Echocardiographic findings in acromegaly: prevalence of concentric left ventricular remodeling in a large single-center cohort.

PURPOSE: Acromegaly is a rare disease and is associated with increased cardiovascular (CV) morbidity and mortality, especially in patients with uncontrolled disease. We aimed to analyze the prevalence and severity of cardiomyopathy and valvular heart disease in a large cohort of patients with a confirmed acromegaly diagnosis, at baseline and after treatment. METHODS: We retrospectively reviewed an institutional approved database; 190 patients with confirmed acromegaly and follow-up data available (years 2006-2018). Patients with at least one baseline echocardiogram, were included. Demographic, disease control and echocardiogram variables were collected for analysis. RESULTS: Of the 190 patients 110 (58%) had a baseline echocardiogram and 43 (39.1%) had at least one follow-up echocardiogram after surgical, medical or multimodal treatment. Baseline left ventricular hypertrophy (LVH) prevalence was 17.8% (64.7% concentric; 35.3% eccentric), diastolic and systolic dysfunction, and overt cardiomyopathy with heart failure were 15.8, 7.9, and 3.0%, respectively. Concentric remodeling of the left ventricle (LV) was noted in 31.4% of patients without LVH. Valve defects were found in 87.3% of patients (14.6% with significant valvular heart disease). CONCLUSION: Early diagnosis of acromegaly and disease control should be attempted to prevent LVH/LV dysfunction and development of valvular heart disease. Concentric LV remodeling develops prior to obvious LV hypertrophy in almost a third of patients with acromegaly, which is a novel finding. Similar to other epidemiological studies, we found a high prevalence of LVH/LV dysfunction. Although possible, reversal of systolic and diastolic dysfunction is sporadic after treatment of acromegaly.

Scheduled food hastens re-entrainment more than melatonin does after a 6-h phase advance of the light-dark cycle in rats.

Circadian desynchrony occurs when individuals are exposed to abrupt phase shifts of the light-dark cycle, as in jet lag. For reducing symptoms and for speeding up resynchronization, several strategies have been suggested, including scheduled exercise, exposure to bright light, drugs, and especially exogenous melatonin administration. Restricted feeding schedules have shown to be powerful entraining signals for metabolic and hormonal daily cycles, as well as for clock genes in tissues and organs of the periphery. This study explored in a rat model of jet lag the contribution of exogenous melatonin or scheduled feeding on the re-entrainment speed of spontaneous general activity and core temperature after a 6-h phase advance of the light-dark cycle. In a first phase, the treatment was scheduled for 5 days prior to the phase shift, while in a second stage, the treatment was simultaneous with the phase advance of the light-dark cycle. Melatonin administration and especially scheduled feeding simultaneous with the phase shift improved significantly the re-entrainment speed. The evaluation of the free-running activity and temperature following the 5-day treatment proved that both exogenous melatonin and specially scheduled feeding accelerated re-entrainment of the SCN-driven general activity and core temperature, respectively, with 7, 5 days (p < 0.01) and 3, 3 days (p < 0.001). The present results show the relevance of feeding schedules as entraining signals for the circadian system and highlight the importance of using them as a strategy for preventing internal desynchrony.

The nigrostriatal pathway: axonal collateralization and compartmental specificity.

This paper reviews two of the major features of the nigrostriatal pathway, its axonal collateralization, and compartmental specificity, as revealed by single-axon labeling experiments in rodents and immunocytological analysis of human postmortem tissue. The dorsal and ventral tiers of the substantia nigra pars compacta harbor various types of neurons the axons of which branch not only within the striatum but also in other major components of the basal ganglia. Furthermore, some nigrostriatal axons send collaterals both to thalamus and to brainstem pedunculopontine tegmental nucleus. In humans, the compartmental specificity of the nigrostriatal pathway is revealed by the fact that the matrix compartment is densely innervated by dopaminergic fibers, whereas the striosomes display different densities of dopaminergic terminals depending on their location within the striatum. The nigral neurons most severely affected in Parkinson's disease are the ventral tier cells that project to the matrix and form deep clusters in the substantia nigra pars reticulata.

Formation and characterization of nanotubes of La(OH)(3) obtained using porous alumina membranes.

An electrodeposition process is used to synthesize nanotubes of a lanthanum-containing phase, employing porous alumina membranes as templates. This method should lead to the formation of La(OH)(3) nanowires, according to the previous results presented by Bocchetta et al (2007 Electrochem. Commun. 9 683-8), which can be decomposed to La(2)O(3), as the latter shows more interest for different applications. The results obtained by means of different electron microscopy techniques indicate that this method leads to the formation of nanotubes of about 200 nm in diameter and 30-40 µm in length, instead of the nanowires proposed in the literature. Additionally, the chemical characterization demonstrates that the material synthesized is composed of lanthanum hydroxycarbonate. The presence of carbonates is found to be crucial in determining the conditions for the preparation of La(2)O(3) from the nanotubes here obtained.

