Genetic correlations between categorical morphological traits in Nelore cattle by applying Bayesian analysis under a threshold animal model

P>In this study, Bayesian analysis under a threshold animal model was used to estimate genetic correlations between morphological traits (body structure, finishing precocity and muscling) in Nelore cattle evaluated at weaning and yearling. Visual scores obtained from 7651 Nelore cattle at weaning and from 4155 animals at yearling, belonging to the Brazilian Nelore Program, were used. Genetic parameters for the morphological traits were estimated by two-trait Bayesian analysis under a threshold animal model. The genetic correlations between the morphological traits evaluated at two ages of the animal (weaning and yearling) were positive and high for body structure (0.91), finishing precocity (0.96) and muscling (0.94). These results indicate that the traits are mainly determined by the same set of genes of additive action and that direct selection at weaning will also result in genetic progress for the same traits at yearling. Thus, selection of the best genotypes during only one phase of life of the animal is suggested. However, genetic differences between morphological traits were better detected during the growth phase to yearling. Direct selection for body structure, finishing precocity and muscling at only one age, preferentially at yearling, is recommended as genetic differences between traits can be detected at this age.

An animal model for the study of Chamomilla in stress and depression: pilot study

The behavioral and hematological effects of treatment with Chamomilla 6cH in mice subjected to experimental stress are described. Swiss mice were randomly divided into pairs, one animal was inoculated with Ehrlich's tumor, the other was treated daily with Chamomilla 6cH or control or received no treatment. After 7 days, the animals were observed in an open-field arena and blood samples taken. Mice who cohabitated with a sick cage-mate showed a decrease in their general activity, but those treated with Chamomilla 6cH were less severely affected (p = 0.0426). No hematologicall changes were observed.In a second experiment, the forced swimming test was applied to mice pre-treated with Chamomilla 6cH, controls were: water, 10% ethanol or amitriptyline. Only the amitriptyline and ethanol treated groups showed significant excitatory behavior (p = 0.0020), Chamomilla 6cH treated animals' scores intermediate between water control and ethanol or amitriptyline. A decrease in the leukocyte count was observed in the amitriptyline and Chamomilla 6cH treated groups (p = 0.039). These data suggest that treatment with Chamomilla 6cH is related to the recovery of basal behavioral conditions in mice subjected to stressful conditions.

Fluorescence spectroscopy for tongue carcinoma detection: Study in an animal model

Fluorescence diagnosis of malignant lesions has been showed as an attractive optical technique due especially to its real-time response and a more objective and quantitative evaluation. Even though the oral cavity allows a direct examination many lesions are diagnosed when it is already in advanced stage, compromising the patient prognosis. In this study, the fluorescence spectroscopy was used to the detection of chemically induced carcinoma at the lateral border of the tongue in a hamster model. Two excitations wavelengths in visible region were applied: 442 and 532 nm. All the spectra results were analyzed comparing with the histopathological diagnosis. The better results were achieved with the 442 nm laser excitation. The spectra from carcinoma showed new emission bands and these were used to determined different ratios for a quantitative analysis. Using the 625-645 nm fluorescence range under 442 nm excitation (A3 coefficient) the percentage of false negative was of 9.1%, however the false positive percentage was of 18.5%. The 532 nm excitation provided a better normal tissue detection compared to 442 nm excitation. The ideal clinical condition is probably the use of multiple wavelengths excitation for a broader tissue fluorescence investigation.

The use of planarians as in vivo animal model to study laser biomodulation effects

A variety of effects is attributed to the photo stimulation of tissues, such as improved healing of ulcers, analgesic and anti-inflammatory effects, stimulation of the proliferation of cells of different origins and stimulation of bone repair. Some investigations that make qualitative evaluations, like wound healing and evaluation of pain and edema, can be conducted in human subjects. However, deeper investigations on the mechanisms of action of the light stimulus and other quantitative works that requires biopsies or destructive analysis has to be carried out in animal models or in cell cultures. In this work, we propose the use of planarians as a model to study laser-tissue interaction. Contrasting with cell cultures and unicellular organisms, planarians are among the simplest organism having tissue layers, central nerve system, digestive and excretory system that might have been platforms for the evolution of the complex and highly organized tissues and organs found in higher organisms. For the present study, 685 nm laser radiation was employed. Planarians were cut transversally, in a plane posterior to the auricles. The body fragments were left to regenerate and the proliferation dynamics of stem cells was studied by using histological analysis. Maximum cell count was obtained for the laser treated group at the 4th experimental day. At that experimental time, we also had the largest difference between the irradiated and the non-irradiated control group. We concluded that the studied flatworm could be an interesting animal model for in vivo studies of laser-tissue interactions.

