Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case-control study was performed to determine the role of rural factors including occupation and previous malaria exposure in the development of classic Kaposi's sarcoma (CKS) in a high incidence area of Europe. The occurrence of CKS association with other malignancies was also examined. The results showed that the risk of having CKS was significantly increased in subjects farming cereals, while a previous history of malaria did not influence the risk of developing CKS. A near-significant increase in associated tumours was found.
Br J Cancer 1997
PMID:The role of occupation and a past history of malaria in the etiology of classic Kaposi's sarcoma: a case-control study in north-east Sardinia. 940 Sep 51

Initially the impetus to develop iron (Fe) chelators for clinical use was based upon the need for a drug to treat Fe-overload diseases such as beta-thalassemia. However, it has become clear that Fe chelators may be useful for the treatment of a wide variety of disease states, including cancer, malaria, and free radical mediated injury. In particular, over the last 10 years a number of studies have shown that Fe chelators may be of use in the treatment of a number of aggressive human cancers, including neuroblastoma and leukemia, and several clinical trials have substantiated their potential. In the current review the role of Fe in cellular proliferation will be discussed, followed by the possible sites and mechanism of action of some of the most effective ligands. Attention will then be turned to examine the Fe chelators shown to possess antiproliferative activity and the clinical trials performed to assess their efficacy.
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PMID:Potential of iron chelators as effective antiproliferative agents. 943 40

The causes of post operative pyrexia in an orthopaedic unit was studied prospectively in 520 patients who underwent surgery. Two hundred patients (38.4%) developed postoperative pyrexia as defined by having recorded high temperatures of over 38 degrees C on two occasions within 24 hours (excluding the first 24 hours post-operatively). The commonest causes of post-operative pyrexia were wound infection in 70 (13.4%), respiratory tract infections in 40 (7.6%) and malaria in 30 (5.7%) patients, while other causes were urinary tract infection in 20 (3.8%), thrombophlebitis in 15 (2.8%) and deep vein thrombosis in 15 (2.8%) of the patients; while ten (1.9%) patients had pyrexia of undetermined cause despite exhaustive clinical and laboratory workup. The other associated conditions in patients who developed pyrexia were diabetes mellitus in 20 (3.8%), HIV seropositivity and malignancy in 30 (5.7%) and six (1.1%) patients, respectively.
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PMID:Post-operative pyrexia in an orthopaedic unit. 948 22

The Epstein-Barr virus (EBV) is an ubiquitous virus infecting nearly the entire adult human population. The EBV is closely associated with rhinopharyngeal cancer in Southern China and Northern Africa. Three geographic subtypes of EBV have been identified to date. They differ by their nuclear antigene EBNA2. The EBNA2 AC strains predominate in Asia; EBNA2 AD strains predominate in the United States; EBNA2 B strains have all been identified in black Africa. Burkitt's lymphoma is the most frequent tumor in children aged 5 to 9 years in equatorial Africa. A prospective study in 42,000 children in Ouganda demonstrated that children who develop Burkitt's lymphoma have severe EBV infection during the first months of life. Very early EBV infection observed in North or equatorial Africa increases the risk of Burkitt's lymphoma by 20-times that in Europe. Hyperendemic malaria observed in the equatorial zone increases the incidence of tumors by a factor of 20. An association between EBV and rhinopharyngeal cancer is a constant feature only in South China, in North and East Africa, as well as in arctic regions as cases of carcinoma not associated with EBV infection have been reported in Greece. Surveys in the Democratic Republic of China concerning several hundred thousand persons have shown that serum IgA/VCA allows early diagnosis of cancer. It is estimated that the risk of rhinopharyngeal cancer is 20% in Chinese with high levels of IgA/VCA.
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PMID:[Epstein-Barr virus and associated diseases. Course of Medical Virology, Institut Pasteur, 1995/1996]. 953 9

