Vanessa A. Areco

New perspectives in melatonin uses

This review summarizes the metabolism, secretion, regulation and sites of action of melatonin. An updated description of the melatonin receptors, including their signal transduction mechanisms, distribution and characterization of receptor genes, is given. Special emphasis is focused on the clinical aspects and potential uses of melatonin in the sleep-wake rhythms, in the immune function, in cancer therapy, in neuroprotection against oxidative damage and antioxidant activities in different tissues. Finally, combined effects of melatonin with other drugs are discussed.

Terpenes: Natural Products for Controlling Insects of Importance to Human Health—A Structure-Activity Relationship Study

Many insects affect food production and human health, and in an attempt to control these insects the use of synthetic insecticides has become widespread. However, this has resulted in the development of resistance in these organisms, human diseases, contamination of food, and pollution of the environment. Plants natural products and essential oil components such as terpenes and phenylpropenes have been shown to have a significant potential for insect control. However, the molecular properties related to their insecticidal activity are not well understood. The purpose of this review is to provide an overview of the toxicity of terpene compounds against three insects of importance to human health: lice, cockroaches, and Triatominae bugs and to evaluate which molecular descriptors are important in the bioactivity of terpenes. For the insects studied, quantitative structure-activity relationship (QSAR) studies were performed in order to predict the insecticidal activity of terpene compounds. The obtained QSAR models indicated that the activity of these compounds depends on their ability to reach the targets and to interact with them. The QSAR analysis can be used to predict the bioactivities of other structurally related molecules. Our findings may provide an important contribution in the search for new compounds with insecticidal activity.

Melatonin not only restores but also prevents the inhibition of the intestinal Ca2 + absorption caused by glutathione depleting drugs

We have previously demonstrated that melatonin (MEL) blocks the inhibition of the intestinal Ca(2+) absorption caused by menadione (MEN). The purpose of this study were to determine whether MEL not only restores but also prevents the intestinal Ca(2+) absorption inhibited either by MEN or BSO, two drugs that deplete glutathione (GSH) in different ways, and to analyze the mechanisms by which MEN and MEL alter the movement of Ca(2+) across the duodenum. To know this, chicks were divided into four groups: 1) controls, 2) MEN treated, 3) MEL treated, and 4) treated sequentially with MEN and MEL or with MEN and MEL at the same time. In a set of experiments, chicks treated with BSO or sequentially with BSO and MEL or with BSO and MEL at the same time were used. MEL not only restored but also prevented the inhibition of the chick intestinal Ca(2+) absorption produced by either MEN or BSO. MEN altered the protein expression of molecules involved in the transcellular as well as in the paracellular pathway of the intestinal Ca(2+) absorption. MEL restored partially both pathways through normalization of the O2(-) levels. The nitrergic system was not altered by any treatment. In conclusion, MEL prevents or restores the inhibition of the intestinal Ca(2+) absorption caused by different GSH depleting drugs. It might become one drug for the treatment of intestinal Ca(2+) absorption under oxidant conditions having the advantage of low or null side effects.

Past, Present, and Future of Melatonin’s Clinical Uses

Melatonin (MEL) is a pleiotropic hormone which exerts its action through different mechanisms, either by binding to its receptors or by acting as an antioxidant molecule and ROS scavenger. Its mechanisms of action together with the wide distribution of MT1 and MT2 receptors have provoked an ever-increasing number of clinical trials in the last two decades. These studies have evaluated the exogenous administration of MEL in different doses and formulations to prevent or to treat many health disorders. The predominant field of research has been the treatment of insomnia and other circadian rhythm disorders due to the confirmed resynchronizing properties of this indolamine. However, in the last decade, a profound interest has arisen concerning its potential therapeutic value in different conditions such as cancer, cardiovascular diseases, gastrointestinal problems, and inflammatory states, among others. The relatively low toxicity of MEL over a wide range of doses has made the research even more promising. However, new multicenter clinical trials could shed light on different aspects of MEL’s clinical uses contributing thus to clarify the conditions in which MEL might be considered as a first-line therapeutical strategy and to identify when the combination of MEL with other drugs is necessary. In this chapter, we revise the milestones in the field of MEL research from its discovery to the present time and analyze the future perspectives of its clinical uses.

