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1.
Ecotoxicol Environ Saf ; 210: 111870, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33440271

RESUMO

Ammonia is the main harmful gas in livestock houses. However, the toxic mechanism of ammonia is still unclear. Therefore, we examined the effects of ammonia exposure on different tissues of fattening pigs by histological analysis and transcriptome techniques in this study. The results showed that there were varying degrees of pathological changes in liver, kidney, hypothalamus, jejunum, lungs, spleen, heart and trachea of fattening pigs under ammonia exposure. Notably, the extent of damage in liver, kidney, jejunum, lungs, hypothalamus and trachea was more severe than that in heart and spleen. Transcriptome results showed that ammonia exposure caused changes in 349, 335, 340, 229, 120, 578, 407 and 115 differentially expressed genes in liver, kidney, spleen, lung, trachea, hypothalamus, jejunum and heart, respectively. Interestingly, the changes in solute vector (SLC) family genes were found in all 8 tissues, and the verified gene results (SLC11A1, SLC17A7, SLC17A6, SLC6A4, SLC22A7, SLC25A3, SLC28A3, SLC7A2, SLC6A6, SLC38A5, SLC22A12, SLC34A1, SLC26A1, SLC26A6, SLC27A5, SLC22A8 and SLC44A4) were consistent with qRT-PCR results. In conclusion, ammonia exposure can cause pathological changes in many tissues and organs of fattening pigs and changes in the SCL family gene network. Importantly, the SCL family is involved in the toxic mechanism of ammonia. Our findings will provide a new insight for better assessing the mechanism of ammonia toxicity.


Assuntos
Amônia/toxicidade , Proteínas de Membrana Transportadoras/genética , Animais , Feminino , Redes Reguladoras de Genes/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Hipotálamo/patologia , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Jejuno/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Miocárdio/patologia , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/patologia , Suínos , Traqueia/efeitos dos fármacos , Traqueia/metabolismo , Traqueia/patologia , Transcriptoma/efeitos dos fármacos
2.
BMJ Case Rep ; 14(1)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514623

RESUMO

Acute confusion in pregnancy is generally uncommon, given the relatively young and healthy population obstetricians care for. We present an unusual and rare case of acute confusion in a term pregnancy with antecedent history of gastrointestinal (GI) bleeding. A primigravida with no medical history of note, was found to have a haemoglobin of 67 g/L at booking and was commenced on oral iron supplementation. In the third trimester, she presented with haematochezia and had several admissions, requiring 18 units of red blood cells during her pregnancy. At term, she was admitted with acute confusion and GI bleeding, and was subsequently delivered by caesarean section to facilitate ongoing investigation and management of her symptoms. She was diagnosed postnatally with an arteriovenous malformation in the jejunum which required interventional radiology and surgical management for symptom resolution. Her confusion was attributed to hyperammonaemic levels secondary to her high protein load.


Assuntos
Malformações Arteriovenosas/complicações , Confusão/etiologia , Hemorragia Gastrointestinal/etiologia , Jejuno/irrigação sanguínea , Doença Aguda , Malformações Arteriovenosas/terapia , Cesárea/métodos , Angiografia por Tomografia Computadorizada/métodos , Diagnóstico Diferencial , Embolização Terapêutica/métodos , Feminino , Humanos , Hiperamonemia/complicações , Jejuno/diagnóstico por imagem , Jejuno/patologia , Jejuno/cirurgia , Laparotomia/métodos , Gravidez , Resultado do Tratamento , Adulto Jovem
3.
Virology ; 552: 43-51, 2021 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-33059319

RESUMO

This study focused on intestinal restitution including phenotype switching of absorptive enterocytes and the abundance of different enterocyte subtypes in weaned pigs after porcine epidemic diarrhea virus (PEDV) infection. At 10 days post-PEDV-inoculation, the ratio of villus height to crypt depth in both jejunum and ileum had restored, and the PEDV antigen was not detectable. However, enterocytes at the villus tips revealed epithelial-mesenchymal transition (EMT) in the jejunum in which E-cadherin expression decreased while expression of N-cadherin, vimentin, and Snail increased. Additionally, there was reduced expression of actin in microvilli and Zonula occludens-1 (ZO-1) in tight junctions. Moreover, the protein concentration of transforming growth factor ß1 (TGFß1), which mediates EMT and cytoskeleton alteration, was increased. We also found a decreased number of Peyer's patch M cells in the ileum. These results reveal incomplete restitution of enterocytes in the jejunum and potentially impaired immune surveillance in the ileum after PEDV infection.


