Experimental visceral leishmaniasis in high and low antibody - producer mice (selection IV-A)

A leishmaniose é uma infecção parasitária cuja imunidade protetora envolve a ativação de macrófagos. Neste trabalho avaliamos a susceptibilidade de camundongos H e L (bons e maus produtores de anticorpos, respectivamente) da seleção IV-A, à infecção com o protozoário L. donovani. Camundongos H infectados com 10(7) amastigotas por via intravenosa foram mais suscetíveis, apresentando maior carga parasitária tanto no fígado quanto no baço. Após 60 dias de infecção ambas as linhagens apresentaram um aumento no índice esplênico. Esta esplenomegalia foi conseqüência, pelo menos parcialmente, de um aumento no número de células esplênicas. Os resultados indicam que a seleção IV-A é susceptível à infecção com L. donovani e que dentro desta seleção a linhagem H apresenta maior suscetibilidade do que a linhagem L.

Effects of prolonged oral administration of fumonisin B(1) and aflatoxin B(1) in rats

The effects of prolonged oral administration (21 days) of fumonisin B(1) (FB(1)) and aflatoxin B(1) (AFB(1)) were evaluated on male Wistar rats. The animals were housed in individual metabolic cages and submitted to the following treatments: 1-0 mug AFB(1) + 0 mg FB(1)/100g bw.; 2-72 mug AFB(1)+ 0 mg FB(1)/100 g bw; 3-0 mug AFB(1) + 0.5 mg FB(1) g bw; 4-0 mug AFB(1) + 1.5 mg FB(1)/100 g bw; 5-72 mug AFB(1) + 0.5 mg FB(1)/100g bw; 6-72 mu gAFB(1) + 1.5 mg FB(1)/100g bw. on day 21, the rats were sacrificed for evaluation. The results showed that treated animals presented differences in body weight and absolute/relative weights of liver and kidney as well as altered hepatic function and cholesterol blood levels. Rats fed with the greatest doses of AFB(1) and FB(1) gained less weight (2.79 g/day) at the end of the experimental period; their blood concentrations of liver enzymes aspartate aminotransferase (AST) and alkaline phosphatase (AP) were above control levels (130.35 mu /l and 471.00 mu /l, respectively). Blood cholesterol increased in the groups treated with the highest dose of FB(1) or FB(1) associated with AFB(1). Histopathology revealed the occurrence of apoptosis in the liver of rats exposed to FB(1). The association of aflatoxin B(1) with fumonisin B(1) at higher dose probably potentiated the effects of the higher dose of fumonisin B(1)acting singly.

Hepatocyte lesions and cellular immune response in yellow fever infection

The study of the in-situ cellular immune response is very important for the understanding of different liver infections. In the present study, 53 liver samples obtained by viscerotomy from patients who died during the course of jungle yellow fever were analyzed. The diagnosis was confirmed by serology, viral isolation and virus-specific immunohistochemistry. The specimens were analyzed by immunohistochemistry using specific antibodies for apoptosis, CD45RO, CD4, CD8, CD20, S100, CD57 and CD68. Quantitative analysis of the labeling pattern showed a clear predominance of the different phenotypes in the portal tract and midzone region of the acini. There was a predominance of T CD4+ lymphocytes, accompanied by the presence of T CD8+ lymphocytes, natural killer cells (CD57), macrophages and antigen-presenting cells (S100). The disproportion between the intensity of inflammation and the degree of hepatic injury was probably due to the intense apoptotic component, which classically does not induce an inflammatory response. The present study demonstrates that, despite the disproportion between injury and inflammation, the cellular immune response plays an important role in the pathogenesis of the hepatocytic injury observed in yellow fever, probably as a result of cytolytic actions through mechanisms involving MHC II and the activation of Fas receptors and granzymes/perforins. (C) 2006 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Squalene does not exhibit a chemopreventive activity and increases plasma cholesterol in a Wistar rat hepatocarcinogenesis model

