RESUMO
OBJECTIVES: If the benefits of single-event multilevel surgery (SEMS) in ambulatory children with cerebral palsy have already been validated, especially in terms of functional outcomes, fewer studies have evaluated SEMS in terms of quality of life and satisfaction with surgical outcomes, especially pertaining to the opinions of children and their family. The objectives of this study were to confront the perceptions of parents and the experience of their operated children in terms of quality of life and surgical outcomes. MATERIALS AND METHODS: This was an observational, descriptive, single-center study conducted in a regional Pediatric Physical Medicine and Rehabilitation (PM&R) center, which is considered a reference center in this region of France. The subjects recruited were ambulatory children with cerebral palsy (CP) who had SEMS between 2009 and 2011, and one of their parents. The specific "child" and "parent" CP-related modules of the DISABKIDS questionnaire were used to assess these children's quality of life post-surgery. Perceptions of parents and children regarding gait evolution and satisfaction with surgical outcomes were analyzed via a questionnaire developed by the author. Regarding quality of life and surgical outcomes, the correlation between the perception of parents and experience of children was estimated using the intraclass correlation coefficient (ICC) or prevalence-adjusted bias-adjusted kappa values (PABAK). RESULTS: Twelve children (83% of them boys) and their parents participated in the study. For the DISABKIDS questionnaire, a moderate correlation was found regarding functional impact (ICC=0.58; P<0.0178) but a high correlation was reported for the communication item of the questionnaire (ICC=0.73; P=0.0025). Regarding satisfaction with surgical outcomes, results showed a good correlation (PABAK=0.64). CONCLUSION: Concerning quality of life and satisfaction with surgical outcomes, our study showed a good or even high correlation between parents' perceptions and their child's experience. It is however essential to privilege the child's opinion whenever possible.
Assuntos
Paralisia Cerebral/cirurgia , Pais/psicologia , Satisfação do Paciente , Qualidade de Vida , Adolescente , Paralisia Cerebral/fisiopatologia , Criança , Feminino , Marcha , Humanos , Masculino , Percepção , Inquéritos e QuestionáriosRESUMO
Rehabilitation after primary repair of flexor tendons, particularly in the early phase, has changed due to more solid suture repairs. The objectives of this article are to outline the general principles surrounding this rehabilitation, set out the indications for various early mobilization techniques and describe in detail the physiotherapy protocol used by the Physical Medicine and Rehabilitation Department of the Regional Institute of Rehabilitation in collaboration with the Plastic and Reconstructive Surgery Department of the Émile-Gallé Surgical Center in Nancy, France. This protocol is mainly used for adult patients and carried out in four stages over a 12-week period. If there are no contraindications, the patient learns protected early active self-rehabilitation during the first four postoperative weeks. The protocol includes standardized multidisciplinary follow-up until the social and occupational rehabilitation phase to ensure the best chance of functional recovery.
Assuntos
Traumatismos da Mão/cirurgia , Modalidades de Fisioterapia , Cuidados Pós-Operatórios , Traumatismos dos Tendões/cirurgia , Adulto , Humanos , ContençõesRESUMO
The repair of the finger flexor tendons can be complicated by the appearance of ruptures and peritendinous adhesions. Ruptures are often treated with tendon grafts. Peritendinous adhesions can require tenolysis. Following these two surgical procedures, there is a risk of new adhesions and rupture. Rehabilitation after this secondary surgery consists of a tailored, closely supervised protocol. Protocols used by the team at the Physical Medicine and Rehabilitation Department of the Regional Rehabilitation Institute and the team at the Plastic and Reconstructive Surgery Department of the Emile-Gallé Surgical Center of Nancy (France) are described. A close collaboration between these teams of surgeons and physical therapists is essential. After tendon grafting, protected early motion helps to move the transplant immediately while still protecting it. After tenolysis, immediate (several times a day) and extended rehabilitation ensures that the mobility obtained intraoperatively is maintained. It is performed in a specialized rehabilitation center during the first three postoperative weeks. The goal is to prevent new adhesions from forming while taking into account tendon's fragility.
