Direct effects of colchicine on myocardial function - Studies in hypertrophied and failing spontaneously hypertensive rats

The aging spontaneously hypertensive rat (SHR) is a model in which the transition from chronic stable left ventricular hypertrophy to overt heart failure can be observed. Although the mechanisms for impaired function in hypertrophied and failing cardiac muscle from the SHR have been studied, none accounts fully for the myocardial contractile abnormalities. The cardiac cytoskeleton has been implicated as a possible cause for myocardial dysfunction. If an increase in microtubules contributes to dysfunction, then myocardial microtubule disruption by colchicine should promote an improvement in cardiac performance. We studied the active and passive properties of isolated left ventricular papillary muscles from 18- to 24-month-old SHR with evidence of heart failure (SHR-F, n=6), age-matched SHR without heart failure (SHR-NF, n=6), and age-matched normotensive Wistar-Kyoto rats (WKY, n=5). Mechanical parameters were analyzed before and up to 90 minutes after the addition of colchicine (10(-5), 10(-4), and 10(-3) mol/L). In the baseline state, active tension (AT) developed by papillary muscles from the WKY group was greater than for SHR-NF and SHR-F groups (WKY 5.69+/-1.47 g/mm(2) [mean+/-SD], SHR-NF 3.41+/-1.05, SHR-F 2.87+/-0.26; SHR-NF and SHR-F P<0.05 versus WKY rats). The passive stiffness was greater in SHR-F than in the WKY and SHR-NF groups (central segment exponential stiffness constant, K-cs: SHR-F 70+/-25, SHR-NF 44+/-17, WKY 41+/-13 [mean+/-SD]; SHR-F P<0.05 versus; SHR-NF and WKY rats). AT did not improve after 10, 20, and 30 minutes of exposure to colchicine (10(-5), 10(-4), and 10(-3) mol/L) in any group. In the SHR-F group, AT and passive stiffness did not change after 30 to 90 minutes of colchicine exposure (10(-4) mol/L). In summary, the data in this study fail to demonstrate improvement of intrinsic muscle function in SHR with heart failure after colchicine. Thus, in the SHR there is no evidence that colchicine-induced cardiac microtubular depolymerization affects the active or passive properties of hypertrophied or failing left ventricular myocardium.

Semen parameters, fertility and testosterone levels in male rats exposed prenatally to betamethasone

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Exposure time and ventricular remodeling induced by tobacco smoke exposure in rats

Background: We investigated the effects of length of exposure to tobacco smoke on the cardiac remodeling process induced by exposure to cigarette smoke in rats.Material/Methods: Rats were separated into 4 groups: nonsmoking (NS) 2 (n=25; control animals not exposed to tobacco smoke for 2 months), smoking (S)2 (n=22; rats exposed to smoke from 40 cigarettes/d for 2 months), NS6 (n=18; control animals not exposed to tobacco smoke for 6 months), and S6 (n=25; rats exposed to smoke from 40 cigarettes/d for 6 months). All animals underwent echocardiographic, isolated heart, and morphometric studies. Data were analyzed with a 2-way analysis of variance.Results: No interaction among the variables was found; this suggests that length of exposure to tobacco smoke did not influence the effects of exposure to smoke. Values for left ventricular diastolic diameter/body weight and left atrium/body weight were higher (p=0.023 and p=0.001, respectively) in smoking (S2 and S6) than in nonsmoking animals (NS2 and NS6). Left ventricular mass index was higher (p=0.048) in smoking than in nonsmoking animals. In the isovolumetrically beating ventricle, peak systolic pressure was higher (p=0.034) in smoking than in nonsmoking animals. Significantly higher values were found for left ventricular weight (p=0.017) and right ventricular weight (p=0.001) adjusted for body weight in smoking as opposed to nonsmoking animals. Systolic pressure was higher (p=0.001) in smoking (128 +/- 14 mm Hg) than in nonsmoking animals (112 +/- 11 mm Hg).Conclusions: Length of exposure to cigarette smoke did not influence cardiac remodeling caused by exposure to sm oke in rats.

