Expression of ß1- and ß2-adrenergic receptors in oral squamous cell carcinoma and their association with psychological and clinical factors.

BACKGROUND: Psychological stressors have been related to tumor progression through the activation of beta-adrenergic receptors (ß-AR) in several types of cancer. PURPOSE: This study aimed to investigate the expressions of ß1- and ß2-AR and their association with psychological and clinicopathological variables in patients with oral squamous cell carcinoma. METHODS: Tumor samples from 99 patients diagnosed with OSCC were subjected to immunohistochemical reaction to detect the expression of ß1-AR and ß2-AR. Anxiety and depression symptoms were assessed using the Beck Anxiety Inventory and Beck Depression Inventory (BDI), respectively. The Brunel Mood Scale was used for measuring affective mood states. RESULTS: Univariate analyzes revealed that higher expression of ß1-AR was associated with increased alcohol consumption (p = 0.032), higher education (p = 0.042), worse sleep quality (p = 0.044) and increased levels of pain related to the primary tumor (p < 0.001). Higher expression of ß2-AR was related with regional metastasis (p = 0.014), increased levels of pain related to the primary tumor (p = 0.044), anxiety (p < 0.001) and depressive (p = 0.010) symptoms and higher mood scores of angry (p = 0.010) and fatigue (p = 0.010). Multivariate analysis identified that patients with advanced clinical stage had lower ß1-AR expression (OR=0.145, 95% CI=0.025-0.828, p = 0.003). Higher anxiety symptoms and higher mood fatigue are independent factors for increased ß2-AR expression (OR=4256, 95% CI=1439-12606, p = 0.009; OR=3816, 95% CI=1258-11,573, p = 0.018, respectively). CONCLUSION: This study reveal that anxiety, fatigue symptoms, and clinical staging are associated with tumor expression of beta-adrenergic receptors in patients with oral cancer.

Norepinephrine, beyond the Synapse: Coordinating Epigenetic Codes for Memory.

The noradrenergic system is implicated in neuropathologies contributing to major disorders of the memory, including post-traumatic stress disorder and Alzheimer's disease. Determining the impact of norepinephrine on cellular function and plasticity is thus essential for making inroads into our understanding of these brain conditions, while expanding our capacity for treating them. Norepinephrine is a neuromodulator within the mammalian central nervous system which plays important roles in cognition and associated synaptic plasticity. Specifically, norepinephrine regulates the formation of memory through the stimulation of ß-ARs, increasing the dynamic range of synaptic modifiability. The mechanisms through which NE influences neural circuit function have been extended to the level of the epigenome. This review focuses on recent insights into how the noradrenergic recruitment of epigenetic modifications, including DNA methylation and post-translational modification of histones, contribute to homo- and heterosynaptic plasticity. These advances will be placed in the context of synaptic changes associated with memory formation and linked to brain disorders and neurotherapeutic applications.

Propranolol inhibits cell viability and expression of the pro-tumorigenic proteins Akt, NF-ĸB, and VEGF in oral squamous cell carcinoma.

BACKGROUND: Propranolol (PPL) has been suggested as an option for the treatment of various types of cancer. However, data regarding its effectiveness against oral cancer are scarce. Thus, we aimed to evaluate the antitumor potential of PPL in oral squamous cell carcinoma (OSCC) in vitro. METHODS: OSCC cell lines, SCC-9, SCC-25, and Cal27, were treated with PPL at different times and concentrations. OSCC cells were treated with PPL alone or in combination with cisplatin (CDDP) or 5-fluorouracil (5-FU). Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of phosphorylated (p)-Akt, p-S6, p-PTEN, p-P65, and VEGF was verified by immunofluorescence. The migratory activity of OSCC cells was evaluated using a wound-healing assay. RESULTS: PPL reduced OSCC cell viability in a dose- and time-dependent manner. Concentrations above 300 µM, 110 µM, and 100 µM for SCC-9, Cal27, and SCC-25, respectively, significantly eliminated tumor cells. The combination of PPL with CDDP and 5-FU enhanced their antitumor effects. There was a modest difference between the use of the IC30 and IC50 of PPL in the combinatory options. PPL downregulated p-P65 NF-ĸB and VEGF expression in SCC-9 and Cal27 cells but not in SCC-25 cells. PPL inhibited the phosphorylation of Akt and s6 and increased the phosphorylation of PTEN in all OSCC cell lines studied. PPL inhibited OSCC cell migration after 24 h of treatment. CONCLUSION: PPL was effective against oral cancer cells and enhanced standard-of-care. PPL inhibited cell viability and the expression of pAkt, NF-ĸB, and VEGF.

Chromium and energy restriction as substitutes for ractopamine in finishing gilts diet / Cromo e restrição energética em substituição a ractopamina na dieta de leitoas em terminação tardia

This study evaluated chromium supplements and energy restriction as substitutes for ractopamine in the diets of late finishing gilts. Sixty gilts were used, with initial weights of 98.87 ± 0.25 kg and final weights of 122.69 ± 10.97 kg, distributed in a randomized block design with five diets: control; yeast chromium (0.8 ppm); chromium picolinate (0.48 ppm); ractopamine (20 ppm) and energy restriction (reduction of 150 kcal of EM kg-1 of feed), with six replicates and two animals per experimental unit. Feeding diet containing ractopamine enabled better (P<0.05) feed conversion and greater weights of the hot carcass of the gilts. The diet containing ractopamine exhibited a lower (P<0.05) cost of feed per kilogram of gain and higher economic efficiency, when compared to diets containing chromium and energy restriction; these exhibited better outcomes, compared to the control diet. Diets supplemented with chromium and ractopamine resulted in a higher (P<0.05) percentage and quantity of lean meat and a higher rate of carcass bonus, when compared to the control diet and energy restriction. The energy reduction did not harm the gilts' responses, compared to the control diet. Ractopamine supplementation allowed for a better feed conversion, lower feed cost per kilogram of gain, and a higher economic efficiency index. Supplements of chromium and ractopamine increased the percentage and quantity of lean meat and the bonus index of the carcasses. Therefore, chromium picolinate and chromium yeast are potential substitutes for ractopamine for optimizing the gilts carcass characteristics.

