Xanthine oxidase inhibition by febuxostat attenuates experimental atherosclerosis in mice.

Atherosclerosis is a chronic inflammatory disease due to lipid deposition in the arterial wall. Multiple mechanisms participate in the inflammatory process, including oxidative stress. Xanthine oxidase (XO) is a major source of reactive oxygen species (ROS) and has been linked to the pathogenesis of atherosclerosis, but the underlying mechanisms remain unclear. Here, we show enhanced XO expression in macrophages in the atherosclerotic plaque and in aortic endothelial cells in ApoE(-/-) mice, and that febuxostat, a highly potent XO inhibitor, suppressed plaque formation, reduced arterial ROS levels and improved endothelial dysfunction in ApoE(-/-) mice without affecting plasma cholesterol levels. In vitro, febuxostat inhibited cholesterol crystal-induced ROS formation and inflammatory cytokine release in murine macrophages. These results demonstrate that in the atherosclerotic plaque, XO-mediated ROS formation is pro-inflammatory and XO-inhibition by febuxostat is a potential therapy for atherosclerosis.

First Case of Natural Infection in Pigs: Review of Trypanosoma cruzi Reservoirs in Mexico

An epidemiological research project was performed in the State of Morelos including collection of samples for blood smears and culture, serological tests, and xenodiagnoses from a total of 76 domestic and peridomestic mammals. Two strains of Trypanosoma cruzi were isolated by haemocultures; one from a pig (Sus scrofa), the first case of natural infection reported in Mexico, and the other from a dog (Canis familiaris). This study summarizes current information in Mexico concerning confirmed reservoirs of T. cruzi

Epidemiological Characteristics of Schistosoma mansoni Infection in Rural and Urban Endemic Areas of Minas Gerais, Brazil

To compare the epidemiological profile and socioeconomic factors associated to the infection by Schistosoma mansoni in a rural and an urban endemic area a cross-sectional study was performed in Água Branca de Minas (rural area) and Bela Fama (urban area), both situated in the State of Minas Gerais, Brazil. Two hundred and eighty eight individuals were surveyed in the rural area and 787 in the urban area. Water contact and socioeconomic questionnaires were used to identify risk factors for the infection. The prevalences of 38.8% and 9.7% and the geometric mean of eggs per gram of faeces of 117.8 and 62.3 were found in the rural and urban areas, respectively. By multivariate statistical analysis age groups over nine years old and previous specific treatment were associated with the infection in rural area. In urban area age over nine years old, low quality housing, weekly fishing and swimming were associated after adjustment by logistic regression

Factors Involved in Schistosoma mansoni Infection, in Rural Areas of Northeast Brazil

Two contiguous villages in Tracunhaém county (State of Pernambuco), endemic for schistosomiasis, were studied: Itapinassu (138 inhabitants) and São Joaquim (91 inhabitants). Agriculture predominates in the former region while ceramics is the main activity in the latter. Although no statistical difference was found regarding prevalence, severe infection (>400 epg) predominated in Itapinassu, probably related to the kind of occupation. No association was found between parasite burden and severity of disease, in spite of the high infection rates for Schistosoma mansoni in both communities (approx. 60%). Typical epidemiological features of schistosomiasis such as age-related prevalences and intensities of infection (high in children, low in adults) were also mutual characteristics. Nutritional status determined through anthropometric evaluation was carried out by measuring specific anthropometric indicators. A deficit of energy intake, as well as vitamin A and riboflavin deficiencies were detected. The prevalence of moderate or severe undernutrition in patients under 18 years old was 21.9% in Itapinassu and 24.1% in São Joaquim. In this group an association was found between prevalence of schistosomiasis and chronic undernutrition. Similarly, for patients over 18 year old the prevalence of undernutrition was higher than 20%. However, in this case no association between nutritional status and either prevalence of schistosomiasis or parasite burden could be detected. The two communities had not been treated for eight years.

Modulation by IL-10 of antigen-induced allergic responses in mice

Over the last few years, we examined the anti-allergic properties of interleukin (IL)-10 in different models of inflammation in the mouse, as well as against IgE-dependent activation of mouse bone marrow-derived mast cells (BMMC). We showed that IL-10, concurrently administered with ovalbumin, inhibited inflammatory cell accumulation in the airways and in the peritoneal cavity of sensitized mice, as well as the accompanying cytokine release. IL-10 also blocked antigen-induced cytokine generation by IgE-stimulated BMMC. Together, these results identify a novel biological property of IL-10, as a cytokine with potent anti-allergic activities.