Assuntos
Infecções por Coronavirus/veterinária , Enterócitos/patologia , Transição Epitelial-Mesenquimal , Gastroenterite Suína Transmissível/patologia , Nódulos Linfáticos Agregados/patologia , Vírus da Diarreia Epidêmica Suína/patogenicidade , Animais , Caderinas/metabolismo , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Gastroenterite Suína Transmissível/imunologia , Gastroenterite Suína Transmissível/virologia , Íleo/imunologia , Íleo/patologia , Mucosa Intestinal/patologia , Jejuno/imunologia , Jejuno/patologia , Microvilosidades/patologia , Suínos , Junções Íntimas/patologia , Fator de Crescimento Transformador beta1/metabolismo , Desmame
6.
Vet Pathol ; 57(5): 642-652, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32880235

RESUMO

In the small intestine, localized innate mucosal immunity is critical for intestinal homeostasis. Porcine epidemic diarrhea virus (PEDV) infection induces villus injury and impairs digestive function. Moreover, the infection might comprise localized innate mucosal immunity. This study investigated specific enterocyte subtypes and innate immune components of weaned pigs during PEDV infection. Four-week-old pigs were orally inoculated with PEDV IN19338 strain (n = 40) or sham-inoculated (n = 24). At day post inoculation (DPI) 2, 4, and 6, lysozyme expression in Paneth cells, cellular density of villous and Peyer's patch microfold (M) cells, and the expression of polymeric immunoglobulin receptor (pIgR) were assessed in the jejunum and ileum by immunohistochemistry, and interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were measured in the jejunum by ELISA. PEDV infection led to a decrease in the ratios of villus height to crypt depth (VH-CD) in jejunum at DPI 2, 4, and 6 and in ileum at DPI 4. The number of villous M cells was reduced in jejunum at DPI 4 and 6 and in ileum at DPI 6, while the number of Peyer's patch M cells in ileum increased at DPI 2 and then decreased at DPI 6. PEDV-infected pigs also had reduced lysozyme expression in ileal Paneth cells at DPI 2 and increased ileal pIgR expression at DPI 4. There were no significant changes in IL-1ß and TNF-α expression in PEDV-infected pigs compared to controls. In conclusion, PEDV infection affected innate mucosal immunity of weaned pigs through alterations in Paneth cells, villous and Peyer's patch M cells, and pIgR expression.


Assuntos
Infecções por Coronavirus/veterinária , Imunidade Inata , Mucosa Intestinal/imunologia , Vírus da Diarreia Epidêmica Suína , Animais , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Citocinas/análise , Íleo/imunologia , Íleo/patologia , Íleo/virologia , Mucosa Intestinal/química , Mucosa Intestinal/patologia , Mucosa Intestinal/virologia , Jejuno/imunologia , Jejuno/patologia , Jejuno/virologia , Receptores de Imunoglobulina Polimérica/metabolismo , Suínos , Desmame
7.
Ecotoxicol Environ Saf ; 204: 111072, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32758694

