Factors that cause genotype by environment interaction and use of a multiple-trait herd-cluster model for milk yield of Holstein cattle from Brazil and Colombia

Descriptive herd variables (DVHE) were used to explain genotype by environment interactions (G x E) for milk yield (MY) in Brazilian and Colombian production environments and to develop a herd-cluster model to estimate covariance components and genetic parameters for each herd environment group. Data consisted of 180,522 lactation records of 94,558 Holstein cows from 937 Brazilian and 400 Colombian herds. Herds in both countries were jointly grouped in thirds according to 8 DVHE: production level, phenotypic variability, age at first calving, calving interval, percentage of imported semen, lactation length, and herd size. For each DVHE, REML bivariate animal model analyses were used to estimate genetic correlations for MY between upper and lower thirds of the data. Based on estimates of genetic correlations, weights were assigned to each DVHE to group herds in a cluster analysis using the FASTCLUS procedure in SAS. Three clusters were defined, and genetic and residual variance components were heterogeneous among herd clusters. Estimates of heritability in clusters 1 and 3 were 0.28 and 0.29, respectively, but the estimate was larger (0.39) in Cluster 2. The genetic correlations of MY from different clusters ranged from 0.89 to 0.97. The herd-cluster model based on DVHE properly takes into account G x E by grouping similar environments accordingly and seems to be an alternative to simply considering country borders to distinguish between environments.

Spatial and temporal profiles for anti-inflammatory gene expression in leukocytes during a resolving model of peritonitis

The recent appreciation of the role played by endogenous counterregulatory mechanisms in controlling the outcome of the host inflammatory response requires specific analysis of their spatial and temporal profiles. In this study, we have focused on the glucocorticoid-regulated anti-inflammatory mediator annexin 1. Induction of peritonitis in wild-type mice rapidly (4 h) produced the expected signs of inflammation, including marked activation of resident cells (e.g., mast cells), migration of blood-borne leukocytes, mirrored by blood neutrophilia. These changes subsided after 48-96 h. In annexin 1null mice, the peritonitis response was exaggerated (∼40% at 4 h), with increased granulocyte migration and cytokine production. In blood leukocytes, annexin 1 gene expression was activated at 4, but not 24, h postzymosan, whereas protein levels were increased ai both time points. Locally, endothelial and mast cell annexin 1 gene expression was not detectable in basal conditions, whereas it was switched on during the inflammatory response. The significance of annexin 1 system plasticity in the anti-inflammatory properties of dexamethasone was assessed. Clear induction of annexin 1 gene in response to dexamethasone treatment was evident in the circulating and migrated leukocytes, and in connective tissue mast cells; this was associated with the steroid failure to inhibit leukocyte trafficking, cytokine synthesis, and mast cell degranulation in the annexin 1null mouse. In conclusion, understanding how inflammation is brought under control will help clarify the complex interplay between pro- and anti-inflammatory pathways operating during the host response to injury and infection. Copyright © 2006 by The American Association of Immunologists, Inc.

Maxi-K channels contribute to urinary potassium excretion in the ROMK-deficient mouse model of Type II Bartter's syndrome and in adaptation to a high-K diet

Type II Bartter's syndrome is a hereditary hypokalemic renal salt-wasting disorder caused by mutations in the ROMK channel (Kir1.1; Kcnj1), mediating potassium recycling in the thick ascending limb of Henle's loop (TAL) and potassium secretion in the distal tubule and cortical collecting duct (CCT). Newborns with Type II Bartter are transiently hyperkalemic, consistent with loss of ROMK channel function in potassium secretion in distal convoluted tubule and CCT. Yet, these infants rapidly develop persistent hypokalemia owing to increased renal potassium excretion mediated by unknown mechanisms. Here, we used free-flow micropuncture and stationary microperfusion of the late distal tubule to explore the mechanism of renal potassium wasting in the Romk-deficient, Type II Bartter's mouse. We show that potassium absorption in the loop of Henle is reduced in Romk-deficient mice and can account for a significant fraction of renal potassium loss. In addition, we show that iberiotoxin (IBTX)-sensitive, flow-stimulated maxi-K channels account for sustained potassium secretion in the late distal tubule, despite loss of ROMK function. IBTX-sensitive potassium secretion is also increased in high-potassium-adapted wild-type mice. Thus, renal potassium wasting in Type II Bartter is due to both reduced reabsorption in the TAL and K secretion by max-K channels in the late distal tubule. © 2006 International Society of Nephrology.

