Asymmetrical influence of a standard light/dark cycle and constant light conditions on the alanyl-aminopeptidase activity of the left and right retinas in adult male rats.

The retina acts as an independent clock informing the central pacemaker, the suprachiasmatic nucleus, under environmental light conditions, with consequences of such inputs for the central and peripheral nervous system. Differences in the behavior of the left and right retinas depending on environmental light conditions may influence the information projected to the brain hemispheres. The retina possesses neuropeptides that act as neurotransmitters or neuromodulators. Alanyl-aminopeptidase (AlaAP, EC 3.4.11.2) activity regulates some of these neuropeptides and therefore reflects their function. We analyzed AlaAP activity in the left and right retinas of adult male rats at successive time points under standard (12/12 h light/dark cycle) and nonstandard (constant light) conditions. AlaAP activity was measured fluorometrically using alanyl-beta-naphthylamide as the substrate. Under standard conditions, there were no differences in the left or right retina between time points, with the left retina predominating, particularly in the light period. In contrast, under constant light, no left versus right differences were observed, but significant differences between time points appeared. In comparison with standard conditions, constant conditions led to significantly higher AlaAP activity. Considering all the left retina data in comparison with all the right retina data, no correlation was found between the left and right retinas under standard conditions, but a significant positive correlation was observed under constant light. These results demonstrate an asymmetrical response of retinal AlaAP activity to changes in environmental light conditions, which may affect the functions in which the substrates of AlaAP are involved and the information projected to the brain hemispheres.

Angiotensin II, dopamine and nitric oxide. An asymmetrical neurovisceral interaction between brain and plasma to regulate blood pressure.

Vital functions, such as blood pressure, are regulated within a framework of neurovisceral integration in which various factors are involved under normal conditions maintaining a delicate balance. Imbalance of any of these factors can lead to various pathologies. Blood pressure control is the result of the balanced action of central and peripheral factors that increase or decrease. Special attention for blood pressure control was put on the neurovisceral interaction between Angiotensin II and the enzymes that regulate its activity as well as on nitric oxide and dopamine. Several studies have shown that such interaction is asymmetrically organized. These studies suggest that the neuronal activity related to the production of nitric oxide in plasma is also lateralized and, consequently, changes in plasma nitric oxide influence neuronal function. This observation provides a new aspect revealing the complexity of the blood pressure regulation and, undoubtedly, makes such study more motivating as it may affect the approach for treatment.

Cystinyl and pyroglutamyl-beta-naphthylamide hydrolyzing activities are modified coordinately between hypothalamus, liver and plasma depending on the thyroid status of adult male rats.

The hypothalamus determinates metabolic processes in liver through endocrine and autonomic control. Hypothalamic neuropeptides, such as thyrotropin releasing hormone or vasopressin, have been involved in liver metabolism. The thyroid status influences metabolic processes including liver metabolism in modulating those hypothalamic peptides whose functional status is regulated in part by aminopeptidase activities. In order to obtain data for a possible coordinated interaction between hypothalamus, plasma and liver, of some aminopeptidase activities that may partially reflect the hydrolysis of those peptides, pyroglutamyl- (pGluAP) and cystinyl- (CysAP) beta-naphthylamide hydrolyzing activities were determined fluorimetrically, both in their soluble and membrane-bound forms, in eu- hypo- and hyperthyroid adult male rats. Hyperthyroidism and hypothyroidism were induced with daily subcutaneous injections of tetraiodothyronine (300 µg/kg/day) or with 0.03% methimazole in drinking water for 6 weeks. Results demonstrated significant changes depending on the type of enzyme and the thyroid status. The most striking changes were observed for CysAP in liver where it was reduced in hypothyroidism and increased in hyperthyroidism. Significant intra- and inter-tissue correlations were observed. While there were positive inter-tissue correlations between liver, plasma and hypothalamus in eu-and hypothyroid rats, a negative correlation between hypothalamus and liver was observed in hyperthyroidism. These results suggest the influence of thyroid hormones and an interactive role for these activities in the control of liver metabolism. The present data also suggest a role for CysAP and pGluAP activities in liver function linked to their activities in hypothalamus.

