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Query: UMLS:C0021311 (Infection)
 38,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infections due to Cryptococcus neoformans are common in AIDS patients. We investigated the effect of chloroquine, which raises the pH of phagolysosomes, on the anticryptococcal activity of mononuclear phagocytes. C. neoformans multiplied within monocyte-derived macrophages (MDM) in the absence of chloroquine but were killed with the addition of chloroquine. Ammonium chloride was also beneficial, suggesting that effects were mediated by alkalinizing the phagolysosome. Chloroquine inhibits growth of other intracellular pathogens by limiting iron availability. However, chloroquine-induced augmentation of MDM anticryptococcal activity was unaffected by iron nitriloacetate, demonstrating that chloroquine worked by a mechanism independent of iron deprivation. There was an inverse correlation between growth of C. neoformans in cell-free media and pH, suggesting that some of the effect of chloroquine on the anticryptococcal activity of MDM could be explained by relatively poor growth at higher pH. Chloroquine enhanced MDM anticryptococcal activity against all tested cryptococcal strains except for one large-capsule strain which was not phagocytosed. Positive effects of chloroquine were also seen in monocytes from both HIV-infected and -uninfected donors. Finally, chloroquine was therapeutic in experimental cryptococcosis in outbred and severe combined immunodeficient mice. Thus, chloroquine enhances the activity of mononuclear phagocytes against C. neoformans by iron-independent, pH-dependent mechanisms and is therapeutic in murine models of cryptococcosis. Chloroquine might have clinical utility for the prophylaxis and treatment of human cryptococcosis.
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PMID:Chloroquine induces human mononuclear phagocytes to inhibit and kill Cryptococcus neoformans by a mechanism independent of iron deprivation. 929 33

Ehrlichia chaffeensis and E. sennetsu are genetically divergent obligatory intracellular bacteria of human monocytes and macrophages, and the human granulocytic ehrlichiosis (HGE) agent is an obligatory intracellular bacterium of granulocytes. Infection with both E. chaffeensis and E. sennetsu, but not HGE agent, in the acute monocytic leukemia cell line THP-1 almost completely inhibited by treatment with deferoxamine, a cell-permeable iron chelator. Transferrin receptors (TfRs) accumulated on both E. chaffeensis and E. sennetsu, but not HGE agent, inclusions in THP-1 cells or the cells of the promyelocytic leukemia cell line HL-60. Reverse transcription-PCR showed an increase in the level of TfR mRNA 6 h postinfection which peaked at 24 h postinfection with both E. chaffeensis and E. sennetsu infection in THP-1 or HL-60 cells. In contrast, HGE agent in THP-1 or HL-60 cells induced no increase in TfR mRNA levels. Heat treatment of E. chaffeensis or the addition of monodansylcadaverine, a transglutaminase inhibitor, 3 h prior to infection inhibited the up-regulation of TfR mRNA. The addition of oxytetracycline 6 h after E. chaffeensis infection caused a decrease in TfR mRNA which returned to the basal level by 24 h postinfection. These results indicate that both internalization and continuous proliferation of ehrlichial organisms or the production of ehrlichial proteins are required for the up-regulation of TfR mRNA. Results of electrophoretic mobility shift assays showed that both E. chaffeensis and E. sennetsu infection increased the binding activity of iron-responsive protein 1 (IRP-1) to the iron-responsive element at 6 h postinfection and remained elevated at 24 h postinfection. However, HGE agent infection had no effect on IRP-1 binding activity. This result suggests that activation of IRP-1 and subsequent stabilization of TfR mRNA comprise the mechanism of TfR mRNA up-regulation by E. chaffeensis and E. sennetsu infection.
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PMID:Ehrlichia chaffeensis and E. sennetsu, but not the human granulocytic ehrlichiosis agent, colocalize with transferrin receptor and up-regulate transferrin receptor mRNA by activating iron-responsive protein 1. 1022 82

