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1.
Acta Orthop Belg ; 85(4): 437-447, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32374233

RESUMO

Radial head replacement or ORIF are established treatment options for Mason type-III and type-IV fractures. The aim of this study was to provide results for reconstruction of these complex fractures using fine-threaded K-wires. We present results after reconstruction of 15 Mason type-III and 8 Mason type-IV fractures. Parameters used to describe the functional outcome were pain level, range of motion, and clinical scores. To estimate the elbow stability we performed ultrasound examinations under valgus/varus stress. All radial heads could be reconstructed. The average resting pain level was 0.9 of 10. The average ROM for extension/flexion was 134°, average forearm rotation was 159°. For the whole patient collective the mean MEPS was 86.5 points and the mean QuickDASH was 16.8 points with no significant difference for both groups. We can recommend ORIF with fine-threaded K-wires for Mason type-III and type-IV fractures of the radial head. Ligamentous injuries can be addressed successfully with external fixation.


Assuntos
Fios Ortopédicos , Lesões no Cotovelo , Articulação do Cotovelo/cirurgia , Fratura-Luxação/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas do Rádio/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Avaliação da Deficiência , Feminino , Fratura-Luxação/diagnóstico por imagem , Fixação Interna de Fraturas/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Radiografia , Fraturas do Rádio/diagnóstico por imagem , Amplitude de Movimento Articular , Estudos Retrospectivos , Tomógrafos Computadorizados , Ultrassonografia
2.
Br J Surg ; 97(2): 258-65, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20084676

RESUMO

BACKGROUND: : Exogenously applied insulin-like growth factor (rhIGF-1) may improve normal intestinal healing. This study examined the effect of rhIGF-1-coated sutures on anastomotic healing in experimental colitis. METHODS: : Acute colitis was induced in rats by dextran sodium sulphate (DSS). Inflammation was assessed by clinical Disease Activity Index (DAI), myeloperoxidase (MPO) measurement and histological examination. A distal colonic anastomosis was performed using sutures coated with rhIGF-1 dissolved in poly(D,L-lactide) (PDLLA) under general anaesthetic. Anastomotic healing was evaluated histologically, and by hydroxyproline measurement and bursting parameters after 1, 3 and 7 days, and compared with healthy, DSS and DSS + PDLLA controls. RESULTS: : DAI, MPO and histological inflammation scores were significantly increased in all animals treated with DSS. Bursting occurred less often within the anastomotic line on day 3 in the IGF group than in DSS controls (three versus eight of ten). On day 7, the IGF group had significantly increased histological healing scores (mean(s.e.m.) 12.5(0.7) versus 9.2(0.8) (P < 0.050)) and hydroxyproline content (4.6(0.3) versus 3.6(0.1) mg/g tissue; P < 0.050) compared with DSS controls. CONCLUSION: : IGF-1-coated sutures improve important aspects of anastomotic healing in rats with experimental colitis.


Assuntos
Colite/cirurgia , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/administração & dosagem , Suturas , Cicatrização/efeitos dos fármacos , Anastomose Cirúrgica , Animais , Colite/induzido quimicamente , Sulfato de Dextrana/toxicidade , Feminino , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Deiscência da Ferida Operatória/etiologia , Deiscência da Ferida Operatória/prevenção & controle
4.
Surg Radiol Anat ; 29(3): 225-30, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17342570

RESUMO

INTRODUCTION: Exact anatomical description of the proximal radius is imperative for the development of radial head prostheses. The purpose of this study was to measure the anatomical parameters of the radial head. METHODS: Optosil imprints of 18 pairs of proximal radii fixed with formalin were taken. All possessed their native cartilage joint surface free of any arthritic defects. After being cut into 3 mm slices, the diameter of each slice was measured in steps of 30 degrees of rotation with the margo interosseous acting as a reference point. RESULTS: Maximum radial head diameter was seen from the 0 to the 9 mm slice at a rotation of 30 degrees to full supination perpendicular to the proximal radioulnar joint. The diameter increased from the radiocapitular joint surface to the 6 mm slice, and then it decreased (P < 0.001). At the level of 6 mm the maximum radial head diameter was 24.13 mm (range 21.2-27.3 mm). The minimum diameter was seen perpendicular to the maximum; it also increased from the radiocapitular joint surface to the 6 mm slice and then decreased. There was a significant difference between the minimum and maximum diameter of each slice at a P-level of P < 0.001. Left and right sides were not significantly different at a P-level of 0.01. CONCLUSION: Our data show that the radial head is neither round nor conical. It has a complex shape with an increasing size from the radiocapitular joint surface to the middle of the proximal radioulnar joint surface. No statistically significant differences could be observed between right and left radii.


