Strontium ranelate as a possible disease-modifying osteoarthritis drug: a systematic review

Considering that osteoarthritis (OA) is the most prevalent joint disease worldwide, multiple pharmacological treatments have been proposed to alter the articular structure with potential benefit in the progression of the disease. The so-called disease-modifying OA drugs have been frequently investigated but conclusive findings are rare. Strontium ranelate (SrRan) is a drug usually prescribed to treat osteoporosis, with proven effects in decreasing the risk of fractures and possible effect in reducing the progression of OA. The objective of this review was to demonstrate the current panorama of knowledge on the use of SrRan in clinical and experimental models, clarifying its mechanisms of action and describing possible anti-nociceptive and anti-inflammatory effects. The systematic review was based on the PRISMA statement and included articles that are indexed in scientific databases. Fifteen studies were included: seven pre-clinical and eight clinical studies. Despite the limited number of studies, the results suggest a positive effect of SrRan in patients with OA, through changes in functional capacity and reduction of progression of morphological parameters and joint degradation, with moderate quality of evidence for those clinical outcomes. Novel studies are necessary to elucidate the molecular targets of SrRan, focusing on anti-inflammatory effects and histological changes promoted by SrRan, which seemed to reduce the progression of OA in the experimental and clinical studies.

Naringenin regulates production of matrix metalloproteinases in the knee-joint and primary cultured articular chondrocytes and alleviates pain in rat osteoarthritis model

Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs) are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA) osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1β activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4) and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis.

Pharmacologic management of pain in patients with Chikungunya: a guideline

Abstract From the arrival of Chikungunya virus in the Americas in 2013 until March 2016, approximately two million cases of the disease have been reported. In Brazil, the virus was identified in 2014 and thousands of people have been affected. The disease has high attack rates, infecting 50% of a population within a few months. Approximately 50% of infected people develop chronic symptoms lasting for months or years. Joint involvement is the main clinical manifestation of Chikungunya. It is characterized by swelling and intense pain that is poorly responsive to analgesics, both in the acute and chronic phase of the disease. This significantly compromises quality of life and may have immeasurable psychosocial and economic repercussions, constituting therefore, a serious public health problem requiring a targeted approach. Physicians are often not familiar with how to approach the management of pain, frequently prescribing limited analgesics, such as dipyrone, in sub-therapeutic doses. In addition, there are few published studies or guidelines on the approach to the treatment of pain in patients with Chikungunya. Some groups of specialists from different fields have thus developed a protocol for the pharmacologic treatment of Chikungunya-associated acute and chronic joint pain; this will be presented in this review.

Transdermal methyl alcohol intoxication cause of pain relief / Intoxicación transdérmica con alcohol metílico tratando de aliviar un dolor

A 60-year old female patient was found comatosed at home and taken to the hospital's Emergency Department by her relatives. It was learnt that she wrapped her knees with spirit-impregnated cotton pad for pain for one week. On physical examination, only a colour change of purple violet on her knees was noted. Metabolic acidosis with increased anion gap was detected by arterial blood analysis. The patient underwent haemodialysis. She was discharged from the hospital with no complaints, alert and rational following five days of follow-up treatment, with the diagnosis of methyl alcohol poisoning.

Una paciente de 60 años de edad fue hallada en estado comatoso en su casa, y trasladada por sus familiares al departamento de emergencias del hospital. Se supo que la paciente había sentido dolor en sus rodillas, y las cubrió con almohadillas de algodón impregnadas de metanol por espacio de una semana. Al realizarse el examen físico, sólo se observó un cambio de color violeta púrpura en sus rodillas. El análisis de sangre arterial reveló acidosis metabólica con hiato iónico elevado. A la paciente se le practicó una hemodiálisis. Fue dada de alta del hospital sin dolencias, consciente, y en su sano juicio, luego de cinco días de seguimiento de su tratamiento, tras de haber sido diagnosticada con envenamiento por alcohol metílico.

Analysis of patients with post-chemotherapy Arthralgia and Arthritis in breast cancer.