The eventual chemopreventive effect of squalene (SQ), a triterpene present in olive oil, was evaluated when administered to Wistar rats during a period comprising the initiation and selection/promotion of the resistant hepatocyte (RH) model of hepatocarcinogenesis. During 8 consecutive wk, animals received by gavage SQ (100 or 150 mg/100 g body weight) dissolved in corn oil (CO) daily. Animals treated with only CO and submitted to the RH model were used as controls. Treatments with SQ did not result in inhibition of macroscopically visible hepatocyte nodules (P > 0.05) or of hepatic placental glutathione S-transferase-positive preneoplastic lesions (PNL; P > 0.05). Hepatic cell proliferation and apoptosis indexes were not different (P > 0.05) among the different experimental groups, both regarding PNL and surrounding normal tissue areas. There were no significant differences (P > 0.05) among comets presented by rats treated with the two SQ doses or with CO. on the other hand, SQ increased total plasma cholesterol levels when administered at both doses (P < 0.05). This indicates that the isoprenoid was absorbed. Thus, SQ did not present chemopreventive activity during hepatocarcinogenesis and had a hypercholesterolemic effect, suggesting caution when considering its use in chemoprevention of cancer.

Common bile duct obstruction associated with platinosoma concinum in cat

Extrahepatic obstruction in cat,can be caused by cholelithiasis, inspissated bile, pancreatic inflammation or fibrosis, duodenal inflammation, bile duct carcinoma or liver fluke infection (Amphimerus pseudofelineus e Platynosomurn concinum). A three-year-old, female neutered siames cat was present with a two-month history of progressive letargy, anorexia and emaciation. She had severe icterus of the mucous membranes, skin, and sclerae. A diagnosis of extrahepataic biliary obstruction was made based on the increased levels of conjugated bilirubin in the serum and the ultrasonography. Hepatic fluke eggs were not diagnosed in the feces because the fibrotic bile ducts were occluded and no eggs were shed into the intestine. Cholecystoduodenostomy was done to relieve posthepatic-biliary obstruction.

Hydrolyzed alpha-lactalbumin as a source of protein to the exercising

This work describes the effect of feeding enzymatically hydrolyzed a-lactalbumin on blood sugar, albumin and fatty acids, muscular and hepatic glycogen of rats subjected to physical exercise. Three normoenergetic/normoproteic diets, containing either casein (C), alpha-lactalbumin (L) or alpha-lactalbumin hydrolyzate (H) were fed to thirty male Wistar rats for five weeks. During this period, half of the rats swam for 1 hr daily (T category) while the other half remained sedentary (S category). At the end of training, all rats were required to swim to exhaustion. The results showed that those rats of the T-category consuming diet H reached exhaustion with significantly higher concentrations of serum glucose ([H] 56.0 and [L] 32.3 mg/100ml), serum albumin ([H] 3.8 and [L] 2.1 mg/dl) and muscle glycogen ([H] 2.1 and [L] 0.6 mg/g), while no differences were observed between diets regarding the time of arrival to exhaustion. Results from diets C and L differed minimally. It was concluded that feeding the hydrolyzed protein may result in nutritional advantage to the exercising rat. (C) 1998 Elsevier B.V.

Differential/combined effect of water contamination with cadmium and nickel on tissues of rats

The contamination of water by metal compounds is a worldwide environmental problem. Concentrations of metals are widely related to biochemical values which are used in disease diagnosis due to environmental toxicity. The acute combined effects of cadmium and nickel on biochemical parameters were determined and compared with those of Cd2+ or Ni2+ alone in rats. Male adult rats were given drinking solutions of CdCl2 [Cd(II) cation, 100 mg/liter] or NiSO4 [Ni(II) cation, 100 mg/liter]. For the combined treatment, the animals (Ni+Cd) received both Ni(II)) cation (100 mg/liter) and Cd(II) cation (100 mg/liter). Nickel treatment induced increased alanine transaminase (ALT) activity and hepatotoxicity, but not renal injury. In contrast, cadmium exposure produced hepatic, renal and myocardial damage, characterized by increased creatinine, total and direct bilirubin concentrations and increased ALT and lactate dehydrogenase (LDH) activities. The combined effect Ni-Cd is less toxic than cadmium alone, suggesting antagonism between these toxicants. The toxicity of nickel and cadmium, alone and in combination, decreased Cu-Zn superoxide dismutase (SOD) activity and increased lipoperoxide formation. (C) 1998 Elsevier B.V. Ltd. All rights reserved.