Assuntos
Traumatismos dos Dedos/cirurgia , Modalidades de Fisioterapia , Cuidados Pós-Operatórios , Traumatismos dos Tendões/cirurgia , Humanos , Reoperação , Ruptura/cirurgia , Contenções , Tendões/transplante , Aderências Teciduais/prevenção & controle , Aderências Teciduais/cirurgiaRESUMO
STUDY DESIGN: Case report. OBJECTIVES: To describe a case of suprascapular nerve entrapment (SNE) in a patient with a spinal cord injury (SCI) as a cause of shoulder pain. SETTING: Physical Medicine and Rehabilitation Institute, Nancy, France. REPORT: Six months after the occurrence of acute paraplegia T9 ASIA, a 45-year-old man complained of pain in the posterior and lateral areas of the left shoulder. A clinical assessment found an atrophy of the infraspinatus muscle and a muscular weakness during external shoulder rotation. SNE was suggested as a cause of pain and confirmed by nerve conduction recording. Magnetic resonance imaging excluded any compressive cyst. SNE at the spinoglenoid notch, related to upper limb overuse, was suggested. A gluco-corticoid injection in the proximity of the suprascapular nerve eliminated the pain in a few hours. Two months after the injection, the pain had not reappeared, the infraspinatus muscle atrophy was resolved, and supraspinal nerve conduction was normalized. CONCLUSION: Shoulder pain is common in individuals with paraplegia, but this is the first time that SNE has been reported as a cause of pain. This micro-traumatic pathology, well known in athletes, is probably under-diagnosed in patients with SCI who overuse their upper limbs for wheelchair propulsion and body transfers.
Assuntos
Transtornos Traumáticos Cumulativos/fisiopatologia , Síndromes de Compressão Nervosa/etiologia , Síndromes de Compressão Nervosa/fisiopatologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/fisiopatologia , Transtornos Traumáticos Cumulativos/tratamento farmacológico , Transtornos Traumáticos Cumulativos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes de Compressão Nervosa/tratamento farmacológico , Dor de Ombro/etiologia , Traumatismos da Medula Espinal/patologiaRESUMO
PURPOSE: The purpose of this article is to present a case of tuberculous arthritis of the knee and discuss the importance of early diagnosis and rehabilitatin in management outcome. CASE REPORT: A 57-year-old Moroccan man with no medical history presented with a mass in the left knee associated with pain and fever. Analysis of aspirated fluid demonstrated sterile inflammatory liquid. Presumptive antibiotic therapy was ineffective. Diagnosis of tuberculous arthritis was made based on positive tuberculin skin test and interferon-release assays. Diagnosis was confirmed by arthroscopic biopsy. Physiotherapy allowed improvement in both function and analytical test findings. DISCUSSION: Tuberculous arthritis is rare occurring in only 2 to 5% of people with tuberculosis. It can be very destructive. Diagnosis is often delayed leading to joint pain, tissue damage, and functional disability (e.g. inability to walk). Since prompt treatment (antibiotics then physiotherapy) can limit complications, early diagnosis is necessary and often requires deep biopsy, except endemic zones. In the acute phase, immobilization of the extremity in a functional position is necessary. When inflammatory signs subside, physiotherapy can be undertaken in short but frequent sessions without excessive weight or resistance. CONCLUSION: The functional outcome of tuberculous arthritis depends on early multidisciplinary care involving the rheumatologist, infectious disease specialist, orthopedic surgeon and attending physician.