RESUMO

Zearalenone (ZEN) is a mycotoxin that causes serious health problems in humans and animals. However, few studies have focused on the destruction of the intestinal barrier caused by ZEN. In this study, rats were exposed to different dosages of ZEN (0, 0.2, 1.0 and 5.0 mg/kg bw) by gavage for 4 weeks. The results showed that 1.0 and 5.0 mg/kg ZEN impaired gut morphology, induced the inflammatory response, reduced mucin expression, increased intestinal permeability, decreased the expression of TJ proteins and activated the RhoA/ROCK pathway. However, 0.2 mg/kg ZEN had no significant effect on intestinal barrier except for reducing the expression of some TJ proteins and mucins. Moreover, exposure to ZEN led to slight imbalance in microbiota. In conclusion, ZEN exposure resulted in intestinal barrier dysfunction by inducing intestinal microbiota dysbiosis, decreasing the expression of TJ proteins, activating the RhoA/ROCK pathway, and inducing the inflammatory response.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Relação Dose-Resposta a Droga , Disbiose/induzido quimicamente , Feminino , Microbioma Gastrointestinal/genética , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Jejuno/microbiologia , Jejuno/patologia , Masculino , Mucinas/metabolismo , Permeabilidade , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
8.
J Virol ; 94(17)2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32554697

RESUMO

Coronaviruses (CoVs) have repeatedly emerged from wildlife hosts and infected humans and livestock animals to cause epidemics with significant morbidity and mortality. CoVs infect various organs, including respiratory and enteric systems, as exemplified by newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The constellation of viral factors that contribute to developing enteric disease remains elusive. Here, we investigated CoV interferon antagonists for their contribution to enteric pathogenesis. Using an infectious clone of an enteric CoV, porcine epidemic diarrhea virus (icPEDV), we generated viruses with inactive versions of interferon antagonist nonstructural protein 1 (nsp1), nsp15, and nsp16 individually or combined into one virus designated icPEDV-mut4. Interferon-responsive PK1 cells were infected with these viruses and produced higher levels of interferon responses than were seen with wild-type icPEDV infection. icPEDV-mut4 elicited robust interferon responses and was severely impaired for replication in PK1 cells. To evaluate viral pathogenesis, piglets were infected with either icPEDV or icPEDV-mut4. While the icPEDV-infected piglets exhibited clinical disease, the icPEDV-mut4-infected piglets showed no clinical symptoms and exhibited normal intestinal pathology at day 2 postinfection. icPEDV-mut4 replicated in the intestinal tract, as revealed by detection of viral RNA in fecal swabs, with sequence analysis documenting genetic stability of the input strain. Importantly, icPEDV-mut4 infection elicited IgG and neutralizing antibody responses to PEDV. These results identify nsp1, nsp15, and nsp16 as virulence factors that contribute to the development of PEDV-induced diarrhea in swine. Inactivation of these CoV interferon antagonists is a rational approach for generating candidate vaccines to prevent disease and spread of enteric CoVs, including SARS-CoV-2.IMPORTANCE Emerging coronaviruses, including SARS-CoV-2 and porcine CoVs, can infect enterocytes, cause diarrhea, and be shed in the feces. New approaches are needed to understand enteric pathogenesis and to develop vaccines and therapeutics to prevent the spread of these viruses. Here, we exploited a reverse genetic system for an enteric CoV, porcine epidemic diarrhea virus (PEDV), and outline an approach of genetically inactivating highly conserved viral factors known to limit the host innate immune response to infection. Our report reveals that generating PEDV with inactive versions of three viral interferon antagonists, nonstructural proteins 1, 15, and 16, results in a highly attenuated virus that does not cause diarrhea in animals and elicits a neutralizing antibody response in virus-infected animals. This strategy may be useful for generating live attenuated vaccine candidates that prevent disease and fecal spread of enteric CoVs, including SARS-CoV-2.


Assuntos
Infecções por Coronavirus/imunologia , Coronavirus/imunologia , Interferons/imunologia , Vírus da Diarreia Epidêmica Suína/imunologia , Vacinas Atenuadas/imunologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Animais , Betacoronavirus/imunologia , Chlorocebus aethiops , Infecções por Coronavirus/prevenção & controle , Diarreia/patologia , Diarreia/virologia , Modelos Animais de Doenças , Endorribonucleases/antagonistas & inibidores , Fezes/virologia , Íleo/patologia , Imunidade Inata , Jejuno/patologia , Pandemias , Pneumonia Viral/imunologia , Vírus da Diarreia Epidêmica Suína/genética , RNA Viral , Suínos , Doenças dos Suínos/virologia , Células Vero , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/imunologia
10.
PLoS One ; 15(4): e0224720, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348301

