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2.
Hepatology ; 55(4): 1154-63, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22095436

RESUMO

UNLABELLED: Liver cirrhosis is associated with bacterial translocation (BT) and endotoxemia. Most translocating bacteria belong to the common intestinal microbiota, suggesting a breakdown of intestinal barrier function. We hypothesized that diminished mucosal antimicrobial host defense could predispose to BT. Two rodent models of portal hypertension with increased BT were used, CCl(4)-induced ascitic cirrhosis and 2-day portal vein-ligated (PVL) animals. BT was assessed by standard microbiological techniques on mesenteric lymph nodes. Total RNA was isolated systematically throughout the intestinal tract, and expression of Paneth cell α-cryptdins and ß-defensins was determined by real-time quantitative polymerase chain reaction (qPCR). To determine functional consequences, mucosal antimicrobial activity was assessed with a fluorescence-activated cell sorting assay. BT was detectable in 40% of rats with cirrhosis. Compared with the group without BT, these animals exhibited diminished intestinal Paneth cell α-cryptdin 5 and 7 expression. In contrast, PVL was associated with BT in all animals but did not affect antimicrobial peptides. The decrease in Paneth cell antimicrobials was most pronounced in the ileum and the coecum. Other antimicrobials showed no changes or even an induction in the case of BT at different sites. Antimicrobial activity toward different commensal strains was reduced, especially in the distal ileum and the cecum in experimental cirrhosis with BT (excluding PVL). CONCLUSION: Compromised Paneth cell antimicrobial host defense seems to predispose to BT in experimental cirrhosis. Understanding this liver-gut axis including the underlying mechanisms could help us to find new treatment avenues.


Assuntos
Translocação Bacteriana/fisiologia , Intestinos/microbiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Celulas de Paneth/metabolismo , Precursores de Proteínas/metabolismo , beta-Defensinas/metabolismo , Animais , Bacteroides fragilis/fisiologia , Bifidobacterium/fisiologia , Tetracloreto de Carbono/efeitos adversos , Ceco/microbiologia , Modelos Animais de Doenças , Enterococcus faecalis/fisiologia , Escherichia coli/fisiologia , Hipertensão Portal/etiologia , Hipertensão Portal/fisiopatologia , Íleo/microbiologia , Ligadura/efeitos adversos , Cirrose Hepática/induzido quimicamente , Masculino , Celulas de Paneth/patologia , Veia Porta/fisiopatologia , Ratos , Ratos Endogâmicos
3.
Mol Nutr Food Res ; 55(11): 1724-9, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21957076

RESUMO

Bilberries have positive effects in acute and chronic diarrhea. Patients with inflammatory bowel disease (IBD) report on improved symptoms upon ingestion. Bilberries contain approximately 10% of anthocyanins (ACs), which have anti-oxidative, anti-carcinogenic, and anti-inflammatory properties. We investigated whether experimental colitis can be ameliorated by dried bilberries or ACs. Acute and chronic dextrane sodium sulphate (DSS) colitis were induced in Balb/c mice by 2.5% DSS in the drinking water. Mice were fed with dried bilberries or ACs, respectively. Cytokines were determined in supernatants from mesenteric lymph nodes (MLNs) by ELISA and apoptosis was investigated by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assays. Oral administration of bilberries during acute DSS-induced colitis ameliorated disease severity and reduced secretion of IFN-γ and tumor necrosis factor from mesenteric lymph node cells. Dried bilberries also improved chronic DSS-colitis. Ingestion of ACs reduced intestinal inflammation in acute and chronic DSS-colitis with decreased histological scores and cytokine secretion. Both bilberries and ACs prevented inflammation-induced apoptosis in colonic epithelial cells. Taken together, ingestion of dried bilberries had positive effects on various parameters especially in acute DSS-colitis. Oral administration of ACs resulted in an amelioration of acute colitis as well as chronic colitis. These promising results justify a clinical study on their therapeutic effect in inflammatory bowel disease patients.