Realizou-se este estudo com o objetivo de avaliar as suplementações de cromo e a restrição energética em substituição a ractopamina para leitoas em terminação tardia. Foram utilizadas 60 leitoas, com pesos inicial de 98,87±0,25 kg e final de 122,69 ± 10,97 kg, distribuídas em delineamento de blocos ao acaso com cinco dietas: controle; cromo levedura (0,8 ppm); picolinato de cromo (0,48 ppm); ractopamina (20 ppm) e restrição energética (redução de 150 kcal de EMkg-1 de ração), com seis repetições e dois animais por unidade experimental. A dieta contendo ractopamina proporcionou melhor (P<0,05) conversão alimentar e maior peso de carcaça quente das leitoas. A dieta contendo ractopamina apresentou menor (P<0,05) custo de ração por quilograma de ganho e maior índice de eficiência econômica em relação as dietas contendo cromo e restrição energética que, por sua vez, foram superiores em comparação a dieta controle. Dietas suplementadas com cromo e ractopamina apresentaram maior (P<0,05) percentual e quantidade de carne magra e maior índice de bonificação de carcaça em relação a dieta controle e restrição energética. Concluiu-se que a redução energética não prejudica as respostas das leitoas em relação a dieta controle. A suplementação de ractopamina possibilita melhor conversão alimentar, menor custo de ração por quilograma de ganho e maior índice de eficiência econômica. As suplementações de cromo e ractopamina expressam aumento do percentual e quantidade de carne magra e do índice de bonificação das carcaças. O picolinato de cromo e o cromo levedura são potenciais substitutos a ractopamina para otimizar as características de carcaça das leitoas.

Beta-adrenergic blocker inhibits oral carcinogenesis and reduces tumor invasion.

PURPOSE: Beta-adrenergic signaling can influence cancer progression and the use of beta blockers as adjuvant drugs in oncologic patients has been suggested. However, the involvement of beta-adrenergic blockers in tumorigenesis is poorly understood. This study investigated the action of beta-adrenergic blocker propranolol on tumor onset using a preclinical model of chemically induced oral cancer. METHODS: Thirty-two male Wistar rats were subjected to daily subcutaneous injection of beta-blocker propranolol (10 mg/kg; SubQ), while another 32 rats received only a PBS injection (sham group). One week after starting propranolol treatment, all rats were submitted to chemical induction of oral carcinogenesis with 4-nitroquinoline-1-oxide (4NQO). After 16 weeks, they were assessed for occurrence of oral squamous cell carcinoma (OSCC), in addition to measurement of tumor volume and thickness, and tissue levels of cytokines IL-6, TNF-alpha and IL-10 in the tumor microenvironment. RESULTS: Propranolol treatment reduced the occurrence of OSCC by 31%, 95% CI ( - 127, 216). Beta-adrenergic blocker significantly decreased thickness of OSCC when compared with PBS. Rats treated with propranolol exhibited a lower tumor volume when compared with control rats, but this result did not reach statistical significance. Tumors from propranolol-treated rats exhibited reduced concentrations of pro-inflammatory cytokines IL-6 and TNF-α. There was no difference in the IL-10 levels between tumors from propranolol- and sham-treated rats. CONCLUSION: Beta-adrenergic signaling may be one of the mechanisms associated with chemically induced oral carcinogenesis.

Variants in ADRB1 and CYP2C9: Association with Response to Atenolol and Losartan in Marfan Syndrome.

OBJECTIVE: To test whether variants in ADRB1 and CYP2C9 genes identify subgroups of individuals with differential response to treatment for Marfan syndrome through analysis of data from a large, randomized trial. STUDY DESIGN: In a subset of 250 white, non-Hispanic participants with Marfan syndrome in a prior randomized trial of atenolol vs losartan, the common variants rs1801252 and rs1801253 in ADRB1 and rs1799853 and rs1057910 in CYP2C9 were analyzed. The primary outcome was baseline-adjusted annual rate of change in the maximum aortic root diameter z-score over 3 years, assessed using mixed effects models. RESULTS: Among 122 atenolol-assigned participants, the 70 with rs1801253 CC genotype had greater rate of improvement in aortic root z-score compared with 52 participants with CG or GG genotypes (Time × Genotype interaction P = .005, mean annual z-score change ± SE -0.20 ± 0.03 vs -0.09 ± 0.03). Among participants with the CC genotype in both treatment arms, those assigned to atenolol had greater rate of improvement compared with the 71 of the 121 assigned to losartan (interaction P = .002; -0.20 ± 0.02 vs -0.07 ± 0.02; P < .001). There were no differences in atenolol response by rs1801252 genotype or in losartan response by CYP2C9 metabolizer status. CONCLUSIONS: In this exploratory study, ADRB1-rs1801253 was associated with atenolol response in children and young adults with Marfan syndrome. If these findings are confirmed in future studies, ADRB1 genotyping has the potential to guide therapy by identifying those who are likely to have greater therapeutic response to atenolol than losartan.

