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The establishment of the dominant-subordinate status implies a clear behavioral asymmetry between contenders that arises immediately after the resolution of the agonistic encounter and persists during the maintenance of stable dominance hierarchies. Changes in the activity of the brain social behavior network (SBN) are postulated to be responsible for the establishment and maintenance of the dominant-subordinate status. The hypothalamic nonapeptides of the vasopressin (AVP) and oxytocin (OT) families are known to modulate the activity of the SBN in a context-dependent manner across vertebrates, including status-dependent modulations. We searched for status-dependent asymmetries in AVP-like (vasotocin, AVT) and OT-like (isotocin, IT) cell number and activation immediately after the establishment of dominance in males of the weakly electric fish, Gymnotus omarorum, which displays the best understood example of non-breeding territorial aggression among teleosts. We used immunolabeling (FOS, AVT, and IT) of preoptic area (POA) neurons after dyadic agonistic encounters. This study is among the first to show in teleosts that AVT, but not IT, is involved in the establishment of the dominant-subordinate status. We also found status-dependent subregion-specific changes of AVT cell number and activation. These results confirm the involvement of AVT in the establishment of dominance and support the speculation that AVT is released from dominants' AVT neurons.

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We have developed two ligand- and receptor-based computational approaches to study the physicochemical properties relevant to the biological activity of vasopressin V2 receptor (V2R) antagonist and eventually to predict the expected binding mode to V2R. The obtained quantitative structure activity relationship (QSAR) model showed a correlation of the antagonist activity with the hydration energy (EH2O), the polarizability (P), and the calculated partial charge on atom N7 (q6) of the common substructure. The first two descriptors showed a positive contribution to antagonist activity, while the third one had a negative contribution. V2R was modeled and further relaxed on a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocoline (POPC) membrane by molecular dynamics simulations. The receptor antagonist complexes were guessed by molecular docking, and the stability of the most relevant structures was also evaluated by molecular dynamics simulations. As a result, amino acid residues Q96, W99, F105, K116, F178, A194, F307, and M311 were identified with the probably most relevant antagonist-receptor interactions on the studied complexes. The proposed QSAR model could explain the molecular properties relevant to the antagonist activity. The contributions to the antagonist-receptor interaction appeared also in agreement with the binding mode of the complexes obtained by molecular docking and molecular dynamics. These models will be used in further studies to look for new V2R potential antagonist molecules.

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Abstract The present study aimed to measure the mortality burden caused by premature death due to substance abuse in different geographical regions of Iran from 2014-17. In this serial cross-sectional study, the data related to individuals who had died of drug abuse were first collected from two sources (Iranian Ministry of Health and Medical Education and the Iranian Legal Medicine Organization). Then, using the capture-recapture method, the number of drug-related deaths was estimated. The years of life lost (YLLs) for all provinces of Iran was calculated based on age, sex, and year. During these four years, the total number of deaths was 12029. The mean age of the individuals was 37.3±14.1. The mean age of dead people was constant in women and men over this period; however, the mean age of dead women due to substance abuse was lower than that of men. The mean YLLs per dead person was 70131.3329 years for men and 9321.1125 years for women. The potential years of life lost (YLLs) showed an upward trend, which was stronger in women than men. It is necessary to perform more regional overviews for finding differences in the number of YLLs due to substance abuse so that specific regional policies can be adopted.

Resumo O presente estudo teve como objetivo medir a carga de mortalidade causada por morte prematura por abuso de substâncias em diferentes regiões do Irã de 2014-17. Neste estudo transversal serial, os dados relacionados aos indivíduos que morreram por abuso de drogas foram coletados primeiramente em duas fontes (Ministério da Saúde e Educação Médica do Irã e Organização de Medicina Legal do Irã). Em seguida, usando o método de captura-recaptura, estimou-se o número de mortes relacionadas a drogas. Os anos de vida perdidos (AVP) para todas as províncias do Irã foram calculados com base na idade, sexo e ano. Durante quatro anos, o número total de óbitos foi de 12029. A média de idade dos indivíduos foi de 37,3±14,1. A média de idade dos mortos foi constante em mulheres e homens ao longo desse período; entretanto, a média de idade das mulheres mortas por abuso de substâncias foi menor do que a dos homens. O AVP médio por pessoa morta foi de 70131,3329 anos para homens e 9321,1125 anos para mulheres. Os anos potenciais de vida perdidos (APVP) apresentaram tendência ascendente, sendo mais forte nas mulheres do que nos homens. É necessário realizar mais análises regionais para encontrar diferenças no número de AVP devido ao abuso de substâncias.

