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In recent years, many healthcare systems, along with healthcare professionals, have provided services in a patient-centered manner, in which patients are key actors in the care process. Encouraging self-care creates responsible patients, but it must be practiced responsibly. This study aims to analyze the tendency towards self-medication for patients from a rural area in Northeastern Romania. Data were collected using a questionnaire, which consisted of 25 questions, that has been developed by the research team. Student’s T test or one-way ANOVA was used, and the reliability of the questionnaire was calculated using Cronbach’s alpha coefficient. Fifty-eight patients agreed to participate and were interviewed. The results of the study suggest that respondents practice self-medication, which they resort to when their condition cannot be treated with natural remedies or herbs and when it impairs their ability to do their daily activities. Self-medication could be explained by the lack of self-care services as well as the trust patients have in the specific treatment. Patients prefer asking the pharmacist for drugs instead of visiting a physician, which could be due to higher accessibility and time-efficiency, while also being prone to stock up on certain medications due to limited access to healthcare.

The brain represents an important site for the action of insulin. Besides the traditionally known importance in glucoregulation, insulin has significant neurotrophic properties and influences the brain activity: insulin influences eating behavior, regulates the storage of energy and several aspects concerning memory and knowledge. Insulin resistance and hyperinsulinism could be associated with brain aging, vascular and metabolic pathologies. Elucidating the pathways and metabolism of brain insulin could have a major impact on future targeted therapies.

Nanosecond pulsed electric fields (nsPEFs) were used to investigate the different responses arising in myocardial tissues when exposed to a 100 ns electrical pulse and to understand the influence of the electrical parameters on induced phenomena. Nanosecond pulse electric fields can affect the intracellular structures of cells in vitro. Nanosecond pulse electric fields applied to the cardiac tissue are considered to be a possible tool for treatment of arrhythmias or to improve blood circulation inside the myocardial tissue. For this study were used myocardial tissue surgically removed from Wistar rats. The tissue was suspended in KrebsHenseleit solution, placed under an electrode and subjected to 100 ns voltage pulses (2.5 – 10 kV/cm). 300 and 500 pulses at 0.5 Hz were applied. For an early indication in particular, histological investigations of the myocardial tissues exposed to nanosecond pulsed electric fields (nsPEFs) were performed to determine the extent of the morphological modifications produced at the cellular level. After exposure, tissues were prepared for optical microscopy, in order to observe any changes in cell morphology. Histopathological assessment has shown important modifications, such as significant capillary congestion, an aspect which may be explored as a potential application for treating the myocardial ischemia.

Alzheimer’s disease, a major and increasing global health challenge, is an irreversible, progressive form of dementia, associated with an ongoing decline of brain functioning. The etiology of this disease is not completely understood, and no safe and effective anti-Alzheimer’s disease drug to prevent, stop, or reverse its evolution is currently available. Current pharmacotherapy concentrated on drugs that aimed to improve the cerebral acetylcholine levels by facilitating cholinergic neurotransmission through inhibiting cholinesterase. These compounds, recognized as cholinesterase inhibitors, offer a viable target across key sign domains of Alzheimer’s disease, but have a modest influence on improving the progression of this condition. In this paper, we sought to highlight the current understanding of the cholinergic system involvement in Alzheimer’s disease progression in relation to the recent status of the available cholinesterase inhibitors as effective therapeutics.