Substitution of ractopamine by safflower or coconut oil as an additive in finishing pig diets / Substituição da ractopamina por óleo de cártamo ou óleo de coco como aditivos em dietas para suínos em terminação

The objective of this study was to explore the substitution of ractopamine by coconut or safflower oil in finishing pig diets. The study included 24 crossbred barrows weighing 78.00 ± 8.76 kg distributed in a randomized block design with four treatments and six replicates composed of: basal ration (BR), BR + 10 ppm ractopamine, BR + four 1 g capsules of safflower oil, and BR + four 1 g capsules of coconut oil. Performance evaluation showed that safflower oil, ractopamine, and coconut oil supplementation had a significant effect (P 0.05) on weight gain and feed conversion. Carcass-related variables were also affected by the treatments (P 0.05), with fat thickness 3 (FT3) reduced by the use of safflower oil, ractopamine, and coconut oil. Rib eye area was positively affected (P 0.05) by diet, with ractopamine, coconut oil, and safflower oil supplementation treatments showing higher values than control diet treatment. The diets also affected fatty acid profiles (P 0.05), with decreased myristic acid content in animals supplemented with ractopamine and safflower oil and increased deposition of palmitoleic and oleic acids in animals supplemented with coconut oil and safflower oil, respectively. Results suggested that both safflower oil and coconut oil can be used as substitutes for ractopamine.(AU)

Objetivou-se avaliar a substituição da suplementação da ractopamina pelo uso dos óleos de coco ou cártamo nas dietas de suínos em terminação. Foram utilizados 24 suínos machos castrados mestiços com peso médio de 78,00±8,76 kg, distribuídos em um delineamento de blocos casualizados, contendo quatro tratamentos e seis repetições compostos por: Ração Basal (RB); RB + 10 ppm de ractopamina; RB + 4 cápsulas de 1 grama cada de óleo de cártamo e RB + 4 cápsulas de 1 grama cada de óleo de coco. Na avaliação do desempenho foi observado o efeito (P 0,05) da suplementação das dietas com óleo de cártamo, ractopamina e coco no ganho de peso e conversão alimentar. As variáveis relacionadas com as carcaças também foram afetadas pelos tratamentos (P 0,05), sendo a espessura de toucinho 3 (ET3) reduzida pelo uso do óleo de cártamo, ractopamina e coco. Na avaliação da área de olho de lombo foram observados efeitos positivos (P 0,05), com maiores valores para os tratamentos suplementados com ractopamina, óleo de coco e com óleo de cártamo, quando comparados com a dieta controle. As dietas também afetaram o perfil dos ácidos graxos (P 0,05) de forma positiva, com a redução do ácido míristico do toucinho nas dietas com ractopamina e óleo de cártamo e aumento na deposição dos ácidos graxos palmitoleico e oleico do lombo nas dietas suplementadas com óleo de coco e cártamo, respectivamente. Conclui-se que tanto o óleo de coco quanto o de cártamo podem ser utilizados como substitutos da ractopamina.(AU)

Carvedilol as primary prophylaxis for gastric variceal bleeding in portal hypertension model in rats / Carvedilol como profilaxia de sangramento em varizes gástricas em modelo de hipertensão portal em ratos

ABSTRACT Background: Portal hypertension (PH) can be measured indirectly through a hepatic vein pressure gradient greater than 5 mmHg. Cirrhosis is the leading cause for PH and can present as complications ascites, hepatic dysfunction, renal dysfunction, and esophagogastric varices, characterizing gastropathy. Aim: To evaluate the use of carvedilol as primary prophylaxis in the development of collateral circulation in rats submitted to the partial portal vein ligament (PPVL) model. Method: This is a combined qualitative and quantitative experimental study in which 32 Wistar rats were divided into four groups (8 animals in each): group I - cirrhosis + carvedilol (PPVL + C); group II - cirrhosis + vehicle (PPVL); group III - control + carvedilol (SO-sham-operated + C); group IV - control + vehicle (SO-sham-operated). After seven days of the surgical procedure (PPVL or sham), carvedilol (10 mg/kg) or vehicle (1 mL normal saline) were administered to the respective groups daily for seven days. Results: The histological analysis showed no hepatic alteration in any group and a decrease in edema and vasodilatation in the PPVL + C group. The laboratory evaluation of liver function did not show a statistically significant change between the groups. Conclusion: Carvedilol was shown to have a positive effect on gastric varices without significant adverse effects.

RESUMO Racional: A hipertensão portal (HP), medida indiretamente através do gradiente pressórico da veia hepática >5 mmHg, tem como principal causa etiológica a cirrose. Possui como complicações a ascite, disfunção hepática, disfunção renal e varizes esofagogástricas, que caracterizam o quadro de gastropatia. Objetivo: Avaliar o uso do carvedilol como profilaxia primária no desenvolvimento da circulação colateral em ratos submetidos ao modelo de ligadura parcial de veia porta (LPVP). Método: Estudo experimental qualitativo e quantitativo no qual foram utilizados 32 ratos Wistar, divididos em quatro grupos (n=8): grupo I - cirrose + carvedilol (LPVP+C); grupo II - cirrose + veículo (LPVP); grupo III - controle + carvedilol (SO - sham-operated+C); grupo IV - controle + veículo (SO - sham-operated). Após transcorridos sete dias do procedimento cirúrgico, foi administrado carvedilol (10 mg/kg) e veículo (1mL) para os respectivos grupos por sete dias consecutivos. Resultados: A análise histológica não mostrou alteração hepática em nenhum grupo e diminuição de edema e vasodilatação no grupo LPVP+C. A avaliação laboratorial da função hepática não mostrou alteração com significância estatística entre os grupos. Conclusão: Carvedilol mostrou ser fármaco com efeito positivo no sangramento das varizes gástricas e sem efeitos adversos significantes.

