PSYCHOPHARMACOLOGIC TARGETS IN PERSONALIZED PSYCHIATRY

The advances made on genetic influence on response and side effects of psychiatric pharmacotherapy improved the concept of personalized psychiatry. The current evidence suggests that testing can be useful in patients who did not respond or tolerate at least one previous pharmacotherapy. Approximately 90% of all drugs are metabolized by only few different cytochrome enzymes. Pharmacogenetic research has provided important evidence of CYP functional polymorphisms in psychiatric treatment, with numerous studies associating their presence with the variability observed in response to treatment. The study of candidate genes involved in the pharmacokinetics of antidepressants has provided sufficiently strong scientific evidence for clinical applications. These genes encode the cytochrome P450 enzymes and are responsible for the metabolism of antidepressants. Pharmacogenetic testing is thus becoming a useful and increasingly useful tool for antidepressant pharmacotherapy. The efficacy of antidepressant action has been associated with several polymorphisms, located on the gene encoding proteins considered to be involved in the various mechanisms of action of antidepressant treatments

GENETIC VARIABILITY OF PHARMACOKINETICS AND PHARMACODYNAMICS OF ANALGESICS (LAYERED MEDICINE)

Pain therapy, the most widely spread disorder, tends more as other diseases, to administration of drug molecules targeted to the affected tissue at the right dose, or to the patient or patient groups (personalized medicine). A decisive determinant of this strategy is the genetic one, which is to some extent the basis of the variability of pharmacokinetic and pharmacodynamic response to analgesics in the patient population. The differences in action and response to analgesics are due in these cases to hyperfunctional or nonfunctional uni-nucleotide gene polymorphisms encoding enzyme-modified transport proteins or receptors involved in the biotransformation and dynamics of analgesics. Genomic testing increases therapeutic efficacy and avoids adverse effects especially in patients with long-term therapies.   &nbsp

GENETIC VARIABILITY OF PHARMACOKINETICS AND PHARMACODYNAMICS OF ANALGESICS (LAYERED MEDICINE)

Pain therapy, the most widely spread disorder, tends more as other diseases, to administration of drug molecules targeted to the affected tissue at the right dose, or to the patient or patient groups (personalized medicine). A decisive determinant of this strategy is the genetic one, which is to some extent the basis of the variability of pharmacokinetic and pharmacodynamic response to analgesics in the patient population. The differences in action and response to analgesics are due in these cases to hyperfunctional or nonfunctional uni-nucleotide gene polymorphisms encoding enzyme-modified transport proteins or receptors involved in the biotransformation and dynamics of analgesics. Genomic testing increases therapeutic efficacy and avoids adverse effects especially in patients with long-term therapies.   &nbsp

Molecular docking study on the potency of glycosaminoglycans (GaGs) as co-activators of fibroblasts proliferation and differentiation

Fibroblast growth factors (FGF) are heparin-binding polypeptides that control differentiation, growth and migration of many cell types. The signaling in the FGF pathway implies the dimerization of their corresponding cell surface receptors and consequently their activation through autophosphorylation of their cytoplasmatic domains. This process is modulated by heparan-sulfates (HS) or heparan-sufate-proteoglycans (HSPG) present in great abundance on cell surfaces. Different aspects of this modulation were a matter of debate in the last years in the field literature and some of them still remains unclear. The present study is trying to give some answers to a part of these problems by using quantitatively physical theoretical models of the molecules involved in these processes. We aimed to explain, through the aid of molecular docking techniques, the experimental findings about the activation of FGF receptors by small saccharides (di- and tetrasaccharides) and as a result we propose a model for this process. Also, the findings resulted from docking experiments of longer oligosaccharides (hexa- and octasaccharides) offer insights about the stoichiometry of the receptorial complex, supporting a (2:2:2)FGF:FGFR:HS ratio scheme rather than a (2:2:1)FGF:FGFR:HS one, in accordance with recent experiments on the subject published in the literature

A semiquantitative analysis technique regarding immunohistochemical detection for matrix metalloproteinases

Modern image processing techniques are used today in order to evaluate immunohistochemical detection for various markers, especially those important for malignant tumor diagnosis and remodeling processes. Evaluating the immunohistochemical markers detection may be completed by a quantitative analysis. We have used samples of normal and fibrous tissue from surgical scars harvested after 2 months from surgery. We have investigated the immunohistochemically marked areas and we have performed a semiquantitative image analysis, using an academic, open sourcesoftware, ImageJ v. 1.38. After image adjustments (binarization) and correction, we have applied a deconvolution filter after which we have performed and analyzed a histogram of the selected area. The binarized areas were measured and compared for three samples of each tissue. We have followed the semiquantitative analysis of MMP-2 and MMP-9 presence on the investigated samples. This technique, even if controversial, allows us a fast analysis of common markers detected by immunohistochemistr

NEW MOLECULES USEFUL IN THE MIGRAINE TREATMENT

Migraine is a neurovascular condition characterized by episodes of severe headache with inter-individual variability. Inflammation of neurogenic origin contributes to the mechanism of occurrence of migraine and other primary headaches. Neurovascular headache is a condition in which neural events have as a result dilation of blood vessels and the appearance of painful sensation. CGRP (calcitonin-gene-related peptide) is a neuropeptide widespread both in the central and peripheral nervous system, being one of the most potent vasodilator substances with important role in controlling blood pressure in both normal and abnormal conditions. The releasing of perivascular peptides relaxes cerebral arteries while stimulating cAMP accumulation or release of EDRF (endothelium derived relaxing factor). An alternative to acute treatment of migraine used so far is the CGRP receptor blockade with selective antagonists. They represent potential therapeutic molecules with superior advantages to triptans and a longer duration of action