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Resumen Introducción: México atraviesa por un contexto de violencia creciente que incluye el aumento de homicidios y feminicidios a lo largo del territorio nacional. Los estudios existentes presentan vacíos de corte regional y de grupos de edad, en particular, el de 0 a 17 años. El objetivo de este artículo es describir el impacto de la mortalidad por homicidios sobre la población de 0 a 17 años en el sureste mexicano, una de las regiones más sacrificadas en materia de derechos humanos y bienestar social. Metodología: mediante las estadísticas de mortalidad general del Instituto Nacional de Estadística y Geografía, se calcularon las tasas brutas de mortalidad y las tasas específicas por sexo y grupos de edad correspondientes al período 2000-2017. Se estimó el promedio de Años de Vida Perdidos. El tipo de estudio es descriptivo y analiza el efecto de los homicidios en la tendencia de la mortalidad y la esperanza de vida. Resultados: los resultados mostraron que el más alto porcentaje de homicidios lo obtuvieron los hombres de todos los grupos etarios. En términos del promedio de AVP, las mujeres adolescentes del conjunto de 12 a 17 años evidenciaron los mayores incrementos. Conclusiones: las tasas de mortalidad por homicidio se comportaron heterogéneamente; resalta la vigencia y aumento de ataques letales contra niñas, niños y, especialmente, adolescentes.

Abstract Introduction: Mexico is currently facing a context of raising violence that includes the increase of homicides and feminicides in the nation-wide territory. The existent studies present certain gaps regarding regional and age groups information. In particular, those gaps are relevant for population from 0 to 17 years old. That is why this article aims to describe the mortality impacts by means of homicides among that age group in Southeast Mexico. This region is one of the most abandoned in terms of Human Rights and Social Well-Being. Methodology: The article uses the general mortality statistics of the National Institute of Statistics and Geography to calculate the gross mortality rates as well as the specific rates by age and sex groups from 2000 to 2017. Likewise, the average years of life lost are calculated. The study is descriptive and analyzes the impact of homicides within the trend of mortality and life expectancy. Results: A main result shows to the highest percentage of homicides occur among men. However, in terms of the average number of YLL and for the age group 12 to 17 years the largest increases occur among adolescent women. Conclusions: The Southeast region of Mexico presents heterogeneous behavior in homicide mortality rates for the age group 0 to 17 years, highlights the validity and increase of lethal violence against girls, boys and particularly adolescents.

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The origin and functional significance of vasopressin (AVP)-containing fibres in limbic regions has been an ongoing subject of investigation for several years. We have previously identified AVP-magnocellular neurones of rat hypothalamus that provide glutamatergic projections to the hippocampus, amygdala, lateral habenula and locus coeruleus. However, we also reported AVP-immunopositive fibres in those regions that are thin and make Gray type II synapses, which are unlikely to be of magnocellular origin. Therefore, in the present study, we characterised AVP mRNA co-expression with expression of mRNAs marking glutamatergic (vesicular glutamate transporter [VGLUT]) and GABAergic (vesicular GABA transporter [VGAT]) neuronal traits in rat and mouse brain, using high-resolution in situ hybridisation methods, including a radio-ribonucleotide and RNAscope 2.5 HD duplex assay, with Slc17a7, Slc17a6, Slc32a1 and Avp probes corresponding to mRNAs of VGLUT1, VGLUT2, VGAT and AVP, respectively. We located 18 cell groups expressing Avp and identified their molecular signatures for VGLUT and VGAT mRNA expression. Avp cell groups of hypothalamus and midbrain are mainly VGLUT mRNA-expressing, whereas those in regions derived from cerebral nuclei are mainly VGAT mRNA-expressing, suggesting a functional segregation of glutamate/GABA co-transmission with AVP. A newly identified Slc17a7 and Slc17a6 (but not Slc32a1) expressing vasopressinergic cell group was found in layer II-III neurones of the central entorhinal cortex, which projects to the hippocampus. These data support the notion of a complex role for AVP with respect to modulating multiple central circuits controlling behaviour in specific ways depending on co-transmission with glutamate or GABA, potentially giving rise to a functional classification of AVPergic neurones in the central nervous system.