Backgound : the purpose of the study is to consider the utility of Transcranial Magnetic Stimulation (TMS) in patients with Multiple Sclerosis (MS) and walking impairment, treated with Fampridine, as correlated with the 25-Foot-Walk test (T25-FW). It is known that clinical benefits should be identified within two to four weeks after starting the treatment; otherwise, if there is no benefit reported by patients, it should be discontinued. Methods: 15 MS patients with walking impairment, ranked between 3.5 and 7 on the Expanded Disability Status Scale (EDSS), were investigated by T25-FW and TMS. Evaluations were performed prior to Fampridine 10 mg twice daily administration, 5 and 12 days afterwards, and also 1 and 3 months later. The medium age was 42.8 years and an average duration of the disease was 12.06 years. Results: we assessed an improvement of walking by 2.1 seconds measured on the T25-FW after the first 12 days in 9 patients, which correlated with a 2 miliseconds improvement of the Central Motor Conduction Time (CMCT). For the other 6 patients there was no visible clinical improvement. Nevertheless, CMCT dropped by 0.5 ms and the motor conduction speed by 1 millisecond in 4 of these 6 patients. Fampridine administration was continued in the 4 cases. At the end of the 3 months period, their walking speed measured as on the T25-FW also improved by 2 sec. Conclusions: the amelioration of TMS parameters anticipated the improvement of speed on the T25-FW. In spite of the early false negative clinical response, electrophysiological findings could predict a future clinical improvement if treatment is continued.

Pain continues to be a global unmet medical need, and the current recommendations for its management require a constant exploration of new drugs that target multiple pain mechanisms, with an improved safety profile and increased treatment adherence. Currently, the enriched distribution and localization within nociceptors of the selective channel blockers and the critical role played by sodium channels in neuronal excitability nominate isoforms as specific targets to generate innovative compounds. In the present report, we verified the hypothesis that coadministration of Protoxin-II, a selective sodium channel inhibitor, and trace elements has direct and improved antinociceptive effects. Groups of seven Wistar rats were treated intracerebroventricularly with a combination of MgCl2, CdCl2, and ZnCl2and Protoxin-II, respectively, and with Protoxin-II alone (positive) or saline (negative) for controls. Evaluations were performed by nociception assay. Coadministration of these drugs caused an increase in the maximum possible effect of up to 40% as compared with the control groups. Our findings indicate that selective channel blockers continue to be an important nociception target and that the use of trace elements may provide simple but effective means of control over sodium channel blockers’ risks, potentially lowering the necessary analgesic doses, thus improving the efficacy and safety profile.

This study was designed to evaluate the spatial working memory (as studied in Y-maze) or short-term and long-term spatial memory (assessed in radial 8 arms-maze task), in a scopolamine-induced memory deficits model in mice, by the oral administration of 2 angiotensin-converting enzyme inhibitors—captopril and ramipril and also the effects of the AT1 receptor antagonist, losartan. The present article was initiated as a reaction to the clinical setting of hypertensive disease, which involves lifelong administration of antihypertensive drugs, dietary or lifestyle constraints, and aging, which all take a toll on the higher functions of the nervous system. Most of the patients with cognitive decline suffer of various metabolic imbalances, hypertension, cardiac and kidney disease, many of them which are treated with oral administration of Renin–angiotensin aldosterone system-altering agents like those presented above. Our results showed a protective effect of captopril, ramipril, and losartan prescopolamine administration on spontaneous alternation in Y-maze task, as compared to scopolamine-alone treated mice, as well as decreased number of working memory errors and reference memory errors in radial-arm maze for both losartan + scopolamine and ramipril + scopolamine groups versus scopolamine alone. This could have a therapeutical relevance, especially since oral administration was preferred in our report, as it is used in the therapeutic procedures in humans, further enhancing the similarities with the clinical conditions.

Primary and secondary cardiac involvements in lymphomas are extremely rare and sometimes ill-defined entities. Thorough clinical and imagistic investigation is crucial to evaluate disease extension and its impact on cardiac function. Chemotherapeutic agents with potential cardiovascular toxicity must be cautiously employed in high risk patients. We present the case of a young female patient with classical limited stage Hodgkin lymphoma and unfavorable prognostic factors, cardiac tumor mass with significant mediastinal extension, pleural effusion and subsequent cardiac dysfunction. Potentially cardiotoxic ABVD regimen yielded complete remission and progressive reversal of parameters of cardiac function.