Assuntos
Antocianinas/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Colite/dietoterapia , Suplementos Nutricionais , Frutas/química , Vaccinium myrtillus/química , Animais , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Colite/tratamento farmacológico , Colite/imunologia , Colite/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana , Relação Dose-Resposta a Droga , Feminino , Doenças Inflamatórias Intestinais/dietoterapia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Linfonodos/metabolismo , Linfonodos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Índice de Gravidade de Doença
4.
Scand J Gastroenterol ; 46(10): 1257-66, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21815863

RESUMO

OBJECTIVE: Alcohol-toxic liver cirrhosis (ALC) is one of the main indications for liver transplantation (LT). The aim of the study is to define predictors for alcohol recidivism and to identify the outcome and quality of life of such patients. MATERIAL AND METHODS: From March 2003 to July 2009, 226 patients underwent LT in our centre. In 53% liver cirrhosis was caused by alcohol abuse (sole/cofactor). Outcome and alcohol recidivism were assessed using patients' records, laboratory tests and interviews (patient, family members and family doctor). Furthermore, patients received an SF-36 quality of life and a self-designed questionnaire anonymously. RESULTS: Mean follow-up after LT was 31 + 23 months. The 5-year survival rate after LT in patients with ALC was significantly better compared to patients with other indications (78 vs. 64%; p = 0.016). Quality of life of both patient groups was comparable. After LT, alcohol recidivism rate was 16%. Patients with an alcohol abstinence of <3 months before LT had a significantly higher (p = 0.012) rate of alcohol recidivism in comparison to those with an abstinence of >3 months. Another predictor for alcohol recidivism was the patients' non-acceptance of having an alcohol problem before LT (p = 0.001). CONCLUSIONS: ALC is a good indication for LT. An alcohol abstinence of <3 months before LT and a non-acceptance of having an alcohol problem are strong predictors for alcohol recidivism after LT.


Assuntos
Alcoolismo/psicologia , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado , Adolescente , Adulto , Idoso , Negação (Psicologia) , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Recidiva , Estatísticas não Paramétricas , Resultado do Tratamento , Adulto Jovem
5.
Inflamm Bowel Dis ; 17(8): 1641-50, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21744420

RESUMO

BACKGROUND: Blood translocation of bacterial-DNA has been described in patients with Crohn's disease (CD). The host's immune cell types cooperate to respond against bacterial insults. Some antimicrobial peptides are inducible after culture with bacterial products and a linkage has been established between them and NOD2/CARD15. The aim was to test whether defensins and cathelicidin (LL-37) expression and NOD2/CARD15 mutations in blood neutrophils are related to molecular bacterial translocation events in CD patients. METHODS: Fifty consecutively admitted CD patients and 15 healthy controls were included. Clinical and analytical characteristics of patients were considered. NOD2/CARD15 genotyping, presence of bacterial-DNA, defensin and cathelicidin gene, and protein levels in neutrophils and serum cytokine levels were studied. RESULTS: Twenty patients (40%) presented bacterial-DNA in blood. Eleven were active and 9 were in remission. Bacterial-DNA was not present in controls. NOD2/CARD15 mutations were identified in 25 patients (50%), 15 of which were in remission. Sixty percent of bacterial-DNA(+) and 43% of bacterial-DNA(-) patients showed a NOD2/CARD15 mutation. ß-Defensin 2 and LL-37 mRNA and protein levels were upregulated in bacterial-DNA(+) patients. ß-Defensin 2 and LL-37 expression correlated with bacterial-DNA concentration only in patients with a wildtype NOD2/CARD15 genotype. Cultured neutrophils of bacterial-DNA(-) patients confirmed the muramyl dipeptide-independent association between DEFB2 and LL-37 with bacterial-DNA concentration in wildtype NOD2/CARD15 patients. Cytokine levels were increased in bacterial-DNA(+) patients and correlated with bacterial-DNA concentration. NOD2/CARD15 genotype did not influence this correlation. CONCLUSIONS: ß-Defensin 2, LL-37, and proinflammatory cytokines are increased in CD patients with bacterial-DNA in a concentration-dependent manner. NOD2/CARD15 plays a key role in the regulation of this response.