Impact of an environmentally realistic intake of water contaminants and superoxide formation on tissues of rats

Water contaminants have a high potential risk for the health of populations and for this reason their toxic effects urgently should be established. The present study was carried out to determine whether an environmentally realistic intake of water contaminants can induce tissue lesions, and to clarify the contribution of superoxide radical (O-2(.-)) formation to this effect. Male Wistar rats were given drinking water from the Tiett River (group A) and from the Capivara River (group B). The increased creatinine, glucose, alanine transaminase and amylase levels in serum reflected the toxic effects of river-water contaminants to renal, pancreatic and hepatic tissues of rats. As changes in lipoperoxide were observed in rats after river-water intake while superoxide dismutase activities decreased in these animals, it is assumed that the superoxide anion elicits lipoperoxide formation and induces tissue damage. There is evidence that oxygen tension reflects water pollution, since river-water with a-low oxygen tension induced more elevated toxicity in rat tissues. (C) 1999 Elsevier B.V. Ltd. All rights reserved.

Antiplasmodial activity of aryltetralone lignans from Holostylis reniformis

Extracts from Holostylis reniformis were tested in vivo against Plasmodium berghei and in vitro against a chloroquine-resistant strain of Plasmodium falciparum. The hexane extract of the roots was the most active, causing 67% reduction of parasitemia in vivo. From this extract, six lignans, including a new (7 ' R,8S,8 ' S)-3 ',4 '-methylenedioxy-4,5-dimethoxy-2,7 '-cyclolignan-7-one, were isolated and tested in vitro against P. falciparum. The three most active lignans showed 50% inhibitor concentrations of <= 0.32 mu M. An evaluation of minimum lethal dose (30%) values showed low toxicity for these lignans in a hepatic cell line (Hep G2A16). Therefore, these compounds are potential candidates for the development of antimalarial drugs.

Infecção experimental pelo Encephalitozoon cuniculi em camundongos imunossuprimidos com dexametasona

Objective Microsporidian Encephalitozoon cuniculi has been recognized as an opportunistic pathogen in immunosuppressed individuals, such as AIDS patients. The objective of the study was to develop pharmacologically immunosuppressed animals as a model of the natural occurring E. cuniculi infection.Methods Distint groups of adult Balb-C mice were immunosuppressed with different doses of dexamethasone (Dx, 3 or 5 mg/kg/day, intraperitoneal route - IP) and inoculated with E. cuniculi spores by IP route intraperitoneally. Control groups (inoculated animals but non-immunosuppressed and non-inoculated animals but immunosuppressed) were also used. The spores of E. cuniculi were previously cultivated in MDCK cells. The animals were sacrificed and necropsied at 7, 14, 21, 28 and 35 days post-inoculation. Tissue fragments were collected and processed for light microscopy studies, using Gram-chromotrope and hematoxylin-eosin staining techniques.Results In all immunosupressed and inoculated inoculated immunosuppressed mice,specially in those that received 5 mg/kg/day of dexamethasone, the most prominent necropsy findings were hepatomegaly and splenomegaly. The experimental inoculation resulted in a disseminated non-lethal infection, characterized by granulomatous lesions in several organs (liver lungs, kidneys, gut and brain) but notably in the hepatic tissue. Spores of E. cuniculi were only seen in few animals treated with 5 mg/kg/day of Dx at 35 days post-infection.Conclusions Microsporidiosis in Dx-immunosuppressed mice provides a useful model for studies of the microsporidial infection, resembling that one naturally occurring in immunodeficient individuals with AIDS.

