Experimental paracoccidioidomycosis in the mouse. III. Histopathological and immunological findings after intravenous infection in the presence or absence of previous immunization

Fifty male white Swiss mice aged 4 weeks were inoculated with 5 x 10(5) viable yeast forms of Paracoccidioides brasiliensis (strain 18). Ten of these animals had been previously immunized with particulate P. brasiliensis antigenfor 4 weeks by intradermal injection. The controls consisted of 10 animals that were only immunized and 10 animals submitted to no treatment. The animals were sacrificed 2, 4, 7,11 and 16 weeks later. We studied: 1) the anti-P. brasiliensis delayed hypersensitivity response measured by the footpad test 24 hours prior to sacrifice; 2) the specific antibody production measured by double immunodiffusion in agar gel; 3) the histopathology of lungs, liver, spleen, adrenals and kidneys. We observed that: a) the immunized animals developed more intense cell-immune responses than the infected ones; b) infection reduced the cell- immune response of the immunized animals; c) intravenous infection of mice with P. brasiliensis was characterized by a systemic and progressive granulomatous inflammation. The animals infected after previous immunization showed less extensive lung inflammation, with smaller granulomas and fewer fungi. The results indicate that the present murine model mimics some findings of the human subacute form of paracoccidioidomycosis (systemic disease with depressed cellular immunity) and that the extrapulmonary immunization scheme was able to induce a certain degree of protection of the lung from infection with P. brasiliensis

Differing phagocytic function of monocytes and neutrophils in Chagas' cardiopathy according to the presence or absence of congestive heart failure

We evaluated the in vitro phagocytic function and the production of microbicidal oxygen radicals by monocytes and neutrophils of 9 Chagas' heart disease subjects with heart failure and 9 without the syndrome in comparison with 11 healthy subjects, by assessing phagocytosis of Saccharomyces cerevisiae and NBT reduction by peripheral blood phagocytes. Phagocytic index of monocytes of chagasics without heart failure was significantly 6.7 and 10.6 times lower than those of controls and chagasics with the congestive syndrome, respectively, due to a lesser engagement in phagocytosis and to an inability of these cells to ingest particles. Neutrophils also show in chagasics without heart failure PI 11.2 and 19.8 times lower than that of controls and chagasics with heart failure, respectively. The percent of NBT reduction was normal and similar for the three groups. Balanced opposite effects of cardiovascular and immune disturbances may be acting in Chagas' disease subjects with heart failure paradoxically recovering the altered phagocytic function.

New host and locality records for Tetrameres (Gynaecophila) spirospiculum Pinto & Vicente, 1995 (Nematoda: Tetrameridae), with new morphological data

We report the finding of Tetrameres spirospiculum Pinto & Vicente, 1995 from Theristicus melanopis melanopis (Threskiornithidae) from Patagonia, Argentina. These constitute new host and locality records. We propose the assignation of this species to the subgenus T. (Gynaecophila) Gubanov, 1950, based on the presence of labia and the absence of cuticular flanges at the anterior end. Some new morphological data are provided, such as the arrangement of cuticular spines and the presence of a pair of somatic papillae at beginning of posterior third of body length. T. (G.) spirospiculum may probably be regarded as specific to birds of the genus Theristicus.

