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1.
Arch Orthop Trauma Surg ; 137(1): 73-79, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27670876

RESUMO

INTRODUCTION: Chronic exertional compartment syndrome (CECS) is a common injury in young athletes, causing pain in the involved leg compartment during strenuous exercise. The gold standard treatment is fasciotomy, but most of the reports on its effectiveness include relatively small cohorts and relatively short follow-up periods. This study reports the long-term results of a large cohort of young athletes who underwent single-incision fasciotomy for CECS. MATERIALS AND METHODS: This a retrospective case-series study. All patients treated by fasciotomies performed for CECS between 2007 and 2011, in a tertiary medical institution. CECS was diagnosed following history taking and clinical evaluation, and confirmed by compartment pressure measurements. Ninety-five legs that underwent single-incision subcutaneous fasciotomy were included. Data on the numerical analog scale (NAS), Tegner activity score, and quality-of-life (QOL) as measured via the short form-12 (SF-12) were retrieved from all patients preoperatively and at the end of follow-up. RESULTS: The average time to diagnosis was 22 months and the mean follow-up was 50.1 months. Sixty-three legs underwent anterior compartment fasciotomy (an additional 30 legs also underwent lateral compartment release), and two legs underwent lateral and peroneal compartment releases. The average change in Tegner score was an improvement of 14.6 points. Similarly, the patients reported a significant improvement in the SF-12 and NAS scores. Satisfaction rates were high (average 75.5 %). The main complications were wound infection (2 patients) and nerve injuries (4 patients). Eight patients had recurrence. CONCLUSION: Single-incision fasciotomy leads to long-term improvement in the activity level and QOL of patients with CECS.


Assuntos
Síndromes Compartimentais/cirurgia , Fasciotomia/métodos , Perna (Membro)/cirurgia , Adolescente , Adulto , Doença Crônica , Síndromes Compartimentais/etiologia , Fasciotomia/efeitos adversos , Feminino , Humanos , Escore de Lysholm para Joelho , Masculino , Dor/etiologia , Esforço Físico , Complicações Pós-Operatórias , Pressão , Qualidade de Vida , Recidiva , Estudos Retrospectivos , Adulto Jovem
2.
Arthritis Rheum ; 65(3): 599-607, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23203906

RESUMO

OBJECTIVE: The binding of abatacept (CTLA-4Ig) to the B7 ligands CD80 and CD86 prevents the engagement of CD28 on T cells and thereby prevents effector T cell activation. In addition, a direct effect of CTLA-4Ig on antigen-presenting cells (APCs) could contribute to the therapeutic effect. To further elucidate the mechanism of CTLA-4Ig, we performed phenotype and functional analyses of APCs in patients with rheumatoid arthritis (RA) before and after the initiation of CTLA-4Ig therapy. METHODS: Peripheral blood mononuclear cells were analyzed before and at 2 and 4 weeks after the initiation of CTLA-4Ig therapy. Proportions of APCs were determined by flow cytometry. CD14+ monocytes were further analyzed for the expression of costimulatory and adhesion molecules and for their transendothelial migratory capacity in vitro. In addition, CD14+ monocytes from healthy controls were analyzed for their migratory and spreading capacity. RESULTS: Proportions and absolute numbers of monocytes were significantly increased in RA patients treated with CTLA-4Ig. The expression of several adhesion molecules was significantly diminished. In addition, monocytes displayed a significant reduction in their endothelial adhesion and transendothelial migratory capacity upon treatment with CTLA-4Ig. Likewise, isolated monocytes from healthy controls revealed a significant reduction in their migratory and spreading activity after preincubation with CTLA-4Ig or anti-CD80 and anti-CD86 antibodies. CONCLUSION: We describe direct effects of CTLA-4Ig therapy on phenotype and functional characteristics of monocytes in RA patients that might interfere with the migration of monocytes to the synovial tissue. This additional mechanism of CTLA-4Ig might contribute to the beneficial effects of CTLA-4Ig treatment in RA patients.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Movimento Celular/efeitos dos fármacos , Imunoconjugados/uso terapêutico , Monócitos/efeitos dos fármacos , Monócitos/patologia , Abatacepte , Células Apresentadoras de Antígenos/efeitos dos fármacos , Células Apresentadoras de Antígenos/metabolismo , Células Apresentadoras de Antígenos/patologia , Antirreumáticos/uso terapêutico , Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Moléculas de Adesão Celular/metabolismo , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo
3.
Int J Clin Pract ; 68(11): 1383-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25040243

