Assuntos
Animais , Cães , Zoonoses , Doenças do Cão/epidemiologia , SARS-CoV-2 , COVID-19/veterináriaRESUMO
Monosodium l-glutamate (MSG)-induced obesity is a useful model for non-alcoholic fatty liver disease (NAFLD) studies. However, there is limited data on its initiation and progression. Thus, this study aimed to characterize the onset of metabolic and histopathological features of NAFLD and its progression to non-alcoholic steatohepatitis (NASH) in this model. To perform this study, Swiss mice pups were neonatally injected with MSG (4 g/kg/day, s.c.) or equiosmolar saline and followed up to 60, 120 or 180 days old. At each age, blood, liver, as well as periepididymal and retroperitoneal fat pads were collected for morphometric, biochemical and histological analyses, the later according to NAFLD activity score. MSG mice presented hypertriglyceridemia and central obesity at all ages, but peripheral insulin-resistance was verified only in 120- and 180-day-old mice. Hepatic total fat and triglycerides content were higher in MSG mice at all ages. Accordingly, histopathological analysis showed that 60-day-old MSG mice had microvesicular steatosis with occasional ballooning, which evolved into NASH from 120 days old. Retroperitoneal fat accumulation was the only variable to independently correlate with NAFLD activity total score upon multivariate analysis (R 2=71.45%). There were no differences in IL-6 and TNF-α serum levels among groups. Overall, this study shows that NAFLD is a precocious outcome in MSG-obese mice, whereas the period comprised between 60 and 120 days old seems to be a crucial metabolic window for comprehending pathophysiological events involved in NAFLD-to-NASH progression in this model.
Assuntos
Modelos Animais de Doenças , Hipertrigliceridemia/metabolismo , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/complicações , Gordura Abdominal/metabolismo , Adolescente , Adulto , Fatores Etários , Idade de Início , Animais , Animais Recém-Nascidos , Progressão da Doença , Feminino , Humanos , Hipertrigliceridemia/diagnóstico , Hipertrigliceridemia/etiologia , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/induzido quimicamente , Obesidade/metabolismo , Glutamato de Sódio/toxicidade , Adulto JovemRESUMO
The present study aimed to evaluate the feedlot performance, profitability and carcass traits of Brahman bulls classified according to the residual feed intake (RFI). Twenty-four bulls (19-month old, 370±34kg live weight) were housed in individual pens for 54 days and had the daily feed intake (observed dry matter intake, DMIobs; DMI % live weight, LW) and average daily gain (ADG) measured. Ultrasound carcass evaluations were performed at the initial and final weighings, when measurements were taken of Longissimus dorsi area, ratio, Longissimus and Biceps femoris fat thickness. The animals were ranked and divided into high (>+0.5 standard deviation; SD), medium (between ±0.5 SD from the mean), and low (<-0.5 SD) RFI groups. Low-RFI animals had lower DMIobs (P<0.10) and DMI % LW (P<0.05). No significant differences in initial and final weight or ADG were noticed (P>0.05). Low-RFI animals showed lower weight gain cost and higher daily profit (P<0.05). Carcass traits were similar between groups, regardless of evaluation date (P>0.05). Selection for RFI lead to animals with lower feed intake without affecting weight gain or carcass traits, thereby providing increased profitability for beef cattle farming.(AU)
Objetivou-se avaliar o desempenho, o lucro e as características de carcaça de tourinhos Brahman classificados de acordo com o consumo alimentar residual (CAR). Vinte e quatro tourinhos (19 meses de idade e 370±34kg de peso vivo) foram alojados em baias individuais por 54 dias para avaliação do consumo de alimentos (CMSobs; CMS % peso vivo, PV) e ganho de peso diário (GMD). Avaliações de carcaça por ultrassonografia foram realizadas nas pesagens inicial e final, com mensurações da área do Longissimus dorsi, ratio, espessura de gordura sobre o Longissimus e sobre o Biceps femoris. Os animais foram ranqueados e divididos em grupos de alto (>+0,5 desvio-padrão; DP), médio (entre ±0,5 DP da média) e baixo (<-0,5 DP) CAR. Animais de baixo CAR apresentaram menor CMSobs (P<0,10) e menor CMS % PV (P<0,05). Não houve diferença nos pesos inicial e final e GMD (P>0,05). Animais de baixo CAR apresentaram menor custo do ganho de peso e maior lucro diário (P<0,05). As características de carcaça foram semelhantes entre os grupos independentemente da data de avaliação (P>0,05). A seleção para CAR leva a animais de menor consumo, sem afetar o ganho de peso e as características de carcaça, fornecendo maior lucro para a atividade pecuária.(AU)
Assuntos
Animais , Bovinos , Bovinos/genética , Bovinos/fisiologia , Ingestão de Alimentos , Carne/análiseRESUMO
