Alternative to antimicrobial growth promoters in the diets of broilers challenged with subclinical necrotic enteritis.

Necrotic enteritis (NE) is a disease of worldwide distribution, which affects young broilers and causes economic losses on a scale of 6 billion dollars per year. For decades, NE was controlled in poultry flocks by dietary administration of low doses of antimicrobial growth promoters (AGPs). However, an increase in NE incidence was noted after the AGP ban. This study aimed to compare the effect of an antibiotic (Enramycin) diet to a combination of sodium butyrate, hydrolyzed yeast, and zinc proteinate (ViligenTM) on broiler diets regarding performance, blood parameters, intestinal permeability, morphology and lesions, and carcass yield of broilers challenged with Eimeria spp. and Clostridium perfringens to simulate subclinical necrotic enteritis. A total of 1,150 one-day-old male broiler chickens with an initial average weight of 43.9 ± 0.65 g were allocated to 50 experimental pens. Animals were divided into 5 groups: Negative control (NC) without additives; Positive control (PC) with 0.12 g/ton of Enramycin (8%); V500, V1000, and V1500 with the addition of 500, 1.000, and 1.500 g/ton of Viligen, respectively. All animals were challenged by Eimeria spp. at 7 d of age and by C. perfringens at 17, 18, and 19 d for induction of subclinical NE. The broilers fed with all concentrations of Viligen showed similar performance, blood parameters, intestinal permeability, and carcass yield compared to PC broilers. However, NC broilers showed higher FCR compared to PC broilers from 1 to 33 d (1.42 vs. 1.39) (P = 0.048) and from 1 to 42 d (1.51 vs. 1.49) (P < 0.001). V1500 broilers had fewer intestinal lesions at 28 d when compared to the PC treatment (P < 0.05) and showed that higher Viligen inclusion resulted in lower intestinal damage. At 21 d, the V500 group showed higher intestinal morphology characteristics (VH:VD 4.9 vs. 3.5) compared to the PC treatment (P < 0.001). Thus, in this study, the dietary addition of Viligen to broilers challenged by an experimental model of subclinical NE resulted in lower intestinal damage and similar performance to that obtained by the addition of Enramycin.

Autolyzed yeast and sodium butyrate supplemented alone to diets promoted improvements in performance, intestinal health and nutrient transporter in weaned piglets.

This study investigated the effects of supplemental nucleotides, autolyzed yeast (Saccharomyces cerevisiae), and sodium butyrate in diets for nursery pigs on growth performance, diarrhea incidence, blood profile, intestinal morphology, mRNA expression of nutrient transporters, inflammatory markers, antioxidant profile, and tight junction proteins in the small intestine. One hundred eighty 21-day-old pigs (5.17 ± 0.57 kg) were assigned in a randomized block design to 1 of 4 dietary treatments: (1) CON: control, basal diet, (2) NUC: CON + nucleotides, (3) YSC: CON + lysed yeast S. cerevisiae, (4) ASB: CON + acidifier sodium butyrate. Pigs were fed for 24 days, phase 1 (21-32 days) and 2 (32-45 days). During phase 1, YSC and ASB improved average daily gain (ADG) and feed conversion (FC) compared with CON. At the overall period, ASB improved ADG and YSC improved FC compared with CON. The NUC diet did not affect growth performance. The ASB increased ileal villus height compared to CON. The YSC and ASB reduced the number of Peyer's patches in the ileum compared with CON. The YSC increased mRNA expression of nutrient transporters (SMCT2, MCT1, and PepT1), tight junction proteins (OCL and ZO-1), antioxidants (GPX), and IL1-ß in the jejunum compared with CON. The ASB increased mRNA expression of nutrient transporters (SGLT1 and MCT1), tight junction proteins (OCL and ZO-1), and antioxidants (GPX and SOD) compared with CON. In conclusion, autolyzed yeast and sodium butyrate promoted growth performance by improving the integrity of the intestinal barrier, the mRNA expression of nutrient transporters, and antioxidant enzymes in the jejunum of nursery pigs whereas supplementation of nucleotides did not show such effects.

GPR43 regulates sodium butyrate-induced angiogenesis and matrix remodeling.

