RESUMO
Background: In patients with cardiogenic shock the clinical treatment often involves temporary mechanical circulatory support for initial haemodynamic stabilization to enable further assessment of therapeutic strategies. The surgically implanted Impella 5.5 can be used for several indications like ventricular unloading, haemodynamic support during high-risk interventions, and as a bridge-to-transplant strategy.We present an interdisciplinary managed case of using Impella 5.5 for multiple indications and treatment strategies in one patient. Case summary: A 66-year-old patient with known dilated cardiomyopathy was admitted with non-ST-elevation myocardial infarction and underwent urgent coronary bypass grafting. His native heart function did not recover and he experienced recurrent episodes of sustained ventricular tachycardia (VT) and electrical storm. He was evaluated for heart transplantation (OHT) and received a VT-ablation. However, he suffered an in-hospital cardiac arrest (IHCA) with subsequent implantation of an extracorporeal life support system (ECLS). After surgical placement of an Impella 5.5 due to left ventricular distension and pulmonary congestion, the ECLS was successfully weaned. He showed good neurological outcomes and underwent another high-risk VT-ablation. The patient was further stabilized under Impella 5.5 support in a bridge-to-transplant strategy. After 34 days he underwent a successful OHT. Discussion: In this interdisciplinary case report the surgically implanted Impella 5.5 as temporary mechanical circulatory support was used for multiple different indications and treatment strategies like ventricular unloading, haemodynamic support during high-risk interventions, and as bridge-to-transplant strategy in one patient.
RESUMO
The cytotoxicity of deoxynivalenol (DON) as well as the induction of cytokines and related genes was investigated in porcine pulmonary alveolar macrophages (PAM) in absence or presence of lipopolysaccharides (LPS). IC(20) values were 1.1, 0.4 and 1.0microM DON in the MTT, neutral red and alamar blue assay, respectively, and did not differ significantly in the presence of LPS. The mRNA expression of tumour necrosis factor (TNF)-alpha peaked at 3h, whereas LPS and DON showed synergistic effects resulting in an approximately 20-fold increase at 500nM DON as compared to untreated controls. The supernatant concentrations of TNF-alpha showed similar synergistic effects. The expression of interleukin (IL)-1beta was significantly induced by DON (except for 12h) and LPS. An induction of the mRNA expression of IL-6 by DON was evident only at 3h, whereas the supernatant concentrations of LPS stimulated PAM incubated with 500nM DON were significantly decreased at most time points. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression did not seem to contribute to the effects of DON in porcine macrophages. The results of the present investigation suggest a contribution of cytokines, especially TNF-alpha and IL-1beta, induced by DON in porcine macrophages to the effects observed in vivo.
Assuntos
Citocinas/genética , Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Tricotecenos/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/imunologia , Interpretação Estatística de Dados , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Macrófagos Alveolares/citologia , Macrófagos Alveolares/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Suínos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
The trichothecene mycotoxin deoxynivalenol (DON) causes systemic immuno-suppression in pigs and possibly also in humans after chronic dietary exposure. Since the outcome of every immune response is largely controlled by dendritic cells (DC), we hypothesised that a direct influence of DON on DC function might play a role in mediating DON immunotoxicity. To test this hypothesis, a 2x2 factorial design study was performed. Pigs were fed a control diet or a diet containing DON (DON-diet); monocyte-derived DC (MoDC) from these pigs were then treated with DON in vitro or left untreated. Phenotype and function of the MoDC were analysed. In vitro DON-treatment of MoDC from pigs fed the control diet resulted in a down-regulation of CD80/86 and CD40. This was associated with an activation of the mitogen-associated protein kinases ERK1/2 and JNK. The endocytic activity of MoDC was decreased after in vitro DON-exposure while their T cell stimulatory capacity was not altered. MoDC derived from pigs that had been fed the DON-diet failed to up-regulate MHC-II in response to LPS/TNFalpha. Dietary exposure of pigs to DON inhibited endocytosis of FITC-dextran by MoDC, but did not influence T cell stimulatory capacity. ERK1/2 and JNK were constitutively activated in MoDC from pigs fed the DON-diet. If MoDC derived from pigs fed the DON-diet were exposed to DON in vitro, this resulted in an up-regulation of MHC-II and CD80/86, but not CD40. In comparison to untreated MoDC from pigs fed DON-diet, endocytic capacity was further down-regulated, whereas mitogen-activated protein kinase activation was increased. In summary, DON disrupts porcine DC function in vitro and in vivo, which might contribute to the immunosuppressive effects of this mycotoxin.