Chemical architecture of the posterior striatum in the human brain.

The neurochemical organization of the posterior caudate nucleus (CN) (body, gyrus and tail) and putamen (Put) was analyzed in the human brain using adjacent sections stained for acetylcholinesterase (AChE), limbic system-associated membrane protein (LAMP), enkephalin (ENK), parvalbumin (PV), calbindin (CB) and tyrosine hydroxylase (TH). Striosomes were visualized in all striatal regions but the anterior two thirds of the CN tail. They were highly immunoreactive (-ir) for ENK and LAMP, devoid of PV and AChE staining, and surrounded by a ring of tissue with pale TH- and CB-ir neuropil. In the Put, other rings of tissue completely free of ENK labeling surrounded certain striosomes (clear septa). In the CN body, gyrus and tail some markers revealed gradients and heterogeneities along the dorsoventral and mediolateral axes. A rim of striatal tissue densely stained for ENK and LAMP and poorly labeled for PV was noticeable along the lateral edge of the Put and the dorsolateral sector of the CN body. Our results illustrate a chemical architecture in the posterior striatum that is heterogeneous and slightly different from that found in the more anterior striatum.

[The amygdaloid complex and its implication in psychiatric disorders]. / El complejo amigdalino humano y su implicación en los trastornos psiquiátricos.

The amygdaloid complex is a group of nuclei located deep in the temporal lobe and closely involved in the limbic system. Its alteration has been associated with some psychiatric processes. In this article, an overall review was made of the published data concerning the amygdaloid complex in the most common psychiatric diseases. A damaged amygdaloid complex is commonly observed, that in the Klüver-Bucy syndrome presents the fullest expression. A decrease in the amygdaloid complex of schizophrenic patients has been observed. This finding was found bilaterally in men whereas in women it was only located in one hemisphere. This finding suggests that morphometric alterations in the amygdaloid complex are more diffuse and more severe in men with schizophrenia. This subcortical complex is larger in children with autism, but not in adolescents, in whom the amygdaloid complex volume matches the normal volume of an adolescent or an adult without this pathology. However, neuroanatomical studies have shown microscopic alterations. In patients with mood disorders, it has been reported that the left amygdaloid complex presents a lesser volume. Moreover, in frontotemporal dementia and Alzheimer disease a slight amygdaloid atrophia was found related to the healthy controls. It can be concluded that the amygdaloid complex is involved in several psychiatric processes, due to structural or functional damage. However, more studies are still needed in order to delimitate the real influence of the amygdaloid complex in these disorders.

El complejo amigdalino humano y su implicación en los trastornos psiquiátricos / The amygdaloid complex and its implication in psychiatric disorders

El complejo amigdalino es un conjunto de núcleos que se localizan en la profundidad del lóbulo temporal, y que guardan estrecha relación con el sistema límbico. Su alteración se ha asociado a un gran número de procesos psiquiátricos. En este artículo se pretende hacer una revisión de lo publicado en referencia a la implicación amigdalina en trastornos psiquiátricos comunes. En ellos se observa un complejo amigdalino alterado, siendo su máxima expresión el síndrome de Klüver-Bucy. En pacientes esquizofrénicos se ha observado una reducción del volumen amigdalino, bilateral en varones y unilateral en mujeres. Esto sugiere que las alteraciones morfométricas del complejo amigdalino están más extendidas en varones esquizofrénicos. El complejo amigdalino está aumentado en niños autistas, no siendo así en adolescentes, donde se iguala al volumen de cualquier adolescente o adulto sano. Sin embargo, estudios neuroanatómicos han demostrado patología microscópica. En los pacientes con trastornos en el estado de ánimo, se observa una cierta tendencia a presentar un complejo amigdalino izquierdo de menor volumen. El volumen amigdalino de los grupos con demencia frontotemporal y enfermedad de Alzheimer era diferente a los del grupo de control, y se ha visto una predisposición al incremento de la atrofia amigdalina. Se puede afirmar que el complejo amigdalino está implicado en numerosos procesos psiquiátricos, tanto por daño estructural de dicho complejo como por daño funcional. Sin embargo, hacen falta más estudios para delimitar la influencia real del complejo amigdalino en dichos trastornos