Bidirectional asymmetry in the neurovisceral communication for the cardiovascular control: New insights.

The cardiovascular control involves a bidirectional functional connection between the brain and heart. We hypothesize that this connection could be extended to other organs using endocrine and autonomic nervous systems (ANS) as communication pathways. This implies a neuroendocrine interaction controlling particularly the cardiovascular function where the enzymatic cascade of the renin-angiotensin system (RAS) plays an essential role. It acts not only through its classic endocrine connection but also the ANS. In addition, the brain is functionally, anatomically, and neurochemically asymmetric. Moreover, this asymmetry goes even beyond the brain and it includes both sides of the peripheral nervous and neuroendocrine systems. We revised the available information and analyze the asymmetrical neuroendocrine bidirectional interaction for the cardiovascular control. Negative and positive correlations involving the RAS have been observed between brain, heart, kidney, gut, and plasma in physiologic and pathologic conditions. The central role of the peptides and enzymes of the RAS within this neurovisceral communication, as well as the importance of the asymmetrical distribution of the various RAS components in the pathologies involving this connection, are particularly discussed. In conclusion, there are numerous evidences supporting the existence of a neurovisceral connection with multiorgan involvement that controls, among others, the cardiovascular function. This connection is asymmetrically organized.

[Brain asymmetry and dopamine: beyond motor implications in Parkinson's disease and experimental hemiparkinsonism]. / Asimetria cerebral y dopamina: mas alla de las implicaciones motoras en la enfermedad de Parkinson y hemiparkinsonismo experimental.

INTRODUCTION: Brain asymmetry could be defined as the existence of functional, anatomic or neurochemical differences between both hemispheres. It is a dynamic phenomenon, regulated by endogenous and exogenous factors. Its functional significance is poorly clarified and is only partially understood in very specific cases such as the relationship between the lateralized brain content of dopamine and its motor effects which is specially patent in Parkinson's disease. DEVELOPMENT: The asymmetric brain content of dopamine not only displays lateralized motor effects but also behavioral and autonomic asymmetric consequences. In fact, Parkinson's disease is characterized not only by unilateral motor symptoms that arise at the early stages, but has other non-motor symptoms such as autonomic or cognitive alterations that are also revealed asymmetrically. CONCLUSIONS: Brain asymmetry has been underestimated when analyzing the pathogeny of brain diseases and it has been partially studied only in some specific cases, such as Parkinson's disease. However, in order to appropriately understand some brain diseases such as Parkinson's disease, the need to consider this phenomenon has been highlighted.

TITLE: Asimetria cerebral y dopamina: mas alla de las implicaciones motoras en la enfermedad de Parkinson y hemiparkinsonismo experimental.Introduccion. La asimetria cerebral se puede definir como la existencia de diferencias funcionales, anatomicas o neuroquimicas entre los dos hemisferios cerebrales. Se trata de un fenomeno dinamico modulable por factores endogenos y exogenos. Su significado funcional esta apenas aclarado y solo lo esta en algunos casos muy concretos como, por ejemplo, la relacion existente entre el contenido cerebral lateralizado de dopamina y sus efectos motores, que se manifiesta especialmente en la enfermedad de Parkinson. Desarrollo. El contenido asimetrico cerebral de dopamina no solo da lugar a efectos motores lateralizados, sino que se extiende a consecuencias autonomicas y de conducta igualmente lateralizadas. De hecho, la enfermedad de Parkinson se caracteriza por sintomas motores unilaterales, que surgen en las fases iniciales de la enfermedad, y por otros sintomas no motores, como alteraciones autonomicas o cognitivas, que tambien se manifiestan de forma lateralizada. Conclusiones. La asimetria cerebral ha sido un aspecto infravalorado a la hora de analizar la patogenia de las enfermedades cerebrales, y solo en determinados casos, como en la enfermedad de Parkinson, se ha profundizado parcialmente en su estudio. Sin embargo, se ha puesto en evidencia que es necesario considerar este fenomeno para la adecuada comprension de algunas patologias cerebrales, como es el caso de la enfermedad de Parkinson.