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Introducción: El guayacán real (Guaiacum sanctum; Zygophyllaceae) de Mesoamérica y las Antillas está amenazado en gran parte de su área de distribución. Evaluamos si una población de G. sanctum en el Parque Nacional Palo Verde en Costa Rica es viable a largo plazo. Métodos Usando dos estudios demográficos, uno en 1997 y otro en 2017, estimamos las tasas de supervivencia y fecundidad para cada clase de edad, la tasa de crecimiento poblacional (lambda), y las elasticidades para cada tasa vital, y usamos un modelo determinístico denso-independiente para proyectar la trayectoria a largo plazo de la población. Resultados: Las tasas vitales estimadas durante los últimos 20 años sugieren que esta población está disminuyendo rápidamente, con un lambda estimado de 0.62. Aunque algunas clases de edad aumentaron en abundancias, los renovales son raros y los individuos reclutados en 1997 aún no alcanzaron la madurez reproductiva. Nuestros resultados sugieren que la abundancia actual de G. sanctum dentro del Parque Nacional podría no ser un buen indicador del estado de conservación a largo plazo, y por nuestro análisis de viabilidad poblacional, estimamos que la población estudiada disminuiría a menos del 1 % de su actual abundancia en los próximos 200 años. Conclusiones: El deterioro ecosistémico a escala de paisaje esta afectando la región del Parque Nacional Palo Verde, como la pérdida de dispersores de semillas y la supresión de alteraciones, podría compensar la protección pasiva de G. sanctum dentro de los límites del Parque Nacional. Confiar en la estricta protección dada por la locación de la población dentro del parque podría no ser suficiente para conservar esta población de G. sanctum. Recomendamos incorporar, dentro de un programa de investigación, una protección experimental más proactiva y/o medidas de restauración, posiblemente incluyendo tratamientos de alteraciones.

Introduction: The Lignum-vitae (Guaiacum sanctum; Zygophyllaceae) of Mesoamerica and the Greater Antilles, is threatened over much of its range. We evaluated whether a G. sanctum population in the Palo Verde National Park of Costa Rica is viable in the long term. Methods: Using two demographic studies, one in 1997 and the other in 2017, we estimated survival and fecundity rates for each tree age class, population growth rate (lambda), and vital rates elasticity, and we used a density-independent deterministic population model to project the long-term trend of that population. Results: The estimated vital rates during the last 20 years suggested that this population is rapidly decreasing. Although some age classes increased in abundance, seedlings are rare and the plants that recruited in 1997 have not yet reached reproductive maturity. Our results suggest that the current abundance of G. sanctum within the national park may not be a good indicator of its long-term conservation status, and from our population viability analysis, we estimated that the population we studied would decrease to less than 1 % of its current size within the next 200 years. Conclusions: Landscape-scale ecosystem deterioration affecting the greater PVNP region, such as loss of seed dispersers and suppression of disturbances, may offset the passive protection of G. sanctum within park boundaries. Relying on the overall strict protection afforded by the location of the population within the Palo Verde National Park may not be sufficient to conserve this population of G. sanctum. We recommend that more proactive experimental protection and/or restoration measures, possibly including disturbance treatments, be implemented within a research program.

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Resumen Paciente de 48 años con historia de fibrilación auricular paroxística, dislipidemia y antecedente de ablación de vía accesoria (2013). Anti coagulado con Rivaroxaban 20 mg PO. Paciente es llevado a aislamiento percutáneo de venas pulmonares (AVP) con sistema de navegación tridimensional Carto 3. 48 horas post AVP inicia con cuadro de distrés respiratorio agudo que requiere hospitalización en unidad de cuido intensivo, que resuelve con manejo diurético y antiinflamatorio. Describimos la importancia del manejo hídrico en relación al AVP.

