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.

Cause of death in mild cognitive impairment: a prospective study (NEDICES).

BACKGROUND AND PURPOSE: Previous studies have reported the occurrence of increased mortality rates among individuals with mild cognitive impairment (MCI), but possible links between MCI subtypes and cause-specific mortality need to be explored. To examine short-term mortality (5 years), long-term mortality (13 years) and cause-specific mortality of individuals over 65 years of age suffering from MCI compared with cognitively unimpaired individuals in the Neurological Disorders in Central Spain (NEDICES) cohort. METHODS: Mild cognitive impairment was classified using standardized psychometric and functional assessment in accordance with diagnostic convention. Cox's proportional hazards models, adjusted by sociodemographics and comorbidity factors, were used to assess the risk of death at 5 and 13 years of MCI subtypes compared with a reference group of older people without cognitive impairment (N = 2329). Causes of death were obtained from the National Population Register of Spain. RESULTS: There were 1484 deceased individuals at 13 years. MCI subtypes were defined as amnestic single domain (N = 259), amnestic multiple domain (N = 197) and non-amnestic (N = 641). After adjusting for covariates, only the amnestic multiple domain MCI subtype showed an increased hazard ratio (HR) for mortality at 5 years versus the reference group. However, the HR for mortality at 13 years was increased for all MCI subtypes. The HR by MCI subtype was 1.19 in the non-amnestic subtype (95% CI 1.05-1.36), 1.31 in the amnestic single domain subtype (95% CI 1.10-1.56) and 1.67 in the amnestic multiple domain subtype (95% CI 1.38-2.02). In terms of cause-specific mortality, the chance of death from dementia was statistically higher in all MCI subtypes. CONCLUSION: Amnestic multiple domain MCI showed the greatest risk of mortality in comparison with other MCI subtypes at different intervals. Dementia was the only cause-specific mortality that was increased in MCI individuals.

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.

Angiotensinase and vasopressinase activities in hypothalamus, plasma, and kidney after inhibition of angiotensin-converting enzyme: basis for a new working hypothesis.

Reducing angiotensin II (Ang II) production via angiotensin-converting enzyme (ACE) inhibitors is a key approach for the treatment of hypertension. However, these inhibitors may also affect other enzymes, such as angiotensinases and vasopressinase, responsible for the metabolism of other peptides also involved in blood pressure control, such as Ang 2-10, Ang III, Ang IV, and vasopressin. We analyzed the activity of these enzymes in the hypothalamus, plasma, and kidney of normotensive adult male rats after inhibition of ACE with captopril. Aspartyl- (AspAP), glutamyl- (GluAP), alanyl- (AlaAP) and cystinyl-aminopeptidase (CysAP) activities were measured fluorimetrically using arylamides as substrates. Systolic blood pressure (SBP), water intake, and urine flow were also measured. Captopril reduced SBP and increased urine flow. In the hypothalamus, GluAP and AspAP increased, without significant changes in either AlaAP or CysAP. In contrast with effects in plasma, GluAP was unaffected, AspAP decreased, while AlaAP and CysAP increased. In the kidney, enzymatic activities did not change in the cortex, but decreased in the medulla. These data suggest that after ACE inhibition, the metabolism of Ang I in hypothalamus may lead mainly to Ang 2-10 formation. In plasma, the results suggest an increased formation of Ang IV together with increased vasopressinase activity. In the kidney, there is a reduction of vasopressinase activity in the medulla, suggesting a functional reduction of vasopressin in this location. The present data suggest the existence of alternative pathways in addition to ACE inhibition that might be involved in reducing BP after captopril treatment.

Hypothalamic and plasmatic angiotensin metabolism in L-NAME treated rats.

In order to study the interaction between the renin-angiotensin system (RAS) and nitric oxide (NO), we analyzed the activity of aspartyl- (AspAP), glutamyl- (GluAP), alanyl- (AlaAP), and cystinylaminopeptidase (CysAP) enzymes involved in the RAS cascade, in the hypothalamus, and plasma of normotensive adult male rats after the inhibition of NO production with the NO synthase inhibitor L-NAME (L-N (G)-nitroarginine methyl ester). L-NAME treatment produced a significant increase of systolic blood pressure (SBP). In plasma, while GluAP activity decreased significantly, suggesting a lower Ang III formation, the other aminopeptidases did not change after L-NAME treatment. In hypothalamus, the activities of AspAP and CysAP were not affected after L-NAME treatment. In contrast, GluAP and AlaAP increased significantly. These results suggested mainly a higher formation of Ang III, but also higher levels of Ang IV in the hypothalamus of L-NAME treated rats. Both peptides have hypertensive properties at central level. On the contrary, Ang III may counteract the hypertensive action of Ang II at the periphery. Therefore, the increased SBP in L-NAME treated rats may be due in part to the increased activity of GluAP and AlaAP in hypothalamus and to a decreased activity of GluAP in plasma.