Assuntos
Articulação do Cotovelo/anatomia & histologia , Rádio (Anatomia)/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
Transplant Proc ; 38(3): 664-5, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16647437

RESUMO

PURPOSE: Due to the persistant organ shortage for kidney transplantation, donor selection has changed in the past years. Although hypertension and diabetes mellitus are known to be risk factors for renal insufficiency, kidneys from donors with these diagnoses in their history have been accepted for kidney transplantation even with an increased risk of poor graft function. Herein we have reported our experience with kidney transplantation using grafts from donors with both, a history of type II diabetes and hypertension. METHODS: Between 2000 and 2005, ten patients were grafted using donors with history of type II diabetes mellitus and hypertension. Mean donor age was 58 +/- 7.5 years and recipient age, 52.2 +/- 15.7 years. Mean HLA mismatch was 0.8 (A); 1.2 (B) and 0.9 (DR). Cold ischemia time was 17.4 +/- 4.1 hours. Immunosuppression was based on CyA (n = 7), tacrolimus (n = 2) or sirolimus (n = 1). RESULTS: Six patients (60%) showed good initial function, and four (40%) had delayed graft function (DGF). One patient died at ten weeks due to multiorgan failure. Two (20%) biopsy-proven rejections were diagnosed, one of which was resistant to therapy. Six months after kidney transplantation, 7 (77%, n = 9) showed good graft function (creatinine 1.3 to 2.4 mg/dL), but one patient displayed long-lasting DGF with poor function. CONCLUSION: Grafts from donors with a history of diabetes mellitus and hypertension are suitable for kidney transplantation. Elevated rate of DGF (40%) would justify allocation of these organs to local transplant centers to shorten ischemia time and thereby reduce DGF and achieve better long-term results. Identification and detailed evaluation of these donors prior to allocation (eg, HbAlc, biopsy) may help transplant centers to accept these kidneys.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Nefrectomia , Doadores de Tecidos/estatística & dados numéricos , Idoso , Teste de Histocompatibilidade , Humanos , Pessoa de Meia-Idade , Seleção de Pacientes , Obtenção de Tecidos e Órgãos
6.
Transplant Proc ; 38(3): 691-2, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16647446

RESUMO

PURPOSE: Ureteral necrosis is a serious problem in kidney transplantation. Sometimes re-ureterocystostomy is possible, while other cases require an elaborate reconstruction to maintain kidney function. We report our experience with ileum interposition for ureteral reconstruction. METHODS: After 9 years of dialysis treatment a 58-year-old patient was grafted using the left kidney of a 59-year-old donor with a cold ischemic time of 9.5 hours. The early postoperative course was uneventful apart from delayed graft function. Immunosuppression consisted of an IL-2-receptor antibody, calcineurin inhibitor, mycophenolate mofetil, and corticosteroids. Discharge serum creatinine was 2.3 mg/dL. In month 4 the patient showed a pararenal urinoma; cystoscopy revealed necrosis of the distal ureter. Operative revision showed urine leakage from the renal pelvis through the urinoma into the bladder. As the whole ureter was necrotic, a re-ureterocystostomy was not possible. The patient's own ureter had been extirpated, and the bladder was too small to do a direct anastomosis between it and the kidney. Consequently, an ileum interposition was performed. RESULTS: The postoperative course was uneventful. Kidney function was stable with a nadir creatinine concentration of 2.0 mg/dL 18 months' posttransplantation, and 14 months' post ileal interposition the kidney function was still satisfactory, with a creatinine level of 2.0 mg/dL. CONCLUSION: Ureteral necrosis is a serious complication following kidney transplantation. Whenever a re-ureterocystostomy or an uretero-ureterostomy is not possible, the interposition of the ileal segment represented a safe procedure to deal with this problem.