Abstract 48 years old male, previous history of paroxysmal atrial fibrillation, hiperlipemia and previous accesory pathway ablation an 2013. Anticoagulated with Rivaroxaban 20mg PO. Patient underwent pulmonary vein insolation (PVI) with Carto 3 tridimensional navigation and mapping system. Discharged on day 1 after PVI, readmitted with acute respiratory distress that required intensive care unit admission that resolves with diuretics and anti-inflammatory management. We describe the role of hydric management related with PVI procedure.

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AIM: Development of compounds with therapeutic application requires the interaction of different disciplines. Several tumors express vasopressin (AVP; arginine vasopressin) receptors with contrasting effects depending on receptor subtype. Desmopressin (dDAVP) is an AVP-selective analog with antiproliferative properties. In this work, an evolutionary approach and a rational strategy were applied in order to design novel AVP analogs. RESULTS: We designed two novel analogs; dDInotocin (dDINT, insect analog), and [V4Q5]dDAVP, and demonstrated the importance of the dDAVP conformational loop for its antiproliferative activity. [V4Q5] dDAVP showed major cytostatic effect on lung cancer cells than dDAVP and its cytostatic effect was abolished by V2R blockade. CONCLUSION: Combination of these strategies could provide the basis for future studies for the development of improved compounds with potential therapeutic applications.

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RATIONALE: The amygdala plays a paramount role in the modulation of anxiety and numerous studies have shown that arginine vasopressin (AVP) elicits anxiogenic effects following either its systemic or septal administration. OBJECTIVES: The aim of this paper was to study the involvement of vasopressinergic neurotransmission in the amygdaloid modulation of unconditioned anxiety and to ascertain whether or not AVP receptor subtypes may have a differential role in this modulation. METHODS: Anxiety behavior was evaluated both in Shock-Probe Burying Test and Light-Dark Box following the bilateral microinfusion of AVP alone or AVP together with either AVP 1a or AVP 1b receptor antagonists into the central amygdala (CeA). RESULTS: AVP microinfusion elicited at low (1 ng/side) but not at high doses (10 ng/side) anxiogenic-like responses in the Shock-Probe Burying Test but not in the Light-Dark Box. SSR149415, an AVP 1b antagonist unlike Manning compound, an AVP 1a antagonist, fully prevented AVP effects in the Shock-Probe Burying Test when it was administered simultaneously with AVP. In addition, oxytocin receptor blockade also failed to affect AVP effects. No effects of any AVP antagonist by itself were observed in both anxiety paradigms. CONCLUSIONS: Our results indicate that AVP 1b receptor contribute to the amygdaloid modulation of anxiety at least in the context of the Shock-Probe Burying Test since no effects were noticed in the Light-Dark Box. It remains to the future to ascertain whether AVP receptor subtypes have indeed differential actions either in the modulation of global or specific features of unconditioned anxiety.

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Exposure to an altered osmotic environment during a pre/postnatal period can differentially program the fluid intake and excretion pattern profile in a way that persists until adulthood. However, knowledge about the programming effects on the underlying brain neurochemical circuits of thirst and hydroelectrolyte balance, and its relation with behavioral outputs, is limited. We evaluated whether early voluntary intake of hypertonic NaCl solution may program adult offspring fluid balance, plasma vasopressin, neural activity, and brain vasopressin and angiotensinergic receptor type 1a (AT1a)-receptor gene expression. The manipulation (M) period covered dams from 1 week before conception until offspring turned 1-month-old. The experimental groups were (i) Free access to hypertonic NaCl solution (0.45 M NaCl), food (0.18% NaCl) and water [M-Na]; and (ii) Free access to food and water only [M-Ctrol]. Male offspring (2-month-old) were subjected to iv infusion (0.15 ml/min) of hypertonic (1.5M NaCl), isotonic (0.15M NaCl) or sham infusion during 20 min. Cumulative water intake (140 min) and drinking latency to the first lick were recorded from the start of the infusion. Our results indicate that, after systemic sodium overload, the M-Na group had increased water intake, and diminished neuronal activity (Fos-immunoreactivity) in the subfornical organ (SFO) and nucleus of the solitary tract. They also showed reduced relative vasopressin (AVP)-mRNA and AT1a-mRNA expression at the supraoptic nucleus and SFO, respectively. The data indicate that the availability of a rich source of sodium during the pre/postnatal period induces a long-term effect on drinking, neural activity, and brain gene expression implicated in the control of hydroelectrolyte balance.

