Nectomys squamipes (Rodentia: Cricetidae) as an experimental model for schistosomiasis mansoni

Twenty specimens of Nectomys squamipes born in captivity, were infected with 500 cercariae by the transcutaneous route. Coprologic examinations were carried out from the 5th to 23rd week after infection. On the 7th, 8th, 12th, 16th, and 23rd weeks the animals were sacrificed and perfused. The oogram was performed in segments of the small intestine (proximal, medial and distal portions) and the large intestine. The average pre-patent period was of 42 days. The average number of eggs varied from 350 on 6th week, to 800 on the 13th. From the 14th week on, the average number of eggs eliminated was lower than 50 per gram of feces. The recovery of worms kept steady on the 7th, 8th, and 12th week (16.85%; 15.45% and 11.95%), decreasing to 7.70% on the 16th week and 8.45% on the 23rd week. The proportion of male/female worms was about the same on the first two weeks, but from the 12th week on, the proportion was: 1,4/1 on the 12th week; 2,5/1 on the 16thweek and 1,8/1 on the 23rd weekThese observations suggest that N. squamipes may used as an experimental model for schistosomiasis mansoni, to wich it develops resistance mechanism, useful for immunity studies.

Transcriptional regulation of CD4 gene expression by T cell factor-1/beta-catenin pathway.

By interacting with MHC class II molecules, CD4 facilitates lineage development as well as activation of Th cells. Expression of physiological levels of CD4 requires a proximal CD4 enhancer to stimulate basic CD4 promoter activity. T cell factor (TCF)-1/beta-catenin pathway has previously been shown to regulate thymocyte survival via up-regulating antiapoptotic molecule Bcl-xL. By both loss and gain of function studies, in this study we show additional function of TCF-1/beta-catenin pathway in the regulation of CD4 expression in vivo. Mice deficient in TCF-1 displayed significantly reduced protein and mRNA levels of CD4 in CD4+ CD8+ double-positive (DP) thymocytes. A transgene encoding Bcl-2 restored survival but not CD4 levels of TCF-1(-/-) DP cells. Thus, TCF-1-regulated survival and CD4 expression are two separate events. In contrast, CD4 levels were restored on DP TCF-1(-/-) cells by transgenic expression of a wild-type TCF-1, but not a truncated TCF-1 that lacks a domain required for interacting with beta-catenin. Furthermore, forced expression of a stabilized beta-catenin, a coactivator of TCF-1, resulted in up-regulation of CD4. TCF-1 or stabilized beta-catenin greatly stimulated activity of a CD4 reporter gene driven by a basic CD4 promoter and the CD4 enhancer. However, mutation of a potential TCF binding site located within the enhancer abrogated TCF-1 and beta-catenin-mediated activation of CD4 reporter. Finally, recruitment of TCF-1 to CD4 enhancer was detected in wild-type but not TCF-1 null mice by chromatin-immunoprecipitation analysis. Thus, our results demonstrated that TCF/beta-catenin pathway enhances CD4 expression in vivo by recruiting TCF-1 to stimulate CD4 enhancer activity.

Raillietina (Raillietina) guaricana n. sp. (Cestoda-Davaineidae), parasite of wild rats from the environmental protection area of Guaricana, Paraná, Brazil

Raillietina (Raillietina) guaricanae n. sp. is described from the wild rats Oryzomys intermedius, O. nigripes and O. ratticeps, captured in the Environmental Protection Area of Guaricana, from November 1988 to December 1989. Raillietina (Railietina) guaricanae n. sp. is closely related to the Neotropical mammalian Raillietina, however it differs by the fewer number of rostellar hooks, and tests different number of eggs capsules and host species. The number of known species of Raillietina (Raillietina), parasites of mammals in the Neotropical Region, is increased to four.

Notes on the biology of Amblyomma dissimile Kock, 1844 (Acari: Ixodida) on Bufo marinus (Linnaeus, 1758) from Brazil

Amblyomma dissimile is a common ectoparasite of cold blooded animals and is an accidental ectoparasite of some wild mammals. Details of the biology of specimens from the State of Amapá were studied in the laboratory in a humidity chamber at an average environmental temperature of 19.5 °C, using Bufo marinus as host for the time in Brazil. We also report the first record of this species in the State of Minas Gerais.