Beta-blockers and salbutamol limited emotional memory disturbance and damage induced by orchiectomy in the rat hippocampus.

AIM: To evaluate the therapeutic potential of ligands of beta-adrenoceptors in cognitive disorders. Testosterone and adrenergic pathways are involved in hippocampal and emotional memory. Moreover, is strongly suggested that androgen diminishing in aging is involved in cognitive deficit, as well as beta-adrenoceptors, particularly beta2-adrenoceptor, participate in the adrenergic modulation of memory. In this regard, some animal models of memory disruption have shown improved performance after beta-drug administration. MATERIAL AND METHODS: In this work, we evaluated the effects of agonists (isoproterenol and salbutamol) and antagonists (propranolol and carvedilol) on beta-adrenoceptors in orchiectomized rats, as well as their effects in the performance on avoidance task and damage in hippocampal neurons by immunohistochemistry assays. KEY FINDINGS: Surprisingly, we found that both antagonists and salbutamol (but not isoproterenol) modulate the effects of hormone deprivation, improving memory and decreasing neuronal death and amyloid-beta related changes in some regions (particularly CA1-3 and dentate gyrus) of rat hippocampus. SIGNIFICANCE: Two ß-antagonists and one ß2-agonist modulated the effects of hormone deprivation on memory and damage in brain. The mechanisms of signaling of these drugs for beneficial effects remain unclear, even if used ß-ARs ligands share a weak activity on ß-arrestin/ERK-pathway activation which can be involved in these effects as we proposed in this manuscript. Our observations could be useful for understanding effects suggested of adrenergic drugs to modulate emotional memory. But also, our results could be related to other pathologies involving neuronal death and Aß accumulation.

Differential function of medial prefrontal cortex catecholaminergic receptors after long-term sugar consumption.

The medial prefrontal cortex (mPFC) has reciprocal projections with many cerebral structures that are crucial in the control of food ingestion behavior and reward processing; Thus the mPFC has an important function in taste memory recognition. Previous results indicate that long-term consumption of sugar produces changes in appetitive re-learning and suggest that this could trigger an escalating consumption due to the inability to learn new negative consequences related to the same taste. Further evidence suggests that general identity reward value could be encoded in the mPFC. Therefore, the purpose of this study was to evaluate in rats whether after 21 days of sugar consumption the increase in sweet taste preference and latent inhibition of conditioned taste aversion (CTA) were affected differentially by pharmacological activation or blockage of dopaminergic and ß-adrenergic receptors, in the mPFC, during CTA acquisition. Results showed that after long-term sugar exposure, mPFC activation of ß-adrenergic receptors with clenbuterol delayed aversive memory extinction, but the blockade with propranolol or activation of dopaminergic receptors with apomorphine increased CTA latent inhibition and accelerated aversive memory extinction only after acute sugar exposure. Only dopaminergic blockade with haloperidol prevented sweet taste preference expression after long-term sugar consumption, increased CTA latent inhibition and accelerated extinction after acute sugar exposure. Taken together, the present data provide evidence that catecholaminergic receptors in the mPFC after prolonged sugar consumption underwent functional changes related to re-learning and new aversive taste learning.

A step-up ractopamine feeding program for finishing pigs / Niveles incrementales de ractopamina para cerdos en ceba / Plano de níveis aumentados de ractopamina para suínos em terminação

Abstract Background: Ractopamine (RAC) supplementation in the feed has been evaluated as a strategy to increase productive efficiency in finishing pigs. Objective: To evaluate the effects of different RAC dietary levels on performance, carcass traits, efficiency of lysine (ELU) and energy (EEU) utilization, and economic viability in finishing pig. Methods: A total of 40 barrows (74.75 ± 5.22 kg) were fed four RAC levels (0, 5, 10 and 5-10 mg/kg step-up program) from 0-14, 15-31 and 0-31 days. Performance, carcass characteristics, ELU, EEU, cost per unit of weight gain (CWG), payment and profit parameters were measured. The animals were distributed in a completely randomized design in four treatments, with ten replicates per treatment. The experimental unit was each animal. Results: Pigs fed RAC diets showed increased body weights at 14 and 31 days, average daily gain (ADG) at 0-14 and 0-31 days, ELU at 0-14 days, and hot carcass weight as compared with those fed the control diet. The step-up program as compared to the 10 mg/kg RAC concentration resulted in increased body weight, feed/gain ratio (FGR), ADG, ELU, EEU and CWG at 0-14 days. Payment by weight and bonus payment were better for treatments with RAC as compared to control. Conclusions: Pigs fed RAC improved performance, carcass weight, ELU, EEU and economic viability. The results were better for the step-up program compared with the intermittent use of 10 mg/kg RAC.

