Small cell lung cancer associated with multiple paraneoplastic syndromes / Cáncer de pulmón de células pequeñas asociado a múltiples síndromes paraneoplásicos

Abstracts We report the case of a patient presenting with multiple severe electrolyte disturbances who was subsequently found to have small cell lung cancer. Upon further evaluation, she demonstrated three distinct paraneoplastic processes, including the syndrome of inappropriate antidiuretic hormone, Fanconi syndrome, and an inappropriate elevation in fibroblast growth factor-23 (FGF23). The patient underwent one round of chemotherapy, but she was found to have progressive disease. After 36 days of hospitalization, the patient made the decision to enter hospice care and later she expired.

Resumen Se reporta el caso de una paciente que ingresó al hospital para evaluación de múltiples trastornos electrolíticos y, posteriormente, se le hizo el diagnóstico de cáncer de pulmón de células pequeñas. Tras la evaluación médica, se detectaron tres síndromes paraneoplásicos: síndrome de secreción inadecuada de hormona antidiurética, síndrome de Fanconi y elevación inapropiada del factor 23 de crecimiento de fibroblastos. Se le administró quimioterapia sin éxito, por lo cual se decidió darle tratamiento paliativo y, un tiempo después, falleció.

Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia with abnormal cortisol secretion mediated by catecholamines

No abstract available.

Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: roles of the peripheral vasopressin and central cholinergic systems

Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300 g) female rats (N = 7 in each group) the effects of intracerebroventricularly (icv) injected adrenomedullin (ADM) on blood pressure and heart rate (HR), and to determine if ADM and calcitonin gene-related peptide (CGRP) receptors, peripheral V1 receptors or the central cholinergic system play roles in these cardiovascular effects. Blood pressure and HR were observed before and for 30 min following drug injections. The following results were obtained: 1) icv ADM (750 ng/10 µL) caused an increase in both blood pressure and HR (DMAP = 11.8 ± 2.3 mmHg and ΔHR = 39.7 ± 4.8 bpm). 2) Pretreatment with a CGRP receptor antagonist (CGRP8-37) and ADM receptor antagonist (ADM22-52) blocked the effect of central ADM on blood pressure and HR. 3) The nicotinic receptor antagonist mecamylamine (25 µg/10 µL, icv) and the muscarinic receptor antagonist atropine (5 µg/10 µL, icv) prevented the stimulating effect of ADM on blood pressure. The effect of ADM on HR was blocked only by atropine (5 µg/10 µL, icv). 4) The V1 receptor antagonist [β-mercapto-β-β-cyclopentamethylenepropionyl¹, O-me-Tyr²,Arg8]-vasopressin (V2255; 10 µg/kg), that was applied intravenously, prevented the effect of ADM on blood pressure and HR. This is the first study reporting the role of specific ADM and CGRP receptors, especially the role of nicotinic and muscarinic central cholinergic receptors and the role of peripheral V1 receptors in the increasing effects of icv ADM on blood pressure and HR.

Oxitocina, vasopresina y conducta social: hipótesis neuropéptida para el trastorno autista / Oxytocin, vasopressin and social behavior: neuropeptide hypothesis

Introducción: El Trastorno Autista es una patología de inicio temprano que evoluciona hacia la cronicidad y se caracteriza principalmente por un desarrollo marcadamente anormal o deficiente de la interacción y comunicación social. Es más frecuente en hombres y si bien se presume que es de origen multifactorial, se plantea que puede ser explicado, al menos en parte, por una alteración en la neurobiología que da sustento a las conductas sociales normales. La Oxitocina y la Vasopresina han sido ampliamente relacionadas con las conductas sociales tanto en animales como en humanos, específicamente han sido relacionadas con las conductas de apego, de filiación y con el Trastorno Autista. Objetivos: Entregar un marco teórico que contribuya a organizar el amplio conocimiento que existe sobre la fisiopatología del Trastorno Autista y que entregue luces tanto para la investigación como para la clínica. Método: Se realiza una revisión bibliográfica sobre el rol que juegan la Oxitocina y la Vasopresina en las conductas sociales sanas y anormales tanto en animales como en humanos centrándose la discusión en la relación que tienen estos neuropéptidos con el Trastorno Autista. Conclusiones: Si bien se presume que la fisiopatología del Trastorno Autista es de origen multifactorial, se logra organizar un marco teórico para la comprensión de la fisiopatología del trastorno desde una hipótesis neuropéptida, lo cual tiene implicancias tanto para la investigación como para la clínica.