Mechanism and effect of esculetin in an experimental animal model of inflammatory bowel disease

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

Ginkgo Biloba Extract in an Animal Model of Parkinson's Disease: A Systematic Review

Although the exact cause of neuronal loss in Parkinson's disease is not known, evidence points to oxidative stress and the production of reactive oxygen species as the main events that occur in the substantia nigra pars compacta of the brain of parkinsonians. EGb761 is an extract of the leaves from the Ginkgo biloba tree that has been reported as an antioxidant and neuroprotective agent. The objective of this work was to perform a systematic review of the studies that analysed the effect of Ginkgo biloba extract on Parkinson's disease or Parkinsonism. This research was conducted using the following databases: Medline, PsycInfo, Cinahl, Sigle, Lilacs, Scielo, Cochrane Library, and Embase. Initially, we selected 32 articles. After a more detailed analysis, only 10 articles remained. One of the hypotheses for the positive effect of EGb761 on Parkinson's disease is the reduction or inhibition of monoamine-oxidase activity. This enzyme metabolises dopamine, inducing the formation of free radicals, which in turn damage nigrostriatal neurons. Another hypothesis is that the neuroprotective effect of EGb761 against 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and MPP+ toxins. As there are few studies on the effect of EGb761 on humans, this review could contribute new data to further the discussion of this issue.

The effect of simvastatin treatment on bone repair of femoral fracture in animal model

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

Influence of a probiotic soy product on fecal microbiota and its association with cardiovascular risk factors in a animal model

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

Early detection of doxorubicin myocardial injury by ultrasonic tissue characterization in an experimental animal model

In the clinical setting, the early detection of myocardial injury induced by doxorubicin (DXR) is still considered a challenge. To assess whether ultrasonic tissue characterization (UTC) can identify early DXR-related myocardial lesions and their correlation with collagen myocardial percentages, we studied 60 rats at basal status and prospectively after 2mg/Kg/week DXR endovenous infusion. Echocardiographic examinations were conducted at baseline and at 8,10,12,14 and 16 mg/Kg DXR cumulative dose. The left ventricle ejection fraction (LVEF), shortening fraction (SF), and the UTC indices: corrected coefficient of integrated backscatter (IBS) (tissue IBS intensity/phantom IBS intensity) (CC-IBS) and the cyclic variation magnitude of this intensity curve (MCV) were measured. The variation of each parameter of study through DXR dose was expressed by the average and standard error at specific DXR dosages and those at baseline. The collagen percent (%) was calculated in six control group animals and 24 DXR group animals. CC-IBS increased (1.29 +/- 0.27 x 1.1 +/- 0.26-basal; p=0.005) and MCV decreased (9.1 +/- 2.8 x 11.02 +/- 2.6-basal; p=0.006) from 8 mg/Kg to 16mg/Kg DXR. LVEF presented only a slight but significant decrease (80.4 +/- 6.9% x 85.3 +/- 6.9%-basal, p=0.005) from 8 mg/Kg to 16 mg/Kg DXR. CC-IBS was 72.2% sensitive and 83.3% specific to detect collagen deposition of 4.24%(AUC=0.76). LVEF was not accurate to detect initial collagen deposition (AUC=0.54). In conclusion: UTC was able to early identify the DXR myocardial lesion when compared to LVEF, showing good accuracy to detect the initial collagen deposition in this experimental animal model.

Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders

Rationale Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa, possesses a large number of pharmacological effects including anticonvulsive, sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective, as demonstrated in clinical and preclinical studies. Many neurodegenerative disorders involve cognitive deficits, and this has led to interest in whether cannabidiol could be useful in the treatment of memory impairment associated to these diseases. Objectives We used an animal model of cognitive impairment induced by iron overload in order to test the effects of cannabidiol in memory-impaired rats. Methods Rats received vehicle or iron at postnatal days 12-14. At the age of 2 months, they received an acute intraperitoneal injection of vehicle or cannabidiol (5.0 or 10.0 mg/kg) immediately after the training session of the novel object recognition task. In order to investigate the effects of chronic cannabidiol, iron-treated rats received daily intraperitoneal injections of cannabidiol for 14 days. Twenty-four hours after the last injection, they were submitted to object recognition training. Retention tests were performed 24 h after training. Results A single acute injection of cannabidiol at the highest dose was able to recover memory in iron-treated rats. Chronic cannabidiol improved recognition memory in iron-treated rats. Acute or chronic cannabidiol does not affect memory in control rats. Conclusions The present findings provide evidence suggesting the potential use of cannabidiol for the treatment of cognitive decline associated with neurodegenerative disorders. Further studies, including clinical trials, are warranted to determine the usefulness of cannabidiol in humans suffering from neurodegenerative disorders.

Effects of Repeated Stress on Distal Airway Inflammation, Remodeling and Mechanics in an Animal Model of Chronic Airway Inflammation

Background/Aims: Epidemiological studies suggest that stress has an impact on asthmatic exacerbations. We evaluated if repeated stress, induced by forced swimming, modulates lung mechanics, distal airway inflammation and extracellular matrix remodeling in guinea pigs with chronic allergic inflammation. Methods: Guinea pigs were submitted to 7 ovalbumin or saline aerosols (1-5 mg/ml during 4 weeks; OVA and SAL groups). Twenty-four hours after the 4th inhalation, guinea pigs were submitted to the stress protocol 5 times a week during 2 weeks (SAL-S and OVA-S groups). Seventy-two hours after the 7th inhalation, guinea pigs were anesthetized and mechanically ventilated. Resistance and elastance of the respiratory system were obtained at baseline and after ovalbumin challenge. Lungs were removed, and inflammatory and extracellular matrix remodeling of distal airways was assessed by morphometry. Adrenals were removed and weighed. Results: The relative adrenal weight was greater in stressed guinea pigs compared to non-stressed animals (p < 0.001). Repeated stress increased the percent elastance of the respiratory system after antigen challenge and eosinophils and lymphocytes in the OVA-S compared to the OVA group (p < 0.001, p = 0.003 and p < 0.001). Neither collagen nor elastic fiber contents were modified by stress in sensitized animals. Conclusions: In this animal model, repeated stress amplified bronchoconstriction and inflammatory response in distal airways without interfering with extracellular matrix remodeling. Copyright (C) 2011 S. Karger AG, Basel

Horse spleen segmentation technique as large animal model of preclinical trials

The parenchymal distribution of the splenic artery was studied in order to obtain anatomical basis for partial splenectomy. Thirty two spleens were studied, 26 spleens of healthy horses weighing 320 to 450kg, aged 3 to 12 years and 6 spleens of fetus removed from slaughterhouse. The spleens were submitted to arteriography and scintigraphy in order to have their vascular pattern examined and compared to the external aspect of the organ aiming establish anatomo-surgical segments. All radiographs were photographed with a digital camera and the digital images were submitted to a measuring system for comparative analysis of areas of dorsal and ventral anatomo-surgical segments. Anatomical investigations into the angioarchitecture of the equine spleen showed a paucivascular area, which coincides with a thinner external area, allowing the organ to be divided in two anatomo-surgical segments of approximately 50% of the organ each.