Vitamin A deficiency (VAD) and iron deficiency anemia (IDA) have been recognized as public health problems in Honduras for over 30 years. This paper, based on the 1996 National Micronutrient Survey on 1678 children 12-71 months of age, presents the results for vitamin A status and anemia prevalence, as well as the level of vitamin A in sugar at the household level. The results showed that 14% of the children were subclinically vitamin A deficient (plasma retinol < 20 micrograms/dL) and 32% were at risk of VAD (plasma retinol 20-30 micrograms/dL). These data indicate that VAD is a moderate public health problem in Honduras. Logistic regression analysis showed that children 12-23 months old living in areas other than the rural south of the country were at greatest risk of subclinical VAD. Infection, indicated by an elevated alpha-1-acid-glycoprotein level, increased the risk of subclinical VAD more than three-fold. Children from households that obtained water from a river, stream, or lake were at twice the risk of subclinical VAD compared with other children. That same doubled risk was found for children from a household with an outside toilet. VAD can be controlled by fortifying sugar. Retinol levels in sugar at the household level were about 50% of those mandated by Honduran law. There appears to be significant leakage of unfortified sugar into the market. This is particularly true in the rural north, where 33% of samples contained no retinol. Overall, 30% of children were anemic (Hb < 11 g/dL). Logistic regression analysis showed that children whose fathers lived with them but who had not attended at least grade 4 of primary school were at 33% greater risk of being anemic. Infection and being underweight increased the risk of being anemic by 51% and 21%, respectively. Many of the anemic children had not been given iron supplements, suggesting health care providers may not be aware that anemia is widespread among young children and/or know how to diagnose it.
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PMID:Vitamin A deficiency and anemia among children 12-71 months old in Honduras. 1044 13

Nutritional status and some iron metabolism parameters of acute phase response (APR) positive and APR-negative AIDS patients were studied. Twenty-nine AIDS patients were submitted to 24h food intake recall, anthropometry, and albumin, C-reactive protein (CRP), hemoglobin, ferritin, and total iron binding capacity (TIBC) measurements. Infection plus serum CRP > 7 mg/dl were criteria for APR presence. Protein-energy malnutrition (PEM) was ascertained by body mass index (BMI) lower than 18.5 kg/m2 and height-creatinine index (HCI < 70%). PEM (77.8 vs 40%) and pulmonary tuberculosis (44. 4 vs 9.5%) were more frequent in APR-positive patients, which also had lower serum albumin (3.7 +/- 0.9 vs 4.3 +/- 0.9 g/dl), TIBC (165. 8 +/- 110.7 vs 265.9 +/- 74.6 mg/dl) and blood hemoglobin (10.5 +/- 1. 8 vs 12.6 +/- 2.3g/dl). Iron intake was similar between groups; however, serum ferritin levels (median, range) were higher among APR-positive (568, 45.3-1814 vs 246, 18.4-1577 ng/ml) patients. HIV-positive adults with systemic response to invading pathogens showed worse nutritional status than those APR-negative. In APR-positive AIDS patients, anemia appears to be unrelated to recent iron intake.
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PMID:[Iron status, malnutrition and acute phase response in HIV-positive patients]. 1088 Nov 30

This article tests the hypothesis that the presence of gastrointestinal parasites in Colombian boys is negatively associated with anthropometric characteristics, physical work capacity, blood hemoglobin (Hb) levels, and nutritional status. Anthropometric, Hb, &Vdot;O(2) max, and parasite load data were collected on 1,016 boys in Cali, Colombia. The boys were classified as lower socioeconomic class (SEC) from either urban or rural environments, and upper SEC from an urban environment. Sixty-three percent of the boys were infected with gastrointestinal parasites and, of the infected boys, 80-95% had light parasite loads. Parasites found included Necator americanus, Ascaris lumbricoides, Entamoeba histolytica, Trichuris trichiura, Giardia spp., and Enterobius vermicularis. Infected boys had significantly lower weight, stature, weight-for-height (among 6-9-year-old boys), Hb levels, and &Vdot;O(2) max (ANCOVA, controlling for age and SEC). In terms of nutritional status, infected boys were 1.47 times more likely to be classified as iron deficient than noninfected boys (chi-square, P < 0.001), and 1.61 times more likely to be classified as stunted (P < 0.001). Infection was not associated with wasting in any SEC group. In conclusion, light to moderate gastrointestinal parasite loads were associated with significantly lower weight, stature, weight-for-height (in 6-9-year-old boys), Hb levels, and &Vdot;O(2) max, and a significantly higher frequency of IDA and stunting. These data suggest that comprehensive analyses of the nutritional status of populations in regions endemic for parasitic infection should include testing for the presence of infection. Am. J. Hum. Biol. 11:763-771, 1999. Copyright 1999 Wiley-Liss, Inc.
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PMID:Gastrointestinal parasitic infection, anthropometrics, nutritional status, and physical work capacity in Colombian boys. 1153 92