The present study aimed to evaluate the feedlot performance, profitability and carcass traits of Brahman bulls classified according to the residual feed intake (RFI). Twenty-four bulls (19-month old, 370±34kg live weight) were housed in individual pens for 54 days and had the daily feed intake (observed dry matter intake, DMIobs; DMI % live weight, LW) and average daily gain (ADG) measured. Ultrasound carcass evaluations were performed at the initial and final weighings, when measurements were taken of Longissimus dorsi area, ratio, Longissimus and Biceps femoris fat thickness. The animals were ranked and divided into high (>+0.5 standard deviation; SD), medium (between ±0.5 SD from the mean), and low (<-0.5 SD) RFI groups. Low-RFI animals had lower DMIobs (P<0.10) and DMI % LW (P<0.05). No significant differences in initial and final weight or ADG were noticed (P>0.05). Low-RFI animals showed lower weight gain cost and higher daily profit (P<0.05). Carcass traits were similar between groups, regardless of evaluation date (P>0.05). Selection for RFI lead to animals with lower feed intake without affecting weight gain or carcass traits, thereby providing increased profitability for beef cattle farming.(AU)
Objetivou-se avaliar o desempenho, o lucro e as características de carcaça de tourinhos Brahman classificados de acordo com o consumo alimentar residual (CAR). Vinte e quatro tourinhos (19 meses de idade e 370±34kg de peso vivo) foram alojados em baias individuais por 54 dias para avaliação do consumo de alimentos (CMSobs; CMS % peso vivo, PV) e ganho de peso diário (GMD). Avaliações de carcaça por ultrassonografia foram realizadas nas pesagens inicial e final, com mensurações da área do Longissimus dorsi, ratio, espessura de gordura sobre o Longissimus e sobre o Biceps femoris. Os animais foram ranqueados e divididos em grupos de alto (>+0,5 desvio-padrão; DP), médio (entre ±0,5 DP da média) e baixo (<-0,5 DP) CAR. Animais de baixo CAR apresentaram menor CMSobs (P<0,10) e menor CMS % PV (P<0,05). Não houve diferença nos pesos inicial e final e GMD (P>0,05). Animais de baixo CAR apresentaram menor custo do ganho de peso e maior lucro diário (P<0,05). As características de carcaça foram semelhantes entre os grupos independentemente da data de avaliação (P>0,05). A seleção para CAR leva a animais de menor consumo, sem afetar o ganho de peso e as características de carcaça, fornecendo maior lucro para a atividade pecuária.(AU)
Assuntos
Animais , Bovinos , Carne/análise , Ingestão de Alimentos , Bovinos/fisiologia , Bovinos/genéticaRESUMO
Essentials Inhibitors of protein disulfide isomerase (PDI) have been considered a new antithrombotic class. CxxC is a PDI-targeted peptide that has been previously shown to inhibit its reductase activity. CxxC binds to surface PDI and inhibits ADP- and thrombin-evoked platelet activation and aggregation. CxxC binds to Cys400 on CGHC redox motif of PDI a' domain, a site for PDI prothrombotic activity. SUMMARY: Background Protein disulfide isomerase (PDI) plays a major role in platelet aggregation, and its inhibitors have emerged as novel antithrombotic drugs. In previous work, we designed a peptide based on a PDI redox motif (CGHC) that inhibited both PDI reductase activity and PDI-modulated superoxide generation by neutrophil Nox2. Thus, we hypothesized that this peptide would also inhibit platelet aggregation by association with surface PDI. Methods Three peptides were used: CxxC, containing the PDI redox motif; Scr, presenting a scrambled sequence of the same residues and AxxA, with cysteines replaced by alanine. These peptides were tested under platelet aggregation and flow cytometry protocols to identify their possible antiplatelet activity. We labeled membrane free thiol and electrospray ionization liquid chromatography tandem mass spectrometry to test for an interaction. Results CxxC decreased platelet aggregation in a dose-dependent manner, being more potent at lower agonist concentrations, whereas neither AxxA nor Scr peptides exerted any effect. CxxC decreased aIIbb3 activation, but had no effect on the other markers. CxxC also decreased cell surface PDI pulldown without interfering with the total thiol protein content. Finally, we detected the addition of one CxxC molecule to reduced PDI through binding to Cys400 through mass spectrometry. Interestingly, CxxC did not react with oxidized PDI. Discussion CxxC has consistently shown its antiplatelet effects, both in PRP and washed platelets, corroborated by decreased aIIbb3 activation. The probable mechanism of action is through a mixed dissulphide bond with Cys400 of PDI, which has been shown to be essential for PDI's actions. Conclusion In summary, our data support antiplatelet activity for CxxC through binding to Cys400 in the PDI a0 domain, which can be further exploited as a model for sitedriven antithrombotic agent development.