RESUMO

Small intestinal strangulation associated with ischaemia-reperfusion injury (IRI) is common in horses. In laboratory animals IRI can be ameliorated by ischaemic preconditioning (IPC) and pharmacological preconditioning (PPC) with dexmedetomidine. The aim of this study was to determine the effect of PPC with dexmedetomidine or IPC in an equine model of small intestinal ischaemia-reperfusion (IR). In a randomized controlled experimental trial, 15 horses were assigned to three groups: control (C), IPC, and PPC with dexmedetomidine (DEX). All horses were placed under general anaesthesia and 90% jejunal ischaemia was induced for 90 minutes, followed 30 minutes of reperfusion. In group IPC, three short bouts of ischaemia and reperfusion were implemented, and group DEX received a continuous rate infusion of dexmedetomidine prior to the main ischaemia. Jejunal biopsies were collected before ischaemia (P), and at the end of ischaemia (I) and reperfusion (R). Mucosal injury was assessed by the Chiu-Score, inflammatory cells were stained by cytosolic calprotectin. The degree of apoptosis and cell necrosis was assessed by cleaved-caspase-3 and TUNEL. Parametric data were analyzed by two-way ANOVA for repeated measurements followed by Dunnetts t-test. Non parametric data were compared between groups at the different time points by a Kruskal-Wallis-Test and a Wilcoxon-2-Sample-test. The mucosal injury score increased during I in all groups. After reperfusion, IRI further progressed in group C, but not in IPC and DEX. In all groups the number of cleaved caspase-3 and TUNEL positive cells increased from P to I. The number of TUNEL positive cells were lower in group DEX compared to group C after I and R. Infiltration with calprotectin positive cells was less pronounced in group DEX compared to group C, whereas in group IPC more calprotectin positive cells were seen. In conclusion, IPC and DEX exert protective effects in experimental small intestinal ischaemia in horses.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Dexmedetomidina/uso terapêutico , Isquemia/terapia , Precondicionamento Isquêmico/métodos , Jejuno/irrigação sanguínea , Traumatismo por Reperfusão/terapia , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Animais , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacologia , Cavalos , Isquemia/tratamento farmacológico , Jejuno/efeitos dos fármacos , Jejuno/patologia , Distribuição Aleatória , Traumatismo por Reperfusão/tratamento farmacológico
11.
J Med Chem ; 63(8): 4306-4314, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32223141

RESUMO

We report for the first time a novel series of tellurides bearing sulfonamide as selective and potent inhibitors of the ß-class carbonic anhydrase (CA; EC 4.2.1.1) enzyme expressed in Leishmania donovani protozoa. Such derivatives showed high activity against axenic amastigotes, and among them, compound 5g (4-(((3,4,5-trimethoxyphenyl)tellanyl)methyl)benzenesulfonamide) showed an IC50 of 0.02 µM being highly selective for the parasites over THP-1 cells with a selectivity index of 300. The in vitro and in vivo toxicity experiments showed compound 5g to possess a safe profile and thus paving the way for tellurium-containing compounds as novel drug entities.


Assuntos
Inibidores da Anidrase Carbônica/farmacologia , Leishmania donovani/efeitos dos fármacos , Sulfonamidas/farmacologia , Tripanossomicidas/farmacologia , Animais , Inibidores da Anidrase Carbônica/química , Relação Dose-Resposta a Droga , Feminino , Jejuno/efeitos dos fármacos , Jejuno/patologia , Leishmania donovani/fisiologia , Técnicas de Cultura de Órgãos , Ratos , Ratos Wistar , Sulfonamidas/química , Tripanossomicidas/química
12.
Medicine (Baltimore) ; 99(16): e19888, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32312016