RESUMO

BACKGROUND: Lateral epicondylitis (LE) is a common cause of elbow pain. Despite a relatively high prevalence and morbidity, there is still no single effective ('gold standard') treatment for LE. We hypothesised that a surgeon's experience, country of origin and area of expertise would influence choices concerning patient management. The purpose of this survey was to describe the current trends and common practices in treating LE worldwide. MATERIAL AND METHODS: A total of 291 orthopaedic surgeons of 12 subspecialties from 57 countries were surveyed on their choice of LE treatment modalities. Their preferences were analysed according to country of origin, field of expertise and seniority. The results were compared with current published level-1 evidence. RESULTS: The most popular modalities of treatment among all of the surveyed orthopaedic surgeons were non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroid (CS) injection (38% of recommendations each). The most popular Modalities of treatment among the hand surgeons was NSAIDs (48%) and CS injection (30%). There was no significant difference in recommendations based on geography, seniority or specialisation (i.e., hand surgeons among others). CONCLUSIONS: Neither geography, seniority nor medical specialty affects surgeons' preferences in the treatment of LE. There appears to be little correlation between scientific evidence and therapeutic choices for managing LE. LEVEL OF EVIDENCE: Level V, Study.


Assuntos
Ortopedia/métodos , Cotovelo de Tenista/tratamento farmacológico , Corticosteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Artralgia/tratamento farmacológico , Comportamento de Escolha , Humanos , Cirurgiões , Inquéritos e Questionários , Cotovelo de Tenista/mortalidade
4.
Clin Exp Rheumatol ; 30(1): 73-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22325451

RESUMO

OBJECTIVES: Heme oxygenase-1 (HO-1) which degrades Heme to free iron, biliverdin and carbon monoxide (CO) plays an important role in inflammation. There are, however, conflicting data concerning the role of HO-1 in rheumatoid arthritis (RA) and the therapeutic potential of individual heme degradation products remains to be determined. We therefore investigated the effect of CO and biliverdin upon therapeutic administration in the murine collagen induced arthritis (CIA) model of RA. METHODS: CIA was induced in DBA/1 mice. Anti-CII antibody levels were determined by ELISA. Mice were scored for paw swelling and grip strength. After the first clinical signs of arthritis one group of animals was treated with biliverdin, the second group was treated with CO. After 60 days all animals were sacrificed and analysed for histomorphological signs of arthritis. RESULTS: All animals immunised with CII developed serum anti-CII antibodies. Antibody levels were decreased in the CO-treated group. Both, Biliverdin and the CO-treated animals, showed an improvement in clinical disease activity. Histological analysis revealed significantly less inflammation, erosion and reduced numbers of osteoclasts in CO-treated animals only, whereas cartilage degradation was prevented in both biliverdin and CO-treated animals. CONCLUSIONS: Our data demonstrate a beneficial effect of CO, in particular, and biliverdin, on inflammation and bone destruction in the CIA mouse model.


Assuntos
Artrite Experimental/tratamento farmacológico , Biliverdina/uso terapêutico , Monóxido de Carbono/uso terapêutico , Heme Oxigenase-1/metabolismo , Articulações/efeitos dos fármacos , Administração por Inalação , Animais , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Biliverdina/administração & dosagem , Biliverdina/metabolismo , Monóxido de Carbono/administração & dosagem , Monóxido de Carbono/metabolismo , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Articulações/metabolismo , Articulações/patologia , Camundongos
5.
Bone Joint J ; 100-B(7): 984-988, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29954214