Assuntos
Íleo/cirurgia , Transplante de Rim/métodos , Ureter/patologia , Ureter/cirurgia , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Pessoa de Meia-Idade , Necrose , Procedimentos de Cirurgia Plástica
7.
Am J Physiol Gastrointest Liver Physiol ; 290(6): G1131-7, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16423918

RESUMO

Recent clinical trials of the gum resin of Boswellia serrata have shown promising results in patients with ulcerative colitis. The objective of this study was to determine whether a semisynthetic form of acetyl-11-keto-beta-boswellic acid (sAKBA), the most potent anti-inflammatory component of the resin, also confers protection in experimental murine colitis induced by dextran sodium sulfate (DSS) to compare its effects with those standard medications of ulcerative colitis like steroids and to examine whether leukocyte-endothelial cell adhesion is a major target of action of sAKBA. Clinical measurements of disease activity and histology were used to assess disease progression, and intravital microscopy was employed to monitor the adhesion of leukocytes and platelets in postcapillary venules of the inflamed colon. sAKBA treatment significantly blunted disease activity as assessed both grossly and by histology. Similarly, the recruitment of adherent leukocytes and platelets into inflamed colonic venules was profoundly reduced in mice treated with sAKBA. Because previous studies in the DSS model have shown that P-selectin mediates these blood cell-endothelial cell interactions, the expression of P-selectin in the colonic microcirculation was monitored using the dual-radiolabeled antibody technique. The treatment of established colitis with sAKBA largely prevented the P-selectin upregulation normally associated with DSS colitis. All of the protective responses observed with sAKBA were comparable to that realized in mice treated with a corticosteroid. Our findings demonstrated an anti-inflammatory effect of sAKBA and indicated that P-selectin-mediated recruitment of inflammatory cells is a major site of action for this novel anti-inflammatory agent.


Assuntos
Colite/tratamento farmacológico , Colite/imunologia , Modelos Animais de Doenças , Leucócitos/imunologia , Ativação Plaquetária/imunologia , Triterpenos/administração & dosagem , Animais , Anti-Inflamatórios/administração & dosagem , Adesão Celular/efeitos dos fármacos , Colite/induzido quimicamente , Colite/patologia , Sulfato de Dextrana , Relação Dose-Resposta a Droga , Feminino , Leucócitos/efeitos dos fármacos , Leucócitos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Ativação Plaquetária/efeitos dos fármacos , Resultado do Tratamento
8.
Transplant Proc ; 37(3): 1616-7, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15866688

RESUMO

INTRODUCTION: Recipients of related (R) and unrelated (NR) living donor kidney transplantations (LDKTX) receive immunosuppressive (IS) therapy 5 days in advance in order to achieve low rates of acute rejection episodes. We herein report the different IS regimens for R and NR transplants as well as acute rejection and primary function rates. METHODS: Ninety-five LDKTX (69% R, 31% NR) were performed with mean cold ischemia time (CIT) of 145 +/- 32 minutes. In R-LDKTX mean age of recipients was 31 +/- 12.5 years. This cohort included 41 men and 25 women whose mean age was 50 +/- 11.1 years. The therapeutic regimen for R-LDKTX included CyA/MMF/prednisone; for NR-LDKTX, FK/MMF/prednisone. Among the recipients of NR grafts the mean recipient age was 51 +/- 8.5 years. This cohort included 23 men and 6 women whose donor mean age was 50 +/- 8.8 years. The mean HLA mismatch among R-LDKTX (2.3) was significantly less than that in the NR-LDKTX cohort (3.51). RESULTS: At a mean follow-up of 35 months, 94.7% of grafts were functioning. DGF was seen in only one recipient (1%). Three grafts were lost due to acute (R) or chronic (NR) rejection or to multiorgan failures. Two recipients died with functioning grafts. Biopsy-proven rejection episodes were observed in 17.2% of NR-LDKTX and 9% of R-LDKTX. In R-LDKTX 50% of rejection episodes were corticoid-sensitive, while 33% needed ATG, and 16% were treated by a switch to FK. In NR-LDKTX 20% of rejections were corticoid-sensitive, 40% needed ATG, and 40% were treated with rapamycin rescue therapy. CONCLUSION: Although HLA mismatching is significantly different between R- and NR-LDKTX, no difference in outcome was observed, which may be due to the specific therapeutic regimen and short CIT.