Butyrate is a short-chain fatty acid (SCFA) derived from microbiota and is involved in a range of cell processes in a concentration-dependent manner. Low concentrations of sodium butyrate (NaBu) were shown to be proangiogenic. However, the mechanisms associated with these effects are not yet fully known. Here, we investigated the contribution of the SCFA receptor GPR43 in the proangiogenic effects of local treatment with NaBu and its effects on matrix remodeling using the sponge-induced fibrovascular tissue model in mice lacking the Gpr43 gene (Gpr43-KO) and the wild-type (WT) mice. We demonstrated that NaBu (0.2 mM intraimplant) treatment enhanced the neovascularization process, blood flow, and VEGF levels in a GPR43-dependent manner in the implants. Moreover, NaBu was able to modulate matrix remodeling aspects of the granulation tissue such as proteoglycan production, collagen deposition, and α-smooth muscle actin (α-SMA) expression in vivo, besides increasing transforming growth factor (TGF)-ß1 levels in the fibrovascular tissue, in a GPR43-dependent manner. Interestingly, NaBu directly stimulated L929 murine fibroblast migration and TGF-ß1 and collagen production in vitro. GPR43 was found to be expressed in human dermal fibroblasts, myofibroblasts, and endothelial cells. Overall, our findings evidence that the metabolite-sensing receptor GPR43 contributes to the effects of low dose of NaBu in inducing angiogenesis and matrix remodeling during granulation tissue formation. These data provide important insights for the proposition of new therapeutic approaches based on NaBu, beyond the highly explored intestinal, anti-inflammatory, and anticancer purposes, as a local treatment to improve tissue repair, particularly, by modulating granulation tissue components.NEW & NOTEWORTHY Our data show the contribution of the metabolite-sensing receptor GPR43 in the effects of low dose of sodium butyrate (NaBu) on stimulating angiogenesis and extracellular matrix remodeling in a model of granulation tissue formation in mice. We also show that human dermal fibroblasts, myofibroblasts, and endothelial cells express the receptor GPR43. These data provide important insights for the use of NaBu in local therapeutic approaches applicable to tissue repair in sites other than the intestine.

Effect of dialyzable leukocyte extract, sodium butyrate, and valproic acid in the development of anergy in murine leprosy.

Background: Murine leprosy is a chronic granulomatous disease caused by Mycobacterium lepraemurium (MLM) in mice and rats. The disease evolves with the development of cellular anergy that impedes the production of interferon gamma (IFNγ), tumor necrosis factor-alpha (TNFα), and nitric oxide (NO) required to kill the microorganism. In this study we investigated whether histone deacetylase inhibitors (HDACi) (valproic acid and sodium butyrate [NaB]) and the immunomodulator transfer factor in dialyzable leukocyte extracts (DLE) can prevent anergy in murine leprosy. Methods: Five groups of six Balb/c mice were intraperitoneally inoculated with 2 × 107 MLM. Thirty-days post inoculation, treatment was started; one group received no treatment, one was treated with rifampicin-clofazimine (R-C), one with sodium valproate (VPA), one with NaB, and one with DLE. The animals were monitored for the evidence of disease for 96 days. After euthanasia, their spleens were removed and processed for histologic, bacteriologic, and cytokine studies. Results: R-C completely controlled the ongoing disease. DLE and NaB significantly reduced the development of lesions, including granuloma size and the number of bacilli; VPA was less effective. DLE, NaB, and VPA reverted the anergic condition in diverse grades and allowed the expression of IFNγ, TNFα, and inducible NO synthase, also in diverse grades. Conclusion: Anergy in leprosy and murine leprosy allows disease progression. In this study, anergy was prevented, in significant degree, by DLE (an immunomodulator) and NaB (HDACi). VPA was less effective. These results suggest potential beneficial effects of DLE and NaB in the ancillary treatment of leprosy.

Prebiotics and butyric acid can replace colistin as a growth promoter for nursery piglets / [Prebióticos e ácido butírico podem substituir a colistina como promotor de crescimento para leitões em fase de creche]