Absence of peripheral blood mononuclear cells priming in hemodialysis patients

As a consequence of the proinflammatory environment occurring in dialytic patients, cytokine overproduction has been implicated in hemodialysis co-morbidity. However, there are discrepancies among the various studies that have analyzed TNF-alpha synthesis and the presence of peripheral blood mononuclear cell (PBMC) priming in this clinical setting. We measured bioactive cytokine by the L929 cell bioassay, and evaluated PBMC TNF-alpha production by 32 hemodialysis patients (HP) and 51 controls. No difference in TNF-alpha secretion was observed between controls and HP (859 ± 141 vs 697 ± 130 U/10(6) cells). Lipopolysaccharide (5 µg/ml) did not induce any further TNF-alpha release, showing no PBMC priming. Paraformaldehyde-fixed HP PBMC were not cytotoxic to L929 cells, suggesting the absence of membrane-anchored TNF-alpha. Cycloheximide inhibited PBMC cytotoxicity in HP and controls, indicating lack of a PBMC TNF-alpha pool, and dependence on de novo cytokine synthesis. Actinomycin D reduced TNF-alpha production in HP, but had no effect on controls. Therefore, our data imply that TNF-alpha production is an intrinsic activity of normal PBMC and is not altered in HP. Moreover, TNF-alpha is a product of de novo synthesis by PBMC and is not constitutively expressed on HP cell membranes. The effect of actinomycin D suggests a putative tighter control of TNF-alpha mRNA turnover in HP. This increased dependence on TNF-alpha RNA transcription in HP may reflect an adaptive response to hemodialysis stimuli.

Mesenchymal stem cells from patients with chronic myeloid leukemia do not express BCR-ABL and have absence of chimerism after allogeneic bone marrow transplant

Bone marrow is a heterogeneous cell population which includes hematopoietic and mesenchymal progenitor cells. Dysregulated hematopoiesis occurs in chronic myelogenous leukemia (CML), being caused at least in part by abnormalities in the hematopoietic progenitors. However, the role of mesenchymal stem cells (MSCs) in CML has not been well characterized. The objectives of the present study were to observe the biological characteristics of MSCs from CML patients and to determine if MSCs originate in part from donors in CML patients after bone marrow transplantation (BMT). We analyzed MSCs from 5 untreated patients and from 3 CML patients after sex-mismatched allogeneic BMT. Flow cytometry analysis revealed the typical MSC phenotype and in vitro assays showed ability to differentiate into adipocytes and osteoblasts. Moreover, although some RT-PCR data were contradictory, combined fluorescence in situ hybridization analysis showed that MSCs from CML patients do not express the bcr-abl gene. Regarding MSCs of donor origin, although it is possible to detect Y target sequence by nested PCR, the low frequency (0.14 and 0.34%) of XY cells in 2 MSC CML patients by fluorescence in situ hybridization analysis suggests the presence of contaminant hematopoietic cells and the absence of host-derived MSCs in CML patients. Therefore, we conclude that MSCs from CML patients express the typical MSC phenotype, can differentiate into osteogenic and adipogenic lineages and do not express the bcr-abl gene. MSCs cannot be found in recipients 12 to 20 months after BMT. The influence of MSCs on the dysregulation of hematopoiesis in CML patients deserves further investigation.

Risk factors for basal cell carcinoma: a case-control study

A controlled trial was performed with the purpose of investigating which factors could be considered of significant risk for the development of basal cell carcinoma. A total of 259 cases of basal cell carcinoma diagnosed from July 1991 to July 1992 were compared with 518 controls matched for age and sex. All subjects in both groups were white. Protocol data were submitted to statistical analysis by the chi-square test and by multiple conditional logistic regression analysis and the following conclusions were reached: 1) light skin color (types I and II of the Fitzpatrick classification), odds ratio of 2.8; outdoor work under constant sunlight, odds ratio of 5.0; the presence of actinic lesions due to exposure to the sun, odds ratio of 4.9, are risk factors perse. 2) Type III skin in the Fitzpatrick classification only represents a risk factor when the patient reports a history of intense sunburns, but not in the absence of such a history. 3) Sunburns per se do not represent a risk factor althorig the point made in item 2 of these conclusions is valid. 4) Other suspected risk factors whose significance was not confirmed by multiple conditioned logistic regression analysis were: residence in rural areas, light eyes and blond hair color, extent of the awareness of the "sun x skin cancer" relationship, familial occurrence of skin cancer, excessive exposure to the sun, and freckles appearing in childhood.

