Inhibition of diabetes mellitus-induced knee joint injury in rats by a combination of metformin and captopril / Inhibición de la lesión de la articulación de la rodilla inducida por diabetes mellitus en ratas mediante una combinación de metformina y captopril

SUMMARY: Osteoarthritis (OA) is an inflammatory disease that damages the joints and affects millions of people worldwide. The potential inhibitory effects of the antidiabetic drug metformin combined with captopril, the angiotensin-converting enzyme inhibitor, on diabetes-induced damage to the knee joint articular cartilage associated with the inhibition of glycemia, dyslipidemia, and inflammation has not been investigated before. Therefore, we induced diabetes in rats using high carbohydrate and fat diets and a single injection of streptozotocin (50 mg/kg). The protective group of rats was pre-treated with combined daily doses of metformin (Met; 200 mg/kg body weight) and captopril (Cap; 150 mg/kg body weight) for 14 days before diabetic induction and continued on metformin and resveratrol until the end of the experiment at week 12. Harvested tissues obtained from knee joints were prepared for basic histology staining with haematoxylin and eosin (H&E) and examined under light microscopy. Representative H&E images showed that OA was developed in the diabetic rats as demonstrated by a profound damage to the knee joints such as irregular eroded and a sharp decrease in the thickness of the articular cartilage surface and abnormal remodeling of the subchondral bone that were substantially ameliorated by Met+Cap. Met+Cap also significantly (p< 0.05) reduced blood levels of glucose, glycated hemoglobin (HbA1c), dyslipidemia, and the inflammatory biomarkers, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-α) induced by diabetes. In addition, a significant (p≤ 0.0014) correlation between the articular cartilage thickness and the blood levels of glucose, HbA1c, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein- cholesterol (HDL-C), and hs-CRP were observed. Thus, we demonstrate that Met+Cap effectively protect the knee joint against injuries induced secondary to diabetes in rats, possibly due to the inhibition of glycemia, dyslipidemia, and biomarkers of inflammation.

RESUMEN: La osteoartritis (OA) es una enfermedad inflamatoria que daña las articulaciones y afecta a millones de per- sonas en todo el mundo. No se han investigado los posibles efectos inhibidores del fármaco antidiabético metformina combinado con captopril, el inhibidor de la enzima convertidora de angiotensina, sobre el daño inducido por la diabetes en el cartílago articular de la articulación de la rodilla asociado con la inhibición de la glucemia, dislipidemia e inflamación. En este estudio fue inducida la diabetes en ratas con dietas altas en carbohidratos y grasas y una sola inyección de estreptozotocina (50 mg / kg). El grupo protector de ratas se pretrató con dosis diarias combinadas de metformina (Met; 200 mg / kg de peso corporal) y captopril (Cap; 150 mg / kg de peso corporal) durante 14 días antes de la inducción diabética. El tratamiento se continuó con metformina y resveratrol hasta el final del experimento en la semana 12. Los tejidos obtenidos de las articulaciones de la rodilla se prepararon para la tinción de histología básica con hematoxilina y eosina (H&E) y se examinaron con microscopía óptica. Imágenes representativas de H&E mostraron que la OA se desarrolló en las ratas diabéticas, como lo evidencia un daño profundo en las articulaciones de la rodilla, como la erosión irregular y una fuerte disminución en el grosor de la superficie del cartílago articular y remodelación anor- mal del hueso subcondral que fueron mejorados sustancialmente por Met + Cap. Met + Cap. También redujo significativamente (p <0.05) los niveles sanguíneos de glucosa, hemoglobina glicosilada (HbA1c), dislipidemia y los biomarcadores inflamatorios, proteína C reactiva de alta sensibilidad (hs-CRP), interleucina-6 (IL-6), y factor de necrosis tumoral alfa (TNF-α) inducido por diabetes. Además, una correlación significativa (p≤ 0,0014) entre el grosor del cartílago articular y los niveles sanguíneos de glucosa, HbA1c, triglicéridos (TG), lipoproteínas-colesterol de baja densidad (LDL- C), lipoproteínas de alta densidad-colesterol (HDL-C) ) y hs-CRP. Así, demostramos que Met + Cap protege eficazmente la articulación de la rodilla contra lesiones inducidas por diabetes en ratas, posiblemente debido a la inhibición de la glicemia, dislipidemia y biomarcadores de inflamación.

