Ablation of C-type natriuretic peptide/cGMP signaling in fibroblasts exacerbates adverse cardiac remodeling in mice.

Excessive activation of cardiac fibroblasts (CFs) in response to injury provokes cardiac fibrosis, stiffness, and failure. The local mediators counterregulating this response remain unclear. Exogenous C-type natriuretic peptide (CNP) exerts antifibrotic effects in preclinical models. To unravel the role of the endogenous hormone, we generated mice with fibroblast-restricted deletion (KO) of guanylyl cyclase-B (GC-B), the cGMP-synthesizing CNP receptor. CNP activated GC-B/cGMP signaling in human and murine CFs, preventing proliferative and promigratory effects of angiotensin II (Ang II) and TGF-ß. Fibroblast-specific GC-B-KO mice showed enhanced fibrosis in response to Ang II infusions. Moreover, after 2 weeks of mild pressure overload induced by transverse aortic constriction (TAC), such KO mice had augmented cardiac fibrosis and hypertrophy, together with systolic and diastolic contractile dysfunction. This was associated with increased expression of the profibrotic genes encoding collagen I, III, and periostin. Notably, such responses to Ang II and TAC were greater in female as compared with male KO mice. Enhanced Ang II-induced CNP expression in female hearts and augmented GC-B expression and activity in female CFs may contribute to this sex disparity. The results show that paracrine CNP signaling in CFs has antifibrotic and antihypertrophic effects. The CNP/GC-B/cGMP pathway might be a target for therapies combating pathological cardiac remodeling.

Cardiac morphological and functional changes induced by C-type natriuretic peptide are different in normotensive and spontaneously hypertensive rats.

OBJECTIVE: Inflammation and fibrosis are key mechanisms in cardiovascular remodeling. C-type natriuretic peptide (CNP) is an endothelium-derived factor with a cardiovascular protective role, although its in-vivo effect on cardiac remodeling linked to hypertension has not been investigated. The aim of this study was to determine the effects of chronic administration of CNP on inflammatory and fibrotic cardiac mechanisms in normotensive Wistar rats and spontaneously hypertensive rats (SHR). METHODS: Twelve-week-old male SHR and normotensive rats were infused with CNP (0.75 µg/h/100 g) or isotonic saline (NaCl 0.9%) for 14 days (subcutaneous micro-osmotic pumps). Echocardiograms and electrocardiograms were performed, and SBP was measured. After treatment, transforming growth factor-beta 1, Smad proteins, tumor necrosis factor-alpha, interleukin-1 and interleukin-6, nitric oxide (NO) system and 2-thiobarbituric acid-reactive substances were evaluated in left ventricle. Histological studies were also performed. RESULTS: SHR showed lower cardiac output with signs of fibrosis and hypertrophy in left ventricle, higher NO-system activity and more oxidative damage, as well as higher pro-inflammatory and pro-fibrotic markers than normotensive rats. Chronic CNP treatment-attenuated hypertension and ventricular hypertrophy in SHR, with no changes in normotensive rats. In left ventricle, CNP induced an anti-inflammatory and antifibrotic response, decreasing both pro-fibrotic and pro-inflammatory cytokines in SHR. In addition, CNP reduced oxidative damage as well as collagen content, and upregulated the NO system in both groups. CONCLUSION: Chronic CNP treatment appears to attenuate hypertension and associated end-organ damage in the heart by reducing inflammation and fibrosis.

Embarazo adolescente: Resultados perinatales en la maternidad de un hospital de la Ciudad de Corrientes / Adolescent pregnancy: Perinatal results in the maternity ward of a hospital in the City of Corrientes

