Prevention of bacterial translocation using β-(1-3)-D-glucan in small bowel ischemia and reperfusion in rats

To investigate the role of β-(1-3)-D-glucan on 99mTc labelled Escherichia coli translocation and cytokines secretion in rats submitted to small bowel ischemia/reperfusion injury. Methods: Five groups (n=10 each) of Wistar rats were subjected to control(C), sham(S), group IR subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R), and group I/R+glucan subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R) and injected with 2mg/Kg intramuscular. Translocation of labelled bacteria to mesenteric lymph nodes, liver, spleen, lung and serum was determined using radioactivity/count and colony forming units/g(CFU/g). Serum TNFα, IL-1β, IL-6, IL-10 were measured by ELISA. Results: CFU/g and radioactivity/count were higher in I/R than in I/R+glucan rats. In C, S and S+glucan groups, bacteria and radioactivity/count were rarely detected. The I/R+glucan rats had enhancement of IL-10 and suppressed production of serum TNFα, IL-1β and, IL-6, compared to I/R untreated animals. Conclusion: The β-(1-3)-D-glucan modulated the production of pro-inflammatory and anti-inflammatory cytokines during bowel ischemia/reperfusion, and attenuated translocation of labelled bacteria

Atividade antiplasmódica e toxicológica de plantas medicinais usadas popularmente no Brasil : uma abordagem etnobotânica

Malaria is a disease of global distribution, recognized by governments around the world as a serious public health problem, affecting more than 109 countries and territories and endangering more than 3.3 billion people. The economic costs of this disease are also relevant: the African continent itself has malaria-related costs of about $ 12 billion annually. Nowadays, in addition to chloroquine, Plasmodium falciparum is resistant to many drugs used in the treatment of malaria, such as amodiaquine, mefloquine, quinine and sulfadoxine-pyrimethamine; resistance of Plasmodium vivax to treatments, although less studied, is also reported. Nature, in general, is responsible for the production of most known organic substances, and the plant kingdom is responsible for the most of the chemical diversity known and reported in the literature. Most medicinal plants commercialized in Brazil, however, are of exotic origin, which makes the search for endemic medicinal plants, besides a patent necessity, a fascinating subject of academic research and development. This study aimed to: (i) verify the antimalarial activity of ethanolic and hydroalcoholic extracts of Boerhavia paniculata Rich. And acetonic extract of Clethra scabra Pers. in Swiss albino mice infected by Plasmodium berghei NK65, (ii) observe possible combined effects between the course of infection by P. berghei NK65 and administration of these extracts in Swiss albino mice, and (iii) conduct a preliminary study of the acute toxicity of these extracts in Swiss albino mice. All extracts notable pharmacological activities - with parasite infections inhibitions ranging from 22% to 54%.These characteristics suggest that the activities are relevant, although comparatively lower than the activity displayed by the positive control group (always above 90%). The general framework of survival analysis demonstrates an overall reduction in survival times for all groups. Necroscopy has not pointed no change in color, shape, size and/or consistency in the evaluated organs - the only exception was the livers of rats submitted to treatment to hydroalcoholic extracts: these organs have been presented in a slightly congestive aspect with mass increasing roughly 28% higher than the other two groups and a p-value of 0.0365. The 250 mg/Kg ethanolic group has been pointed out by the Dunn s post test, as the only class with simultaneous inequalities (p<0.05) between positive and negative control groups. The extracts, notably ethanol extract, have, in fact, a vestigial antimalarial activity, although well below from the ones perceived to chloroquine-treated groups; nevertheless, the survival times of the animals fed with the extracts do not rise by presence of such therapy. Both the toxicopharmacological studies of the synergism between the clinical course of malaria and administration of extracts and the isolated evaluation of toxicity allow us to affirm the absence of toxicity of the extracts at the level of CNS and ANS, as well as their non-influence on food and water consumption patterns, until dosages of 500 mg/Kg. Necroscopic analysis leads us to deduct a possible hepatotoxic effect of hydroalcoholic extract at dosages of 500 mg/Kg, and an innocuous tissue activity of the ethanol extract, in the same dosage. We propose a continuation of the studies of these extracts, with protocol modifications capable of addressing more clearly and objectively their pharmacological and toxicological aspects