Assuntos
Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Quimioterapia Combinada , Família , Feminino , Seguimentos , História do Século XVI , Humanos , Terapia de Imunossupressão/métodos , Doadores Vivos , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
Proc AMIA Symp ; : 280-4, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12463831

RESUMO

Beneficial effects of clinical practice guidelines (CPGs) have not yet reached expectations due to limited routine adoption. Electronic distribution and reminder systems have the potential to overcome implementation barriers. Existing electronic CPG repositories like the National Guideline Clearinghouse (NGC) provide individual access but lack standardized computer-readable interfaces necessary for automated guideline retrieval. The aim of this paper was to facilitate automated context-based selection and presentation of CPGs. Using attributes from the NGC classification scheme, an XML-based metadata repository was successfully implemented, providing document storage, classification and retrieval functionality. Semi-automated extraction of attributes was implemented for the import of XML guideline documents using XPath. A hospital information system interface was exemplarily implemented for diagnosis-based guideline invocation. Limitations of the implemented system are discussed and possible future work is outlined. Integration of standardized computer-readable search interfaces into existing CPG repositories is proposed.


Assuntos
Sistemas de Informação , Guias de Prática Clínica como Assunto , Linguagens de Programação , Software
11.
Gut ; 51(4): 529-35, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12235075

RESUMO

BACKGROUND: Recruitment of circulating cells to the inflamed intestine is modulated by adhesion molecules expressed on the surface of both leucocytes and endothelial cells. AIMS: The objective of this study was to test whether 2'-O-methoxyethyl chimeric antisense oligonucleotides directed against endothelial intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) can downregulate leucocyte-endothelial interactions and thereby attenuate inflammation in rat experimental ileitis. METHODS: Indomethacin (7.5 mg/kg ) was injected subcutaneously into Sprague-Dawley rats 48 and 24 hours prior to intravital microscopy. Animals were treated with either ICAM-1 (ISIS 17470), VCAM-1 (ISIS 18155), or scrambled control antisense oligonucleotides administered subcutaneously or intravenously in parallel with indomethacin. Leucocyte trafficking was observed in ileal submucosal collecting venules. Macroscopic and histological grades of inflammation were measured 48 hours after the first indomethacin application. ICAM-1 and VCAM-1 expression in ileal submucosal venules was detected by immunohistochemistry. RESULTS: Intravenous administration of ICAM-1 oligonucleotides 2 mg/kg (rolling leucocytes 5.7 (2.4)/0.01 mm(2) endothelial surface, adherent leucocytes 0.8 (1.1)) and VCAM-1 oligonucleotides 8 mg/kg (9.2 (4.4), 0.6 (0.8)) significantly reduced leucocyte adhesion compared with diseased controls (27.8 (5.3), 14 (4.4)) in a dose dependent manner whereas subcutaneous treatment did not. Correspondingly, macroscopic and histological inflammation was significantly decreased. ICAM-1 oligonucleotides markedly reduced endothelial ICAM-1 expression while VCAM-1 oligonucleotides clearly diminished endothelial VCAM-1 expression. CONCLUSIONS: Both ICAM-1 and VCAM-1 2'-O-methoxyethyl chimeric antisense oligonucleotides attenuate rat ileitis by downregulation of leucocyte adherence and thus are potential candidates for anti-inflammatory treatment in inflammatory bowel disease.


Assuntos
Ileíte/terapia , Molécula 1 de Adesão Intercelular/genética , Leucócitos/efeitos dos fármacos , Oligonucleotídeos Antissenso/farmacologia , Molécula 1 de Adesão de Célula Vascular/genética , Animais , Adesão Celular/efeitos dos fármacos , Ileíte/patologia , Indometacina/farmacologia , Molécula 1 de Adesão Intercelular/administração & dosagem , Masculino , Oligonucleotídeos Antissenso/administração & dosagem , Ratos , Ratos Sprague-Dawley , Molécula 1 de Adesão de Célula Vascular/administração & dosagem
12.
J Surg Res ; 101(2): 166-75, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11735272