Assuntos
Joelho/fisiopatologia , Tuberculose Osteoarticular/fisiopatologia , Tuberculose Osteoarticular/reabilitação , Humanos , Joelho/diagnóstico por imagem , Joelho/patologia , Masculino , Pessoa de Meia-Idade , Marrocos , Modalidades de Fisioterapia , Prognóstico , Radiografia , Recuperação de Função Fisiológica , Tuberculose Osteoarticular/diagnóstico , Tuberculose Osteoarticular/terapiaRESUMO
OBJECTIVES: Retrospective analysis of the efficiency of a protocol for care of chronic vegetative states (CVS) and minimally conscious state (MCS) in Lorraine. MATERIAL AND METHOD: Two indicators are used: protocol activity (number of patients hospitalized between 1988 and 2006, number of admissions per year, of requests per year, origin of requests, waiting time) and the epidemiological data (age, sex ratio, etiology, length of stay, geographic origin, number of deaths, number of hospital discharges). The number of CVS and MCS and patients having progressed towards arousal is specified as well as the technical procedures (orthopedic surgery, number of tracheotomies). RESULTS: Forty-seven patients (30 males and 17 females) were hospitalized in a 12-bed unit. The number of admissions per year was 2.4, and the annual number of requests varied between five and 15. Hospitalization times ranged from six to 18 months. The average length of hospitalization was 41 months. Eighty-eight percent of the cases were residents of Lorraine. The etiology was traumatic (53%), vascular (38% including 12% anoxia), miscellaneous (9%). Fifteen percent rate of return to arousal (average time period: 28.41 months, traumatic etiology) with hospital discharge in four cases. CONCLUSION: The protocol is managed as part of a local scheme and enables an appropriate response to a specific clinical profile by providing up-to-date multidiscipline follow-up care and a rapid solution should intercurrent events occur (signs of arousal, orthopedic deterioration, change of environment). Typical limitations are geographical remoteness and difficulties with family support care.
Assuntos
Protocolos Clínicos , Assistência de Longa Duração , Estado Vegetativo Persistente/terapia , Atividades Cotidianas , Adulto , Nível de Alerta , Dano Encefálico Crônico/reabilitação , Feminino , França/epidemiologia , Humanos , Transtornos da Linguagem/etiologia , Transtornos da Linguagem/reabilitação , Expectativa de Vida , Assistência de Longa Duração/métodos , Assistência de Longa Duração/estatística & dados numéricos , Masculino , Equipe de Assistência ao Paciente , Estado Vegetativo Persistente/diagnóstico , Estado Vegetativo Persistente/epidemiologia , Estado Vegetativo Persistente/reabilitação , Autonomia Pessoal , Recuperação de Função Fisiológica , Estudos Retrospectivos , Adulto JovemRESUMO
In breast cancers, clinical symptoms of inflammation localised around the tumour at the time of diagnosis have been considered to have poor prognosis significance. In this study, the biological mechanisms responsible for the deleterious action of monocytes in cancer were investigated. The incubation of the breast-cancer-derived MDA-MB231 cells with monocytes resulted in an increase in factors involved in cell invasion (i.e. both cancer cells and monocytes-associated urokinase and Tissue Factor, and PAI-1 and MMP-9 secretion). Moreover, the functions of monocytes were also modified. Incubation of monocytes with MDA-MB231 cancer cells resulted in a downregulation in the secretion of the antiproliferative cytokine Oncostatin M, while the apoptotic factor TNF alpha was dramatically increased. However, MDA-MB231 cancer cells have been shown to be resistant towards the apoptotic action of TNF alpha. These findings demonstrate that incubation of MDA-MB231 cancer cells with monocytes induced a crosstalk, which resulted in an increased expression of factors involved in cancer cell invasiveness and in a modification of monocytes function against cancer cells, while inflammatory effects were increased.
Assuntos
Neoplasias da Mama/fisiopatologia , Monócitos/fisiologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Técnicas de Cocultura , Feminino , Humanos , Metaloproteinases da Matriz/sangue , Metaloproteinases da Matriz/metabolismo , Monócitos/citologia , Oncostatina M , Peptídeos/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Valores de Referência , Fator de Necrose Tumoral alfa/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismoRESUMO
Human urotensin-II (hU-II) is a cyclic peptide recently cloned in humans and present in human cardiac tissue and human arteries. The effects of hU-II were studied on human coronary bypass grafts in vitro. In three out of eight human mammary arteries, and two out of three human radial arteries, hU-II caused contraction; human saphenous veins did not respond to hU-II. When it exists, the contraction slowly develops and has a low-to-moderate intensity. All radial arteries obtained from young healthy non-human primates contracted strongly to hU-II.