This study aimed to assess different prebiotic concentrations and principles, in addition to calcium butyrate, aiming to replace colistin as a growth promoter. The sample consisted of 120 piglets weaned at 22 days old with mean initial weight of 5.475 ± 0.719kg. The animals were assigned to random blocks in six treatments corresponding to the use of the following dietary additives: T1) colistin (40 ppm); T2) ß-glucan/mannan-oligosaccharides (0.2%); T3) calcium butyrate (0.1%); T4) ß-glucan/mannan-oligosaccharides (0.1%) + fructooligosaccharides (0.01%) + galactooligosaccharides (0.09%); T5) ß-glucan/mannan-oligosaccharides (0.1%) + fructooligosaccharides (0.03%) + galactooligosaccharides (0.07%); and T6) ß-glucan/mannan-oligosaccharides (0.1%) + fructooligosaccharides (0.05%) + galactooligosaccharides (0.05%). The results showed no difference among treatments for the performance parameters in any of the phases evaluated. For diarrhea incidence and intensity, the results indicated that the treatments with alternative additives had similar effects as the group treated with colistin. A significant difference was found for the profile of propionic acid (0.23% colistin and 0.32%, 0.36%, 0.37% additives) and total fatty acids (0.67% colistin and 0.97% additives) values in the caecum. The supplementation with different compositions and concentrations of prebiotics and butyric acid may viably replace colistin in controlling diarrhea and modulating volatile fatty acid production in the caecum.(AU)

O objetivo deste trabalho foi avaliar as diferentes concentrações e princípios de prebióticos e do butirato de sódio, visando substituir a colistina como promotor de crescimento. Foram utilizados 120 leitões, desmamados aos 22 dias de idade, com peso médio inicial de 5,475 ± 0,719kg. Os animais foram distribuídos em blocos ao acaso, em seis tratamentos, que corresponderam ao uso dos seguintes aditivos dietéticos: T1) colistina (40ppm); T2) ß-glucanos/mananoligossacarídeos (0,2%); T3) butirato de cálcio (0,1%); T4) ß-glucanos/mananoligossacarídeos (0,1%) + frutoligossacarídeos (0,01%) + galactoligossacarídeos (0,09%); T5) ß-glucanos/mananoligossacarídeos (0,1%) + frutoligossacarídeos (0,03%) + galactoligossacarídeos (0,07%); e T6) ß-glucanos/mananoligossacarídeos (0,1%) + frutoligossacarídeos (0,05%) + galactoligossacarídeos (0,05%). Os resultados mostraram que não houve diferença entre os tratamentos para nenhum dos parâmetros de desempenho em nenhuma das fases avaliadas. Para a incidência e a intensidade de diarreia, os resultados apontam que os tratamentos com os aditivos alternativos apresentaram efeitos semelhantes aos do grupo tratado com colistina. Foi encontrada diferença significativa para perfil dos ácidos graxos propiônicos (0,23% colistina e 0,32%, 0,36%, 0,37% aditivos) e ácidos totais (0,67% colistina e 0,97% aditivos) no ceco. A suplementação com diferentes composições e concentrações de prebióticos e do ácido butírico pode substituir a colistina de forma viável no controle da diarreia e na modulação da produção volátil de ácidos graxos no ceco.(AU)

Prebiotics and butyric acid can replace colistin as a growth promoter for nursery piglets / [Prebióticos e ácido butírico podem substituir a colistina como promotor de crescimento para leitões em fase de creche]

This study aimed to assess different prebiotic concentrations and principles, in addition to calcium butyrate, aiming to replace colistin as a growth promoter. The sample consisted of 120 piglets weaned at 22 days old with mean initial weight of 5.475 ± 0.719kg. The animals were assigned to random blocks in six treatments corresponding to the use of the following dietary additives: T1) colistin (40 ppm); T2) ß-glucan/mannan-oligosaccharides (0.2%); T3) calcium butyrate (0.1%); T4) ß-glucan/mannan-oligosaccharides (0.1%) + fructooligosaccharides (0.01%) + galactooligosaccharides (0.09%); T5) ß-glucan/mannan-oligosaccharides (0.1%) + fructooligosaccharides (0.03%) + galactooligosaccharides (0.07%); and T6) ß-glucan/mannan-oligosaccharides (0.1%) + fructooligosaccharides (0.05%) + galactooligosaccharides (0.05%). The results showed no difference among treatments for the performance parameters in any of the phases evaluated. For diarrhea incidence and intensity, the results indicated that the treatments with alternative additives had similar effects as the group treated with colistin. A significant difference was found for the profile of propionic acid (0.23% colistin and 0.32%, 0.36%, 0.37% additives) and total fatty acids (0.67% colistin and 0.97% additives) values in the caecum. The supplementation with different compositions and concentrations of prebiotics and butyric acid may viably replace colistin in controlling diarrhea and modulating volatile fatty acid production in the caecum.(AU)