Evaluation and Management of Subchondral Calcium Phosphate Injection Technique to Treat Bone Marrow Lesion.

PURPOSE: This study aimed to compile available data in medical literature about subchondral calcium phosphate injection, comparing results obtained with this technique, as well as indications, complications, and other important factors in treatment of bone marrow lesions. DESIGNS: A literature review using PubMed and Medline database in order to identify works with terms "subchondral calcium phosphate injection," " subchondroplasty®," "bone marrow lesion," and "knee." Eight relevant articles were found. RESULTS: A total of 164 patients with bone marrow lesion mainly on femoral condyle and tibial plateau recovered with significant functional improvement of knee after subchondral calcium phosphate treatment. Although 25% of them still had some type of pain complaint, they also showed improvement. There were few complications reported and return to activities occurred after 3 months on average. CONCLUSIONS: Few studies evaluate the result of using subchondral calcium phosphate injection technique. However, all presented favorable results regarding pain and improvement of knee function. In addition, within 2 years, there was a 70% reduction in conversion to total knee arthroplasty in patients with previous surgical indication who choose calcium phosphate treatment.

Associação de sulfato de glicosamina e sulfato de condroitina para pacientes portadores de osteoartrose de joelho / Association of glucosamine sulphate and chondroitin sulphate for patients with osteoarthritis of the knee

Objetivo: O presente estudo teve como objetivo avaliar a eficácia e a segurança da associação de sulfato de glicosamina e sulfato de condroitina Eurofarma* na forma de sachê, comparado ao Condroflex®*1 (Zodiac) no tratamento de pacientes portadores de osteoartrose do joelho.Materiais e métodos: Foram incluídos no estudo, 100 pacientes, sendo que 95 receberam a administração da medicação em estudo uma vez ao dia, pela manhã, durante no mínimo um mês. Ao final do tratamento se realizou avaliação através da Escala Visual Analógica (EVA), avaliação do investigador através da Escala de Likert e avaliação de tolerabilidade.Resultados: A maioria da população avaliada apresentou as classificações ?ótima?, ?muito boa? e ?boa? para ambas as associações, totalizando 70,5% (67 pacientes) dos casos avaliados, demonstrando que o tratamento teste é tão eficiente quanto o comparador. Nota-se que 94,7% (90 pacientes) dos pacientes apresentaram ótima tolerabilidade e apenas 5,3% (5 pacientes) apresentaram tolerabilidade muito boa e boa.Conclusão: Os resultados obtidos demonstraram a eficácia e a segurança do uso da associação de sulfato de glicosamina e sulfato de condroitina da Eurofarma no tratamento de osteoartrose do joelho e no alívio dos sinais e sintomas estudados, não havendo diferença significante com relação ao medicamento referência.

[Jumper's knee. Surgery and arthroscopic treatment with scraping and povidone collagen in high-performance athletes]. / Rodilla del saltador. Tratamiento quirúrgico artroscópico combinado con rastrillaje y colágeno povidona en deportistas de alto rendimiento.

UNLABELLED: The jumper's knee or patellar tendonitis is a common injury in the athlete with an incidence between 14% and 16% among high-performance athletes. In addition to an overuse injury, there are some intrinsic factors for its development. Conservative treatment is indicated for the initial form, but when it fails, surgical treatment should be performed with an appropriate rehabilitation program. MATERIAL AND METHODS: We retrospectively studied 18 high performance athletes in various disciplines, with an average age of 22 years, operated by arthroscopy and mini-arthrotomy scraping and application of povidone collagen sponge between March 2001 and December 2005. There after patients underwent a rehabilitation program specific for their return to their athletic activity. RESULTS: The patients returned to their sports activity in an average of 15 weeks, with functional knees without pain, with full range of motion. We did not find postoperative fibrosis. DISCUSSION: The results were similar and slightly better in time of return to sports activities to those reported in the world literature, with the difference in follow up. According to the clinical evaluation, treatment performed allows functional improvement with a return to athletic activity in a reasonable time.

Stereoselective disposition of fenoprofen in plasma and synovial fluid of patients with rheumatoid arthritis.