Effects of uracil calculi on cell growth and apoptosis in the BBN-initiated Wistar rat urinary bladder mucosa

The different potential of initiated and non-initiated urinary bladder mucosa (UBM) to develop neoplasia was quantitatively evaluated in the male Wistar rat. Initiation of carcinogenesis was accomplished with N-butyl-N- (4-hydroxybutyl) -nitrosamine (BBN). Stimuli for cell proliferation and apoptosis were obtained by exposure followed by withdrawal of 3% Uracil in the diet. The proliferation index (PI) was estimated in UBM immunostained for the proliferating nuclear cell antigen (PCNA). The apoptotic index (AI) and the density of papillary/nodular hyperplasia (PNH) were estimated in hematoxilin-eosin stained sections. PNH was the main proliferative response to the mechanical irritation by uracil, irrespective of previous initiation with BBN. Uracil exposure induced higher PI and PNH density in the initiated rats. After uracil withdrawal, there was a significant increase of the AI in both uracil-treated groups, which correlated well to the respective PNH density. However, at the end of the experiment, PNH incidence and density were significantly higher in the BBN-initiated mucosa, which also presented 18% incidence of papillomas and 27% of carcinomas. Therefore, under prolonged uracil calculi trauma, the UBM of BBN-initiated Wistar rats gives rise to epithelial proliferative lesions that progress to neoplasia through acquired resistance to apoptosis. (C) 1999 Wiley-Liss, Inc.

EFFECTS of DIURON on MALE RAT REPRODUCTIVE ORGANS: A DEVELOPMENTAL and POSTNATAL STUDY

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

Diuron exposure induces systemic and organ-specific toxicity following acute and sub-chronic exposure in male Wistar rats

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

Effects of Lidocaine Infusion during Experimental Endotoxemia in Horses

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

Effects of neonatal castration and androgenization on sexual dimorphism in bone, leptin and corticosterone secretion

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Use of vitamin C in delayed tooth replantation

O objetivo deste trabalho foi avaliar microscopicamente, em reimplantes tardios de dentes de rato, os efeitos do tratamento da superfície radicular com diferentes soluções. Foram utilizados 30 ratos Rattus norvegicus albinos da linhagem Wistar que tiveram seus incisivos centrais extraídos e deixados sobre a bancada por 6 h. As polpas foram extirpadas e os canais irrigados com solução de hipoclorito de sódio a 1%. Após o preparo endodôntico, a superfície radicular de cada dente foi tratada com solução de hipoclorito de sódio a 1% por 10 min (trocada a cada 5 min) seguida de soro fisiológico por 10 min, e os dentes foram divididos em três grupos com 10 espécimes em cada um. Nos Grupos I, II e III, respectivamente, a superfície radicular foi tratada com fluoreto de sódio fosfato acidulado a 2%, vitamina C e vitamina C efervescente (2 g, Redoxon®). Após obturação com pasta de hidróxido de cálcio os dentes foram reimplantados e os animais foram sacrificados aos 10 e 60 dias. O Grupo I apresentou maiores áreas de reabsorção por substituição e anquilose. Comparando as formas de vitamina C utilizadas, a efervescente (Grupo III) foi a que apresentou resultados mais favoráveis com mais áreas de anquilose e reabsorção por substituição que áreas de reabsorção inflamatória.

Effects of two chronic stress models on ligature-induced periodontitis in Wistar rats

Objectives: The present study aims at comparing the effects of physical and variable chronic stress on ligature-induced periodontitis in rats.Design: Forty-eight adult Wistar rats were randomly assigned to four groups (n = 12): physical stress, variable stress, positive control and negative control. The models of physical stress were immobilization and immobilization associated with exposure to cold. The models of variable stress were exposure to intermittent light, 24 h isolation, oral cavity examination, crowded environment, smell of blood and noise. After 10 days of physical or variable stress animals underwent experimental induction of periodontal disease in one oral side. Positive control also underwent experimental induction of periodontal disease on the 10th day. Negative control did not receive any type of intervention. At the end of the experimental period (60 days), all animals were euthanized. After routine laboratory processing, images of the histological sections were digitised and submitted to histometric measurement using two parameters: histologic attachment loss and bone loss.Results: Histological attachment loss and bone loss were greater (p < 0.05) in the physical stress group than in the other groups (variable stress, positive and negative control groups). on the non-periodontitis side, these same histological parameters did not significantly differ amongst groups.Conclusions: Physical stress negatively modulated the response pattern to experimentally induced periodontitis in rats. (C) 2011 Elsevier Ltd. All rights reserved.

Saliva substitute in combination with high-concentrated fluoride toothpaste: Effects on demineralised dentin in vitro