Resumen Antecedentes: La suplementación de cerdos con ractopamina (RAC) es una estrategia para aumentar la eficiencia productiva en ceba. Objetivo: Evaluar el efecto de diferentes planes de suplementación con RAC en dietas de cerdos en ceba sobre el rendimiento productivo, características de la canal, eficiencia de utilización de lisina (ELU) y energía (EEU), y viabilidad económica. Métodos: Un total de 40 machos castrados (74,75 ± 5,22 kg) fueron alimentados con cuatro niveles de RAC (0, 5, 10 y 5-10 mg/kg de plano escalonado) de 0-14, 15-31 y 0-31 días. Se evaluó el rendimiento, características de la canal, ELU, EEU, el costo por unidad de ganancia de peso (CWG), los tipos de pago y ganancias. Los animales se distribuyeron en un diseño completamente aleatorizado en cuatro tratamientos, con diez repeticiones por tratamiento. La unidad experimental fue cada animal. Resultados: Los animales suplementados con RAC tuvieron mayor peso corporal a los 14 y 31 días, ganancia de peso diaria (ADG) de 0-14 y 0-31 días, ELU de 0-14 días y peso de la canal caliente en comparación con el grupo control. En comparación con la concentración de 10 mg/kg de RAC, el plano escalonado resultó en un aumento de peso corporal, conversión alimenticia (FGR), ADG, ELU, EEU y CWG a los 0-14 días. El pago por peso y el pago por bonificación fueron mejores para los tratamientos con RAC en comparación con el control. Conclusiones: Los cerdos en ceba alimentados con RAC tienen mejor rendimiento, peso de la canal, ELU, EEU y viabilidad económica. Los resultados de los parámetros estudiados son mejores con el uso del plano escalonado en comparación con el uso continuo de 10 mg/kg de RAC.

Resumo Antecedentes: Suplementação de ractopamina (RAC) em dietas para suínos foi avaliada como uma estratégia para aumentar eficiência de produção de suínos em terminação. Objetivo: Avaliar os efeitos de diferentes planos de suplementação de RAC em dietas para suínos em terminação sobre o desempenho, características de carcaça, eficiência de utilização de lisina (ELU) e energia (EEU), e viabilidade econômica. Métodos: Um total de 40 machos castrados (74.75 ± 5.22 kg) foram alimentados com quatro níveis de RAC (0, 5, 10 e 5-10 mg/kg plano escalonado) em 0-14, 15-31 e 0-31 dias. Desempenho, características de carcaça, ELU, EEU, custo por unidade de ganho de peso (CWG), tipos de pagamento e lucro foram mensurados. Os animais foram distribuídos em um delineamento inteiramente casualizado em quatro tratamentos, dez repetições para cada tratamento. A unidade experimental foi cada animal. Resultados: Os animais alimentados com dietas contendo RAC mostraram aumento de peso corporal aos 14 e 31 dias, ganho de peso diário (ADG) de 0-14 e 0-31 dias, ELU de 0-14 dias e peso de carcaça quente comparado ao grupo controle. O plano escalonado comparado ao nível de 10 mg/kg de RAC mostrou maior peso corporal, conversão alimentar (FGR), ADG, ELU, EEU e CWG de 0-14 dias. Pagamento por peso e pagamento por bonificação foram melhor para tratamentos com RAC em comparação ao controle. Conclusões: Suínos alimentados com RAC mostram melhor desempenho, peso de carcaça, ELU, EEU e viabilidade econômica. Os resultados dos parâmetros estudados foram melhores com uso do plano escalonado quando comparado com uso constante de 10 mg/kg de RAC para suínos em terminação.

ß-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes.

Melatonin (5-methoxy-N-acetylserotonin), the pineal hormone, is also synthesized by immune-competent cells. The pineal hormone signals darkness, while melatonin synthesized on demand by activated macrophages at any hour of the day acts locally, favoring regulatory/tolerant phenotypes. Activation of ß-adrenoceptors in pinealocytes is the main route for triggering melatonin synthesis. However, despite the well-known role of ß-adrenoceptors in the resolution macrophage phenotype (M2), and the relevance of macrophage synthesized melatonin in facilitating phagocytic activity, there is no information regarding whether activation of ß-adrenoceptors would induce melatonin synthesis by monocytes. Here we show that catecholamines stimulate melatonin synthesis in bone marrow-derived dendritic cells and RAW 264.7 macrophages. Activation of ß-adrenoceptors promotes the synthesis of melatonin by stimulating cyclic AMP/protein kinase A (PKA) pathway and by activating the nuclear translocation of NF-κB. Considering the great number of macrophages around sympathetic nerve terminals, and the relevance of this system for maintaining macrophages in stages compatible to low-grade inflammation, our data open the possibility that extra-pineal melatonin acts as an autocrine/paracrine signal in macrophages under resolution or tolerant phenotypes.

Ghrelin potentiates cardiac reactivity to stress by modulating sympathetic control and beta-adrenergic response.

Prior evidence indicates that ghrelin is involved in the integration of cardiovascular functions and behavioral responses. Ghrelin actions are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), which is expressed in peripheral tissues and central areas involved in the control of cardiovascular responses to stress. AIMS: In the present study, we assessed the role of ghrelin - GHS-R1a axis in the cardiovascular reactivity to acute emotional stress in rats. MAIN METHODS AND KEY FINDINGS: Ghrelin potentiated the tachycardia evoked by restraint and air jet stresses, which was reverted by GHS-R1a blockade. Evaluation of the autonomic balance revealed that the sympathetic branch modulates the ghrelin-evoked positive chronotropy. In isolated hearts, the perfusion with ghrelin potentiated the contractile responses caused by stimulation of the beta-adrenergic receptor, without altering the amplitude of the responses evoked by acetylcholine. Experiments in isolated cardiomyocytes revealed that ghrelin amplified the increases in calcium transient changes evoked by isoproterenol. SIGNIFICANCE: Taken together, our results indicate that the Ghrelin-GHS-R1a axis potentiates the magnitude of stress-evoked tachycardia by modulating the autonomic nervous system and peripheral mechanisms, strongly relying on the activation of cardiac calcium transient and beta-adrenergic receptors.

