Intoxicação por veneno de cobra: necrose symetrica da cortex renal: uremia

Em um caso fatal de ophidismo, em individuo de 15 annos de edade, picado por uma cobra jararaca (Bothrops jararaca) na face externa da perna direita e que veio a fallecer 26 dias apoz o accidente, os A.A, descrevem as lesões anatomo-pathologicas encontradas e as modificações do metabolismo, evidenciadas pelos exames chimicos do sangue. As principaes alterações existentes, acham-se localisadas nos rins os quaes apresentam lesões de glomerulonephrite diffusa e o aspecto typico da necrose cortical symmetrica. Como alterações de maior significação observam-se ainda lesões vasculares de grande intensidade e constituidas essencialmente por processo de endoarterite productiva. A necrose symmetrica da cortex renal, a vista das intensas alterações vasculares (endoarterite productiva) que acarretaram a obliteração das arterías, é considerada como a consequencia immediata de taes lesões vasculares. Os vasos renaes, séde do processo inflammatorio, são as arterias interlobar, arciforme e interlobular, mas principalmente as arteriolares da camada cortical. O processo de endoarterite assume sempre o carater progressivo, de modo que a luz vascular vae sendo aos poucos, totalmente obstruida. Ao contrario do que se tem observado nos casos de necrose cortical symmetrica, citados na literatura, em que as alterações parenchymatosas são consequentes a thrombose dos vasos reanes, no caso presente esse aspecto não foi verificado mas tão sómente a existencia da endoarterite productiva obliterante. Consideram os A.A. as lesões renaes no caso que estudaram, como a resultante da actuação lenta e prolongada do veneno de cobra sobre as estructuras renaes, baseados nos seguintes factos já conhecidos e admittidos: eliminação do veneno de cobra pelos rins; capacidade do mesmo veneno, determinar a glomerulo-nephrite diffusa e acção do veneno de cobra sobre o endothelio vascular, facilitada essencialmente pela funcção especifica do orgão. As modificações do metabolismo se traduziram por alterações urinarias e sanguineas. As urinas foram emitidas em muito pequena quantidade (50 cc. em 24 horas) não havendo comtudo, anuria absoluta. Cylindros hyalinos e granulosos, bem como leucocytos e cellulas renaes, associadas á albuminoria, era presentes. Os exames chimicos do sangue, revelaram: Proteinas totaes 7,61 grs. em 1000 cc.; Albumina 2,39 grs em 1000 cc.; Globulina 5,22 grs. em 1000 cc.; Uréa 6,42 grs. em 1000 cc.; Fibrinogeneo 0,324 grs. em 1000 cc.; Indican +++; Cl. plasmatico 339 mgrs. em 100 cc.; Cl. globular 170 mgrs. em 100 cc.; Cholesterol 163 mgrs. em 100 cc.; Creatinia 260 mgrs. em 100 cc.; Ph. inorganico 13,4 mgrs. em 100 cc.; Calcio 10,3 mgrs em 100 cc.; Potassio 28 mgrs. em 100 cc.; Sodio 328 mgrs. em 100 cc.. O exame hematologico revelou 11% de hemoglobina; 960.000 hematias por mm.³; e 5.200 leucocytos por mm.³. A formula leucocytaria revelou augmento dos neutrophilos, com 74% dos segmentados. A proporção entre sôro o coagulo foi 9 x 3 cc. A reacção de Wassermann no sôro sanguineo foi negativa. A insufficiencia renal se traduziu no caso em estudo, por modificações humoraes, particularmente pela azotemia elevada, pelo augmento da creatinina, do phosphoro inorganico e do indican. Em contraste com a existencia de taes modificações, o doente não apresentou os signaes clinicos observados nos casos emque a azotemia se mantem elevada, reproduzindo tal facto, o quadro clinico descripto para a necrose symmetrica da cortex renal.