Experimental model of pulmonary carcinogenesis in Wistar rats

Purpose: To elaborate an experimental model of pulmonary carcinogenesis in Wistar rats. Methods: Male Rattus norvegicus albinus, Wistar lineage was carried through an intra-pulmonary instillation of the Benzo[a]pyrene (B[a]P) dilution in alcohol 70%, a polycyclic aromatic hydrocarbon widely known by its power of tumoral induction. Three experimental groups had been formed with 08 animals each: Control Group (Alcohol 70%); B[a]P Group 10 mg/kg; e B[a]P Group 20mg/ kg, submitted to euthanasia 08, 10, 12 and 14 weeks after the experimental procedure. The pulmonary sections had been colored by hematoxilin-eosin (HE) and submitted to the morphometrical analysis to describe the tissue alterations. Results: The presence of diffuse inflammatory alterations was observed in all groups, however, at the analysis of the pulmonary tissue of the experimental groups, it had been observed hyperplasic alterations (BALT hyperplasia), and in one of the animals of the experimental group 20mg/kg (12 weeks), it was noticed the presence of cellular epithelial tracheal pleomorphism, suggesting the adenocarcinoma formation in situ. Conclusion: The main secondary alterations to the intra-pulmonary instillation of B[a]P in Wistar rats were: cellular proliferation, inflammatory alterations of several degrees and nodular lymphoid hyperplasias. The association of an activator agent of the pulmonary metabolic reply is necessary to establish the ideal reply-dose to the development of the lung cancer.

Intestinal anti-inflammatory activity of coumarin and 4-hydroxycoumarin in the trinitrobenzenesulphonic acid model of rat colitis

Coumarins represent an important class of phenolic compounds with multiple biological activities, including inhibition of lipidic peroxidation and neutrophil-dependent anion superoxide generation, anti-inflammatory and immunosuppressor actions. All of these proprieties are essential for that a drug may be used in the treatment of inflammatory bowel disease. The present study examined intestinal anti-inflammatory activity of coumarin and its derivative, the 4-hydroxycoumarin on experimental ulcerative colitis in rats. This was performed in two different experimental settings, i.e. when the colonic mucosa is intact or when the mucosa is in process of recovery after an initial insult. The results obtained revealed that the coumarin and 4-hydroxycoumarin, at doses of 5 and 25 mg/kg, significantly attenuated the colonic damage induced by trinitrobenzenesulphonic acid (TNBS) in both situations, as evidenced macroscopically, microscopically and biochemically. This effect was related to an improvement in the colonic oxidative status, since coumarin and 4-hydroxycoumarin prevented the glutathione depletion that occurred as a consequence of the colonic inflammation. © 2008 Pharmaceutical Society of Japan.

Test-day model for milk yield of dairy buffaloes in colombia

The test-day model is the preferred method for genetic evaluations in dairy cattle. For this study, 28372 test-day records of 1220 lactations from 1997 to 2009 were used. The (co)variance components for milk in test-day were estimated using a Uni and multiple-traits repeated animal model with the Restricted Maximum Likelihood method (REML). The Contemporary Group (herd, year, and season of parity) and the age of parity (linear and quadratic) fixed effects, and the additive genetic, permanent environmental, and residual random effects were included in the model. The heritabilities ranged between 0.06 and 0.45 during lactation. The genetic correlations were greater than 0.93. In conclusion, the test-day model is appropriate for the genetic evaluation of dairy buffaloes in Colombia.