O objetivo deste trabalho foi avaliar as diferentes concentrações e princípios de prebióticos e do butirato de sódio, visando substituir a colistina como promotor de crescimento. Foram utilizados 120 leitões, desmamados aos 22 dias de idade, com peso médio inicial de 5,475 ± 0,719kg. Os animais foram distribuídos em blocos ao acaso, em seis tratamentos, que corresponderam ao uso dos seguintes aditivos dietéticos: T1) colistina (40ppm); T2) ß-glucanos/mananoligossacarídeos (0,2%); T3) butirato de cálcio (0,1%); T4) ß-glucanos/mananoligossacarídeos (0,1%) + frutoligossacarídeos (0,01%) + galactoligossacarídeos (0,09%); T5) ß-glucanos/mananoligossacarídeos (0,1%) + frutoligossacarídeos (0,03%) + galactoligossacarídeos (0,07%); e T6) ß-glucanos/mananoligossacarídeos (0,1%) + frutoligossacarídeos (0,05%) + galactoligossacarídeos (0,05%). Os resultados mostraram que não houve diferença entre os tratamentos para nenhum dos parâmetros de desempenho em nenhuma das fases avaliadas. Para a incidência e a intensidade de diarreia, os resultados apontam que os tratamentos com os aditivos alternativos apresentaram efeitos semelhantes aos do grupo tratado com colistina. Foi encontrada diferença significativa para perfil dos ácidos graxos propiônicos (0,23% colistina e 0,32%, 0,36%, 0,37% aditivos) e ácidos totais (0,67% colistina e 0,97% aditivos) no ceco. A suplementação com diferentes composições e concentrações de prebióticos e do ácido butírico pode substituir a colistina de forma viável no controle da diarreia e na modulação da produção volátil de ácidos graxos no ceco.(AU)

HDAC inhibitors reverse mania-like behavior and modulate epigenetic regulatory enzymes in an animal model of mania induced by Ouabain.

BACKGROUND: The etiology of bipolar disorder (BD) is multifactorial, involving both environmental and genetic factors. Current pharmacological treatment is associated with several side effects, which are the main reason patients discontinue treatment. Epigenetic alterations have been studied for their role in the pathophysiology of BD, as they bridge the gap between gene and environment. OBJECTIVE: Evaluate the effects of histone deacetylase inhibitors on behavior and epigenetic enzymes activity in a rat model of mania induced by ouabain. METHODS: Adult male rats were subjected to a single intracerebroventricular injection of ouabain (10-3 M) followed by 7 days of valproate (200 mg/kg) or sodium butyrate (600 mg/kg) administration. Locomotor and exploratory activities were evaluated in the open-field test. Histone deacetylase, DNA methyltransferase, and histone acetyltransferase activity were assessed in the frontal cortex, hippocampus, and striatum. RESULTS: Ouabain induced hyperactivity in rats, which was reversed by valproate and sodium butyrate treatment. Ouabain did not alter the activity of any of the enzymes evaluated. However, valproate and sodium butyrate decreased the activity of histone deacetylase and DNA methyltransferase. Moreover, there was a positive correlation between these two enzymes. CONCLUSION: These results suggest that targeting epigenetic mechanisms may play an important role in mania-like behavior management.

Failure to detect the action of antidepressants in the forced swim test in Swiss mice.

OBJECTIVE: The aims of this study were to replicate previously published experiments and to modify the protocol to detect the effects of chronic antidepressant treatment in mice. METHODS: Male Swiss mice (n=6-8/group) housed in reversed light/dark cycle were randomly assigned into receive vehicle (10% sucrose), sub-effective doses (1 and 3 mg/kg) or effective doses (10 and 30 mg/kg) of bupropion, desipramine, and fluoxetine and a candidate antidepressant, sodium butyrate (1-30 mg/kg) per gavage (p.o.) 1 h before the forced swim test (FST). Treatments continued daily for 7 and 14 days during retests 1 and 2, respectively. In an additional experiment, mice received fluoxetine (20 mg/kg) or vehicle (10% sucrose or 0.9% saline) p.o. or i.p. before the FST. Mice housed in reversed or standard light/dark cycles received fluoxetine (20 mg/kg) prior FST. Video recordings of behavioural testing were used for blind assessment of the outcomes. RESULTS: According to the expected, doses of antidepressants considered sub-effective failed to affect the immobility time of mice in the FST. Surprisingly, acute and chronic treatment with the high doses of bupropion, desipramine, and fluoxetine or sodium butyrate also failed to reduce the immobility time of mice in the FST. Fluoxetine 20 mg/kg was also ineffective in the FST when injected i.p. or in mice housed in normal light/dark cycle. CONCLUSION: Data suggest the lack of efficacy of orally administered bupropion, desipramine, fluoxetine in the FST in Swiss mice. High variability, due to high and low immobility mice, may explain the limited effects of the treatments.