The influence of health expenditures on household impoverishment in Brazil

OBJECTIVE To analyze the variation in the proportion of households living below the poverty line in Brazil and the factors associated with their impoverishment. METHODS Income and expenditure data from the Household Budget Survey, which was conducted in Brazil between 2002-2003 (n = 48,470 households) and 2008-2009 (n = 55,970 households) with a national sample, were analyzed. Two cutoff points were used to define poverty. The first cutoff is a per capita monthly income below R$100.00 in 2002-2003 and R$140.00 in 2008-2009, as recommended by the Bolsa Família Program. The second, which is proposed by the World Bank and is adjusted for purchasing power parity, defines poverty as per capita income below US$2.34 and US$3.54 per day in 2002-2003 and 2008-2009, respectively. Logistic regression was used to identify the sociodemographic factors associated with the impoverishment of households. RESULTS After subtracting health expenditures, there was an increase in households living below the poverty line in Brazil. Using the World Bank poverty line, the increase in 2002-2003 and 2008-2009 was 2.6 percentage points (6.8%) and 2.3 percentage points (11.6%), respectively. Using the Bolsa Família Program poverty line, the increase was 1.6 (11.9%) and 1.3 (17.3%) percentage points, respectively. Expenditure on prescription drugs primarily contributed to the increase in poor households. According to the World Bank poverty line, the factors associated with impoverishment include a worse-off financial situation, a household headed by an individual with low education, the presence of children, and the absence of older adults. Using the Bolsa Família Program poverty line, the factors associated with impoverishment include a worse-off financial situation and the presence of children. CONCLUSIONS Health expenditures play an important role in the impoverishment of segments of the Brazilian population, especially among the most disadvantaged.

Contextual and individual indicators associated with the presence of teeth in adults

OBJECTIVE The objective of this study was to analyze whether socioeconomic conditions and the period of availability of fluoridated water are associated with the number of teeth present.METHODSThis cross-sectional study analyzed data from 1,720 adults between 20 and 59 years of age who resided in Florianópolis, SC, Southern Brazil, in 2009. The outcome investigated was the self-reported number of teeth present. The individual independent variables included gender, age range, skin color, number of years of schooling, and per capita household income. The duration of residence was used as a control variable. The contextual exposures included the period of availability of fluoridated water to the households and the socioeconomic variable for the census tracts, which was created from factor analysis of the tract’s mean income, education level, and percentage of households with treated water. Multilevel logistic regression was performed and inter-level interactions were tested.RESULTS Residents in intermediate and poorer areas and those with fluoridated water available for less time exhibited the presence of fewer teeth compared with those in better socioeconomic conditions and who had fluoridated water available for a longer period (OR = 1.02; 95%CI 1.01;1.02). There was an association between the period of availability of fluoridated water, per capita household income and number of years of education. The proportion of individuals in the poorer and less-educated stratum, which had fewer teeth present, was higher in regions where fluoridated water had been available for less time.CONCLUSIONS Poor socioeconomic conditions and a shorter period of availability of fluoridated water were associated with the probability of having fewer teeth in adulthood. Public policies aimed at reducing socioeconomic inequalities and increasing access to health services such as fluoridation of the water supply may help to reduce tooth loss in the future.

Rabies in the state of São Paulo: the rodents question

The authors looked over the epidemiological data on the aggression by rodents in the period 1976-1985 in the records of the Instituto Pasteur in the State of São Paulo (Brazil). They observed that out of 367 379 people attacked, 22 250 were victims of rodents. Mainly responsible for these accidents were urban rodents, whose capture, however, was a limiting factor for the sending of samples to the laboratory. Laboratory diagnosis carried out in 1 083 samples of rodents did not show any positive case in the period, in spite of the presence of rabies in other animals species. It is conclude that, as rabies is rare among rodents, tests are necessary for the identification of the virus whenever suspicion of a positive case occurs; in addition, in the absence of reported cases of human death caused by rabies related to rodents, possibility exists for a reduction of antirabies treatments following exposure to these animals.

