Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Testosterone induces a lethal outcome in otherwise self-healing blood-stage malaria caused by Plasmodium chabaudi. Here, we examine possible testosterone effects on the antimalaria effectors spleen and liver in female C57BL/6 mice. Self-healing malaria activates gating mechanisms in the spleen and liver that lead to a dramatic reduction in trapping activity, as measured by quantifying the uptake of 3-mum-diameter fluorescent polystyrol particles. However, testosterone delays malaria-induced closing of the liver, but not the spleen. Coincidently, testosterone causes an approximately 3- to 28-fold depression of the mRNA levels of nine malaria-responsive genes, out of 299 genes tested, only in the liver and not in the spleen, as shown by cDNA arrays and Northern blotting. Among these are the genes encoding plasminogen activator inhibitor (PAI1) and hydroxysteroid sulfotransferase (STA2). STA2, which detoxifies bile acids, is suppressed 10-fold by malaria and an additional 28-fold by testosterone, suggesting a severe perturbation of bile acid metabolism. PAI1 is protective against malaria, since disruption of the PAI1 gene results in partial loss of the ability to control the course of P. chabaudi infections. Collectively, our data indicate that the liver rather than the spleen is a major target organ for testosterone-mediated suppression of resistance against blood-stage malaria.
 ...
PMID:Testosterone suppresses protective responses of the liver to blood-stage malaria. 1561 82

Young children spend more than 90% of their time in the household environment--a likely place of exposure to hazardous substances. In the developing world, childhood diarrheal disease and acute lower respiratory infections represent a large portion of the global burden of disease and are strongly related to housing conditions. In the developed world, allergies and asthma are also strongly linked to housing conditions. Therefore, intervention to improve housing is essential to improve and maintain children's health. This paper will review several factors that have been shown to mediate housing and health relations, including psychosocial, environmental, socioeconomic, behavior-cultural, and physiological factors, and will provide examples of intervention to improve child health, with housing as a focus. Environmental contaminants found in the household include biological (for example, vector-borne diseases, dustmites, mold, water- and sanitation-related), chemical (for example, lead, volatile organic compounds, asbestos) or physical (for example, radon, electric and magnetic fields). Socioeconomic factors include household income, the ability to obtain adequate and appropriate housing, and the ability to implement ongoing preventative maintenance. Housing tenure has been used as a proxy for socioeconomic status and shown some relation with health outcome. Socioeconomic factors can be relevant to the ability of households to create social networks that affect health. Psychosocial factors, including stress and depression, can also be related to housing type or design. Behavioral-cultural factors include practices that might influence exposure to chemical, biological, or radiation hazards like time-activity patterns, including gender relations and household decision-making patterns. Physiological factors include genetics or the nutritional and immune status of household members, which can influence the extent to which other housing factors like biological or chemical contaminants adversely affect children. Examples of intersectoral interventions and strategies to improve child health globally, with housing and health as a focus, include integrated pest-management programs to control vector-borne diseases like malaria and Chagas disease and energy-efficiency programs to improve thermal comfort and to reduce the presence of allergens like mold and dustmites. Other interventions include housing and health policy, regulation and standard setting, education, training, and participation.
 ...
PMID:Interventions to improve children's health by improving the housing environment. 1574 71

Data on the effects of Plasmodium gallinaceum on domesticated fowl are sparse, justifying a full investigation of its pathology. Clinical signs following blood-induced infections with the Wellcome line of strain 8A included depression, fever, anorexia, reduced weight gain, poor feed conversion, anaemia, green faeces and often death. After administration of 10(6) erythrocytic parasites, mortality 5 to 10 days after infection was 10% to 93% in chickens 7 to 84 days old. The older the birds, the lower the mortality and the longer the time to death. Onset of detectable parasitaemia occurred mostly during the second day after infection (59% of birds). Peak parasitaemia (approximately 70%) occurred on the sixth day in 85% of surviving birds. The patent period was usually 7 to 19 days. Abnormally low haematocrit values of < or =24% and high colonic temperatures of > or =42 degrees C were recorded. A febrile response is demonstrated conclusively here in P. gallinaceum malaria for the first time. Weight gain of malarious birds was reduced by approximately 18% to 51%, and feed conversion efficiency was often reduced by approximately 12% to 41%. Growth reduction was due entirely to anorexia. Liver weight relative to body weight (normally approximately 2% to 3%) increased to approximately 4.5% by 8 days, and relative spleen weight (normally approximately 0.2%) increased to 1.6% by 12 days. Specific gravities of livers and spleens in healthy and infected birds were approximately 1.09. Gall bladder volume in malarious birds 8 days after infection was approximately four times that of normal birds. Statistically significant changes occurred in the proportions of plasma proteins in malarious birds 8 days after infection; albumin and alpha2-globulin were reduced, while gamma1-globulin and gamma2-globulin were increased. Those changes coincided with significant increases in concentrations of plasma total protein and the enzymes aspartate aminotransferase, glutamate dehydrogenase and gamma-glutamyltransferase, and a decrease in creatinine. Green (biliverdin) colouration of the faeces was a consistent sign of malaria. Birds acquired non-sterile immunity after a single primary infection. The quantitative data presented facilitate selection of the most useful criteria for field diagnosis, estimation of potential economic losses, and assessment of potential avian antimalarial drugs.
 ...
PMID:Avian malaria: clinical and chemical pathology of Plasmodium gallinaceum in the domesticated fowl Gallus gallus. 1576 37