Circulating leukocyte heat shock protein 70 (HSP70) and oxidative stress markers in rats after a bout of exhaustive exercise

A novel method to measure oxidative stress resulting from exhaustive exercise in rats is presented. In this new procedure we evaluated the erythrocyte antioxidant enzymes, catalase ( CAT) and glutathione reductase (GR), the plasma oxidative attack markers, reactive carbonyl derivatives (RCD) and thiobarbituric reactive substances (TBARS). Muscular tissue damage was evaluated by monitoring plasma creatine kinase (CK) and plasma taurine ( Tau) concentrations. Also, we monitored total sulphydryl groups (TSG) and uric acid (UA), and the level of the 70 kDa heat shock protein (HSP70) in leukocytes as a marker of oxidative stress. In the study we found a correspondence between erythrocyte CAT and GR activities and leukocyte HSP70 levels, principally 3 h after the acute exercise, and this suggested an integrated mechanism of antioxidant defense. The increase in levels of plasma Tau was coincident with the increasing plasma levels of CK and TBARS, principally after two hours of exercise. Thus tissue damage occurred before the expression of any anti-oxidant system markers and the monitoring of Tau, CK or TBARS may be important for the estimation of oxidative stress during exhaustive exercise. Furthermore, the integrated analyses could be of value in a clinical setting to quantify the extent of oxidative stress risk and reduce the need to perform muscle biopsies as a tool of clinical evaluation.

Effects of elevated calcium on motor and exploratory activities of rats

The effects of serum and brain calcium concentration on rat behavior were tested by maintaining animals on either distilled water (N = 60) or water containing 1% calcium gluconate (N = 60) for 3 days. Animals that were maintained on high calcium drinking water presented increased serum calcium levels (control = 10.12 ± 0.46 vs calcium treated = 11.62 ± 0.51 µg/dl). Increase of brain calcium levels was not statistically significant. In the behavioral experiments each rat was used for only one test. Rats that were maintained on high calcium drinking water showed increased open-field behavior of ambulation (20.68%) and rearing (64.57%). on the hole-board, calcium-supplemented animals showed increased head-dip (67%) and head-dipping (126%), suggesting increased ambulatory and exploratory behavior. The time of social interaction was normal in animals maintained on drinking water containing added calcium. Rats supplemented with calcium and submitted to elevated plus-maze tests showed a normal status of anxiety and elevated locomotor activity. We conclude that elevated levels of calcium enhance motor and exploratory behavior of rats without inducing other behavioral alterations. These data suggest the need for a more detailed analysis of several current proposals for the use of calcium therapy in humans, for example in altered blood pressure states, bone mineral metabolism disorders in the elderly, hypocalcemic states, and athletic activities.

Effect of heat stress or lipopolysaccharide (E-coli) injection on HSP70 levels in the liver and brain of adrenalectomized rats

Hsp70 content (ng Hsp70 mu g total protein(-1)) in the liver and brain of control and adrenalectomized male rats was investigated by Western Blotting after heat stress (40 degrees C) or endotoxin-induced fever (E. coli lipopolysaccharide injection). The increase in rectal temperature was higher after heat stress than after LPS injection, Heat stress affected Hsp70 content of the liver, but not of the brain; however adrenalectomy did not influence any parameter. These results suggest that, under these circumstances, there is no relationship between the hypothalamic-pituitary-adrenal axis and Hsp70 synthesis in liver and brain. (C) 2000 Elsevier B.V. Ltd. All rights reserved.

Hypercapnic ventilatory response of anesthetized female rats subjected to neonatal maternal separation: Insight into the origins of panic attacks?

