Role of inflammation, oxidative stress, and autonomic nervous system activation during the development of right and left cardiac remodeling in experimental pulmonary arterial hypertension.

This study investigated the impact of experimental pulmonary arterial hypertension (PAH) progression by evaluating morphometric and functional parameters, oxidative stress, autonomic nervous system (ANS) activation, and inflammation in the right (RV) and left (LV) ventricles. Male rats were first divided into two groups: monocrotaline (MCT) and control. The MCT group received a single MCT injection (60 mg/kg, intraperitoneal), while control received saline. The MCT and control groups were further divided into four cohorts based on how long they were observed: 1, 2, 3, and 4 weeks. Animals were submitted to echocardiographic and hemodynamic analysis. RV and LV were used for morphometric, biochemical, and histological measurements. Autonomic modulation was evaluated by cardiac spectral analysis, considering two components: low frequency (LF) and high frequency (HF). Lung and liver weight was used for morphometric analysis. MCT induced 100% mortality at 4 weeks. In the RV, disease progression led to mild inflammation and enhanced reactive oxygen species (ROS) in week 1, followed by moderate inflammation, ROS production, and hypertrophy in week 2. By week 3, there was moderate inflammation, oxidative stress, and ANS imbalance, with development of right heart dysfunction. LV biochemical changes and inflammation were observed at week 3. The initial changes appeared to be related to inflammation and ROS, and the later ones to inflammation, oxidative stress, and ANS imbalance in MCT animals. This study reinforces the severity of the disease in the RV, the late effects in the LV, and the role of ANS imbalance in the development of heart dysfunction.

Effects of aerobic exercise training on metabolism of nitric oxide and endothelin-1 in lung parenchyma of rats with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and proliferative obstruction of pulmonary vessels, which promotes a progressive increase in pulmonary vascular resistance (PVR). The effect of exercise training on oxidative stress, metabolism, and markers of nitric oxide (NO) and endothelin-1 (ET-1) was analyzed in the lung tissue of rats with PAH induced by monocrotaline (MCT).Twenty-four Wistar rats were divided into four groups (5-7 animals): sedentary control (SC), sedentary MCT (SM), trained control (TC), and trained MCT (TM). The TC and TM groups participated in a treadmill training protocol (60% VO2 max) for 5 weeks, 3 weeks of which were performed after the injection of MCT (60 mg/kg i.p.) or saline. MCT administration promoted an increase in PVR and right ventricle hypertrophy, and reduction of right ventricle systolic function assessed by echocardiography. These changes were not improved by exercise training. The activity of NO synthase was reduced in the animals of the TC, TM, and SM groups. No significant differences were found in total nitrite concentration and expression of endothelial NO synthase. Moreover, the TM group showed strong staining for iNOS and nitrotyrosine, suggesting an increase in oxidative stress in these animals. In parallel, reduced expression of type B ET-1 receptors was noticed in the SM and TM groups in comparison to controls. In conclusion, the aerobic training protocol was unable to mitigate changes in the metabolism of NO and ET-1, probably because of the disease severity in these animals, especially in the TM group.

Coat color genotypes and risk and severity of melanoma in gray quarter horses.

BACKGROUND: Both graying and melanoma formation in horses have recently been linked to a duplication in the STX17 gene. This duplication, as well as a mutation in the ASIP gene that increases MC1R pathway signaling, affects melanoma risk and severity in gray horses. OBJECTIVE: To determine if melanoma susceptibility in gray Quarter Horses (QH) is lower than gray horses from other breeds because of decreased MC1R signaling resulting from a high incidence of the MC1R chestnut coat color allele in the QH population. ANIMALS: A total of 335 gray QH with and without dermal melanomas. METHODS: Blood or hair root samples were collected from all horses for DNA extraction and genotyping for STX17, ASIP, and MC1R genotypes. Age, sex, and external melanoma presence and grade were recorded. The effect of age and genotype on melanoma presence and severity was evaluated by candidate gene association. RESULTS: Melanoma prevalence (16%) and grade (0.35) in this QH cohort was lower than that reported in other breeds. Age was significantly associated with melanoma prevalence (P = 5.28 × 10(-11)) and severity (P = 2.2 × 10(-13)). No significant effect of MC1R genotype on melanoma prevalence or severity was identified. An effect of ASIP genotype on melanoma risk was not detected. Low STX17 homozygosity precluded evaluation of the gray allele effect. CONCLUSION AND CLINICAL IMPORTANCE: Melanoma prevalence and severity is lower in this population of gray QH than what is reported in other breeds. This could be because of the infrequent STX17 homozygosity, a mitigating effect of the MC1R mutation on ASIP potentiation of melanoma, other genes in the MC1R signaling pathway, or differences in breed genetic background.

Estudo de características de produção de matrizes de corte por meio da análise de componentes principais / Study of meat-type chickens production traits by principal components analysis

Avaliou-se o descarte de variáveis de produção, em análises de componentes principais, de três linhagens de matrizes de corte do Programa de Melhoramento Genético da Universidade Federal de Viçosa, utilizando informações de 270 aves, sendo 90 de cada linhagem. As características analisadas foram dias para postura do primeiro ovo (DPPO), taxa de postura da 22ª a 56ª semana (TP), peso médio individual na 32ª (PMI1), na 40ª (PMI2), na 48ª (PMI3), na 56ª (PMI4) e na 64ª semana (PMI5) e peso médio do ovo, obtido pela média da pesagem de três ovos na 32ª (PMO1), na 40ª (PMO2), na 48ª (PMO3), na 56ª (PMO4) e na 64ª semana (PMO5). Dos 12 componentes principais, sete apresentaram variância menor do que 0,7 (autovalor menor do que 0,7), sugerindo-se sete variáveis para descarte. As variáveis descartadas foram aquelas que apresentaram maiores coeficientes, em valor absoluto, a partir do último componente principal. Observou-se correlação linear simples e significativa entre as variáveis descartadas e as não descartadas, que indica redundância de variáveis, razão do descarte. Recomendam-se as variáveis: DPPO, TP, PM14, PMO1 e PMO4 para o estudo de características da produção de matrizes de frango de corte por meio da análise de componentes principais.

Records of 270 meat-type chickens from three lines, 90 of each one, were used to discard variables in a principal component analysis. Data were obtained from meat-type chicken lines of the genetic breeding program of the Universidade Federal de Viçosa. The following traits were evaluated: days at first egg (DFE), egg production rate (EPR) from 22nd to 56th week, body weights at 32nd (BW1), 40th (BW2), 48th (BW3), 56th (BW4), and 64th weeks of age (BW5), and average of three egg weights, at 32nd (EW1), 40th (EW2), 48th (EW3), 56th (EW4) and at 64th weeks (EW5). From the 12 principal components, seven showed variance lower than 0,7 (eigenvalue lower than 0,7), suggesting seven variables to be discarded. Variables which showed the highest coefficients, in absolute value, in the last principal component were discarded. Highly correlated variables with the smaller principal components variance explain a small part of the whole variation. In addition, discarded variables in function of the significant simple linear correlation with the nondiscorded variable, were considered redundants. The variables DFE, EPR, BW4, EW1, and EW4 are recommended for principal component analysis of broiler matrix.