Inhibition of spinal p38 MAPK prevents articular neutrophil infiltration in experimental arthritis via sympathetic activation.

The central nervous system controls the innate immunity by modulating efferent neuronal networks. Recently, we have reported that central brain stimulation inhibits inflammatory responses. In the present study, we investigate whether spinal p38 mitogen-activated protein kinase (MAPK) affects joint inflammation in experimental arthritis. Firstly, we observed that intra-articular administration of zymosan in mice induces the phosphorylation of the spinal cord p38 MAPK. In addition, we demonstrated that spinal p38 MAPK inhibition with intrathecal injection of SB203580, a conventional and well-characterized inhibitor, prevents knee joint neutrophil recruitment, edema formation, experimental score and cytokine production. This local anti-inflammatory effect was completely abolished with chemical sympathectomy (guanethidine) and beta-adrenergic receptors blockade (nadolol). In conclusion, our results suggest that pharmacological strategies involving the modulation of spinal p38 MAPK circuit can prevent joint inflammation via sympathetic networks and beta-adrenoceptors activation.

Metabolic and histologic responses of pacu (Piaractus mesopotamicus) fed diets supplemented with increasing concentrations of ractopamine

An experiment was conducted during 60 days with forty pacu males fed diets supplemented with increasing concentrations of ractopamine (0.00, 11.25, 22.50, 33.75, and 45.00 mg kg−1). Eight fish were evaluated for each experimental diet. Performance and survival rate of the fish were measured. At the end of the experiment, blood was collected to determine the levels of cortisol, triacylglycerol, and protein. Moreover, the liver was collected to determine the activities of glucose-6-phosphate dehydrogenase and malic enzymes. The fillets were collected to determine chemical composition, and histologic cuts were analyzed to verify muscle growth and deposition of adipose tissue between muscle fibers. Increasing concentrations of dietary ractopamine did not change feed intake, fillet yield, fillet content of protein and ash, and frequency of relative distribution of muscle fibers. By increasing the dietary ractopamine concentration, the serum cortisol level was elevated. Ractopamine supplementation (45.00 mg kg−1) increased serum levels of triacylglycerol and protein and reduced the activity of hepatic lipogenic enzymes and the survival rate of the fish, probably in response to the high concentration of circulating cortisol. In addition, the higher level of ractopamine supplementation evaluated in this research impaired the weight gain and feed conversion. However, 11.25 mg kg−1 ractopamine reduced the ether extract level determined in the fillet and the fat deposition between muscle fibers, improving the nutritional quality of meat.(AU)

Standardized ileal digestible lysine in diets for pigs fed ractopamine in commercial production system / Lisina digestível para suínos recebendo ractopamina em sistema comercial de produção

Two consecutive experiments were conducted using 480 pigs each with six replicate pens per treatment and 10 pigs per pen to evaluate the effect of standardized ileal digestible (SID) Lys (0.81, 0.91, 1.01, and 1.11%) in diets containing ractopamine (RAC; 10 or 20 mg kg-1) on growth and carcass traits of barrows in a commercial production system. There were no effects of either RAC levels or the interaction between RAC and SID Lys levels on any of the performance and carcass variables. No lack of fit was detected in the response surface analysis. From d 0 to 21, there was no effect of SID Lys levels on ADFI. However, as SID Lys increased, there was a linear increase in ADG and G:F. As SID Lys increased, the ADG, G:F, loin depth, and lean percentage improved linearly from d 0 to 28, with no effect on ADFI and backfat thickness. In conclusion, performance and carcass traits of pigs fed RAC (10 or 20 mg kg-1) in a commercial finishing facility are improved by up to 1.11% SID Lys supplementation. There is no additional benefit of feeding 20 mg kg-1 RAC in comparison with 10 mg kg-1 RAC.

Dois experimentos consecutivos foram conduzidos com 480 suínos cada um, com 6 repetições (baia) por tratamento e 10 suínos por baia para avaliar o efeito da lisina digestível LISD (0,81; 0,91; 1,01 e 1,11%) em rações com ractopamina (RAC; 10 ou 20 mg kg-1) no desempenho e características de carcaça de suínos em sistema de produção comercial. Não houve efeito dos níveis de RAC nem interação entre os níveis de RAC e LISD para nenhuma das variáveis de desempenho e de características de carcaça. Não foi detectada falta de ajuste na análise de superfície de resposta. De 0 a 21 dias, não houve efeito dos níveis de LISD no CRMD. No entanto, com o aumento dos níveis de LISD houve aumento linear no GPD e na eficiência alimentar (G:F). De 0 a 28 dias, com o aumento dos níveis de LISD o GPD, a G:F, a profundidade de lombo e a porcentagem de tecido magro aumentaram linearmente, sem efeito no CRMD e na espessura de toucinho. Em conclusão, os melhores resultados de desempenho e de características de carcaça de suínos alimentados com ractopamine (10 ou 20 mg kg-1) em sistema de produção comercial foram obtidos com 1,11% de LISD na ração. Não há benefício adicional com a suplementação de 20 mg kg-1 de RAC em comparação com 10 mg kg-1.