Assuntos
Células Dendríticas/efeitos dos fármacos , Monócitos/citologia , Monócitos/efeitos dos fármacos , Micotoxinas/toxicidade , Tricotecenos/toxicidade , Animais , Apoptose/efeitos dos fármacos , Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Antígenos CD40/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/análise , Células Dendríticas/imunologia , Células Dendríticas/ultraestrutura , Relação Dose-Resposta a Droga , Regulação para Baixo , Endocitose/efeitos dos fármacos , Endocitose/imunologia , Fusarium/química , Fusarium/metabolismo , Humanos , Imunotoxinas/sangue , Imunotoxinas/toxicidade , Técnicas In Vitro , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Monócitos/imunologia , Monócitos/ultraestrutura , Fenótipo , Sus scrofa , Tricotecenos/sangue , Fator de Necrose Tumoral alfa/metabolismo , Regulação para CimaRESUMO
The aim of the present experiment was to determine if a niacin supplementation of 6 g/d to lactating dairy cow diets can compensate negative effects of a rumen nitrogen balance (RNB) deficit. A total of nine ruminally and duodenally fistulated lactating multiparous German Holstein cows were successively assigned to one of three diets consisting of 10 kg maize silage (dry matter [DM] basis) and 7 kg DM concentrate: Diet RNB- (n = 6) with energy and utilisable crude protein at the duodenum (uCP) according to the average requirement of the animals but with a negative RNB (-0.41 g N/MJ metabolisable energy [ME]); Diet RNB0 (n = 7) with energy, uCP and a RNB (0.08 g N/MJ ME) according to the average requirement of the animals and, finally, Diet NA (n = 5), which was the same diet as RNB-, but supplemented with 6 g niacin/d. Samples of milk were taken on two consecutive days, blood samples were taken on one day pre- and post-feeding and faeces and urine were collected completely over five consecutive days. The negative RNB reduced milk and blood urea content and apparent total tract digestibility of DM, organic matter (OM) and neutral detergent fibre (NDF). Also N excretion with urine, the total N excreted with urine and faeces and the N balance were reduced when the RNB was negative. Supplementation of niacin elevated plasma glucose concentration after feeding and the N balance increased. Supplementing the diet with a negative RNB with niacin led to a more efficient use of dietary N thereby avoiding the negative effects of the negative RNB on the digestibility of DM, OM and NDF.
Assuntos
Bovinos/sangue , Digestão/efeitos dos fármacos , Leite/química , Niacina/farmacologia , Nitrogênio/metabolismo , Vitaminas/farmacologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Suplementos Nutricionais , Digestão/fisiologia , Feminino , Lactação/fisiologia , Niacina/administração & dosagem , Nitrogênio/química , Vitaminas/administração & dosagemRESUMO
SCOPE: Aim of this study was to investigate urinary excretion and metabolism of procyanidins a group of secondary plant metabolites with many beneficial health effects described in literature. METHODS AND RESULTS: To investigate the metabolism of procyanidins in the absence of flavan-3-ols, centrifugal partition chromatography was used for their reduction in a grape seed extract to a level of almost zero. After administration of the monomer reduced grape seed extract (mredGSE) containing procyanidins B1, B2, B3, B4, C1 to pigs flavan-3-ols, their methyl derivatives, dimeric and trimeric procyanidins were determined in urine by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Maximal concentrations of procyanidins 6 h after administration vary from 5 to 30 ng/mg creatinine. Total excretion of flavan-3-ols and their methyl derivatives indicates an increasing trend for pigs given mredGSE in comparison to pigs of the control group. Flavan-3-ols were conjugated and methylated to a great extent in comparison to dimeric and trimeric procyanidins. In the case of low molecular weight metabolites, an increasing trend was observed for hippuric acid, not for phenolic acids. CONCLUSIONS: Ratios of total excretion of procyanidins to administrated amounts between 0.004% (C1) and 0.019% (B4) suggest a poor urinary excretion by pigs. A transfer of these results to humans is possible due to their similar gastrointestinal tract.