Introduction: Autistic disorder is an early onset disease that evolves into chronicity, characterized by the presence of markedly abnormal or deficient development of social interaction and communication. It is more common in men and although presumed to be of multifactorial origin, it is proposed that it can be explained, at least in part, by alterations in the neurobiology which gives supports to normal social behavior. Oxytocin and vasopressin have been widely associated with social behavior in animals and humans, specifically with attachment behaviors, affiliation and Autistic Disorder. Objectives: To provide a theoretical framework in order to help organize the extensive knowledge that exists about the pathophysiology of autistic disorder and to deliver light for both research and clinic. Methods: We performed a systematic review of the role played by oxytocin and vasopressin in healthy and abnormal social behavior in both animals and humans and focused the discussion on the relationship that have these neuropeptides with Autistic Disorder. Conclusions: Understanding the pathophysiology of the Autistic Disorder from a neuropeptide hypothesis, provides a theorethical framework which has implications for both research and clinic.

Emerging role of vasopressin.

Ionotropic agents are frequently used in vasodilatory shock like conditions of septic or nonseptic origin. Conventional catecholamines such as norepinephrine are used at a very high dose with possibility of adverse effects in many patients. One often encounters refractoriness to these drugs. Infusion of vasopressin (VP) which is detectable at inappropriately low level in advanced phase of septic shock might allow withdrawal of catecholamines, as it maintains adequate mean arterial pressure (MAP), improves urine output and leaves perfusion of vital organs unhindered. Vasopressin has been found to be superior to epinephrine in animal models and some human trials, especially in patients with resistant ventricular fibrillation (VF) while doing cardiopulmonary resuscitation (CPR). Analogues of VP have also been used for diuresis in patients of hepatorenal syndrome.

Uso de la vasopresina en el estado de choque / Vasopressin Use in Shock

La arginina-vasopresina (VP) también conocida como hormona antidiurética es esencial para mantener el equilibrio hídrico. Su síntesis y liberación depende de la interacción de estímulos osmóticos, hipovolémicos, hormonales y no osmóticos. Se ha demostrado que en estados de choque es fundamental para mantener la homeostasis cardiovascular a través de la regulación del tono vasomotor, el cual determina las resistencias vasculares sistémicas y la presión arterial media, a través de los receptores VI. El estado de choque con vasodilatación refractaria que se presenta en sepsis, respuesta inflamatoria sistémica, hipovolemia, paro cardiaco, politraumatismo, etc... se caracteriza por una fase inicial en la que hay liberación y aumento en los niveles séricos de VP, ésta es seguida por una segunda fase en la que se presentan niveles inapropiadamente bajos de la hormona y éstos se asocian con refractariedad al manejo con volumen, inotrópicos y vasopresores. Se ha demostrado, en estudios experimentales y clínicos, que en esta condición el tratamiento con vasopresina exógena incrementa la resistencia vascular sistémica, la presión de perfusión y el aporte de oxígeno a los tejidos periféricos lo cual hace posible la disminución y suspensión de los vasopresores e incrementa la supervivencia.

Arginine-vasopresin (VP), also known as the antidiuretic hormone, is essential for water homeostasis. Its synthesis and liberation depends on regulation of osmotic, hypovolemic, hormonal, and nonosmotic stimuli. It has been demonstrated that it is key for maintenance of cardiovascular homeostasis through vasomotor regulation, the determinant of systemic vascular resistance and mean arterial pressure, a process acting through VI receptors. Shock state with refractary vasodilation seen in sepsis, systemic inflamatory response, hypovolemia, cardiac arrest, polytrauma, etc., is characterized by an initial phase of liberation and increased levels of VP followed by a second phase caracterized by inappropirately low levels of this hormone that are associated with refractariness to management with volume, inotropics, and vasopressors. It has been demonstrated in clinical and experimental studies that exogenous VP treatment under this condition increases systemic vascular resistance, perfusion pressure, and oxygen supply to peripheral tissues, which makes it possible to decrease and to suspend vasopressors and also to increase survival.

