RESUMO
Ochratoxin A (OTA) is a fungal secondary metabolite produced by certain species of Aspergillus and Penicillium, and exerts immunosuppressive effect on humans and animals. Quercetin (QUE) is one of the flavonoids produced as a plant-secondary metabolite. The present study was designed to evaluate the efficacy of QUE against the immunotoxic hazard of OTA in broiler chickens. Forty one-day-old broiler chicks were randomly and equally allocated into four groups; control, OTA (0.5 mg/kg feed), QUE (0.5 g/kg feed) and OTA + QUE (0.5 mg/kg OTA + 0.5 g/kg QUE). The results revealed that dietary OTA induced a significant decrease in the antibody response to Newcastle Disease (ND), Infectious Bronchitis (IB) and Avian Influenza (AI) vaccination and in the lymphoproliferative response to Phytohemagglutinin-P (PHA-P). Ochratoxin A also induced oxidative stress and lipid peroxidation in the bursa of Fabricius, spleen and thymus tissues of chickens as demonstrated by decreased CAT and GSH levels and increased TBARS content. In addition, administration of OTA resulted in apoptosis, which was evident by the increased expression level of PTEN, Bax and Caspase-3 genes and decreased expression level of PI3K, AKT and Bcl-2 genes. Furthermore, exposure to OTA resulted in various pathological lesions in the bursa of Fabricius, spleen and thymus of chickens. On the other hand, administration of QUE ameliorated most of the immunotoxic effects of OTAby its immunomodulatory, antioxidant and anti-apoptotic activities. Taken together, the results suggested that QUE potentially alleviated the OTA-induced immunotoxicity in broiler chickens, probably through amelioration of oxidative stress and activation of the PI3K/AKT signaling pathway.
Assuntos
Antioxidantes/uso terapêutico , Fatores Imunológicos/uso terapêutico , Ocratoxinas/toxicidade , Quercetina/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Formação de Anticorpos/efeitos dos fármacos , Proteínas Aviárias/metabolismo , Bolsa Sinovial/efeitos dos fármacos , Bolsa Sinovial/patologia , Galinhas , Expressão Gênica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Baço/efeitos dos fármacos , Baço/patologia , Timo/efeitos dos fármacos , Timo/patologiaRESUMO
Hemiplegic shoulder pain (HSP), which occurs in most patients with hemiplegia, causes considerable distress and worsens outcomes in rehabilitation. Although they have received the treatments such as anti-inflammatory drugs or physical therapy, many of the individuals remain suffering from shoulder pain 6 months after acute stroke event. In this retrospective study, we evaluated the effectiveness of ultrasound guided subacromial-subdeltoid (SASD) bursa injections with botulinum toxin type A (BoNT/A) compared to steroids for refractory HSP.The data were collected retrospectively by reviewing the patient's medical records and pain questionnaires in our rehabilitation center. In total, 38 patients who received ultrasound guided SASD bursa injection (BoNT/A group, nâ=â18; corticosteroid group, nâ=â20) were included. The pain visual analog scale (VAS) score at rest and during arm passive abduction, Fugl-Meyer score of upper limbs (F-M score) were evaluated before, 2, 4, 8, and 12 weeks after injection.Both 2 groups obtained a significant improvement of VAS score at rest or during arms passive abduction compared to baseline score (within group compare, Pâ<â.05). There were no significant differences of pain score improvement between two groups at week 2, 4, 8, and 12 after injection either at rest or during passive arm abduction (between 2 groups compare, Pâ>â.05). There were also no differences in results of the post treatment F-M score between 2 groups (between 2 groups compare, Pâ>â.05). Similarly, during the follow-up period no collateral effects were reported after BoNT/A injection.SASD bursa BoNT/A injection can substantially reduce the pain as corticosteroid in patients with HSP. BoNT/A injection could be a useful strategy for replacing steroids as a treatment for refractory HSP especially in the patients who cannot tolerate the steroids injection.
Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Fármacos Neuromusculares/administração & dosagem , Dor de Ombro/tratamento farmacológico , Idoso , Anti-Inflamatórios/administração & dosagem , Betametasona/administração & dosagem , Betametasona/análogos & derivados , Bolsa Sinovial/efeitos dos fármacos , Estudos de Casos e Controles , Feminino , Hemiplegia/complicações , Humanos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dor de Ombro/etiologia , Acidente Vascular Cerebral/complicações , Resultado do Tratamento , Ultrassonografia de Intervenção/métodosRESUMO
BACKGROUND: Recent studies have shown that ultrasound-guided injection of glucocorticoids is superior to blind puncture methods. OBJECTIVE: To evaluate clinical efficacy of ultrasound-guided drug injection in the treatment of olecranon subcutaneous bursitis. METHODS: From June 2016 to September 2018, 45 patients diagnosed with obvious synovial effusion and treated with ultrasound-guided injection therapy for olecranon bursitis were included in this study. Under the guidance of ultrasound, the synovial effusion aspiration was performed and 2âml of the compound betamethasone mixture was injected into the bursae and dressed under pressure. Ultrasound examination was performed 2 weeks after operation and the secondary fluid aspiration and drug injection treatment were performed. The depth of synovial effusion, the thickness of synovial hyperplasia and the blood flow signal were measured 4 weeks after operation to evaluate the therapeutic effect. RESULTS: After first treatment, the recurrence rate of the olecranon mass were 40%. After secondary treatment, recurrence of olecranon mass occurred in 6 of the 45 patients with a recurrence rate of 13.3%. After 4 weeks of follow-up, the depth of olecranon synovial effusion, the average thickness of synovial hyperplasia and the blood flow signal decreased significantly after treatment (Pâ<â0.05). CONCLUSIONS: Ultrasound-guided drug injection is safe and effective in treating olecranon subcutaneous bursitis. Although the recurrence rate is high after the first treatment, the second treatment is simple and can reduce the recurrence rate. The patients have a high acceptance rate, which is worthy of clinical promotion.