Objective: Evaluate the characteristics of arthropathy and musculoskeletal pain after chemotherapy in patients with breast cancer. Materials and Methods: In this study, we evaluate the characteristics of 15 patients with joint symptoms after receiving chemotherapy for breast cancer. Demographic information including sex, age, time of rheumatologic findings after starting of chemotherapy, and time of improvement after starting of medication, and laboratory findings detected for each patient. Results: Patients comprised 15 women with mean age 43.4 ± 10.6 years that received classic chemotherapy for breast cancer according to stage of disease including cyclophosphamide, and tamoxifen. Joint symptoms usually began about 6 months after the first session of chemotherapy. Patients had an average of 2 tender joints and 1 hour of morning stiffness. None of patients were positive for anti-nuclear antibody, and just 1 patient was positive for rheumatoid factor. Non-steroidal anti-inflammatory drugs, disease modifying anti-rheumatic drugs (DMARD), corticosteroids, and venlafaxine were prescribed. 5 patients did not show an improvement and were also given low dose oral corticosteroids. Follow-up was available for all patients. 13 patients showed favorable responses, characterized by a significant decrease (more than 50%) in morning stiffness, pain, and tender joint counts after a mean of 3 months' treatment. 9 patients had complete resolution of symptoms and stopped all medications. Conclusion: Chemotherapy-related arthropathy is not rare, and the prognosis is fairly good with early treatment using NSAID, DMARD, and corticosteroids.

Farmacopuntura en el dolor osteomioarticular resistente a otros tratamientos / Pharmacoacupuncture in osteomioarticular pain resistance to other treatments

Se realizó un estudio prospectivo, descriptivo, con análisis inferencial, donde se tomó como universo todos los pacientes remitidos al Centro Provincial para el Desarrollo de la Medicina Tradicional y Natural Dr Mario E Dihigo de Matanzas, con diagnóstico de dolor osteomioarticular. De ellos se tomó una muestra de 20 pacientes, que fueron la totalidad de aquéllos que no presentaron una respuesta favorable a los tratamientos previos (alopático convencional y otros de MTN). Con el objetivo de evaluar la intensidad del dolor se aplicó al inicio y al final del tratamiento el Test de Likert. Además, en la primera consulta se evaluó a cada paciente de forma individual, localizándose el sitio del dolor y estableciéndose así la selección del medicamento y los puntos acupunturales a utilizar. El tratamiento fue aplicado utilizando jeringuillas de insulina desechables, y todos los medicamentos utilizados fueron aplicados a razón de 0.25 cc por punto, habiéndose previamente diluido éste a razón de una parte en nueve partes de agua para inyección. Como criterio de efectividad se tuvo la desaparición del dolor. A pesar de tratarse de una muestra corta, los resultados obtenidos meritan extender la aplicación de la Farmacopuntura a un mayor número de pacientes para obtener una mejor evidencia de su efecto analgésico. Se concluye que el tratamiento con Farmacopuntura resulta efectivo en pacientes con dolor osteomioarticular resistente a otros tratamientos y en los casos en que no se logra una eliminación del dolor es posible al menos obtener una mejoría del cuadro doloroso.

We carried out a prospective, descriptive study, with inferential analysis, where as the universe were taken all the patients sent to the Provincial Center for Developing Traditional and Natural Medicine Dr Mario E Dihigo of Matanzas with osteomioarticular pain. From them was taken a sample of 20 patients, the totality of those who did not present a favorable answer to previous treatments (conventional allopathic and other natural medicine treatments). With the objective of evaluating pain intensity, we applied the Test of Likert at the beginning and at the end of the treatment. Besides that, each patient was evaluated individually during the first visit, locating the pain place and selecting the drug and acupuntural points to use. The treatment was applied using disposable insulin syringes, and all the medical preparations used were applied in a reason of 0.25 cc per point, previously diluting it in nine parts of injection water. We took the extinction of pain as criteria of effectiveness. Although the sample was short, the obtained results make it worth to extend the application of pharmacoacupuncture to a bigger number of patients to obtain a better evidence of its analgesic effect. We concluded that the treatment with pharmacoacupuncture is effective in patients with osteomioarticular pain resistant to other treatments and, in the cases there is not achieved a pain elimination, it is possible to obtain an improvement of the pain status.

Intra-articular injection of deproteinized hemodialysate in osteoarthritis of the knee: a case-series.