RESUMO

RATIONALE: Although percutaneous endoscopic gastrojejunostomy (PEG-J) tubes are believed to reduce the side effect of aspiration, cautious catheter management is required. Intussusception is a serious complication of these tubes. PATIENT CONCERNS: A 7-year-old boy bedridden with hypoxic encephalopathy owing to drowning at the age of 1 year was admitted our hospital with urinary retention for 1 month. At the age of 4 years, a PEG-J tube was inserted. Concomitant with hyperaldosteronemia, an intestinal intussusception from the duodenum to the jejunum was observed via computed tomography (CT). The patient's condition worsened dramatically; gastrointestinal perforation was suspected, and laparotomy was performed. DIAGNOSIS: Jejuno-jejunal intussusception. INTERVENTIONS: Open surgery was performed to release the intussusception. By assessing the reduced intestinal tract, the intussusception starting from a 50 cm portion from the Treitz ligament had been extended to 100 cm from the Treitz ligament. The oral side jejunum was dilated. No evidence of intestinal perforation or strangulated ileus was observed, and the intussusception was manually remediable. OUTCOMES: Preoperative CT examination showed intussusception from the duodenum to the jejunum. Laparotomy showed intussusception on the anal side of the Treitz ligament. With regard to the CT findings associated with the progression of intussusception to the duodenal site, as a result of the telescope phenomenon extending to the duodenum due to the relaxation of the Treitz ligament through repeated intussusception, it was considered that CT examination revealed intussusception extending from the jejunum to the duodenum of oral side. After 3 postoperative weeks, the patient was finally able to return home. LESSONS: If the ileus is observed during the insertion of a PEG-J, clinicians should consider the possibility of intussusception even in the duodenum.


Assuntos
Endoscopia Gastrointestinal/métodos , Derivação Gástrica/efeitos adversos , Intussuscepção/etiologia , Jejunostomia/efeitos adversos , Estômago/cirurgia , Criança , Duodeno/patologia , Duodeno/cirurgia , Derivação Gástrica/instrumentação , Humanos , Doença Iatrogênica , Íleus/diagnóstico , Íleus/etiologia , Intussuscepção/patologia , Doenças do Jejuno/diagnóstico por imagem , Doenças do Jejuno/etiologia , Doenças do Jejuno/patologia , Jejuno/patologia , Jejuno/cirurgia , Laparotomia/métodos , Masculino , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
13.
J Surg Res ; 252: 116-124, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32278965

RESUMO

BACKGROUND: Proximal (duodenal) small bowel adenocarcinomas have a worse prognosis than distal (jejuno-ileal) tumors, but differences in patient, tumor, and treatment factors between locations remain unclear. METHODS: Patients in the National Cancer Database with surgically resected pathologic stage I-IV small bowel adenocarcinomas between 2004 and 2015 were analyzed. Clinical stage IV patients were excluded. RESULTS: Proximal tumors (n = 3767) were more likely to be higher grade (OR 1.52, CI 1.22-1.85 for moderately; OR 1.83, CI 1.49-2.33 for poorly differentiated, P < 0.01 for both) and have positive lymph nodes (OR 2.04, CI 1.30-3.23, P < 0.01), while distal tumors (n = 3252) were likely to be larger (OR 1.31, CI 1.07-1.60 for size > 5 cm, P < 0.01). Proximal tumors were associated with worse overall survival (OS) and stage-specific survival compared with distal tumors (all P < 0.01). Cox regression analysis of the entire cohort showed worse survival with community versus academic cancer programs, higher comorbidity scores, pathologic stage IV, poorly differentiated histology, positive nodal or margin status, and proximal location, while female gender, larger tumor size, and chemotherapy predicted better survival. On separate Cox regression analyses of each location, neoadjuvant chemotherapy was associated with better OS in the proximal cohort (HR 0.70, CI 0.55-0.88, P < 0.01), while adjuvant chemotherapy was associated with better OS for both proximal (HR 0.49, CI 0.42-0.57, P < 0.01) and distal tumors (HR 0.68, CI 0.57-0.81, P < 0.01). CONCLUSIONS: Proximal small bowel adenocarcinomas are associated with worse overall and stage-specific survival. This may be due to tumor biologic differences as proximal tumors were more likely to have higher grade. Future studies should further investigate differences between proximal and distal tumors to guide targeted treatment algorithms.


