the technology on which the project was based — a process that genetically altered yeast to produce artemisinic acid ; [51] and Amyris, Inc. In , a team from UC Berkeley reported they had engineered Saccharomyces cerevisiae yeast to produce small amount of the precursor artemisinic acid. In this effort of synthetic biology , a modified mevalonate pathway was used, and the yeast cells were engineered to express the enzyme amorphadiene synthase and a cytochrome P monooxygenase CYP71AV1 , both from A.

A three-step oxidation of amorpha-4,diene gives the resulting artemisinic acid. This physical stimulation appears to enhance the cell-repair effects of the inflammatory response.

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The first large scale application of ultrasound was around World War II. Sonar systems were being built and used to navigate submarines. It was realized that the high intensity ultrasound waves that they were using were heating and killing fish. Since the s, ultrasound has been used by physical and occupational therapists for therapeutic effects. Ultrasound is applied using a transducer or applicator that is in direct contact with the patient's skin. Gel is used on all surfaces of the head to reduce friction and assist transmission of the ultrasonic waves.

Therapeutic ultrasound in physical therapy is alternating compression and rarefaction of sound waves with a frequency of 0. Intensity decreases as the waves penetrate deeper. They are absorbed primarily by connective tissue: Conditions for which ultrasound may be used for treatment include the following examples: From Wikipedia, the free encyclopedia.

Expert Opinion on Drug Delivery. Proceedings of Meetings on Acoustics. Retrieved March 12, Archived at the Wayback Machine. Magnetic Resonance in Medicine. Journal of biomaterials applications. Lewis Jr, and D.