The production of pro-inflammatory cytokines, such as interleukins 1 and 6 and tumour necrosis factors, occurs rapidly following trauma or invasion of the body by pathogenic organisms. The cytokines mediate the wide range of symptoms associated with trauma and infection, such as fever, anorexia, tissue wasting, acute phase protein production and immunomodulation. In part, the symptoms result from a co-ordinated response, in which the immune system is activated and nutrients released, from endogenous sources, to provide substrate for the immune system. Although the cytokine mediated response is an essential part of the response to trauma and infection, excessive production of pro-inflammatory cytokines, or production of cytokines in the wrong biological context, are associated with mortality and pathology in a wide range of diseases, such as malaria, sepsis, rheumatoid arthritis, inflammatory bowel disease, cancer and AIDS. Cytokine biology can be modulated by antiinflammatory drugs, recombinant cytokine receptor antagonists and nutrients. Among the nutrients, fats have a large potential for modulating cytokine biology. A number of trials have demonstrated the anti-inflammatory effects of fish oils, which are rich in n-3 polyunsaturated fatty acids, in rheumatoid arthritis, inflammatory bowel disease, psoriasis and asthma. Animal studies, conducted by ourselves and others, indicate that a range of fats can modulate pro-inflammatory cytokine production and actions. In summary fats rich in n-6 polyunsaturated fatty acids enhance IL1 production and tissue responsiveness to cytokines, fats rich in n-3 polyunsaturated fatty acids have the opposite effect, monounsaturated fatty acids decrease tissue responsiveness to cytokines and IL6 production is enhanced by total unsaturated fatty acid intake. There are a large number of potential cellular mechanisms which may mediate the effects observed. The majority relate to the ability of fats to alter the composition of membrane phospholipids. As a consequence of alterations in phospholipid composition, membrane fluidity may change, altering binding of cytokines to receptors and G protein activity. The nature of substrate for various signalling pathways associated with cytokine production and actions may also be changed. Consequently, alterations in eicosanoid production and activation of protein kinase C may occur. We have examined a number of these potential mechanisms in peritoneal macrophages of rats fed fats with a wide range of fatty acid composition. We have found that the total C18:2 and 20:4 diacyl species of phosphatidylethanolamine in peritoneal macrophages relates in a positive curvilinear fashion with dietary linoleic acid intake; that TNF induced IL1 and IL6 production relate in a positive curvilinear fashion to linoleic acid intake; that leukotriene B4 production relates positively with dietary linoleic acid intake over a range of moderate intakes and is suppressed at high intakes, while PGE2 production is enhanced. There was no clear relationship between linoleic acid intake and membrane fluidity, however fluidity was influenced in a complex manner by the type of fat in the diet, the period over which the fat was fed and the presence of absence of TNF stimulation. None of the proposed mechanisms, acting alone, can explain the positive effect of dietary linoleic acid intake on pro-inflammatory cytokine production. However each may be involved, in part, in the modulatory effects observed.
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PMID:Modulation of pro-inflammatory cytokine biology by unsaturated fatty acids. 955 30

Artemisia species, widespread in nature, are frequently utilized for the treatment of diseases such as malaria, hepatitis, cancer, inflammation, and infections by fungi, bacteria, and viruses. Furthermore, some Artemisia constituents were found to be potential insecticides and allelopathic chemicals. This genus is receiving growing attention presumably due to: (i) the diversified biology and chemistry of the constituents, (ii) the frequent application in traditional medical practice, and (iii) the rich source of the plant material. This review summarizes mainly the biological results obtained in the past decade. The significance and trends in this field are briefly discussed.
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PMID:Biologically active substances from the genus Artemisia. 961 8