The introduction of recombinant human erythropoietin (rh-Epo, epoetin) as a treatment for the anaemia of renal failure has transformed the management of this condition. Nevertheless, a significant number of patients fail to respond. There are many different possible causes of inadequate response to epoetin. Iron deficiency, whether absolute or functional, is considered to be the most important, and it is widely accepted that maintaining adequate iron levels reduces rh-Epo dosage requirement and improves efficacy in haemodialysis patients. Infection and inflammation have been shown to influence responsiveness to rh-Epo by disrupting iron metabolism and eliciting the release of cytokines that inhibit erythropoiesis. Another factor for consideration is severe hyperparathyroidism, which can lead to a reduced number of responsive erythroid progenitor cells. Inadequate dialysis can also negatively impact on rh-Epo therapy, and aluminium overload interferes with iron metabolism and reduces the efficacy of rh-Epo. Deficiencies in vitamin B(12), folic acid and potentially vitamin C can all reduce the efficacy of treatment with rh-Epo. Optimizing patient response to rh-Epo therapy, therefore, requires consideration of many factors, some well established and others that are more controversial, and the list continues to grow with the identification of new factors.
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PMID:Hyporesponsiveness to recombinant human erythropoietin. 1159 Feb 53

Infections caused by zygomycetes, which have been increasing in recent years, are known for their difficulty of diagnosis and treatment. Because little is known about this fungus and its infection, vigorous research is now in serious demand. As in many other systemic mycoses, animal model studies are essential in the investigation of zygomycosis, particularly for the study of pathogenesis, diagnosis and treatment. Unfortunately, such studies have been limited when compared with those of aspergillosis. To help investigating the disease, here in this review article, the profile of human zygomycosis is briefly described, followed by a review of the heretofore used animal models of zygomycosis. Among clinically important zygomycetes causing human infection, animal models are available for Absidia corymbifera, Rhizopus oryzae, R. microsporus var. rhizopodiformis, Rhizomucor pusillus and Cunninghamella bertholletiae. Mice are the most commonly used animals, but models using guinea pigs and rabbits are also available. Pretreatment of animals with cyclophosphamide, corticosteroid, alloxan or streptozocine is frequently done to create an immunocompromised state. Treatment with desferrioxamine, an iron chelator, is also used to make animal models. In terms of the route of infection, the airborne route is used for pathophysiological studies in pulmonary infection models, but sometimes intravenous injection is preferred, particularly for antifungal drug studies. When pathophysiological analysis is the purpose of the study, the animals must be cautiously examined both histopathologically and mycologically. For the most part, zygomycosis model studies can be performed in a similar manner to those of aspergillosis. However, Aspergillus spp. and zygomycetes are completely different fungi, and researchers should be aware of the specific, critical aspects when handling zygomycosis models, such as homogenization of infected organs and staining of pathological samples.
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PMID:Animal models of zygomycosis--Absidia, Rhizopus, Rhizomucor, and Cunninghamella. 1169 96

Infection of the stomach mucosa by the gastric pathogen Helicobacter pylori is accompanied by a large infiltration of neutrophils and monocytes which are believed to contribute substantially to H. pylori-induced gastritis. A protein was identified (HP-NAP for neutrophil-activating protein from H. pylori) that was capable of increasing the adhesion of neutrophils to endothelial cells. We have demonstrated that HP-NAP is a dodecamer composed of identical 17-kDa subunits that induces the production of reactive oxygen radicals (ROIs) by neutrophils via a cascade of intracellular activation events. HP-NAP has also been shown to be chemotactic for neutrophils and monocytes, and a majority of H. pylori-infected patients have been found to produce antibodies specific for HP-NAP making it a strong vaccine candidate. More recently it has been shown that HP-NAP can stimulate tissue factor and plasminogen activator inhibitor-2 production by human monocytes. While structurally similar to the Escherichia coli DNA-binding protein Dps, HP-NAP has characteristics that are more similar to bacterioferritins being capable of binding up to 500 atoms of iron in vitro. Further study, however, has revealed that synthesis of HP-NAP in H. pylori is not altered by the addition or subtraction of metal ions from its growth medium suggesting that the primary role of the protein in vivo is not as a metal-binding protein. A number of other reports have proposed that HP-NAP acts as an adhesin being capable of binding several different compounds in vitro. Sequence analysis of the genomes of several other bacteria reveal that many possess Dps/HP-NAP-like proteins. The preliminary characterisation of some of these proteins will be discussed.
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PMID:The neutrophil-activating protein of Helicobacter pylori. 1189 May 56

