A Randomized Control Trial Study to Determine the Effect of Melatonin on Serum Levels of IL-1ß and TNF-α in Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is the most common neurological disease that happens at a young age. MS is an inflammatory disease; associated with the demyelination of the central nervous system. Therefore, some inflammatory factors are effective in the mechanism and progression of the disease. Melatonin, as a multi-effect substance including anti-inflammatory effects, can reduce symptoms of MS in patients with a change in their inflammatory factors level. In this study, 50 MS patients who were referred to the MS Society of Markazi Province were randomly selected. All patients were treated with routine MS treatment (interferon) and were divided into control (25 placebo recipients) and treatment (25 recipients of 3 mg melatonin per day for 24 weeks) groups. Anthropometric data of patients including height, weight, and age were determined. Blood samples were collected after fasting in order to determine serum levels of interleukin 1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α). Then, samples were immediately centrifuged for serum separation and sera were transferred to a freezer at -80°C and serum levels of these factors were determined; using ELISA kit. The results of this study showed that there was no significant difference between the control and treatment groups in terms of serum levels of TNF-α. However, the level of IL-1ß was significantly reduced in the treatment group compared to the control group, indicating that melatonin decreases this inflammatory substance. Our findings suggest a valuable strategy in the treatment of patients who suffer from MS.

Epidural administration of neostigmine-loaded nanofibers provides extended analgesia in rats.

BACKGROUND: In this study, neostigmine-loaded electrospun nanofibers were prepared and then their efficacy and duration of analgesic action were studied after epidural administration in rats by repeated tail flick and formalin tests. METHODS: The neostigmine poly vinyl alcohol (PVA) nanofibers were fabricated by electrospinning methods. The nanofibers (1 mg) were injected into the lumbar epidural space (L5-L6) of rats (n = 6). Cerebrospinal fluid samples of rats were collected 1, 5 and 24 hours after injection and then were sampled once weekly for 4 weeks. Free-neostigmine concentration was measured in the samples spectrophotometrically. Rat nociceptive responses were evaluated by repeated tail-flick and formalin tests for 5 weeks after the nanofibers (1 mg) injection. Locomotor activity of rats was measured in the open-field at the same period. RESULTS: The cerebrospinal fluid concentration of free neostigmine reached 5 µg/ml five hours after injection and remained constant until the end of the experiments. The tail-flick latency of treated rats was significantly (p < 0.01) increased and remained constant up to 4 weeks. Pain scores of the rats in both phases of formalin test were significantly (p < 0.01) reduced during the same periods, Epidural injection of the nanofibers had no effect on locomotor activity of rats in an open-field. CONCLUSIONS: Our results indicate that the neostigmine nanofibers can provide sustained release of neostigmine for induction of prolonged analgesia after epidural administration. High tissue distribution and penetration of the nanofibers in dorsal horn can increase thermal and chemical analgesia duration without altering locomotor activity in rats for 4 weeks.