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Mammalian target of rapamycin (mTOR) complex is a key regulator of autophagy, cell growth and proliferation. Here, we studied the effects of arginine vasopressin (AVP) on mTOR activation in vascular smooth muscle cells cultured in high glucose concentration. AVP induced the mTOR phosphorylation in A-10 cells grown in high glucose, in contrast to cells cultured in normal glucose; wherein, only basal phosphorylation was observed. The AVP-induced mTOR phosphorylation was inhibited by a PI3K inhibitor. Moreover, the AVP-induced mTOR activation inhibited autophagy and increased thymidine incorporation in cells grown in high glucose. This increase was abolished by rapamycin which inhibits the mTORC1 complex formation. Our results suggest that AVP stimulates mTOR phosphorylation by activating the PI3K/Akt signaling pathway and, subsequently, inhibits autophagy and raises cell proliferation in A-10 cells maintained in high glucose concentration.

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Over the years it has become crystal clear that a variety of processes encode time-of-day information, ranging from gene expression, protein stability, or subcellular localization of key proteins, to the fine tuning of network properties and modulation of input signals, ultimately ensuring that physiology and behavior are properly synchronized to a changing environment. The purpose of this review is to put forward examples (as opposed to generate a comprehensive revision of all the available literature) in which the circadian system displays a remarkable degree of plasticity, from cell autonomous to circuit-based levels. In the literature, the term circadian plasticity has been used to refer to different concepts. The obvious one, more literally, refers to any change that follows a circadian (circa=around, diem=day) pattern, i.e. a daily change of a given parameter. The discovery of daily remodeling of neuronal structures will be referred herein as structural circadian plasticity, and represents an additional and novel phenomenon modified daily. Finally, any plasticity that has to do with a circadian parameter would represent a type of circadian plasticity; as an example, adjustments that allow organisms to adapt their daily behavior to the annual changes in photoperiod is a form of circadian plasticity at a higher organizational level, which is an emergent property of the whole circadian system. Throughout this work we will revisit these types of changes by reviewing recent literature delving around circadian control of clock outputs, from the most immediate ones within pacemaker neurons to the circadian modulation of rest-activity cycles.

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El cierre percutáneo del conducto arterioso permeable (CAP) es una modalidad de tratamiento bien establecida. El Amplatzer vascular plug II (AVP II) es un dispositivo oclusor autoexpandible, indicado para oclusiones arteriales o venosas en la vasculatura periférica. Describimos nuestra experiencia clínica inicial en el cierre percutáneo del CAP, utilizando el AVP II en la edad pediátrica. El tamaño del dispositivo fue seleccionado de acuerdo al tamaño y morfología del CAP, con un diámetro mayor al 100% del diámetro mínimo del CAP. Los dispositivos fueron implantados a través de una vaina por vena o arteria femoral. En 18 pacientes, el AVP II se utilizó para oclusión del CAP. La mediana de edad fue 24 meses (intervalo: 6-51) y la media de peso, 10.5 kg (intervalo: 4.8-16.5). El diámetro más estrecho del CAP mostró una mediana de 1.1 mm (intervalo: 0.3-7.0). Se logró el implante exitoso y la oclusión angiográfica en 14 pacientes (77.8%). El tamaño del dispositivo implantado mostró una media de 3.9 ± 2.4 veces el diámetro mínimo del CAP. Dos pacientes fueron enviados a cirugía. Ocurrieron dos embolizaciones. El ecocardiograma transtorácico de 24 horas confirmó oclusión total en 13 casos (72.2%). Durante el periodo de seguimiento no se han reportado complicaciones. El cierre percutáneo de CAP < 2 mm con AVP II es una técnica segura y efectiva, particularmente para oclusión de vasos de pequeño diámetro con bajo flujo.

