Neuroprotection by nitric oxide against hydroxyl radical-induced nigral neurotoxicity

We investigated the effects of nitric oxide on an in vitro and in vivo generation of hydroxyl radicals, and in vivo neurotoxicity caused by intranigral infusion of ferrous citrate in rats. The formation of hydroxyl radicals in vitro, without exogenous hydrogen peroxide, was dose-dependent. Some nitric oxide donors (e.g. sodium nitroprusside) stimulated, while others (nitroglycerin, diethylamine/nitric oxide, nitric oxide in Ringer's solution) suppressed hydroxyl radical generation in vitro. A significant increase in extra-cellular hydroxyl radicals was detected in a brain microdialysis study. Intranigral infusion of ferrous citrate caused long-lasting lipid peroxidation and dopamine depletion in the ipsilateral nigral region and striatum, respectively. Sub-acute dopamine depletion in the striatum was positively correlated with acute lipid peroxidation in substantia nigra. Intranigral administration of nitric oxide did not affect striatal dopamine. Interestingly, nitric oxide in Ringer's protected nigral neurones against the oxidative injury. The results demonstrate that a regional increase in the levels of iron can result in hydroxyl radical generation and lipid peroxidation leading to neurotoxicity. It also demonstrates that exogenous nitric oxide can act as hydroxyl radical scavenger and protect neurones from oxidative injury.     

Practical aspects of management of recurrent aphthous stomatitis

Treatment of recurrent aphthous stomatitis (RAS) remains, to date, empirical and non-specific. The main goals of therapy are to minimize pain and functional disabilities as well as decrease inflammatory reactions and frequency of recurrences. Locally, symptomatically acting modalities are the standard treatment in simple cases of RAS. Examples include topical anaesthetics and analgesics, antiseptic and anti-phlogistic preparations, topical steroids as cream, paste or lotions, antacids like sucralfate, chemically stable tetracycline suspension, medicated toothpaste containing the enzymes amyloglucosidase and glucoseoxidase in addition to the well-known silver nitrate application. Dietary management supports the treatment. In more severe cases, topical therapies are again very useful in decreasing the healing time but fail to decrease the interval between attacks. Systemic immunomodulatory agents, like colchicine, pentoxifylline, prednisolone, dapsone, levamisol, thalidomide, azathioprine, methotrexate, cyclosporin A, interferon alpha and tumour necrosis factor (TNF) antagonists, are helpful in resistant cases of major RAS or aphthosis with systemic involvement.     

An update on Behçet''s disease

Behçet's disease (Adamantiades‐Behçet's disease, ABD) is a multisystemic inflammatory disease, the pathogenesis of which is still a mystery. Many questions are still to be answered and the available diverse data need to be brought together to be compared and analysed. There is at least consensus on the effect of possible, but currently unknown, environmental triggering factor(s) against a background of genetic susceptibility. The possible aetiological factors form a broad spectrum, with infectious agents being the most probable ones. Whatever the stimulus is, the target tissue seems to be the small blood vessels, with various consequences of either vasculitis and/or thrombosis in many organ systems. The endothelium seems to be the primary target in this disease; however, it may just be the subject of the bizarre behaviour of the immune system. The diverse existing data could be interpreted in favour of either explanation. A similar confusion exists about the thrombotic tendency in Adamantiades‐Behçet's disease, in terms of whether a primary hypercoagulability is present or whether it is secondary to inflammation. Recent interesting immunological data promise a way out of the existing dilemma. These findings will be outlined within the context of possible hypotheses and attention will be paid to further investigations that are needed.     

Comparative localization of neurotensin receptors on nigrostriatal and mesolimbic dopaminergic terminals

Neurotensin (NT), a brain-gut peptide, possesses many biological actions similar to those reported for neuroleptics. Moreover, it has been shown that NT alters dopaminergic activity of both nigrostriatal and mesolimbic pathways. We now report that NT receptors are located on dopaminergic cell bodies in both systems. However, the proportion of NT receptors on presynaptic dopaminergic terminals appears to be different. NT receptor sites are mainly found on presynaptic dopaminergic terminals in the caudate-putamen while they are pre- and post-synaptically located in the nucleus accumbens and the olfactory tubercule. NT receptors differential localization in these two pathways could be used as a model to study the comparative physiology of various dopaminergic brain systems.