Effects of lipid sources, lysophospholipids and organic acids in maize-based broiler diets on nutrient balance, liver concentration of fat-soluble vitamins, jejunal microbiota and performance.

Three experiments with a 2 × 2 × 2 factorial arrangement were conducted to evaluate maize-based diets for broilers containing different lipid sources [soybean oil (S) or beef tallow (T)] supplemented with or without lysophospholipids and organic acids on nutrient balance (Experiment I, evaluation period of 10-14 d), on liver concentration of fat-soluble vitamins, on jejunal microbiota (Experiment II, sampling at d 14) and on performance (Experiment III, accumulated periods of 1-14, 1-21 and 1-42 d). A total of 1344 male chicks were used. In each experiment, the birds were allotted in a completely randomised design with 8 replications. The lysophospholipids were mainly composed of lysolecithins and the organic acids blend was constituted by lactic (40%), acetic (7%) and butyric acids (1%). An interaction between lipid sources and lysophospholipids was observed on faecal apparent digestibility of lipid (ADL), which improved with lysophospholipids addition in T diets. Broilers fed on S had higher ADL and faecal apparent digestibility of nitrogen-corrected gross energy (ADGEN). It was not possible to demonstrate a significant treatment effect on the liver concentration of vitamins A and E, even with the differences in fatty acid profile between S and T. Enterobacteria values were below the detection threshold. Lysophospholipid supplementation reduced gram-positive cocci in T-fed birds. S diets promoted lower total anaerobe counts compared with T diets, independent of additives. S diets increased BW gain and feed:gain ratio in all evaluation periods. Lysophospholipids and organic acids improved feed:gain ratio at 1-21 d in T diets. Furthermore, main effects were observed for lysophospholipids and organic acids at 1-42 d, which increased BW gain and improved feed:gain ratio, respectively. No positive interactions between additives were found.

Histone deacetylase inhibition prevents the impairing effects of hippocampal gastrin-releasing peptide receptor antagonism on memory consolidation and extinction.

Hippocampal gastrin-releasing peptide receptors (GRPR) regulate memory formation and extinction, and disturbances in GRPR signaling may contribute to cognitive impairment associated with neurodevelopmental disorders. Histone acetylation is an important epigenetic mechanism that regulates gene expression involved in memory formation, and histone deacetylase inhibitors (HDACis) rescue memory deficits in several models. The present study determined whether inhibiting histone deacetylation would prevent memory impairments produced by GRPR blockade in the hippocampus. Male Wistar rats were given an intrahippocampal infusion of saline (SAL) or the HDACi sodium butyrate (NaB) shortly before inhibitory avoidance (IA) training, followed by an infusion of either SAL or the selective GRPR antagonist RC-3095 immediately after training. In a second experiment, the infusions were administered before and after a retention test trial that served as extinction training. As expected, RC-3095 significantly impaired consolidation and extinction of IA memory. More importantly, pretraining administration of NaB, at a dose that had no effect when given alone, prevented the effects of RC-3095. In addition, the combination of NaB and RC-3095 increased hippocampal levels of the brain-derived neurotrophic factor (BDNF). These findings indicate that HDAC inhibition can protect against memory impairment caused by GRPR blockade.