Morphological aspects of the myocarditis and myositis in Calomys callosus experimentally infected with Trypanosoma cruzi: fibrogenesis and spontaneous regression of fibrosis

Calomys callosus a wild rodent, is a natural host of Trypanosoma cruzi. Twelve C. callosus were infected with 10(5) trypomastigotes of the F strain (a myotropic strain) of T. cruzi. Parasitemia decreased on the 21 st day becoming negative around the 40th day of infection. All animals survived but had positive parasitological tests, until the end of the experiment. The infected animals developed severe inflammation in the myocardium and skeletal muscle. This process was pronounced from the 26 th to the 30th day and gradually subsided from the 50 th day becoming absent or residual on the 64 th day after infection. Collagen was identified by the picro Sirius red method. Fibrogenesis developed early, but regression of fibrosis occurred between the 50th and 64th day. Ultrastructural study disclosed a predominance of macrophages and fibroblasts in the inflammatory infiltrates, with small numbers of lymphocytes. Macrophages had active phagocytosis and showed points of contact with altered muscle cells. Different degrees of matrix expansion were present, with granular and fibrilar deposits and collagen bundles. These alterations subsided by the 64th days. Macrophages seem to be the main immune effector cell in the C. callosus model of infection with T. cruzi. The mechanisms involved in the rapid fibrogenesis and its regression deserve further investigation.

The NLRP3 inflammasome promotes renal inflammation and contributes to CKD.

Inflammation significantly contributes to the progression of chronic kidney disease (CKD). Inflammasome-dependent cytokines, such as IL-1β and IL-18, play a role in CKD, but their regulation during renal injury is unknown. Here, we analyzed the processing of caspase-1, IL-1β, and IL-18 after unilateral ureteral obstruction (UUO) in mice, which suggested activation of the Nlrp3 inflammasome during renal injury. Compared with wild-type mice, Nlrp3(-/-) mice had less tubular injury, inflammation, and fibrosis after UUO, associated with a reduction in caspase-1 activation and maturation of IL-1β and IL-18; these data confirm that the Nlrp3 inflammasome upregulates these cytokines in the kidney during injury. Bone marrow chimeras revealed that Nlrp3 mediates the injurious/inflammatory processes in both hematopoietic and nonhematopoietic cellular compartments. In tissue from human renal biopsies, a wide variety of nondiabetic kidney diseases exhibited increased expression of NLRP3 mRNA, which correlated with renal function. Taken together, these results strongly support a role for NLRP3 in renal injury and identify the inflammasome as a possible therapeutic target in the treatment of patients with progressive CKD.

Ecoepidemiological aspects of american cutaneous leishmaniasis in the state of São Paulo, Brazil

The aim of this study is to review some of the ecoepidemiological aspects of american cutaneous leishmaniasis (ACL) in the state of São Paulo, Brazil. During the first half of this century ACL occured in São Paulo, predominantly on the bank of the Tietê river, where there were railroad constructions and there was inevitable contact between and forested areas. Man's activities resulted in a drastic reduction of the forested regions of the state and molded the present landscape found in São Paulo, which brought a gradual change in the epidemiology of ACL during this century. Currently ACL can be considered as an endemic disease. Nowadays, ACL is found in different regions of São Paulo state, and is no longer limited to the bank of the Tietê river. The disease occurs in all age groups and sexes. Lack of knowledge about wild reservoir hosts of Leishmania (V.) braziliensis has simulated speculation about the possible role played by domestic animals (dogs and equines). Man's activities also favoured Lutzomyia intermedia a sandfly species which can clearly thrive in changed environments L. (V.) braziliensis continues to be transmitted, even after decades of forest destruction in São Paulo.

American cutaneous leishmaniasis in Pernambuco, Brazil: eco-epidemiological aspects in "Zona da Mata" region

American cutaneous leishmaniasis (ACL) has been increasing in Pernambuco, thus becoming an important problem for Public Health. The incindence is predominant in the region called "Zona da Mata", in the east of this state. This region corresponds geographically to the primitive area of the Atlantic forest. In order to characterize the eco-epidemiology expression of ACL in this region, two localities situated in the municipalities of Amaraji e Cortes have been selected by the criterion of higher incindence of human cases. Five stocks of patients were characterized and identified on the basis of enzyme profiles as a new variant of Leishmania (V.) braziliensis. A survey of wild and domestic animals was carried out by means of a parasitological and serological diagnosis. Through the analysis of the spleen and liver imprints, were detected amastigotes compatible with Leishmania in five Nectomys s. squamipes, five Bolomys l. pixuna, two Rattus r. alexandrinus and one Rattus r. frugivorus. For two years we carried out monthly sandflies captures using CDC light traps as well as manual captures. Lutzomyia whitmani was predominant, which accounted for 97.4 por cento of the total. These data indicate a strong evidence on the vector and the potential reservoirs of L. braziliensis in this region.

Differential involvement of peroxisome-proliferator-activated receptors alpha and delta in fibrate and fatty-acid-mediated inductions of the gene encoding liver fatty-acid-binding protein in the liver and the small intestine.