Anti-nociceptive effects of Carpolobia lutea G. Don (Polygalaceae) leaf fractions in animal models

Leaves from Carpolobia lutea (Polygalaceae) were screened to establish the antiulcer ethnomedicinal claim and to quantitatively isolate, elucidate the active compounds by semi-preparative HPLC. The anti-nociceptive effects of Carpolobia lutea (CL) G. Don (Polygalaceae) organic leaf extracts were tested in experimental models in mice. The anti-nociceptive mechanism was determined using tail-flick test, acetic acid-induced abdominal constrictions, formalin-induced hind paw licking and the hot plate test. The fractions (ethanol, ethyl acetate, chloroform, n-hexane) and crude ethyl acetate extract of CL (770 mg/kg, i.p.) produced significant inhibitions of both phases of the formalin-induced pain in mice, a reduction in acetic acid-induced writhing as well as and an elevation of the pain threshold in the hot plate test in mice. The inhibitions were greater to those produced by indomethacin (5 mg/kg, i.p.). Ethyl acetate fraction revealed cinnamic and coumaric acids derivatives, which are described for the first time in literature. These cinnamalglucosides polyphenols characterised from CL may in part account for the pharmacological activities. These findings confirm its ethnomedical use in anti-inflammatory pain and in pains from gastric ulcer-associated symptoms. © 2011 Springer Basel AG.

Importância do modelo animal para testar hipóteses sobre a fisiopatologia do binômio diabetes e incontinência urinária feminina

Aims: To discuss the importance of studying animal models to test hypotheses about the mechanisms of urinary continence and pathophysiology of diabetes and urinary incontinence. Source of Data: A literature review was conducted in PubMed and SciELO. The key words used were diabetes, urinary incontinence, urethra, human and rats. Summary of Findings: There is a strong relation between the genesis of urinary incontinence and diabetes mellitus. Due to the similarity of normal distribution of skeletal muscle and urethra anatomy between humans and rats, these animal models have been used in current research about these disorders. Conclusions: The use of rats as an animal model is suitable for experimental studies that test hypotheses about the mechanisms of continence and pathophysiology of the binomial diabetes mellitus and urinary incontinence, thus enabling solutions of great value in clinical practice.

Continuous measurement of cerebral oxygen saturation (rSO 2) for assessment of cardiovascular status during hemorrhagic shock in a swine model

Background: Early trauma care is dependent on subjective assessments and sporadic vital sign assessments. We hypothesized that near-infrared spectroscopy-measured cerebral oxygenation (regional oxygen saturation [rSO 2]) would provide a tool to detect cardiovascular compromise during active hemorrhage. We compared rSO 2 with invasively measured mixed venous oxygen saturation (SvO2), mean arterial pressure (MAP), cardiac output, heart rate, and calculated pulse pressure. Methods: Six propofol-anesthetized instrumented swine were subjected to a fixed-rate hemorrhage until cardiovascular collapse. rSO 2 was monitored with noninvasively measured cerebral oximetry; SvO2 was measured with a fiber optic pulmonary arterial catheter. As an assessment of the time responsiveness of each variable, we recorded minutes from start of the hemorrhage for each variable achieving a 5%, 10%, 15%, and 20% change compared with baseline. Results: Mean time to cardiovascular collapse was 35 minutes ± 11 minutes (54 ± 17% total blood volume). Cerebral rSO 2 began a steady decline at an average MAP of 78 mm Hg ± 17 mm Hg, well above the expected autoregulatory threshold of cerebral blood flow. The 5%, 10%, and 15% decreases in rSO 2 during hemorrhage occurred at a similar times to SvO2, but rSO 2 lagged 6 minutes behind the equivalent percentage decreases in MAP. There was a higher correlation between rSO 2 versus MAP (R =0.72) than SvO2 versus MAP (R =0.55). Conclusions: Near-infrared spectroscopy- measured rSO 2 provided reproducible decreases during hemorrhage that were similar in time course to invasively measured cardiac output and SvO2 but delayed 5 to 9 minutes compared with MAP and pulse pressure. rSO 2 may provide an earlier warning of worsening hemorrhagic shock for prompt interventions in patients with trauma when continuous arterial BP measurements are unavailable. © 2012 Lippincott Williams & Wilkins.