Assuntos
Adenocarcinoma/mortalidade , Neoplasias Duodenais/mortalidade , Neoplasias do Íleo/mortalidade , Neoplasias do Jejuno/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Quimiorradioterapia Adjuvante , Neoplasias Duodenais/patologia , Neoplasias Duodenais/terapia , Duodeno/patologia , Duodeno/cirurgia , Feminino , Humanos , Neoplasias do Íleo/patologia , Neoplasias do Íleo/terapia , Íleo/patologia , Íleo/cirurgia , Neoplasias do Jejuno/patologia , Neoplasias do Jejuno/terapia , Jejuno/patologia , Jejuno/cirurgia , Estimativa de Kaplan-Meier , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Taxa de Sobrevida , Resultado do Tratamento
14.
Food Chem Toxicol ; 138: 111222, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32145353

RESUMO

Low-level contamination of food and feed by deoxynivalenol (DON) is unavoidable. We investigated the effects of subclinical treatment with DON, and supplementation with probiotic yeast Saccharomyces cerevisiae boulardii I1079 as a preventive strategy in piglets. Thirty-six animals were randomly assigned to either a control diet, a diet contaminated with DON (3 mg/kg), a diet supplemented with yeast (4 × 109 CFU/kg), or a DON-contaminated diet supplemented with yeast, for four weeks. Plasma and tissue samples were collected for biochemical analysis,1H-NMR untargeted metabolomics, and histology. DON induced no significant modifications in biochemical parameters. However, lesion scores were higher and metabolomics highlighted alterations of amino acid and 2-oxocarboxylic acid metabolism. Administering yeast affected aminoacyl-tRNA synthesis and amino acid and glycerophospholipid metabolism. Yeast supplementation of piglets exposed to DON prevented histological alterations, and partial least square discriminant analysis emphasised similarity between the metabolic profiles of their plasma and that of the control group. The effect on liver metabolome remained marginal, indicating that the toxicity of the mycotoxin was not eliminated. These findings show that the 1H-NMR metabolomics profile is a reliable biomarker to assess subclinical exposure to DON, and that supplementation with S. cerevisiae boulardii increases the resilience of piglets to this mycotoxin.


Assuntos
Dieta , Suplementos Nutricionais/análise , Contaminação de Alimentos/análise , Micotoxinas/análise , Probióticos/análise , Espectroscopia de Prótons por Ressonância Magnética/métodos , Aminoácidos/metabolismo , Ração Animal/análise , Animais , Indóis/metabolismo , Intestinos , Jejuno/patologia , Rim/patologia , Metabolismo dos Lipídeos , Fígado/patologia , Masculino , Redes e Vias Metabólicas , Metaboloma , Metabolômica , Micotoxinas/toxicidade , Saccharomyces cerevisiae , Suínos
15.
Molecules ; 25(4)2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32075045

RESUMO

Climatic changes and heat stress have become a great challenge in the livestock industry, negatively affecting, in particular, poultry feed intake and intestinal barrier malfunction. Recently, phytogenic feed additives were applied to reduce heat stress effects on animal farming. Here, we investigated the effects of ginseng extract using various in vitro and in vivo experiments. Quantitative real-time PCR, transepithelial electrical resistance measurements and survival assays under heat stress conditions were carried out in various model systems, including Caco-2 cells, Caenorhabditis elegans and jejunum samples of broilers. Under heat stress conditions, ginseng treatment lowered the expression of HSPA1A (Caco-2) and the heat shock protein genes hsp-1 and hsp-16.2 (both in C. elegans), while all three of the tested genes encoding tight junction proteins, CLDN3, OCLN and CLDN1 (Caco-2), were upregulated. In addition, we observed prolonged survival under heat stress in Caenorhabditis elegans, and a better performance of growing ginseng-fed broilers by the increased gene expression of selected heat shock and tight junction proteins. The presence of ginseng extract resulted in a reduced decrease in transepithelial resistance under heat shock conditions. Finally, LC-MS analysis was performed to quantitate the most prominent ginsenosides in the extract used for this study, being Re, Rg1, Rc, Rb2 and Rd. In conclusion, ginseng extract was found to be a suitable feed additive in animal nutrition to reduce the negative physiological effects caused by heat stress.