Assuntos
Doença de Crohn/genética , Doença de Crohn/imunologia , DNA Bacteriano/imunologia , Proteína Adaptadora de Sinalização NOD2/genética , RNA Mensageiro/sangue , Adulto , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , Células Cultivadas , Doença de Crohn/sangue , Citocinas/sangue , DNA Bacteriano/sangue , Feminino , Genótipo , Humanos , Interferon gama/sangue , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/metabolismo , Polimorfismo de Nucleotídeo Único , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem , beta-Defensinas/sangue , beta-Defensinas/genética
6.
Inflamm Bowel Dis ; 17(6): 1415-22, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21560202

RESUMO

Crohn's disease (CD) is a chronic progressive destructive disease. Currently available instruments measure disease activity at a specific point in time. An instrument to measure cumulative structural damage to the bowel, which may predict long-term disability, is needed. The aim of this article is to outline the methods to develop an instrument that can measure cumulative bowel damage. The project is being conducted by the International Program to develop New Indexes in Crohn's disease (IPNIC) group. This instrument, called the Crohn's Disease Digestive Damage Score (the Lémann score), should take into account damage location, severity, extent, progression, and reversibility, as measured by diagnostic imaging modalities and the history of surgical resection. It should not be "diagnostic modality driven": for each lesion and location, a modality appropriate for the anatomic site (for example: computed tomography or magnetic resonance imaging enterography, and colonoscopy) will be used. A total of 24 centers from 15 countries will be involved in a cross-sectional study, which will include up to 240 patients with stratification according to disease location and duration. At least 120 additional patients will be included in the study to validate the score. The Lémann score is expected to be able to portray a patient's disease course on a double-axis graph, with time as the x-axis, bowel damage severity as the y-axis, and the slope of the line connecting data points as a measure of disease progression. This instrument could be used to assess the effect of various medical therapies on the progression of bowel damage.


Assuntos
Colo/patologia , Doença de Crohn/patologia , Colo/diagnóstico por imagem , Colonoscopia , Doença de Crohn/diagnóstico por imagem , Progressão da Doença , Humanos , Imagem por Ressonância Magnética , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Ultrassonografia
7.
Gut ; 60(8): 1122-32, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21317421

RESUMO

BACKGROUND: Splanchnic vasodilation triggers the development of the hyperdynamic circulatory syndrome in portal hypertension. Neuropeptide Y (NPY), a sympathetic co-transmitter of norepinephrine, improves contractility in mesenteric arteries of pre-hepatic portal hypertensive rats. Therefore, we investigated the effect of NPY on mesenteric arterial contractility in vitro and in vivo in cirrhotic ascitic rats, as well as the vasoactive pathways involved. METHODS: All experiments were performed in CCl4-induced cirrhotic rats with ascites and compared to controls. In vivo haemodynamic characterisation was assessed before and after cumulative application of NPY i.v. using the microspheres technique. In vitro mesenteric arterial perfusion was used to analyse the effect of NPY on the response to α1-adrenergic, as well as nitrergic stimulation. The NPY effects on vasoactive pathways (RhoA/Rho-kinase and NOS/NO) were analysed by western blot in mesenteric arteries. RESULTS: NPY decreased portal-venous blood flow and reduced portal pressure in cirrhotic rats, without changes in mean arterial pressure. This was accompanied by decreased cardiac output and normalised systemic vascular resistance in cirrhotic rats. By contrast, no significant splanchnic or systemic haemodynamic effect of NPY was seen in controls. NPY enhanced arterial contractility in cirrhotic but not in control rats. Furthermore, NO-mediated vasodilation was reduced to a greater extent than in controls. These findings were paralleled by an increased expression and activity of the constrictive Rho-kinase pathway and decreased activation of vasodilating NOS/NO signalling after NPY administration in mesenteric arteries. CONCLUSIONS: NPY exerts marked portal hypotensive effects and ameliorates the hyperdynamic circulation in cirrhotic ascitic rats. This is mediated mainly by a pronounced splanchnic vasoconstriction and reduction in splanchnic blood flow due to enhanced Rho-kinase expression and activity, as well as reduced NOS activation and NO effect.