RESUMO

There is growing clinical evidence suggesting that certain secondary lymphoid tissues (e.g., appendix and spleen) contribute to the initiation and/or perpetuation of ulcerative colitis. In this study, the importance of secondary lymphoid tissues in inducing colitis was assessed experimentally by removing the spleen and/or appendix (or sham operation) prior to inducing colitis in mice. Feeding 2.5% dextran sulphate sodium (DSS) in drinking water over 7 days induced colitis. Clinical disease activity was assessed based on weight loss, stool consistency, and presence of blood in stools. Additional measurements included white blood cell count and hematocrit, and myeloperoxidase activity (MPO) in colon samples. Colonic injury was assessed by histology and computerized image analysis. DSS treatment in sham-operated mice produced colitis associated with weight loss, bloody diarrhea, and mucosal ulceration. Clinical assessment of DSS-treated mice subjected to appendectomy or combined appendectomy/splenectomy exhibited a delayed onset and course of disease activity. Histomorphologic examination revealed significantly lower damage scores and a reduction in ulcerated mucosal surface area. Colonic MPO activity, which correlated with tissue injury and disease activity, was lowest in appendectomized mice. No beneficial effects of splenectomy were observed after 7 days of colitis. These findings support the hypothesis that appendicular lymphoid tissue, but not the spleen, contributes to the development of colitis.


Assuntos
Apêndice/fisiologia , Colite/etiologia , Baço/fisiologia , Animais , Apendicectomia , Colo/efeitos dos fármacos , Colo/enzimologia , Colo/patologia , Sulfato de Dextrana/toxicidade , Doenças Inflamatórias Intestinais/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo , Esplenectomia
13.
Am J Physiol Gastrointest Liver Physiol ; 281(6): G1432-9, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11705748

RESUMO

P-selectin-dependent leukocyte-endothelial cell adhesion has been implicated in the pathogenesis of ischemia/reperfusion (I/R) injury in several vascular beds, including the gut. Because platelet-endothelial (P/E) cell adhesion also occurs in postischemic venules, the possibility exists that the expression of P-selectin on the surface of platelets that are adherent to venular endothelial cells may mediate the leukocyte recruitment elicited by I/R. P-selectin expression [dual radiolabeled monoclonal antibody (MAb) technique] and neutrophil accumulation [myeloperoxidase (MPO) activity] were measured in the postischemic small intestine of untreated rats and rats treated with either antiplatelet serum (APS) or MAbs directed against either P-selectin, GPIIb/IIIa, or fibrinogen. The increases in P-selectin expression and tissue MPO normally elicited by I/R were significantly attenuated in the different treatment groups, suggesting that I/R-induced neutrophil recruitment is a platelet-dependent, P-selectin-mediated process. Intravital microscopy was then employed to examine this process relative to leukocyte-endothelial cell adhesion in postischemic rat mesenteric venules. The recruitment of adherent and emigrated leukocytes after I/R was attenuated by pretreatment with a MAb against, either P-selectin, GPIIb/IIIa, or fibrinogen, as well as an Arg-Gly-Asp peptide. Whereas thrombocytopenia greatly blunted leukocyte emigration, it did not alter the leukocyte adherence response to I/R. These findings suggest that platelet-associated P-selectin contributes to the accumulation of leukocytes in postischemic tissue via a mechanism that alters transendothelial leukocyte migration.


Assuntos
Plaquetas/fisiologia , Leucócitos/fisiologia , Oclusão Vascular Mesentérica , Traumatismo por Reperfusão , Circulação Esplâncnica , Animais , Anticorpos/farmacologia , Anticorpos Monoclonais/farmacologia , Plaquetas/imunologia , Adesão Celular , Quimiotaxia de Leucócito , Fibrinogênio/imunologia , Fibrinogênio/fisiologia , Fragmentos Fab das Imunoglobulinas/farmacologia , Leucócitos/patologia , Masculino , Artérias Mesentéricas/fisiopatologia , Oclusão Vascular Mesentérica/patologia , Oclusão Vascular Mesentérica/fisiopatologia , Veias Mesentéricas/patologia , Veias Mesentéricas/fisiopatologia , Oligopeptídeos/farmacologia , Selectina-P/imunologia , Selectina-P/fisiologia , Peroxidase/metabolismo , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/imunologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/fisiologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia
14.
J Exp Med ; 194(9): 1207-18, 2001 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-11696587