Assuntos
Artérias/efeitos dos fármacos , Ponte de Artéria Coronária , Urotensinas/farmacologia , Vasoconstrição/efeitos dos fármacos , Idoso , Animais , Artérias/fisiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Macaca fascicularis , Masculino , Artéria Torácica Interna/efeitos dos fármacos , Artéria Torácica Interna/fisiologia , Artéria Radial/efeitos dos fármacos , Artéria Radial/fisiologia , Ratos , Veia Safena/efeitos dos fármacos , Veia Safena/fisiologia , Vasoconstrição/fisiologiaRESUMO
OBJECTIVE: Relationships between the vestibular system and the body schema have been suggested but never demonstrated in amputees. We studied the effects of vestibular stimulation on body representation in amputees focusing on the phantom limb phenomenon. METHOD: Prospective study in 31 amputated subjects of one or several limbs before the age of 16 years. The amputees underwent a caloric vestibular stimulation test, ipsilateral (n = 31) and contralateral (n = 8) to the side of amputation. Amputees were asked to report their perceptions spontaneously and to answer open questions. Four types of perceptions were analyzed: normal phantom, deformed phantom, painful phantom, and no phantom, before, during, and after the vestibular stimulation test. Data were compared between the two groups for pre- and post-test perceptions (chi2 test). RESULTS: Vestibular caloric stimulation provoked temporary perception of a normal phantom limb in 16 of 17 amputees who previously did not experience phantoms. For 12 of 12 amputees who currently experienced deformed or painful phantom limbs, caloric stimulation led to temporary replacement of the abnormal phantom with a non-painful normal phantom. CONCLUSIONS: The phenomena observed: 1) throw light on assumed mechanisms controlling construction of static and dynamic engrams used to produce the body schema; 2) complete the neuromatrix theory proposed to explain the phantom limb phenomenon; and 3) suggest that the vestibular system triggers the procedure of reconstruction of the global body schema.
Assuntos
Amputados , Testes Calóricos/efeitos adversos , Membro Fantasma/etiologia , Testes de Função Vestibular , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Membro Fantasma/diagnóstico , Estudos Prospectivos , Fatores de TempoRESUMO
Sodium phenylacetate (NaPa), a non-toxic phenylalanine metabolite, has been shown to induce in vivo and in vitro cytostatic and antiproliferative effects on various cell types. In this work, we analysed the effect of NaPa on the invasiveness of breast cancer cell (MDA-MB-231, MCF-7 and MCF-7 ras). Using the highly invasive breast cancer cell line MDA-MB-231, we demonstrated that an 18-hour incubation with NaPa strongly inhibits the cell invasiveness through Matrigel (86% inhibition at 20 mM of NaPa). As cell invasiveness is greatly influenced by the expression of urokinase (u-PA) and its cell surface receptor (u-PAR) as well as the secretion of matrix metalloproteinases (MMP), we tested the effect of NaPa on these parameters. An 18-hour incubation with NaPa did not modify u-PA expression, either on MDA-MB-231 or on MCF-7 and MCF-7 ras cell lines, and induced a small u-PA decrease after 3 days of treatment of MDA-MB-321 with NaPa. In contrast, an 18 h incubation of MDA-MB-231 increased the expression of u-PAR and the secretion of MMP-9. As u-PAR is a ligand for vitronectin, a composant of the extracellular matrix, these data could explain the increased adhesion of MDA-MB-231 to vitronectin, while cell adhesivity of MCF-7 and MCF-7 ras was unmodified by NaPa treatment. NaPa induced also an increased expression of both Lymphocyte Function-Associated-1 (LFA-1) and Intercellular Adhesion Molecule-1 (ICAM-1), which was obvious from 18 hour incubation with NaPa for the MDA-MB-231 cells, but was delayed (3 days) for MCF-7 and MCF-7 ras. Only neutralizing antibodies against LFA-1 reversed the decreased invasiveness of NaPa-treated cells. Therefore we can conclude that the strong inhibition of MDA-MB-231 invasiveness is not due to a decrease in proteases involved in cell migration (u-PA and MMP) but could be related both to the modification of cell structure and an increased expression of adhesion molecules such as u-PAR and LFA-1.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Moléculas de Adesão Celular/metabolismo , Invasividade Neoplásica , Fenilacetatos/farmacologia , Neoplasias da Mama/metabolismo , Humanos , Células Tumorais CultivadasRESUMO