Assuntos
Extrato de Sementes de Uva/farmacocinética , Extrato de Sementes de Uva/urina , Proantocianidinas/farmacocinética , Proantocianidinas/urina , Suínos/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Creatinina/administração & dosagem , Flavonoides/farmacologia , Espectrometria de Massas em TandemRESUMO
The aim of this study was to examine the effects of a control diet (CON) or a Fusarium toxin contaminated diet (FUS) with and without HS (CON-HS and FUS-HS, respectively) on pigs during a 10-week growth trial starting at 35.1±3.2 kg live weight (n=12/group). Moreover, 2 additional choice feeding groups were included to test the ability of the pigs to differentiate between the CON and FUS diet. Feeding the FUS diets (â¼3 mg DON/kg) did not depress feed intake irrespective of HS addition. However, the pigs of the choice feeding groups recognised the FUS diets and acquired an ability to avoid these diets. DON residues were detected exclusively in the blood of pigs exposed to the FUS diets (7-21 ng/mL) but their levels were not affected by HS, suggesting their inefficiency in preventing DON absorption. While zonula occludens-1 protein expression and villus height in jejunum and ileum were not compromised by FUS feeding, the jejunal crypts were significantly deepened at 31% compared to the CON group. These changes had no consequences for nutrient digestibility or LPS levels in systemic blood (0.02-0.08 EU/mL). As portal LPS levels were not measured, FUS effects on intestinal LPS translocation cannot be excluded.
Assuntos
Suplementos Nutricionais , Fusarium/química , Substâncias Húmicas , Tricotecenos/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Imunofluorescência , Íleo/efeitos dos fármacos , Absorção Intestinal , Jejuno/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Suínos , Tricotecenos/sangueRESUMO
Future livestock production is likely to be affected by both rising ambient temperatures and indirect effects mediated by modified growth conditions of feed plants such as increased atmospheric CO2 concentrations and drought. Corn was grown at elevated CO2 concentrations of 550 ppm and drought stress using free air carbon dioxide enrichment technology. Whole plant silages were generated and fed to sheep kept at three climatic treatments. Differential blood count was performed. Plasma DON and de-epoxy-DON concentration were measured. Warmer environment increased rectal and skin temperatures and respiration rates (p < 0.001 each) but did not affect blood parameters and the almost complete metabolization of DON into de-epoxy-DON. Altered growth conditions of the corn fed did not have single effects on sheep body temperature measures and differential blood count. Though the thermoregulatory activity of sheep was influenced by the thermal environment, the investigated cultivation factors did not indicate considerable impacts on the analysed parameters.