Assuntos
Hipertensão Portal/tratamento farmacológico , Cirrose Hepática Experimental/complicações , Neuropeptídeo Y/uso terapêutico , Pressão na Veia Porta/efeitos dos fármacos , Circulação Esplâncnica/fisiologia , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Animais , Western Blotting , Hipertensão Portal/etiologia , Hipertensão Portal/fisiopatologia , Infusões Intravenosas , Cirrose Hepática Experimental/enzimologia , Cirrose Hepática Experimental/fisiopatologia , Masculino , Neuropeptídeo Y/administração & dosagem , Óxido Nítrico Sintase/metabolismo , Perfusão/métodos , Pressão na Veia Porta/fisiologia , Ratos , Ratos Sprague-Dawley , Circulação Esplâncnica/efeitos dos fármacos , Síndrome , Resultado do Tratamento , Proteína rhoA de Ligação ao GTP/metabolismo
9.
Ann N Y Acad Sci ; 1193: 167-75, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20398025

RESUMO

This study was performed to evaluate whether specific patterns of cerebral lesions can be identified in different rheumatic disease entities. In 132 patients with different connective tissue diseases and vasculitides (systemic lupus erythematosus [SLE], systemic sclerosis [SSc], mixed connective tissue disease [MCTD], Wegener's granulomatosis [WG], immunocomplex vasculitides, antiphospholipid antibody syndrome [APS]), cerebral magnetic resonance imaging scans were performed. Patients were examined clinically, and laboratory parameters including autoantibodies were determined. Distinct distibution patterns could be identified; in WG, most lesions were seen in the cortex, the periventricular region, basal ganglia, and pons. In both SSc and MCTD, highest numbers of lesions could be detected in the corticomedullary junction. In APS, basal ganglia and periventricular white matter were involved predominantly. Generally, the maximum score of cerebral lesions correlated significantly with patients' age. Pathological values for antinuclear antibodies and increased levels of antiphospholipid antibodies were significantly correlated with the presence of cerebral lesions. WG patients and patients with other vasculitides most frequently showed neurological abnormalities. This study in patients with different rheumatic diseases showed distinct distribution patterns of cerebral lesions, which might help to differentiate between them.


Assuntos
Cérebro/patologia , Doenças do Tecido Conjuntivo/imunologia , Vasculite Sistêmica/imunologia , Adulto , Síndrome Antifosfolipídica/imunologia , Cérebro/diagnóstico por imagem , Feminino , Seguimentos , Granulomatose com Poliangiite/imunologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia
10.
Inflamm Bowel Dis ; 16(8): 1311-21, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20232407

RESUMO

BACKGROUND: Recent insights into the pathogenesis of Crohn's disease (CD) point to an important role of the mucosal barrier and intestinal microflora that may induce a chronic inflammation after crossing the intestinal barrier. The first detected susceptibility gene for CD, NOD2, is a pattern recognition receptor (PRR) for the recognition of the bacterial cell wall component muramyldipeptide (MDP). Binding of MDP to NOD2 is followed by activation of proinflammatory pathways mainly regulated by nuclear factor kappa B (NF-kappaB). In this study we investigated whether impaired recognition of MDP via NOD2 variants is associated with increased bacterial translocation across the epithelial barrier and whether this is followed by increased or decreased NF-kappaB activation. METHODS: NOD2 variants were analyzed in 36 CD patients and 30 controls. Endotoxin was stained by immunohistochemistry in 30 intestinal biopsies from patients carrying NOD2 variants (NOD2-mut) or being NOD2 wildtype (WT). Junctional proteins were visualized by immunofluorescence and quantified by Western blotting. NF-kappaB activation was analyzed by immunohistochemistry in specimens from NOD2-WT and NOD2-mut CD and control patients. RESULTS: We demonstrated the increased presence of endotoxin in the mucosal lamina propria of CD patients carrying NOD2 variants. This was associated with an altered composition of epithelial cell-cell contacts. Patients carrying NOD2 variants displayed increased NF-kappaB activation in the mucosa. CONCLUSIONS: This study for the first time demonstrates that translocation of luminal bacteria and/or bacterial products into the intestinal mucosa is increased in patients carrying NOD2 variants, leading to higher activation of proinflammatory signaling cascades.


