1 Castor oil (2 ml orally) produced copious diarrhoea in rats 3 h after its administration. 2 Pretreatment (intraperitoneal, i.p.) of rats with the NO synthesis inhibitors Na-nitro-L-arginine methyl ester (L-NAME, 1-25 mg kg-') and NG-monomethyl-L-arginine (L-NMMA, 2.5-100mg kg-') inhibited or prevented castor-oil-induced diarrhoea. L-Arginine (150-600 mg kg-', i.p.) administered to rats pretreated with L-NAME 10 mg kg-', drastically reduced the antidiarrhoeal activity of L-NAME in a dose-related manner. D-Arginine (900 mg kg-') did not modify the protection by L-NAME. 3 Pretreatment (i.p.) of rats with L-NAME (2.5-25 mg kg-') decreased the intestinal fluid accumulation and Na+ secretion induced by castor oil. L-Arginine (600 mg kg-') but not D-arginine (900 mg kg-') counteracted the inhibitory effect of L-NAME (10mg kg-'). 4 L-NAME (10 and 25 mg kg-) had no significant effect on the intestinal transit in normal rats or those given castor oil. 5 These results provide evidence that nitric oxide (NO) could play an important role in castor-oilinduced diarrhoea.

Palmitoylethanolamide (PEA) is an endogenous lipid mediator known to reduce pain and inflammation. However, only limited clinical studies have evaluated the effects of PEA in neuroinflammatory and neurodegenerative diseases. Multiple sclerosis (MS) is a chronic autoimmune and inflammatory disease of the central nervous system. Although subcutaneous administration of interferon (IFN)-β1a is approved as first-line therapy for the treatment of relapsing-remitting MS (RR-MS), its commonly reported adverse events (AEs) such as pain, myalgia, and erythema at the injection site, deeply affect the quality of life (QoL) of patients with MS. In this randomized, double-blind, placebocontrolled study, we tested the effect of ultramicronized PEA (um-PEA) added to IFN-β1a in the treatment of clinically defined RR-MS. The primary objectives were to estimate whether, with um-PEA treatment, patients with MS perceived an improvement in pain and a decrease of the erythema width at the IFN-β1a injection site in addition to an improvement in their QoL. The secondary objectives were to evaluate the effects of um-PEA on circulating interferon-γ, tumor necrosis factor-α, and interleukin-17 serum levels, N-acylethanolamine plasma levels, Expanded Disability Status Scale (EDSS) progression, and safety and tolerability after 1 year of treatment. Patients with MS receiving um-PEA perceived an improvement in pain sensation without a reduction of the erythema at the injection site. A significant improvement in QoL was observed. No significant difference was reported in EDSS score, and um-PEA was well tolerated. We found a significant increase of palmitoylethanolamide, anandamide and oleoylethanolamide plasma levels, and a significant reduction of interferon-γ, tumor necrosis factor-α, and interleukin-17 serum profile compared with the placebo group. Our results suggest that um-PEA may be considered as an appropriate add-on therapy for the treatment of IFN-β1a-related adverse effects in RR-MS.

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Idiopathic intracranial hypertension (IIH) is a rare neurological disorder usually affects overweight woman aged between 15 and 45 years, characterized by increased cerebrospinal fluid (CSF) pressure without clinical and radiological evidences of intracranial pathology.\ud \ud IIH is characterized by headache, occurring in more than 90 % of cases , and papilloedema. This is a self-limiting disease usually associated with a variety of medical and endocrinological conditions such as obesity, steroid withdrawal, hypothyroidism and hyperthyroidism It has also been described in patients with differentiated thyroid carcinoma on l-thyroxin replacement therapy\ud \ud We report a case of a young patient who develop IIH together with a thyroid carcinoma in absence of any treatment, clinically and biochemically euthyroid at the time of her evaluation