OBJECTIVE: To describe RMI aspects of leg stump neuroma and to evaluate RMI scan interest for neuroma diagnosis and management. POPULATION AND METHOD: During a 2 years period, 224 amputated patients consulting for pain or prostetics problems were studied. In 10 cases, a characteristic pain leads to neurona diagnosis. This is described as a sensation of ascending or descending electric shock induced by the stimulation of an identified point with a reproducible topography. In all these cases, RMI scans were performed. In thirty two other cases, a RMI scan was performed to confirm a pathology (bursitis, bone abnormality) or in order to establish an etiologic diagnosis. Twelve neuromas were diagnosed. RESULTS: RMI scan showed a neuroma in the ten cases with a clinical suspicion and two asymptomatic neuromas were diagnosed out of the 32 patients without clinical suspicion. Medium delay between amputation and neuroma diagnosis is 11,6 year. In six cases, staking was modified and in six other cases, surgery was necessary. In aIl cases, clinical manifestations disappeared. Vanous RMI aspects ofneuromas are described and illustrated. Neuroma is observed on the extremity of a nerve that have a wavy aspect on its top. The neuroma is an oblong structure, with clear limits. There is an hyposignal with Ti sequence and variable signal with T2 and after gadolinium injection. DISCUSSION: RMI scan is a good way to diagnose amputee neuroma. It makes it possible to demonstrate the pathological character of the neuroma. It has to be performed when a neuroma is suspected. It enables to confirm the diagnosis and establish the exact topography and anatomic connection. Mechanical strains role as a factor of discovering the neuroma is discussed because of the concomitant evolution of associated lesions (bursitis, bone edema). Surgical repair takes place after correcting abnormal mechanical strains.
Assuntos
Cotos de Amputação/patologia , Amputação Cirúrgica/efeitos adversos , Imageamento por Ressonância Magnética , Neuroma/patologia , Neoplasias de Tecidos Moles/patologia , Humanos , Neuroma/etiologia , Neoplasias de Tecidos Moles/etiologiaRESUMO
Phantom limbs in amputees, or body illusion in hemiplegics, have been the subject of wide ranging descriptions. The detected abnormalities involve morphological, postural and/or kinetic features. The aim of this prospective study carried out in 25 amputees and 10 adult paraplegics was to describe the typology of these perceptions. Data were collected from free and semi-directive investigations before and after caloric vestibular stimulation. Amputees and paraplegics perceived normal, deformed and painful body phantom segments, reffered perceptions and "normal limbs" which took on the request posture considering the general body position (illusion of body normality). This perception corresponds to an image of the body, such as it should be and not such as it is. In amputees, the limb follows the movements of the prothesis. These perceptions conform quite well reality so that the loss of the paralyzed limb is not perceived as a missing limb. This illusion of body normality should be distinguished from the normal phantom limb, characterized by a stronger perception of the lost limb compared with the other. In both amputees and paraplegics, vestibular stimulation can generate or modify phantoms limbs or body illusion and can abolish painful phantom limbs. The neuromatrix, which rebuilds body representations, could get its information from reorganized cortical areas (instantaneous body image), autobiographical engrams (painful phantoms limbs), or innate engrams (identity body schema) that, via congruence mechanisms, could be identified as a somatic reference, particularly for motor programming. This interpretation is compatible with current knowledge and suggests how amputees can easily use a prothesis.
Assuntos
Imagem Corporal , Córtex Cerebral/fisiopatologia , Ilusões/fisiologia , Paraplegia/fisiopatologia , Membro Fantasma/fisiopatologia , Vestíbulo do Labirinto/fisiopatologia , Adulto , Idoso , Testes Calóricos , Feminino , Humanos , Cinestesia/fisiologia , Masculino , Pessoa de Meia-Idade , Regeneração Nervosa/fisiologia , Vias Neurais/fisiopatologia , Paraplegia/psicologia , Paraplegia/terapia , Membro Fantasma/psicologia , Membro Fantasma/terapia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/psicologia , Traumatismos da Medula Espinal/terapiaRESUMO
Several postoperative complications associated with pain may develop in the stump of an amputated lower limb. Clinical findings are often nonspecific; however, radiologic evaluation, especially with magnetic resonance (MR) imaging, is useful in the early diagnosis of these complications, thereby helping minimize physical disability with its psychologic and socioeconomic implications. Conventional radiography can demonstrate evidence of osseous origins of pain (eg, aggressive bone edge, heterotopic ossification, osteomyelitis) and should be the first imaging study performed after clinical examination. Videofluoroscopy can help evaluate improper prosthetic fit by demonstrating abnormal residual limb motion, piston action, rolling of soft tissues, and abnormal angle between the limb axis and the prosthesis during gait. Ultrasonography can demonstrate inflammatory changes in the stump as well as soft-tissue fluid collections. However, MR imaging is the modality of choice when clinical and other imaging findings are indeterminate. Because of its high spatial and contrast resolution, MR imaging can demonstrate subtle inflammatory changes, fluid collections, cancers, neuromas, and subtle traumatic bone lesions. Knowledge of various surgical and rehabilitation techniques is required for accurate diagnosis of complications associated with stump pain. Correct diagnosis allows choice of the most appropriate therapy, which may involve treating the stump, remodeling the prosthesis, or both.