RESUMO

Aims: Intra-articular 90Yttrium (90Y) is an adjunct to surgical treatment by synovectomy for patients with diffuse-type tenosynovial giant-cell tumour (dtTGCT) of the knee, with variable success rates. Clinical information is, however, sparse and its value remains unclear. We investigated the long-term outcome of patients who underwent synovectomy with and without adjuvant treatment with 90Yttrium. Patients and Methods: All patients with dtTGCT of the knee who underwent synovectomy between 1991 and 2014 were included in the study. Group A patients underwent synovectomy and an intra-articular injection of 90Yttrium between six and eight weeks after surgery. Group B patients underwent surgery alone. Results: There were 34 patients in group A and 22 in group B. Recurrence of dtTGCT was identified by MRI, which was undertaken in patients with further symptoms. At a mean follow-up of 7.3 years (2.5 to 25.4), there was residual disease in 15 patients in group A and 11 in group B (p < 0.363). The mean Musculoskeletal Tumor Society (MSTS) score at final follow-up was 85% and 83%, respectively (p < 0.91). Conclusion: There were no significant differences in outcome between patients treated surgically for dtTGCT of the knee with or without an adjuvant intra-articular injection of 90Yttrium. We were unable to provide conclusive evidence of any benefits derived from the adjuvant treatment. Cite this article: Bone Joint J 2018;100-B:984-8.


Assuntos
Durapatita/administração & dosagem , Articulação do Joelho/patologia , Sinovectomia/métodos , Sinovite Pigmentada Vilonodular/cirurgia , Radioisótopos de Ítrio/administração & dosagem , Adulto , Feminino , Seguimentos , Humanos , Injeções Intra-Articulares , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Radioterapia Adjuvante/métodos , Estudos Retrospectivos , Membrana Sinovial/patologia , Sinovite Pigmentada Vilonodular/patologia , Sinovite Pigmentada Vilonodular/radioterapia , Resultado do Tratamento
6.
Biochim Biophys Acta ; 618(1): 18-27, 1980 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-7378430

RESUMO

The relationship of developing obesity and hyperinsulinaemia to fatty acid synthesis in whole body and major tissues has been studied in two strains of genetically obese (ob/ob) mice using in vivo incorporation of 3H2O into fatty acids. Rates of fatty acid synthesis were not increased in pre-weaning C57BL/6J obese mice even though hyperinsulinaemia and obesity occurred. Post-weaning, rates of fatty acid synthesis increased to 5 weeks of age in adipose tissue, liver and carcass, the latter being the major site of synthesis. Synthesis then declined in carcass and adipose tissue, but remained unchanged in liver at 3 months. Increased fatty acid synthesis developed earlier in Imperial College obese mice as compared to the C57BL/6J strain and total rates of synthesis were 3--5 times greater. Adipose tissue was the major site of synthesis in Imperial College obese mice, while carcass was of only minor importance. Thus genetic background and age strongly affected rates of fatty acid synthesis and also the extent to which various tissues contributed.


Assuntos
Ácidos Graxos/biossíntese , Camundongos Obesos/metabolismo , Tecido Adiposo/metabolismo , Fatores Etários , Animais , Genótipo , Mucosa Intestinal/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos/genética , Pele/metabolismo , Especificidade da Espécie
7.
Endocr Relat Cancer ; 22(3): 387-97, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25972245

RESUMO

Mitochondrial dysfunction, due to mutations of the gene encoding succinate dehydrogenase (SDH), has been implicated in the development of adrenal phaeochromocytomas, sympathetic and parasympathetic paragangliomas, renal cell carcinomas, gastrointestinal stromal tumours and more recently pituitary tumours. Underlying mechanisms behind germline SDH subunit B (SDHB) mutations and their associated risk of disease are not clear. To investigate genotype-phenotype correlation of SDH subunit B (SDHB) variants, a homology model for human SDH was developed from a crystallographic structure. SDHB mutations were mapped, and biochemical effects of these mutations were predicted in silico. Results of structural modelling indicated that many mutations within SDHB are predicted to cause either failure of functional SDHB expression (p.Arg27*, p.Arg90*, c.88delC and c.311delAinsGG), or disruption of the electron path (p.Cys101Tyr, p.Pro197Arg and p.Arg242His). GFP-tagged WT SDHB and mutant SDHB constructs were transfected (HEK293) to determine biological outcomes of these mutants in vitro. According to in silico predictions, specific SDHB mutations resulted in impaired mitochondrial localisation and/or SDH enzymatic activity. These results indicated strong genotype-functional correlation for SDHB variants. This study reveals new insights into the effects of SDHB mutations and the power of structural modelling in predicting biological consequences. We predict that our functional assessment of SDHB mutations will serve to better define specific consequences for SDH activity as well as to provide a much needed assay to distinguish pathogenic mutations from benign variants.