Assuntos
Dióxido de Carbono/farmacologia , Fusarium/efeitos dos fármacos , Carneiro Doméstico/sangue , Tricotecenos/sangue , Zea mays/efeitos dos fármacos , Animais , Biotransformação , Regulação da Temperatura Corporal , Castração , Secas , Fusarium/fisiologia , Masculino , Silagem/análise , Silagem/microbiologia , Estresse Fisiológico , Temperatura , Zea mays/química , Zea mays/microbiologiaRESUMO
Twenty-five primiparous Holstein cows were divided into five experimental groups (five animals per group) by different feeding (control fat preparation [CON] or conjugated linoleic acid [CLA] supplement) and slaughtering times. The daily consumption of CLA was 6.0 g of the trans-10, cis-12 CLA-isomer and 5.7 g cis-9, trans-11 CLA isomer. An initial group (IG) was slaughtered one day post partum (pp) and the remaining 20 animals after 42 and 105 days pp, respectively. Blood for peripheral blood mononuclear cells (PBMC) separation was taken seven days ante partum and immediately before slaughter. The spleen was removed during dissection for isolation of splenocytes and samples for histopathological examination. Cell viability and Concanavalin A-stimulated proliferation was analysed by MTT and Alamar Blue assay. Basal expression of cytokines (interleukin [IL]-4, IL-10, IL-12, tumour necrosis factor alpha [TNF-alpha] and interferon gamma [IFN-gamma]) was measured by quantitative real time polymerase chain reaction (qRT-PCR) in unstimulated PMBC and splenocytes. With PBMC, stimulation indices increased from 1 day pp to 105 days pp with no differences between CLA and CON groups. With splenocytes, the stimulation index of the CLA group was lower compared to CON group 105 days pp. Baseline expression of cytokines was not effected by CLA feeding comparing similar time points. Also, no differences occurred in the expression of IL-4 in PBMC and IL-10 as well as TNF-alpha in both cell populations, when comparing the feeding groups separately with IG. IL-4 was more frequently expressed in CLA group 42 days pp in splenocytes. IFN-gamma expression was increased 105 days pp in CLA group in splenocytes and PBMC. IL-12 was higher expressed 105 days (PBMC) or 42 days pp (splenocytes) when compared to IG. There was no effect of CLA feeding or slaughter time on histopathology of the spleen. In conclusion, the present results demonstrate an inhibiting effect of CLA on the mitogen-induced activation of splenocytes.
Assuntos
Bovinos , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Ácidos Linoleicos Conjugados/farmacologia , Baço/citologia , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Citocinas/genética , Dieta/veterinária , Suplementos Nutricionais , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Baço/efeitos dos fármacos , Baço/metabolismoRESUMO
The contamination of cereal grains with toxic secondary metabolites of fungi, mycotoxins, is a permanent challenge in animal nutrition as health and performance of the animals may be compromised as well as the quality of animal derived food. Therefore the present article reviews the issue of mycotoxins in animal nutrition. As the Fusarium toxins deoxynivalenol (DON) and zearalenone (ZON) are of particular importance under the production conditions in central Europe and Germany, with respect to their frequent occurrence in toxicologically relevant concentrations, special emphasis is layed on those mycotoxins. The effects of DON and ZON on susceptible animals as well as management strategies to cope with the contamination of grain with those toxins are reviewed.
Assuntos
Ração Animal/microbiologia , Contaminação de Alimentos , Tricotecenos/química , Tricotecenos/intoxicação , Zearalenona/química , Zearalenona/intoxicação , AnimaisRESUMO
The Fusarium toxin deoxynivalenol (DON) often co-occurs along with the acetylated derivatives 3-acetyl-DON and 15-acetyl-DON in diets for ruminants. De-epoxy-DON is formed by rumen micro-organisms, while the acetylated DON derivatives might also undergo ruminal metabolism with de-epoxy-DON as an end product. However, despite the fact that de-epoxy-DON is the predominant substance finally absorbed, a complete degradation of the mother compounds can not be assumed for all feeding and metabolic situations of the cow, and thus raising the question of their possible post-absorptive effects. Hence, the aim of the study was to examine the effects of all four compounds on the concanavalin A stimulated proliferation of bovine peripheral blood mononuclear cells (PBMC) using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) as indicator in vitro and ex vivo. Among the DON-related compounds, DON and 15-acetyl-DON resulted in a similar IC50 (i.e. the concentration where the proliferation was inhibited by 50%) of 0.5 µM, whereas 3-acetyl-DON was less toxic (IC50 = 2.6 µM), while actually no IC50 could be estimated for de-epoxy-DON which was characterized by a maximum inhibition of approximately 24% at the highest tested in vitro concentration of 18.29 µM. For the in vivo experiment, 14 Holstein cows were used and fed either an uncontaminated control diet (CON) or a diet contaminated with Fusarium toxins, with DON being the predominating toxin for 18 weeks when blood was collected for PBMC isolation and subsequent proliferation/viability assay. The complete diets for the CON and FUS group contained 0.4 and 4.6 mg DON/kg DM, respectively, at that time. Exposure of dairy cows to the FUS diet resulted in maximum serum de-epoxy-DON levels of 52 ng/ml (0.19 µM), while levels of the unmetabolized DON reached maximum levels of 9 ng/ml (0.03 µM). The PBMC of these cows were slightly less viable, by approximately 18% (p = 0.057), while stimulation capability was not decreased at the same time. Although de-epoxy-DON was characterized by the lowest in vitro toxicity among the tested DON-related compounds, there appeared to be a lower viability of the PBMC isolated from cows fed the FUS diet, which had nearly exclusively de-epoxy DON in serum beside slight traces of unmetabolized DON. Thus, the factors responsible for these apparent discrepancies need to be clarified.