Assuntos
Translocação Bacteriana , Doença de Crohn/imunologia , Doença de Crohn/microbiologia , Proteína Adaptadora de Sinalização NOD2/genética , Acetilmuramil-Alanil-Isoglutamina/análise , Caderinas/análise , Claudinas/análise , Endotoxinas/análise , Humanos , Junções Intercelulares/imunologia , Junções Intercelulares/microbiologia , Interleucina-8/biossíntese , Proteínas de Membrana/análise , Membrana Mucosa/imunologia , Membrana Mucosa/microbiologia , NF-kappa B/análise , Ocludina , beta Catenina/análise
11.
Mod Rheumatol ; 20(3): 311-5, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20169391

RESUMO

We report on a 33-year-old female patient with a relatively mild clinical case of TNF-receptor associated periodic syndrome (TRAPS) and her 58-year-old father in whom end-stage renal disease due to TRAPS-related AA-amyloidosis has already developed. TRAPS was caused by a I170N mutation that has previously not been associated with amyloidosis. It remains unclear if an only mildly affected patient such as ours would benefit from treatment considering her father's severe course of disease. The relevant literature on this problem is reviewed.


Assuntos
Doenças Hereditárias Autoinflamatórias/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Adulto , Amiloidose/genética , Amiloidose/imunologia , Feminino , Doenças Hereditárias Autoinflamatórias/imunologia , Humanos , Falência Renal Crônica/genética , Falência Renal Crônica/imunologia , Mutação , Receptores Tipo I de Fatores de Necrose Tumoral/imunologia
13.
Hepatogastroenterology ; 56(91-92): 871-6, 2009 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19621720

RESUMO

BACKGROUND/AIMS: The objective of this study was to assess the outcome in a large unselected population of patients with acute pancreatitis treated at a single university center. METHODOLOGY: We performed a retrospective analysis of 364 patients with acute pancreatitis and evaluated outcome, morbidity and mortality in relation to different treatment modalities. RESULTS: 238 patients suffered from interstitial-edematous pancreatitis, 126 patients from the necrotizing form. ICU treatment was necessary for 174 patients (48%). Minimally-invasive CT guided drainage techniques were used in 73 patients (20%) with pancreatic necroses but also in seven patients with edematous pancreatitis (2%), which showed extrapancreatic tissue necrosis. The overall hospital mortality was 14% (5.5% for patients with edematous pancreatitis vs. 30% for patients with necrotizing pancreatitis). CONCLUSIONS: In patients with the edematous form a small subpopulation showed peripancreatic tissue necrosis without necrosis of the pancreas itself, which was related to higher mortality rates than expected for patients with edematous pancreatitis. Regarding therapeutic procedures interventional treatment modalities should be considered as alternative treatment modalities.


Assuntos
Pancreatite/diagnóstico , Pancreatite/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colangiopancreatografia Retrógrada Endoscópica , Estudos de Coortes , Cuidados Críticos , Drenagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Pancreatite/mortalidade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
Immunology ; 126(2): 233-45, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18624726

RESUMO

To study the effects of fatty acids and the involvement of the Toll-like receptor-4/nuclear factor-kappaB (TLR-4/NF-kappaB) pathway with respect to the secretion of adipokines from adipocytes 3T3-L1 adipocytes were stimulated with increasing doses of fatty acids. The secretion of adiponectin, resistin and monocyte chemoattractant protein-1 (MCP-1) was measured by enzyme-linked immunosorbent assay. The NF-kappaB p65 nuclear translocation and TLR-4 expression were investigated by Western blot. The effects mediated by NF-kappaB were tested using a specific NF-kappaB-inhibitor and TLR-4-induced effects were analysed with a neutralizing TLR-4 antibody. Binding of (14)C-labelled fatty acids to TLR-4/MD-2 was investigated using a FLAG-tagged extracellular part of TLR-4 fused to full-length MD-2 via a linker (lipopolysaccharide-Trap). The messenger RNA (mRNA) expression of adipokines in abdominal adipose tissue of rats fed a standard chow or a high-fat diet was investigated by reverse transcription-polymerase chain reaction. The TLR-4 is induced during adipocyte differentiation and its expression is enhanced following fatty acid stimulation. The stimulatory effects of stearic and palmitic acids on MCP-1 secretion and of palmitoleic acid on resistin secretion are mediated via NF-kappaB. The stimulatory effects of stearic, palmitic and palmitoleic acids on resistin secretion and the stimulatory effect of stearic acid on MCP-1 secretion are mediated via TLR-4. Fatty acid-mediated effects are caused by an endogenous ligand because fatty acids were shown not to bind directly to TLR-4/MD-2. Adipose tissue mRNA expression and serum levels of adipokines did not differ in rats fed a high-fat diet. These data provide a new molecular mechanism by which fatty acids can link nutrition with innate immunity.