RESUMO

Several reports have implicated reactive oxygen and nitrogen metabolites (RONS) in the initiation and/or progression of inflammatory bowel diseases (IBDs). We have investigated the role of three key RONS-metabolizing enzymes (inducible nitric oxide synthase [iNOS], superoxide dismutase [SOD], nicotinamide adenine dinucleotide phosphate [NADPH] oxidase) in a murine model of IBD. Mice genetically deficient ((-/-)) in either iNOS or the p47phox subunit of NADPH oxidase, transgenic (Tg) mice that overexpress SOD, and their respective wild-type (WT) littermates were fed dextran sulfate sodium (DSS) in drinking water for 7 days to induce colitis. In addition, the specific iNOS inhibitor 1400W was used in DSS-treated WT and p47phox(-/-) mice. WT mice responded to DSS feeding with progressive weight loss, bloody stools, elevated serum NO(X) and colonic mucosal injury with neutrophil infiltration. Both the onset and severity of colitis were significantly attenuated in iNOS(-/-) and 1400W-treated WT mice. While the responses to DSS did not differ between WT and p47phox(-/-) mice, enhanced protection was noted in 1400W-treated p47phox(-/-) mice. Interestingly, SOD(Tg) mice exhibited more severe colitis than their WT littermates. These findings reveal divergent roles for superoxide and iNOS-derived NO in intestinal inflammation.


Assuntos
Colite Ulcerativa/enzimologia , NADPH Oxidases/fisiologia , Óxido Nítrico Sintase/fisiologia , Fosfoproteínas/fisiologia , Superóxido Dismutase/fisiologia , Amidinas/farmacologia , Animais , Benzilaminas/farmacologia , Colite Ulcerativa/patologia , Colo/imunologia , Sulfato de Dextrana/efeitos adversos , Sistema Digestório/anatomia & histologia , Fenômenos Fisiológicos do Sistema Digestório , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Expressão Gênica , Humanos , Doenças Inflamatórias Intestinais/enzimologia , Doenças Inflamatórias Intestinais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , NADPH Oxidases/genética , Infiltração de Neutrófilos/imunologia , Neutrófilos/imunologia , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Fosfoproteínas/genética , Espécies Reativas de Oxigênio/metabolismo , Organismos Livres de Patógenos Específicos , Superóxido Dismutase/genética , Superóxidos/metabolismo , Fatores de Tempo , Fator de Necrose Tumoral alfa/análise
15.
Acta Physiol Scand ; 173(1): 83-91, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11678730

RESUMO

Reperfusion of ischaemic tissues often leads to microvascular dysfunction that is manifested as impaired endothelium-dependent dilation of arterioles, enhanced fluid filtration and leucocyte plugging in capillaries, and the trafficking of leucocytes and plasma protein extravasation in postcapillary venules. Efforts to define the mechanisms that underlie these microvascular responses to ischaemia and reperfusion have largely relied on pharmacological agents and monoclonal antibodies. Gene-targeting technology has been applied to the production of transgenic and knockout mice that are rapidly gaining acceptance as tools for mechanistic studies of ischaemia-reperfusion (I/R) injury that obviate some of the concerns (e.g. specificity) raised about previously employed experimental strategies. This review summarizes some of our efforts to apply gene-targeted mice to the study of I/R injury in the splanchnic vascular bed. A role for endothelial cell adhesion molecules (CAMs) and reactive oxygen metabolites is supported by results from mutant mice. Low density lipoprotein receptor mice also reveal that the microvascular and inflammatory responses to I/R are greatly exaggerated during chronic hypercholesterolaemia. The wide variety of mutant mice that have been produced for inflammation-related research makes this experimental strategy particularly promising for mechanistic investigations of the tissue responses to I/R.