RESUMO
Rare earth elements (REE) are possible performance enhancers in animal production, but little is known about their effects on ruminants. Therefore a feeding trial was conducted with 40 fattening bulls who received 0, 100, 200 or 300mg REE-citrate/kg dry matter (DM), containing 34.30% La, 58.09% Ce and 7.61% other REE. DM intake was measured daily and live weight weekly. Ex vivo ConcanavalinA (ConA)-stimulated cell proliferation of peripheral blood mononuclear cells (PBMC) was tested by MTT and alamar blue (AB) assay. Serum was analysed for clinical chemical parameters, ion (Mg, Ca and P) and REE concentrations. The effects of LaCl(3), CeCl(3), NdCl(3) and YCl(3) on ConA-stimulated proliferation of PBMC were tested in vitro, using MTT and AB assay. REE-citrate supplementation did affect DM intake, but not live weight gain, clinical chemical parameters, and ion concentrations significantly. In REE-300 group ex vivo proliferation of PBMC was significantly increased. In vitro ConA-stimulated proliferation decreased with rising REE-chloride concentrations. At least at the highest tested concentration (approximately 290µM) the inhibition reached significance. Proliferation of non-stimulated PBMC was not affected dose-dependently. REE affect the proliferation of PBMC, thus an effect on the bovine immune system is possible. However, the great differences in effective doses in vitro and ex vivo (serum REE concentrations) might explain the different results from the experiments.
Assuntos
Crescimento/efeitos dos fármacos , Metais Terras Raras/farmacologia , Mitógenos/farmacologia , Monócitos/efeitos dos fármacos , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Análise Química do Sangue , Peso Corporal/efeitos dos fármacos , Bovinos , Proliferação de Células/efeitos dos fármacos , Separação Celular , Corantes , Técnicas In Vitro , Masculino , Metais Terras Raras/sangue , Sais de Tetrazólio , Tiazóis , Aumento de Peso/efeitos dos fármacosRESUMO
Mycotoxins are known to affect the health and performance of farm animals. In contrast to cereal grains, the straw is only rarely analysed for mycotoxins, although contaminated straw could additionally expose farm animals to mycotoxins. For this reason, two experiments were carried out to examine the effect of pre-harvest Fusarium infection (inoculation with F. culmorum) and different storage conditions on the mycotoxin concentrations in straw. In the first experiment, both the inoculated and the identically cultivated control straw were stored in rectangular bales either in a barn or outdoors for a time period of 32 weeks (farm-scale experiment). The second experiment was aimed to examine the mycotoxin concentrations during storage under controlled conditions in a temperature-controlled climatic chamber, with target dry matter contents of 86%, 82% and 78% using 1.5-l preservation jars (laboratory-scale experiment). While the concentration of deoxynivalenol and its derivates decreased in the farm-scale experiment when inoculated straw was stored outdoors, the zearalenone concentration increased within the same time period. The latter effect was also detected for the control straw. These opposite effects were probably caused by the massive water uptake during the outdoor storage. The only effect we observed in the laboratory-scale experiment with dry matter contents between 78% and 86% was a more pronounced decrease of the 3-acetyl-deoxynivalenol concentrations in the inoculated straw with increasing moisture contents.