Indole butyric acid and substrates influence on multiplication of blackberry Xavante / Influência do ácido indol butírico e substratos na propagação de amoreira-preta Xavante

Blackberry is a shrubby plant specie which has a high economic importance among agriculture crops. Brazil is the major country of Latin America with the highest future scope for blackberries. For availability of good quality and maximum quantity of seedlings, the present study was carried out at the Universidade Estadual de Londrina,PR from January to March in 2013. The aim of the study was to evaluate the multiplication of blackberry 'Xavante' cuttings under different type of substrates treated with different levels of indole butyric acid (IBA). The experiment was laid out in randomized complete block design with 2 factors, i.e., substrate (rice husk, vermiculite and coconut fiber) and IBA (0; 1,000; 2,000 and 3,000mg L-1), with 5 replications. Each replicate consisted of 10 cuttings. The variables studied were: cutting rooting, cutting survival, leaf retention, cuttings with new leaves, number of major roots, length of major roots and roots dry weight. Most of the variables were significantly affected by both substrate and IBA. Rice husk and vermiculite performed better than coconut fiber and provided the same results for most of the variables, while coconut fiber showed lower performance for all of the variables studied. IBA significantly affected the rooting and the number of major roots. It is concluded that for multiplication of blackberry 'Xavante', both rice husk and vermiculite can be used along 2,000mg L-1 of IBA.(AU)

A amoreira-preta é uma espécie vegetal arbustiva que apresenta relevante importância econômica entre as culturas frutíferas. O Brasil é o maior produtor da América Latina. Para disponibilidade de boa qualidade e alta quantidade de mudas, o presente estudo foi realizado na Universidade Estadual de Londrina, PR, de janeiro a março, em 2013.O objetivo foi avaliar a mulitiplicação de amoreira-preta 'Xavante' em vários tipos de substratos sob diferentes níveis de ácido indol butírico (AIB). O delineamento experimental foi em blocos casualizados com dois fatores: substrato (casca de arroz carbonizada, vermiculita e fibra de coco) e AIB (0, 1.000, 2.000 e 3.000mg L-1), com cinco repetições, sendo cada repetição constituída por 10 estacas. As variáveis avaliadas foram: estacas enraizadas, sobrevivência das estacas, retenção de folhas, estacas com folhas novas, número de raízes, comprimento de raízes e massa seca dos raízes. A maioria das variáveis foi significativamente afetada pelos substratos e AIB. A casca de arroz e vermiculita apresentaram melhor desempenho quanto à maioria das variáveis, enquanto a fibra de coco apresentou dempenho inferior. O AIB afetou significativamente a porcentagem de enraizamento e o número de principais raízes. Conclui-se que, para a otimizar a multiplicação de mudas de amoreira-preta 'Xavante' , tanto a casca de arroz carbonizada como a vermiculita podem ser usadas, associadas a 2.000mg L-1 de AIB.(AU)

Improvement of the boron neutron capture therapy (BNCT) by the previous administration of the histone deacetylase inhibitor sodium butyrate for the treatment of thyroid carcinoma.

We have shown that boron neutron capture therapy (BNCT) could be an alternative for the treatment of poorly differentiated thyroid carcinoma (PDTC). Histone deacetylase inhibitors (HDACI) like sodium butyrate (NaB) cause hyperacetylation of histone proteins and show capacity to increase the gamma irradiation effect. The purpose of these studies was to investigate the use of the NaB as a radiosensitizer of the BNCT for PDTC. Follicular thyroid carcinoma cells (WRO) and rat thyroid epithelial cells (FRTL-5) were incubated with 1 mM NaB and then treated with boronophenylalanine ¹°BPA (10 µg ¹°B ml⁻¹) + neutrons, or with 2, 4-bis (α,ß-dihydroxyethyl)-deutero-porphyrin IX ¹°BOPP (10 µg ¹°B ml⁻¹) + neutrons, or with a neutron beam alone. The cells were irradiated in the thermal column facility of the RA-3 reactor (flux = (1.0 ± 0.1) × 10¹° n cm⁻² s⁻¹). Cell survival decreased as a function of the physical absorbed dose in both cell lines. Moreover, the addition of NaB decreased cell survival (p < 0.05) in WRO cells incubated with both boron compounds. NaB increased the percentage of necrotic and apoptotic cells in both BNCT groups (p < 0.05). An accumulation of cells in G2/M phase at 24 h was observed for all the irradiated groups and the addition of NaB increased this percentage. Biodistribution studies of BPA (350 mg kg⁻¹ body weight) 24 h after NaB injection were performed. The in vivo studies showed that NaB treatment increases the amount of boron in the tumor at 2-h post-BPA injection (p < 0.01). We conclude that NaB could be used as a radiosensitizer for the treatment of thyroid carcinoma by BNCT.