Use of ractopamine during compensatory gain of finishing pigs on carcass and meat performance and quality / Uso de ractopamina durante ganho compensatório de suínos em terminação sobre o desempenho e a qualidade da carcaça e de carne

The objective of this study was to evaluate the effects of compensatory gain associated with the use of 10ppm ractopamine after a period of feed restriction in finishing pigs on performance, carcass and meat quality. Twenty castrated males and 20 females, at 110 days of age and 66.137±6.13kg live weight, were submitted to four treatments using a 2 x 2 factorial design (fed ad libitum or with 20% restriction between 0(21 days of age and fed with or without 10ppm ractopamine for 22(42 days of experimentation), with 10 replicates (animals). There was no interaction between the factors for any of the evaluated parameters. Animals treated with ractopamine presented better weight gain (1.083 versus 1.259kg), feed conversion (2.910 versus 2.577), warm and cold carcass weight (86.08 versus 89.00 and 83.46 versus 87.20kg, respectively), loin depth (63.02 versus 68.40mm), loin eye area (41.43 versus 46.59mm2) and muscle fiber diameter (27.48 versus 35.85µm). Animals submitted to feed restriction followed by ad libitum feed presented compensatory gain without losses to carcass and meat characteristics, but with a reduction in the ethereal extract (2.19 versus 1.64%) and lower water loss due to thawing in the meat (11.35 versus 9.42%). The effects of compensatory gain after food restriction and ractopamine are independent of the parameters evaluated.(AU)

Objetivou-se avaliar os efeitos do ganho compensatório associado ao uso de 10ppm de ractopamina após um período de restrição alimentar, em suínos em terminação, sobre características de desempenho, carcaça e qualidade de carne. Foram utilizados 20 machos castrados e 20 fêmeas, com 110 dias de idade e 66,137±6,13kg de peso vivo, submetidos a quatro tratamentos, fatorial 2 x 2 (alimentação à vontade ou com 20% de restrição entre zero e 21 dias de experimentação; e alimentação à vontade, sem ou com 10ppm de ractopamina, durante 22 a 42 dias de experimentação), com 10 repetições, sendo o animal a repetição. Não houve interação entre os fatores para nenhum dos parâmetros avaliados. Animais tratados com ractopamina apresentaram melhor ganho de peso (1,083 versus 1,259kg), conversão alimentar (2,910 versus 2,577), peso da carcaça quente e fria (86,08 versus 89,00 e 83,46 versus 87,20kg, respectivamente), profundidade do lombo (63,02 versus 68,40mm), área de olho de lombo (41,43 versus 46,59mm2) e diâmetro de fibras musculares (27,48 versus 35,85µm). Animais submetidos à restrição alimentar seguida de arraçoamento ad libitum apresentaram ganho compensatório sem prejuízos às características de carcaça e à carne, mas com redução do extrato etéreo (2,19 versus 1,64%) e menor perda de água por descongelamento na carne (11,35 versus 9,42%) Os efeitos do ganho compensatório após a restrição alimentar e da ractopamina mostram-se independentes sobre os parâmetros avaliados.(AU)

Standardized ileal digestible lysine in diets for pigs fed ractopamine in commercial production system / Lisina digestível para suínos recebendo ractopamina em sistema comercial de produção

Two consecutive experiments were conducted using 480 pigs each with six replicate pens per treatment and 10 pigs per pen to evaluate the effect of standardized ileal digestible (SID) Lys (0.81, 0.91, 1.01, and 1.11%) in diets containing ractopamine (RAC; 10 or 20 mg kg-1) on growth and carcass traits of barrows in a commercial production system. There were no effects of either RAC levels or the interaction between RAC and SID Lys levels on any of the performance and carcass variables. No lack of fit was detected in the response surface analysis. From d 0 to 21, there was no effect of SID Lys levels on ADFI. However, as SID Lys increased, there was a linear increase in ADG and G:F. As SID Lys increased, the ADG, G:F, loin depth, and lean percentage improved linearly from d 0 to 28, with no effect on ADFI and backfat thickness. In conclusion, performance and carcass traits of pigs fed RAC (10 or 20 mg kg-1) in a commercial finishing facility are improved by up to 1.11% SID Lys supplementation. There is no additional benefit of feeding 20 mg kg-1 RAC in comparison with 10 mg kg-1 RAC.(AU)

Dois experimentos consecutivos foram conduzidos com 480 suínos cada um, com 6 repetições (baia) por tratamento e 10 suínos por baia para avaliar o efeito da lisina digestível LISD (0,81; 0,91; 1,01 e 1,11%) em rações com ractopamina (RAC; 10 ou 20 mg kg-1) no desempenho e características de carcaça de suínos em sistema de produção comercial. Não houve efeito dos níveis de RAC nem interação entre os níveis de RAC e LISD para nenhuma das variáveis de desempenho e de características de carcaça. Não foi detectada falta de ajuste na análise de superfície de resposta. De 0 a 21 dias, não houve efeito dos níveis de LISD no CRMD. No entanto, com o aumento dos níveis de LISD houve aumento linear no GPD e na eficiência alimentar (G:F). De 0 a 28 dias, com o aumento dos níveis de LISD o GPD, a G:F, a profundidade de lombo e a porcentagem de tecido magro aumentaram linearmente, sem efeito no CRMD e na espessura de toucinho. Em conclusão, os melhores resultados de desempenho e de características de carcaça de suínos alimentados com ractopamine (10 ou 20 mg kg-1) em sistema de produção comercial foram obtidos com 1,11% de LISD na ração. Não há benefício adicional com a suplementação de 20 mg kg-1 de RAC em comparação com 10 mg kg-1.(AU)

Use of ractopamine during compensatory gain of finishing pigs on carcass and meat performance and quality / Uso de ractopamina durante ganho compensatório de suínos em terminação sobre o desempenho e a qualidade da carcaça e de carne