Assuntos
Adipócitos/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Animal/imunologia , Ácidos Graxos/farmacologia , NF-kappa B/biossíntese , Receptor 4 Toll-Like/biossíntese , Gordura Abdominal/metabolismo , Adipócitos/imunologia , Adipócitos/metabolismo , Adiponectina/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , Quimiocina CCL2/metabolismo , Dieta , Gorduras na Dieta/administração & dosagem , Ácidos Graxos/metabolismo , Imunidade Inata/fisiologia , Masculino , NF-kappa B/antagonistas & inibidores , Ratos , Ratos Wistar , Resistina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Transdução de Sinais/imunologia , Receptor 4 Toll-Like/antagonistas & inibidores
15.
World J Gastroenterol ; 14(35): 5467-70, 2008 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-18803361

RESUMO

We present three cases of patients (at the age of 56 years, 49 years and 74 years respectively) with severe acute pancreatitis (SAP), complicated by intra-abdominal compartment syndrome (ACS) and respiratory insufficiency with limitations of mechanical ventilation. The respiratory situation of the patients was significantly improved after decompression laparotomy (DL) and lung protective ventilation was re-achieved. ACS was discussed followed by a short review of the literature. Our cases show that DL may help patients with SAP to recover from severe respiratory failure.


Assuntos
Pancreatite Necrosante Aguda/complicações , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/cirurgia , Abdome/fisiopatologia , Idoso , Síndromes Compartimentais/complicações , Descompressão Cirúrgica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão
16.
Obesity (Silver Spring) ; 16(7): 1481-6, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18421280

RESUMO

BACKGROUND: Cartonectin (collagenous repeat-containing sequence of 26-kDa protein; CORS-26) was described as a new adipokine of the C1q/TNF molecular superfamily C1q/TNF-related protein-3 (CTRP-3), secreted by the adipocytes of mice and humans. The receptor and function of cartonectin are unknown and the recombinant protein is not commercially available. OBJECTIVE: To investigate the effects of recombinant cartonectin on the secretion of adipokines such as adiponectin, leptin, and resistin from adipocytes of human and murine origin. The effect of the BMI of the adipocyte donor was also investigated. METHODS AND PROCEDURES: Human adipocytes from pooled lean and preobese healthy individuals and murine 3T3-L1 adipocytes were used for stimulation experiments. Recombinant cartonectin was expressed in insect H5 cells. Adipokine secretion was measured using enzyme-linked immunosorbent assay. In addition, western blot analysis and luciferase reporter gene assays were employed. RESULTS: Cartonectin (1, 10, 50, and 250 ng/ml) in higher doses stimulates the secretion of adiponectin and resistin from murine adipocytes. This effect is not caused by an induction of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) protein expression, as confirmed by western blot analysis. Also, luciferase reporter gene assay revealed that cartonectin failed to induce luciferase activity at the peroxisome proliferator-activated receptor responsive element site containing the adiponectin/luciferase promoter fragment. Human adipocytes from lean individuals secrete higher amounts of adiponectin and leptin when compared with adipocytes of individuals with a preobesity BMI (25-30 kg/m(2)). Cartonectin failed to stimulate adiponectin or leptin secretion from human adipocytes, irrespective of the BMI value. DISCUSSION: Cartonectin is a new adipokine that differentially regulates the secretion of classical adipokines, with marked differences between the human and the murine systems. These effects are species-dependent, while basal adipokine secretion is influenced by the BMI.


Assuntos
Adipócitos/metabolismo , Adipocinas/metabolismo , Gordura Subcutânea Abdominal/metabolismo , Fatores de Necrose Tumoral/metabolismo , Células 3T3-L1 , Adipocinas/genética , Adiponectina/metabolismo , Animais , Western Blotting , Índice de Massa Corporal , Ensaio de Imunoadsorção Enzimática , Genes Reporter , Humanos , Interleucina-6/metabolismo , Leptina/metabolismo , Camundongos , PPAR gama/metabolismo , Regiões Promotoras Genéticas , Proteínas Recombinantes/metabolismo , Resistina/metabolismo , Especificidade da Espécie
17.
World J Gastroenterol ; 13(7): 1032-41, 2007 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-17373737