Assuntos
Betametasona/administração & dosagem , Bursite/diagnóstico por imagem , Bursite/tratamento farmacológico , Olécrano , Adulto , Idoso , Biópsia por Agulha , Bolsa Sinovial/diagnóstico por imagem , Bolsa Sinovial/efeitos dos fármacos , Bolsa Sinovial/patologia , Bursite/patologia , Feminino , Humanos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
OBJECTIVE: Despite the ubiquity of intra-articular and bursal injections for the treatment of joint pain and bursitis, relatively little literature is available on the prevalence of infection after these procedures. The aim of this study was to identify the number of infections recalled by sports medicine physicians who perform injections of large joints and bursae at least once per month. DESIGN: A survey of physician members of the American Medical Society for Sports Medicine identified the reported number of recalled infections for each large joint/bursal location. RESULTS: Of a total of 554 physicians, only 31 infections were recalled by 27 physicians. Only 4.87% of all physicians were aware of an infection after an injection during their career. On average, one infection was recalled of 170 physician-years in practice. No differences in infection rates were observed when comparing primary specialties (P = 0.281). CONCLUSIONS: This study, the largest to date, demonstrates that sports medicine physicians rarely encounter infections after large joint and bursa injections. Though rare, because of their catastrophic nature, risk mitigation strategies should be maintained.
Assuntos
Bolsa Sinovial/efeitos dos fármacos , Bolsa Sinovial/microbiologia , Bursite/tratamento farmacológico , Glucocorticoides/administração & dosagem , Injeções Intra-Articulares/métodos , Artrite Infecciosa/etiologia , Bursite/complicações , Humanos , Injeções Intra-Articulares/efeitos adversos , Medicina Esportiva , Resultado do TratamentoRESUMO
We hypothesized that ultrasound (US) guidance improves outcomes of corticosteroid injection of trochanteric bursitis. 40 patients with greater trochanteric pain syndrome defined by pain to palpation over the trochanteric bursa were randomized to injection with 5 ml of 1% lidocaine and 80 mg of methylprednisolone using (1) conventional anatomic landmark palpation guidance or (2) US guidance. Procedural pain (Visual Analogue Pain Scale), pain at outcome (2 weeks and 6 months), therapeutic duration, time-to-next intervention, and costs were determined. There were no complications in either group. Ultrasonography demonstrated that at least a 2-in (50.8 mm) needle was required to consistently reach the trochanteric bursa. Pain scores were similar at 2 weeks: US: 1.3 ± 1.9 cm; landmark: 2.2 ± 2.5 cm, 95% CI of difference: - 0.7 < 0.9 < 2.5, p = 0.14. At 6 months, US was superior: US: 3.9 ± 2.0 cm; landmark: 5.5 ± 2.6 cm, 95% CI of difference: 0.8 < 1.6 < 2.4, p = 0.036. However, therapeutic duration (US 4.7 ± 1.4 months; landmark 4.1 ± 2.9 months, 95% CI of difference - 2.2 < - 0.6 < 1.0, p = 0.48), and time-to-next intervention (US 8.7 ± 2.9 months; landmark 8.3 ± 3.8 months, 95% CI of difference - 2.8 < - 0.4 < 2.0, p = 0.62) were similar. Costs/patient/year was 43% greater with US (US $297 ± 99, landmark $207 ± 95; p = 0.017). US-guided and anatomic landmark injection of the trochanteric bursa have similar 2-week and 6-month outcomes; however, US guidance is considerably more expensive and less cost-effective. Anatomic landmark-guided injection remains the method of choice, but should be routinely performed using a sufficiently long needle [at least a 2 in (50.8 mm)]. US guidance should be reserved for extreme obesity or injection failure.
