Biodistribution of samarium-153-EDTMP in rats treated with docetaxel

Purpose: Many patients with metastatic bone disease have to use radiopharmaceuticals associated with chemotherapy to relieve bone pain. The aim of this study was to assess the influence of docetaxel on the biodistribution of samarium-153-EDTMP in bones and other organs of rats. Methods: Wistar male rats were randomly allocated into 2 groups of 6 rats each. The DS (docetaxel/samarium) group received docetaxel (15 mg/kg) intraperitoneally in two cycles 11 days apart. The S (samarium/control) group rats were not treated with docetaxel. Nine days after chemotherapy, all the rats were injected with 0.1ml of samarium-153-EDTMP via orbital plexus (25μCi). After 2 hours, the animals were killed and samples of the brain, thyroid, lung, heart, stomach, colon, liver, kidney and both femurs were removed. The percentage radioactivity of each sample (% ATI/g) was determined in an automatic gamma-counter (Wizard-1470, Perkin-Elmer, Finland). Results: On the 9th day after the administration of the 2nd chemotherapy cycle, the rats had a significant weight loss (314.50±22.09g) compared (p<0.5) to pre-treatment weight (353.66± 22.8). The % ATI/g in the samples of rats treated with samarium-153-EDTMP had a significant reduction in the right femur, left femur, kidney, liver and lungs of animals treated with docetaxel, compared to the control rats. Conclusion: The combination of docetaxel and samarium-153-EDTMP was associated with a lower response rate in the biodistribution of the radiopharmaceutical to targeted tissues. Further investigation into the impact of docetaxel on biodistribution of samarium-153-EDTMP would complement the findings of this study

Bacterial translocation in rats nonfunctioning diverted distal colon

To investigate whether the alterations of the diverted colon segment mucosa, evidenced in fecal colitis, would be able to alter Bacterial Translocation (BT). Methods: Sixty-two Wistar male rats ranging from 220 to 320 grams of weight, were divided in two groups: A (Colostomy) and B (Control), with 31 animals each one. In group A, all animals underwent end colostomy, one stoma, in ascending colon; and in the 70th POD was injected in five rats, by rectal route – diverted segment - 2ml of a 0.9% saline solution in animals (A1 subgroup); in eight it was inoculated, by rectal route, 2ml of a solution containing Escherichia coli ATCC 25922 (American Type Culture Collection), in a concentration of 108 Colony Forming Unit for milliliters (CFU/ml) - A2 Subgroup; in ten animals the same solution of E. coli was inoculated, in a concentration of 1011 CFU/ml (A3 Subgroup); and in eight it was collected part of the mucus found in the diverted distal colonic segment for neutral sugars and total proteins dosage (A4 subgroup). The animals from the group B underwent the same procedures of group A, but with differences in the colostomy confection. In rats from subgroups A1, A2, A3, B1, B2, and B3 2ml of blood were aspirated from the heart, and fragments from mesenteric lymphatic nodule, liver, spleen, lung and kidney taken for microbiological analysis, after their death. This analysis consisted of evidencing the presence of E. coli ATCC 25922 CFU. Mann-Whitney and ANOVA Tests were applied as analytic techniques for association of variables. Results: The occurrence of BT was evidenced only in those animals in which inoculated concentration of E. coli ATCC 25922, reached levels of 1011CFU/ml, i.e. in Subgroups A3 and B3, although, being significantly greater (80%) in those animals without colostomy (subgroup B3) when compared to the ones with colostomy (20%) from the subgroup A3 (P <0.05). Lung, liver and mesenteric lymphatic nodules were the tissues with larger percentile of bacterial recovery, so much in subgroup A3, as in B3. Blood culture was considered positive in 60% of the animals from subgroup B3 and in 10% of those from subgroup A3 (p <0.05). There was greater concentration of neutral sugars, in subgroup A4 - mean 27.3mg/ml -, than in subgroup B4 - mean 8.4mg/ml - (P <0.05). Conclusion: The modifications in the architecture of intestinal mucosa in colitis following fecal diversion can cause alterations in the intestinal barrier, but it does not necessarily lead to an increased frequency of BT

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.

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.

Behavioral and neuroendocrine effects of the exposure to chronic restraint or variable stress in early adolescent rats

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

Involvement of the cholinergic pathway in glucocorticoid-induced hyperinsulinemia in rats

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

Lapachol Induces Clastogenic Effects in Rats

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

Malignant lesions in the ventral prostate of alloxan-induced diabetic rats

The aim of this study was to evaluate the changes caused by chronic diabetes in the rat ventral prostate and to establish a correlation between diabetes and the development of prostatic lesions. Male rats received alloxan (42 mg/kg b.w.) to induce diabetes. Ninety days after diabetes diagnosis, animals were sacrificed and the ventral prostate was removed and prepared for general and immunohistochemical analyses. The total area showing different types of lesions was estimated. Diabetes led to a decrease in the body and prostatic weights, as well as in testosterone levels. The prostate morphology and stereology showed high variation in the diabetic group. Some animals had light changes; the great majority had an intense epithelial atrophy; and other rats showed premalignant and malignant lesions in the prostate. Such epithelial atrophy was, in some samples, combined with chronic inflammation, similar to proliferative inflammatory atrophy (PIA). The diabetic group also presented high incidence of prostatitis, adenocarcinoma and prostatic intra-epithelial neoplasia (PIN). Samples with adenocarcinoma had poorly differentiated acini with high levels of cellular proliferation and nuclear atypia. These lesions exhibited an invasive feature showing Bcl-2-positive cells and interruptions in the basement membrane. An association of PIA, PIN and adenocarcinoma was detected in one sample. Reduced androgen levels have a synergic effect to insulin dysfunction promoting negative effects in the rat prostate. Diabetic individuals had a high incidence of prostatitis, and this inflammation could stimulate the incidence of other forms of prostatic pathology.