Assuntos
Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/fisiopatologia , Circulação Esplâncnica/fisiologia , Animais , Camundongos , Camundongos Mutantes
16.
Inflamm Res ; 50(6): 289-93, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11475329

RESUMO

OBJECTIVE: Metallothioneins (MT) are cytoprotective against the damaging effects of oxygen-derived free radicals. Therefore MT may be involved in defence mechanisms to counter Crohn's disease (CD) and ulcerative colitis (UC). MATERIALS: 107 routinely processed tissue samples from 22 patients with CD and 48 patients with UC were tested with the monoclonal anti-MT antibody E9. METHODS: Immunohistochemistry was used to assess MT staining in a semiquantitative manner. Chi-square test was used for statistical analysis. RESULTS: MT overexpression was found in the fibroblasts of all ulcerative and/or fissural lesions in UC and CD. MT overexpression in intestinal epithelial cells of 40% of UC and CD lesions correlated significantly with the grade of inflammation. CONCLUSIONS: MT-immunoreactivity in fibroblasts supports a protective role for MT in inflammatory bowel disease. It remains unclear whether MT overexpression in epithelial cells is also important in this protection.


Assuntos
Doenças Inflamatórias Intestinais/metabolismo , Metalotioneína/biossíntese , Humanos , Imuno-Histoquímica , Metalotioneína/análise
17.
Biochem Biophys Res Commun ; 282(2): 635-42, 2001 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-11401508

RESUMO

Adhesion molecules have been implicated in the pathogenesis of inflammatory bowel diseases. We investigated their expression and contribution to leukocyte recruitment in experimental intestinal inflammation. Ileitis was induced in Sprague-Dawley rats by two injections of indomethacin (7.5 mg/kg), given 24 h apart. Endothelial intercellular adhesion molecule-1 (ICAM-1) expression was quantified using the dual radiolabeled monoclonal antibody technique and Mac-1 (CD11b/CD18) expression on leukocytes by flow cytometry. Leukocyte infiltration was monitored by tissue myeloperoxidase (MPO) activity. The first indomethacin injection induced a time- and site-dependent increase of ICAM-1 expression in ileal mucosa and muscularis. The second injection resulted in a reduction of ICAM-1 expression below constitutive levels whereas Mac-1 was upregulated. MPO changes paralleled lesion development over 48 h. ICAM-1 and MPO values were correlated for the first 24 h. Immunoneutralization of either ICAM-1 or Mac-1 attenuated mucosal injury. We conclude that (i) indomethacin-induced ileitis is associated with a temporally disassociated upregulation of ICAM-1 and (ii) despite a reduction in ICAM-1 after 24 h, ICAM-1, in concert with Mac-1, contributes to mucosal injury and leukocyte infiltration elicited by indomethacin.


Assuntos
Ileíte/induzido quimicamente , Ileíte/fisiopatologia , Indometacina/toxicidade , Molécula 1 de Adesão Intercelular/metabolismo , Animais , Anticorpos Monoclonais , Modelos Animais de Doenças , Endotélio/efeitos dos fármacos , Endotélio/patologia , Endotélio/fisiopatologia , Ileíte/patologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/fisiopatologia , Leucócitos/enzimologia , Leucócitos/imunologia , Leucócitos/patologia , Antígeno de Macrófago 1/metabolismo , Masculino , Testes de Neutralização , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley
18.
Am J Hypertens ; 14(6 Pt 2): 44S-54S, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11411765

RESUMO

A variety of recently discovered glycoproteins have been implicated in cell-cell interactions that are critical for normal hemostasis, immune surveillance, and vascular wall integrity. These cell adhesion molecules (CAM) are known to mediate blood cell (leukocyte, platelet)-endothelial cell interactions that can occur in all segments of the microvasculature under certain physiological (eg, hemostasis) and pathological (eg, inflammation) conditions. The multistep process of leukocyte recruitment illustrates how the coordinated and regulated expression of structurally and functionally distinct families of CAM can elicit a highly reproducible vascular response to inflammation. Selectins mediate the initial, low-affinity leukocyte-endothelial cell interaction that is manifested as leukocyte rolling. This transient binding results in further leukocyte activation and subsequent firm adhesion and transendothelial migration of leukocytes, both of which are mediated by interactions between members of the integrin and immunoglobulin superfamily of CAM. This CAM-regulated process of leukocyte recruitment often results in endothelial cell dysfunction, which can be manifested as either impaired endothelium-dependent vasorelaxation in arterioles, excess fluid filtration in capillaries, and enhanced protein extravasation in venules. Consequently, CAM have been implicated in a variety of vascular disorders (eg, ischemia/reperfusion, atherosclerosis, allograft dysfunction, and vasculitis) and an enhanced expression of these CAM has been invoked to explain the exaggerated microvascular dysfunction associated with some of the risk factors (hypertension, hypercholesterolemia, diabetes) for cardiovascular disease. Monoclonal antibodies and genetically engineered mice have proven to be valuable tools for defining the contribution of CAM to disease progression and provide hope for new diagnostic and therapeutic strategies for cardiovascular diseases.


