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)

The causes of mortality and frequency of diseases were tabulated in 304 autopsies performed at Hopital Mama Yemo, Kinshasa, between July 1973 and December 1974. 78 of these autopsies were performed on subjects who died at Hopital Mama Yemo, 36 encompassed subjects from other hospitals, and 190 were of medicolegal cases in which the cause of death was not apparent from external examination. Men comprised 63.5% of autopsied cases. The mean age was 30.19 +or- 1.31 for men and 19.84 +or- 1.76 for women. 16.8% of deaths were due to homicide, 6.3% to suicide, and 8.9% to accidents, yielding an overall prevalence for trauma of 32%. Cancer accounted for only 3% of deaths, and cardiovascular diseases 8.2%. Bacterial infections (predominantly streptococcal disease, lobar pneumonia, and pulmonary tuberculosis) represented the largest single cause of death (17.4%). Parasitic infections comprised a further 6.3% of mortality and viral infections 7.2%, giving infectious diseases a combined frequency of 30.9%. Metabolic diseases were responsible for an additional 11.8% of deaths. Obstetric causes were identified in 3.9% of fatalities, and 95% of these cases represented hemorrhagic and septic complications of illegal abortion. Neonatal deaths (4.3%) were largely due to pneumonitis from aspirated amniotic fluid. A final 5.9% of deaths were unexplained. Also analyzed were cases of sudden death occurring outside the hospitals. 31.3% of these deaths were attributed to cardiovascular diseases and 46.3% to infection (including 2.5% due to septic abortion). Finally, the frequency of major diseases in this series was tabulated. Malaria was most frequently found (41.8%), followed by intravascular erythrocytic sickling (18.3%) and hypertension (16%). 12% of females in this series (20% of those dying traumatically) showed evidence of pelvic inflammatory disease. This series is considered to overestimate the frequency of trauma because of the large number of medicolegal cases that fall in this category. This selection for trauma further led to an oversampling of adult men. Nonetheless, it represents the 1st and best qualitative estimate of disease mortality and prevalence in Zaire. The trends in mortality and morbidity identified through this study provide a basis for planning health care and health education.
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PMID:Autopsy analysis of disease frequency in Kinshasa, Republic of Zaire. 96 86

Insights gained by a group of American maternal and child helath (MCH) care nurses during a 1983 exchange tour to Kenya, sponsored by Professional Seminar Counsultants, are decribed. Kenya is a poor, predominantly rural country. The annual population growth rate is 4.1%, and 60% of the population is under the age of 16. The government's annual per capita health expenditure is only US$4, there is little emphasis on pediatrics as a speciality, and the linguistic diversity of the population complicates the delivery of health care services. As a result of these factors, the MCH care system in Kenya differed markedly from the systems observed in previous exchange tours to China and the USSR. Kenya's population is served by a variety of government, private, and missionary hospitals and by government health centers. The health centers are staffed by 2 nurses and 2 assistants who provide maternity, family planning, and immunization services. The staff also diagnoses and treats common illnesses. Service are provided free for patients under the age of 16, and minimal fees are collected from older patients. The largest hospital in the country is the 1600 bed, Joma Kenyatta National hospital which employs 900 nurses and serves as a refereal hospital for complicated cases and as a teaching and research center. 42% of the hospital staff nurses are registered nurses and 58% are enrolled nurses. Disease patterns in Kenya and the US are markedly different. In Kenya, infectious diseases are more common than chronic diseases, and amony children the major causes of death are starvation, measles, whooping cough, malaria, tubercluosis, and diarrhea. Marasmus and protein calorie deficiency are the 2 major types of childhood malnutrition found in Kenya. Nurses frequently provide health education services and even teach mothers how to grow nutritious foods for their children. Rh incompatibility is rare in Kenya, but ABO incompatibility is common. Othr common diseases, raraly found in temperate climates, include Burkitt's lymphoma, leprosy, and tropical ataxic neuropathies. The visiting nurses were at 1st shocked by some of the practices and customs they observed; however, as they learned more about the rationall behind these practices, shock gave way to appreciation. Children's wards lacked playthings, the walls were devoid of pictures, and the rooms were sparsely furnished. The lack of material items, however, was more than compensated for by the rich stimuli provided family members and friends, who not only visited the chilren, but performed a variety of nursing tasks. The family centered approach also provided a sense of security for the patients. A Masai paramedic explained how the custom of polygamy ensures adherence to the 2-year postpartum sexual taboo which, in turn, facilitates prolonged breast feeding. The nurses also became acquainted with the social value of adolescent circumcision rites. These rites are illegal but still performed in many rural areas. The rites are physically painful, but they provide a mechanism for easing the transition from adolescent to adult status. The rites help young people assume measningful roles in the society and provide them with clearly specified identities. As a result, adolescent suicide is rara among the rural villagers.
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PMID:Health care in Africa. 646 42