Doxorubicin induced dilated cardiomyopathy in a rabbit model: An update

Dilated cardiomyopathy (DCM) is characterized by chamber dilation and cardiac dysfunction. Because of the poor prognosis, models are needed for the investigation of and development of new therapeutic approaches, as well as stem cell therapy. Doxorubicin (DOX), used as chemotherapeutic agent, is reported to be cumulative cardiotoxic causing DCM. The aim of the study was to investigate the onset of systolic dysfunction using echocardiography in rabbits receiving two different doses of DOX (1. mg/kg twice a week and 2. mg/kg once a week). Twenty rabbits were treated with doxorubicin in two different doses for 6. weeks and compared with a control group treated with NaCl 0.9%. The effect of doxorubicin on the myocardium was investigated with histological analysis and scanning electron microscopy of left ventricle (LV), as well as in the interventricular septum (IVS) and right ventricle (RV). The results showed a high mortality rate for rabbits receiving 2. mg/kg once a week. A significant reduction in systolic function was present in animals treated with DOX after 6. weeks, with decreased ejection fraction and shortening fraction. Histology and electron microscopy revealed vacuolization, intracytoplasmic granulation, necrosis and interstitial fibrosis in LV, as well as in the IVS and RV. Doxorubicin induced changes are present in the LV, RV and IVS, and the administration at the dose of 1. mg/kg twice a week for only 6. weeks is safe and sufficient to induce DCM in rabbits. © 2012 Elsevier Ltd.

Anti-inflammatory intestinal activity of Arctium lappa L. (Asteraceae) in TNBS colitis model

Ethnopharmacological relevance: In Brazilian traditional medicine, Arctium lappa (Asteraceae), has been reported to relieve gastrointestinal symptoms. Aim of the study: In the present study, we investigated the effects of the lactone sesquiterpene onopordopicrin enriched fraction (ONP fraction) from Arctium lappa in an experimental colitis model induced by 2,4,6 trinitrobenzene sulfonic acid and performed experiments to elucidate the underlying action mechanisms involved in that effect. Materials and methods: ONP fraction (25 and 50 mg/kg/day) was orally administered 48, 24 and 1 h prior to the induction of colitis and 24 h after. The inflammatory response was assessed by gross appearance, myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-α) levels and a histological study of the lesions. We determined cyclooxygenase (COX)-1 and -2 protein expressions by western blotting and immunohistochemistry assays. Results: TNBS group was characterized by increased colonic wall thickness, edema, diffuse inflammatory cell infiltration, increased MPO activity and TNF-α levels. On the contrary, ONP fraction (25 and 50 mg/kg) treatment significantly reduced the macroscopic inflammation scores (p<0.05 and p<0.01, respectively) and morphological alterations associated with an increase in the mucus secretion. Similarly, the degree of neutrophil infiltration and the cytokine levels were significantly ameliorated. Moreover, COX-2 expression was up regulated in TNBS-treated rats. In contrast, ONP fraction (50 mg/kg) administration reduced COX-2 overexpression. Conclusions: We have shown that the ONP fraction obtained from Arctium lappa exert marked protective effects in acute experimental colitis, confirming and justifying, at least in part, the popular use of this plant to treat gastrointestinal diseases. © 2013 Elsevier B.V. All rights reserved.

Chronic administration of risperidone in a rat model of schizophrenia: A behavioural, morphological and molecular study

In the present work we analyzed the effect of the chronic administration of risperidone (2mg/kg over 65 days) on behavioural, morphological and molecular aspects in an experimental model of schizophrenia obtained by bilateral injection of ibotenic acid into the ventral hippocampus of new-born rats. Our results show that during their adult lives the animals with hippocampal lesions exhibit different alterations, mainly at behavioural level and in the gene expression of dopamine D2 and 5-HT2A receptors. However, at morphological level the study performed on the prefrontal cortex did not reveal any alterations in either the thickness or the number of cells immunoreactive for c-Fos, GFAP, CBP or PV. Overall, risperidone administration elicited a trend towards the recovery of the values previously altered by the hippocampal lesion, approaching the values seen in the animals without lesions. It may be concluded that the administration of risperidone in the schizophrenia model employed helps to improve the altered functions, with no significant negative effects. © 2013.