Percutaneous closure of patent ductus arteriosus (PDA) is a well established treatment modality. The Amplatzer vascular plug II (AVP II) is a self-expandable occluder device, indicated for arterial or venous occlusions in the peripheral vasculature. We describe our initial clinical experience in percutaneous closure of PDA using the AVP II in children. Device size was selected according to the size and morphology of the CAP, with a diameter greater than 100% of the minimum diameter of the CAP. The devices were implanted through a pod femoral vein or artery. In 18 patients, AVP II was used for occlusion of PDA. The median age was 24 months (range 6-51) and mean weight 10.5 kg (range 4.8-16.5). The narrowest diameter of the CAP showed a median of 1.1 mm (range 0.3-7.0). Successful implantation was achieved and angiographic occlusion in 14 patients (77.8%). The size of the implanted device showed a mean of 3.9 ± 2.4 times the minimum diameter of the CAP. Two patients were referred for surgery. There were two embolizations. Transthoracic echocardiography 24 hours confirmed total occlusion in 13 cases (72.2%). During the monitoring period there are no reported complications. Percutaneous closure of PDA < 2 mm AVP II is a safe and effective, particularly for occlusion of small-diameter vessels with low flow.

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Introducción: la meningitis bacteriana constituye una preocupación para los médicos y los sistemas de salud en general de cualquier país, así como para los organismos internacionales. Objetivo: estimar las cargas por morbilidad y mortalidad por meningitis bacteriana en Cuba para 2006. Métodos: se utilizaron los datos de mortalidad y de incidencia de la encuesta epidemiológica de la Vigilancia Nacional de Meningitis Bacteriana del Instituto de Medicina Tropical "Pedro Kourí". Los procedimientos de estimación se basaron en las recomendaciones de la Organización Mundial de la Salud con el uso del DISMOD y las hojas de cálculos establecidas al efecto. Resultados: la carga global de meningitis bacteriana se estimó en 3527,26 años de vida ajustados por discapacidad (AVAD), lo que representó la pérdida de 31,3 años por cada 100 000 habitantes. La carga por morbilidad y mortalidad de meningitis bacteriana sin ponderar la secuela resultó 2056,25 años de vida ajustados por discapacidad, 55,9 por ciento correspondió sin agente etiológico identificado, seguida de las originadas por Streptococcus pneumoniae (30,9 por ciento), Neisseria meningitidis (9,5 por ciento) y por Haemophilus influenzae tipo b (3,6 por ciento). La carga por mortalidad fue aproximadamente 2 039 años de vida perdidos (AVP) por muerte prematura, o sea 57,8 por ciento. Los menores de 5 años aportaron la mayor carga global de años de vida ajustados por discapacidad y dentro de ellos S. pneumoniae el que generó la mayor carga. Conclusión: la carga por meningitis bacteriana resultó elevada y corroboró su alta utilidad para evaluar los problemas de salud.

Introduction: bacterial meningitis is a real concern for physicians and general health systems of any country as well as the international bodies. Objective: to estimate burdens of disease from morbidity and mortality caused by bacterial meningitis in Cuba during 2006. Methods: the mortality and the incidence data of the epidemiological survey from the National Surveillance of Bacterial Meningitis of "Pedro Kourí" Institute of Tropical Medicine were used. The estimation methods were based on the WHO recommendations by using the DISMOD and the required Excel spreadsheets. Results: the global burden of bacterial meningitis was estimated at a total of 3527.26 Disability Adjusted Lost Years (DALYs), which accounted for 31.3 years lost per 100 000 inhabitants. Morbidity and mortality burden of bacterial meningitis without sequel weighing was 2056.25 disability adjusted lost years, being the 55.9 percent caused by unidentified agent, followed by S. pneumoniae (30.9 percent), N. meningitidis (9.5 percent) and H influenza type b (3.6 percent). The mortality burden was 2 039 years of life lost from premature death, that is, 57.8 percent of the global burden. Children under five years of age contributed the biggest global burden of disability adjusted lost years, and S. penumoniae generated the biggest burden. Conclusion: the burden of bacterial meningitis was high. Burden of disease is an important measure to assess health problems.