In individual donors which have never been exposed to malaria parasites, the CD4+ T cell precursor frequencies for tetanus toxoid (TT) and Plasmodium falciparum responses are similar (range 1:850-1:4800). Limiting dilution cultures set up in response to P. falciparum trophozoites can be re-stimulated with the same stage of the parasite or TT and respond with similar frequencies. A substantial overlap in the responses to different agents was confirmed in suicide selection experiments where cells responding to malaria parasite, TT or influenza virus antigens were deleted using the cell cycle inhibitor cytosine arabinoside (Ara-C). The responses of the remaining cells to P. falciparum were almost completely abrogated and only weak responses were observed to different recall antigens (0.2-21% of untreated control). Little or no effect was observed on the responses to superantigen or mitogen. Furthermore, in contrast to superantigen, the observed responses to TT and Plasmodium were polyclonal, the blastoid cells generated reacting with a range of anti-TCR Vbeta antibodies with little preferential usage.
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PMID:Evidence for CD4+ T cell responses common to Plasmodium falciparum and recall antigens. 946 13

Death by apoptosis regulates cell numbers in metazoan tissues and it is mediated by activation of caspases and results in characteristic morphological and biochemical changes. We report here that the malaria protozoan, Plasmodium berghei, exhibits features typical of metazoan apoptotic cells including condensation of chromatin, fragmentation of the nuclear DNA and movement of phosphatidylserine from the inner to the outer lamellae of the cell membrane. In addition, proteins with caspase-like activity were identified in the cytoplasm of the ookinete suggesting that the cellular mechanism of cell death may be similar to that of multicellular eukaryotes. Our data show that more than 50% of the mosquito midgut stages of the parasite die naturally by apoptosis before gut invasion. Cell death was prevented by a caspase inhibitor, treatment resulting in a doubling of parasite intensity. All these features also occur in vitro. Cell suicide thus plays a major and hitherto unrecognised role in controlling parasite populations and could be a novel target for malaria control strategies.
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PMID:Apoptosis in the malaria protozoan, Plasmodium berghei: a possible mechanism for limiting intensity of infection in the mosquito. 1211 96

In mammals four deoxyribonucleoside kinases, with a relatively restricted specificity, catalyze the phosphorylation of the four natural deoxyribonucleosides. When cultured mosquito cells, originating from the malaria vector Anopheles gambiae, were examined for deoxyribonucleoside kinase activities, only a single enzyme was isolated. Subsequently, the corresponding gene was cloned and over-expressed. While the mosquito kinase (Ag-dNK) phosphorylated all four natural deoxyribonucleosides, it displayed an unexpectedly higher relative efficiency for the phosphorylation of purine versus pyrimidine deoxyribonucleosides than the fruit fly multisubstrate deoxyribonucleoside kinase (EC 2.7.1.145). In addition, Ag-dNK could also phosphorylate some medically interesting nucleoside analogs, like stavudine (D4T), 2-chloro-deoxyadenosine (CdA) and 5-bromo-vinyl-deoxyuridine (BVDU). Although the biological significance of multisubstrate deoxyribonucleoside kinases and their diversity among insects remains unclear, the observed variation provides a whole range of applications, as species specific and highly selective targets for insecticides, they have a potential to be used in the enzymatic production of various (di-)(deoxy-)ribonucleoside monophosphates, and as suicide genes in gene therapy.
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PMID:Mosquito has a single multisubstrate deoxyribonucleoside kinase characterized by unique substrate specificity. 1262 8