Handedness and gender influence blood pressure in young healthy men and women: A pilot study.

OBJECTIVE: The type and level of sex steroids influence blood pressure (BP). It has been suggested that functional brain asymmetries may be influenced by sex hormones. In addition, there are inter-arm differences in BP not yet related with handedness. In this study, we hypothesize a possible association between sex hormones, handedness, and inter-arm differences in blood pressure. METHODS: To analyze this hypothesis, we measured BP in the left and right arm of the left and right handed adult young men and women in menstrual and ovulatory phase and calculated their mean arterial pressure (MAP). RESULTS: Significant differences depending on sex, arm, handedness or phase of the cycle were observed. MAP was mostly higher in men than in women. Remarkably, in women, the highest levels were observed in the left handed in menstrual phase. Interestingly, the level of handedness correlated negatively with MAP measured in the left arm of right-handed women in the ovulatory phase but positively with the MAP measured in the right arm of right-handed women in the menstrual phase. CONCLUSIONS: These results may reflect an asymmetrical modulatory influence of sex hormones in BP control.

Eficacia del tratamiento con toxina botulínica en la hiperhidrosis palmar en nuestro medio / Efficacy of botulinum toxin in palmar hyperhidrosis in our environment

Introducción. La hiperhidrosis primaria (HP) es un trastorno de etiología desconocida caracterizada por una secreción incontrolada y excesiva de sudor en la superficie de las palmas de las manos, las axilas, las ingles y las plantas de los pies debido a un incremento de la actividad simpático colinérgica de los nervios. El objetivo de este estudio es determinar la eficacia de la toxina botulínica en esta afección. Material y método. Estudio prospectivo de 16 pacientes con hiperhidrosis severa (grado iv), a los que se les realizó la encuesta hyperhidrosis disease severity scale antes del tratamiento, al mes, a los 3 meses y a los 6 meses. Resultados. Un paciente fue no respondedor primario, por lo que abandonó el estudio. De los 15 restantes el 93,8% mejora, pasando de un estadio 4 al 1 a los 3 meses, y solo uno pasa de un estadio 4 a 3. A los 6 meses 3 empeoran pasando de un nivel 1 a nivel 3, mientras que el resto se mantiene en estadio 1. El cambio es estadísticamente significativo entre el inicio y el mes (p < 0,001) y el cambio es estadísticamente significativo entre el inicio y los 6 meses (p < 0,001). El empeoramiento de algunos pacientes no es estadísticamente significativo (p = 0,083). Entre los efectos secundarios observados: un caso de debilidad de la eminencia tenar autolimitada a 4 semanas. Conclusiones. La toxina botulínica es un tratamiento eficaz y seguro en el tratamiento de la hiperhidrosis palmar severa, realizándose un mejor control del dolor mediante bloqueo locorregional. Es necesario estandarizar la dosis a utilizar (AU)

Introduction. Primary hyperhidrosis (PH) is a disorder of unknown etiology characterized by uncontrolled and excessive secretion of sweat on the surface of the palms, armpits, groin and soles of the feet due to increased cholinergic activity of the sympathetic nerves. The aim of this study was to determine the effectiveness of botulinum toxin in this disease. Material and method. A prospective study was conducted in 16 patients with severe hyperhidrosis (grade IV). The Hyperhidrosis Disease Severity Scale was administered before treatment, and at 1, 3, and 6 months after treatment. Results. One patient was not the primary responder and therefore withdrew from the study. Of the 15 remaining patients, 93.8% improved, with a reduction in hyperhidrosis stage from 4 at baseline to 1 at 3 months. Only one patient showed a reduction in stage from 4 to 3. At 6 months, 3 patients showed a worsening, with an increase in stage from 1 to 3, while stage 1 was maintained in the remainder. The change was statistically significant between baseline and 1 month (P < .001) and between baseline and 6 months (P < .001). Worsening in some patients was not statistically significant (P = .083). Adverse effects included 1 case of self-limiting weakness of the thenar that resolved at 4 weeks. Conclusions. Botulinum toxin is safe and effective in treating severe palmar hyperhidrosis. Pain control was better through locoregional block. The dose used should be standardized (AU)

Influence of thyroid disorders on the kidney expression and plasma activity of aminopeptidase A.