Assuntos
Anestésicos Locais/administração & dosagem , Anestésicos Locais/economia , Bolsa Sinovial/efeitos dos fármacos , Bursite/tratamento farmacológico , Bursite/economia , Custos de Medicamentos , Glucocorticoides/administração & dosagem , Glucocorticoides/economia , Lidocaína/administração & dosagem , Lidocaína/economia , Metilprednisolona/administração & dosagem , Metilprednisolona/economia , Ultrassonografia de Intervenção/economia , Adulto , Idoso , Pontos de Referência Anatômicos , Anestésicos Locais/efeitos adversos , Bolsa Sinovial/diagnóstico por imagem , Bolsa Sinovial/fisiopatologia , Bursite/diagnóstico por imagem , Bursite/fisiopatologia , Análise Custo-Benefício , Desenho de Equipamento , Feminino , Fêmur , Glucocorticoides/efeitos adversos , Humanos , Injeções Intralesionais , Lidocaína/efeitos adversos , Masculino , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Agulhas/economia , Medição da Dor , Palpação/economia , Dados Preliminares , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia de Intervenção/efeitos adversos , Estados UnidosRESUMO
RATIONALE: Pes anserine (PA) bursitis is an inflammatory condition of the medial knee. The PA bursa becomes more painful when infected, damaged, or irritated. Although various treatment options have been attempted to treat PA bursitis, optimal treatments are still debated. This study aims to investigate the effect of polydeoxyribonucleotide (PDRN) injection on reducing pain and inflammation in a patient presenting with PA bursitis. PATIENT CONCERNS: A 50-year-old female patient was admitted to our pain clinic with symptoms of tenderness and pain over the medial knee. Physical examination revealed the pain to be located over the proximal medial tibia at the insertion of the conjoined tendons of the PA. The knee had lost its range of movement and strength, and resisted knee flexion. DIAGNOSES: She was diagnosed as having PA bursitis. INTERVENTIONS: Ultrasound guided PA bursa injection was carried out. OUTCOMES: Follow-up for the patient was more than eight months. She showed good improvement in PA bursitis without any complications. LESSONS: This is the first successful report of successful PDRN injection for PA bursa.
Assuntos
Artralgia , Bursite , Articulação do Joelho , Polidesoxirribonucleotídeos/administração & dosagem , Analgésicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Artralgia/tratamento farmacológico , Artralgia/etiologia , Bolsa Sinovial/efeitos dos fármacos , Bursite/diagnóstico , Bursite/tratamento farmacológico , Bursite/etiologia , Bursite/fisiopatologia , Feminino , Humanos , Injeções/métodos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Pessoa de Meia-Idade , Resultado do Tratamento , Ultrassonografia/métodosAssuntos
Bolsa Sinovial/efeitos dos fármacos , Bursite/tratamento farmacológico , Clostridium histolyticum/enzimologia , Colagenase Microbiana/administração & dosagem , Articulação do Ombro/efeitos dos fármacos , Dor de Ombro/tratamento farmacológico , Distinções e Prêmios , Fenômenos Biomecânicos , Bolsa Sinovial/fisiopatologia , Bursite/diagnóstico , Bursite/fisiopatologia , Humanos , Injeções Intralesionais , Colagenase Microbiana/efeitos adversos , Colagenase Microbiana/isolamento & purificação , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Articulação do Ombro/fisiopatologia , Dor de Ombro/diagnóstico , Dor de Ombro/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND: Conservative and even surgical management of adhesive capsulitis often is prolonged and painful. Management of adhesive capsulitis is lacking evidence-based controlled clinical trials. QUESTIONS/PURPOSES: We asked: (1) Does a collagenase clostridium histolyticum (CCH) injection lyse shoulder capsule collagen in adhesive capsulitis and at what dose? (2) Can a shoulder capsule injection be administered extraarticularly? (3) Do CCH injections result in better scores for pain and function than can be achieved with physical therapy among patients with adhesive capsulitis? METHODS: First, 60 patients with adhesive capsulitis were evaluated by clinical examination. To make the diagnosis of adhesive capsulitis, a patient had to have restricted active ROM of at least 60° in total active ROM in the affected shoulder compared with the unaffected contralateral shoulder; with the scapula stabilized, external rotation with the elbow at the side was a very important determinant. Patients were randomized to receive a single injection of 0.5 mL placebo or 0.145, 0.29, or 0.58 mg CCH. All 60 patients were followed up at 30 days. After that, if patients did not attain treatment thresholds they were eligible for up to five open-label 0.58-mg collagenase injections. For the longer-term followup in the open-label phase, 53 patients (83%) were followed to 12 months, 46 (77%) for 24 months, 36 (60%) for 36 months, 37 (62%) for 48 months, and 25 (42%) for 60 months. The extraarticular injection was directed at the anterior shoulder capsule with the patient in the supine position. To prove that these injections could be delivered reliably to the anterior shoulder capsule extraarticularly, the next study involved volunteers without adhesive capsulitis, in which 10 volunteers received a 10-mL injection of normal saline under ultrasound guidance. Finally, to determine the efficacy and dosing of CCH, four cohorts of 10 patients received up to three ultrasound-guided injections separated by 21 days. These injections were administered at one of four dose-volume levels. A fifth cohort of 10 patients was used as a control group and performed standardized home shoulder exercises only. All patients performed standardized home shoulder exercises three times daily. For Study 3, followup was at 22, 43, 64, and 92 days. No patients were lost to followup. RESULTS: In the first study, a single CCH injection did not provide clinically important improvements from baseline in active ROM, passive ROM, and function and pain scores compared with patients who received placebo. Ultrasound guidance confirmed extraarticular injection of the shoulder capsule in Study 2. The CCH injection was more effective than exercise therapy alone at 0.58 mg/1 mL and 0.58 mg/2 mL compared with exercise only in the primary measure of efficacy (active forward flexion) as shown in Study 3. For active forward flexion the mean in degrees in the 0.58 mg/2 mL group was 38° compared with 12° in the exercise-only group (p = 0.03). For active forward flexion the mean in the 0.58 mg/1mL group was 43° compared with 12° in the exercise-only group (p = 0.01). CONCLUSIONS: Extraarticular injections of CCH for treatment of adhesive capsulitis were well tolerated and seem effective compared with exercise therapy. Future FDA-regulated clinical trials must verify CCH injection therapy for adhesive capsulitis. LEVEL OF EVIDENCE: Level II, therapeutic study.