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.

Comparative studies on the properties of the extrinsic manganese-stabilizing protein from higher plants and of a synthetic peptide of its C-terminus.

The present study describes a comparative analysis on the fluorescence properties of the manganese-stabilizing protein (MSP), a synthetic peptide corresponding to its C terminus and a 7:1 (molar ratio) mixture of N-acetyl-tyrosine and N-acetyl-tryptophan, respectively, together with reconstitution experiments of oxygen evolution in MSP-depleted photosystem II (PS II) membrane fragments. It is found: (i) at neutral pH, the fluorescence from Trp(241) is strongly diminished in MSP solutions, whereas it highly dominates the overall emission from the C-terminus peptide; (ii) at alkaline pH, the emission of Tyr and Trp is quenched in both, MSP and C-terminus peptide, with increasing pH but the decline curve is shifted by about two pH units towards the alkaline region in MSP; (iii) a drastically different pattern emerges in the 7:1 mixture where the Trp emission even slightly increases at high pH; (iv) the anisotropy of the fluorescence emission is wavelength-independent (310-395 nm) and indicative of one emitter type (Trp) in the C-terminus peptide and of two emitter types (Tyr, Trp) in MSP; and (v) in MSP-depleted PS II membrane fragments the oxygen evolution is restored (up to 85% of untreated control) by rebinding of MSP but not by the C-terminus peptide, however, the presence of the latter diminishes the restoration effect of MSP. A quenching mechanism of Trp fluorescence by a next neighbored tyrosinate in the peptide chain is proposed and the relevance of the C terminus of MSP briefly discussed.

Carbonic anhydrase activities in pea thylakoids.

Pea thylakoids with high carbonic anhydrase (CA) activity (average rates of 5000 micromol H(+) (mg Chl)(-1) h(-1) at pH 7.0) were prepared. Western blot analysis using antibodies raised against the soluble stromal beta-CA from spinach clearly showed that this activity is not a result of contamination of the thylakoids with the stromal CA but is derived from a thylakoid membrane-associated CA. Increase of the CA activity after partial membrane disintegration by detergent treatment, freezing or sonication implies the location of the CA in the thylakoid interior. Salt treatment of thylakoids demonstrated that while one part of the initial enzyme activity is easily soluble, the rest of it appears to be tightly associated with the membrane. CA activity being measured as HCO(3) (-) dehydration (dehydrase activity) in Photosystem II particles (BBY) was variable and usually low. The highest and most reproducible activities (approximately 2000 micromol H(+) (mg Chl)(-1) h(-1)) were observed in the presence of detergents (Triton X-100 or n-octyl-beta-D-glucopyranoside) in low concentrations. The dehydrase CA activity of BBY particles was more sensitive to the lipophilic CA inhibitor, ethoxyzolamide, than to the hydrophilic CA inhibitor, acetazolamide. CA activity was detected in PS II core complexes with average rate of 13,000 micromol H(+) (mg Chl)(-1) h(-1) which was comparable to CA activity in BBY particles normalized on a PS II reaction center basis.

Spontaneous carotid and vertebral artery dissection in children.

Carotid and vertebral artery dissection is a rarely reported cause of stroke in childhood and adolescence, especially if there is not a direct trauma to the neck. Four patients, under 15 years of age, presented with an internal carotid artery dissection, and one patient presented with a vertebral artery dissection. They were all making a physical effort when the event occurred. The five patients had ischemic symptoms, and in two the events were preceded by transient ischemic attacks. Headache was associated in four patients. The diagnosis was made by magnetic resonance imaging and angiography, which included transfemoral angiography in two patients. All improved before leaving the hospital, and four patients did not suffer recurrent episodes. The diagnostic accuracy of artery dissection has improved because of noninvasive neuroimaging testing, but it should still be suspected in any pediatric ischemic stroke, especially if there is headache or cervical pain associated.

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.

[Usefulness of short tests in dementia screening]. / Utilidad de los test breves en el cribado de demencia.

INTRODUCTION: As life expectancy increases, and the prevalence of cognitive impairment and dementia continues to grow, the number of patients with cognitive complaints seen in primary care or specialized out-patient clinics has increased in the last few years. The assessment of these patients requires time, and a step-by-step organization to optimize medical resources. DEVELOPMENT: This review presents the most important dementia screening tools with Spanish validation. We focus on those that are brief (less than ten minutes) and easy to use in primary care settings. Two groups of tests can be distinguished: brief cognitive tests and functional activities scales. The first can be considered a part of the mental status examination, and the second an organized history taking. Informant questionnaires and the possibility of self-administered cognitive tests are briefly reviewed. CONCLUSION: There are no ideal screening tests. The election of the most appropriate will depend on the physicians time and knowledge of each test. It is advisable to be familiar with a reduced number of tests, and be aware of their strengths and limitations. Finally, we suggest personal recommendations for the most useful tests in each clinical setting.