Deuterium-depleted water (DDW) has a concentration of deuterium 6-7 times lower than naturally occurring water (20-25 ppm vs. 150 ppm). When administered for a longer period, it can reduce the concentration of deuterium throughout the body, activating cellular mechanisms that depend on protons. The aim of the present work was to investigate the influence of chronic DDW administration on anxiety-related processes in Wistar rats when compared to a control group that received distilled water, as studied in an elevated plus maze behavioral test. Our results describe a possible anxiolytic-like effect of DDW administration on rats, as shown by the increase in the percentage of time and number of entries in the open arms of the elevated plus maze. The administration of DDW also resulted in stimulated head-dipping behavior in the open arms, which is a behavioral change that characterizes the exploratory behavior and decreased inhibition/ fear in an unfamiliar environment. We conclude that the change in this balance may have important consequences for many biological mechanisms. A deuterium desaturation treatment with DDW might have a use in anxiety disorders.

Ciobica Alin »Alexandru Ioan Cuza« University Dept. of Biology B dul Carol I, 11 700506, Iasi, Romania Tel :0040751218264; Fax 0040232201472 e-mail: alin.ciobicaauaic.ro Summary: It has already been demonstrated that a complete brain renin–angiotensin system (RAS) exists distinctly separate from the peripheral system and is implicated in complex functions such as memory, emotional responses and pain. Regarding the implications of angiotensin II (the main bioactive peptide of RAS) in pain, although there are many studies in this area of research, most of the results are contro versial. Also, it seems that oxidative stress follows angio tensin II infusion, but the role of AT1 vs. AT2 receptors is not well established. In this context, we were interested in studying the effects of central RAS on nociception, through the in tra cerebroventricular administration of losartan and PD123177 (antagonists for the AT1/AT2 receptors), as well as an ACE inhibitor (captopril) and also angiotensin II in rats, which were subsequently tested using the hot-plate task, a well known behavio ral test for pain perception. We present here the analgesic effect of angiotensin II administration, as shown by in crea sed latency-time in the hot-plate, as well as a nociceptive effect of angiotensin II blockers like AT1 and AT2 specific antagonists (losartan and PD-123177) and an ACE inhibitor (captopril), as their administration resulted in decreased la ten cy-time. Moreover, we demonstrated a significant correlation between the results of the nociceptive Kratak sadr`aj: Do sada je ve} pokazano da kompletan mo`dani renin–angiotenzin sistem (RAS) postoji zasebno od perifernog sistema i da je uklju~en u slo`ene funkcije kao {to su memorija, emocionalni odgovori i bol. [to se ti~e im plikacija angiotenzina II (glavnog bioaktivnog peptida RAS) u bolu, mada u ovoj oblasti istra`ivanja postoje mnoge studije, rezultati su ve}inom opre~ni. Tako|e, izgleda da infuziju angiotenzina II prati oksidativni stres, ali uloga receptora AT1 i AT2 jo{ nije razja{njena. U tom kontekstu hteli smo da prou~imo efekte centralnog RAS na nocicepciju preko intra cerebroventrikularne administracije lozartana i PD-123177 (antagonista za receptore AT1/AT2) kao i jednog ACE in hi bitora (kaptopril) i angiotenzina II kod pacova, koji su potom testirani metodom grejne plo~e, poznatim bihevioralnim testom za percepciju bola. Predstavljamo analgeti~ki efekat administracije angiotenzina II pokazan kroz pove}anu latenciju na grejnoj plo~i, kao i nociceptivni efekat blokatora angiotenzina II kao {to su antagonisti specifi~ni za AT1 i AT2 (lozartan i PD-123177) i ACE inhibitora (kaptopril), po{to je rezultat njihove administracije bila smanjena latencija. [ta vi{e, uo~ili smo zna~ajnu korelaciju izme|u rezultata nociceptivnog bihevioralnog testa i nivoa nekih od glavnih mar kera oksidativnog stresa. Na taj na~in obezbe|eni su novi