RESUMO

AIM: To examine the factor(s) involved in differentiation of intestinal macrophages (IMACs) using a recently established in vitro model. METHODS: To test whether soluble or membrane bound factors induce IMAC-differentiation, freshly elutriated monocytes (MO) were incubated with conditioned media or cell membranes of intestinal epithelial cells (IEC) or cultured with IEC in transwell systems. To determine the importance of an active migration of MO, three-dimensional aggregates from a 1:1-mixture of MO and IEC were examined by immunohistochemistry and flow cytometry. Apoptosis was examined by caspase-3 Western blots. Extracellular matrix production in differentiation models was compared by immunohistochemistry. RESULTS: IMAC differentiation was observed in a complex three-dimensional co-culture model (multicellular spheroid, MCS) with IEC after migration of MO into the spheroids. By co-culture of MO with conditioned media or membrane preparations of IEC no IMAC differentiation was induced. Co-culture of MO with IEC in transwell-cultures, with the two cell populations separated by a membrane also did not result in intestinal-like differentiation of MO. In contrast to IEC-spheroids with immigrating MO in mixed MCS of IEC and MO only a small subpopulation of MO was able to survive the seven day culture period. CONCLUSION: Intestinal-like differentiation of MO in vitro is only induced in the complex three-dimensional MCS model after immigration of MO indicating a role of cell-matrix and/or cell-cell interactions during the differentiation of IMACs.


Assuntos
Comunicação Celular/fisiologia , Diferenciação Celular/fisiologia , Matriz Extracelular/fisiologia , Mucosa Intestinal/citologia , Macrófagos/citologia , Apoptose/fisiologia , Comunicação Celular/efeitos dos fármacos , Técnicas de Cultura de Células/métodos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Células Cultivadas , Técnicas de Cocultura , Meios de Cultivo Condicionados/farmacologia , Humanos , Mucosa Intestinal/fisiologia , Macrófagos/fisiologia , Monócitos/citologia , Monócitos/fisiologia
18.
Intensive Care Med ; 33(5): 841-844, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17364166

RESUMO

OBJECTIVE: This study analyzed 400 ultrasound examinations in the ICU to assess the indications of this imaging modality. DESIGN AND SETTING: Retrospective analysis on prospectively collected data on 400 patients in a tertiary care hospital. PATIENTS AND PARTICIPANTS: The observational, prospective, clinical study examined 400 bedside abdominal ultrasound examinations performed in the ICU, of which 2% were performed emergently, 56% urgently, and 42% electively. MEASUREMENTS AND RESULTS: Environmental conditions impaired the examination slightly in 54%, moderately in 27%, and severely in 4%. Total time per study ranged from 1 to 45 min (median 10). New pathological findings were detected in 31% while 33% confirmed already known pathologies. In 53% there was no therapeutic consequence, in 27% treatment was continued based on the sonographic findings, in 10% an intervention was necessary, in 6% other therapeutic changes followed, and in 4% additional evaluation was deemed necessary. In 80% no other imaging test had to be performed. CONCLUSIONS: Ultrasound studies are deemed sufficient in a large proportion of patients and help to avoid other, more elaborate imaging studies. However, more focused indications for studies may help to improve cost-effectiveness.


Assuntos
Abdome/diagnóstico por imagem , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Estudos Retrospectivos , Ultrassonografia
19.
Cryobiology ; 54(2): 164-72, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17303105