Artesunate (AS) is being developed as a potential agent for the treatment of severe and complicated malaria. A risk assessment of the therapeutic index and related hematological changes of AS and artelinate (AL) following daily intravenous injection for 3 days was conducted in Plasmodium berghei-infected and uninfected rats. The minimum doses of AS and AL for parasitemia suppression were 2.3 and 2.5 mg/kg, respectively, and the suppressive doses for half parasitemia (SD50) were 7.4 and 8.6 mg/kg, respectively. The maximum tolerated dose (MTD) for AS was 240 mg/kg with a therapeutic index of 32.6. The MTD for AL was 80 mg/kg with a therapeutic index of 9.3. Hematological changes were studied on days 1 and 8 after the final dosing. In both AS- and AL-treated rats, dose-dependent and rapidly reversible hematological changes (significant reductions in RBC, HCT, Hb, and reticulocyte levels) were seen in the peripheral blood. Bone marrow evaluation revealed a statistically significant reduction in the myeloid/erythroid ratio only at the highest dose of AS (240 mg/kg), albeit still within the normal ratio range (1.0-1.5:1.0). Looking at the respective therapeutic indices the authors have concluded that AS is much safer than AL. Both drugs induced hematological changes in rats that parallel the dose-dependent, reversible anemia and reticulocytopenia previously reported in animals and humans. However, no significant bone marrow depression was seen for either agent.
 ...
PMID:Risk assessment and therapeutic indices of artesunate and artelinate in Plasmodium berghei-infected and uninfected rats. 1612 19

Costly resistance mechanisms have been cited as an explanation for the widespread occurrence of parasitic infections, yet few studies have examined these costs in detail. A malaria-mosquito model has been used to test this concept by making a comparison of the fitness of highly susceptible lines of mosquitoes with lines that are resistant to infection. Malaria infection is known to cause a decrease in fecundity and fertility of mosquitoes; resistant mosquitoes were thus predicted to be fitter than susceptible ones. Anopheles gambiae were selected for refractoriness/resistance or for increased susceptibility to infection by Plasmodium yoelii nigeriensis. Additional lines that acted as controls for inbreeding depression were raised in parallel but not exposed to selection pressure. Selections were made in triplicate so that founder effects could be detected. Resistance mechanisms that were selected included melanotic encapsulation of parasites within 24 h postinfection and the complete disappearance of parasites from the gut. Costs of immune surveillance were assessed after an uninfected feed, and costs of immune deployment were assessed after exposure to infection and to infection and additional stresses. Mosquito survivorship was unaffected by either resistance to infection or by an increased burden of infection when compared with low levels of infection. In most cases reproductive fitness was equally affected by refractoriness or by infection. Resistant mosquitoes did not gain a fitness advantage by eliminating the parasites. Costs were consistently associated with larval production and egg hatch rate but rarely attributed to changes in blood feeding and never to changes in mosquito size. No advantages appeared to be gained by the offspring of resistant mosquitoes. Furthermore, we were unable to select for refractoriness in groups of mosquitoes in which 100% or 50% of the population were exposed to infection every generation for 22 generations. Under these selection pressures, no population had become completely refractory and only one became more resistant. Variations in fitness relative to control lines in different groups were attributed to founder effects. Our conclusion from these findings is that refractoriness to malaria is as costly as tolerance of infection.
 ...
PMID:Evaluating the costs of mosquito resistance to malaria parasites. 1652 4

It has been reported that malaria infection impairs hepatic drug clearance and causes a down-regulation of CYP-mediated monooxygenase activities in rodents and humans. In the present study, we investigated the effects of Plasmodium berghei infection on the activity of liver monooxygenases in female DBA/2 and C57BL/6 mice. In both mouse strains, P. berghei infection decreased activities mediated by CYP1A (EROD: DBA/2 65.3%, C57BL/6 44.7%) and 2B (BROD: DBA/2 64.3%, C57BL/6 49.8%) subfamily isoforms and increased activities mediated by 2A5 (COH: DBA/2 182.4%, C57BL/6 148.5%) and 2E1 (PNPH: DBA/2 177.8%, C57BL/6 128.5%) isoforms as compared to non-infected controls. Since malaria infection also produced an increase in ALT (273.1%) and AST (354.1%) activities in the blood serum, our findings are consistent with the view that CYP2A5 activity is induced by liver injury. An almost generalized depression of CYP-mediated activities has been found with numerous infections and inflammatory stimuli but an induction of CYP2A5 had been previously noted only in some viral hepatitis and trematode (liver fluke) infections.
 ...
PMID:Plasmodium berghei (ANKA): infection induces CYP2A5 and 2E1 while depressing other CYP isoforms in the mouse liver. 1654 Jan 9