OBJECTIVE: Thyroid disorders may affect blood pressure and renal function modifying factors of the plasmatic and kidney renin-angiotensin system such as aminopeptidase A (AP A) that metabolizes angiotensin II to angiotensin III. We investigated the expression of AP A in the kidney, as well as its enzymatic activity in the plasma of euthyroid, hyperthyroid, and hypothyroid adult male rats. METHODS: Hyperthyroidism was induced by daily subcutaneous injections of tetraiodothyronine. Hypothyroid rats were obtained by administration of methimazole in drinking water. Expression of AP A was determined by Western blot analysis. Plasma AP A activity was measured fluorometrically using glutamyl-ß-naphthylamide as substrate. RESULTS: While hyperthyroid rats exhibited lower levels of plasma AP A activity than controls, the kidney of hyperthyroid animals expressed significantly higher AP A than controls and hypothyroid animals. CONCLUSIONS: A discrepancy between the high expression of AP A in kidney of hyperthyroid rats and the low activity of AP A measured in plasma and kidney of hyperthyroid animals was found. The posttranslational influence of environmental biochemical factors may be in part responsible for that divergence.

Serum pyroglutamyl aminopeptidase activity: a promising novel biomarker candidate for liver cirrhosis.

OBJECTIVE: As a reflect of tissue damage, serum aminopeptidases have been proposed as biomarkers of various diseases. In order to search new serologic markers for liver cirrhosis we conducted a preliminary study in which we analyzed a broad range of aminopeptidase activities in serum of controls and patients diagnosed with pancreatitis, hepatitis, and liver cirrhosis without distinction among the etiological type or the degree of severity of each condition. METHODS: Alanyl-, arginyl-, glutamyl-, cystinyl- pyroglutamyl-, and aspartyl-aminopeptidase activities were analyzed fluorometrically, using aminoacyl-ß-naphthylamides as substrates. In addition, various parameters, such as alanine transaminase, aspartate transaminase, alkaline phosphatase, total bilirubin, direct bilirubin, and gamma glutamyl transpeptidase were assayed as routine laboratory test for liver function. RESULTS: Compared with control group, alanyl- and arginyl-aminopeptidase activities increased nonspecifically in pancreatitis, hepatitis and liver cirrhosis, glutamyl- and cystinyl-aminopeptidases did not differ between groups and pyroglutamyl-aminopeptidase demonstrated that while pancreatitis and hepatitis did not differ between them and with controls, this activity decreased selectively in liver cirrhosis compared with all the rest of groups (p<0.001 vs. control and p<0.01 vs. pancreatitis and hepatitis). Aspartyl-aminopeptidase also decreased significantly (p<0.05) in liver cirrhosis compared with controls. Routine parameters for liver function test increased, as expected, in the three pathologies analyzed. CONCLUSIONS: Despite the heterogeneous composition of the three patient groups, the specific reduction of the levels of pyroglutamyl-aminopeptidase activity in serum of liver cirrhosis patients might be considered as a potential candidate to be included in a combination of markers for the diagnosis of this disease.

Bendamustine as salvage treatment for patients with relapsed or refractory mantle cell lymphoma patients: a retrospective study of the Spanish experience.