OBJECTIVE: To report the efficacy of intra-articular injection of deproteinized hemodialysate including its side effects in a case-series of knee osteoarthritic (OA) patients. MATERIAL AND METHOD: Intra-articular injection of deproteinized hemodialysate was performed in 17 subjects (3 male and 14 female) with primary knee OA. Their average age was 63 years (min, max = 50, 80 yrs). The X-ray appearance was grade II-III according to Kellgren-Lawrence criteria. MEASUREMENTS: 100 mm visual analogue scale (VAS) and any side effects. RESULTS: The mean (95% CI) of the VAS before and after injection were 70.0 (59.9-80.1) and 42.7 (31.2-54.2) respectively, with a p-value of < 0.001. The mean difference in pain score was 27.35 (95% CI = 17.0-37.7). The symptoms of knee pain resolved in an average of 4.8 (2.9) days (min, max = 1, 10). No side effects were found. CONCLUSION: Intra-articular injection of deproteinized hemodialysate is effective and safe. However, a further controlled trial with an adequate sample size should be performed to confirm the efficacy as well as to detect any adverse effects of this drug.

Ulceras gástricas sangrantes y hepatitis aguda: dos reacciones adversas simultáneas por nimesulida en un caso / Bleeding gastric ulcers and acute hepatitis: 2 simultaneous adverse reactions due to nimesulide in 1 patient

A 66 year-old obese woman with arthrosis, self-medicated with oral nimesulide, 200 mg daily. After 6 weeks she developed nausea, jaundice and dark urine. Two weeks later she had recurrent hematemesis and was hospitalized. Besides obesity and anemia her physical examination was unremarkable. An upper GI endoscopy revealed 3 acute gastric ulcers and a 4th one in the pyloric channel. Abdominal ultrasonogram showed a slightly enlarged liver with diffuse reduction in ecogenicity; the gallbladder and biliary tract were normal. Blood tests demonstrated a conjugated hyperbilirubinemia (maximal total value: 18,4 mg/dl), ALAT 960 U/l, ASAT 850 U/l, GGT 420 U/l, alkaline phosphatases mildly elevated, pro-time 49 percent and albumin 2.7 mg/dl. Serum markers for hepatitis A, B and C viruses were negative. ANA, AMA, anti-SmA, were negative. Ceruloplasmin was normal. A liver biopsy showed bridging necrosis and other signs of acute toxic liver damage. Gastric ulcers healed after conventional treatment and hepatitis subsided after 2 months leaving no signs of chronic liver damage. The diagnosis of toxic hepatitis due to nimesulide was supported by the time-course of drug usage, sex, age, absence of other causes of liver disease, a compatible liver biopsy and the improvement after drug withdrawal. Peptic ulcers or toxic hepatitis have been previously described as independent adverse reactions in patients taking nimesulide or other NSAIDs but their simultaneous occurrence in a single patient is a unique event that deserves to be reported

Uso de esteroides intraarticulares en rodilla y hombro / Intra-articular steroid use in the knee and shoulder

La aplicación intraarticular de esteroides es una garantía como tratamiento de una variedad de síndromes dolorosos de la rodilla. En el presente trabajo se revisan las indicaciones, contraindicaciones y posibles complicaciones de este tratamiento, así como las técnicas de infiltración en la articulación de la rodilla y en el hombro. La infiltración de lidocaína junto con betametasona usualmente proporciona alivio inmediato del dolor, y puede ser utilizada como auxiliar diagnóstico complementario.

Síndrome de Sweet asociado a compromiso articular y renal / Sweet syndrome associated with articular and renal involvement

We report a 29 years old female presenting with fever and painful infiltrated erythematous and violaceous plates with pseudo vesicles in the surface, located in both arms, four days after having suffered a tonsillitis. She was admitted with the diagnosis of Sweet syndrome and the lesions disappeared spontaneously. Two months later, she presented with a similar condition, again after an upper respiratory infection. Five months later, she was admitted with arthralgias with positive rheumatoid factor and antinuclear antibodies. Three years after the first admission, she was admitted with an acute glomerulonephritis and renal failure after another upper respiratory infection. Sweet syndrome was described in 1964 and, although initially considered benign, its association with inflammatory diseases or cancer has been reported