Mefloquine is indicated as oral treatment and as prophylaxis for malaria in areas where chloroquine-resistant malaria is present. Gastrointestinal and neuropsychiatric side effects of mefloquine are well known. More severe neuropsychiatric disorders such as psychosis, depression, hallucinations, and seizures are also reported in the literature. We are reporting a case of drug-induced pneumonia due to mefloquine. This diagnosis was confirmed 4 months after the adverse event, after restarting the same malaria prophylaxis, which could be considered as an unintentional provocation test. This is the third case report in the literature of acute lung injury caused by mefloquine.
 ...
PMID:Mefloquine-induced pneumonitis. 1670 49

Any planning process for health development ought to be based on a thorough understanding of the health needs of the population. This should be sufficiently comprehensive to include the causes of premature death and of disability, as well as the major risk factors that underlie disease and injury. To be truly useful to inform health-policy debates, such an assessment is needed across a large number of diseases, injuries and risk factors, in order to guide prioritization. The results of the original Global Burden of Disease Study and, particularly, those of its 2000-2002 update provide a conceptual and methodological framework to quantify and compare the health of populations using a summary measure of both mortality and disability: the disability-adjusted life-year (DALY). Globally, it appears that about 56 million deaths occur each year, 10.5 million (almost all in poor countries) in children. Of the child deaths, about one-fifth result from perinatal causes such as birth asphyxia and birth trauma, and only slightly less from lower respiratory infections. Annually, diarrhoeal diseases kill over 1.5 million children, and malaria, measles and HIV/AIDS each claim between 500,000 and 800,000 children. HIV/AIDS is the fourth leading cause of death world-wide (2.9 million deaths) and the leading cause in Africa. The top three causes of death globally are ischaemic heart disease (7.2 million deaths), stroke (5.5 million) and lower respiratory diseases (3.9 million). Chronic obstructive lung diseases (COPD) cause almost as many deaths as HIV/AIDS (2.7 million). The leading causes of DALY, on the other hand, include causes that are common at young ages [perinatal conditions (7.1% of global DALY), lower respiratory infections (6.7%), and diarrhoeal diseases (4.7%)] as well as depression (4.1%). Ischaemic heart disease and stroke rank sixth and seventh, retrospectively, as causes of global disease burden, followed by road traffic accidents, malaria and tuberculosis. Projections to 2030 indicate that, although these major vascular diseases will remain leading causes of global disease burden, with HIV/AIDS the leading cause, diarrhoeal diseases and lower respiratory infections will be outranked by COPD, in part reflecting the projected increases in death and disability from tobacco use.
 ...
PMID:Measuring the global burden of disease and epidemiological transitions: 2002-2030. 1689 50

Poverty and associated health, nutrition, and social factors prevent at least 200 million children in developing countries from attaining their developmental potential. We review the evidence linking compromised development with modifiable biological and psychosocial risks encountered by children from birth to 5 years of age. We identify four key risk factors where the need for intervention is urgent: stunting, inadequate cognitive stimulation, iodine deficiency, and iron deficiency anaemia. The evidence is also sufficient to warrant interventions for malaria, intrauterine growth restriction, maternal depression, exposure to violence, and exposure to heavy metals. We discuss the research needed to clarify the effect of other potential risk factors on child development. The prevalence of the risk factors and their effect on development and human potential are substantial. Furthermore, risks often occur together or cumulatively, with concomitant increased adverse effects on the development of the world's poorest children.
 ...
PMID:Child development: risk factors for adverse outcomes in developing countries. 1735 Apr 48

This paper is the third in the Child Development Series. The first paper showed that more than 200 million children under 5 years of age in developing countries do not reach their developmental potential. The second paper identified four well-documented risks: stunting, iodine deficiency, iron deficiency anaemia, and inadequate cognitive stimulation, plus four potential risks based on epidemiological evidence: maternal depression, violence exposure, environmental contamination, and malaria. This paper assesses strategies to promote child development and to prevent or ameliorate the loss of developmental potential. The most effective early child development programmes provide direct learning experiences to children and families, are targeted toward younger and disadvantaged children, are of longer duration, high quality, and high intensity, and are integrated with family support, health, nutrition, or educational systems and services. Despite convincing evidence, programme coverage is low. To achieve the Millennium Development Goals of reducing poverty and ensuring primary school completion for both girls and boys, governments and civil society should consider expanding high quality, cost-effective early child development programmes.
 ...
PMID:Strategies to avoid the loss of developmental potential in more than 200 million children in the developing world. 1724 Feb 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>