Antioxidant activity in rat models of nociceptive stress.

UNLABELLED: Pain is an important problem and has been the subject of many studies in recent years. MATERIAL AND METHOD: The present study has investigated the response of the antioxidant defense systems in contention stress, which mimics nociceptive stress. Contention stress was made by immobilizing the rat, Wistar rats, on an operating table in a specific position with paws tied, for thirty minutes. The determinations evaluate the levels of oxidative stress markers like reduced glutathione (GSH) and malondialdehyde (MDA) and the levels of the protecting enzymes against of free radicals in brain. RESULTS: After the application of contention stress, GSH level increased insignificantly, while MDA level increased significantly compared with the normal animals. These have demonstrated that in our model of nociceptive stress actioned the mechanisms of membrane lipid peroxidation. The activity of the antioxidant enzymes GSH, GPX and SOD decreased in the stressed animals compared with the normal group. This experiment has revealed that in our model of nociception stress, many reactive oxygen species (ROS) were generated, which reduced the enzymatic defense mechanisms and activated lipid peroxidation mechanisms.

Relaxing effects of adrenomedullin in rat mesenteric resistance arteries.

UNLABELLED: Exogenous adrenomedullin (ADM) is hypotensive in very small doses, through direct vasodilation of resistance arteries. In different region this is variably mediated by ADM and CGRP receptors. Mechanisms involve ADM effects upon smooth muscle to increase cAMP and to activate K+ channels, plus stimulation of endothelial NO release and inhibition of sympathetic noradrenaline release. AIM: We studied the mechanism of the vasodilator effect of ADM in vitro. METHOD: Rat mesenteric resistance arteries (RMRA) in isometric conditions, were stimulated using four contracting agents: K+ 40 microM, phenylephrine 10 mM, PGF2alpha 10 microM, angiotensin II 1 microM. We used methylene blue 10 microM to examine the involvement of soluble guanylate cyclase (GC) in the relaxation induced by ADM. RESULTS: We found that relaxation induced by ADM is endothelium-independent, similar regardless of the contracting agent (including high K+), and partially sensitive to methylene blue. CONCLUSIONS: K+ channel activation by ADM is not essential for relaxation. Opposite to other authors, we suggest that ADM-induced vasodilation may involve endothelium-independent activation of soluble GC.

Biosynthesis and physio-pharmacological actions of angiotensin peptides: 2. Physio-pharmacological properties.

The classic concept of the renin-angiotensin system being substantially accomplished by the new cognitive and applicative acquisitions, a natural reconsideration and completion is imposed. In consequence, ample referrals are made to the main central and peripheral actions of Angiotensins through specific receptors. Emphasis is given to the effects of Angiotensin IV and Angiotensin 1-7 which are different of those of Angiotensin II, underlining their possible role as counteracting factors to its actions, in order to remove the imbalances created by the predominating stimulation of vasoconstricting AT, receptors. There are also taken into account the mainly central neural actions of Angiotensin IV, while Angiotensin 1-7 seems to be active only in the periphery. At the end are mentioned the results of our own research on the vasodilating effects of Angiotensin 1-7 and its interrelations with Angiotensin II. New experimental proofs are brought both in favor of the endocrine, paracrine and autocrine role of the circulating and tissue renin-Angiotensin system and of the counteracting of the effects of Angiotensin II by a part of its metabolism products.

Biosynthesis and physio-pharmacological actions of angiotensin peptides: 1. Synthetic enzymes.

The present work introduces a brief review of the actual knowledge concerning the enzymes involved in the biosynthesis of the active angiotensins, followed by a presentation of their main physio-pharmacological actions. The enzymatic pathways that generate active ang. II (1-8) are complemented with data concerning its transformation into angiotensin III (2-8), ang. IV (3-8), ang. V (1-5) and ang. 1-7. Besides the classic renin of renal origin, the tissue isorenins, represented by tonin and cathepsins D and G, inactive angiotensin-I-forming are also reviewed. Furthermore, chymase and the new angiotensin-converting enzyme 2 (ACE2), which generates angiotensin 1-7, having opposite properties from the mother-substance (Ang. II) are discussed at length. The presentation of properties of angiotensin-generating enzymes is followed by the presentation of the action of angiotensinases (aminopetidases, carboxypeptidase and endopeptidases), which are involved both in the generation of biologically active angiotensin peptides and in their inactivation.

New bioactive angiotensins formation pathways and functional involvements.