Assuntos
Neoplasias das Glândulas Suprarrenais/enzimologia , Paraganglioma/enzimologia , Feocromocitoma/enzimologia , Succinato Desidrogenase/química , Succinato Desidrogenase/metabolismo , Neoplasias das Glândulas Suprarrenais/genética , Técnicas de Cultura de Células , Predisposição Genética para Doença , Células HEK293 , Humanos , Mitocôndrias/enzimologia , Mitocôndrias/patologia , Modelos Moleculares , Mutação , Paraganglioma/genética , Feocromocitoma/genética , Estrutura Secundária de Proteína , Succinato Desidrogenase/genética , Transfecção
8.
Am J Sports Med ; 29(4): 410-4, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11476377

RESUMO

We evaluated 18 of 23 patients who had undergone cryopreserved meniscal allograft transplantation for compartmental pain after total meniscectomy 2 to 8 years (mean, 5.4) after the operation. The Short Form-36 scores revealed a decrease in pain with a significant improvement in function, although function remained limited. There was no significant decrease in joint space on 45 degrees posteroanterior weightbearing radiographs through the duration of the study. Eight of 22 allograft menisci (36%) tore during the study period, necessitating 6 partial and 2 total meniscectomies. Two patients subsequently underwent reimplantation. Histologic examination of the removed tissue revealed reduced cellularity as compared with normal or torn native menisci. Four specimens also underwent detailed cytokine evaluation and demonstrated reduced cytokine expression compared with controls. While successful in alleviating compartmental pain that may be a late consequence of major meniscectomy, allograft menisci are repopulated with fewer cells than are present in normal or torn native menisci. These cells also demonstrate potentially reduced function, as measured by decreased growth factor production. This decreased biologic activity may be a factor that contributes to the high frequency of retears noted in this and prior studies.


Assuntos
Meniscos Tibiais/transplante , Adulto , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior , Artralgia/etiologia , Artralgia/prevenção & controle , Artroscopia , Feminino , Seguimentos , Humanos , Instabilidade Articular/etiologia , Instabilidade Articular/fisiopatologia , Instabilidade Articular/prevenção & controle , Articulação do Joelho/diagnóstico por imagem , Masculino , Meniscos Tibiais/diagnóstico por imagem , Meniscos Tibiais/patologia , Estudos Prospectivos , Radiografia , Recuperação de Função Fisiológica , Reoperação , Lesões do Menisco Tibial , Transplante Homólogo , Resultado do Tratamento
9.
J Bone Joint Surg Br ; 79(2): 304-6, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9119862

RESUMO

Simultaneous bilateral posterior dislocation of the hip is very uncommon and most cases are caused by road accidents. Simultaneous bilateral posterior dislocation of the hip due to convulsions is extremely rare. We report the case of a man who was diagnosed late and operated on 15 weeks after the injury. We discuss the treatment of chronic dislocation of the hip and review the literature.


Assuntos
Luxação do Quadril/etiologia , Convulsões/complicações , Adulto , Terapia Combinada , Síndrome de Down/complicações , Necrose da Cabeça do Fêmur/etiologia , Necrose da Cabeça do Fêmur/cirurgia , Luxação do Quadril/diagnóstico por imagem , Luxação do Quadril/cirurgia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Prótese de Quadril , Humanos , Masculino , Radiografia , Tração
10.
Chirurg ; 48(11): 728-31, 1977 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-923367

RESUMO

In the period between January 1974 and 1977, a total of 358 selective proximal vagotomies were performed in patients with gastroduodenal ulcers avoiding pyloroplasty if possible. This report is concerned with intra- and postoperative experience with Burge's operating technique, incorporating LDS instruments from the USSC. The use of the instrument in preparing the proximal stomach is discussed. The instrument is recommended for reducing the time needed for emergency and simultaneous operations and for performing vagotomy in high risk patients.