Melatonin, Gastrointestinal Protection, and Oxidative Stress

Abstract We have tried to summarize the actions of melatonin (MEL) in different organs of the gastrointestinal tract (GIT) and the potential usefulness as a drug to ameliorate or cure a variety of gastrointestinal disorders. A brief description of MEL receptors and their localization throughout the GIT is also presented. Analyses of experimental and clinical trials for healing or protection of gastrointestinal disorders, such as reflux esophagitis, peptic ulcers, ulcerative colitis, intestinal ischemia/reperfusion, and others, are performed. Finally, the effects of MEL treatment on the intestinal Ca2+ absorption under conditions of oxidative stress are discussed.

Melatonin: Basic and Clinical Aspects

Melatonin (MEL), the “hormone of darkness,” is an indolamine mainly secreted at night by the pineal gland. It is also synthesized by other tissues, being the enterochromaffin cells the most important extrapineal sites. The ubiquity, pleiotropy, and complexity are the three terms that summarize the properties and actions of MEL. Two well-characterized enzymes participate in its synthesis: N-acetyltransferase, the first-rate limiting enzyme in MEL production, which converts serotonin to N-acetylserotonin (NAS), and hydroxyindole-O-methyltransferase, which converts NAS to MEL. Most of the MEL’s actions are mediated by membrane (MT1 and MT2) and nuclear (ROR/RZR) receptors. However, some MEL effects seem to be independent of the involvement of receptors or related to Ca2+-binding proteins. The signal transduction pathways triggered by MEL involve the AC/cAMP/PKA/CREB, phospholipase C (PLC)-β and PLC-η, and Rafs/MEK1/2/ERK1/2 cascades. MEL participates in the circadian rhythms, the modulation of season changes, in reproduction, as well as an antioxidant, antiapoptotic, anti-inflammatory, oncostatic, and anticonvulsant drug. Exogenous MEL is employed in a number of physiopathological conditions, mainly for the treatment of sleep disorders and jet lag. The antioxidant properties of MEL have been proven to be beneficial to patients with rheumatoid arthritis, females with infertility, elderly patients with primary essential hypertension, and multiple sclerosis patients. The spectrum of the uses of MEL seems to be wide, although more investigation is needed in order to know better the molecular mechanisms and the possible side effects.

Melatonin: A protective hormone of intestinal calcium absorption?

Introduction: Osteogenesis distraction (DO) is a surgical technique that allows distraction of the fracture callus. It has been used extensively in endochondral long bones but not in the craniofacial skeleton of endomembranous origin. Mandibular alveolar bone of endomembranous origin contains teeth sockets; it is a functional bone that undergoes bone turnover at a higher rate than other bone tissues. The aim of our work was to present the development of an experimental model of DO in rat mandibular alveolar bone including all stages, i.e. animal procedures, laboratory determinations, histological procedures and histomorphometric measurements. Methods: 8 Wistar rats, 80 g bw, underwent extraction of all mandibular molars. At 400 g bw, right hemimandibular osteotomy was performed and the device was placed. After 6 days (latency) it was activated (0.175 mm/d once a day/ 6 days) and then left in place 28 days (consolidation phase). Rats were sacrificed and hemimandibles were resected. The technique was standardized to perform radiographs and hemimandible orientation was adjusted to allow obtaining comparable histologic sections. A method to record and compare these measurements was designed. H&E stained mesiodistally oriented hemimandible sections were obtained. Screw loosening and loss of the device during the consolidation phase were initial problems (SAIO, 2008). The original design was perfected to avoid mobility. Results: The new, improved device remained in place throughout the experiment. Comparable mesiodistally oriented sections were obtained. Conclusion: This experimental model of mandibular DO will allow studying the cellular and molecular events that take place during DO under different experimental conditions. This article is part of a Special Issue entitled AAOMM 2010 Abstracts.