Role of the hypothalamic pituitary adrenal axis in the control of the response to stress and infection

The release of adrenocorticotropin (ACTH) from the corticotrophs is controlled principally by vasopressin and corticotropin-releasing hormone (CRH). Oxytocin may augment the release of ACTH under certain conditions, whereas atrial natriuretic peptide acts as a corticotropin release-inhibiting factor to inhibit ACTH release by direct action on the pituitary. Glucocorticoids act on their receptors within the hypothalamus and anterior pituitary gland to suppress the release of vasopressin and CRH and the release of ACTH in response to these neuropeptides. CRH neurons in the paraventricular nucleus also project to the cerebral cortex and subcortical regions and to the locus ceruleus (LC) in the brain stem. Cortical influences via the limbic system and possibly the LC augment CRH release during emotional stress, whereas peripheral input by pain and other sensory impulses to the LC causes stimulation of the noradrenergic neurons located there that project their axons to the CRH neurons stimulating them by alpha-adrenergic receptors. A muscarinic cholinergic receptor is interposed between the alpha-receptors and nitric oxidergic interneurons which release nitric oxide that activates CRH release by activation of cyclic guanosine monophosphate, cyclooxygenase, lipoxygenase and epoxygenase. Vasopressin release during stress may be similarly mediated. Vasopressin augments the release of CRH from the hypothalamus and also augments the action of CRH on the pituitary. CRH exerts a positive ultrashort loop feedback to stimulate its own release during stress, possibly by stimulating the LC noradrenergic neurons whose axons project to the paraventricular nucleus to augment the release of CRH.

Endogenous vasopressin and the central control of heart rate during dynamic exercise

The present article contains a brief review on the role of vasopressinergic projections to the nucleus tractus solitarii in the genesis of reflex bradycardia and in the modulation of heart rate control during exercise. The effects of vasopressin on exercise tachycardia are discussed on the basis of both the endogenous peptide content changes and the heart rate response changes observed during running in sedentary and trained rats. Dynamic exercise caused a specific vasopressin content increase in dorsal and ventral brainstem areas. In accordance, rats pretreated with the peptide or the V1 blocker into the nucleus tractus solitarii showed a significant potentiation or a marked blunting of the exercise tachycardia, respectively, without any change in the pressure response to exercise. It is proposed that the long-descending vasopressinergic pathway to the nucleus tractus solitarii serves as one link between the two main neural controllers of circulation, i.e., the central command and feedback control mechanisms driven by the peripheral receptors. Therefore, vasopressinergic input could contribute to the adjustment of heart rate response (and cardiac output) to the circulatory demand during exercise.

Exercício físico e memória / Physical exercise and memory

A memória é susceptível às influências endógena, hormonal e neuro-humoral especialmente logo após a aquisiçäo da informaçäo. A amígdala, o septo medial, o hipocampo e o córtex entorrinal estäo envolvidos nos processos de consolidaçäo, armazenamento e evocaçäo. A resposta ao problema dos mecanismos de armazenamento podem encontrar-se tanto pelo caminho da potenciaçäo delonga duraçäo como pelo das redes neurais, através de uma interaçäo complementar. A modulaçäo da memória enfoca a atençäo na análise das condiçöes sob as quais a consolidaçäo da memória pode ser alterada. Uma informaçäo adquirida em um determinado contexto neuro-humoral será melhor evocada se durante o processo de evocaçäo o contexto neuro-humoral for similar ao do momento da aquisiçäo, caracterizando a existência de uma periférica pós-treino de hormônios normalmente liberados por experiências emocionais e estresses, tais como: catecolaminas, ACTH, vasopressina, além do peptídio opióide B-endorfina. Os hormônios e opióides envolvidos na regulaçäo da memória também estäo envolvidos na regulaçäo, homeostática do exercício. Estudos têm demonstrado que a liberaçäo das catecolaminas, vasopressina, ACTH e B-endorfina é estimulada pelo exercício, fazendo-se uma relaçäo do efeito do exercício na regulaçäo da memória, especialmente exercícios intensos e os moderados de longa duraçäo

Renal actions of angiotensin-(1-7)

The heptapeptide angiotensin-(1-7) is considered to be a biologically active endproduct of the renin-angiotensin system. This angiotensin, which is devoid of the most known actions of angioatensin II such as induction of drinking behavior and vasoconstriction, has several selective effects in the brain and periphery. In the present article we briefly review recent evidence for a physiological role of angiotensin-(1-7) in the control of hydroelectrolyte balance.