The objective of this study was to evaluate the effects of compensatory gain associated with the use of 10ppm ractopamine after a period of feed restriction in finishing pigs on performance, carcass and meat quality. Twenty castrated males and 20 females, at 110 days of age and 66.137±6.13kg live weight, were submitted to four treatments using a 2 x 2 factorial design (fed ad libitum or with 20% restriction between 0(21 days of age and fed with or without 10ppm ractopamine for 22(42 days of experimentation), with 10 replicates (animals). There was no interaction between the factors for any of the evaluated parameters. Animals treated with ractopamine presented better weight gain (1.083 versus 1.259kg), feed conversion (2.910 versus 2.577), warm and cold carcass weight (86.08 versus 89.00 and 83.46 versus 87.20kg, respectively), loin depth (63.02 versus 68.40mm), loin eye area (41.43 versus 46.59mm2) and muscle fiber diameter (27.48 versus 35.85µm). Animals submitted to feed restriction followed by ad libitum feed presented compensatory gain without losses to carcass and meat characteristics, but with a reduction in the ethereal extract (2.19 versus 1.64%) and lower water loss due to thawing in the meat (11.35 versus 9.42%). The effects of compensatory gain after food restriction and ractopamine are independent of the parameters evaluated.(AU)

Objetivou-se avaliar os efeitos do ganho compensatório associado ao uso de 10ppm de ractopamina após um período de restrição alimentar, em suínos em terminação, sobre características de desempenho, carcaça e qualidade de carne. Foram utilizados 20 machos castrados e 20 fêmeas, com 110 dias de idade e 66,137±6,13kg de peso vivo, submetidos a quatro tratamentos, fatorial 2 x 2 (alimentação à vontade ou com 20% de restrição entre zero e 21 dias de experimentação; e alimentação à vontade, sem ou com 10ppm de ractopamina, durante 22 a 42 dias de experimentação), com 10 repetições, sendo o animal a repetição. Não houve interação entre os fatores para nenhum dos parâmetros avaliados. Animais tratados com ractopamina apresentaram melhor ganho de peso (1,083 versus 1,259kg), conversão alimentar (2,910 versus 2,577), peso da carcaça quente e fria (86,08 versus 89,00 e 83,46 versus 87,20kg, respectivamente), profundidade do lombo (63,02 versus 68,40mm), área de olho de lombo (41,43 versus 46,59mm2) e diâmetro de fibras musculares (27,48 versus 35,85µm). Animais submetidos à restrição alimentar seguida de arraçoamento ad libitum apresentaram ganho compensatório sem prejuízos às características de carcaça e à carne, mas com redução do extrato etéreo (2,19 versus 1,64%) e menor perda de água por descongelamento na carne (11,35 versus 9,42%) Os efeitos do ganho compensatório após a restrição alimentar e da ractopamina mostram-se independentes sobre os parâmetros avaliados.(AU)

Meat quality in pigs fed diets with gradual ractopamine supplementation and nutritional adjustments / Suplementação de ractopamina e ajustes nutricionais das dietas na qualidade da carne suína

This study evaluated the effects that gradual ractopamine supplementation in diets with nutritional adjustments on pig meat. Were used 80 finishing crossbred barrows in a randomized block design with a 2×5 factorial arrangement (two diets: with and without nutritional adjustment; five levels of ractopamine supplementation: 5-5, 10-10, 20-20, 5-10 and 10-20 ppm) in the 14 initial and 14 final study days, four replicates with two animals by experimental unit. Higher shear force values (P<0.05) were obtained using the 5-5 and 10-20 ppm ractopamine supplementation plans in the diets without nutritional adjustment. With nutritionally adjusted diets, the 5-10 ppm of ractopamine supplementation plan yielded higher shear force values (P<0.05). Water retention capacity was higher (P<0.05) for animals fed adjusted diets and 5-5 and 10-20 ppm of ractopamine plans. In the 10-20 ppm of ractopamine supplementation plan, meat pH was higher (P<0.05) for diets without nutritional adjustment, whereas in the 20-20 ppm of supplementation plan, pH was higher for adjusted diets.

O objetivo do estudo foi avaliar a qualidade da carne de suínos alimentados com dietas suplementadas gradualmente com ractopamina e ajustadas nutricionalmente. Foram utilizados 80 suínos, machos castrados, em terminação. O delineamento experimental foi o de blocos ao acaso em esquema fatorial 2x5 (dietas com e sem ajustes nutricionais; e cinco suplementações de ractopamina: 5-5; 10-10; 20-20; 5-10; 10-20 ppm, respectivamente nos 14 dias iniciais e 14 dias finais do experimento) e quatro repetições com dois animais por unidade experimental. Constatou-se maior força de cisalhamento (P<0,05) nos planos de suplementação de 5-5 e 10-20 ppm de ractopamina para as dietas sem ajustes nutricionais. Nas dietas com ajustes nutricionais, o plano de suplementação de 5-10 ppm apresentou maior força de cisalhamento (P<0,05) e os planos com suplementação de 5-5 e 10-20 ppm apresentaram maior capacidade de retenção de água (P<0,05) em relação aos demais. Observou-se aumento do pH (P<0,05) com a suplementação de 10-20 ppm de ractopamina em dietas não ajustadas nutricionalmente. Na suplementação de 20-20 ppm de ractopamina o pH foi maior (P<0,05) em relação ao plano com suplementação de ractopamina em dietas não ajustadas nutricionalmente.