Patients with mantle cell lymphoma (MCL) have an adverse outcome after relapse. Bendamustine has demonstrated a good efficacy and toxicity profile in previously reported trials. In this study, we present a retrospective analysis of the Spanish experience in relapsed/refractory MCL treated with bendamustine in combination or alone with the objective of knowing the efficacy and toxicity profile of this treatment in our current clinical practice. Fifty eight patients were registered: 67 % male with median age of 71 years, and 2 is the median number of previous lines. The most frequent bendamustine regimen was bendamustine plus rituximab (83 %). The median number of cycles was 5 (range 1-8). The overall response rate was 84 % with 53 % of complete response/unconfirmed complete response (CR/uCR). Median progression-free survival (PFS) was 16 months (95 % confidence interval (CI) 13.3-18.8), and for patients who achieved CR/uCR, it was 33 months (95 % CI 11.1-54.2). Median overall survival (OS) was 30 months (95 % CI 25.6-34.9). For PFS, only blastoid histology and not achieving CR after bendamustine had a significant negative impact on the univariate and multivariate analyses (p < 0.05). Nevertheless, for OS, only an elevated lactate dehydrogenase (LDH) had negative impact on both, univariate and multivariate analyses (p < 0.05). Only one case of treatment-related mortality in a 79-year-old patient with very bad performance status was reported. In 280 cycles, 12 (4 %) hospitalizations for febrile neutropenia were reported. In our population, bendamustine has been a good salvage treatment with a favorable toxicity profile in a non selected and heavily pretreated population of patients with MCL.

Relationship of angiotensinase and vasopressinase activities between hypothalamus, heart, and plasma in L-NAME-treated WKY and SHR.

The renin-angiotensin system (RAS), vasopressin, and nitric oxide (NO) interact to regulate blood pressure at central and peripheral level. To improve our understanding of their interaction and their relationship with the hypothalamus and the cardiovascular system, we analyzed angiotensin- and vasopressin-metabolizing activities in hypothalamus (HT), left ventricle (LV), and plasma, collected from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) treated or not with L-NAME [N(G)-nitro-L-arginine methyl ester], which inhibits the formation of NO and over-activates the sympathetic nervous system. Previous observations in WKY suggested higher formation of Ang III and Ang IV in the HT and higher availability of Ang II in plasma after L-NAME treatment. Our current results show higher formation of Ang IV and higher metabolism of vasopressin after treatment with L-NAME in the LV of WKY rats. In SHR treated with L-NAME, there is higher availability of Ang III in the HT leading to higher release of vasopressin together with lower formation of Ang 2-10. In their LV, however, there is an increase of vasopressinase. Interestingly, while the enzymatic activities in the HT and LV of WKY rats and control SHR are poorly correlated, they are well but inversely correlated in the L-NAME treated SHR. On the other hand, no significant correlations between enzymatic activities in HT or LV and plasma were noticed. Our results suggest that eNOS inhibition in SHR induces or enhances an inverse reciprocal interaction between HT and LV involving the RAS and vasopressin, which may be mediated by the autonomic nervous system.

Tratamiento precoz con estatinas en el infarto agudo de miocardio / Early statin therapy in acute myocardial infarction

OBJETIVOS: Evaluar el efecto de la administración precoz de estatinas durante la fase aguda del infarto de miocardio (IM). DISEÑO: Estudio de cohortes retrospectivo. Ámbito: Nacional. PACIENTES O PARTICIPANTES: Pacientes incluidos en el registro ARIAM desde enero de 1999 hasta diciembre de 2008 con diagnóstico de IM. INTERVENCIONES: Ninguna. Variables de interés principales: Se utilizaron análisis de regresión logística y de propensión para determinar si la administración de estatinas, durante las primeras 24h del IM, se comportaba como un factor protector frente a: 1) la mortalidad, 2) la incidencia de arritmias letales o 3) el shock cardiogénico. RESULTADOS: Se incluyeron 36.842 pacientes en el estudio. En un 50,2% de los pacientes las estatinas se administraron de forma precoz. Su administración se asoció a pacientes más jóvenes, con dislipidemia previa conocida, obesidad, antecedentes personales de cardiopatía isquémica, insuficiencia cardiaca, presencia de taquicardia inusal, uso de betabloqueantes, inhibidores de la enzima convertidora de angiotensina, trombolisis e intervencionismo coronario percutáneo. La mortalidad fue del 8,2% (13,2% sin estatinas vs. 3% con estatinas; p < 0,001). El análisis multivariante demostró que la administración de estatinas actuó como factor protector frente a la mortalidad (OR ajustada 0,518; IC 95% 0,447-0,601). La continuación de la administración de estatinas se asoció con una reducción en la mortalidad (OR ajustada 0,597; IC 95% 0,449-0,798), y el inicio del tratamiento fue un factor protector frente a la mortalidad (OR ajustada 0,642; IC 95% 0,544-0,757). El tratamiento con estatinas también fue factor protector contra la incidencia de arritmias letales y shock cardiogénico. CONCLUSIONES: Estos resultados sugieren que el tratamiento precoz con estatinas en los pacientes con IM se asocia con una reducción de la mortalidad