Neonatal maternal separation (NMS) is a form of stress that interferes with the regulation of the stress response, an effect that predisposes to the emergence of panic and anxiety related disorders. We previously showed that at adulthood, awake female (but not male) rats subjected to NMS show a hypercapnic ventilatory response (HCVR; 5% CO(2)) that is 63% greater than controls (Genest et al., 2007). To understand the mechanisms underlying the sex-specific effects of NMS on the ventilatory response to CO(2), we used two different anesthetized female rat preparations to assess central CO(2) chemosensitivity and contribution of sensory afferents (stretch receptors and peripheral chemoreceptors) that influence the HCVR. Data show that anesthesia eliminated the respiratory phenotype observed previously in awake females and CO(2) chemosensitivity did not differ between groups. Finally, the assessment of the ovarian hormone levels across the oestrus cycle failed to reveal significant differences between groups. Since anesthesia did not affect the manifestation of NMS-related respiratory dysfunction in males (including the hypercapnic ventilatory response) (Kinkead et al., 2005; Dumont and Kinkead, 2010), we propose that the panic or anxiety induced by CO(2) during wakefulness is responsible for enhancement of the HCVR in NMS females. (C) 2011 Elsevier B.V. All rights reserved.

Opioid mu-receptors in the rostral medullary raphe modulate hypoxia-induced hyperpnea in unanesthetized rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

CONTROL of THE CENTRAL CHEMOREFLEX BY A5 NORADRENERGIC NEURONS IN RATS

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chloramphenicol restores the polymorphonuclear accumulation in carrageenin-induced pleurisy in diabetic rats

Investigou-se o efeito do succinato de cloranfenicol (30 mg/kg, a cada 12 h, durante 4 dias, IP) sobre o acúmulo de leucócitos polimorfonucleares (PMN) na pleurisia induzida pela carragenina (150 mig) em ratos (Wistar, machos, 180-230 g, n = 12) diabéticos (40 mg/kg de aloxana, IV). O antibiótico produziu aumento de 36% no número de PMN (p<0,05) migrados para a cavidade pleural de animais normais. O estado diabético provocou redução de 45% dos PMN (p<0,05) acumulados no exsudato pleural de animais não tratados com o antibiótico. Por outro lado, animais diabéticos tratados com succinato de cloranfenicol apresentaram resposta de PMN que não diferiu estatisticamente do observado em animais controle, não tratados. A contagem total e diferencial dos leucócitos circulantes realizada antes e 4 h depois da aplicação da carragenina não diferiu estatisticamente entre os grupos.

Hepatoprotective treatment attenuates oxidative damages induced by carbon tetrachloride in rats

The present study evaluated the hepatoprotective effect of an N-acetyl or-methionine + choline chloride + caffeine + thiamine hydrochloride + nicotinamide + pyridoxine hydrochloride compound at doses of 0.2, 0.6 and 1.0 mL/kg of b.w., and the assessment was done by the investigation of serum-enzymatic activity, metabolic functions of the liver and histophatological changes in female Wistar rats, which were subjected to experimental intoxication with CCl4. One hundred and nineteen rats were randomly distributed into 17 groups, performing five different treatments, being evaluated seven animals per treatment in four periods: 2, 4, 6 and 8 days after CCl4-induced intoxication. Treated rats with the hepatoprotective medicine (HM) presented a significant reduction in infiltration of inflammatory cells, steatosis, necrosis and liver congestion when compared to non-treated rats (control). Beside these results, the treatment showed a positive effect on circulatory alterations in the intoxicated animals, with reduction of spleen and renal congestion, as well as, promotion of a significant improvement in ALT, AST, LDH, ALP, GGT enzymatic serum activity reduction and in recovering liver function regarding the metabolism of urea, triglycerides and glucose. These findings indicate therapeutic usefulness of the compound when administered at dose 0.6 and 1.0 mL/kg of b.w. in female Wistar rats. (C) 2010 Elsevier GmbH. All rights reserved.