Assuntos
Transtornos de Estresse por Calor/tratamento farmacológico , Resposta ao Choque Térmico/efeitos dos fármacos , Panax/química , Extratos Vegetais/farmacologia , Animais , Células CACO-2 , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Galinhas , Claudina-1/genética , Claudina-3/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Transtornos de Estresse por Calor/genética , Transtornos de Estresse por Calor/patologia , Resposta ao Choque Térmico/genética , Humanos , Jejuno/efeitos dos fármacos , Jejuno/patologia , Panax/classificação , Extratos Vegetais/química
17.
Obes Surg ; 30(1): 279-289, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31605365

RESUMO

BACKGROUND: Duodenal-jejunal bypass (DJB) can dramatically improve type 2 diabetes independent of weight loss and food restriction. Increasing evidence has demonstrated that brain insulin signaling plays an important role in the pathophysiology of type 2 diabetes. This study explores whether the antidiabetic effect of DJB is involved in brain insulin signaling activation and brain glucose utilization. METHODS: A diabetic rat model was established by high-fat and high-glucose diet. DJB or sham surgery was performed in diabetic rats. 18F-FDG PET scanning was used to detect glucose uptake in different organs, particularly in the brain. The levels of glucose transporters, glucose utilization-related proteins (HK1 and PFK2), insulin, and insulin signaling pathway-related proteins (InsR, IRS1/2, PI3K, and p-Akt) in the brain tissues were evaluated and analyzed. RESULTS: The results showed that DJB significantly improved basal glycemic parameters and reversed the decreasing glucose uptake in the brains of type 2 diabetic rats. DJB significantly increased not only the expression levels of brain insulin, IRS1/2, PI3K, and p-Akt but also the levels of the glucose utilization enzymes HK1 and PFK2 in the brain. CONCLUSION: These results indicate that enhanced brain insulin signaling transduction and brain glucose utilization play important roles in the antidiabetic effect of DJB.


Assuntos
Encéfalo/metabolismo , Diabetes Mellitus Tipo 2/cirurgia , Duodeno/cirurgia , Derivação Gástrica/métodos , Glucose/metabolismo , Insulina/metabolismo , Jejuno/cirurgia , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/cirurgia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Duodeno/patologia , Resistência à Insulina/fisiologia , Jejuno/patologia , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Transdução de Sinais/fisiologia , Resultado do Tratamento , Perda de Peso
19.
J Plast Reconstr Aesthet Surg ; 73(3): 590-597, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31734236