Valproic acid: an anticonvulsant drug with potent antinociceptive and anti-inflammatory properties.

Valproic acid (VA) is a major antiepileptic drug, used for several therapeutic indications. It has a wide activity spectrum, reflecting on mechanisms of action that are not fully understood. The objectives of this work were to study the effects of VA on acute models of nociception and inflammation in rodents. VA (0.5, 1, 10, 25, and 50 mg/kg, p.o.) effects were evaluated on the carrageenan-induced paw edema, carrageenan-induced peritonitis, and plantar tests in rats, as well as by the formalin test in mice. The HE staining and immunohistochemistry assay for TNF-α in carrageenan-induced edema, from paws of untreated and VA-treated rats, were also carried out. VA decreased paw edema after carrageenan, and maximum effects were seen with doses equal to or higher than 10 mg/kg. VA also preserved the tissue architecture as assessed by the HE staining. Immunohistochemical studies revealed that VA significantly reduced TNF-α immunostaining in carrageenan-inflamed rat paws. In addition, the anti-inflammatory action of VA was potentiated by pentoxifylline (a phosphodiesterase inhibitor, known to inhibit TNF-α production), but not by sodium butyrate or by suberoylanilide hydroxamic acid (SAHA), nonspecific and specific inhibitors, respectively, of histone deacetylase. However, the decrease in the number of positive TNF-α cells in the rat paw was drastically potentiated in the VA + SAHA associated group. VA also reduced leukocytes and myeloperoxidase (MPO) releases to the peritoneal exudate, in the carrageenan-induced peritonitis. Although in the formalin test, VA inhibited both phases, the inhibition was mainly on the second phase. Furthermore, VA significantly increased the reaction time to thermal stimuli, as assessed by the plantar test. VA is a multi-target drug, presenting potent antinociceptive and anti-inflammatory properties at a lower dose range. These effects are partly dependent upon its inhibitory action on TNF-α-related pathways. However, the participation of the HDAC inhibition with the VA anti-inflammatory action cannot be ruled out. Inflammatory processes are associated with free radical damage and oxidative stress, and their blockade by VA could also explain the present results.

Ácido fumárico e sua combinação com os ácidos butírico ou fórmico em dietas de leitões recém desmamados / Fumaric, butyric and formic acid combinations in feed formulation for recently weaned piglets

Avaliaram-se o desempenho e as características morfológicas e morfométricas do intestino delgado de 210 leitões, desmamados aos 15 dias de idade, com peso médio inicial 4,04±0,66kg, em dois períodos experimentais (15-30 e 15-36 dias de idade). O delineamento experimental foi em blocos ao acaso, com sete tratamentos (T1: ração-controle sem adição de acidificante; T2: ração-controle + 0,5 por cento de ácido fumárico; T3: ração-controle + 1,0 por cento de ácido fumárico; T4: ração-controle + 0,5 por cento de ácido fumárico +0,1 por cento de ácido butírico; T5: ração-controle + 0,5 por cento de ácido fumárico + 0,5 por cento de ácido fórmico; T6: ração-controle + 1,0 por cento de ácido fumárico + 0,1 por cento de ácido butírico e T7: ração-controle + 1,0 por cento de ácido fumárico +0,5 por cento de ácido fórmico), cinco repetições e seis animais por unidade experimental. O peso dos leitões aos 30 dias de idade não foi influenciado pelos tratamentos, mas houve efeito significativo de tratamento sobre ganho de peso e consumo alimentar diário no período de 15-30 dias de idade, com maior desempenho para os leitões alimentados com dietas suplementadas com ácido fumárico. Não houve efeito significativo dos tratamentos sobre o peso médio aos 36 dias, o ganho de peso, o consumo diário e a conversão alimentar dos leitões de 15 a 36 dias de idade. Houve diferença entre tratamentos para a altura do epitélio do duodeno, porém não houve diferença em relação à do jejuno e à do íleo. As eletromicrografias do duodeno dos leitões alimentados com as diferentes dietas experimentais revelaram vilosidades com características normais(AU)