OBJECTIVES: To evaluate the effects of the early administration of statins during acute myocardial infarction (MI). DESIGN: A retrospective cohort study was carried out. Setting National (Spain). PATIENTS OR PARTICIPANTS: Patients included in the ARIAM registry from January 1999 to December 2008 with a diagnosis of MI. INTERVENTIONS: None MAIN VARIABLES: We used logistic regression analysis and propensity scoring to determine whether the administration of statins during the first 24h of MI acts as a protective factor against: 1) mortality, 2) the incidence of lethal arrhythmias, or 3) cardiogenic shock. RESULTS: A total of 36 842 patients were included in the study. Statins were administered early in 50.2% of the patients. Statin administration was associated with younger patients with known previous dyslipidemia, obesity, a history of ischemic heart disease, heart failure, presence of sinus tachycardia, use of beta-blockers, angiotensin-converting enzyme inhibitors, thrombolysis and percutaneous coronary intervention. Mortality was 8.2% (13.2% without statin versus without statin versus 3% with statin, P < .001). Multivariate analysis demonstrated that statin administration acted as a protective factor against mortality (adjusted OR 0.518, 95%CI 0.447 to 0.601). Continued use of statins was associated with a reduction in mortality (adjusted OR 0.597, 95%CI 0.449 to 0.798), and the start of treatment was a protective factor against mortality (adjusted OR 0.642, 95%CI 0.544 -0.757). Statin therapy also exerted a protective effect against the incidence of lethal arrhythmias and cardiogenic shock. CONCLUSIONS: These results suggest that early treatment with statins in patients with MI is associated with reduced mortality

[Early statin therapy in acute myocardial infarction]. / Tratamiento precoz con estatinas en el infarto agudo de miocardio.

OBJECTIVES: To evaluate the effects of the early administration of statins during acute myocardial infarction (MI). DESIGN: A retrospective cohort study was carried out. SETTING: National (Spain). PATIENTS OR PARTICIPANTS: Patients included in the ARIAM registry from January 1999 to December 2008 with a diagnosis of MI. INTERVENTIONS: None. MAIN VARIABLES: We used logistic regression analysis and propensity scoring to determine whether the administration of statins during the first 24h of MI acts as a protective factor against: 1) mortality, 2) the incidence of lethal arrhythmias, or 3) cardiogenic shock. RESULTS: A total of 36 842 patients were included in the study. Statins were administered early in 50.2% of the patients. Statin administration was associated with younger patients with known previous dyslipidemia, obesity, a history of ischemic heart disease, heart failure, presence of sinus tachycardia, use of beta-blockers, angiotensin-converting enzyme inhibitors, thrombolysis and percutaneous coronary intervention. Mortality was 8.2% (13.2% without statin versus 3% with statin, P<.001). Multivariate analysis demonstrated that statin administration acted as a protective factor against mortality (adjusted OR 0.518, 95%CI 0.447 to 0.601). Continued use of statins was associated with a reduction in mortality (adjusted OR 0.597, 95%CI 0.449 to 0.798), and the start of treatment was a protective factor against mortality (adjusted OR 0.642, 95%CI 0.544 -0.757). Statin therapy also exerted a protective effect against the incidence of lethal arrhythmias and cardiogenic shock. CONCLUSIONS: These results suggest that early treatment with statins in patients with MI is associated with reduced mortality.