Accumulating evidence suggests that the nongenomic cardiovascular actions of aldosterone are produced by varied cellular pathways and mediated by a multitude of messenger systems including the reactive oxygen and nitrogen species. Considering the involvement of the oxidative and nitrosative stress in the pathways leading to the activation of the angiotensin — aldosterone system, in the current study we tried to evaluate the functional interactions between aldosterone, angiotensin II and antioxidants in isolated vascular smooth muscle of aortic rings from rats. Our data provide additional arguments that the nongenomic actions of aldosterone on aortic smooth muscle cells of rats are a question of cross-talk and balance between its rapid vasoconstrictor and vasodilator effects, as result of the activation of reactive oxygen species in the first case and of nitrogen species in the second. In this way, it seems that at low ambient oxidative stress, aldosterone promotes nitric oxide (NO) production and vasodilatation, while in situations with increased oxidative stress the endothelial dysfunction and detrimental effects induced by vasoconstriction will prevail. Thus, aldosterone could be considered both “friend and foe”. This could be relevant for the ways in which aldosterone damages cardiovascular functions and could lead to significant therapeutic improvements.

Aspects Regarding the Neurobiology of Psycho-Affective FunctionsIn this mini-review we were interested in analyzing the main achievements concerning the neurobiological substrate of the human psycho-affective functions. The cortico-subcortical areas implicated in the elaboration and the control of the sensorial and psycho-affective reactions of the human brain are described, as well as the neurobiological basis of the psychic and affective manifestations, with focus on the new achievements in understanding the genetic, morpho-chemical and electromagnetic bases of the psycho-affective and behavioral manifestations, both normal and pathological. It is known that emotional states like anxiety, fear or anger generate complex psycho-affective reactions that are controlled by the limbic system, which is called the emotional brain. This is connected with the polyneuronal circuits of the Papez loop, the hypothalamic-pituitary complex and the reticular formation of the brainstem. Some imagistic aspects concerning the implication of the amygdala and the cingulate gyrus in laughing and crying are mentioned, as well as the cerebral areas implicated in romantic and maternal love. Also, some electromagnetic manifestations of the brain are presented, introducing the concept of «electromagnetic plasma», as a possible component of the human brain activity.

The renin-angiotensin system (RAS) is one of the most important neuropeptide systems in the brain and it isknown now that in addition to the regulation of blood pressure, RAS is also implicated in the modulation of somesuperior functions involving the emotional responses, pain or cognitive functions. However, in the last few years variousstudies regarding the modulatory effects of Ang II on learning and memory showed conflicting results, with both positiveand negative reports. In addition, the effects of Ang II on oxidative stress and its relations to the cognitive processes arenot very well understood.We report here the amnesic effects of Ang II icv 0.1μg/kg b.w administration in rats, as showed by decreasedspontaneous alternation in Y-maze. Also, we noticed a significant correlation between the behavioral deficits in Y-mazeand the levels of some oxidative stress markers. This could also have a possible therapeutic importance, since thereduction in blood pressure via manipulation of RAS can results in enhanced cognitive effects. Also, both oxidative andnitrosative stress seems to play an important part in the aforementioned aspects.

In addition to its known classical roles, the renin angiotensin system (RAS) has more subtle functions which include the regulation of emotional responses. Previous studies regarding the anxiety related behavior of RAS have showed controversial results. There is also evidence that oxidative stress accompanies angiotensin II infusion, but the role of AT1/AT2 specific receptors is not clear. The aim of this study was to evaluate the effects of central angiotensin II receptor blockers on anxiety state and oxidative stress. Behavioral testing included elevated plus maze, while oxidative stress status was measured though the extent of a lipid peroxidation product (malondialdehyde-MDA) and the specific activity of some defense antioxidant enzymes (superoxide dismutase-SOD and glutathione peroxidase-GPx). The rats treated with angiotensin II spent significantly less time in the open-arms of elevated-plus-maze, while the administration of losartan resulted in a significant increase of this time. We observed a significant increase of MDA concentration in the angiotensin II group and a decrease of MDA levels in both losartan and PD-123177 groups. In addition, a significant correlation was seen between the time spent in the open arms and oxidative stress markers. These findings could lead to important therapeutic aspects regarding the use of angiotensin II receptor blockers in anxiety-related disorders.