RESUMO

Kupffer cells (KC) are the resident macrophages of the liver and represent about 80% of the total fixed macrophage population. They are involved in disease states such as endotoxin shock, alcoholic liver diseases and other toxic-induced liver injury. They release physiologically active substances such as eicosanoids and inflammatory cytokines (IL-1, IL-6, TNFalpha), and produce free radical species. Thus, KC are attractive targets for anti-inflammatory therapies and potential candidates responsible for differences in inflammation in liver disease seen between different individuals. However, to perform parallel in vitro experiments with KC from different donors a suitable method for conservation of KC would be necessary. Therefore, the present study evaluated, whether rat and human KC can be frozen, stored and recovered without losing their functional integrity. Rat and human KC were isolated and either cultured under standard conditions (fresh KC) or cryopreserved in special freezing medium (cryopreserved KC). At least 24 h later, cryopreserved KC were thawed, brought into suspension and seeded in the same density as fresh cells for subsequent experiments. Viability of cultured KC was analyzed by trypan blue exclusion. LPS (or PBS as control) stimulation was performed at different time points and cytokine release was analyzed with IL-6 and TNFalpha ELISAs, respectively. Phagocytic capacity was investigated by using a specific phagocytosis assay and FACS analysis. The recovery rate after thawing was around 57% for rat and around 65% for human cryopreserved KC. The results indicate, that KC can successfully be cryopreserved with an adequate recovery rate of viable cells. The properties of fresh and frozen KC can also be compared after thawing. Freshly isolated and cryopreserved cultured KC showed near-normal morphology and did not differ in the cultivation profiles over a period of 72 h. One to three days after seeding, frozen rat or human KC also retained inducible functions such as the production of TNFalpha or IL-6 after LPS challenge. Finally, regardless if they were cryopreserved or not, no differences in the phagocytic activities of the cells were obtained. Taken together, it is concluded that cryopreservation of KC does not change the physiological characteristics of the cells in vitro. Therefore, the method used here for cryopreservation of especially human KC allows the accumulation of KC from several donors for parallel in vitro experiments.


Assuntos
Criopreservação , Macrófagos do Fígado , Animais , Sobrevivência Celular , Citocinas/metabolismo , Humanos , Macrófagos do Fígado/metabolismo , Macrófagos do Fígado/fisiologia , Masculino , Microesferas , Fagocitose/fisiologia , Ratos , Ratos Sprague-Dawley
20.
Gastroenterology ; 132(2): 587-600, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17258732

RESUMO

BACKGROUND & AIMS: Colonic epithelial cells (CECs) receive important survival signals from the extracellular matrix and undergo detachment-induced apoptosis (anoikis) as soon as they lose their cell-matrix anchorage. In contrast to the established role of cell-matrix contact, the role of cell-cell contacts as a physiologic survival factor for CECs is less clear. METHODS: Intact CEC crypts gently centrifuged to form a cell aggregate in which cell-cell contacts were maintained. Induction of apoptosis was assessed by Western Blot analysis, colorimetric assays, DNA electrophoresis, 4',6-diamidino-2-phenylindole staining, and flow cytometry. Activation of survival pathways was analyzed by Western blot. The role of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (Erk)1/2, epidermal growth factor receptor, phosphatidylinositol 3-kinase (PI3-K), and Src signaling was investigated using specific inhibitors. RESULTS: Despite a complete loss of cell-matrix adhesion after CEC isolation, activation of caspases was blocked and anoikis was prevented when cell-cell contacts were preserved. CECs with preserved cell-cell contacts exhibited a rapid dephosphorylation of focal adhesion kinase. Aggregated CECs had stable levels of active beta-catenin and phosphorylated Akt, Erk1/2, and epidermal growth factor receptor, but CECs undergoing anoikis rapidly degraded beta-catenin and dephosphorylated Akt. Inhibition of Src- and PI3-K-dependent signaling reversed the antiapoptotic effect of cell-cell contact preservation, while inhibition of the MEK pathway had no effect. CONCLUSIONS: Integrity of cell-cell contacts compensates for the loss of cell-matrix contact-mediated survival signals in CECs and prevents apoptosis. Cell-cell contact-triggered CEC survival involves antiapoptotic signaling through beta-catenin-, Src-, and PI3-K/Akt- but not through MEK- and focal adhesion kinase-dependent pathways.


Assuntos
Anoikis , Comunicação Celular , Células Epiteliais/metabolismo , Mucosa Intestinal/metabolismo , Transdução de Sinais , Caderinas/metabolismo , Caspases/metabolismo , Agregação Celular , Forma Celular , Sobrevivência Celular , Fragmentação do DNA , Células Epiteliais/citologia , Células Epiteliais/fisiologia , Receptores ErbB/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Quinase 1 de Adesão Focal/metabolismo , Humanos , Técnicas In Vitro , Mucosa Intestinal/citologia , Mucosa Intestinal/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Tempo , beta Catenina/metabolismo , Quinases da Família src/metabolismo
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