Dumitru Lupuliasa

Correlations Between the Monoaminergic Status and the Psychoneuroendocrine Typology in a Murine Model – Possible Biomolecular Predictions for an Individualized Pharmacotherapy

The neurons represent unique anatomical fractions, with the ability to forward the information in a network system, which justifies the experience-dependent mechanisms such as memorization, learning or consciousness. In order to fulfill these functions, the neurons are, structurally and functionally polarized. This aspect is obvious in their tripartite composition: cell body, axon and dendrites. While the body comprises the biosynthesis structure (nucleus, ribosomes, endoplasmic reticulum, Golgi apparatus and mitochondria for energy storage), the axon is equipped with molecular and under-cellular components for the propagation of the action potential from the cell body to distant targets, the dendrites represent a set of branched endings which prolong from the cell body and have as result an increase of it, in order to receive the signal. The structural connections for the signal transmission are the basis of the neural architecture. Inside the mature nervous system, normally, the neural circuit (neuroarchitecture) supports adaptive changes. Inside an old synapses neural cells can involute (until their disappearance), with simultaneous formation of new branches (new neuritis) which will establish new synapses. These changes in the neurotic and synaptic architecture prove the great plasticity (capacity) of the nervous system to adapt to the environmental conditions. Today we consider that there are two major intracellular classes of factors (signals) which adjust the neuronal development and adaptation: growth factors (the growth factor fibroblasts, the ciliary neutrophil factor, etc.) and the neurotransmitters factors (dopamine, serotonin, acetylcholine, glutamate, etc.). The loss of balance between the two systems of factors leads to the development of the pathological states.

Cardiovascular risk assessment in osteoporotic patients using osteoprotegerin as a reliable predictive biochemical marker

Osteoprotegerin (OPG), a member of the tumour necrosis factor receptor (TNFR) superfamily of proteins known to be involved in a large number of biological systems, plays a pivotal role in bone remodelling. In addition to the roles of OPG in bone metabolism, it has been reported to be associated with a high cardiovascular risk in patients with metabolic syndrome. In most cases, the exact functions of OPG remain to be established; however, the widespread expression of OPG suggests that this molecule may have multiple biological activities, mainly in the cardiometabolic environment. The aim of this study was to evaluate the value of OPG as a predictive marker for cardiovascular and metabolic risk in osteoporotic patients. The study group comprised patients with osteoporosis, in order to evaluate the association between OPG serum levels and cardiovascular pathology. Our results revealed significant correlations between classical biochemical bone and metabolic parameters, such as osteocalcin and parathyroid hormone with lipid and glucose biomarkers, sustaining the crosstalk between calcium and bone parameters and cardiovascular risk. The OPG serum level proved to have a significant and independent predictive value for metabolic syndrome (MetS) as a cardiovascular risk standard in osteoporotic patients. The OPG serum levels were increased in patients with MetS as a protective response against the atherosclerotic lesions. The serum levels of 25-hydroxy vitamin D had significant and independent predictive value for cardiovascular and metabolic risk in our subjects, sustaining the active role of vitamin D beyond the area of bone metabolism.

In Vitro Effects of Cetylated Fatty Acids Mixture from Celadrin on Chondrogenesis and Inflammation with Impact on Osteoarthritis

Objective Cetylated fatty acids are a group of naturally occurring fats of plant and/or animal origin. Cetyl myristoleate, in particular, was initially involved in osteoarthritis related research as its therapeutic administration prevented experimentally induced arthritis in Swiss Albino mice. In this context, the aim of our study was to investigate the possible mechanisms of Celadrin cetylated fatty acids action at the cellular level inflammation related pain relief and chondrogenesis. Design For this, we tested the effects of the cetylated fatty acids mixture from Celadrin on an in vitro scaffold-free 3-dimensional mesenchymal stem cells culture model of chondrogenesis. Furthermore, we treated stimulated mouse macrophage cells with the cetylated fatty acids mixture to investigate the expression profile of secreted inflammatory cytokines. Results The cetylated fatty acids mixture from Celadrin significantly decreased the production of IL-6, MCP-1, and TNF, key regulators of the inflammatory process, in stimulated RAW264.7 mouse macrophage cells. The treatment with cetylated fatty acids mixture initiated and propagated the process of chondrogenesis as demonstrated by the increased expression and deposition of chondrogenic markers by the differentiating mesenchymal cells. Conclusion The cetylated fatty acids mixture from Celadrin reduces inflammation in vitro by significantly decreasing the expression of IL-6, MCP-1, and TNF in stimulated RAW264.7 mouse macrophage cells. These compounds facilitate the chondrogenic differentiation process of human adipose-derived stem cells by stimulating the expression of chondrogenic markers under chondrogenic induction conditions.

Murine Models for Developping an Individualized Neuropsychopharmacotherapy Based on the Behaviour Typology

A drug administered in the same dosage, under similar conditions, to adult individuals from a population homogeneous in race, gender and age, triggers different pharmacological effects. This phenomenon represents the pharmacological variability in a relatively homoge‐ neous population, as a natural expression of the biological variability of the response to any stimulus. The cause of the pharmacological variability to a drug is often considerably differ‐ ent between the individuals of the same population. The pharmacology variability (pharma‐ cokinetics, pharmaco-dynamics and pharmaco-toxicological) is therefore of two types: interindividual (on population level) and, respectively, intra-individual (on individual level).