Assuntos
Distinções e Prêmios , Bolsa Sinovial/efeitos dos fármacos , Bursite/tratamento farmacológico , Clostridium histolyticum/enzimologia , Colagenase Microbiana/administração & dosagem , Articulação do Ombro/efeitos dos fármacos , Dor de Ombro/tratamento farmacológico , Adulto , Fenômenos Biomecânicos , Bolsa Sinovial/diagnóstico por imagem , Bolsa Sinovial/fisiopatologia , Bursite/diagnóstico , Bursite/fisiopatologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Intralesionais , Masculino , Colagenase Microbiana/efeitos adversos , Colagenase Microbiana/isolamento & purificação , Pessoa de Meia-Idade , Medição da Dor , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/fisiopatologia , Dor de Ombro/diagnóstico , Dor de Ombro/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia de Intervenção , Estados UnidosRESUMO
REASONS FOR PERFORMING STUDY: Controversy exists about the specificity of diagnostic analgesia of the digital flexor tendon sheath (DFTS) in horses. OBJECTIVES: To evaluate the degree of diffusion of mepivacaine from the equine DFTS to adjacent synovial structures. STUDY DESIGN: Crossover experiment. METHODS: Under general anaesthesia, the DFTS of one front and one hindlimb of 8 horses were injected simultaneously with mepivacaine. Synovial fluid samples of the injected DFTS, the adjacent metacarpo-/metatarsophalangeal (MCP/MTP) joint, proximal interphalangeal joint, distal interphalangeal joint, navicular bursa and contralateral MCP/MTP joint were collected 15 min post injection (T15) from one of the injected limbs and 60 min post injection (T60) from the other limb. Venous blood samples were obtained at T0, T15 and T60 to evaluate systemic distribution of mepivacaine. After a 2-week washout period, the procedure was repeated using the same limbs but reversing the time of sampling (front vs. hindlimbs). The concentration of mepivacaine in samples was measured with a commercial ELISA kit. RESULTS: Mepivacaine concentrations in the DFTS samples, at both T15 (5077 mg/l) and T60 (3503 mg/l), exceeded those estimated sufficient to produce synovial analgesia (100 mg/l or 300 mg/l). Mepivacaine was found in all synovial structures adjacent to the injected DFTS and in the contralateral MCP/MTP joints, but concentrations were low, with a maximum value of only 3.2 mg/l. With the exception of the navicular bursa samples, the mepivacaine concentrations in the adjacent synovial structures were significantly higher at T60 than at T15 (P<0.03). Significantly higher mepivacaine concentrations were found in the ipsilateral than the contralateral MCP/MTP joints at T60 (P<0.001). Blood samples had significantly higher mepivacaine concentrations at T15 and T60 than at T0 (P<0.001). CONCLUSIONS: Mepivacaine injected into the DFTS of horses diffuses towards adjacent synovial structures without achieving clinically relevant concentrations.
Assuntos
Anestésicos Locais/farmacocinética , Mepivacaína/farmacocinética , Membrana Sinovial/metabolismo , Analgesia/métodos , Analgesia/veterinária , Anestésicos Locais/administração & dosagem , Animais , Bolsa Sinovial/efeitos dos fármacos , Estudos Cross-Over , Feminino , Pé , Membro Anterior , Membro Posterior , Masculino , Mepivacaína/administração & dosagem , Distribuição TecidualRESUMO
OBJECTIVE: This systematic review and meta-analysis aimed to assess the effectiveness of ultrasound-guided (USG) versus blind (landmark-guided, LMG) corticosteroid subacromial-subdeltoid bursa injection in adults with shoulder pain. METHODS: The searches were performed on PubMed, Ovid MEDLINE, Ovid EMBASE, Ovid CochraneCENTRAL, Web of Science, Google Scholar, and Scopus from database inception through March 27, 2015. Studies were included trials comparing USG versus LSG injections for the treatment of adults with subacromial-subdeltoid bursitis. Two reviewers independently performed data extraction and appraisal of the studies. The outcome measures collected were the decreased VAS and SDQ scores, the increased shoulder function scores and shoulder abduction motion range, and the effective rate at 6 weeks after injection. RESULTS: Seven papers including 445 patients were reviewed; 224 received LMG injections and 221 received USG injections. There was a statistically significant difference in favor of USG for pain score [MD = 1.19, 95% CI (0.39, 1.98), P = 0.003] and SDQ score [MD = 5.01, 95% CI (1.82, 8.19), P = 0.02] at 6 weeks after injection. Also there was a statistically significant difference between the groups, with greater improvement reported of shoulder function scores [SMD = 0.89, 95% CI (0.56, 1.23), P < 0.001] and shoulder abduction motion range [MD 32.69, 95% CI (14.82, 50.56), P < 0.001] in the USG group. More effective rate was also reported with USG group and the difference was statistically significant [risk ratio = 1.6, 95% CI (1.02, 2.50), P = 0.04]. CONCLUSIONS: Ultrasound-guided corticosteroid injections potentially offer a significantly greater clinical improvement over blind SASD bursitis injections in adults with shoulder pain.