Potential infectivity of blood from HBsAG asymptomatic carriers due to the presence of HBV-DNA and comparison with other markers of hbv infection

Serum samples from 356 HBsAg positive asymptomatic carriers, which were titrated by reverse passive hemagglutination, were analysed for the presence of HBV-DNA, HBsAg and IgM anti-HBc. The samples were divided in three classes, according to the titers of HBsAg and IgM anti-HBc and the distribution of HBV-DNA and HBsAg among these classes was studied. In the high titer class of HBsAg, 65% of samples have one or both markers against only 19% in the low titer class. From the total of 356 samples, 121 gave positive results for IgM anti-HBc (33.9%). From these, 38.9% of HBV-DNA and 47.9% of HBeAg were observed, whereas in samples with absence of IgM anti-HBc, 18.3% and 16.6% were respectively found. A higher frequency of agreement between all these markers was found in the class of high titers of HBsAg; however, HBV-DNA was detected in the low titer class of HBsAg and little or no IgM anti-HBc, showing potential blood infectivity even in HBsAg positive borderline samples.

Hepatocellular carcinoma in Brazil: report of a national survey (Florianópolis, SC, 1995)

In order to investigate epidemiological aspects of hepatocellular carcinoma (HCC) in Brazil, basic informations about cases diagnosed from January 1992 to December 1994 were requested to several medical centers of different Brazilian States. A simple questionnaire included age, sex, alcohol abuse (over 80g/day), associated liver cirrhosis, persistent HBV infection (HBsAg), HCV infection (anti-HCV) and serum levels of alpha fetoprotein. 287 cases, over 16 years old, from 19 medical centers of 8 States (Pará, Bahia, Minas Gerais, Espirito Santo, Rio de Janeiro, São Paulo, Paraná and Rio Grande do Sul) were analysed. The results showed: (a) Mean age was 56.3 ± 14.4 for men and 54.7 ± 16.8 yr for women and the male/female ratio was 3.4:1. (b) 69.6% were caucasians, 21.8% mullatoes, 4.8% orientals and 3.7% blacks. (c) HBsAg (+) in 77/236 cases (41.6%) without differences between males and females. (d) Anti-HCV (+) in 52/193 cases (26.9%). (e) 7/180 cases were positive both for HBsAg and anti-HCV (3.8%). (f) There was chronic alcoholism in 88/235 cases (37%). (g) HCC was found in cirrhotic livers in 71.2% of 202 cases in which the presence or absence of cirrhosis was reported. (h) Alpha-fetoprotein above 20 ng/ml was found in 124/172 cases (72%) and above 500 ng/ml only in 40 cases (23.2%). These results showed that the HCC in Brazil has an intermediate epidemiological pattern as compared to those from areas of low and high incidence of the tumor. In spite of the high frequency of the association of HCC with the HBV and/or HCV infections, 42% of 180 cases were negative both for HBsAg and anti-HCV, indicating the possible role of other etiological factors. The comparison of data from different States showed some regional differences: higher frequency of associated HBsAg in Pará, Bahia, Minas Gerais and Espírito Santo, higher frequency of associated HCV infection in Rio de Janeiro, São Paulo and States of the Southern region and low frequency of associated liver cirrhosis in Salvador and Rio de Janeiro (55.5 and 50% respectively). Further investigation will be necessary to study the presence of other possible etiological factors as aflatoxins, suggested by the favourable climatic conditions for food contamination by fungi in the majority Brazilian regions

Toxoplasma encephalitis in AIDS patients in São Paulo during 1988 and 1991. A comparative retrospective analysis

