Potential immunological consequences of pharmacological suppression of gastric acid production in patients with multiple sclerosis

Corticosteroids are standard treatment for patients with multiple sclerosis experiencing acute relapse. Because dyspeptic pain is a common side effect of this intervention, patients can be given a histamine receptor-2 antagonist, proton pump inhibitor or antacid to prevent or ameliorate this disturbance. Additionally, patients with multiple sclerosis may be taking these medications independent of corticosteroid treatment. Interventions for gastric disturbances can influence the activation state of the immune system, a principal mediator of pathology in multiple sclerosis. Although histamine release promotes inflammation, activation of the histamine receptor-2 can suppress a proinflammatory immune response, and blocking histamine receptor-2 with an antagonist could shift the balance more towards immune stimulation. Studies utilizing an animal model of multiple sclerosis indicate that histamine receptor-2 antagonists potentially augment disease activity in patients with multiple sclerosis. In contrast, proton pump inhibitors appear to favor immune suppression, but have not been studied in models of multiple sclerosis. Antacids, histamine receptor-2 antagonists and proton pump inhibitors also could alter the intestinal microflora, which may indirectly lead to immune stimulation. Additionally, elevated gastric pH can promote the vitamin B12 deficiency that patients with multiple sclerosis are at risk of developing. Here, we review possible roles of gastric acid inhibitors on immunopathogenic mechanisms associated with multiple sclerosis

A systematic review of randomised controlled trials assessing effectiveness of prosthetic and orthotic interventions.

BACKGROUND: Assistive products are items which allow older people and people with disabilities to be able to live a healthy, productive and dignified life. It has been estimated that approximately 1.5% of the world's population need a prosthesis or orthosis. OBJECTIVE: The objective of this study was to systematically identify and review the evidence from randomized controlled trials assessing effectiveness and cost-effectiveness of prosthetic and orthotic interventions. METHODS: Literature searches, completed in September 2015, were carried out in fourteen databases between years 1995 and 2015. The search results were independently screened by two reviewers. For the purpose of this manuscript, only randomized controlled trials which examined interventions using orthotic or prosthetic devices were selected for data extraction and synthesis. RESULTS: A total of 342 randomised controlled trials were identified (319 English language and 23 non-English language). Only 4 of these randomised controlled trials examined prosthetic interventions and the rest examined orthotic interventions. These orthotic interventions were categorised based on the medical conditions/injuries of the participants. From these studies, this review focused on the medical condition/injuries with the highest number of randomised controlled trials (osteoarthritis, fracture, stroke, carpal tunnel syndrome, plantar fasciitis, anterior cruciate ligament, diabetic foot, rheumatoid and juvenile idiopathic arthritis, ankle sprain, cerebral palsy, lateral epicondylitis and low back pain). The included articles were assessed for risk of bias using the Cochrane Risk of Bias tool. Details of the clinical population examined, the type of orthotic/prosthetic intervention, the comparator/s and the outcome measures were extracted. Effect sizes and odds ratios were calculated for all outcome measures, where possible. CONCLUSIONS: At present, for prosthetic and orthotic interventions, the scientific literature does not provide sufficient high quality research to allow strong conclusions on their effectiveness and cost-effectiveness

Effect of exercise on cytokines and growth mediators in prepubertal children.

Many of the anabolic effects of exercise are mediated through insulin-like growth factor-I (IGF-I), but in adolescents, brief exercise training leads to reductions, rather than the expected increase, in circulating IGF-I. Certain cytokines--interleukin-(IL) 1beta (IL-1beta), IL-6 (IL-6), and tumor necrosis factor-alpha--are increased by exercise in adults and are known to inhibit IGF-I. To test the hypothesis that these cytokines might play a role in the adaptation to exercise, we measured the acute effects of exercise on selected cytokines and growth factors in 17 healthy 8- to 11-y-old children (4 females). Designed to mimic patterns and intensity of exercise found in the real lives of American children, the exercise protocol consisted of a 1.5-h soccer practice (of which about 40 min constituted of vigorous exercise). Pre- and postexercise urine and saliva samples were obtained in all subjects and both blood and urine in nine subjects. The exercise led to significant increases in circulating tumor necrosis factor-alpha (18 +/- 7%, p < 0.05) and IL-6 (125 +/- 35%, p < 0.01) as well as a significant increase in the antiinflammatory cytokine IL-1 receptor antagonist (33 +/- 10%, p < 0.01). Urine levels of IL-6 were also substantially increased by exercise (440 +/- 137%, p < 0.0001). Circulating levels of IGF-I were reduced to a small but significant degree (-6.4 +/- 3.2%, p < 0.05), although IGF-binding protein-1 (known to inhibit IGF-I) was substantially increased (156 +/- 40%, p < 0.001). Cytokines are systemically increased after relatively brief exercise in healthy children. This increase may alter critical anabolic agents such as IGF-I and its binding proteins