Prevalence of Helicobacter pylori Infection in a Rural Area of the State of Mato Grosso, Brazil

The prevalence of Helicobacter pylori infection was evaluated by ELISA in 40 children and teenagers and in 164 adults from a rural area of the State of Mato Grosso, Brazil. Antibodies to H. pylori were detected in the serum of 31 (77.5%) children and teenagers and in 139 (84.7%) adults. The prevalence of infection increased with age (c2 for trend, p < 0.01) even though no variations occurred in the region in the present century in terms of living conditions or sanitation, economical development and migratory influx supporting the hypothesis that the infection is also acquired during later life in developing countries. An inverse correlation was observed between the prevalence of infection and annual family income (c2 for trend, p < 0.013). There was no correlation between type of system for sewage disposal and prevalence of infection (p = 0.8). In conclusion, the prevalence of H. pylori infection in Nossa Senhora do Livramento, a rural area from Brazil, is very high and similar to that observed in other developing countries. Furthermore, the increase in the prevalence of infection with age observed in this population seems to be due to both, cohort effect and acquisition of the infection during later life

Immunodiagnosis of Trypanosoma cruzi (Chagas' Disease) Infection in Naturally Infected Dogs

This study reports on the standardization of an enzyme-linked immunosorbent assay (ELISA) for detecting specific antibodies anti-Trypanosoma cruzi in naturally infected dogs. Sera from 182 mongrel dogs of all ages residing in four rural villages in Santiago del Estero, Argentina, were collected in November 1994 and preserved in buffered neutral glycerin. All sera were tested by indirect hemagglutination test (IHAT), indirect immunofluorescence test (IFAT), and ELISA using the flagellar fraction of T. cruzi as antigen. Dog sera from an area without vectorial transmission were used to calculate ELISA specificity and cut-off value. Eighty-six percent of sera had concordant results for all tests. All sera reactive for IHAT and IFAT were also reactive for ELISA, except in one case. Sera tested by ELISA when diluted 1:200 allowed a clearer division between non-reactive and reactive sera than when 1:100 with greater agreement among serologic techniques. The specificity of ELISA was 96.2%. Among 34 adult dogs with a positive xenodiagnosis, sensitivity was 94% both for ELISA and IFAT. ELISA is the first choice for screening purposes and one of the pair of techniques recommended for diagnostic studies in dog populations

Parasite Genotypically Related to a Monoxenous Trypanosomatid of Dog's Flea Causing Opportunistic Infection in an HIV Positive Patient

An HIV positive patient presenting a clinical picture of visceral leishmaniasis co-infection was submitted to a bone marrow aspiration after admission to hospital. Amastigotes forms were seen in the bone marrow aspirate and the parasite grew in culture as promastigotes. Molecular analyses showed that the flagellates isolated did not belong to the genera Leishmania, Trypanosoma or Sauroleishmania. It was not possible to establish infection in laboratory animals. In vitro culture of mouse peritoneal macrophages revealed the invasion of the host cells by the flagellates and their killing 48 hr after infection. Opportunistic infection with an insect trypanosomatid was suspected. Further hybridization analyses against a pannel of different monoxenous and heteroxenous trypanosomatids showed kDNA cross-homology with Leptomonas pulexsimulantis a trypanosomatid found in the dog's flea

The separate and combined effects of MHC genotype, parasite clone, and host gender on the course of malaria in mice.

BACKGROUND: The link between host MHC (major histocompatibility complex) genotype and malaria is largely based on correlative data with little or no experimental control of potential confounding factors. We used an experimental mouse model to test for main effects of MHC-haplotypes, MHC heterozygosity, and MHC x parasite clone interactions. We experimentally infected MHC-congenic mice (F2 segregants, homo- and heterozygotes, males and females) with one of two clones of Plasmodium chabaudi and recorded disease progression. RESULTS: We found that MHC haplotype and parasite clone each have a significant influence on the course of the disease, but there was no significant host genotype by parasite genotype interaction. We found no evidence for overdominance nor any other sort of heterozygote advantage or disadvantage. CONCLUSION: When tested under experimental conditions, variation in the MHC can significantly influence the course of malaria. However, MHC heterozygote advantage through overdominance or dominance of resistance cannot be assumed in the case of single-strain infections. Future studies might focus on the interaction between MHC heterozygosity and multiple-clone infections.