Cerebral malaria, one of the most serious complications of Plasmodium falciparum infection, is characterized by the sequestration of parasitized red blood cells (PRBCs) in cerebral microvascular beds. The precise mechanisms involved in the onset of neuropathology remain unknown, but parasite sequestration in the brain, metabolic disturbances, and host immune responses all play a role. Sequestration of PRBCs is mediated by different endothelial cell surface receptors, mainly ICAM-1 and CD36. In vitro studies demonstrated that PRBC adhesion to endothelial cells induces over-expression of various adhesion molecules including ICAM-1, expression of iNOS, oxidative stress and finally apoptosis in endothelial cells. In vivo studies, in humans and in mice models of cerebral malaria brought striking evidence of the implication of brain infiltrating cytotoxic effector CD8T lymphocytes in the development of murine cerebral malaria pathogenesis. These cells probably act by direct cytotoxicity against endothelial cells. Cytotoxicity and apoptosis potentially lead blood-brain-barrier disruption and could contribute to the development of cerebral malaria. We propose a key role for endothelial cells in the pathogenesis of cerebral malaria, both by suicide / apoptosis, and / or by murder / cytotoxicity.
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PMID:Blood-brain barrier breakdown during cerebral malaria: suicide or murder? 1611 23

The risk of students contracting HIV on electives has received much coverage. Few data exist, however, on risks of other adverse events. Medical schools gave comprehensive advice on infectious disease but little on personal safety. There were no reported parenteral infections or deaths from infection, despite cases of malaria and one needle-stick injury. Accidents were responsible for six deaths and three serious injuries from just nine medical schools. A further student committed suicide after return to the UK. Personal violence and events related to the political situation of the elected country were also reported. This paper is based on a retrospective survey of elective convenors from UK medical schools examining advice given and adverse events. Accidents appear to pose significant risk to medical students on elective and there appears to be a lack of advice on personal safety issues. Further research should examine behaviours that put students at risk of accidents, and strategies that could prevent such events.
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PMID:Safety on elective: a survey on safety advice and adverse events during electives. 1668 72

Glutathione reductase is an important housekeeping enzyme for redox homeostasis both in human cells and in the causative agent of tropical malaria, Plasmodium falciparum. Glutathione reductase inhibitors were shown to have anticancer and antimalarial activity per se and to contribute to the reversal of drug resistance. The development of menadione chemistry has led to the selection of 6-[2'-(3'-methyl)-1',4'-naphthoquinolyl]hexanoic acid, called M(5), as a potent reversible and uncompetitive inhibitor of both human and P. falciparum glutathione reductases. Here we describe the synthesis and kinetic characterization of a fluoromethyl-M(5) analogue that acts as a mechanism-based inhibitor of both enzymes. In the course of enzymatic catalysis, the suicide substrate is activated by one- or two-electron reduction, and then a highly reactive quinone methide is generated upon elimination of the fluorine. Accordingly the human enzyme was found to be irreversibly inactivated with a k(inact) value of 0.4 +/- 0.2 min(-1). The crystal structure of the alkylated enzyme was solved at 1.7 A resolution. It showed the inhibitor to bind covalently to the active site Cys58 and to interact noncovalently with His467', Arg347, Arg37, and Tyr114. On the basis of the crystal structure of the inactivated human enzyme and stopped-flow kinetic studies with two- and four-electron-reduced forms of the unreacted P. falciparum enzyme, a mechanism is proposed which explains naphthoquinone reduction at the flavin of glutathione reductase.
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PMID:A fluoro analogue of the menadione derivative 6-[2'-(3'-methyl)-1',4'-naphthoquinolyl]hexanoic acid is a suicide substrate of glutathione reductase. Crystal structure of the alkylated human enzyme. 1691 Jun 73