Inhibition of Central Angiotensin Converting Enzyme Exerts Anxiolytic Effects by Decreasing Brain Oxidative StressThis study investigated the effects of angiotensin II and captopril intracerebroventricular administration on anxiety status and brain oxidative stress. Elevated plus maze was used in order to asses the anxiety-like behavior, while the biochemical analysis included the determination of some antioxidant defense enzymes like superoxide dismutase and glutathione peroxidase and also a lipid peroxidation product (malondialdehyde). Our results provide additional evidence of angiotensin II induced anxiety-like effects and increased prooxidant status. Moreover, the blockade of angiotensin II, by the administration of an angiotensin converting enzyme inhibitor (captopril) resulted in anxiolytic effects and decreased oxidative stress status. In addition, we found a significant correlation between the time spent by rats in the open arms of the elevated plus maze and oxidative stress markers. This could raise important therapeutic issues regarding the anxiolytic effects of some angiotensin converting enzyme inhibitors used primarily for hypertension, such as captopril. Also, it seems that oxidative stress could play an important part in these actions.

Mild cognitive impairment (MCI) is a nosological entity proposed as an intermediate state between normal aging and dementia. MCI seems to represent an early stage of Alzheimer's disease (AD) and there is a great interest in the relationship between MCI and the progression to AD. Some studies have demonstrated an accumulation of products of free radical damage in the central nervous system and in the peripheral tissues of subjects with AD or mild cognitive impairment. The aim of the present work was to evaluate the serum levels of some enzymatic antioxidant defences like superoxide dismutase (SOD) and glutathione peroxidase (GPX), as well as lipid peroxidation markers like MDA (malondialdehyde), in MCI and AD patients, compared with age-matched healthy controls. The subjects of this study (45 patients) consisted of 15 individuals with mild cognitive impairment (MCI), 15 with Alzheimer's disease (AD) and 15 healthy age-matched controls. Biochemical analyses showed a similar decrease of the main enzymatic antioxidant defences (SOD and GPX) and increased production of lipid peroxidation marker (MDA) in the serum of the MCI and AD patients, compared to age-matched control group. This study clearly demonstrates that oxidative stress damage occurs in patients with MCI and AD. Moreover, some enzymatic markers of oxidative stress are similar in MCI and AD patients, suggesting that oxidative damage could be one important aspect for the onset of AD.

The concept of tissue renin-angiotensin systems (RAS) is now well established and it is now usual to think in terms of renal and tissue systems. At the same time it has emerged that angiotensin II (Ang II) is not the only biologically active peptide generated by the RAS. At least three others have been identified: the heptapeptide Ang III, the hexapeptide Ang IV and Ang 1-7. Specific receptors exits for the last two peptides. In addition, the range of possible physiological and pathophysiological properties for Ang II„ has been expanding. The current perception of the RAS is therefore that of a much more complex system than previously believed, with autocrine, paracrine and endocrine properties extending beyond the cardiovascular system. This mini-review focuses on the synthetic pathways of the Ang peptides and describes some of their pleiotropic actions.