Assuntos
Instrumentos Cirúrgicos , Vagotomia/métodos , Alemanha Ocidental , Humanos , Complicações Pós-Operatórias , Estudos Retrospectivos , Vagotomia/instrumentação
11.
Artigo em Inglês | MEDLINE | ID: mdl-11665375

RESUMO

Although inferior alveolar and lingual nerve injuries appear to occur more often, there are undoubtedly cases of ION injury that require evaluation and possible surgical intervention by the oral and maxillofacial surgeon. Patients with ION injuries will require a neurosensory examination for the determination of the level of sensory impairment, or the localization of pain of peripheral origin (centrally mediated pain will not benefit from peripheral nerve surgery). The surgical management of ION injury might be as relatively simple as decompression of the nerve by reduction of a zygomatic complex fracture, or may require extensive mobilization of the nerve and surrounding soft tissue and bone to allow for primary anastomosis or a nerve autograft. In specific instances, improvement in ION sensory function or alleviation of pain within the distribution of the ION can be expected.


Assuntos
Nervo Maxilar/lesões , Órbita/inervação , Anastomose Cirúrgica , Descompressão Cirúrgica , Humanos , Nervo Maxilar/patologia , Nervo Maxilar/cirurgia , Síndromes de Compressão Nervosa/cirurgia , Exame Neurológico , Órbita/cirurgia , Nervos Periféricos/transplante , Sensação/fisiologia , Transtornos de Sensação/diagnóstico , Transtornos de Sensação/cirurgia , Transplante Autólogo , Fraturas Zigomáticas/cirurgia
12.
Harefuah ; 133(9): 357-9, 415, 1997 Nov 02.
Artigo em Hebraico | MEDLINE | ID: mdl-9418336

RESUMO

Adhesive capsulitis is a problem for the orthopedic surgeon due to the difficulty of treatment. Although it is self-limited, few patients will wait for spontaneous resolutions while suffering pain and progressive loss of motion. Our aim was to modify the course of the disease and to shorten recovery time by combining intensive physiotherapy with intra-articular infiltration and gentle manipulation. 49 patients with 50 frozen shoulders were enrolled in the study. All patients were treated initially with physiotherapy for 4-8 weeks. If no improvement was noted the affected shoulder was infiltrated and gently manipulated. 27 of 49 patients (55%) improved dramatically with the initial physiotherapy regimen. They achieved full or nearly full range of motion, with significant relief of pain. 22 patients were infiltrated and manipulated. Elevation improved significantly from an average of 110.95 to 165.71 degrees (p < 0.001), external rotation from an average of 9.52 to 43.57 degrees (p < 0.001) and internal rotation also improved significantly (p < 0.001). Self assisted physiotherapy is the corner stone of treatment in adhesive capsulitis. When pain and limitation of passive range of motion persist, infiltration and gentle manipulation dramatically shortens the debilitating process.


Assuntos
Anestésicos Locais/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Betametasona/uso terapêutico , Bursite/terapia , Lidocaína/uso terapêutico , Modalidades de Fisioterapia , Articulação do Ombro , Anestésicos Locais/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Betametasona/administração & dosagem , Bursite/fisiopatologia , Terapia Combinada , Feminino , Humanos , Injeções Intra-Articulares , Lidocaína/administração & dosagem , Masculino , Pessoa de Meia-Idade , Dor , Amplitude de Movimento Articular
13.
Harefuah ; 134(4): 269-70, 335, 1998 Feb 15.
Artigo em Hebraico | MEDLINE | ID: mdl-10909503

RESUMO

Insufficiency fractures of the pelvis may be overlooked as a cause of hip or groin pain. These fractures occur in the elderly, usually those with pronounced osteopenia of the pelvis. Predisposing factors include corticosteroids, local irradiation and postmenopausal osteoporosis. These fractures are difficult to detect clinically and plain radiographs and other studies may be misleading, delaying diagnosis and treatment. A 65-year-old woman had left groin and hip pain for 2 months with no history of trauma. Plain radiographs showed lytic lesions in the left pubic rami. Bone scan revealed increased uptake in that region, suggesting metastatic bone disease. Computed tomography and magnetic resonance imaging demonstrated fractures in the left superior and inferior pubic rami, with callus formation with no involvement of soft tissues. Quantitative computed tomography indicated low calcium concentration, below fracture threshold. The diagnosis of insufficiency fractures of the pelvis was confirmed by the favorable clinical and radiographic outcome. It is therefore important to be familiar with the appearance and location of these fractures.