Objectives: The aim of this in vitro study was to assess the effects of saliva substitutes (modified with respect to calcium, phosphates, and fluorides) in combination with a high-concentrated fluoride toothpaste on demineralised dentin.Methods: Before and after demineralisation of bovine dentin specimens (subsurface lesions; 37 degrees C, pH 5.0, 5 d), one-quarter of each specimen's surface was covered with nail varnish (control of sound/demineralised tissue). Subsequently, specimens were exposed to original Saliva natura (saturation with respect to octacalciumphosphate [S(OCP)]: 0.03; SN 0), or to three lab-produced Saliva natura modifications (S(OCP): 1, 2, and 3; SN 1-3) for 2 and 5 weeks (37 degrees C). An aqueous solution (S(OCP): 2.5) served as positive control (PC). Two times daily (2 min each), Duraphat toothpaste (5000 ppm F(-); Colgate)/saliva substitute slurry (ratio 1:3) was applied gently. Differences in mineral losses (Delta Delta Z) and lesion depths (Delta LD) between values before and after exposure were microradiographically evaluated.Results: After both treatment periods specimens immersed in SN 0 revealed significantly higher mineral losses (lower Delta Delta Z values) and lesion depths (lower Delta LD) compared to PC (p < 0.05; ANOVA). After 5 weeks, specimens stored in SN 1 and 2 showed significantly higher mineral losses compared to PC (p < 0.05), while those stored in SN 3 showed similar results (p > 0.05). No differences in mineral loss could be observed between SN 2 and 3 (p > 0.05).Conclusions: Under the conditions of this limited protocol, the combination of Saliva natura solutions slightly saturated with respect to OCP in combination with a high-concentrated fluoride toothpaste enabled remineralisation of dentin in vitro. Crown Copyright (c) 2009 Published by Elsevier Ltd. All rights reserved.

Structural evaluation of the effects of chronic ethanol ingestion on the testis of Calomys callosus

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

Antioxidant defense in rat brain regions after developmental lead exposure

Oxidative stress is considered a possible molecular mechanism involved in Pb neurotoxicity. Considering the vulnerability of the developing brain to Pb neurotoxicity, this study was carried out to investigate the effects of low-level developmental Pb exposure on brain regions antioxidant enzymes activities. Wister dams were exposed to 500 ppm of Pb, as Pb acetate, or to 660 ppm Na acetate in the drinking water during pregnancy and lactation. The activities of superoxide dismutase (SOD), glutathione peroxidase and glutathione reductase were determined in the hypothalamus, hippocampus and striatum of male pups at 23 (weaned) or 70 days (adult) of age. In the Pb-exposed 23-day-old pups, the activity of SOD was decreased in the hypothalamus. Regarding adults, there was no significant treatment effect in any of the enzymes and regions evaluated. Based on the present results, it seems that oxidative stress due to decreased antioxidant function may occur in weaned rats but it is suggested that this should not be the main mechanism involved in the neurotoxicity of low-level Pb exposure. (C) 2001 Elsevier B.V. Ireland Ltd. All rights reserved.

Sexual behavior, neuroendocrine, and neurochemical aspects in male rats exposed prenatally to stress

The present study was designed to examine some short- and long-term effects of maternal restraint stress-during the period of sexual brain differentiation-on reproductive and endocrine systems, sexual behavior, and brain neurotransmitters in male rat descendants. Pregnant rats were exposed to restraint stress for 1 h/day from gestational days (GDs) 18 to 22. Prenatal stress did not influence the wet weight of sexual organs and the quantity of germ cells in adult male pups; however, these animals showed reduced testosterone levels, delayed latency to the first mount and first intromission, and also decreased number of ejaculations. Additionally, there was an increase in the dopamine and serotonin levels in the striatum. Our results indicate that prenatal stress had a long-term effect on neurotransmitter levels and sexual behavior. In this sense, reproductive problems caused by injuries during the fetal period can compromise the later success of mating as well as the capacity to generate descendants. (C) 2004 Elsevier B.V. All rights reserved.

Puberty installation and adrenergic response of seminal vesicle from rats exposed prenatally to hydrocortisone

We investigated the effects of hydrocortisone during the prenatal period and its repercussion on puberty installation and adrenergic response of seminal vesicle in adult rats. The efficacy of the hydrocortisone treatment in reducing adrenal wet weight immediately after delivery in both the treated mothers and respective pups at birth may indicate impairment of the hypothalamus-pituitary-adrenal axis. This parameter was unchanged in the adult phase of these descendants, suggesting recuperation of this axis. In addition, the treatment with hydrocortisone delayed the age of puberty installation, probably by absence of both physiologic production and liberation of luteinizing hormone and testosterone. Despite the significant reduction in testosterone level as well as of wet weights of both vas deferens and testis in the adult phase, no difference was observed in the sensitivity of the seminal vesicle to the studied sympathetic agonist. However, the observed reduction in contractile response of the seminal vesicle may be a consequence of contractile-system damage in this organ. It is possible that this alteration may cause a reduction in the amount of vesicular secretion so important in the process of ejaculation. In conclusion, these results suggest that administration of hydrocortisone in late prenatal life did not influence the hypothalamus-pituitary-adrenal axis in adult life, although it altered the hypothalamus-pituitary-gonadal axis, and reduced testosterone production starting at puberty, as a consequence of an incomplete masculinization of the hypothalamus plus a reduction in the contractile response of the seminal vesicle. (c) 2005 Elsevier B.V. All rights reserved.