After a brief review of the actual knowledge concerning the circulating and tissue Renin-Angiotensin System (RAS) as a unitary hormonal system, the cognitive acquisitions regarding the formation and action mechanisms of the new biologically active angiotensins will be presented. The review of the enzymatic pathways for their synthesis and inactivation, as metabolism products of angiotensin II (1-8), will be followed by the presentation of the main physio-pharmacological actions of angiotensin III (2-8), angiotensin IV (3-8) and angiotensin (1-7). The functional involvements of the cerebral angiotensin IV in what concerns its possible participation in the normal neurochemical processes of memory and in the neurodegenerative processes of Alzheimer disease will be exposed, together with the vasodilating effects of angiotensin (1-7) as counteracting factor for the constricting effects of angiotensin II. The data concerning the bioactive fragments of angiotensin II will be accompanied by those regarding its implication in the cardiovascular modeling and the induction of oxidative stress, inflammation, atherogenesis, etc. In their turn, personal researches bring new experimental evidences in favor of interactions between angiotensin (1-7) and angiotensin II within the rat thoracic aorta. Biphasic, dose-dependent effects were observed for angiotensin (1-7), induced both through nitric oxide, kinins and prostaglandin release for counteracting the vasoconstricting effects of angiotensin II and the modulation of its own vasodilator action.

In vivo and in vitro research on the biological effects of deuterium-depleted water: 1. Influence of deuterium-depleted water on cultured cell growth.

Deuterium depleted-water (DDW) is a new available tool for decreasing deuterium concentration in the environment of cells in culture. Several types of established cell lines, both normal and neoplastic were grown in culture media dissolved with DDW and compared with the same strains, in the same amounts, grown in media dissolved with normal distilled water. Naive mice splenocytes were grown, under stimulation with proliferation triggers, like bacterial lipopolysaccharide (LPS) and Concanavalin A (ConA) in the same conditions. The growth and proliferation were estimated using the MTT assay. Both established cell types and explanted splenocytes in the DDW-media had a significantly higher growth rate than cell cultured in normal media. In an attempt to identify the membrane mechanisms involved in the growth stimulation by DDW, the membrane proton transporters Na+/H+ antiporter and H+/K+ATP-ase were inhibited with their selective blockers amiloride and respectively lansoprazole. The results, however incomplete, point towards a lack of involvement of the Na+/H+ antiporter and a possible implication of the H+/K+ATP-ase.

Experimental data regarding the implications of certain minimum structure enkephalin-like peptides in nociceptive processing.

The aim of this study was to investigate the importance of the amino acidic sequence at N-terminal end of certain minimum structure enkephalin-like peptides for the analgesic activity. Different groups of mice or rats were treated with 1) L-tyrosine (i.p. 200 mg/kg), 2) Tyr-Phe (i.t. 0.5 mg/rat), 3) Tyr-Pro-Phe (i.t. 0.5 mg/rat), 4) Gly-Tyr (i.t. 0.5 mg/rat), 5) Tyr-Gly-Gly (i.t. 0.5 mg/rat). Different tests were utilized to evaluate the antinociceptive effect of the substances tested: thermal nociception (hot plate test, plantar test), mechanical nociception (analgesymeter test). Tyr-Pro-Phe, Tyr-Gly-Gly, Tyr-Phe, but not Gly-Tyr, elicited analgesic activity. So, the presumption made in the case of atypical opioid peptides that opioid-like activity in case of peptides presumes a tyrosine residue at the N-terminal sequence, applies for shorter peptides. It appears also that minimal structure brain peptides with an N-terminal Tyr-Pro, rather than the Tyr-Gly-Gly-Phe sequence typical of other endogenous opioids, can provide better affinity for the opioid receptors and stronger analgesic activity. The inhibition of their analgesic effect by previous administration of naloxone proves that this effect is mediated through the endogenous opioid system.

[Protective effects of vegetable polyphenols on the dynamic metabolism of lipids]. / Efectele protectoare ale polifenolilor vegetali asupra dinamicii metabolismului lipidic.

Epidemiological studies generally showed a strong inverse association between red wine consumption and mortality for coronary heart disease (CHD). Antiatherogenic alteration in plasma lipoproteins, particularly increase in high-density lipoprotein (HDL) cholesterol, is considered as the most plausible mechanism of the protective effect of alcohol consumption on CHD. The aim of our study was to investigate the in vivo effects of regular consumption of 300 ml red wine/day, for three weeks, on human serum lipid profile. Thirty healthy volunteers on no medication, abstained from alcohol for 21 days prior the study, were included in our study, and blood samples were taken for serum lipids at base line and after 21 days of wine consumption. This study confirmed that moderate consumption of red wine exerts cardioprotective effects through beneficial changes in lipid profile.

[Myocardial remodeling]. / Remodelarea miocardica (I).

Chamber remodeling and myocardial systolic dysfunction play an important role in the development of cardiac failure after myocardial infarction. The process is accompanied by qualitative and quantitative changes in the expression and reexpression of genes regulating cell growth and contractile function. The article tries to explain some of the mechanisms of the myocardial remodeling that permit the modifications and adaptation of the heart to normal and pathological conditions from a clinical point of view and, in the same time, from a molecular point of view.

[Implication of methylglyoxal in diabetes mellitus]. / Implicatiile metilglioxalului în diabetul zaharat.

Methylglyoxal (MG) is an early glycation product which is implicated in genesis of diabetic complications either as a direct toxin or as a precursor for advanced glycation end products. It is metabolized via S-D-lactoylglutathione to D-lactate by means of the enzymes glyoxalase I and II, which depend on glutattione as cofactor. MG is highly reactive and can bind to and modify proteins by chemical interaction with cellular proteins, action on energy production, induce free radical generation and cell killing. That way MG play a role in the events of the development of diabetic complications.