Involvement of nitric oxide in the gastroprotective effects of an aqueous extract of Pfaffia glomerata (Spreng) Pedersen, Amaranthaceae, in rats

The plants belonging to Pfaffia genus are used in folk medicine to treat gastric disturbances. This study examined the effects of an aqueous extract of Pfaffia glomerata (Spreng) Pedersen (AEP) on the gastrointestinal tract. Wistar rats were pretreated orally (p.o.) with the AEP (125, 250, 500 and 1000 mg.kg(-1)) before induction of ulcers by hypothermic restraint stress (HRS, 3 h restraint stress at 4 degreesC), ethanol (ET, 70%; 0.5 ml/animal; p.o.) or indomethacin (IND, 20 mg.kg(-1); s.c.). Control animals received water (C) or ranitidine (60 mg.kg(-1)) p.o. The AEP protected rats against HRS and ET-induced ulcers, but was not able to protect the gastric mucosa against IND-induced ulcers. When injected into the duodenal lumen, the AEP reduced total acidity and both basal and histamine-stimulated acid secretion in pylorus-ligated rats. In addition, gastric secretion from AEP-treated animals exhibited increased concentrations of nitrite and nitrate. Treatment of animals with L-NAME (120 mg.kg(-1), p.o.) prevented both the reduction of total acidity and the increase in NO, levels promoted by AEP treatment. In conclusion, AEP effectively protected the gastric mucosa and inhibited gastric acid secretion in rats, probably by involving the histaminergic pathway and an enhanced production of nitric oxide in the stomach. (C) 2003 Elsevier B.V. All rights reserved.

Longitudinal study of daily variation of rats' behavior in the elevated plus-maze

We conducted a longitudinal study about daily variation of Wistar male rats' behavior in the elevated plus-maze (EPM) evaluated in the 1st, 2nd, 3rd, 6th, 12th, and 18th months of life. Animals were submitted to the plus-maze in 12 sessions at 2-h intervals (n=72, 6 per time point). Spontaneous rest-activity rhythm of four animals was assessed by observation of 24-h videotape records. Time series were analyzed by Cosinor method. Behavioral rates on the six occasions and in light and dark phases were compared by means of two-way ANOVA with repeated measures. Exploratory behavior in EPM was smaller in the light phase and in older animals. Higher values of open and closed arms exploration were observed in the first and third months of the dark phase, and in the first month of the light phase. Adjustment to the 24-h period was significant at all stages for rest-activity data, number of entries in closed arms, and time on center, and for three to five stages for open-arm exploration. In general, 24 h variability was more pronounced in younger animals compared with older ones. The present study showed that: (1) a significant amount of total variability of the behavioral indexes analyzed could be attributed to 24 h variation, (2) light/dark phases differences in EPM exploration were present at all developmental stages, (3) older Wistar rats explored less the EPM and were less active in their home cage compared with younger ones, and (4) behavioral indexes (EPM) decrease was phase related and partially related to a reorganization of rest-activity rhythm. (C) 2003 Elsevier B.V. All rights reserved.

Histological assessment of ovaries and uterus of rats subjected to nandrolone decanoate treatment

This study aimed to analyze the effects of nandrolone decanoate on the ovaries and uterus of adult females rats. This drug was administered intraperitoneally, at one, two and three doses of 3 mg nandrolone decanoate/kg of body weight, respectively, in the first, second and third week of treatment. The females of the control group received a physiological solution. The rats treated with nandrolone decanoate showed estral acyclicity and there was destruction of follicular units and an absence of corpus luteum in the ovaries. In the uterus, the drug promoted morphological alterations, characterized by vacuolated epithelium and endometrial stroma fibrosis. Ovary, uterus and pituitary weights were not affected by the steroid treatment. Nandrolone decanoate affects the sexual cycle and promotes histological alterations in the ovaries and uterus of adult female rats. (C) 2005 Elsevier B.V. All rights reserved.