The amygdaloid complex is a group of nuclei located deep in the temporal lobe and closely involved in the limbic system. Its alteration has been associated with some psychiatric processes. In this article, an overall review was made of the published data concerning the amygdaloid complex in the most common psychiatric diseases. A damaged amygdaloid complex is commonly observed, that in the Klüver-Bucy syndrome presents the fullest expression. A decrease in the amygdaloid complex of schizophrenic patients has been observed. This finding was found bilaterally in men whereas in women it was only located in one hemisphere. This finding suggests that morphometric alterations in the amygdaloid complex are more diffuse and more severe in men with schizophrenia. This subcortical complex is larger in children with autism, but not in adolescents, in whom the amygdaloid complex volume matches the normal volume of an adolescent or an adult without this pathology. However, neuroanatomical studies have shown microscopic alterations. In patients with mood disorders, it has been reported that the left amygdaloid complex presents a lesser volume. Moreover, in frontotemporal dementia and Alzheimer disease a slight amygdaloid atrophia was found related to the healthy controls. It can be concluded that the amygdaloid complex is involved in several psychiatric processes, due to structural or functional damage. However, more studies are still needed in order to delimitate the real influence of the amygdaloid complex in these disorders

Chemical parcellation of the anterior thalamic nuclei in the human brain.

The anterior thalamic nuclei (ATN) encompass a large region of the anteromedial aspect of the human thalamus. Three ATN have been classically described: anteroventral (AV), anteromedial (AM) and anterodorsal (AD). The present study has carried out histochemical and immunohistochemical procedures in the ATN of normal individuals to analyze whether these nuclei are chemically distinct. The markers used in this study were acetylcholinesterase (AChE), limbic system-associated membrane protein (LAMP), the calcium binding proteins calbindin D-28k (CB), parvalbumin (PV), and calretinin (CR), and the neuropeptides substance P (SP) and enkephalin (ENK). Other cytoarchitectural and myeloarchitectural techniques, specifically Nissl and Gallyas stainings, were used to delineate the boundaries of the ATN. The main findings of this study are: 1) AChE was very abundant in the AD and was irregular or heterogeneously distributed in the AV and AM; 2) LAMP immunoreactive (ir) neuropil was present throughout the ATN and its distribution was heterogeneous in the AV and AM; 3) the ATN harbored CB-, PV- and CR-ir neurons and neuropil; and, 4) the neuropeptide analysis revealed numerous SP positive varicose fibers scattered throughout the ATN in contrast to very few ENK-ir varicose fibers. These morphological findings describe a heterogeneous chemical anatomy in the human ATN which may reflect regional differences in the functional organization of the ATN with respect to the other thalamic nuclei and the cerebral cortex.

Algunas reflexiones sobre la utilización del índice de impacto como medida de calidad en la investigación / Some considerations upon the use of the impart factor as measure for research quality

En este artículo se presentan algunas consideraciones sobre la utilización del índice de impacto como medida de calidad en la investigación. Después de hacer una referencia histórica del concepto de índice de impacto, se analizan algunos aspectos a tener en cuenta cuando se utiliza esta medida de las citaciones. También se comentan algunas críticas a su uso como parámetro de evaluación de calidad de una investigación individual o de curricula en la promoción y contratación de investigadores y en la concesión de ayudas científicas. (AU)

Barrel pattern formation requires serotonin uptake by thalamocortical afferents, and not vesicular monoamine release.

Thalamocortical neurons innervating the barrel cortex in neonatal rodents transiently store serotonin (5-HT) in synaptic vesicles by expressing the plasma membrane serotonin transporter (5-HTT) and the vesicular monoamine transporter (VMAT2). 5-HTT knock-out (ko) mice reveal a nearly complete absence of 5-HT in the cerebral cortex by immunohistochemistry, and of barrels, both at P7 and adulthood. Quantitative electron microscopy reveals that 5-HTT ko affects neither the density of synapses nor the length of synaptic contacts in layer IV. VMAT2 ko mice, completely lacking activity-dependent vesicular release of monoamines including 5-HT, also show a complete lack of 5-HT in the cortex but display largely normal barrel fields, despite sometimes markedly reduced postnatal growth. Transient 5-HTT expression is thus required for barrel pattern formation, whereas activity-dependent vesicular 5-HT release is not.

Striatal input from the ventrobasal complex of the rat thalamus.

