Allopurinol partially prevents disuse muscle atrophy in mice and humans.

Disuse muscle wasting will likely affect everyone in his or her lifetime in response to pathologies such as joint immobilization, inactivity or bed rest. There are no good therapies to treat it. We previously found that allopurinol, a drug widely used to treat gout, protects muscle damage after exhaustive exercise and results in functional gains in old individuals. Thus, we decided to test its effect in the prevention of soleus muscle atrophy after two weeks of hindlimb unloading in mice, and lower leg immobilization following ankle sprain in humans (EudraCT: 2011-003541-17). Our results show that allopurinol partially protects against muscle atrophy in both mice and humans. The protective effect of allopurinol is similar to that of resistance exercise which is the best-known way to prevent muscle mass loss in disuse human models. We report that allopurinol protects against the loss of muscle mass by inhibiting the expression of ubiquitin ligases. Our results suggest that the ubiquitin-proteasome pathway is an appropriate therapeutic target to inhibit muscle wasting and emphasizes the role of allopurinol as a non-hormonal intervention to treat disuse muscle atrophy.

Alopurinol y su papel en el tratamiento de la sarcopenia / Allopurinol and its role in the treatment of sarcopenia

La xantina oxidasa (XO) es la enzima que cataliza la oxidación de hipoxantina a xantina y de esta a ácido úrico, por lo que desempeña un importante papel en el catabolismo de las purinas. El alopurinol, un análogo de las purinas, es un conocido inhibidor de la XO ampliamente utilizado en la práctica clínica para el tratamiento de la gota. Estudios recientes indican que el alopurinol reduce el estrés oxidativo y mejora la función vascular en diversas enfemedades cardiometabólicas, aumenta el tiempo de ejercicio en pacientes con angina de pecho y mejora la eficiencia de la contractilidad miocárdica en la insuficiencia cardiaca. La XO también ejerce un papel importante en la generación de radicales libres durante la contracción muscular, y por tanto se ha relacionado con el daño muscular asociado al ejercicio físico agotador. Diversos grupos de investigación han demostrado el efecto protector del alopurinol en la prevención de este tipo de daño. Teniendo en cuenta estos antecedentes, en este trabajo nos hemos planteado revisar el posible papel del alopurinol en el tratamiento de la sarcopenia, un síndrome geriátrico caracterizado por la progresiva y generalizada pérdida de masa y fuerza muscular, que supone un aumento del riesgo de discapacidad, baja calidad de vida y muerte (AU)

Xanthine oxidase (XO) is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and uric acid and plays an important role in purine catabolism. The purine analogue, allopurinol, is a well-known inhibitor of XO widely used in the clinical management of gout and conditions associated with hyperuricemia. More recent data indicate that allopurinol reduces oxidative stress and improves vascular function in several cardiometabolic diseases, prolongs exercise time in angina, and improves the efficiency of cardiac contractility in heart failure. XO also plays an important role in free radical generation during skeletal muscle contraction and thus, it has been related to the muscle damage associated to exhaustive exercise. Several research groups have shown the protective effect of allopurinol in the prevention of this type of damage. Based on this background, a critical overview is presented on the possible role of allopurinol in the treatment of sarcopenia, a geriatric syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes, such as physical disability, poor quality of life and death (AU)

[Allopurinol and its role in the treatment of sarcopenia]. / Alopurinol y su papel en el tratamiento de la sarcopenia.

Xanthine oxidase (XO) is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and uric acid and plays an important role in purine catabolism. The purine analogue, allopurinol, is a well-known inhibitor of XO widely used in the clinical management of gout and conditions associated with hyperuricemia. More recent data indicate that allopurinol reduces oxidative stress and improves vascular function in several cardiometabolic diseases, prolongs exercise time in angina, and improves the efficiency of cardiac contractility in heart failure. XO also plays an important role in free radical generation during skeletal muscle contraction and thus, it has been related to the muscle damage associated to exhaustive exercise. Several research groups have shown the protective effect of allopurinol in the prevention of this type of damage. Based on this background, a critical overview is presented on the possible role of allopurinol in the treatment of sarcopenia, a geriatric syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes, such as physical disability, poor quality of life and death.

Parapharyngeal abscess in a patient receiving etanercept.