RESUMO
A 35-day piglet experiment starting from weaning (21 days of age, 7.7+/-1.1 kg), was performed to examine the effects of feeding a control diet (CTR) and of a Fusarium toxin-contaminated diet (FUS) in the absence (-) or presence (+) of a probiotic additive (2.3 x 10(6) colony-forming units per g diet of a one-to-one ratio of Bacillus subtilis and B. licheniformis) (deoxynivalenol [DON] concentrations of the CTR-, CTR+, FUS- and FUS+ diets were 0.21, 0.20, 2.75 and 2.45 mg/kg, respectively) on performance, blood concentration of DON and on liver function as evaluated by a breath test. Feeding of the FUS diets significantly depressed performance while the probiotic supplement failed to improve performance either when added to the CTR or to the FUS diet. The DON concentrations in the blood of the piglets fed both FUS diets were not significantly different, while the concentration of its degradation metabolite, de-epoxy-DON, was lower than the detection limit. Thus, it can be concluded that the fed probiotic bacteria neither bound nor degraded DON prior to absorption. Taken together, the tested probiotic additive is not suited to prevent the performance depressing effects of DON in piglets.
Assuntos
Bacillus subtilis/química , Bacillus/química , Fusarium/química , Absorção Intestinal/efeitos dos fármacos , Micotoxinas/farmacocinética , Micotoxinas/toxicidade , Probióticos/farmacologia , Esporos Bacterianos/química , Tricotecenos/farmacocinética , Tricotecenos/toxicidade , Acetamidas/química , Animais , Peso Corporal/efeitos dos fármacos , Testes Respiratórios , Dieta , Contaminação de Alimentos/análise , Micotoxinas/antagonistas & inibidores , Suínos , Tricotecenos/antagonistas & inibidores , Triticum/químicaRESUMO
A case of Epstein-Barr virus-related acute giant cell myocarditis in a 16-year-old boy is reported. Fulminant heart failure was successfully treated with extracorporeal membrane oxygenation as a bridge to urgent heart transplantation, and was again necessary after transplantation because of acute right heart failure. Clinical management and postoperative surveillance of this unusual problem are presented and discussed.
Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Células Gigantes/patologia , Transplante de Coração/métodos , Miocardite/terapia , Miocárdio/patologia , Adolescente , Biópsia , Diagnóstico Diferencial , Seguimentos , Humanos , Masculino , Miocardite/diagnósticoRESUMO
To evaluate the transfer of deoxynivalenol (DON) and its de-epoxy metabolite (de-epoxy-DON) in the plasma of chicken, mashed oats naturally contaminated with 9.5 mg DON/kg were fed to four broilers (35 days age) at a dose of 20 g/bird. Blood samples were then collected from two birds at 1 h, 3 h, and 5 h post-feeding, while from the other two birds at 2 h, 4 h, and 6 h post-feeding. Analysis of DON and de-epoxy-DON was carried out by using liquid chromatography-tandem mass spectrometry after clean-up with immunoaffinity columns. At 1 h, 3 h, and 5 h post-feeding, the average values of plasma DON were 0.35 ng/ml, 0.20 ng/ml, and 0.15 ng/ml, respectively. The corresponding average values of de-epoxy-DON at these time points were 0.70 ng/ml, 0.80 ng/ml, and 0.25 ng/ml, respectively. The sum of DON and de-epoxy-DON appearing in the plasma at 1 h post-feeding in these birds was estimated to be 0.044% of the total DON fed. At 2 h, 4 h, and 6 h post-feeding, the average values of plasma DON were 0.85 ng/ml, 0.45 ng/ml, and 0.30 ng/ml. De-epoxy-DON could not be detected in the birds sampled at 2 h, 4 h, and 6 h post-feeding. The total amount of DON appearing in the plasma at 2 h post-feeding in these birds was estimated to be 0.036% of the DON fed. These data show that the absorption rate of DON is very low in broilers and that there is also a rapid transformation, and clearance from plasma. Furthermore, there appeared to be individual variability in the capacity of birds to de-epoxidise DON.