We have analyzed whether caudal regions of the caudate putamen receive direct projections from thalamic sensory relay nuclei such as the ventrobasal complex. To this aim, the delivery of the retrograde neuroanatomical tracer Fluoro-Gold into the caudal caudate putamen resulted in the appearance of retrogradely labeled neurons in the ventral posteromedial and ventral posterolateral thalamic nuclei. These projections were further confirmed with injections of the anterograde tracers biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin into these thalamic nuclei, by showing the existence of axonal terminal fields located in the caudal striatum. These results support the existence of direct projections linking the thalamic ventrobasal complex and the caudal striatum in the rat, probably via collateralization of thalamocortical axons when passing through the caudate putamen, and therefore supporting the putative involvement of the caudal striatum in sensory-related functions.

Thalamic distribution of zinc-rich terminal fields and neurons of origin in the rat.

Several cortico-cortical and limbic-related circuits are enriched in zinc, which is considered as an important modulator of glutamatergic transmission. While heavy metals have been detected in the thalamus, the specific presence of zinc has not been examined in this region. We have used two highly sensitive variations of the Timm method to study the zinc-rich innervation in the rat thalamus, which was compared to the distribution of acetylcholinesterase activity. The origin of some of these zinc-rich projections was also investigated by means of retrograde transport after intracerebral infusions of sodium selenium (Na2SeO3). The overall zinc staining in the thalamus was much lower than in the neocortex, striatum or basal forebrain; however, densely stained terminal fields were observed in the dorsal tip of the reticular thalamic nucleus, the anterodorsal and lateral dorsal thalamic nuclei and the zona incerta. In addition, moderately stained zinc-rich terminal fields were found in the rostral intralaminar nuclei, nucleus reuniens and lateral habenula. Intracerebral infusions of Na2SeO3 in the lateral dorsal nucleus resulted in retrogradely labeled neurons that were located in the postsubiculum, and also in the pre- and parasubiculum. These results are the first to establish the existence of a zinc-rich subicular-thalamic projection. Similar infusions in either the intralaminar nuclei or the zona incerta resulted in labeling of neurons in several brainstem structures related to the reticular formation. Our results provide morphological evidence for zinc modulation of glutamatergic inputs to highly selective thalamic nuclei, arising differentially from either cortical limbic areas or from brainstem ascending activation systems.

Double retrograde tracer study of the corticostriatal projections to the cat caudate nucleus.

The distribution of corticostriatal neurons projecting to the caudate nucleus was examined in the cat by retrograde fluorescent tracers. Thus, Fast Blue and Diamidino Yellow were concomitantly injected in different rostrocaudal, dorsoventral, or mediolateral sectors of the caudate nucleus. The main findings of this study are: 1) few double-labeled cells were found after two injections in different sectors of the caudate nucleus; 2) double-labeled neurons were more abundant after adjacent injections and they were mainly located in 6 alpha beta, dorsolateral prefrontal, dorsomedial prefrontal, prelimbic, anterior limbic, sylvian anterior, and rostral part of cingulate cortical areas; and 3) there were variations in the spatial organization of the corticostriatal neurons in different cortical areas projecting to various parts of the caudate nucleus.

[The use of the impact index as a quality measure in research]. / Algunas reflexiones sobre la utilización del índice de impacto como medida de calidad en la investigación.

In this article some considerations are made upon the use of the impact factor as a measure for the quality in research. A historical view of the term "impact factor" is presented together with other aspects to keep in mind when the impact factor is used as a measure of citations. In addition, some criticisms are pointed out in the use of the impact factor as a tool to evaluate the quality of research, funding, employment and tenure.

Complex brain circuits studied via simultaneous and permanent detection of three transported neuroanatomical tracers in the same histological section.

Experimental neuroanatomical tracing methods lie at the basis of the study of the nervous system. When the scientific question is relatively straightforward, it may be sufficient to derive satisfactory answers from experiments in which a single neuroanatomical tracing method is applied. In various scientific paradigms however, for instance when the degree of convergence of two different projections on a particular cortical area or subcortical nucleus is the subject of study, the application of single tracing methods can be either insufficient or uneconomical to solve the questions asked. In cases where chains of projections are the subjects of study, the simultaneous application of two tracing methods or even more may be compulsory. The present contribution focuses on combinations of several neuroanatomical tract-tracing strategies, enabling in the end the simultaneous, unambiguous and permanent detection of three transported markers according to a three-color paradigm. A number of combinations of three tracers or of two tracers plus the immunocytochemical detection of a neuroactive substance can be conceived; we describe several of these combinations implemented by us using the present multitracer protocol.

Considerations on the thalamostriatal system with some functional implications.