OBJECTIVE: To report a case of parapharyngeal abscess associated with Streptococcus viridans in a patient with rheumatoid arthritis receiving treatment with etanercept. CASE SUMMARY: A 40-year-old man diagnosed with rheumatoid arthritis had received treatment with nonsteroidal antiinflammatory drugs, methotrexate, and deflazacort. Six months prior to admission, the patient had a Disease Activity Score of 3.4; clinicians decided to start treatment with etanercept. Chest X-rays were normal and the tuberculin skin test was negative. Treatment with etanercept plus methotrexate was started. Three months later, methotrexate was discontinued. Six months after etanercept therapy was started, the patient presented to our emergency department with a swelling of his neck, odynophagia, otalgia, and trismus. The clinical course was consistent with parapharyngeal abscess. Etanercept treatment was suspended. The parapharyngeal abscess was drained and intravenous methylprednisolone, amoxicillin/clavulanic acid, and clindamycin were administered. The parapharyngeal abscess secretion culture was positive for S. viridans and Bacteroides spp. The patient's condition improved with antibiotic therapy; he was discharged 5 days after admission. DISCUSSION: Tumor necrosis factor-alpha plays an essential role in the immune-mediated response to infection. In our patient, the most possible cause of parapharyngeal abscess was considered to be etanercept because of the temporal relationship between exposure to the drug and onset of symptoms. Etanercept was the only drug administered before the abscess developed. Based on the Naranjo probability scale, an association between etanercept and the adverse reaction could be considered possible. CONCLUSIONS: Patients initiated on etanercept therapy should be closely monitored for the development of tuberculosis and other infections. During treatment, all febrile or novel illnesses should be evaluated promptly. If clinical evaluation leads to the suspicion of tuberculosis and other infections associated with etanercept, it should be discontinued immediately.

Proposal and validation of a new functional ambulation classification scale for clinical use.

OBJECTIVE: To validate a new functional ambulation classification. DESIGN: Validity study. SETTING: In- and outpatients of a district hospital rehabilitation service. PARTICIPANTS: Thirty-one patients with poststroke hemiplegic gait disorders compared with a control group of 5 healthy people. Interventions Not applicable. MAIN OUTCOME MEASURES: Three independent examiners assessed the functional ambulation levels of each patient in blind trials. Interrater reliability was analyzed among the examiners. Walking velocity (slow, normal, fast) was measured with a manual chronometer, and the number of steps taken over a 48-hour period was recorded with a step counter. The linear correlation was calculated from among functional level classification, walking velocity, and the number of steps taken. RESULTS: There was a good interrater reliability among the examiners (kappa=.74). A significant association and a linear correlation were found between functional ambulation level, walking velocity, and the number of steps taken. CONCLUSIONS: The proposed classification is reliable and valid for determining the different levels of walking abilities.

Walking recovery after an acute stroke: assessment with a new functional classification and the Barthel Index.

OBJECTIVES: To investigate walking recovery after an acute stroke by using both a new functional classification and the Barthel Index, and to identify factors associated with good recovery. DESIGN: A 1-year inception cohort study. SETTING: In- and outpatient setting in a district hospital. PARTICIPANTS: Twenty-six patients with a prognosis of intermediate walking recovery. INTERVENTION: Conventional physical rehabilitation under professional supervision. MAIN OUTCOME MEASURES: Walking capacity was assessed with a new classification scale and the Barthel Index during 5 patient evolution stages (admission to the hospital, hospital and physiotherapy discharge, clinical review, end of study). We also assessed the severity of the paresis of the affected lower limb, the time lapse between the stroke until the recovery of the weight-bearing capacity of the affected leg, and finally the time until standing balance was regained. RESULTS: We detected improvement in walking capacity throughout the follow-up process with our new classification scale, but not with the Barthel Index. Significant improvements were observed from the initial assessment, from 1 month onward, and from 3 to 12 months. The functional level of the final ambulation correlated negatively and significantly with the initial time to achieve weight-bearing capacity on the affected leg and also with the standing balance. There was also a significant correlation with the severity of lower-extremity paresis. CONCLUSIONS: Patients experienced an improvement in walking recovery throughout the first year after their stroke. The early weight-bearing capacity of the affected leg and standing balance were associated with higher walking levels 1 year after the stroke.