The renin-angiotensin system: new insight into old therapies.

Although the renin-angiotensin system (RAS) is already an old acquaintance, there are often exciting discoveries that improve our knowledge of it and open new therapeutic possibilities. Moreover, well-established drugs, such as angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), or beta-blockers, show that their mechanism of action may be the result of parallel pathways other than the ones initially established. A detailed analysis of the RAS can be carried out in part through the study of the enzymes, named angiotensinases, involved in its cascade, whose activity is a reflection of the functionality of their peptide substrates. The study of these enzymes offers the possibility of controlling the effects of angiotensins through various pharmacological manipulations. For example, angiotensinase inhibitors or activators are being used or have been proposed as antihypertensive agents. They have also been suggested as analgesic and antidepressant drugs or targets for drug development against different pathologies such as Alzheimer's disease, epilepsy or ischemia. On the other hand, the analysis of brain asymmetry has revealed surprising results about the laterality of central and peripheral components of the RAS. Such studies indicate that the neurovisceral integration, already proposed by Claude Bernard (1867) should also be analyzed from a bilateral perspective. In this review, the RAS and the role of various angiotensinases implicated in the cascade are revisited. Therapeutic strategies involving some components of the RAS with an unusual vision resulting from a bilateral perspective added to their study are discussed.

Effects of antihypertensive drugs on angiotensinase activities in the testis of spontaneously hypertensive rats.

Sexual dysfunction is a frequent adverse effect during antihypertensive therapy. However, the mechanisms responsible for these effects are not well understood. The renin-angiotensin system has been identified in testis where it may play a role in testicular function and be involved in the detrimental effects of antihypertensive drugs. Therefore, our objective was to compare the influence of captopril and propranolol on plasma testosterone levels and on hydrolyzing angiotensin's enzymes (angiotensinases) in the testis of spontaneously hypertensive rats (SHRs) and in control animals. Twenty-four adult male SHRs were used in this study; eight were treated with captopril in drinking water, 8 with propranolol, and 8 were controls. At the end of the 4 weeks treatment period, systolic blood pressure (SBP) was recorded, blood samples were collected, and the right testis was dissected after perfusion of the rat with saline. The soluble (Sol) and membrane-bound (MB) fractions were obtained after solubilization and ultracentrifugation. Fluorometric measurement of Sol and MB angiotensinase activities were performed using arylamide derivatives as substrates. Testosterone was measured by enzyme immunoassay. SBP decreased after captopril but did not change with propranolol treatment. Whereas captopril did not affect angiotensinase activities, highly significant reductions in Sol and MB angiotensinase activities, particularly glutamyl- and aspartyl-aminopeptidases, were observed after treatment with propranolol. Plasma testosterone decreased in captopril treated rats but propranolol had a greater effect. The present results support a general functional depression of the RAS cascade in the testis of propranolol-treated SHR, which may influence the sexual function of these animals.

Blood pressure increased dramatically in hypertensive rats after left hemisphere lesions with 6-hydroxydopamine.