Assuntos
Cotos de Amputação , Perna (Membro) , Imageamento por Ressonância Magnética , Dor/diagnóstico , Membros Artificiais/efeitos adversos , Doenças Ósseas/diagnóstico , Neoplasias Ósseas/diagnóstico , Cinerradiografia , Edema/diagnóstico por imagem , Fluoroscopia , Humanos , Perna (Membro)/diagnóstico por imagem , Neuroma/diagnóstico , Ossificação Heterotópica/diagnóstico por imagem , Osteomielite/diagnóstico por imagem , Dor/diagnóstico por imagem , Ajuste de Prótese , Neoplasias de Tecidos Moles/diagnóstico , Tíbia/diagnóstico por imagem , Ultrassonografia , Gravação em VídeoRESUMO
The soluble IL-6 receptor (sIL-6R) can increase IL-6-induced signalling by forming a complex with IL-6 and membrane-bound gp130 (the receptor beta chain which transduces signals). The conditions affecting this response to sIL-6R were studied using fibrinogen release from HepG2 hepatocytes. Exogenous sIL-6R had no effect alone or in the presence of a submaximal concentration of IL-6, but increased responses to supramaximal IL-6 concentrations in a concentration-related manner. Dexamethasone increased the expression of the membrane IL-6R and endogenous sIL6R release, and increased responses to supramaximal but not submaximal IL-6 concentrations. The amount of endogenous sIL-6R released is relatively small and is unlikely to influence the effects of the exogenous sIL-6R. The observed concentration-related decrease in sIL-6R production in the presence of IL-6 may indicate internalization of ligand/receptor complexes. This would significantly decrease the amount of IL-6R (soluble or membrane) available for signalling and limit continued functional response later in the cultures. These data indicate that the major factor influencing responses to exogenous sIL-6R is an excess of IL-6 which is necessary to form complexes with the sIL-6R, which can then interact with gp130 to increase signalling.
Assuntos
Interleucina-6/genética , Interleucina-6/farmacologia , Receptores de Interleucina-6/fisiologia , Carcinoma Hepatocelular , Membrana Celular/imunologia , Dexametasona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Humanos , Neoplasias Hepáticas , Receptores de Interleucina-6/genética , Transdução de Sinais , Células Tumorais CultivadasAssuntos
Neovascularização Patológica , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Medula Óssea/irrigação sanguínea , Criança , Fator 2 de Crescimento de Fibroblastos/urina , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/urina , Valor Preditivo dos Testes , PrognósticoRESUMO
Epidemiological studies have demonstrated that levels of plasma fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (tPA) are associated with the incidence of vascular disease. Since oncostatin M dramatically induces fibrinogen biosynthesis by hepatocytes and could be implicated in vascular injury leading to atherosclerosis, we have analyzed the effect of oncostatin M on PAI-1, vWf and tPA secretion by endothelial cells. A 2-h incubation of human umbilical vein endothelial cells with oncostatin M increases thrombin-induced secretion of vWf to the same extent as tumour necrosis factor-alpha or interleukin-1 (137+/-26% of control for 5 ng/ml oncostatin M, P < 0.001, n=5). The effects on tPA and PAI-1 secretion were different depending on the type of endothelial cells tested. On human umbilical vein endothelial cells, oncostatin M induced an increase in PAI-1 and a decrease in tPA secretion, which could explain the thrombogenicity of oncostatin M on large vessels. On a human microvasculature endothelial cell line, oncostatin M did not modify PAI-1 but induced an increase in tPA secretion. This observation of the effects of oncostatin M on both macro- and microvasculature could explain the increased levels of vWf, PAI-1 and tPA in the plasma of atherosclerotic subjects identified in epidemiological studies, suggesting that oncostatin M could play a key role in the development of atherosclerotic lesions.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Inibidores do Crescimento/farmacologia , Peptídeos/farmacologia , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Ativador de Plasminogênio Tecidual/metabolismo , Fator de von Willebrand/metabolismo , Arteriosclerose/etiologia , Coagulação Sanguínea , Linhagem Celular , Humanos , Oncostatina MRESUMO