Our work on targeting redox equilibria of malarial parasites propagating in red blood cells has led to the selection of six 1,4-naphthoquinones, which are active at nanomolar concentrations against the human pathogen Plasmodium falciparum in culture and against Plasmodium berghei in infected mice. With respect to safety, the compounds do not trigger hemolysis or other signs of toxicity in mice. Concerning the antimalarial mode of action, we propose that the lead benzyl naphthoquinones are initially oxidized at the benzylic chain to benzoyl naphthoquinones in a heme-catalyzed reaction within the digestive acidic vesicles of the parasite. The major putative benzoyl metabolites were then found to function as redox cyclers: (i) in their oxidized form, the benzoyl metabolites are reduced by NADPH in glutathione reductase-catalyzed reactions within the cytosols of infected red blood cells; (ii) in their reduced forms, these benzoyl metabolites can convert methemoglobin, the major nutrient of the parasite, to indigestible hemoglobin. Studies on a fluorinated suicide-substrate indicate as well that the glutathione reductase-catalyzed bioactivation of naphthoquinones is essential for the observed antimalarial activity. In conclusion, the antimalarial naphthoquinones are suggested to perturb the major redox equilibria of the targeted infected red blood cells, which might be removed by macrophages. This results in development arrest and death of the malaria parasite at the trophozoite stage.
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PMID:Glutathione reductase-catalyzed cascade of redox reactions to bioactivate potent antimalarial 1,4-naphthoquinones--a new strategy to combat malarial parasites. 2168 7

Suicide is amongst the top ten causes of death for all age groups in most countries of the world. It is the second most important cause of death in the younger age group (15-19 yrs.) , second only to vehicular accidents.Attempted suicides are ten times the successful suicide figures, and 1-2% attempted suicides become successful suicides every year. Male sex, widowhood, single or divorced marital status, addiction to alcohol ordrugs, concomitant chronic physical or mental illness, past suicidal attempt, adverse life events, staying in lodging homes or staying alone,or in areas with a changing population, all these conditions predispose people to suicides. The key factor probably is social isolation. An important WHO Study established that out of a total of 6003 suicides,98% had a psychiatric disorder. Hence mental health professionals havean important role to play in the prevention and management of suicide.Moreover, social disintegration also increases suicides, as was witnessed in the Baltic States following collapse of the Soviet Union. Hence, reducing social isolation, preventing social disintegration and treating mental disorders is the three pronged attack that must be the crux of any public health programme to reduce/prevent suicide. This requires an integrated effort on the part of mental health professionals (including crisis intervention and medication/psychotherapy), governmental measures to tackle poverty and unemployment, and social attempts toreorient value systems and prevent sudden disintegration of norms and mores. Suicide prevention and control is thus a movement which involves the state, professionals, NGOs, volunteers and an enlightened public.Further, the Global Burden of Diseases Study has projected a rise of more than 50% in mental disorders by the year 2020 (from 9.7% in 1990to 15% in 2020). And one third of this rise will be due to Major Depression. One of the prominent causes of preventable mortality issuicidal attempts made by patients of Major Depression. Therefore facilities to tackle this condition need to be set up globally on a warfooting by governments, NGOs and health care delivery systems, if morbidity and mortality of the world population has to be seriously controlled . The need, first of all, is to identify suicide prevention as public health policy, just as we think in terms of Malaria or Polio eradication, or have achieved smallpox eradication.
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PMID:Towards a suicide free society: identify suicide prevention as public health policy. 2281 99


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