Assuntos
Fraturas Ósseas/etiologia , Osteoporose Pós-Menopausa/complicações , Ossos Pélvicos/patologia , Idoso , Feminino , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/patologia , Humanos , Imageamento por Ressonância Magnética , Ossos Pélvicos/diagnóstico por imagem , Dor Pélvica , Tomografia Computadorizada por Raios X
14.
Harefuah ; 135(3-4): 108-9, 167, 1998 Aug.
Artigo em Hebraico | MEDLINE | ID: mdl-9885654

RESUMO

Vacuum phenomenon is well known in degenerative spinal disease in the elderly, but is seldom seen in other joints, especially in children. The phenomenon does not represent a pathological finding, and can be used for imaging of the articular facets, mainly in the hip and knee joints. We report a patient with this phenomenon in the hip joint.


Assuntos
Articulação do Quadril , Artropatias/diagnóstico por imagem , Osteonecrose/diagnóstico por imagem , Artrografia , Cartilagem Articular/diagnóstico por imagem , Pré-Escolar , Diagnóstico Diferencial , Articulação do Quadril/diagnóstico por imagem , Humanos , Artropatias/terapia , Masculino , Tração
15.
Harefuah ; 134(9): 695-7, 750, 1998 May 01.
Artigo em Hebraico | MEDLINE | ID: mdl-10909616

RESUMO

The dramatic course of necrotizing soft tissue infection represents a medical emergency, since it is limb- and life-threatening. Most necrotizing soft tissue infections are caused by mixed aerobic and anaerobic Gram-negative and Gram-positive organisms. Most case have been reported in immuno-compromised hosts after penetrating trauma or surgery. We describe a unique series of cases of necrotizing soft tissue infection. The mainstay of treatment is early and daily debridement of devitalized tissue and broad-spectrum antibiotics. Hyperbaric oxygen therapy should be considered.


Assuntos
Infecções Bacterianas/terapia , Fasciite Necrosante/terapia , Infecções dos Tecidos Moles/terapia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/cirurgia , Desbridamento , Fasciite Necrosante/tratamento farmacológico , Fasciite Necrosante/cirurgia , Feminino , Humanos , Oxigenoterapia Hiperbárica , Masculino , Pessoa de Meia-Idade , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/cirurgia
16.
Mucosal Immunol ; 7(6): 1452-66, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24850428

RESUMO

Loss of intestinal epithelial cell (IEC) homeostasis and apoptosis negatively affect intestinal barrier function. Uncontrolled activation of the unfolded protein response (UPR) in IEC contributes to an impaired barrier and is implicated in the pathogenesis of inflammatory bowel diseases. However, the contribution of the UPR target gene C/EBP homologous protein (CHOP), an apoptosis-associated transcription factor, to inflammation-related disease susceptibility remains unclear. Consistent with observations in patients with ulcerative colitis, we show that despite UPR activation in the epithelium, CHOP expression was reduced in mouse models of T-cell-mediated and bacteria-driven colitis. To elucidate the molecular mechanisms of IEC-specific CHOP expression, we generated a conditional transgenic mouse model (Chop(IEC Tg/Tg)). Chop overexpression increased the susceptibility toward dextran sodium sulfate (DSS)-induced intestinal inflammation and mucosal tissue injury. Furthermore, a delayed recovery from DSS-induced colitis and impaired closure of mechanically induced mucosal wounds was observed. Interestingly, these findings seemed to be independent of CHOP-mediated apoptosis. In vitro and in vivo cell cycle analyses rather indicated a role for CHOP in epithelial cell proliferation. In conclusion, these data show that IEC-specific overexpression impairs epithelial cell proliferation and mucosal tissue regeneration, suggesting an important role for CHOP beyond mediating apoptosis.


Assuntos
Apoptose/imunologia , Ciclo Celular/imunologia , Colite Ulcerativa/imunologia , Mucosa Intestinal/fisiologia , Regeneração/imunologia , Fator de Transcrição CHOP/imunologia , Animais , Apoptose/genética , Ciclo Celular/genética , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Regeneração/genética , Fator de Transcrição CHOP/genética , Resposta a Proteínas não Dobradas/genética , Resposta a Proteínas não Dobradas/imunologia
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