ANP as a neuroendocrine modulator of body fluid homeostasis

The role played by the central nervous system (CNS) in the control of body fluid homeostasis has been demonstrated by several authors. The AV3V plays a key role in central control of sodium excretion since its cholinergic, adrenergic, angiotensinergic and osmotic stimulation enhances and its destruction blocks sodium excretion in rats and goats. Cholinergic stimulation of the AV3V induced an increase in plasma ANP as well as a marked elevation in content of the peptide in medial basal hypothalamus, neuro and adenohypophysis. On the other hand, a decline in plasma ANP after AV3V lesions was accompanied by dramatic declines in content of ANP in these same structures. Our previous work has also indicated the essential role of the AV3V region and its ANPergic neurons in the control of ANP release in response to volume expansion (BVE) and indicated that alpha-adrenergic and muscarinic receptors are critical in mediating these responses. Lesions of the AV3V region, or of the median eminence or posterior lobe of pituitary gland blocked the increase in plasma ANP concentration in response to BVE. That this effect is related to blockage of the activity of the brain ANPergic neurons is supported by fyndings in sheep and in rats that the injection of the antiserum directed against ANP into the AV3V region at least partially blocked the BVE-induced release of ANP. We and others have also previously shown that denervation of baroreceptors inhibits ANP release induced by BVE. Activation of the ANP neurons also cause release of ANP from the anterior and neural lobe of pituitary gland. ANP neurons may activate oxytocinergic neurons in the supraoptic and paraventricular, which projects to neural lobe. Oxytocin would circulate to the atria and may directly activate release of ANP from the atrial myocytes, since i.v. or i.p. injection of oxytocin increases sodium excretion as well as elevates plasma ANP. Oxytoxin is present in the neural lobe in large quantity, which could reach the atria myocytes in high concentration and release ANP that circulate to the kidneys and evokes natriuresis to return circulating blood volume to normal.

Tratamiento farmacológico de la hipertensión portal

Variceal bleeding is the most lethal complication of portal hypertension. Recent estimates have shown worldwide 50 million people with this entity, of which 60 percent have varices at the time of diagnosis and 20 percent bleeds each year. The mortality of each bleeding episode approaches 50 percent, the rate of recurrence in the first year after the initial hemorrhage is 60 percent and even higher in the first six weeks after bleeding. Treatment of portal hypertension must include the following aspects: 1)Treatment of active bleeding, 2)Prevention of recurrence and 3)Prevention of the first bleeding episode. Variceal bleeding never occurs with portal pressure below 12 mmHg, which means that although portal pressure is only one of the factors that determines the incidence of bleeding, reduction of portal pressure is the goal of the treatment. Pharmacologic treatment is based on vasoactive drugs that decrease portal pressure by a reduction of the blood flow that reaches the portal circulation (splanchnic vasoconstrictors), or through a reduction of the portal vein resistance (venodilators). Many drugs can reduce portal pressure, but few have received clinical evaluation. Vasopressin and somatostatin have been used successfully in the treatment of active variceal bleeding, the latter has shown absence of significant cardiovascular side effects commonly seen with the former. Addition of nitrates have increased the positive effects of vasopressin with a salutary reduction of side effects. Non selective batablockers such as propanolol and other compounds have been proved effective by several controlled studies and recent metaanalysis in the control of the recurrence of bleeding and the initial bleeding episode.

