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- Volume 7, Issue 10, 2001
Current Pharmaceutical Design - Volume 7, Issue 10, 2001
Volume 7, Issue 10, 2001
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New Issues about Nitric Oxide and its Effects on the Gastrointestinal Tract
Authors: M.J. Martin, M.D. jimenez and V. MotilvaOver 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, and 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 reparing 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 the clinical utility of NO-donors.
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New Issues About Melatonin and its Effects on the Digestive System
Authors: V. Motilva, J. Cabeza and C. La LastraIn human beings, melatonin is secreted in a cyclic way by the pineal gland, although it has been detected in other tissues. Synthesis of melatonin takes place in the pinealocyte. It depends on adrenergic stimulation, and its secretion is related to the photoperiod in a circadian model of low activity during light phase and high activity at night time Former studies aimed to establish the mechanisms by which melatonin carries out its biological function, proved the existance of high affinity binding sites. However, melatonin can pass through the plasmatic membrane this property suggested a possible activity of the hormone inside the cell trough activation of nuclear receptors. Moreover, melatonin can act by itself as a potent oxygen-free-radical scavenger, which renders it a very strong antioxidant. It is currently accepted that melatonin plays an important role in numerous physiological processes. The gastrointestinal tract of numerous animal species contains melatonin, which is synthesized essentially by intestinal enterochrommaffin cells. Some investigations have revealed that its liberation follows also a circadian rhythm, although its secretion pattern might be influenced by nutritional factors. Receptors for melatonin have been identified in the digestive system, therefore the indolamine might play a leading role in different aspects of the vast digestive physiopathology. The hormone may interact with receptors and subsequently stimulate the synthesis of gastroprotective hormones and also exerts a direct defense on the epithelium, enhances submucosal blood flow and prevents the damage induced by ischemia followed by reperfusion. Moreover, studies have shown that treatment with melatonin reduces the severity of the lesions induced by NSAIDs on gastric mucosa suggesting a beneficial role of melatonin in preventing this gastropathy related to antiinfammatories.
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Mediterrranean Diet and Health Biological Importance of Olive Oil
Authors: C. La Lastra, M.D. Barranco, V. Motilva and J.M. HerreriasOlive oil, the main fatty component of the Mediterranean diet, is characterized by consisting of monounsaturated fatty acids as well as by its elevated content in antioxidant agents. This oil exhibits numerous biological functions which are beneficial for the state of health. A diet rich in monounsaturated fatty acids provides an adequate fluidity to the biological membranes, diminishing the hazard of dants present in olive oil are able to scavenge free radicals and afford an adequate protection against peroxidation. Regarding the heart, olive oil decreases the plasmatic levels of LDL-cholesterol and increases those of HDL-cholesterol, hence diminishing the risk of suffering from heart complaints. In this context, it has been suggested that increased consumption of monounsaturated fatty acids in place of polyunsaturated fatty acids will render circulating lipoproteins less sensitive to peroxidation and thereby diminish the development of atherosclerosis. Olive oil has also been proven to contribute to a better control of the hypertriglyceridemia accompanying diabetes and may reduce the risk of breast cancer and colorectum. On the other hand, several investigations have suggested that olive oil can be beneficial in inflammatory and autoimmune diseases, such as rheumatoid arthritis. In this sense, some reports have indicated that olive oil modifies inflammatory cytokines production. As for the digestive system, olive oil enhances gallbladder emptying consequently reducing cholelithiasis risk, decreases the pancreatic exocrine secretion and gastric secretory function in response to food. Finally, it has been demonstrated that a diet rich in olive oil is associated with a high percentage of gastric ulcer healing and affords a higher resistance against non steroidal antiinflammatory drugs-induced gastric ulcerogenesis.
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Antiinflamatory Agents Less Dangerous for Gastrointestinal Tract
Authors: M. Rodriguez-Tellez, F. Arguelles, J.M. Herrerias Jr., D. Ledro, J. Esteban and J.M. HerreriasNSAIDs represent one of the most commonly used therapeutic drug groups worldwide. 1.5percent of the world population is estimated as taking NSAIDs. However, their use is not risk free and gastrointestinal (GI) lesions do appear, which is indeed the main reason for their toxicity. Frequently (50percent) NSAID-induced GI-Lesions are asymptomatic, 71percent of GI perforations and 50percent of upper gastric hemorrhages (UGH) are associated with taking NSAIDs How frequent GI lesions appear is directly related to whether the patient is in a risk group or not. Factors increasing the risk of GI lesions occurring are the following: being older than 60, using corticoids or other NSAIDs concomitantly, having a history of duodenal ulcer, alcohol consumption, smoking or taking oral anticoagulants. As the toxicity and how frequent the lesions appear depend on which drug is used, there is a need for research into new drugs which are both clinically effective and safer to use.GI toxicity of NSAIDs is mediated by two mechanisms, direct toxicity and prostaglandin synthesis inhibition or sistemic mechanism. Due to the relatively recent discoveries concerning the physiopathology of inflammation and gastric physiology, research into new NSAID derivatives is taking place. Such derivatives are prodrugs, galenic buffer forms, selective COX-2 inhibitors, isomeric compounds, NO-donors, and as a future possibility, phosphodiesterase inhibitors.
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Volumes & issues
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Volume 30 (2024)
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Volume 29 (2023)
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Volume 28 (2022)
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Volume 27 (2021)
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Volume 26 (2020)
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Volume 25 (2019)
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Volume 24 (2018)
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Volume 23 (2017)
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Volume 22 (2016)
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Volume 21 (2015)
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Volume 20 (2014)
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Volume 19 (2013)
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Volume 18 (2012)
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Volume 17 (2011)
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Volume 16 (2010)
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Volume 15 (2009)
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Volume 14 (2008)
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Volume 13 (2007)
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Volume 12 (2006)
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Volume 11 (2005)
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Volume 10 (2004)
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Volume 9 (2003)
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Volume 8 (2002)
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Volume 7 (2001)
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Volume 6 (2000)