Advances in pharmacological studies of silymarin

Silymarin is the flavonoids extracted from the seeds of Silybum marianum (L) Gearth as a mixture of three structural isomers: silybin, silydianin and silychristin, the former being the most active component. Silymarin protects liver cell membrane against hepatotoxic agents and improves liver function in experimental animals and humans. It is generally accepted that silymarin exerts a membrane-stabilizing action preventing or inhibiting membrane peroxidation. The experiments with soybean lipoxygenase showed that the three components of silymarin brought about a concentration-dependent non-competitive inhibition of the lipoxygenase. The experiments also showed an analogous interaction with animal lipoxygenase, thus showing that an inhibition of the peroxidation of the fatty acid in vivo was self-evident. Silybin almost completely suppressed the formation of PG at the highest concentration (0.3 mM) and proved to be an inhibitor of PG synthesis in vitro. In our experiments, silybin at lower dose (65 mg/Kg) decreased liver lipoperoxide content and microsomal lipoperoxidation to 84.5% and 68.55% of those of the scalded control rats respectively, and prevented the decrease of liver microsomal cytochrome p-450 content and p-nitroanisole-0-demethylase activity 24 h post-scalding. Effects of silymarin on cardiovascular systen have been studied in this university since 1980. O. O silymarin 800 mg/Kg/d or silybin 600 mg/Kg/d reduced plasma total cholesterol, LDL-C and VLDL-C. They however, enhanced HDL-C in hyperlipenic rats. Further studies showed that silymarin enhanced HDL-C in hyperlipemic rats. Further studies showed that silymarin enhanced HDL-C but didn't affect HDL-C, a property of this component which is beneficial to treatment of atherosclerosis. The results showed silymarin 80 mg or silybin 60 mg decreased in vitro platelet aggregation (porcentagem) in rats. The maximal platelet aggregation induced by ADP declined significantly, and time to reach maximal platelet aggregation and five-minute disaggregation didn't change. In our experiments, iv silybin 22,4 mg/kg lowered the amplitude and duration of diastolic blood pressure (DBP) more than those of systolic (SBP), but the descending aortic blood flow, cardiac contractility and ECG did not change significantly in anesthetized open-chest cats. The results indicated a reduction of peripheral resistance and dilatatory action on the resistant blood vessels. These effects are beneficial to coronary heart disease. We also observed the effects of silybin on morphological change, the release of glutamic oxaloacetate aminotrasferase (GOT) and lactate dehydrogenase (LDH) as well as the radioactivity of 3H-TdR incorporated into DNA in normal cardiac cells and cells infected by coxsackie B5, virus os newborn rats. The results showed that silynin did not affect the morphology of normal cell, and that the pathological change of cells infected by virus was delayed and reduced as compared to control. We have investigated the effect of silybin on synthesis and release of LTs in the cultured porcine cerebral basilar arteries (PCBA). Silybin 100 and 500 µmol/L declined the amounts of LTs released from the PCBA incubsated in the presence of A 23187, AA and indomenthacin. The result suggests that silybin can inhibit the activity of 5-lipoxygenase of cerebral blood vessel and may protect the brain from ischemia.

Fatty Acid and Sterol Composition of Three Phytomonas Species

Fatty acid and sterol analysis were performed on Phytomonas serpens and Phytomonas sp. grown in chemically defined and complex medium, and P. françai cultivated in complex medium. The three species of the genus Phytomonas had qualitatively identical fatty acid patterns. Oleic, linoleic, and linolenic were the major unsaturated fatty acids. Miristic and stearic were the major saturated fatty acids. Ergosterol was the only sterol isolated from Phytmonas sp. and P. serpens grown in a sterol-free medium, indicating that it was synthesized de novo. When P. françai that does not grow in defined medium was cultivated in a complex medium, cholesterol was the only sterol detected. The fatty acids and sterol isolated from Phytomonas sp. and P. serpens grown in a chemically defined lipid-free medium indicated that they were able to biosynthesize fatty acids and ergosterol from acetate or from acetate precursors such as glucose or threonine.

Nodular typhlitis associated with the nematodes Heterakis gallinarum and Heterakis isolonche in pheasants: frequency and pathology with evidence of neoplasia

An investigation related to the frequency and pathology of Heterakis gallinarum and pathology of Heterakis isolonche in pheasants from Rio de Janeiro, Brazil was conducted by means of clinical examinations, necropsies, and histopathological analysis in 50 ring-necked pheasants from backyard flocks of 11 localities; also, histological sections of caeca of golden pheasants deposited in the Helminthological Collection of the Oswaldo Cruz Institute (CHIOC) have been considered in the present study. During necropsies, only specimens of H. gallinarum were recovered with a prevalence of 90%, mean intensity of 81.9 and range of infection of 1-413. Gross lesions were characterized by congestion, thickening, petechial haemorrhages of the mucosa, intussusception, and nodules in the cecal wall. Under microscopy, chronic difuse typhlitis, haemosiderosis, granulomas with necrotic center in the submucosa and leiomyomas in the submucosa, muscular and serosa associated with immature H. gallinarum worms were observed. The examination of histological sections previously deposited in the CHIOC, revealed more severe alterations associated with concomitant infections with H. gallinarum and H. isolonche in golden pheasants, and were characterized by several necrotic areas with cholesterol clefts in the submucosa, giant cell granulomas in the submucosa, and serosa centralized by necrosis and worm sections and neoplastic nodules in the muscular and submucosa.