Exercise Training and Caloric Restriction Prevent Reduction in Cardiac Ca2+-Handling Protein Profile in Obese Rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Can vitamins C and E restore the androgen level and hypersensitivity of the vas deferens in hyperglycemic rats?

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Evaluation of low intensity laser's action on silicone mammary implant pseudocapsules in rats

OBJETIVO: Avaliar o efeito do laser de baixa intensidade sobre a contração da pseudocápsula que ocorre ao redor de implantes de silicone. MÉTODOS: 60 ratos machos divididos em dois grupos receberam implante de silicone. Grupo I: implante no subcutâneo da região dorsal, sem tratamento após a cirurgia; Grupo II: animais receberam sete sessões de irradiação com laser de baixa intensidade após o implante. Trinta, 60 e 180 dias após a cirurgia, foi feita a tonometria dos implantes, em seguida, os animais foram sacrificados, removendo-se o material de estudo que foi preparado para exame histológico, avaliando-se morfometricamente a espessura da pseudocápsula e a reação inflamatória. A análise estatistica pela técnica da Análise de Variância e Teste de Tukey (P<0.0 5). RESULTADOS: Pressões significativamente menores foram encontradas nos animais do grupo Grupo II. O estudo histológico não mostrou diferença significativa entre os grupos, destacando-se apenas maior quantidade de vasos intumescidos no Grupo II. A espessura da pseudocápsula foi menor no Grupo II. CONCLUSÃO: O laser de baixa intensidade altera o processo de reparação tecidual ao redor dos implantes, sugerindo que o mesmo possa ser útil para a modelação das contraturas que se estabelecem ao redor dos implantes de silicone.

Tomato-oleoresin supplement prevents doxorubicin-induced cardiac myocyte oxidative DNA damage in rats

Doxorubicin (DOX) is an efficient chemotherapeutic agent used against several types of tumors; however, its use is limited due to severe cardiotoxicity. Since it is accepted that reactive oxygen species are involved in DOX-induced cardiotoxicity, antioxidant agents have been used to attenuate its side effects. To determine tomato-oleoresin protection against cardiac oxidative DNA damage induced by DOX, we distributed Wistar male rats in control (C), lycopene (L), DOX (D) and DOX+lycopene (DL) groups. They received corn oil (C, D) or tomato-oleoresin (5 mg/kg body wt. day) (L, DL) by gavage for a 7-week period. They also received saline (C, L) or DOX (4 ma/kg body wt.) (D, DL) intraperitoneally at the 3rd, 4th, 5th, and at 6th week. Lycopene absorption was checked by HPLC. Cardiac oxidative DNA damage was evaluated by the alkaline Comet assay using formamidopyrimidine-DNA glycosylase (FPG) and endonuclease III (endo 111). Cardiomyocyte levels of SBs, SBs FPG and SBs Endo III were higher in rats from D when compared to other groups. DNA damage levels in cardiomyocytes from DL were not different when compared to C and L groups. The viability of cardiomyocytes from D or DL was lower than C or L groups (p < 0.01). Lycopene levels (mean +/- S.D. nmol/kg) in saponified hearts were similar between L (47.43 +/- 11.78) and DL (49.85 +/- 16.24) groups. Our results showed: (1) lycopene absorption was confirmed by its cardiac levels; (2) DOX-induced oxidative DNA damage in cardiomyocyte; (3) tomato-oleoresin supplementation protected against cardiomyocyte oxidative DNA damage. (c) 2007 Elsevier B.V. All rights reserved.

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

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

Gastric proliferative lesions induced by duodenogastric reflux in rats

OBJETIVO: Avaliar as lesões proliferativas que se desenvolvem na mucosa gástrica de ratos Wistar após modelo específico de refluxo duodeno-gástrico. MÉTODOS: Foram utilizados 75 ratos adultos machos divididos em três grupos experimentais: o grupo I (controle) submetido a gastrotomia na parede posterior do estômago glandular (25 animais); o grupo II (RDG), foi submetido a gastrojejunoanastomose látero-lateral na parede posterior do estômago glandular (25 animais) e o grupo III (RDG-P) submetido a gastrojejunoanastomose látero-lateral na parede posterior do estômago glandular, com secção e fechamento da alça (25 animais). Os animais foram observados durante 36 semanas, após o que foram realizados estudos macroscópicos e microscópicos da anastomose gastrojejunal, da região pré-pilórica e região escamosa do estômago. RESULTADOS: Os animais do Grupo I não apresentaram nenhum tipo de lesão. No grupo II observou-se 40% de lesões do tipo hiperplasia adenomatosa na anastomose e 12% de hiperplasia escamosa. No grupo III obteve-se 40% de hiperplasia adenomatosa na mucosa pré-pilórica, 72 % de hiperplasia adenomatosa na mucosa da anastomose, 20% de hiperplasia escamosa e 12 % de adenocarcinoma. CONCLUSÕES: O refluxo duodeno-gástrico induz a alta freqüência de lesões proliferativas na mucosa adjacente à anastomose gastrojejunal ou na mucosa pré-pilórica e o adenocarcinoma é um evento raro neste modelo experimental.