Bovine herpesvirus-5 infection in a rabbit experimental model: Immunohistochemical study of the cellular response in the CNS

Since little information is available regarding cellular antigen mapping and the involvement of non-neuronal cells in the pathogenesis of bovine herpesvirus type 5 (BHV-5) infection, it were determined the BHV-5 distribution, the astrocytic reactivity, the involvement of lymphocytes and the presence of matrix metalloproteinase (MMP)-9 in the brain of rabbits experimentally infected with BHV-5. Twelve New Zealand rabbits that were seronegative for BHV-5 were used for virus inoculation, and five rabbits were used as mock-infected controls. The rabbits were kept in separate areas and were inoculated intranasally with 500 μl of virus suspension (EVI 88 Brazilian isolate) into each nostril (virus titer, 107.5 TCID50). Control rabbits were inoculated with the same volume of minimum essential medium. Five days before virus inoculation, the rabbits were submitted to daily administration of dexamethasone. After virus inoculation, the rabbits were monitored clinically on a daily basis. Seven rabbits showed respiratory symptoms and four animals exhibited neurological symptoms. Tissue sections were collected for histological examination and immunohistochemistry to examine BHV-5 antigens, astrocytes, T and B lymphocytes and MMP-9. By means of immunohistochemical and PCR methods, BHV-5 was detected in the entire brain of the animals which presented with neurological symptoms, especially in the trigeminal ganglion and cerebral cortices. Furthermore, BHV-5 antigens were detected in neurons and/or other non-neural cells. In addition to the neurons, most infiltrating CD3 T lymphocytes observed in these areas were positive for MMP-9 and also for BHV-5 antigen. These infected cells might contribute to the spread of the virus to the rabbit brain along the trigeminal ganglia and olfactory nerve pathways. © 2013 Elsevier Ltd.

Curcumin-mediated photodynamic inactivation of Candida albicans in a murine model of oral candidiasis

In vitro investigations of curcumin-mediated photodynamic therapy (PDT) are encouraging, but there is a lack of reliable in vivo evidence of its efficacy. This study describes the photoinactivation of Candida albicans in a murine model of oral candidiasis, using curcumin as a photosensitizer. Forty immunosuppressed mice were orally inoculated with C. albicans and after five days, they received topical curcumin (20, 40 and 80 μM) and illumination with LED light. The use of curcumin or light alone were also investigated. Positive control animals did not receive any treatment and negative control animals were not inoculated with C. albicans. The number of surviving yeast cells was determined and analyzed by ANOVA and Tukey's post-hoc test (α = 0.05). Histological evaluation of the presence of yeast and inflammatory reaction was also conducted. All exposures to curcumin with LED light caused a significant reduction in C. albicans viability after PDT, but the use of 80 μM curcumin associated with light was able to induce the highest log10 reduction in colony counts (4 logs). It was concluded that curcumin-mediated PDT proved to be effective for in vivo inactivation of C. albicans without harming the host tissue of mice. © 2013 ISHAM.

Peripheral kappa and delta opioid receptors are involved in the antinociceptive effect of crotalphine in a rat model of cancer pain

Cancer pain is an important clinical problem and may not respond satisfactorily to the current analgesic therapy. We have characterized a novel and potent analgesic peptide, crotalphine, from the venom of the South American rattlesnake Crotalus durissus terrificus. In the present work, the antinociceptive effect of crotalphine was evaluated in a rat model of cancer pain induced by intraplantar injection of Walker 256 carcinoma cells. Intraplantar injection of tumor cells caused the development of hyperalgesia and allodynia, detected on day 5 after tumor cell inoculation. Crotalphine (6 μg/kg), administered p.o., blocked both phenomena. The antinociceptive effect was detected 1 h after treatment and lasted for up to 48 h. Intraplantar injection of nor-binaltorphimine (50 g/paw), a selective antagonist of κ-opioid receptors, antagonized the antinociceptive effect of the peptide, whereas N,N-diallyl-Tyr-Aib-Phe-Leu (ICI 174,864, 10 μg/paw), a selective antagonist of δ-opioid receptors, partially reversed this effect. On the other hand, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP, 20 g/paw), an antagonist of μ-opioid receptors, did not modify crotalphine-induced antinociception. These data indicate that crotalphine induces a potent and long lasting opioid-mediated antinociception in cancer pain. © 2013 Elsevier Inc.