Assuntos
Moléculas de Adesão Celular/fisiologia , Doenças Vasculares/fisiopatologia , Animais , Vasos Sanguíneos/fisiopatologia , Adesão Celular/fisiologia , Endotélio Vascular/citologia , Endotélio Vascular/fisiologia , Humanos , Isquemia/fisiopatologia , Leucócitos/fisiologia , Microcirculação , Traumatismo por Reperfusão/fisiopatologia , Fatores de Risco
19.
Int J Colorectal Dis ; 16(2): 88-95, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11355324

RESUMO

The gum resin extract from Boswellia serrata (H15), an herbal product, was recently shown to have positive therapeutic effects in inflammatory bowel disease (IBD). However, the mechanisms and constituents responsible for these effects are poorly understood. This study examined the effect of the Boswellia extract and its single constituent acetyl-11-keto-beta-boswellic acid (AKBA) on leukocyte-endothelial cell interactions in an experimental model of IBD. Ileitis was induced by two subcutaneous injections of indomethacin (7.5 mg/kg) in Sprague-Dawley rats 24 h apart. Rats also received oral treatment with the Boswellia extract (H15) or AKBA at two different doses (low and high) equivalent to recommendations in human disease over 2 days. Controls received only the carriers NaHCO3 (subcutaneously) and tylose (orally). Effects of treatment were assessed by intravital microscopy in ileal submucosal venules for changes in the number of rolling and adherent leukocytes and by macroscopic and histological scoring. Increased leukocyte-endothelial cell adhesive interactions and severe tissue injury accompanied indomethacin-induced ileitis. Treatment with the Boswellia extract or AKBA resulted in a dose-dependent decrease in rolling (up to 90%) and adherent (up to 98%) leukocytes. High-dose Boswellia extract as well as both low- and high-dose AKBA significantly attenuated tissue injury scores. Oral therapy with the Boswellia extract or AKBA significantly reduces macroscopic and microcirculatory inflammatory features normally associated with indomethacin administration, indicating that the anti-inflammatory actions of the Boswellia extract in IBD may be due in part to boswellic acids such as AKBA.


Assuntos
Ileíte/tratamento farmacológico , Ileíte/patologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Triterpenos/farmacologia , Animais , Modelos Animais de Doenças , Seguimentos , Masculino , Extratos Vegetais/farmacologia , Plantas Medicinais , Probabilidade , Ratos , Ratos Sprague-Dawley , Valores de Referência , Resinas Vegetais/farmacologia , Sensibilidade e Especificidade , Resultado do Tratamento
20.
Zentralbl Gynakol ; 122(8): 445-51, 2000.
Artigo em Alemão | MEDLINE | ID: mdl-11005138

RESUMO

Computer-based medical documentation so far proved advantageous especially through standardization of data entry and increased access speed. Additional benefits can be achieved through the implementation of integrated, cross-project documentation tools and their integration into the clinical work-flow, which allow data to be used for a wide variety of applications (e.g. quality management, clinical research, clinic management). The presence of incompatible documentation software often complicates the realization of these goals. Implementation of new documentation tools therefore should consider flexibility and multiple-use of data as primary design goals. In the presented paper requirements for flexible documentation tools are introduced. The Entity-Attribute-Value-Model is described as a possible means of implementation. Practical experiences made with a prototype application are reported.


Assuntos
Administração Hospitalar/tendências , Aplicações da Informática Médica , Sistemas Computadorizados de Registros Médicos/normas , Software/normas , Alemanha , Humanos , Modelos Teóricos , Controle de Qualidade , Software/tendências
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