Growth and metabolism of pacu (Piaractus mesopotamicus Holmberg 1887) juveniles fed diets containing different protein, lipid and carbohydrate levels

To verify the potential of lipids and carbohydrates to spare dietary protein and to understand the intermediary metabolism of interaction of these nutrients in pacu juveniles, an experiment was carried out to evaluate pacu physiological and performance parameters. The experimental design was completely randomized with 12 treatments in a 2 x 2 x 3 factorial arrangement, consisting of diets containing two digestible protein levels (200 and 230 g kg(-1) PD), two lipid levels (40 and 80 g kg(-1)) and three carbohydrate levels (410, 460 and 500 g kg(-1)). Fish-fed 230 g kg(-1) digestable protein (DP) showed increased glycaemia, decreased hepatic glycogen, as well as a smaller intake index and better feed conversion ratio. The higher dietary lipid level (80 g kg(-1)) reduced protein intake and serum protein concentration, increased liver and body fat content, but did not affect growth. At a lipid level of 80 g kg(-1), the increase in dietary carbohydrate levels promoted greater weight gain (WG), crude protein intake (CPI) and better feed conversion ratio (FCR). For fish fed diets containing 40 g kg(-1) lipid, the best energy-productive values (EPV) were obtained at 460 g kg(-1) carbohydrate. Increased levels of the main nutrients in the diets reduced the levels of serum triglycerides, while the increase in energy concentration increased the hepatosomatic (HSI) and glycaemia index values. Pacu used lipids as effectively as carbohydrates in the maximization of protein usage, as long as dietary protein was at a level of 230 g kg(-1) DP. The physiological parameters indicated that the best balance between the DP, dietary lipid and carbohydrate levels within the ranged this trial was obtained at 230, 40 and 460 g kg(-1), respectively, without lower growth.

Neo-clerodane diterpenoid, a new metalloprotease snake venom inhibitor from Baccharis trimera (Asteraceae): anti-proteolytic and anti-hemorrhagic properties

Many plants are used in traditional medicine as active agents against various effects induced by snakebite. Few attempts have been made however to identify the nature of plain natural products with anti-ophidian properties. Baccharis trimera (Less) DC (Asteraceae), known in Brazil as carqueja. has been popularly used to treat liver diseases. rheumatism. diabetes, as well as digestive, hepatic and renal disorders. The active component was identified as 7alpha-hydroxy-3,13-clerodadiene-16,15:18,19-diolide, C20H28O5, (clerodane diterpenoid, Bt-CD). We report now the anti-proteolytic and anti-hemorrhagic propenies against snake venoms of a Bt-CD inhibitor from B. trimera. Bt-CD exhibited full inhibition of hemorrhage and proteolytic activity caused by Bothrops snake venoms. The inhibitor was able to neutralize the hemorrhagic, fibrinogenolytic and caseinolytic activities of class P-I and III metalloproteases isolated from B. neuwiedi and B. jararacussu venoms. No inhibition of the coagulant activity was observed. Bt-CD also partially inhibited the edema induced by other crude venoms, metallopronteases, basic and acidic phospholipases A(2). To further elucidate the inhibitory specificity of Bt-CD against metalloproteases isolated from snake venoms, a deeper understanding of its Structure and function is necessary. Furthermore, the potential use of these inhibitors to complement anti-venom as an alternative treatment of snakebite envenomations needs to be evaluated in future Studies. (C) 2004 Elsevier B.V.. All rights reserved.