Vasopressin: an approach to its actions in the central nervous system

A vasopressina é um hormônio neurohipofisário que age de forma anti-diurética e sobre a pressäo. Além destas açöes periféricas, diversas açöes centrais lhe säo atribuídas, especialmente no que diz respeito aos processos de memória e de aprendizado. O presente estudo enfatiza alguns aspectos neuroanatomofisiológicos e farmacológicos da vasopressina, bem como seu envolvimento nos processos centrais. Discutem-se aqui, ainda, várias teorias que pretendem explicar os mecanismos de açäo deste hormônio sobre os processos cognitivos, seu possível envolvimento em vários processos ligados ao acordar, sono REM, estresse, emotividade, ansiedade, neuromodulaçäo e os efeitos de determinadas drogas

Effect of adrenergic agents on the hydrosmotic action of vasopressin in the isolated toad bladder

O presente trabalho correlaciona os efeitos de drogas que atuam sobre receptores adrenérgicos e as alteraçöes provocadas sobre a resposta hidrosmótica da bexiga de sapo à vasopressina. O fluxo de àgua foi medido gravimetricamente em hemibexigas pareadas, montadas sob a forma de saco e banhadas por soluçäo de Ringer na sua face serosa e por soluçäo de Ringer diluída a 1: 5 na face mucosa. Sem conflito com a literatura, os valores observados para o transporte de àgua em condiçöes basais foram muito baixos e näo se alteram após a adiçäo de adrenalina, ou dopamina, ou isoprenalina. A vasopressina aumentou extraordinariamente (cerca de 20 a 30 vezes) o fluxo de àgua e pôde ser constatada uma independência entre os receptores para vasopressina e os adrenérgicos. A ativaçäo dos receptores adrenérgicos por adrenalina induziu a um significante (cercade 50 por cento ) bloqueio da açäo hidrosmótica da vasopressina. Resultados semelhantes foram observados com dopamina. A adiçäo de isoprenalina provocou pequeno (cerca de 16 por cento ) bloqueio da açäo da vasopressina. A associaçäo desta catecolamina a uma droga bloqueadora de receptores beta-adrenérgicos näo alterou a açäo da vasopressina. Em contraste, a associaçäo da isoprenalina a uma droga bloqueadora de receptores alfa-adrenérgicos restaurou o efeito da vasopressina, evidenciando a participaçäo de receptores alfa-adrenérgicos no bloqueio da açäo hidrosmótica da vasopressina e permitindo maior caracterizaçäo da interaçäo entre catecolaminas e osreceptores alfa-adrenérgicos na bexiga de sapo

Caracterizaçäo do rato com diabetes insípido hereditário - Brattleboro - criado no Brasil / Characterization of the Brattleboro rat bred in Brazil

O rato Brattleboro é um modelo experimental de diabetes insípido, sendo que em ratos homozigotos (di/di) há ausência total do hormônio antidiurético (ADH), enquanto que em heterozigotos (di/+) ocorre apenas a produçäo de 50%. Neste trabalho, os autores comparam a qualidade da colônia durante três anos e determinam algumas variáveis fisiológicas em ratos di/di e di/+. Os resultados sugerem que a boa adaptaçäo dos animais no primeiro ano näo significou o sucesso do programa decriaçäo, uma vez que o número de di/di obtido näo foi satisfatório, indicando possíveis acasalamentos inadequados resultantes de falhas no método de classificaçäo. Ratos di/di apresentaram baixo peso corporal e elevado consumo de água e durese em comparaçäo aos di/+. O Na plasmático e sua excreçäo urinária foram maiores em di/di, enquanto que näo observamos diferenças, em média, no peso do rim, hematócrito e proteínas plasmáticas. Ratos di/di apresentaram menor pressäo arterial média e resistência vascular renal, indicando ausência do efeito vasoconstrictor do ADH. Portanto, sugerimos que, apesar das dificuldades na produçäo e manutençäo, esse animal é excelente modelo experimental para o estudo do ADH em várias situaçöes fisiológicas e fisiopatológicas

Single channel recordings from basolateral membranes of frog urinary bladders

El trabajo describe la metodología necesaria para obtener, a partir de la vejiga urinaria de la rana, capas de células aisladas apropiadas para estudios por "patch-clamp". Este resultado se logró combinando presión negativa, digestión enzimática y microdisección. Se obtuvieron registros de canales únicos en las membranas basolaterales, en una situación en la que el epitelio mantenía su polaridad y estructura general