Fanatismo: interés en psiquiatría forense penal / Fanatism: interest in criminal forensic psychiatry

En el presente trabajo describimos el fanatismo desde una doble dimensión, la cognitiva y la personológica y vemos el carácter gradual de este fenómeno. Desde estos presupuestos conceptuales planteamos las posibles anomalías que pueden hallarse en el continuum sujeto/creencia normal - sujeto/creencia fanático y como tales alteraciones podrían afectar a la capacidad de responder penalmente de estas personas. Para ello deben ser comprendidas las distorsiones cognitivas que suponen la creencia fanática y las eventuales anomalías en la estructura de la personalidad del sujeto fanático (AU)

This paper describes the fanatism from two viewpoints, cognitive and personological and looks at the progressive nature of this phenomenon. Based on these conceptual hypotheses, we present the anomalies which may be found in the continuum of subject/normal belief - subject/ fanatical belief and how these changes affect the capacity of these individuals to respond criminally. This requires the understanding of the cognitive disturbances implied by fanatical belief and the potential anomalies in the structure of the fanatical subject's personality (AU)

A new chloroplast envelope carbonic anhydrase activity is induced during acclimation to low inorganic carbon concentrations in Chlamydomonas reinhardtii.

Using mass-spectrometric measurements of 18O exchange from 13C18O2 we determined the activity of carbonic anhydrase (CA; EC 4.2.1.1) in chloroplast envelope membranes isolated from Chlamydomonas reinhardtii cw-15. Our results show an enrichment of CA activity in these fractions relative to the activity in the crude chloroplast. The envelope CA activity increased about 8-fold during the acclimation to low-CO2 conditions and was completely induced within the first 4 h after the transfer to air levels of CO2. The CA-activity was not dissociated from envelope membranes after salt treatment. In addition, no cross-reactivity with other CA isoenzymes of Chlamydomonas was observed in our chloroplast envelope membranes. All these observations indicated that the protein responsible for this activity was a new CA isoenzyme, which was an integral component of the chloroplast envelopes from Chlamydomonas. The catalytic properties of the envelope CA activity were completely different from those of the thylakoid isoenzyme, showing a high requirement for Mg2+ and a high sensitivity to ethoxyzolamide. Analysis of the integral envelope proteins showed that there were no detectable differences between high- and low-inorganic carbon (Ci) cells, suggesting that the new CA activity was constitutively expressed in both high- and low-Ci cells. Two different high-Ci-requiring mutants of C. reinhardtii, cia-3 and pmp-1, had a reduced envelope CA activity. We propose that this activity could play a role in the uptake of inorganic carbon at the chloroplast envelope membranes.

[Nonconvulsive status epilepticus: experience in 33 patients]. / Status epiléptico no convulsivo: experiencia en 33 pacientes.

BACKGROUND: To review the nonconvulsive status epilepticus diagnosed in a general hospital in order to identify its frequency, electroclinical characteristics and response to medical treatment. PATIENTS ANTS AND METHODS: A retrospective study of 33 cases of nonconvulsive status epilepticus was undertaken. The diagnosis was based on clinical and EEG manifestations. Data regarding their clinical presentation, previous epilepsy, etiology of the status, its medical management and outcome were analysed. RESULTS: The 33 patients comprising the study included 20 men and 13 women. The medium age was 49.8 years. A previous history of epilepsy was present in 51.5% of them. Most of the patients presented impaired consciousness (39.4%) or confusional state (36%). The mean duration of the disorder did not exceed 24 hours (64.5%). There were five cases of absence status and 28 of complex partial status, two of them with secondary generalization. A precipitating factor was found in 80% of the patients and the cerebrovascular etiology was the most frequent. There was a good response to phenytoin (80%), although in the first month death was the final outcome for 25% of them. CONCLUSIONS: Nonconvulsive status epilepticus is an underdiagnosed medical emergency because of its different manifestations, similar to confusional or psyquiatric states. The precipitating factor determines its outcome. A high index of suspicion is needed in order to make a faster diagnosis and treatment.

Utilidad de los test breves en el cribado de demencia / Usefulness of short tests in dementia screening

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Degeneración combinada subaguda medular: hallazgos en la resonancia magnética / Subacute combined degeneration of the spinal cord: MR findings

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