Seroprevalence of Trypanosoma cruzi Infection in Students at the Seven-Fourteen Age Range, Londrina, PR, Brazil, in 1995

Seropositivity for Chagas disease was evaluated in 834 children aged between 7 and 14 from the Municipal Teaching System in the district of Londrina, State of Paraná. A seroprevalence rate of 0.1% was found through the use of an indirect immunofluorescent test and an enzyme-linked immunosorbent assay. This low rate of seroprevalence provides evidence that the vectorial transmission of Chagas disease has been eliminated in Londrina. The main reason for the elimination of vectorial transmission of Trypanosoma cruzi infection, as evaluated by serological tests, may be a remarkable change in the economic structure of the northern region of Paraná in the 1960's. At that time coffee production was almost completely replaced by soy beans, wheat and grazing in the rural areas. This change deeply affected the rural ecology and caused an exodus of the population from rural to urban areas as well as a decrease in the total number of the population of that region. The measures introduced for controlling the disease through the Program of Chagas Disease Control established by the Fundação Nacional de Saúde of the Brazilian Ministry of Health, certainly, had a positive impact on the reduction of American trypanosomiasis prevalence in the area under study. However, it does not seem that this was the most relevant factor responsible for the elimination of vectorial transmission of Chagas disease in Londrina.

Haemolymph and Fat Body Metallo-protease Associated with Enterobacter cloacae Infection in the Bloodsucking Insect, Rhodnius prolixus

Analysis of zymograms with SDS-polyacrilamide gel electrophoresis containing gelatin as substrate, and performed on samples of haemolymph or fat body taken from Rhodnius prolixus inoculated or not with Enterobacter cloacae, demonstrated distinct patterns of protease activities: (i) in the haemolymph two proteases were induced in insects inoculated with bacteria; (ii) two proteases were detected in the fat bodies derived from non-inoculated controls or insect inoculated with sterile culture medium; (iii) haemolymph and fat body had both the same apparent molecular weights proteases (46 and 56 kDa); and (iv) these enzymes were characterized as metallo-proteases. The association of these enzymes in Rhodnius infected with bacteria was discussed.

Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2.

Glut-2 is a low-affinity transporter present in the plasma membrane of pancreatic beta-cells, hepatocytes and intestine and kidney absorptive epithelial cells of mice. In beta-cells, Glut-2 has been proposed to be active in the control of glucose-stimulated insulin secretion (GSIS; ref. 2), and its expression is strongly reduced in glucose-unresponsive islets from different animal models of diabetes. However, recent investigations have yielded conflicting data on the possible role of Glut-2 in GSIS. Whereas some reports have supported a specific role for Glut-2 (refs 5,6), others have suggested that GSIS could proceed normally even in the presence of low or almost undetectable levels of this transporter. Here we show that homozygous, but not heterozygous, mice deficient in Glut-2 are hyperglycaemic and relatively hypo-insulinaemic and have elevated plasma levels of glucagon, free fatty acids and beta-hydroxybutyrate. In vivo, their glucose tolerance is abnormal. In vitro, beta-cells display loss of control of insulin gene expression by glucose and impaired GSIS with a loss of first phase but preserved second phase of secretion, while the secretory response to non-glucidic nutrients or to D-glyceraldehyde is normal. This is accompanied by alterations in the postnatal development of pancreatic islets, evidenced by an inversion of the alpha- to beta-cell ratio. Glut-2 is thus required to maintain normal glucose homeostasis and normal function and development of the endocrine pancreas. Its absence leads to symptoms characteristic of non-insulin-dependent diabetes mellitus.

Epidemiology of hookworm infection in Itagua, Paraguay: a cross sectional study

A cross-sectional study in Itagua, Paraguay tested 192 people for the presence, intensity and species of hookworm infection. Fifty-nine percent of these individuals were found to be infected. Intensity of infection was determined on 92% of infected individuals by quantitative egg counts. The high intensity hookworm infections, which cause the greatest morbidity, were clustered between the ages of five and 14 years. No differences were seen between genders. The species of hookworm was determined for parasites reared from 72% of infected individuals. Both Necator americanus and Ancylostoma duodenale were identified, although the former species predominated. We conclude that hookworm infection continues to be a public health problem in Paraguay, particularly among children and adolescents who suffer from high intensity infections. A. duodenale continues to persist in the Western Hemisphere and has not been completely displaced by N. americanus.