Performance, morphological and morphometric characteristics of the small intestine of 210 recently weaned piglets, averaging 4.04 ± 0.66 kg, during two periods ( from 15 to 30 days of age and from 15 to 36 days of age) were evaluated in a randomized block experimental design with seven treatments, T1: control diet (CD); T2: CD + 0.5 percent fumaric acid; T3: CD + 1.0 percent fumaric acid; T4: CD + 0.5 percent fumaric acid + 0.1 percent butyric acid; T5: CD + 0.5 percent fumaric acid + 0.5 percent formic acid; T6: CD + 1,0 percent fumaric acid + 0.1 percent butyric acid and T7: CD + 1.0 percent fumaric acid + 0.5 percent formic acid, five replicates and six piglets per experimental unit. No effects of treatment (P<0.05) on body weight at 30 days of age was observed but significant differences between treatments were observed for daily weight gain and feed consumption from 15 to 30 days of age. Piglets fed supplemented acid fumaric diets had higher performance during this period. No significant effects of treatments on body weight at 36 days of age, daily weight gain, daily feed intake and feed conversion were observed (P>0.05) from 16 to 36 days of age. Significant differences (P<0.05) between treatments for duodenal epithelium height were observed, but not for jejunum and ileum epithelium heights. Normal villus patterns were observed in the electromicrographs of duodenum from piglets fed all different diets(AU)

Ácido fumárico e sua combinação com os ácidos butírico ou fórmico em dietas de leitões recém desmamados / Fumaric, butyric and formic acid combinations in feed formulation for recently weaned piglets

Avaliaram-se o desempenho e as características morfológicas e morfométricas do intestino delgado de 210 leitões, desmamados aos 15 dias de idade, com peso médio inicial 4,04±0,66kg, em dois períodos experimentais (15-30 e 15-36 dias de idade). O delineamento experimental foi em blocos ao acaso, com sete tratamentos (T1: ração-controle sem adição de acidificante; T2: ração-controle + 0,5 por cento de ácido fumárico; T3: ração-controle + 1,0 por cento de ácido fumárico; T4: ração-controle + 0,5 por cento de ácido fumárico +0,1 por cento de ácido butírico; T5: ração-controle + 0,5 por cento de ácido fumárico + 0,5 por cento de ácido fórmico; T6: ração-controle + 1,0 por cento de ácido fumárico + 0,1 por cento de ácido butírico e T7: ração-controle + 1,0 por cento de ácido fumárico +0,5 por cento de ácido fórmico), cinco repetições e seis animais por unidade experimental. O peso dos leitões aos 30 dias de idade não foi influenciado pelos tratamentos, mas houve efeito significativo de tratamento sobre ganho de peso e consumo alimentar diário no período de 15-30 dias de idade, com maior desempenho para os leitões alimentados com dietas suplementadas com ácido fumárico. Não houve efeito significativo dos tratamentos sobre o peso médio aos 36 dias, o ganho de peso, o consumo diário e a conversão alimentar dos leitões de 15 a 36 dias de idade. Houve diferença entre tratamentos para a altura do epitélio do duodeno, porém não houve diferença em relação à do jejuno e à do íleo. As eletromicrografias do duodeno dos leitões alimentados com as diferentes dietas experimentais revelaram vilosidades com características normais

Performance, morphological and morphometric characteristics of the small intestine of 210 recently weaned piglets, averaging 4.04 ± 0.66 kg, during two periods ( from 15 to 30 days of age and from 15 to 36 days of age) were evaluated in a randomized block experimental design with seven treatments, T1: control diet (CD); T2: CD + 0.5 percent fumaric acid; T3: CD + 1.0 percent fumaric acid; T4: CD + 0.5 percent fumaric acid + 0.1 percent butyric acid; T5: CD + 0.5 percent fumaric acid + 0.5 percent formic acid; T6: CD + 1,0 percent fumaric acid + 0.1 percent butyric acid and T7: CD + 1.0 percent fumaric acid + 0.5 percent formic acid, five replicates and six piglets per experimental unit. No effects of treatment (P<0.05) on body weight at 30 days of age was observed but significant differences between treatments were observed for daily weight gain and feed consumption from 15 to 30 days of age. Piglets fed supplemented acid fumaric diets had higher performance during this period. No significant effects of treatments on body weight at 36 days of age, daily weight gain, daily feed intake and feed conversion were observed (P>0.05) from 16 to 36 days of age. Significant differences (P<0.05) between treatments for duodenal epithelium height were observed, but not for jejunum and ileum epithelium heights. Normal villus patterns were observed in the electromicrographs of duodenum from piglets fed all different diets