RESUMO
The in vitro effects of deoxynivalenol (DON), de-epoxy-DON, DON-sulfonate (DONS) and sodium metabisulfite (Na(2)S(2)O(5), SBS) on porcine peripheral blood mononuclear cells (PBMC), and on the Intestinal Porcine Epithelial Cell lines IPEC-1 and IPEC-J2 were examined by using the MTT assay. In addition, an uncontaminated and a DON contaminated triticale were included in diets either untreated (CON, FUS) or SBS treated (CON-SBS, FUS-SBS) and fed to piglets for 28 d starting from weaning. The diet concentrations of DON and DONS amounted to 0.156, 2.312, 0.084 and 0.275 mg and to<0.05, <0.05, <0.05 and 1.841 mg/kg, respectively. PBMC of the so-exposed piglets were also subjected to the MTT assay. Neither DONS and SBS nor de-epoxy-DON affected the viability of PBMC, IPEC-1 and IPEC-J2 significantly up to concentrations of 17, 8 and 23 microM, respectively. For DON, IC(50) values were estimated at 1.2+/-0.1, 1.3+/-0.5 and 3.0+/-0.8 microM for PBMC, IPEC-1 and IPEC-J2, respectively. PBMC from piglets fed the SBS treated diets were characterized by a significantly decreased stimulation index and an increased IgA supernatant concentration with the SBS effect being significantly more pronounced after feeding the FUS-SBS diet. Further studies should clarify the possible impact of SBS on the porcine immune system.
Assuntos
Monócitos/efeitos dos fármacos , Sulfitos/toxicidade , Tricotecenos/toxicidade , Ração Animal , Animais , Linhagem Celular , Dieta , Digestão , Relação Dose-Resposta a Droga , Enterócitos/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Masculino , SuínosRESUMO
The cytotoxicity of deoxynivalenol (DON), effects on protein synthesis and albumin secretion was investigated in porcine hepatocytes and Kupffer cell-enriched hepatocyte cultures (co-cultures) in the presence and absence of lipopolysaccharides (LPS). Up to 16microM DON did not reduce the metabolic activity of hepatocytes. Lysosomal activity reacted more sensitively as neutral red uptake was decreased starting at 2 or 4microM DON irrespective of LPS exposure. The synthesis of secreted proteins was reduced to 31% and 42%, and of cellular proteins to 47% and 39%, in the absence and presence of LPS, respectively, when hepatocytes were exposed to 2microM DON. Reduced albumin secretion in response to DON was already observed after 3h in hepatocytes as well as co-cultures while LPS-mediated decrease was not evident until 24h, when interactions between DON and LPS resulted from a diminishing difference between LPS stimulated and non-stimulated cultures with increasing concentrations of DON. All observed effects may be biased by the cells' ability to conjugate DON to glucuronic acid as 54% and 64% of DON administered at 5nM were recovered as conjugates after 48h. Glucuronidation rate, as well as total DON recovery, decreased with increasing concentrations of DON, giving rise to assumptions on the formation of undetected metabolites.