Plasma angiotensinase activity, nitric oxide and systolic blood pressure (SBP) were differently affected after unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA), depending on the brain hemisphere injured. Moreover, normotensive and hypertensive rats responded differently suggesting an asymmetry in the organization of the autonomic nervous system of the vessels. The aim of this study was to investigate the evolution of SBP and heart rate (HR) over time after nigrostriatal lesions in normotensive and hypertensive rat strains. Unilateral depletions of brain dopamine were performed by injecting 6-OHDA into the left or right striatum of normotensive and hypertensive rats. Vehicle without 6-OHDA was unilaterally injected in control (sham) groups. SBP and heart rate (HR) were measured in un-anesthetised animals 10 and 3 days before administration of 6-OHDA or vehicle and 3 and 25 days after treatment. In normotensive rats, at the end of study, SBP increased significantly from pre-lesioned values in left-lesioned animals but no differences were observed in right-lesioned or sham groups. Before sacrifice, there was a significant reduction from pre-lesion values in HR. In hypertensive animals, there was a highly significant increase of SBP in left-lesioned and sham left rats and a slight increase in right-lesioned but no differences were observed in sham right group. No differences in HR were observed throughout the study in the groups studied. The present results represent direct experimental evidence of an asymmetrical cardiovascular response to unilateral brain lesions, suggesting that left injury may have a worst prognosis.

The profile of fatty acids in frontal cortex of rats depends on the type of fat used in the diet and correlates with neuropeptidase activities.

The kind of fat in the diet modifies the profile of fatty acids in brain and also affects aminopeptidase activities in tissues. Although modifications in brain fatty acids, neurotransmitters, or enzymes due to dietary fat composition have been reported, no direct relationship has yet been described between specific brain fatty acid changes and neuropeptide metabolism following the fat composition of the diet. We investigated the lipid profile and some neuropeptidase activities in the frontal cortex of adult male rats after a period in which diets were supplemented with fatty acids differing in their degrees of saturation such as fish oil (rich in polyunsaturated fatty acids, PUFAs), olive oil (rich in monounsaturated fatty acids, MUFAs), and coconut oil (rich in saturated fatty acids, SAFAs). It is observed that the diet composition affects fatty acid distribution in the brain. Although there is no change of global aminopeptidase/neuropeptidase, their activities in the brain correlate positively or negatively with the dietary fat composition. It is hypothesized that fatty acid in the diet modifies membrane fluidity, peptidases tertiary structure, and therefore, the availability and function of neuropeptides. The present results support the notion that cognitive functions may be modulated depending on the type of fat used in the diet.

Asimetrías neuroquímicas en las alteraciones psiquiátricas / Neurochemical asymmetries in psychiatric disorders

La asimetría cerebral se podría definir como la existencia de una diferencia anatómica, funcional o bioquímica entre ambos hemisferios cerebrales. Más que estático se trata de un concepto dinámico en el que diversos factores endógenos y ambientales actúan como moduladores. Además, el desarrollo y el envejecimiento modifican la asimetría cerebral y algunas alteraciones neuropsiquiátricas ­como, por ejemplo, la esquizofrenia, la depresión, el autismo infantil o la enfermedad de Alzheimer­ se caracterizan en parte por un desequilibrio en determinadas asimetrías cerebrales. Sin embargo, no está claro si estos cambios son causa o consecuencia de tales alteraciones. Aunque la asimetría cerebral es un fenómeno ampliamente estudiado, su significado funcional y las bases neuroquímicas que subyacen a las asimetrías anatómicas y/o funcionales aún no han sido del todo dilucidados. En el presente trabajo se revisa la bibliografía más significativa referente a la asimetría cerebral en el ser humano, así como las alteraciones psiquiátricas más destacadas en las que se han descrito desequilibrios en la asimetría cerebral, incidiendo especialmente en los aspectos neuroquímicos de ésta

Brain asymmetry can be defined as an anatomical, functional or neurochemical difference between the two hemispheres. It is not a static but is rather a dynamic phenomenon in which both environmental and endogenous factors act as modulators. Moreover, aging modifies brain asymmetry, and an imbalance in specific asymmetries characterizes some brain disorders such as schizophrenia, depression, infantile autism and Alzheimer's disease. However, it is not clear whether these changes are a cause or a consequence of these disorders. Although this phenomenon has been extensively studied, its functional significance is not yet clear, and the neurochemical bases underlying anatomical or functional asymmetries in the brain are still poorly understood. In the present article the most important literature on human brain asymmetry, as well as the most significant psychiatric disorders in which imbalances in brain asymmetry have been described are reviewed, with special emphasis on its neurochemical component