Prenylated proteins have been shown to function in important cellular regulatory processes including signal transduction. The enzymes involved in protein prenylation, farnesyl transferase and geranylgeranyl transferase, have been recent targets for development of cancer chemotherapeutics. We have initiated a systematic study of protein prenyl transferases of the malaria parasite, Plasmodium falciparum, to determine whether these enzymes can be developed as targets for antimalarial chemotherapy. We report here the identification of protein farnesyl transferase and protein geranylgeranyl transferase-I in the malaria parasite, P. falciparum. The farnesyl transferase has been partially purified from the cytosolic fraction through ammonium sulfate precipitation and Mono-Q chromatography. Farnesyl and geranylgeranyl transferase-I activities are present at all stages of P. falciparum intraerythrocytic development with maximum specific activity in the ring stage. Geranylgeranyl transferase-I specific activity is two times that of farnesyl transferase in the ring stage. Peptidomimetics and prenyl analogues of protein farnesyl transferase substrates were tested as in vitro inhibitors of partially purified P. falciparum prenyl transferase and of malaria parasite growth. The peptidomimetics were significantly more potent inhibitors than lipid substrate analogues of both the activity of Mono-Q purified enzyme and parasite growth in intraerythrocytic cultures. Exposure of the parasite to the peptidomimetic L-745,631 also showed significant inhibition of morphological development beyond the trophozoite stage. These studies suggest the potential of designing or identifying differential inhibitors of P. falciparum and mammalian prenyl transferases as an approach to novel malaria therapy.
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PMID:Protein prenyl transferase activities of Plasmodium falciparum. 974 68

Compared with those in industrialised countries, people in developing countries have little access to treatment for HIV infection, or for many other diseases including cancer, tuberculosis, and malaria. Although attention has been paid to areas such as provision of essential drugs, strengthening of infrastructures and service delivery, human rights, and appropriate health technologies, great inequalities remain. The HIV epidemic has highlighted these differences, because technological advances and the response of people infected with HIV have enabled the sharing of experiences across regions and brought the contrast into focus.
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PMID:Access to treatment for HIV in developing countries; statement from international seminar on access to treatment for HIV in developing countries, London, June 5 and 6, 1998. UK NGO AIDS Consortium Working Group on Access to Treatment for HIV in Developing Countries. 1002 30

Trypanothione reductases (TR; EC 1.6.4.8) and thioredoxin reductases (TrxR; EC 1.6.4.5.) are enzymes central to cellular thiol metabolism. Trypanosoma cruzi TR (TcTR) is therefore considered as a potential candidate for drug design against trypanosomiasis. Inhibition of human TrxR (hTrxR) is likely to be beneficial in psoriasis, cancer, and autoimmune diseases, while inhibition of a putative TrxR from Plasmodium falciparum (PfTrxR) might prove effective against malaria. The natural substrates of the first two enzymes are very expensive and difficult to obtain; in the case of PfTrxR, the physiological substrate has not yet been identified. We have therefore synthesized and tested three different 5,5'-dithiobis(2-nitrobenzamides) as alternative substrates of the above enzymes. As with 5, 5'-dithiobis(2-nitrobenzoate) (DTNB), which can be reduced by TRs and TrxRs, the new compounds are converted to their corresponding chromophoric thiolates; however, they have much lower Km values and are therefore less likely to interfere with inhibitor testing. Using the new substrates, a novel enzyme assay has been developed which is identical for all three enzymes, can be performed in a microtiter plate, and is amenable to automation. Thus, the assay provides a versatile and inexpensive tool for kinetic studies and high-throughput inhibitor screening.
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PMID:Synthesis of 5,5'-dithiobis(2-nitrobenzamides) as alternative substrates for trypanothione reductase and thioredoxin reductase: a microtiter colorimetric assay for inhibitor screening. 1003 54

The Philippines is an archipelago of about 7000 islands, with an area about the size of England, situated just above the equator in Southeast Asia. It has a population of 70 million. The Philippines has had extensive commercial and social contact with Asian neighbors, specifically the Chinese, even before the 377 years of Spanish colonization from 1521 to 1898 and the 48 years of American rule from 1898 to 1946. More than 80% of Filipinos are Catholics; the rest are Muslims and Protestants of various denominations, including those who belong to Filipino church groups. Infectious diseases such as tuberculosis, amoebiasis, typhoid fever, and malaria are still prevalent, and arteriosclerosis, cancer, and stroke are common and on the rise.
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PMID:Surgery in the Philippines. 1008 78


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