SUPEROXIDE RADICAL AND TOXICITY OF ENVIRONMENTAL NICKEL EXPOSURE

Three nickel compounds were tested for pancreatic, hepatic and osteogenic damage in rats by a single i.m. injection Ni++ (7 mg kg(-1)). The nickel induced biochemical alterations included significantly increased levels of serum alkaline phosphatase in rats with NiS (75%) and NiO (50%). Amylase and aspartate transaminase were also increased, and lipoperoxide was increased in rats with NiO (5.6-fold) and NiS (3.4-fold). No serum changes were observed with NiCl2. Daily injection of Cu-Zn superoxide dismutase (SOD) conjugated with polyethylene glycol prevented the serum level changes, indicating that superoxide radical is an important intermediate in toxicity of nickel insoluble compounds.

Clinical pathological data and analyses of mineral elements of cattle affected by epizootic botulism in the State of São Paulo

In order to study laboratorial aspects of beef cow mortality, a syndrome popularly known as ''doenca da vaca caida'', examens were made of blood, cerebrospinal fluid, serum, bone and liver samples from 32 naturally affected 4 to 9 year old cows, 27 belonging to the Nellore breed and 5 were crossbred Nellore, all originating from farms located in municipalities near Botucatu, State of São Paulo. Laboratory determinations were analysed by descriptive statistics and included hematological values, total plasma protein, plasma fibrinogen, cerebrospinal fluid analysis, and concentration measurements of serum calcium, phosphorus, magnesium, sodium, potassium, chloride, total protein, albumin, globulin, alkaline phosphatase, aspartate aminotransferase, gama-glutamyltransferase and creatine kinase activities, included bone ash percentage and concentrations of calcium, phosphorus and magnesium, and also hepatic levels of copper, zinc, iron, manganese and cobalt. In addition, mouse bioassays and complement micro-fixation tests were performed to detect botulinum toxins in liver samples. The results indicated leukocytosis (13,3+/-3,9 x10(3)/mm(3)) with neutrophilia (8,9+/-3,2 x10(3)/mm(3)), hypocalcemia (7,8+/-1,7mg/dl), hypophosphatemia (3,6+/-1,6mg/dl), hypoalbuminemia (2,9+/-0,9g/dl), increased creatine kinase activity (691,0+/-829,7 UI/1), and reduced ash percentage (60,3+/-1,9%) and low phosphorus (17,2+/-0,4%) in bone. The other values were ail within normal limits. The diagnosis of botulism, involving type C and D toxins, was confirmed as the cause of the mortality in the region of study, what is strongly consistent with the other laboratorial findings.

Effects of apolipoprotein B-100 on the metabolism of a lipid microemulsion model in rats

In previous studies, it was shown that lipid microemulsions resembling LDL (LDE) but not containing protein, acquire apolipoprotein E when injected into the bloodstream and bind to LDL receptors (LDLR) using this protein as ligand. Aiming to evaluate the effects of apolipoprotein (apo) B-100 on the catabolism of these microemulsions, LDE with incorporated apo B-100 (LDE-apoB) and native LDL, all labeled with radioactive lipids were studied after intraarterial injection into Wistar rats. Plasma decay curves of the labels were determined in samples collected over 10 h and tissue uptake was assayed from organs excised from the animals sacrificed 24 h after injection. LDE-apo B had a fractional clearance rate (FCR) similar to native LDL (0.40 and 0.33, respectively) but both had FCR pronouncedly smaller than LDE (0.56, P<0.01). Liver was the main uptake site for LDE, LDE-apoB, and native LDL, but LDE-apoB and native LDL had lower hepatic uptake rates than LDE. Pre-treatment of the rats with 17 alpha-ethinylestradiol, known to upregulate LDLR, accelerated the removal from plasma of both LDE and LDE-apoB, but the effect was greater upon LDE than LDE-apoB. These differences in metabolic behavior documented in vivo can be interpreted by the lower affinity of LDLR for apo B-100 than for apo E, demonstrated in in vitro studies. Therefore, our study shows in vivo that, in comparison with apo E, apo B is a less efficient ligand to remove lipid particles such as microemulsions or lipoproteins from the intravascular compartment. (C) 1999 Elsevier B.V. B.V. All rights reserved.