Assuntos
Corticosteroides/uso terapêutico , Bolsa Sinovial/efeitos dos fármacos , Dor de Ombro/tratamento farmacológico , Ultrassonografia de Intervenção , Corticosteroides/administração & dosagem , Humanos , Injeções Intra-Articulares/métodosRESUMO
BACKGROUND: To validate the usefulness of subacromial bursa lidocaine for determination of the therapeutic steroid injection site in patients with adhesive capsulitis METHODS: Ninety-two patients with adhesive capsulitis were randomly divided into the LC (lidocaine test) group (n = 46), in which LC injection was performed at the subacromial bursa prior to therapeutic steroid injection, and GH (glenohumeral) group (n = 46), in which the steroid was injected into the GH. Patients in the LC group received steroid injection at the subacromial bursa or GH according to the result of the LC. Both groups underwent the same exercise protocol. Improvement of the shoulder pain was checked at 2 weeks and 3 months postinjection and expressed on an ordinal scale. Passive range of motion was recorded preinjection, and 2 weeks and 3 months postinjection. RESULTS: Two weeks postinjection, 37 patients expressed "much improved" and 7 patients expressed "slightly improved" pain levels in the LC group, whereas 18 patients each expressed "much improved" and "slightly improved" pain levels in the GH group, which was significantly different (p < 0.01). This difference was maintained 3 months postinjection (p < 0.01). Passive range of motion in all directions improved significantly 3 months postinjection in both the LC and GH groups (p < 0.01). However, there was no significant difference between the LC and GH groups. CONCLUSIONS: We found that subacromial lidocaine injection prior to steroid injection resulted in better improvement of pain than conventional GH injection for patients with adhesive capsulitis.
Assuntos
Anestésicos Locais/administração & dosagem , Bursite/tratamento farmacológico , Glucocorticoides/administração & dosagem , Lidocaína/administração & dosagem , Bolsa Sinovial/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Amplitude de Movimento Articular/efeitos dos fármacos , Articulação do Ombro/efeitos dos fármacos , Dor de Ombro/tratamento farmacológicoRESUMO
The tissue availability of active glucocorticoids (cortisol in humans) depends on their rate of synthesis from cholesterol, downstream metabolism, excretion and interconversion. The latter is mediated by the 11ß-hydroxysteroid dehydrogenases (11ßHSDs). In this review, we summarize the features of the two isoenzymes, 11ßHSD1 and 11ßHSD2, and current available experimental data related to 11ßHSDs, which are relevant in the context of synovial cells in rheumatoid arthritis (RA). We conclude that due to complex feedback mechanisms inherent to the hypothalamic-pituitary-adrenal axis, currently available transgenic animal models cannot display the full potential otherwise inherent to the techniques. Studies with tissue explants, mixed synovial cell preparations, cell lines derived from synovial cells, and related primary cells or established cell lines indicate that there are relatively clear differences between the two isoenzymes. 11ßHSD1 is expressed primarily in fibroblasts and osteoblasts, and may be responsible for fibroblast survival and aid in the resolution of inflammation, but it is also involved in bone damage. 11ßHSD2 is expressed primarily in macrophages and lymphocytes, and may be responsible for their survival, suggesting that it is critical in chronic inflammation. The situation in synovial tissue would allow 11ßHSD2-expressing cells to tap the energy resources of 11ßHSD1-expressing cells. The overall properties of this local glucocorticoid interconversion system might limit therapeutic use of glucocorticoids in RA. © 2014 S. Karger AG, Basel.
Assuntos
11-beta-Hidroxiesteroide Desidrogenases/metabolismo , Artrite Reumatoide/patologia , Bolsa Sinovial/efeitos dos fármacos , Glucocorticoides/farmacologia , 11-beta-Hidroxiesteroide Desidrogenases/genética , Animais , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/enzimologia , Artrite Reumatoide/genética , Modelos Animais de Doenças , Glucocorticoides/uso terapêutico , HumanosRESUMO
Tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine with a critical role in osteoarthritis (OA), was primarily produced by monocytes/macrophages and plays a crucial role in the inflammatory response. Here, we investigated the intracellular signaling pathways involved in TNF-α-induced monocyte chemoattractant protein 1 (MCP-1)/CCL2 expression in human synovial fibroblast cells. Stimulation of synovial fibroblasts (OASF) with TNF-α induced concentration- and time-dependent increases in CCL2 expression. TNF-α-mediated CCL2 production was attenuated by TNFR1 monoclonal antibody (Ab). Pretreatment with an apoptosis signal-regulating kinase 1 (ASK1) inhibitor (thioredoxin), JNK inhibitor (SP600125), p38 inhibitor (SB203580), or AP-1 inhibitor (curcumin or tanshinone IIA) also blocked the potentiating action of TNF-α. Stimulation of cells with TNF-α enhanced ASK1, JNK, and p38 activation. Treatment of OASF with TNF-α also increased the accumulation of phosphorylated c-Jun in the nucleus, AP-1-luciferase activity, and c-Jun binding to the AP-1 element on the CCL2 promoter. TNF-α-mediated AP-1-luciferase activity and c-Jun binding to the AP-1 element were inhibited by TNFR1 Ab, thioredoxin, SP600125, and SB203580. Our results suggest that the interaction between TNF-α and TNFR1 increases CCL2 expression in human synovial fibroblasts via the ASK1, JNK/p38, c-Jun, and AP-1 signaling pathway.