Liver fatty-acid-binding protein (L-FABP) is a cytoplasmic polypeptide that binds with strong affinity especially to long-chain fatty acids (LCFAs). It is highly expressed in both the liver and small intestine, where it is thought to have an essential role in the control of the cellular fatty acid (FA) flux. Because expression of the gene encoding L-FABP is increased by both fibrate hypolipidaemic drugs and LCFAs, it seems to be under the control of transcription factors, termed peroxisome-proliferator-activated receptors (PPARs), activated by fibrate or FAs. However, the precise molecular mechanism by which these regulations take place remain to be fully substantiated. Using transfection assays, we found that the different PPAR subtypes (alpha, gamma and delta) are able to mediate the up-regulation by FAs of the gene encoding L-FABP in vitro. Through analysis of LCFA- and fibrate-mediated effects on L-FABP mRNA levels in wild-type and PPARalpha-null mice, we have found that PPARalpha in the intestine does not constitute a dominant regulator of L-FABP gene expression, in contrast with what is known in the liver. Only the PPARdelta/alpha agonist GW2433 is able to up-regulate the gene encoding L-FABP in the intestine of PPARalpha-null mice. These findings demonstrate that PPARdelta can act as a fibrate/FA-activated receptor in tissues in which it is highly expressed and that L-FABP is a PPARdelta target gene in the small intestine. We propose that PPARdelta contributes to metabolic adaptation of the small intestine to changes in the lipid content of the diet.

The pollutant diethylhexyl phthalate regulates hepatic energy metabolism via species-specific PPARalpha-dependent mechanisms.

Background: The modulation of energetic homeostasis by pollutants has recently emerged as a potential contributor to the onset of metabolic disorders. Diethylhexyl phthalate (DEHP) is a widely used industrial plasticizer to which humans are widely exposed. Phthalates can activate the three peroxisome proliferatoractivated receptor (PPAR) isotypes on cellular models and induce peroxisome proliferation in rodents.Objectives: In this study, we aimed to evaluate the systemic and metabolic consequences of DEHP exposure that have remained so far unexplored and to characterize the underlying molecular mechanisms of action.Methods: As a proof of concept and mechanism, genetically engineered mouse models of PPARs were exposed to high doses of DEHP, followed by metabolic and molecular analyses.Results: DEHP-treated mice were protected from diet-induced obesity via PPARalpha-dependent activation of hepatic fatty acid catabolism, whereas the activity of neither PPARbeta nor PPARgamma was affected. However, the lean phenotype observed in response to DEHP in wild-type mice was surprisingly abolished in PPARalpha-humanized mice. These species differences are associated with a different pattern of coregulator recruitment.Conclusion: These results demonstrate that DEHP exerts species-specific metabolic actions that rely to a large extent on PPARalpha signaling and highlight the metabolic importance of the species-specific activation of PPARalpha by xenobiotic compounds. Editor's SummaryDiethylhexyl phthalate (DEHP) is an industrial plasticizer used in cosmetics, medical devices, food packaging, and other applications. Evidence that DEHP metabolites can activate peroxisome proliferatoractivated receptors (PPARs) involved in fatty acid oxidation (PPARalpha and PPARbeta) and adiposite function and insulin resistance (PPARgamma) has raised concerns about potential effects of DEHP on metabolic homeostasis. In rodents, PPARalpha activation also induces hepatic peroxisome proliferation, but this response to PPARalpha activation is not observed in humans. Feige et al. (p. 234) evaluated systemic and metabolic consequences of high-dose oral DEHP in combination with a high-fat diet in wild-type mice and genetically engineered mouse PPAR models. The authors report that mice exposed to DEHP gained less weight than controls, without modifying their feeding behavior; they also exhibited lower triglyceride levels, smaller adipocytes, and improved glucose tolerance compared with controls. These effects, which were observed in mice fed both high-fat and standard diets, appeared to be mediated by PPARalpha-dependent activation of hepatic fatty acid catabolism without apparent involvement of PPARbeta or PPARgamma. However, mouse models that expressed human (versus mouse) PPARalpha tended to gain more weight on a high-fat diet than their DHEP-unexposed counterparts. The authors conclude that findings support species-specific metabolic effects of DEHP mediated by PPARalpha activation.

Ecology of Triatoma rubrovaria (Hemiptera, Triatominae) in wild and peridomestic environments of Uruguay

This paper describes population structure, spatial distribution and habitat selection of wild and peridomestic populations of Triatoma rubrovaria (Blanchard, 1843). Field studies were carried out at Las Piedras and La Bolsa in the Northern Department of Artigas, Uruguay. A semicircular sampling area, divided in seven or eight triangular sectors was sequentially examined from October 1990 to November 1991. At Las Piedras (typical wild habitat) 1063 T. rubrovaria bugs were collected from 84 of the rocky outcroops ("pedregales"). Abundance varied by season peaking in October-November (spring). Throughout the year, most of the population was made up of third, fourth and fifth instar nymphs; adults were found from October to March. In the peridomestic environment of La Bolsa, however T. rubrovaria was less common and showed a more irregular instar distribution. Colonized ecotopes, were those close to houses. In both sites T. rubrovaria was mainly associated with the geckonid Homonota uruguayensis and the cockroach Blaptica dubia.