The impressive progresse in biochemistry, biophysics and cellular biology in the latest decade has achieved many breakthroughs in the inner normal and pathological cellular processes, opening new vistas in the fundamental and applicative biochemical thinking and researches. As a fundamental biomedical science, physiology benefitted of these cognitive and applicative discoveries, becoming the reference system essential for various clinical and paraclinical biomedical acts. The homeostatic mechanisms of regulation, adaptation and neuro-endocrino-metabolic control have been first specified that lie at the basis of the “constant composition of the inner medium”, signalled by Claude Bernard (1852) (1). Brief data concerning homeostasis As a state of dynamic equilibrium of the constituents of liquid medium surrounding cellular level, homeostasis is essential for the survival and obtaining of various activity forms of the cells. About 100 trillion cells of the human body with structure, metabolism and highly differentiated functions are subject to a permanent adaptative control, starting with the self-regulation of the main functions of the organism and ending with the genetic control at the cellular level. The regulation and control systems necessary to maintain the cellular homeostatic equilibria are of two kinds: intrinsic (local) and extrinsic (nervous and endocrine). By these complex mechanisms the direct or reflex selfregulation of vascular tonus is obtained, as well as the differences of volume and circulating blood pressure, the concentration of constituents of the inner medium necessary for both extra and intracellular liquid exchanges (nutrient molecules, oxygen, carbon dioxide, salts, electrolytes, vitamins, hormones, mediators and chemical modulators, etc.) and for the thermal regulation, acido-basic equilibrium, concentration of secretion products and cellular degradation, etc. Thus, each cell, as part of various tissues and organs, contributes to the coordination and maintaining of local and general equilibria, a homeostasis absolutely essential for the organism normal activity.

Using isolated rat aortic rings perfused with Krebs-Henseleit saline, the vascular effects of angiotensin (1-7) (Ang [1-7]) and its interactions with angiotensin II (Ang II) were investigated. Ang (1-7) induced endothelium-dependent relaxation and vasodilating effects in preparations precontracted with phenylephrine. Without preconstriction, Ang (1-7) at high doses (10 -6—10-5 M) produced either a significant inhibition of Ang IIinduced vasoconstriction or a non-tachyphylactic vasopressor response. While losartan inhibited the vasoconstriction induced by Ang (1-7), A779 blocked only its relaxation. Unlike losartan, blockade of AT2-receptors with PD 123319 had no effect. Taking into account the biphasic effects of angiotensin (1-7), we propose that it is one of the active components of the renin-angiotensin system, which is involved as a modulator both in the counter-regulatory actions of Ang II and in the self-regulation of its own vasodilating effects.

Deuterium-depleted water (DDW) is a water which has a 6-7-fold less concentration of the naturally occurring deuterium (20-25ppm vs. 150ppm). While administrated for a longer period, it may reduce the concentration of deuterium throughout the body, thus activating cellular mechanisms which are depending on protons (channels, pumps, enzyme proteins). The aim of the present work was to study, for the first time in our knowledge, the possible influence of deuterium-depleted water (DDW) chronic administration in normal Wistar rats, as compared to a control group which received distilled water, on spatial working memory and the locomotor activity (as studied through Y-maze) or both short-term and long-term spatial memory (assed in radial 8 arms-maze task). Our results presented here showed no significant modifications in terms of spatial working memory (assessed through spontaneous alternation percentage) and locomotor activity (expressed through the number of arm entries) in Y-maze, as a result of DDW ingestion. Also, no significant differences between the DDW and control group were found in terms of the number of working memory errors in the eight-arm radial maze, as a parameter of short-term memory. Still, we observed a significant decrease for the number of reference memory errors in the DDW rats. In this way, we could speculate that the administration of DDW may generate an improvement of the reference memory, as an index of long-term memory. Thus, we can reach the conclusion that the change between the deuterium/hydrogen balance may have important consequences for the mechanisms that govern long-term memory, as showed here especially in the behavioral parameters from the eight-arm radial maze task.