Assuntos
Bolsa Sinovial/metabolismo , Quimiocina CCL2/metabolismo , Fibroblastos/metabolismo , MAP Quinase Quinase Quinase 5/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Antracenos/farmacologia , Anticorpos/farmacologia , Bolsa Sinovial/efeitos dos fármacos , Bolsa Sinovial/patologia , Quimiocina CCL2/genética , Curcumina/farmacologia , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Genes Reporter , Humanos , Imidazóis/farmacologia , Luciferases , MAP Quinase Quinase 4/antagonistas & inibidores , MAP Quinase Quinase 4/genética , MAP Quinase Quinase Quinase 5/antagonistas & inibidores , MAP Quinase Quinase Quinase 5/genética , Osteoartrite/metabolismo , Osteoartrite/patologia , Cultura Primária de Células , Piridinas/farmacologia , Receptores Tipo I de Fatores de Necrose Tumoral/antagonistas & inibidores , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Tiorredoxinas/farmacologia , Fator de Transcrição AP-1/antagonistas & inibidores , Fator de Transcrição AP-1/genética , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
Chemokines produced by synoviocytes of the subacromial bursa are up-regulated in subacromial bursitis and rotator cuff disease. We hypothesized that SDF-1α production in bursal synoviocytes may be induced by local cytokines such as interleukin IL-1ß and IL-6. Subacromial bursa specimens were obtained from patients undergoing shoulder surgery. Bursal specimens were stained with anti-human antibodies to IL-1, IL-6, and SDF-1α by immunohistochemistry and compared to normal and rheumatoid controls. Bursal cells were also isolated from specimens and cultured. Early passaged cells were then treated with cytokines (IL-1ß and IL-6) and SDF-1α expression was measured by ELISA and RT-PCR. SDF-1α, IL-1ß, and IL-6 were expressed at high levels in bursitis specimens from human subacromial bursa compared to normal controls. In cultured bursal synoviocytes, there was a dose-dependent increase in SDF-1α production in the supernatants of cells treated with IL-1ß. SDF-1α mRNA expression was also increased in bursal cells treated with IL-1ß. IL-6 caused a minimal but not statistically significant increase in SDF-1α expression. SDF-1α, IL-1ß, and IL-6 are expressed in the inflamed human subacromial bursal tissues in patients with subacromial bursitis. In cultured bursal synoviocytes, SDF-1α gene expression and protein production are stimulated by IL-1ß. IL-1ß produced by bursal syvoviocytes and inflammatory cells in the human subacromial bursa is an important signal in the inflammatory response that occurs in subacromial bursitis and rotator cuff disease.
Assuntos
Bolsa Sinovial/imunologia , Bursite/imunologia , Quimiocina CXCL12/imunologia , Interleucina-1beta/imunologia , Manguito Rotador/imunologia , Síndrome de Colisão do Ombro/imunologia , Biópsia , Bolsa Sinovial/efeitos dos fármacos , Bolsa Sinovial/patologia , Bursite/patologia , Bursite/fisiopatologia , Células Cultivadas , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Expressão Gênica/imunologia , Humanos , Imuno-Histoquímica , Interleucina-1beta/farmacologia , Interleucina-6/imunologia , Interleucina-6/farmacologia , Manguito Rotador/patologia , Síndrome de Colisão do Ombro/patologia , Síndrome de Colisão do Ombro/fisiopatologia , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/imunologiaRESUMO
INTRODUCTION: The murine air pouch is a bursa-like space that resembles the human synovial membrane. Injection of monosodium urate (MSU) crystals into the pouch elicits an acute inflammatory response similar to human gout. We conducted the present study to identify mRNAs that were highly regulated by MSU crystals in the pouch membrane. METHODS: Air pouch membranes were meticulously dissected away from the overlying skin. Gene expression differences between MSU crystal stimulated and control membranes were determined by oligonucleotide microarray analysis 9 hours after injection of MSU crystals or buffer only. Differential regulation of selected targets was validated by relative quantitative PCR in time course experiments with dissected air pouch membranes and murine peritoneal macrophages. RESULTS: Eleven of the 12 most highly upregulated mRNAs were related to innate immunity and inflammation. They included mRNAs encoding histidine decarboxylase (the enzyme that synthesizes histamine), IL-6, the cell surface receptors PUMA-g and TREM-1, and the polypeptides Irg1 and PROK-2. IL-6 mRNA rose 108-fold 1 hour after crystal injection, coinciding with a surge in mRNAs encoding IL-1beta, tumour necrosis factor-alpha and the immediate early transcription factor Egr-1. The other mRNAs rose up to 200-fold within the subsequent 3 to 8 hours. MSU crystals induced these mRNAs in a dose-dependent manner in cultured macrophages, with similar kinetics but lower fold changes. Among the downregulated mRNAs, quantitative PCR confirmed significant decreases in mRNAs encoding TREM-2 (an inhibitor of macrophage activation) and granzyme D (a constituent of natural killer and cytotoxic T cells) within 50 hours after crystal injection. CONCLUSION: This analysis identified several genes that were previously not implicated in MSU crystal inflammation. The marked rise of the upregulated mRNAs after the early surge in cytokine and Egr-1 mRNAs suggests that they may be part of a 'second wave' of factors that amplify or perpetuate inflammation. Transcript profiling of the isolated air pouch membrane promises to be a powerful tool for identifying genes that act at different stages of inflammation.