Changes in renal glucose transporters in an animal model of metabolic syndrome

Considering the similarity between structural, hemodynamic, and functional changes of obesity-related renal disease and diabetic nephropathy, we hypothesized that renal glucose transporter changes occur in obesity as in diabetes. The aim of the work was to evaluate GLUT1 and GLUT2 in kidneys of an animal model of metabolic syndrome. Neonate spontaneously hypertensive rats (SHR), n=15/group, were treated with monosodium glutamate (5 mg/g) (MetS) for 9 days and compared with saline-treated Wistar-Kyoto (C) and SHR (H) rats. Lee index, systolic arterial pressure (SAP), glycemia, insulin resistance, triglycerides, and HDL cholesterol were evaluated at 3 and 6 months. Medullar GLUT1 and cortical GLUT2 were analyzed by Western blot. MetS vs. C and H rats had the highest Lee index (p<0.001) and insulin resistance (3-months C: 4.3±0.7, H: 3.9±0.9, MetS: 2.7±0.6; 6-months C: 4.2±0.6, H: 3.8±0.5, MetS: 2.4±0.6% • min−1, p<0.001), similar glycemia, and the lowest HDL-cholesterol at 6-months (p<0.001). In the MetS and H rats, SAP was higher vs. C at 3-months (p<0.001) and 6-months (C: 151±15, H: 190±11, MetS: 185±13 mm Hg, p<0.001) of age. GLUT1 was ̴ 13× lower (p<0.001) at 3-months, reestablishing its content at 6-months in MetS group, while GLUT2 was 2× higher (p<0.001) in this group at 6-months of age. Renal GLUT1 and GLUT2 are modulated in kidney of rats with metabolic syndrome, where obesity, insulin resistance and hypertension coexist, despite normoglycemia. Like in diabetes, cortical GLUT2 overexpression may contribute to the development of kidney disease

Changes in tumor stiffness for early prediction of tumor response to sorafenib: a proof-of-concept study with elastosonography in an animal model of Hepatocellular Carcinoma (HCC)

Background and aims: Sorafenib is the reference therapy for advanced Hepatocellular Carcinoma (HCC). No method exists to predict in the very early period subsequent individual response. Starting from the clinical experience in humans that subcutaneous metastases may rapidly change consistency under sorafenib and that elastosonography a new ultrasound based technique allows assessment of tissue stiffness, we investigated the role of elastonography in the very early prediction of tumor response to sorafenib in a HCC animal model. Methods: HCC (Huh7 cells) subcutaneous xenografting in mice was utilized. Mice were randomized to vehicle or treatment with sorafenib when tumor size was 5-10 mm. Elastosonography (Mylab 70XVG, Esaote, Genova, Italy) of the whole tumor mass on a sagittal plane with a 10 MHz linear transducer was performed at different time points from treatment start (day 0, +2, +4, +7 and +14) until mice were sacrified (day +14), with the operator blind to treatment. In order to overcome variability in absolute elasticity measurement when assessing changes over time, values were expressed in arbitrary units as relative stiffness of the tumor tissue in comparison to the stiffness of a standard reference stand-off pad lying on the skin over the tumor. Results: Sor-treated mice showed a smaller tumor size increase at day +14 in comparison to vehicle-treated (tumor volume increase +192.76% vs +747.56%, p=0.06). Among Sor-treated tumors, 6 mice showed a better response to treatment than the other 4 (increase in volume +177% vs +553%, p=0.011). At day +2, median tumor elasticity increased in Sor-treated group (+6.69%, range –30.17-+58.51%), while decreased in the vehicle group (-3.19%, range –53.32-+37.94%) leading to a significant difference in absolute values (p=0.034). From this time point onward, elasticity decreased in both groups, with similar speed over time, not being statistically different anymore. In Sor-treated mice all 6 best responders at day 14 showed an increase in elasticity at day +2 (ranging from +3.30% to +58.51%) in comparison to baseline, whereas 3 of the 4 poorer responders showed a decrease. Interestingly, these 3 tumours showed elasticity values higher than responder tumours at day 0. Conclusions: Elastosonography appears a promising non-invasive new technique for the early prediction of HCC tumor response to sorafenib. Indeed, we proved that responder tumours are characterized by an early increase in elasticity. The possibility to distinguish a priori between responders and non responders based on the higher elasticity of the latter needs to be validated in ad-hoc experiments as well as a confirmation of our results in humans is warranted.