While it is now well established that the independent brain renin-angiotensin system (RAS) has some important central functions besides the vascular ones, the relevance of its main bioactive peptide angiotensin II (Ang II) on the memory processes, as well as on oxidative stress status is not completely understood. The purpose of the present work was to evaluate the effects of central Ang II administration, as well as the effects of Ang II inhibition with either AT1 and AT 2 receptor specific blockers (losartan and PD-123177, respectively) or an angiotensin-converting enzyme (ACE) inhibitor (captopril). These effects were studied on the short-term memory (assessed through Y-maze) or long-term memory (as determined in passive avoidance) and on the oxidative stress status of the hippocampus. Our results demonstrate memory deficits induced by the administration of Ang II, as showed by the significant decrease of the spontaneous alternation in Y-maze (p=0.015) and latency-time in passive avoidance task (p=0.001) when compared to saline. On the other side, the administration of all the aforementioned Ang II blockers significantly improved the spontaneous alternation in Y-maze task, while losartan also increased the latency time as compared to saline in step-through passive avoidance (p=0.042). Also, increased oxidative stress status was induced in the hippocampus by the administration of Ang II, as demonstrated by increased levels of lipid peroxidation markers (malondialdehyde-MDA concentration) (p0.0001) and a decrease in both antioxidant enzymes determined: superoxide dismutase-SOD (p0.0001) and glutathione peroxidase-GPX (p=0.01), as compared to saline. Additionally, the administration of captopril resulted in an increase of both antioxidant enzymes and decreased levels of lipid peroxidation (p=0.001), while PD-123177 significantly decreased MDA concentration (p0.0001) vs. saline. Moreover, significant correlations were found between all of the memory related behavioral parameters and the main oxidative stress markers from the hippocampus, which is known for its implication in the processes of memory and also where RAS components are well expressed. This could be relevant for the complex interactions between Ang II, behavioral processes and neuronal oxidative stress, and could generate important therapeutic approaches.

There is increasing evidence that besides the well-known angiotensin (Ang) II, other renin–angiotensin system (RAS) peptides, including Ang-(1–7), could have important effects at the central level. However, very few things are known about the central actions of Ang-(1–7), while the effects of its administration alone on anxiety have not been tested to date, to the best of our knowledge. In this way, we were interested in studying the effects of Ang-(1–7) intracerebroventricular administration on anxiety levels, as studied through some main behavioral parameters in the elevated plus maze, as well as the importance of Ang-(1–7) in the oxidative stress status from the amygdala, which is one of the key brain regions involved in mediating anxiety. We report here a possible anxiolytic-like effect of Ang-(1–7) administration, as demonstrated by the increased percentage of time spent and frequency of entries in the open arms of the elevated plus maze, as well as increased head-dipping behavior in the open arms and decreased stretching in closed arms. Also some antioxidant effects of Ang-(1–7) are suggested since a significant increase of GPX specific activity and a decrease of the main peroxidation marker MDA were observed in the amygdala. Moreover, we found a significant correlation between most of the behavioral parameters in the elevated plus maze and the levels of the oxidative stress markers. However, further studies are necessary in order to elucidate the effects of Ang-(1–7) administration on anxiety and oxidative stress status and also on the possible correlation that might exists between these aspects.

This mini-review tries to summarize the main interdependences between the free radicals of oxygen, nitrogen, and carbon. Also, the main metabolic pathways for these radical species are described, as well as how these affect their interaction and functional implications. Emphasis is made on the metabolic disturbances induced by stressing aggressions that produce radical species. In this way, cellular oxidative imbalances created by the superiority of reactive oxygen species over the antioxidant systems produce both activation of nitroxide synthases and the oxidation of terminal nitrogen from L-arginine, as well as the metabolization of heme until carbon monoxide by nitric oxide-activated hemoxygenase. Also, multiple cellular protein and nucleoprotein alterations determined by these three kinds of radical species are completed by the involvement of hydrogen sulfide, which results from the degradation of L-cysteine by cistationine-γ-lyase. In this way, sufficient experimental data tend to demonstrate the involvement of hydrogen sulfide and other thiol derivatives in the interrelations between oxygen, nitrogen, and carbon, which results in a true radical cascade. Thus, oxidative stress, together with nitrosative and carbonilic stress, may constitute a central point where other factors of vulnerability meet, and their interactions could have an important impact in many modern diseases. Considering that the actions of reactive species can be most of the time corrected, future studies need to establish the therapeutical importance of various agents which modulate oxidative, nitrosative, or carbonilic stress.