Assuntos
Bolsa Sinovial/fisiologia , Perfilação da Expressão Gênica/métodos , RNA Mensageiro/metabolismo , Transcrição Gênica/fisiologia , Ácido Úrico/farmacologia , Animais , Bolsa Sinovial/efeitos dos fármacos , Bolsa Sinovial/patologia , Cristalização , Feminino , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Transcrição Gênica/efeitos dos fármacos , Ácido Úrico/químicaAssuntos
Bolsa Sinovial/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Síndrome de Colisão do Ombro/diagnóstico , Síndrome de Colisão do Ombro/tratamento farmacológico , Dor de Ombro/diagnóstico , Dor de Ombro/prevenção & controle , Esteroides/administração & dosagem , Adulto , Idoso , Bolsa Sinovial/efeitos dos fármacos , Feminino , Humanos , Injeções/métodos , Masculino , Pessoa de Meia-Idade , Radiografia , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/patologia , Lesões do Manguito Rotador , Estatística como Assunto , Resultado do TratamentoRESUMO
The inhibitory effects of 5,6,3',5'-tetramethoxy 7,4'-hydroxyflavone (labeled as p7F) were elucidated on the productions of proinflammatory cytokines as well as inflammatory mediators in human synovial fibroblasts and macrophage cells. p7F inhibited IL-1beta or TNF-alpha induced expressions of inflammatory mediators (ICAM-1, COX-2, and iNOS). p7F also inhibited LPS-induced productions of nitric oxide and prostaglandin E2 in RAW 264.7 cells. In order to investigate whether p7F would inhibit IL-1 signaling, p7F was added to the D10S Th2 cell line (which is responsive to only IL-1beta and thus proliferates), revealing that p7F inhibited IL-1beta-induced proliferation of D10S Th2 cells in a doseresponse manner. A flow cytometric analysis revealed that p7F reduced the intracellular level of free radical oxygen species in RAW 264.7 cells treated with hydrogen peroxide. p7F inhibited IkappaB degradation and NF-kappaB activation in macrophage cells treated with LPS, supporting that p7F could inhibit signaling mediated via toll-like receptor. Taken together, p7F has inhibitory effects on LPS-induced productions of inflammatory mediators on human synovial fibroblasts and macrophage cells and thus has the potential to be an antiinflammatory agent for inhibiting inflammatory responses.
Assuntos
Anti-Inflamatórios/farmacologia , Artrite Reumatoide/tratamento farmacológico , Bolsa Sinovial/efeitos dos fármacos , Flavonoides/farmacologia , Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/imunologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/fisiopatologia , Bolsa Sinovial/imunologia , Bolsa Sinovial/fisiopatologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citocinas/antagonistas & inibidores , Citocinas/genética , Citocinas/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/imunologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/fisiopatologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismoRESUMO
REASON FOR PERFORMING STUDY: Specific analgesic techniques are required in diagnosis of lameness to isolate the exact origin of pain to the many structures of the foot that may be involved. OBJECTIVE: To determine if analgesia of the digital flexor tendon sheath (DFTS) results in anaesthesia of other portions of the foot, such as the sole, distal interphalangeal joint (DIPJ), or navicular bursa (NB). METHODS: Lameness caused by pain in the dorsal margin or heel region of the sole of the foot was induced in 18 horses by: using set-screws to create solar pressure (Trial 1: n = 5); or administering endotoxin intrasynovially into the DIPJ (Trial 2: n = 6) and NB (Trial 3: n = 7). The gait of each horse was evaluated by examining videotape recorded before and after creation of lameness and after administration of mepivacaine hydrochloride into the DFTS. RESULTS: Median lameness scores in Trial 1 at 10 min post injection of the DFTS were not significantly different from those before administration of local anaesthetic solution into the DFTS (P> or =0.05), but median lameness scores were reduced significantly at 20 min (P< or =0.05). In Trials 2 and 3, median lameness scores were not significantly different at observations made at 10 and 20 min post injection of the DFTS. CONCLUSIONS: Analgesia of the DFTS has little effect on lameness caused by pain originating in the sole, DIPJ or NB. POTENTIAL RELEVANCE: Improvement of lameness in horses after intrasynovial analgesia of the DFTS is probably caused by attenuation of pain within the structures contained in the DFTS.