RESUMO

OBJECTIVE: This study used an experimental model mimicking early postoperative enteral feeding after the transfer of free jejunal flap and tested the hypothesis that jejunal infusion with dextrose or saline is associated with improved tissue perfusion and/or less mucosal damage after ischemia/reperfusion (IR) injury. METHODS: Thirty-five male Sprague Dawley rats were randomly divided into five groups: sham group (no IR and no intraluminal infusion); IR control group (IR but not intraluminal infusion); IR plus intraluminal 0.9% NaCl infusion or 5% dextrose or 10% dextrose infusion groups. A jejunal segment of each rat was isolated. The animals had jejunal ischemia for 40 min, reperfusion, and intestinal infusion on the basis of their allocation. Jejunal tissue perfusion was measured with laser Doppler flowmetry at one hour and two hours after reperfusion, after which the animals were sacrificed and tissue samples were obtained for the scoring of histological damage at superficial and cryptic epithelium, villus structure, and inflammatory cell infiltration and tissue nitric oxide (NO), interleukin (IL)-1, IL-6, and matrix metalloproteinase-1 (MMP) level measurements. RESULTS: At 1 h of reperfusion, IR plus 5% dextrose and 10% dextrose groups both had significantly higher perfusion rates than the IR control group (384.8 ± 26.7 and 462.4 ± 44.7 versus 270.3 ± 34.2 PU, respectively, p < 0.05 for both). These differences were maintained at 2 h of reperfusion (p < 0.05 for both). Saline infusion, however, resulted in improved tissue perfusion only at the early phase of reperfusion. Intraluminal infusion with dextrose solution, either 5% or 10%, was associated with higher tissue NO, IL-1, and IL-6 levels than that in the sham group (p < 0.05 for all). In addition, intraluminal infusion of any fluid resulted in less severe histological damage (8.1 ± 0.9 versus 5.8 ± 1.0, 5.4 ± 0.9, and 5.2 ± 1.9, for IR plus saline, 5% dextrose and 10% dextrose groups, respectively, p < 0.05 for all). CONCLUSIONS: Intraluminal infusion of fluids, particularly dextrose solutions, may be protective against IR injury as demonstrated by improved tissue perfusion and less histological damage. In addition, increases in tissue NO, IL-1, and IL-6 levels in association with dextrose infusion may be explained by the activation of pro-inflammatory and anti-inflammatory protective pathways. These support early enteral feeding after free jejunum flap transfers; however, further studies are warranted.


Assuntos
Jejuno/cirurgia , Traumatismo por Reperfusão/prevenção & controle , Animais , Modelos Animais de Doenças , Retalhos de Tecido Biológico/cirurgia , Glucose/farmacologia , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Mucosa Intestinal/patologia , Jejuno/irrigação sanguínea , Jejuno/metabolismo , Jejuno/patologia , Fluxometria por Laser-Doppler , Masculino , Óxido Nítrico/metabolismo , Ratos , Ratos Sprague-Dawley , Reperfusão/métodos , Traumatismo por Reperfusão/patologia
20.
J Surg Res ; 249: 232-240, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31796217

RESUMO

BACKGROUND: Galactomannan (GAL), a polysaccharide present on the cell wall of several fungi, has shown an ability to modulate inflammatory responses through the dectin-1 receptor in human macrophages. However, studies evaluating the modulatory properties of this polysaccharide in in vivo inflammatory scenarios are scarce. We hypothesized that GAL pretreatment would modulate local and remote damage related to intestinal reperfusion after an ischemic insult. MATERIALS AND METHODS: Adult male Balb/c mice were subjected to intestinal ischemia-reperfusion injury by reversible occlusion of the superior mesenteric artery, consisting of 45 min of ischemia followed by 3 or 24 h of reperfusion. Intragastric GAL (70 mg/kg) was administered 12 h before ischemia, and saline solution was used in the control animals. Jejunum, lung, and blood samples were taken for the analysis of histology, gene expression, plasma cytokine levels, and nitrosative stress. RESULTS: Intestinal and lung histologic alterations were attenuated by GAL pretreatment, showing significant differences compared with nontreated animals. Interleukin 1ß, monocyte chemoattractant protein 1, and IL-6 messenger RNA expression were considerably downregulated in the small intestine of the GAL group. In addition, GAL treatment significantly prevented plasma interleukin 6 and monocyte chemoattractant protein 1 upregulation and diminished nitrate and nitrite levels after 3 h of intestinal reperfusion. CONCLUSIONS: GAL pretreatment constitutes a novel and promising therapy to reduce local and remote damage triggered by intestinal ischemia-reperfusion injury. Further in vivo and in vitro studies to understand GAL's modulatory effects are warranted.


Assuntos
Mucosa Intestinal/efeitos dos fármacos , Isquemia/complicações , Mananas/administração & dosagem , Traumatismo por Reperfusão/prevenção & controle , Animais , Modelos Animais de Doenças , Humanos , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/patologia , Jejuno/irrigação sanguínea , Jejuno/efeitos dos fármacos , Jejuno/patologia , Masculino , Camundongos , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia
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