Infection, mainly related to vascular access, is one of the main causes of morbidity and a preventable cause of death in hemodialysis patients. From January 1994 to April 1998 we conducted a prospective study to assess the incidence and risk factors of catheter-related bacteremia. One hundred and twenty-nine tunneled dual-lumen hemodialysis catheters were inserted percutaneously into the internal jugular vein in 89 patients. Bacteremia (n = 56) occurred at least once with 37 (29%) of the catheters (an incidence of 1.1/1,000 catheter-days); local infection (n = 45, 1/1,000 catheter-days) was associated with bacteremia in 18 cases. Death in 1 case was directly related to Staphylococcus aureus (SA) septic shock, and septicemia contributed to deaths in 2 additional cases. Catheters were removed in 48% of the bacteremic episodes. Treatment comprised intravenous double antimicrobial therapy for 15-20 days. Bacteriological data of bacteremia showed 55% involvement of SA. Nasal carriage of SA was observed in 35% of the patients with catheters. Bacteremic catheters were more frequently observed in patients with diabetes mellitus (p = 0.03), peripheral atherosclerosis (p = 0.001), a previous history of bacteremia (p = 0.05), nasal carriage of SA (p = 0.0001), longer catheter survival time (p = 0.001), higher total intravenous iron dose (p = 0.001), more frequent urokinase catheter infusion (p < 0.01), and local infection (p < 0.001) compared with non-bacteremic catheters. Monovariate survival analysis showed that significant initial risk factors for bacteremia were nasal carriage of SA (p = 0.00001), previous bacteremia (p = 0.0001), peripheral atherosclerosis (p = 0.005), and diabetes (p = 0.04). This study confirms the relatively high incidence of bacteremia with tunneled double-lumen silicone catheters and its potential complications. Possible preventive actions are discussed according to the risk factors.
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PMID:Risk factor analysis for long-term tunneled dialysis catheter-related bacteremias. 1211 69

Malnutrition, one of the world's greatest health problems, is a factor in the death of millions of children each year. Infection is the cause of death in over half these cases. Dietary deficiency, especially of protein, causes serious disturbances in the immune system. The mucus and cutaneous surfaces are the first affected. Studies of the respiratory mucus demonstrate frequent breaches which allow germs to penetrate. Antibodies are synthesized in reduced quantities, lymphocyte counts are often diminished, and reaction with infectious agents is poor. The phagocyte function of polynucleated cells is poor. Malnutrition is often associated with war, ignorance, poverty, and poor hygiene. Deficiencies of iron, vitamin A, and zinc may aggravate immune deficits. Ingestion of contaminated water is the main cause of diarrhea, which is very frequent among the malnourished and may be more serious than among adequately nourished individuals. Colibacillus and salmonella are most frequently isolated. Germs such as shigella, campylobacter, and rotavirus have the same incidence as in well nourished children. Pneumonia is responsible for 4 million deaths in children under 5 annually and is more common in the malnourished. The pathogenic agents may be pneumococci, Hemophilus, or staphylococci. Tuberculosis is also frequent, especially in zones with a prevalence of AIDS. Diagnosis of tuberculosis with cutaneous tests is difficult in the malnourished. Regardless of the pathogenic agent, pneumonia is more serious in the malnourished, and the need for treatment is more urgent. Urinary infections may occur in 10-25% of malnourished children vs. 2% of healthy children. The colibacillus is the most frequent cause. Specticemias, the most severe of infections, are not rare in the malnourished and are usually caused by Salmonella or the colibacillus. 20% of malnourished children are affected by infections acquired in the hospital. Among viral infections affecting them are measles and herpes. The fatality rate from measles may reach 25% in malnourished children. Parasitoses are frequent, but they do not seem to be more serious in malnourished children than in the general population. It is imperative in treating malnourished children to observe rigorous hygiene, use clean water, treat infections early, avoid hospital infections, and apply all available vaccines.
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PMID:[Infections in malnourished infants and children]. 1228 6


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