Assuntos
Analgesia/veterinária , Anestésicos Locais/uso terapêutico , Doenças do Pé/tratamento farmacológico , Doenças dos Cavalos/tratamento farmacológico , Artropatias/veterinária , Mepivacaína/uso terapêutico , Analgesia/métodos , Animais , Bolsa Sinovial/efeitos dos fármacos , Doenças do Pé/diagnóstico , Marcha , Casco e Garras , Doenças dos Cavalos/diagnóstico , Cavalos , Artropatias/diagnóstico , Artropatias/tratamento farmacológico , Coxeadura Animal/diagnóstico , Dor/diagnóstico , Dor/etiologia , Dor/prevenção & controle , Dor/veterinária , Distribuição Aleatória , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Gravação de VideoteipeRESUMO
OBJECTIVE: The purpose of this study was to describe the use of fluoroscopically guided subacromial bursography in the management of rotator cuff impingement and to correlate clinical outcome with preprocedural MRI findings. MATERIALS AND METHODS: Sixty-nine patients with clinically and MRI proven subacromial impingement referred for fluoroscopic subacromial bursography and steroid injection between January 2004 and January 2006 were included in the study. After contrast-enhanced bursography, each patient received an injection of 80 mg of methylprednisolone and 1-2 mL of 0.25% bupivacaine into the bursa. Outcome was determined retrospectively and classified as complete resolution of symptoms, partial resolution of symptoms, or no change. MRI findings of impingement were graded according to severity. Outcome was evaluated as complete resolution and as complete or partial resolution in relation to MRI findings, duration of symptoms, age, and sex. RESULTS: Complete resolution of symptoms was recorded in 40 (58%) of the patients. Fifty-seven (83%) of the patients reported some relief of symptoms after a mean follow-up period of 6 months. Shorter duration of symptoms and minor-grade MRI findings were associated with complete resolution. Younger age and minor-grade MRI findings were associated with complete or partial resolution. CONCLUSION: Imaging-guided subacromial steroid injection may be of benefit in the short-term management of clinically and MRI-proven subacromial impingement, with 83% of 69 patients reporting symptom relief at 6-month follow-up evaluation. Patients with shorter duration of symptoms and minor-grade MRI findings have improved outcome.
Assuntos
Bolsa Sinovial/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Síndrome de Colisão do Ombro/diagnóstico , Síndrome de Colisão do Ombro/tratamento farmacológico , Dor de Ombro/diagnóstico , Dor de Ombro/prevenção & controle , Esteroides/administração & dosagem , Adulto , Idoso , Bolsa Sinovial/efeitos dos fármacos , Feminino , Humanos , Injeções/métodos , Masculino , Pessoa de Meia-Idade , Radiografia , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/patologia , Lesões do Manguito Rotador , Estatística como Assunto , Resultado do TratamentoRESUMO
OBJECTIVE: The purpose of this study was to compare sonographic evaluations of patients referred with suspected snapping of their iliopsoas tendon with the pain relief achieved from anesthetic injection of the iliopsoas bursa, and with the subsequent surgical outcome. This study also assessed the effectiveness of Kenalog injection into the iliopsoas bursa for long-term pain relief. PATIENTS AND METHODS: Dynamic and static sonography was performed in 40 patients with clinically diagnosed snapping hips. The iliopsoas bursa was injected with Bupivicaine and Lidocaine in the first 22 patients, and an additional 1 ml Kenalog-40 was added to this mixture in the last 18 patients. We compared the static and dynamic sonographic findings with change in the patients' level of pain at 2 days after anesthetic injection. The sonographic findings and response to anesthetic injection were also compared to the response to Kenalog injection and the results of any subsequent surgery. RESULTS: Static sonography of the iliopsoas tendon was normal in 38 patients, and detected iliopsoas bursitis in one patient and iliopsoas tendinopathy in another. Snapping of the iliopsoas tendon was observed using dynamic sonography in 9 of the 40 patients. Following anesthetic injection of the iliopsoas bursa, 29 patients had complete or partial pain relief, and 11 patients had no pain relief. Eight of the nine patients with a snapping iliopsoas tendon had complete or partial pain relief from the bursal injection. Twelve of the 29 patients with pain relief after anesthetic injection later had an arthroscopic iliopsoas tendon release, and all of these 12 patients had a good postoperative result. Of the 18 patients who had Kenalog-40 injected into the iliopsoas bursa and did not have iliopsoas surgery, 16 had sustained pain relief following the injection. CONCLUSIONS: Patients with groin pain and a clinically suspected snapping iliopsoas tendon can benefit from injection into the iliopsoas bursa even if the snapping tendon is not visualized sonographically. The use of a corticosteroid may provide long-term pain relief, and pain relief after injection is a predictor of good outcome after surgical release of the iliopsoas tendon.