ALZHEIMER'S DISEASE - ESTROGENS AND SELECTIVE ESTROGEN RECEPTOR MODULATORS, FRIENDS OR FOES?

Alzheimer's disease(AD) is the leading cause of dementia and is characterized by the presence of extensive plaque deposition and neurofibrillary pathology. The aim of the present study was to make an update regarding the influence of estrogens and SERMs on inflammation and on the resolution of inflammation, respectively, focusing on these most important features implicated in the pathophysiology of AD. Several hypothesised mechanisms of action of estrogens and SERM are exposed and also some relevant clinical studies on this subject are analysed. The analyzed studies have a high heterogeneity of preparations used, of administration routes, of the female population included and of the periods of time from the appearance/induction of menopause to the therapeutic intervention and also of follow-up periods of patients and of the means of evaluating their cognitive decline. One can say that all the ways of pharmacological influence on the membrane or intracellular signalling system associated to estrogens that may have clinical importance in the prevention and possibly in the treatment of AD have not been exhausted. Estrogens with selective ERα or G protein-coupled estrogen receptors (GPER1 or GqMER) effects could be used to influence the resolution of inflammation process, with positive effects on AD evolution.

Cannabinoid system and cyclooxygenases inhibitors.

RATIONALE: The cannabinoid system consists of a complex array of receptors, substances with agonist/antagonist properties for those receptors, biosynthetic machineries and mechanisms for cellular uptake and degradation for endocannabinoids. This system is in interrelation with other systems that comprise lipid mediators like prostaglandins/leukotrienes systems. A clear antagonist, additive or synergic effect of nonsteroidal anti-inflammatory drugs (NSAIDs)-cannabinoid associations was not yet demonstrated. Aim. The present study tried to summarize the existent data on NSAIDS-cannabinoid system interactions. METHODS AND RESULTS: A bibliographic research in Medline, Scirus, Embase was made using as keywords cannabinoid, nonsteroidal anti-inflammatory drugs, aspirin, ibuprofen, flurbiprofen, diclofenac, indomethacin, acetaminophen, coxibs, antinociceptive, antinociception, analgesia DISCUSSIONS: A systematization of the results focusing on the NSAIDs drugs interaction with the cannabinoid system was presented. Out of all the substances analyzed in the present review, acetaminophen was studied the most regarding its interferences with the cannabinoid system, mainly due to contradictory results. CONCLUSIONS: Some NSAIDs have additional influences on the cannabinoid system either by inhibiting fatty acid amide hydrolase (FAAH) or by inhibiting a possible intracellular transporter of endocannabinoids. All the NSAIDs that inhibit COX2 can influence the cannabinoid system because a possible important degradative pathway for anandamide and 2-arachidonoyl glycerol might involve COX 2. One of the causes for the variety of experimental results presented might be due to pharmacokinetic mechanisms, depending on the route of administration and the dose

VEGF-induced corneal neovascularisation in a rabbit experimental model.

INTRODUCTION AND PURPOSE: Various conditions may cause vascularization of the normally avascular cornea. The aim of the present study was to create a reproducible experimental model that could enable the investigation of the phenomena leading to corneal vascularization. This involved creating a software to record the experimental data, enabling a subsequent digital analysis based on the growth models. The VEGF-induced pattern of neovascularization was also investigated. MATERIAL AND METHODS: Twenty-seven rabbits divided in groups were used for the purposes of the present study. Some of them underwent intracorneal implants with or without vascular endothelial growth factor (VEGF) pellets, using an original microsurgical technique. Central and peripheral corneal burns were induced to other groups of animals in order to mimic the neovascularization process induced by inflammation. Finally, Dexamethasone (Maxidex) was given intraocularly, on days 1 and 3 after the onset of neovascularisation, in rabbit groups with both corneal burns and VEGF-implants. Video recording and data analysis of the corneal vascularization were made with an advanced biomicroscope, a computerized imaging system and a special software. A histochemical study of the animals' eyes was also carried out. RESULTS AND DISCUSSION: The recorded data showed the simplicity and reproducibility of the present experimental model. The results showed the importance of VEGF as an initiator and promoter of corneal vascularization through a non-inflammatory mechanism, quite different from the inflammation illustrated by the corneal burn. At the same time, Dexamethasone therapy proved its effectiveness in corneal angiogenesis induced by thermal burn, but not by VEGF-implant.

Beta 3 adrenergic receptors: molecular, histological, functional and pharmacological approaches.

Different classes of receptors mediate norepinephrine and epinephrine effects, one of the most recently discovered being the beta 3 adrenergic ones. The paper has proposed itself to present the history of the discovery of beta 3 adrenergic receptors, different techniques for their identification, their structure, localization, genetic data and also the mechanism of regulation of their functions. It also contains an exhaustive approach regarding the histological localization and functions of beta 3 adrenergic receptors in different apparatus and systems, making evident their effect on glucidic, lipidic and energetic metabolism. The substances that influence beta 3 adrenergic receptors activities, especially the agonists, have been studied regarding their practical applications in the treatment of diabetes mellitus and of the disturbances of lipid metabolism.

Influencing vascular reactivity in vivo by histaminergic agonists and antagonists.

The eye is a target organ for the action of several topical or systemic drugs. The aim of the present study is to analyze the differences in reactivity between the iris and conjunctiva vessels after the topical administration of histamine and histamine receptor blockers respectively. Using a novel non-invasive technique for the quantification of the vascular diameters in the eye vessels, the response of these vessels to histamine, to H1 receptor blocker promethazine, and to H2 receptor blocker ranitidine versus vehicle (control) was analyzed. The results show differences in reactivity between iris and conjunctiva vascular territories. This data suggest that the population of histamine receptors differs between these two vascular areas.

[Effects of serotonin on reactivity of ocular vasculature]. / Efectele serotoninei asupra reactivitatii vasculare oculare.

INTRODUCTION: Serotonin presents specific receptors of many types and subtypes. The aim of this study was to analyze the differences in reactivity between the vessels (arteries and veins) of the iris and conjunctiva. The vascular diameter was measured using a noninvasive technique after intraocular administration of different doses of serotonin. MATERIAL AND METHODS: The tests were performed on rats, divided in control and study groups. The modifications of studied vessels' diameters before and after topical administration of the solutions were evaluated by measuring these diameters at fixed time intervals of 30 seconds, for 6 minutes. Differentiation between arteries and veins was made using topical administration of felodipine after the testing 6 minutes interval The statistical significance of differences between the values obtained in each interval of 30 seconds and the control values at the initial moment was evaluated using t-test, the "paired" variant. RESULTS: There were obtained differences in reactivity between iris and conjunctival vessels and between iris arteries and veins for the different concentrations of tested serotonin solutions. CONCLUSIONS: Iris and conjunctival vessels contain serotonin receptors with different types and densities, whose activation produced vasoconstriction in both territories, but with different evolution and intensity. Differences in reactivity were found between iris arteries and veins, probably due to a different density of receptors between those two territories. The different vascular response might be a protective mechanism against dissemination of conjunctival infections.