We conducted a retrospective analysis of Toxoplasma encephalitis patients from Instituto de Infectologia Emílio Ribas, the main AIDS hospital of São Paulo, Brazil, during two different stages of the HIV epidemics, in 1988 (38 patients) and 1991 (33 patients). There were AIDS-related demographic differences, but the clinical presentation and diagnostic efficiency were similar, usually based on tomography and clinical response to therapy, with a clear distinction from other CNS infections, based on clinical and laboratory findings. Specific serologic studies were performed less often in 1991, with a high frequency of therapy change. The direct acute death rate from Toxoplasma encephalitis was high during both periods, i.e. 8/38 in 1988 and 10/33 in 1991. The direct acute death rate for the patients from the two periods as a whole was 25.4% (18/71), related to the time of HIV infection, absence of fever and presence of meningeal irritation at presentation, blood leukocytes higher than 10,000/mm³ and blood lymphocytes lower than 350/mm³. Toxoplasma encephalitis is a preventable disease when adequate prophylactic therapy is used and is relatively easy to treat in diagnosed HIV patients. Unfortunately, this severe and deadly disorder is the HIV diagnostic disease in several patients, and our data support the need for careful management of these patients, especially in those countries with a high toxoplasmosis prevalence where AIDS is concurrent with economic and public health problems.

H antigen presence in an Ascaris lumbricoides extract

Previous experiences have demonstrated the same ABO system and P system antigens in A. lumbricoides extracts and in their hosts. The aim was to show the behavior of an A. lumbricoides extract from an O Group patient against monoclonal antibodies of different specificities. Agglutination Inhibition Tests were carried out facing the extract against monoclonal antibodies (anti A 2.23; anti B 2.54; anti B 2.62; anti AB 2.39 and anti H 2.72) in optimal concentrations. Suspensions of O Group fresh red cells were used as revealing system. The extract only inhibited the agglutination of anti H 2.72 with O erythrocytes. The semiquantitative Agglutination Inhibition Test of the extract was made against two series of anti H 2.72 dilutions by using O Group fresh red cells as revealing system. A difference of five dilutions between the titers of both series has been observed and the presence of H Antigen in the extract has been significantly confirmed. The fact that the extract did not inhibit the agglutination against anti A, anti B and anti AB has corroborated our previous observations about absence of A and B epitopes in A. lumbricoides extracts from O Group patients. The results of the preceding studies and this experience have demonstrated the membrane glycoconjugated importance in A. lumbricoides. They could be involved in molecular mimicry for this parasite.

New data on Echinococcus spp. in Southern Brazil

40 Echinococcus isolates from sheep and cattle in Southern Brazil were genetically analysed in order to obtain further data on the presence of different taxa of the Echinococcus granulosus complex. Differentiation was done using a PCR technique and sequencing of mitochondrial cytochrome c oxidase subunit 1 (CO1). Most samples (38) could be allocated to the sheep strain (G1) of E. granulosus, while two samples belonged to E. ortleppi, previously known as cattle strain (G5) of E. granulosus. Due to the shorter prepatent period in dogs of the latter taxon, this records have important implications for the design of control measures in this endemic region.

Fasciola hepatica IN BOVINES IN BRAZIL: DATA AVAILABILITY AND SPATIAL DISTRIBUTION

Fasciolosis is a disease of importance for both veterinary and public health. For the first time, georeferenced prevalence data of Fasciola hepatica in bovines were collected and mapped for the Brazilian territory and data availability was discussed. Bovine fasciolosis in Brazil is monitored on a Federal, State and Municipal level, and to improve monitoring it is essential to combine the data collected on these three levels into one dataset. Data were collected for 1032 municipalities where livers were condemned by the Federal Inspection Service (MAPA/SIF) because of the presence of F. hepatica. The information was distributed over 11 states: Espírito Santo, Goiás, Minas Gerais, Mato Grosso do Sul, Mato Grosso, Pará, Paraná, Rio de Janeiro, Rio Grande do Sul, Santa Catarina and São Paulo. The highest prevalence of fasciolosis was observed in the southern states, with disease clusters along the coast of Paraná and Santa Catarina and in Rio Grande do Sul. Also, temporal variation of the prevalence was observed. The observed prevalence and the kriged prevalence maps presented in this paper can assist both animal and human health workers in estimating the risk of infection in their state or municipality.