Assuntos
Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/metabolismo , Lipopolissacarídeos/toxicidade , Tricotecenos/toxicidade , Albuminas/metabolismo , Animais , Células Cultivadas , Técnicas de Cocultura , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Imuno-Histoquímica , Masculino , Suínos , Fatores de TempoRESUMO
The effects of deoxynivalenol (DON) on the mRNA expression of cytokines and inflammation-related genes, as well as the cytokine secretion of porcine hepatocytes and Kupffer cell enriched hepatocyte cultures (co-cultures), were investigated in the absence or presence of LPS. DON and LPS acted in a synergistic manner with regard to a significantly increased mRNA expression of TNF-alpha in hepatocytes exposed to 500 nM or 2000 nM DON, or non-significant increase in co-cultures after 3h of exposure. TNF-alpha supernatant concentrations were increased due to LPS but did not reflect the synergistic effects with DON as observed at mRNA level. IL-6 mRNA in hepatocyte cultures at 6h paralleled the TNF-alpha supernatant pattern at this time point. In co-cultures and hepatocytes, a DON dose dependent induction of IL-6 mRNA was detected in cells not exposed to LPS. Supernatant concentrations of LPS-induced IL-6 were significantly decreased by 2000 nM DON in both types of cell cultures. Also the mRNA expression of the anti-inflammatory IL-10 was increased by DON to various degrees depending on DON-dose, stimulation with LPS and time point of measurement. After 6h, expression of iNOS was only induced by 2000 nM DON, but not in LPS treated cells. Even if mRNA induction was not paralleled by related supernatant concentrations of TNF-alpha, IL-6 and IL-10 under the conditions of the present investigations, it was clearly demonstrated that DON has the potential to provoke and modulate immunological reactions of porcine liver cells.
Assuntos
Citocinas/metabolismo , Hepatócitos/efeitos dos fármacos , Células de Kupffer/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , RNA Mensageiro/biossíntese , Tricotecenos/toxicidade , Animais , Células Cultivadas , Técnicas de Cocultura , Citocinas/biossíntese , Relação Dose-Resposta a Droga , Interações Medicamentosas , Hepatócitos/citologia , Hepatócitos/imunologia , Células de Kupffer/citologia , Células de Kupffer/imunologia , Masculino , SuínosRESUMO
A 50-year-old woman who underwent double-lung transplantation suffered a massive cerebral air embolism with severe neurological impairment and temporary hemodynamic deterioration after surveillance bronchoscopy and central line removal. We hypothesize that this was due to microscopic pulmonary parenchymal injury during bronchoscopy as well as air entrainment during removal of the central venous line, with subsequent transpulmonary passage into the cerebral vessels.
Assuntos
Broncoscopia/efeitos adversos , Cateterismo Venoso Central/efeitos adversos , Infarto Cerebral/etiologia , Embolia Aérea/etiologia , Enfisema/cirurgia , Feminino , Humanos , Transplante de Pulmão , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Unground triticale kernels contaminated with 6.63 mg deoxynivalenol (DON) per kg dry matter were stored for up to 63 days at total moisture contents of 13 and 15% in order to study the time-dependent kinetics of DON concentration in dependence on graded levels of sodium metabisulfite [0, 1, 2, 3, 4 and 5 g Na2S2O5 (SBS) per kg], and in the absence and presence of 10 g propionic acid (PA) per kg. The DON concentration decreased with increasing amounts of supplemented SBS and with increasing duration of the preservation period in a bi-exponential fashion when SBS addition was ≥3 g/kg. Lower SBS concentrations yielded inconsistent results. The maximum measured DON reductions after adding 5 g SBS/kg were 3 and 4% of the initial DON concentration after 63 days in the absence and presence of PA at moisture contents of 15%, while the corresponding recovery for the variants preserved at 13% amounted to 21 and 11%, respectively. The 12 variants preserved without PA supplementation were more frequently contaminated by moulds and yeasts (n = 5) than the corresponding variants stored together with PA (n = 1). The overall results and regressive evaluations do suggest that the highest SBS addition of 5 g/kg triticale at a moisture content of 15% preserved for 63 days would be necessary for a maximum DON reduction. Although PA did not exert a direct decontaminating effect, an additional supplementation together with SBS seemed to be advantageous with regard to the prevention of yeast and mould contamination and favouring the decontamination reaction by the acid milieu.