Interleukin-12 (IL-12) or natural killer cell stimulatory factor (NKSF), has multiple effects on T lymphocytes and natural killer cells. In this study, the effect of IL-12 on human hematopoiesis was studied by analyzing the growth of CD34+ peripheral blood stem cells (PBSC), in steady state. In the presence of Epo, IL-12 alone or in combination with IL-3 or SCF had no effect on the formation of colonies from CD34+ cells. In culture with Epo, G-CSF, and IL-3, the effect of Flt3-ligand (FL) on CD34+ PBSC was investigated in the presence or absence of IL-12. No additional effect of IL-12 was observed when combined with FL. We evaluated 5-FU-treated human CD34+ PBSC proliferation in cultures with Epo, G-CSF, and IL-3, in the presence or absence of IL-12. No cytokine combination enhanced colony formation from 5-FU-treated CD34+ cells. However, in cultures of 5-FU-treated human CD34+ cells, the most efficient combination was IL-3 + Epo + G-CSF + Accessory cells (CD34-). Furthermore, IL-12 enhanced this colony formation significantly. To investigate whether immature CD34+ cells were responsible for FL or SCF, 5-FU-treated human CD34+ cells were cultured with or without IL-12. Whereas no synergistic effect was observed in combination with IL-12, SCF alone significantly enhanced colony formation. However, the colony number was found to be smaller than with the potent combination of accessory cells in the presence of IL-12. These results indicate that accessory cells, lost in CD34+ cell purification, could be partly responsible for an IL-12 effect on immature human PBSC proliferation.
Assuntos
Antígenos CD34/sangue , Antimetabólitos Antineoplásicos/farmacologia , Fluoruracila/farmacologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/imunologia , Interleucina-12/farmacologia , Adulto , Divisão Celular/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Proteínas de Membrana/farmacologia , Proteínas Recombinantes/farmacologia , Fator de Células-Tronco/farmacologiaRESUMO
High level of fibrinogen in plasma is recognised as an important vascular risk factor. However, it is not known if the increase in fibrinogen is directly responsible for the vascular risk or is a marker of vascular inflammation. Our data strengthen the hypothesis that the fibrinogen level is a marker of vascular disease, since a parallel effect of cytokines on fibrinogen biosynthesis and on vascular injury was noted. Among the cytokines which induce the synthesis of fibrinogen, oncostatin M (OSM) is the most potent cytokine synthesised by activated monocytes for inducing fibrinogen synthesis by Hep G2 cells (human hepatoma cell line). Interestingly at the same concentrations needed for fibrinogen biosynthesis, OSM induces smooth muscle cell proliferation. In contrast, the cytokines IL-4, IL-10 and IL-13 which have a protective effect against vascular injury leading to atherosclerosis, dose dependently down regulate the biosynthesis of fibrinogen. This was due to both a decrease of IL-6 induced fibrinogen synthesis by hepatocytes, evidenced by a decrease in fibrinogen secretion in the medium and beta chain mRNA expression and to an inhibition of production of the hepatocyte-stimulating activity for fibrinogen biosynthesis (HSF) by LPS-activated monocytes. Noteworthingly, IL-10 induces a significant decrease of the production of OSM by LPS-activated monocytes. In situ activation of monocytes by cytokines in the vessel wall could also contribute to the deposition of fibrin(ogen) derivatives, identified as pathogenic factor.