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INTRODUCTION: Central diabetes insipidus (DI) characterized by polyuria, polydipsia and inability to concentrate urine, has different etiologies including genetic, autoimmune, post-traumatic, among other causes. Autosomal dominant central DI presents the clinical feature of a progressive decline of arginine-vasopressin (AVP) secretion. OBJECTIVE: In this study, we characterized the clinical features and sequenced the AVP-NPII gene of seven long-term follow-up patients with idiopathic central DI in an attempt to determine whether a genetic cause would be involved. METHODS: The diagnosis of central DI was established by fluid deprivation test and hyper-tonic saline infusion. For molecular analysis, genomic DNA was extracted and the AVP-NPII gene was amplified by polymerase chain reaction and sequenced. RESULTS: Sequencing analysis revealed a homozygous guanine insertion in the intron 2 (IVS2 +28 InsG) of the AVP-NPII gene in four patients, which represents an alternative gene assembly. No mutation in the code region of the AVP-NPII gene was found. CONCLUSIONS: The homozygous guanine insertion in intron 2 (IVS2 +28 InsG) is unlikely to contribute to the AVP-NPII gene modulation in DI. In addition, the etiology of idiopathic central DI in children may not be apparent even after long-term follow-up, and requires continuous etiological surveillance.

INTRODUÇÃO: O diabetes insípido (DI) central, caracterizado por poliúria, polidipsia e inabilidade em concentrar a urina, apresenta diferentes etiologias, incluindo causas genética, autoimune, pós-traumática, entre outras. O DI central autossômico dominante apresenta a característica clínica de falência progressiva da secreção da arginina-vasopressina (AVP). OBJETIVO: No presente estudo, caracterizou-se a apresentação clínica e sequenciou-se o gene AVP-NPII de sete pacientes com DI central idiopático seguidos de longa data na tentativa de determinar se uma causa genética estava envolvida na etiologia. MÉTODOS: O diagnóstico do DI central foi estabelecido por meio do teste de jejum hídrico e infusão de salina hipertônica. Para a realização da análise molecular, o DNA genômico foi extraído e o gene AVP-NPII foi amplificado pela reação em cadeia da polimerase e, posteriormente, sequenciado. RESULTADOS: A análise do sequenciamento do gene AVP-NPII revelou uma inserção em homozigose de uma guanina no íntron 2 (IVS2 +28 InsG) em quatro pacientes, correspondendo a um arranjo alternativo do gene. Nenhuma mutação da região codificadora do gene AVP-NPII foi encontrada. CONCLUSÕES: A inserção em homozigose de uma guanina no íntron 2 (IVS2 +28 InsG) provavelmente não contribui na modulação do gene AVP-NPII no DI. Adicionalmente, a etiologia do DI central idiopático em crianças pode não se tornar evidente mesmo após um longo período de seguimento, necessitando de contínua vigilância da etiologia.

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Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a rare autosomal dominant disorder characterized by polyuria and polydipsia due to deficiency of arginine vasopressin (AVP). More than 50 mutations causing adFNDI have been already reported in the AVP gene. The aim of the present study is to analyze the AVP gene in four generations of one Brazilian kindred with adFNDI. The proband was a 31-year old female with huge hypotonic polyuria (10 L/day) dated from childhood. Molecular analysis included amplification of all exons and exon-intron regions of the AVP gene by PCR and direct sequencing. Sequencing analysis showed a novel point mutation in heterozygous: G88V (GGC>GTC). All affected patients presented the same mutation also in heterozygous, while it was absent in four normal members. We expand the repertoire of mutations in AVP describing the novel G88V mutation in one Brazilian kindred with adFNDI.

Diabetes insípido neuro-hipofisário com herança autossômica dominante (adFNDI) é uma doença autossômica dominante rara, caracterizada por poliúria e polidipsia devido à deficiência de arginina-vasopressina (AVP). Mais de 50 mutações causando adFNDI foram descritas no gene AVP. O objetivo deste estudo foi analisar o gene AVP em quatro gerações de uma família brasileira com DINF. O caso-índice é de uma paciente de 31 anos, com volumosa poliúria hipotônica desde a infância (10 L/dia). A análise molecular incluiu amplificação por PCR e seqüenciamento automático dos éxons e regiões éxon-íntron do gene AVP. A análise do seqüenciamento mostrou uma nova mutação de ponto em heterozigose: G88V (GGC>GTC). Todos os pacientes afetados apresentaram a mesma mutação, que não foi encontrada em quatro indivíduos normais da família. Expandimos a lista de mutações no gene AVP, descrevendo a nova mutação G88V em uma família brasileira com adFNDI.

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