The thalamostriatal projections are largely neglected in current reviews dealing with basal ganglia function. In the past few years, however, several studies have re-evaluated these projections and have postulated their implication in more complex tasks within the basal ganglia organization. In this review, we try to focus on the morphological and functional importance of this system in the basal ganglia of the rat, cat and monkey. Special attention is paid to the thalamus as an important place for interaction between the input and the output systems of the basal ganglia through the thalamostriatal projections. Thus, we stress on the overlapping thalamic territories between the thalamic projection of the output nuclei of the basal ganglia and the thalamostriatal neurons. Our experimental data support the existence of several thalamic feedback circuits within the basal ganglia functional design. Finally, some considerations are provided upon the functional significance of these thalamic feedback circuits in the overall organization of the basal ganglia in health and disease.

[Functional anatomy of the cerebral cortex implicated in visual processing]. / Anatomía funcional de la corteza cerebral implicada en los procesos visuales.

INTRODUCTION AND OBJECTIVE: The functional anatomy of the cerebral cortex implicated in vision is reviewed with the purpose of illustrating the complexity of the cortical processing in visual perception. DEVELOPMENT: A brief analysis of the retinogeniculocortical pathway is presented and a summary of the main findings of the physiological and anatomical studies of Hubel and Wiesel in the adult brain is also illustrated. Special attention is paid in showing the visual pathways for object and face recognition as well as spatial cognition. CONCLUSIONS: Visual cortical areas in primates and man can be divided roughly into a ventral stream in relation with the temporal lobe responsible for the processing and storage of information about the identity of objects, their shape, color, and other salient physical features; and a dorsal stream in relation with the parietal lobe and concerned with the analysis of the locations of objects, and their movements in space. These two cortical pathways are not totally segregated and both are related to the prefrontal cortex as well as other subcortical structures such as the thalamus, the basal ganglia, the superior colliculus and the cerebellum through the pontine nuclei.

Considerations upon the anatomical model of reward-based learning in the basal ganglia.

The nigrostriatal pathway appears to be very important in the reward-based learning. The dopaminergic neurons in the substantia nigra pars compacta (SNC) fire in relation to primary rewards and reward-conditioned stimuli, but not to rewards that are expected. It has been hypothesized that the anatomical framework for the selective response of these neurons is organized in the projections from some paralimbic areas in the frontal lobe to the striosomes of the caudate nucleus, which are also directly connected with the dopaminergic neurons of the SNC. Here, we present two additional pathways that may be related with this neurophysiological finding. We hypothesize that the connections of the paralimbic cortices with the ventral system of the basal ganglia and then with the thalamus and the hypothalamus, and the circuit ventral striatum-substantia nigra pars reticulata-thalamus-striatum could be also involved in the reward-based learning.

Anatomical re-evaluation of the corticostriatal projections to the caudate nucleus: a retrograde labeling study in the cat.

The distribution of cortical neurons projecting to the cat caudate nucleus (CN) was examined using retrograde labeling methods. Single injections of either horseradish peroxidase conjugated with wheat germ agglutinin (HRP-WGA), or the fluorescent tracers Fast Blue (FB) or Diamidino Yellow (DY) were made into different regions of the CN. This study confirms the following previous findings. (1) Labeled neurons were observed in the frontal and parieto-temporal cortices. (2) The corticocaudate cells were mainly located in layer V, although some cells were also observed in layer III and occasionally in layers II and VI. (3) Dorsal injections into the rostral CN yielded more dorsal labeling in the cerebral cortex. However, ventral cortical areas such as the ventral part of the prelimbic (PL) cortical area and the insular cortex (sylvian anterior (SA), agranular and disgranular insular areas) presented retrograde labeling after both dorsal and ventral injections into the CN. (4) Dorsal injections into the CN labeled all subdivisions of areas 4 and 6 whereas the ventral ones labeled only the areas 4delta, 6alphabeta, 6aalpha, 6iffu. The novel findings of this study are as follows. (1) The cortical area 6betabeta and the dorsolateral prefrontal area (PfDl) were labeled in all our cases. In addition, PL, anterior limbic, SA and rostral part of cingulate (Cg) cortical areas were also labeled in most of our cases. (2) Ventral injections into the CN elicited a higher number of retrogradely labeled neurons in the ventral prefrontal area than dorsal injections. (3) A topographical relationship was found between the caudal CN and the dorsomedial prefrontal area so that dorsal injections in the caudal CN elicited retrograde labeling in the rostral PfDl, whereas ventral injections labeled the caudal PfDl. (4) A topography from dorsal to rostral and ventral to caudal was also observed between injections into the CN and PL and Cg. (5) A mediolateral topography was observed in the presylvian, cruciate and splenial sulci.