The simultaneous disposition of fenoprofen enantiomers in synovial fluid and plasma was studied in 11 patients with arthritis and chronic knee effusions treated with a single oral dose of 600 mg rac-fenoprofen. A plasma sample and a synovial fluid sample were collected simultaneously from each patient up to 16 h after the administration of fenoprofen. A stereospecific assay for fenoprofen using LC-MS-MS was developed and applied successfully to the analysis of the enantiomers in plasma (LOQ = 10 ng of each enantiomer/ml) and synovial fluid (LOQ = 25 ng of each enantiomer/ml). The values of the area under the curve (AUC) for the S-(+)-fenoprofen eutomer were approximately 2.5 times higher in plasma than in synovial fluid (256 vs 104 microg h/ml), while the values for the R-(-)-fenoprofen distomer were about four times higher in plasma than in synovial fluid (42.5 vs 10.5 microg h/ml). These data demonstrate accumulation of the S-(+)-fenoprofen eutomer in plasma and in synovial fluid, with concentrations versus time AUC (+)/(-) ratios of 6.0 in plasma and 9.9 in synovial fluid, suggesting a greater accumulation of the eutomer at the active site represented by synovial fluid than in plasma. This result demonstrates the importance of enantioselective methods and of analysis of synovial fluid rather than plasma in studies of the pharmacokinetics-pharmacodynamics of fenoprofen.

[Comparison of the efficacy of intraarticular and intraarterial injections of two betamethasone preparations in patients with osteoarthritis or epicondilytis]. / Comparación de la eficacia clínica de una inyección intraarticular o intralesional de dos preparados de betametasona en pacientes con artrosis o epicondilitis.

BACKGROUND: Local infiltration with corticoids is a simple therapy for rheumatic disorders devoid of systemic adverse reactions. AIM: To compare the efficacy of two betametasone preparations from two different pharmaceutical laboratories in the treatment of patients with osteoarthritis or epicondylitis. PATIENTS AND METHODS: Fourty patients with knee osteoarthritis and 12 patients with epicondylitis were studied. Using a double blind protocol, one of the two betametasone preparations was used for local infiltration of the lesions. The change in a global score of clinical variables including pain and disability was assessed after 30 days of the infiltration. RESULTS: In patients with osteoarthritis, the global score decreased significantly with both preparations, but no differences were observed between preparations (7.3 +/- 1.8 to 3.9 +/- 2.3 with preparation A and 7.8 +/- 1.9 to 3.6 +/- 2.3 with preparation B). In patients with epicondylitis, pain was also significantly reduced but no differences between preparations was observed (7 +/- 2.1 to 1.4 +/- 2.5 for preparation A and 4.6 +/- 2.8 to 1.2 +/- 1.6 for preparation B). CONCLUSIONS: Local infiltration with both betametasone preparations was equally effective in the treatment of patients with knee osteoarthritis or epicondilytis.

Mechanism of diclofenac analgesia: direct blockade of inflammatory sensitization.

Indomethacin, a typical cyclo-oxygenase inhibitor, acts as an analgesic by preventing the hyperalgesia induced by prostaglandins during inflammation. Analgesics of the dipyrone type directly block the sensitization of nociceptors. In the present investigation, the analgesic effect of diclofenac was compared with that of indomethacin in two algesimetric tests which permit discrimination between the two types of analgesic: the rat knee joint incapacitation and the rat paw hyperalgesia tests. The analgesics were given either pre- or posttreatment relative to the induction of hyperalgesia with carrageenin or prostaglandin E2. In both tests intraperitoneal pretreatment with indomethacin was equally or slightly more potent than diclofenac. Posttreatment with diclofenac was more effective than posttreatment with indomethacin. This was particularly evident in the paw hyperalgesia test in which posttreatment with indomethacin was not effective while diclofenac caused dose-dependent analgesia. When nociception was induced by PGE2 in both tests, the administration of indomethacin directly into the knee joint or rat paw had no effect while diclofenac continued to cause dose-dependent analgesia. Thus, diclofenac has a direct effect on ongoing hyperalgesia in addition to its ability to block cyclo-oxygenase. Naloxone and N-methyl-nalorphine did not affect diclofenac analgesia, thus indicating that the analgesic effect of the latter is independent of a central or peripheral opioid effect. Local administration of agents which inhibit the formation of nitric oxide (NG-monomethyl-L-arginine) or inhibit the activation of guanylate cyclase by nitric oxide (methylene blue) abolished diclofenac-induced analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)