Studies of membrane fluidity and heart contractile force in Trypanosoma cruzi infected mice

In Chagas disease serious cardiac dysfunction can appear. We specifically studied the cardiac function by evaluating: ventricle contractile force and norepinephrine response, affinity and density of beta-adrenergic receptors, dynamic properties of myocardial membranes, and electrocardiography. Albino swiss mice (n = 250) were infected with 55 trypomastigotes, Tulahuen strain and studied at 35, 75, and 180 days post-infection, that correspond to the acute, indeterminate, and chronic phase respectively. Cardiac beta-adrenergic receptors' affinity, myocardial contractility, and norepinephrine response progressively decreased from the acute to the chronic phase of the disease (p < 0.01). The density (expressed as fmol/mg.prot) of the receptors was similar to non-infected mice (71.96 ± 0.36) in both the acute (78.24 ± 1.67) and indeterminate phases (77.28 ± 0.91), but lower in the chronic disease (53.32 ± 0.71). Electrocardiographic abnormalities began in the acute phase and were found in 65% of the infected-mice during the indeterminate and chronic phases. Membrane contents of triglycerides, cholesterol, and anisotropy were similar in all groups. A quadratic correlation between the affinity to beta-adrenergic receptors and cardiac contractile force was obtained. In conclusion the changes in cardiac beta-adrenergic receptors suggests a correlation between the modified beta-adrenergic receptors affinity and the cardiac contractile force.

Benznidazole vs benznidazole in multilamellar liposomes: how different they interact with blood components?

In spite of its widespread use, benznidazole's (BNZ) toxicity and low efficacy remains as major drawbacks that impair successful treatments against Chagas disease. Previously, attempting to increase the selectivity and reduce its toxicity on infected tissues, multilamellar liposomes (MLV) composed of hydrogenated soybean phosphatidylcholine (HSPC): distearoyl-phosphatidylglycerol (DSPG): cholesterol (CHOL) 2:1:2 mol:mol loaded with BNZ (MLV-BNZ) were designed. In this work we compared different properties of MLV-BNZ with those of BNZ. Opposite to other hydrophobic drugs, the results indicated that slight changes of BNZ×s association degree to proteins and lipoproteins should not modify the percentage of unbound drug available to exert pharmacological action. On the other hand, when loaded in MLV, BNZ reduced its association to plasma proteins in 45% and became refractory to the sinking effect of blood, dropping 4.5 folds. Additionally, when loaded in MLV, BNZ had higher volume distribution (160 ± 20 vs 102 ± 15 ml/kg) and total clearance (35.23 ± 2.3 vs 21.9 ± 1.4 ml/h.kg), and lower concentration-time curve (7.23 ± 0.2 vs 9.16 ± 0.5 µg.h/ml) than BNZ. Hence, these studies showed that for MLV-BNZ, the amount of BNZ can be substantially increased, from 25 to 70%, being this formulation more rapidly cleared from circulation than free drug; also due to the lower interaction with blood components, lower side effects can be expected.

Transferrin uptake may occur through detergent-resistant membrane domains at the cytopharynx of Trypanosoma cruzi epimastigote forms

Uptake of transferrin by epimastigote forms of the protozoan Trypanosoma cruzi occurs mainly through a cytostome/ cytopharynx, via uncoated endocytic vesicles that bud off from the bottom of the cytopharynx. We have here examined whether detergent-resistant membrane (DRM) domains might be involved in this process. Purified whole cell membrane fractions were assayed for cholesterol levels and used in dot blot analyses. Detergent-resistant membrane markers (cholera B toxin and anti-flotillin-1 antibody) presented positive reaction by dot blots in cholesterol-rich/ protein-poor membrane sub-fractions. The positive dot blot fraction was submitted to lipid composition analysis, showing composition similar to that of raft fractions described for other eukaryotic cells. Immunofluorescence assays allowed the localization of punctual positive signal for flotillin-1, matching the precise cytostome/ cytopharynx location. These data were confirmed by immunofluorescence assays with the co-localization of flotillin-1 and the transferrin uptake site. Our data suggest that DRM domains occur and are integrated at the cytostome/ cytopharynx of T. cruzi epimastigotes, being the main route for transferrin uptake.

