Over the last years the important role of nitric oxide (NO) as endogenous modulator of numerous physiological functions has been shown. NO is involved in the regulation of blood flow, maintenance of vascular tone, control of platelet aggregation, and modulation of the activity of the mastocytes. It also plays a key role as neurotransmitter in the central and peripheric nervous system (non adrenergic non colinergic, NANC, neurons), in the nervous control of the cerebral blood flow and in the neuroendocrine regulation or synaptic plasticity. However, NO shows a dual behavior: at physiological concentrations, released through the constitutive synthase (cNOS), it regulates house-keeping functions, whereas its overproduction by the inducible isoenzyme (iNOS) exhibits cytotoxic activity because interacting with reactive species producing peroxinitrites (ONOO) and other compounds, which are highly damaging for the tissues. In the gastrointestinal tract (GIT) NO participates in the modulation of the smooth musculature tone, such as the regulation of intestinal peristaltism, gastric emptying and antral motor activity. It also regulates acid and gastric mucus secretion, alkaline production, and is involved in the maintenance of mucosal blood flow. In physiological conditions, NO acts as an endogenous mediator modulating both, the repairing and integrity of the tissues, and exhibits gastroprotective properties against different types of aggressive agents. However, high concentrations of NO are related to numerous pathological processes of GIT including peptic ulcer, chronic gastritis, gastrointestinal cancer, bacterial gastroenteritis, celiac or chronic inflammatory bowel diseases. Recently, this hypothesis that cNOS is always beneficial and iNOS is always deleterious, has been questioned, since that a series of data suggest that the increase of cNOS activity could be responsible for the derived pathological changes and, by contrast, NO liberated by the inducible isoenzyme might play a repairing effect in certain pathological disorders. The pharmaceutical industry is really interested in proving the clinical benefits of the mediator. Numerous NO-donor drugs, nitrate derivatives, have been frequently used in the cardiovascular diseases due to their vasodilating properties, which allow an enhancement of coronary blood flow. More recently, the protective effect of NO against non steroidal antiinflammatory drugs (NSAID)-gastroenteropathy has been shown, because its vasodilating and antioxidant properties render it a potentially useful agent. Different NSAID, including acetyl salicylic acid, diclofenac or naproxen, have been formulated by attaching a NO releasing-moiety. These NO-NSAID, antiinflammatories combined with precursors of the mediator, or with inhibitors of the inducible synthase, are currently being evaluated. However, although the pharmacotherapeutical possibilities of NO are considerable, it is necessary to elucidate the exact mechanisms derived from stimulation/inhibition of the isoenzymes in order to determine th...

A residual mud sample from the marigold flower dehydration process was screened and 19 putative colonies were isolated for their ability to degrade lutein in a chemically defined medium supplemented with marigold flower flour as a carbon source. Among the colonies isolated, two generated volatile compounds in fermentation and one was chosen for further study for its ability to produce a strong tobacco smell. This colony contained two microorganisms, identified as Geotrichum sp. and Bacillus sp. The aroma production requires the presence of both microorganisms and lutein. Using gas chromatography coupled to mass spectrometry (GC/ MS), four compounds were identified: 7,8-dihydrobeta-ionol, beta-ionone, 7,8-dihydro-beta-ionone, and 3-hydroxy-beta-ionone, in proportions of 84.2%, 9.4%, 3.5%, and 2.9%, respectively.

Polyphenolic compounds from green tea have great interest due to its large CONSUMPTION and therapeutic potential on the age-associated brain decline. The current work compares a similar dose regimen of a whole-green-tea extract and catechin in old rats over the course of 36 days. Results showed a significant improvement in visuo-spatial working memory and episodic memory of old rats after polyphenolic compounds administration assessed by behavioral tests. No effects were observed on the age-associated motor coordination decline. Statistically, results were correlated with significant improvements, mainly in hippocampal and striatal noradrenergic and serotonergic systems, but also with the striatal dopaminergic system. Both polyphenolic treatments also reverted the age-associated reduction of the neuroinflammation by modulating protein sirtuin 1 (SIRT1) expression in hippocampus, but no effects were observed in the usual reduction of the histone-binding protein RBAP46/48 protein linked to aging. These results are in line with previous ones obtained with other polyphenolic compounds, suggesting a general protective effect of all these compounds on the age-associated brain decline, pointing to a reduction of the oxidative stress and neuroinflammatory status reduction as the leading mechanisms. Results also reinforce the relevance of SIRT1-mediated mechanism on the neuroprotective effect and rule out the participation of RBAP46/48 protein.

It has been proposed that neutrophil and oxygen dependent microvascular injuries may be important prime events in gastrointestinal (GI) toxicity of non-steroidal antiinflammatory drugs (NSAIDs). L-arginine (L-ARG) is an essential amino acid which participates in many important biochemical reactions associated to the normal physiology of the organism. In these experimentations, we studied the role of L-ARG, aminoacid precursor of NO synthesis, on ibuprofen (IB) induced gastric lesions, and also on the inflammatory and oxidative mechanisms related to mucosal damage. Oral administration of IB (100 mg kg(-1)), produced severe damage on gastric mucosa, which was more important after 6 h test-period, and was accompanied by a significant increment in myeloperoxidase (MPO) activity, as index of neutrophil activation, as well as lipid peroxidation (LP) levels and xanthine oxidase (XO) activity. However, no changes were observed in total mucosal glutathione (tGSH), nor glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activity. Simultaneous treatment with equimolar doses of L-ARG (oral and i.p.), considerably reduced the number and intensity of lesions, and at the same time (6 h) the maximum protection was also observed. In addition, L-ARG inhibited the IB-induced LP and XO enhancement, but did not produce changes in leukocyte infiltration, tGSH, GSH-Px and SOD activity. These findings suggest that (1) L-ARG protective effect on gastric mucosa against IB-induced mucosal lesions could be explained by a local effect and also might be due to the systemic action of the aminoacid; (2) the active oxygen species, derived both from XO and activated neutrophils, could play a role in the pathogenesis of gastric injury induced by IB, (3) L-ARG exhibit a protective effect against IB-induced mucosal damage, probably through the inhibition of oxidative stress derived via xanthine-XO, but it does not block the oxygen free radical production through polymorphe nuclear leukocytes.

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