Oromandibular Dystonia as a Side Effect of Methotrexate.

Oromandibular dystonia is a focal dystonia characterized by involuntary movements of the jaw, oropharynx, lips, and tongue. The diagnosis of oromandibular dystonia is clinical and can be complex. For effective treatment, it is essential to understand its underlying etiology. A 70-year-old man was referred to our center with a diagnosis of Meige's syndrome, which had been present for five and a half years, for receiving botulinum toxin-A (BoNT-A) injections. Upon physical examination, he exhibited oromandibular dystonia, with a score of 177 points on the Oromandibular Dystonia Rating Scale (OMDRS). He had a history of taking methotrexate for six years, as he was diagnosed with psoriatic arthritis during that time. The possibility of methotrexate-induced dystonia was considered. A switch from methotrexate to sulfasalazine was initiated. Subsequently, the patient showed progressive improvement in his symptoms, as reflected by an OMDRS score of 103 points. After eight weeks, the medical team decided to supplement the treatment with BoNT-A injections, resulting in an OMDRS score of 75. While there is currently no definitive evidence linking the use of methotrexate to the development of dystonia, it is advisable to consider oromandibular dystonia as a potential side effect of methotrexate until more robust evidence becomes available.

Cardiac rehabilitation in patients with type 2 diabetes mellitus and coronary disease: a comparative study.

INTRODUCTION AND AIMS: Diabetic patients have a 2-4 times higher risk of cardiovascular disease than non-diabetic individuals. The aims of this study are to evaluate the effects of a cardiac rehabilitation program (phase II) in patients with diabetes and coronary disease and to compare the results with regard to control of cardiovascular risk factors and improvement in functional capacity with coronary patients without diabetes. METHODS: This was a prospective study of patients diagnosed with ischemic heart disease referred for a cardiac rehabilitation program between January 2009 and June 2013. The population was divided into two groups: diabetic and non-diabetic. Patients were assessed at the beginning of phase II and three months later and the following parameters were recorded: body mass index, waist circumference, lipid profile, blood glucose and glycated hemoglobin in diabetic patients, blood pressure, smoking, physical activity level (using the International Physical Activity Questionnaire) and functional capacity (on treadmill stress testing). RESULTS: The study population consisted of 682 patients (253 diabetic and 429 non-diabetic). Diabetic patients were significantly older, had a worse cardiovascular risk profile (higher prevalence of overweight, dyslipidemia, hypertension and sedentary lifestyle) and lower functional capacity. At the end of phase II, there was a statistically significant improvement (p<0.05) in all risk factors and functional capacity, which was similar in both groups, except for body mass index, triglycerides and functional capacity. CONCLUSIONS: Diabetic patients may benefit from a cardiac rehabilitation program and achieve comparable results to non-diabetic patients.

In vitro scavenging activity for reactive oxygen and nitrogen species by nonsteroidal anti-inflammatory indole, pyrrole, and oxazole derivative drugs.

This study was undertaken to evaluate the scavenging activity for reactive oxygen species (ROS) and reactive nitrogen species (RNS) by several nonsteroidal anti-inflammatory drugs (NSAIDs), namely indole derivatives (indomethacin, acemetacin, etodolac), pyrrole derivatives (tolmetin and ketorolac), and an oxazole derivative (oxaprozin). The inhibition of prostaglandin synthesis constitutes the primary mechanism of the anti-inflammatory action of these drugs. Nevertheless, it has been suggested that the anti-inflammatory activity of NSAIDs may be also partly due to their ability to scavenge ROS and RNS and to inhibit the respiratory burst of neutrophils triggered by various activator agents. Thus, the scavenging activity of these NSAIDs was evaluated against an array of ROS (O(2)(-), HO, HOCl, and ROO) and RNS (NO and ONOO(-)) using noncellular in vitro systems. The results obtained demonstrated that tolmetin, ketorolac, and oxaprozin were not active against O(2)(-), while acemetacin, indomethacin, and etodolac exhibited concentration-dependent effects. Oxaprozin was also the least active scavenger for HO, among all the tested NSAIDs shown to be active. The scavenging effect for HOCl was not observed for any of the tested NSAIDs. The ROO was effectively scavenged by etodolac, with the other tested NSAIDs being much less active. NO and ONOO(-) were scavenged by all the tested NSAIDs. These effects may strongly contribute to the anti-inflammatory therapy benefits that may be attained with some of the studied NSAIDs.

The metabolism of sulindac enhances its scavenging activity against reactive oxygen and nitrogen species.

Sulindac is a sulfoxide prodrug that, in vivo, is converted to the metabolites sulindac sulfide and sulindac sulfone. It is therapeutically used as an anti-inflammatory and analgesic in the symptomatic treatment of acute and chronic rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. In addition to its anti-inflammatory properties, sulindac and its metabolites have been shown to have an important role in the prevention of colonic carcinogenesis. Although the inhibition of prostaglandin synthesis constitutes the primary mechanism of action of sulindac, it is well known that reactive oxygen species (ROS) and reactive nitrogen species (RNS) are implicated in the pathophysiology of inflammation and cancer. Thus, the aim of this study was to evaluate the scavenging activity of sulindac and its sulfone and sulfide metabolites for an array of ROS (HO*, O2(*-), and HOCl) and RNS (*NO and ONOO-) using in vitro systems. The results we obtained demonstrate that the metabolism of sulindac increases its scavenging activity for all RNS and ROS studied, notably with regard to the scavenging of HOCl. These effects may strongly contribute to the anti-inflammatory and anticarcinogenic efficacy that has been shown for sulindac.