Toxoplasma gondii infection induces lipid metabolism alterations in the murine host

Host lipids have been implicated in the pathogenesis of Toxoplasma gondiiinfection. To determine if Toxoplasmainfection influences the lipid status in the normal host, we assessed serum lipids of Swiss-Webster mice during infection with the BGD-1 strain (type-2) at a series of time points. Mice were bled at days zero and 42 post-infection, and subgroups were additionally bled on alternating weeks (model 1), or sacrificed at days zero, 14 and 42 (model 2) for the measurement of total cholesterol (Chl), high density lipoproteins (HDL), low density lipoproteins (LDL) and triglycerides and adiponectin. At day 42, brains were harvested for cyst enumeration. A significant decrease (p = 0.02) in HDL and total Chl was first noted in infected vs. control mice at day 14 and persisted to day 42 (p = 0.013). Conversely, LDL was unaltered until day 42, when it increased (p = 0.043). Serum LDL levels at day 42 correlated only with cyst counts of above 300 (found in 44% mice), while the change in HDL between days zero and 42 correlated with both the overall mean cyst count (p = 0.041) and cyst counts above 300 (p = 0.044). Calculated per cyst, this decrease in HDL in individual animals ranged from 0.1-17 µmol/L, with a mean of 2.43 ± 4.14 µmol/L. Serum adiponectin levels remained similar between infected and control mice throughout the experiment.

High fat diet has a prominent effect upon the course of chronic schistosomiasis mansoni in mice

This study investigated whether a long-term high-fat diet has an effect on the outcome of chronic murine schistosomiasis mansoni compared to a standard diet. Swiss Webster female mice (3 weeks old) were fed each diet for up to six months and were then infected with 50 Schistosoma mansoni cercariae. Their nutritional status was assessed by monitoring total serum cholesterol and body mass. Infected mice were examined 6-17 weeks post infection to estimate the number of eggs in faeces. Mice were euthanised the next day. Total serum cholesterol was lower in infected mice in comparison to uninfected controls (p = 0.0055). In contrast, body mass (p = 0.003), liver volume (p = 0.0405), spleen volume (p = 0.0124), lung volume (p = 0.0033) and faecal (p = 0.0064) and tissue egg density (p = 0.0002) were significantly higher for infected mice fed a high-fat diet. From these findings, it is suggested that a high-fat diet has a prominent effect on the course of chronic schistosomiasis mansoni in mice.

Ergosterol biosynthesis and drug development for Chagas disease

This article presents an overview of the currently available drugs nifurtimox (NFX) and benznidazole (BZN) used against Trypanosoma cruzi, the aetiological agent of Chagas disease; herein we discuss their limitations along with potential alternatives with a focus on ergosterol biosynthesis inhibitors (EBI). These compounds are currently the most advanced candidates for new anti-T. cruzi agents given that they block de novo production of 24-alkyl-sterols, which are essential for parasite survival and cannot be replaced by a host's own cholesterol. Among these compounds, new triazole derivatives that inhibit the parasite's C14± sterol demethylase are the most promising, as they have been shown to have curative activity in murine models of acute and chronic Chagas disease and are active against NFX and BZN-resistant T. cruzi strains; among this class of compounds, posaconazole (Schering-Plough Research Institute) and ravuconazole (Eisai Company) are poised for clinical trials in Chagas disease patients in the short term. Other T. cruzi-specific EBI, with in vitro and in vivo potency, include squalene synthase, lanosterol synthase and squalene epoxidase-inhibitors as well as compounds with dual mechanisms of action (ergosterol biosynthesis inhibition and free radical generation), but they are less advanced in their development process. The main putative advantages of EBI over currently available therapies include their higher potency and selectivity in both acute and chronic infections, activity against NFX and BZN-resistant T. cruzi strains, and much better tolerability and safety profiles. Limitations may include complexity and cost of manufacture of the new compounds. As for any new drug, such compounds will require extensive clinical testing before being introduced for clinical use, and the complexity of such studies, particularly in chronic patients, will be compounded by the current limitations in the verification of true parasitological cures for T. cruzi infections.

Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas disease

Trypanosoma cruzi infection induces progressive cardiac inflammation that leads to fibrosis and modifications in the heart architecture and functionality. Statins, such as 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, have been studied due to their pleiotropic roles in modulating the inflammatory response. Our goal was to evaluate the effects of simvastatin on the cardiac inflammatory process using a cardiotropic strain of T. cruzi in a murine model of Chagas cardiomyopathy. C57BL/6 mice were infected with 500 trypomastigotes of the Colombian strain of T. cruzi and treated with an oral dose of simvastatin (20 mg/Kg/day) for one month and inflammatory and morphometric parameters were subsequently evaluated in the serum and in the heart, respectively. Simvastatin reduced the total cholesterol and inflammatory mediators (interferon-gamma, tumour necrosis factor-alpha, CCL2 and CCL5) in the serum and in the heart tissue at 30 days post-infection. Additionally, a proportional reduction in heart weight and inflammatory infiltration was observed. Simvastatin also reduced epimastigote proliferation in a dose-dependent manner in vitro and was able to reduce blood trypomastigotes and heart amastigote nests during the acute phase of Chagas disease in vivo. Based on these data, we conclude that simvastatin exerts a modulatory effect on the inflammatory mediators that are elicited by the Colombian strain of T. cruzi and ameliorates the heart damage that is observed in a murine model of Chagas disease.

In vivo assessment of antiretroviral therapy-associated side effects

Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI) indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs.

Componentes da síndrome metabólica na hipertensão arterial

Este estudo teve como objetivo identificar e comparar a prevalência da síndrome metabólica entre hipertensos e normotensos. Os aspectos adotados para a definição de síndrome metabólica foram os definidos pelo National Cholesterol Education Program/Adults Treatment Painel (NCEP-ATP III). Os dados referentes aos perfis clínicos e bioquímicos foram processados no programa SPSS para cálculo de frequências absolutas e porcentagens. Utilizou-se o teste t de Student para comparações das médias, sendo as diferenças consideradas estatisticamente significantes para p<0,05. A amostra foi composta por 93 participantes normotensos e 168 hipertensos. Identificou-se a presença de síndrome metabólica em 60,7% dos hipertensos e 18,3% dos normotensos. Os portadores de hipertensão arterial apresentam diferença significante nos valores de pressão arterial (p<0,001), circunferência abdominal (p<0,001), glicemia (p<0,05) e triglicérides plasmáticos (p<0,05). A frequência dos riscos cardiometabólicos associados à síndrome metabólica é maior na presença de doença hipertensiva.

Health indicators associated with poor sleep quality among university students

Objective To associate the sleep quality of Brazilian undergraduate students with health indicators. Method A cross-sectional study was developed with a random sample of 662 undergraduate students from Fortaleza, Brazil. The demographic data, Pittsburgh Sleep Quality Index and health data indicators (smoking, alcoholism, sedentary lifestyle, nutritional condition and serum cholesterol) were collected through a self-administered questionnaire. Blood was collected at a clinical laboratory. In order to estimate the size of the associations, a Poisson Regression was used. Results For students who are daily smokers, the occurrence of poor sleep was higher than in non-smokers (p<0.001). Prevalence rate values were nevertheless close to 1. Conclusion The likelihood of poor sleep is almost the same in smokers and in alcoholics.


Adherence to nutritional recommendations and sociodemographic variables in patients with diabetes mellitus

OBJECTIVETo determine if there is a relationship between adherence to nutritional recommendations and sociodemographic variables in Brazilian patients with type 2 diabetes mellitus.METHODSCross-sectional observational study using a stratified random sample of 423 individuals. The Food Frequency Questionnaire (FFQ) was used, and the Fisher's exact test was applied with 95% confidence interval (p<0.05).RESULTSOf the 423 subjects, 66.7% were women, mean age of 62.4 years (SD = 11.8), 4.3 years of schooling on average (SD = 3.6) and family income of less than two minimum wages. There was association between the female gender and adherence to diet with adequate cholesterol content (OR: 2.03; CI: 1.23; 3.34), between four and more years of education and adherence to fractionation of meals (OR: 1 92 CI: 1.19; 3.10), and income of less than two minimum wages and adherence to diet with adequate cholesterol content (OR: 1.74; CI: 1.03, 2.95).CONCLUSIONAdherence to nutritional recommendations was associated with the female gender, more than four years of education and family income of less than two minimum wages.