[New data about neuroimmunomodulation and its functional implications]. / Date noi privind neuroimunomodularea si implicatiile ei functionale.

After a brief presentation of the immune system as sensorial and effector organ, which recognizes and defends against cellular aggressions, the main psychoneuroendocrine components of immune reaction regulation and modulation are shown. Both central nervous structures that control the hormonal emissions, the vegetative innervation of the lymphoid organs as wells as the afferent neurohumoral pathways involved in the making of the self-regulating and neuromodulating circuits of the humoral and cellular immune responses are mentioned. An important position is held by the interrelations between the hypothalamus-pituitary-corticoadrenal gland, the sympathetic-parasympathetic efferent pathways and the chemical messengers (hormones, neurotransmitters, interleukins, neurotrophins) which make possible the bi-directional neuroimmune communication for maintaining the homeostatic balances on this third effector pathway, too. Also experimental proof concerning the ability of central neurons to secrete neuromodulator cytokines and the presence of specific receptors for the various neuroactive molecules within lymphoid organs and circulating lymphocytes are presented. To close, the psychoemotional components of the neuroimmunomodulator circuits are mentioned, using as examples the changes induced by stress generally and oxidative stress in particular.

Actual data concerning the brain--immune system interface.

After a brief presentation of the immune system as sensorial and effector organ, which recognizes and defends against cellular aggressions, the main psycho-neuro-endocrine components of immune reaction regulation and modulation will be shown. Both central nervous structures that control the hormonal emissions, the vegetative innervation of the lymphoid organs as well as the afferent neurohumoral pathways involved in the making of the self-regulating and neuromodulating circuits of the humoral and cellular immune responses will be mentioned. An important position will be held by the interrelations between the hypothalamus-pituitary-corticoadrenal gland, the sympathetic-parasympathetic efferent pathways and the chemical messengers (hormones, neurotransmitters, interleukins, neurotrophins) which make possible the bi-directional neuroimmune communication for maintaining the homeostatic balances on this third effector pathway, too. Also will be presented experimental proof concerning the ability of central neurons to secrete neuromodulator cytokines and the presence of specific receptors for the various neuroactive molecules within lymphoid organs and circulating lymphocytes. To close, the psychoemotional components of the neuro-immunomodulator circuits will be mentioned, using as examples the changes induced by stress generally and oxidative stress in particular.

[The role of oxidative stress in normal and pathological adaptive reactions]. / Rolul stresului oxidativ în reactiile adaptative normale si patologice.

After a brief presentation of the data concerning the mechanism of production of oxidative stress as an expression of cellular and molecular stressing aggression, the main actions and functional implications of the excess of free radicals at the level of the main tissues and organs are presented. Emphasis is made on the nuclear, cytosolic and membrane alterations produced by the lipid peroxidation phenomena and the cell protein degradation induced by the oxidative stress. Special attention is given to the beneficial and harmful properties of the free radical species of oxygen and nitrogen, beginning with their involvement in the production of the normal adaptive reactions and ending with their involvement in the pathogenesis of various pathological states. In the group of beneficial effects are included along with the antibacterial and antiviral properties of the free radicals and their participation in the autoregulation of the local arteriolar-capillary circulation network. As harmful properties are mentioned the cellular destructive phenomena produced by the free radicals, which are considered as the generators of a true radicals pathology (senescence, atherogenesis, cancerogenesis, neurodegenerative diseases, etc).

[Clinical and biochemical aspects of diabetic nephropathy]. / Aspecte clinico-biologice ale nefropatiei diabetice.

Diabetic nephropathy (DN) is the most important cause of increased morbidity and mortality in patients with diabetes mellitus. Moreover DN is associated with a high risk for cardiovascular complications and progression of renal failure. It is known that there is a cumulative risk of development of DN represented by genetic factors, glycaemic factors, hypertension, alterations in the lipid metabolism, smoking. Functionally, it is represented by increased glomerular filtration rate (silent phase) and renal hypertrophy, increased the urinary albumin excretion rate, increased blood pressure and decline in glomerular filtration rate (end phase). Biochemical DN induced the alterations in lipid metabolism (increased the serum concentrations of triglicerides, VLDL, LDL), alterations in glycaemic metabolism (blood glucose, glycated hemoglobin, glycated albumin). The correlations between clinical and biochemical aspects are developed in this reference.

[From molecular genetics to functional genomic and physiome]. / De la genetica moleculara la genomica functionala si fiziom.

After a brief overview on the advances in the molecular genetics knowledge the paper present new concepts of functional genomics and physiom. First, the results of a group of cell and molecular biology researchers in the filed of genic expression of biologic active endogenous substances, ion receptors and channels are discussed, underlining their influence on actual genomic trend of physiological sciences. Discussions continues on theoretical basis of gene therapy and in the end are presented the researches that made the transition from functional genom to the integrative concepts of physiom, cardiom and proteom, fulfilling the content of the classical notion of normal and pathologic physiology.