El embarazo en la adolescencia constituye un grave problema de la salud pública, más aún en nuestro país donde presenta un alto porcentaje de casos, lo que involucra mayores riesgos de salud reproductiva aumentando de esta manera la morbilidad y mortalidad. El objetivo es analizar los resultados perinatales, en los recién nacidos de las gestantes adolescentes en la maternidad del Hospital "Dr José R. Vidal" de la ciudad de Corrientes. Estudio observacional, retrospectivo, analítico y transversal comprendido entre Agosto-2015 a Julio-2016. La población en estudio estuvo conformada por recién nacidos de madres adolescentes entre 10 a19 años. Las variables fueron edad materna; semanas de gestación al momento del parto; peso del recién nacido de término; puntuación de Apgar y destino del recién nacido. Del total de partos el 22,14% fueron de madres adolescentes, de los cuales 77% correspondieron a nacimientos de término de peso adecuado para la edad gestacional (PAEG) (91,02%), con puntuación de Apgar normal (79%) que ingresaron a internación junto a la madre (82%). Los nacimientos de pretérmino resultaron 22,69%, siendo el 66,66% deprimidos moderados según Apgar y el 79,24% fueron trasladados a unidad de cuidados intensivos neonatales (UCIN). La frecuencia de embarazos adolescentes fue elevada, en cuanto a los resultados perinatales se observó peso adecuado, puntuación de Apgar normal einternación conjunta con la madre predominaron ampliamente en el recién nacido de termino.

[Diagnosis and differential diagnosis of Cushing's syndrome]. / Diagnóstico y diagnóstico diferencial del síndrome de Cushing.

Because of the variability in the clinical expression of Cushing's syndrome, different biochemical tests and imaging techniques must be used for effective diagnosis and treatment. The clinical history is important to assess the general impact of hypercortisolism on organs and systems, as well as to guide suspicion toward more aggressive entities such as overt ectopic ACTH syndrome or to detect an iatrogenic etiology of Cushing's syndrome. The screening phase relies on tests that are sensitive but not specific, such as urinary free cortisol, nocturnal salivary cortisol and 1 mg dexamethasone suppression, which still require established assessment criteria. Confirmation can be obtained by repeating urinary cortisol, 2 mg/day dexamethasone suppression, both alone and combined with corticotropin releasing hormone (CRH), to exclude pseudoCushing states. ACTH dependency can be easily explored by ACTH measurements, but the differential diagnosis between pituitary and ectopic Cushing's disease is difficult and may require invasive procedures such as inferior petrosal sinus sampling. Sophisticated imaging and isotopic techniques play a significant role in locating the source of ACTH in ectopic syndromes but are not always effective. In general, biochemical and imaging tests should be combined in order to assess different mechanisms and perspectives of the syndrome. Rigorous methodology is essential to obtain accurate results, allowing a correct diagnosis and improving therapeutic performance in this devastating disease.

[Thymic hyperplasia in a patient with Graves' disease]. / Hiperplasia tímica en una paciente con enfermedad de Graves.

Benign thymic hyperplasia (TH) is a known feature of hyperthyroidism. In most cases, thymic enlargement is minimal; however, this syndrome may occasionally appear as an appreciable anterior mediastinal mass. Recognition of the benign nature of TH and its regression following treatment of the hyperthyroidism is important to prevent unnecessary surgical procedures. We present a case of TH associated with hyperthyroidism due to Graves' disease.

Diagnóstico y diagnóstico diferencial del síndrome de Cushing / Diagnosis and differential diagnosis of Cushing¿s syndrome

La expresión variable clínica del síndrome de Cushing obliga a emplear diferentes pruebas analíticas y de imagen de forma escalonada para cumplir con las fases diagnósticas y facilitar la aplicación de un tratamiento eficaz. No obstante, la historia clínica desempeña un papel fundamental que evalúa el impacto del hipercortisolismo en órganos y sistemas, puede dirigir la sospecha hacia cuadros más agresivos, como los derivados del síndrome florido de secreción ectópica de corticotropina (ACTH), o detectar una causa iatrogénica del síndrome. La primera fase, de cribado, emplea pruebas sensibles y poco específicas, como el cortisol urinario y la supresión tras dosis baja nocturna de dexametasona, así como el cortisol salival nocturno, que aún precisa de criterios establecidos de valoración. La fase de confirmación se enfrenta a la diferenciación del seudo-Cushing mediante repetición de algunas pruebas de cribado y otras como corticoliberina combinada con dexametasona. Mientras la valoración de la dependencia de ACTH no suele presentar dificultades, el diagnóstico diferencial del origen hipofisario frente al ectópico de la enfermedad de Cushing constituye un reto que puede requerir procedimientos invasivos, como el cateterismo de senos petrosos inferiores. La localización del origen ectópico precisa de sofisticadas técnicas de imagen e isotópicas que no siempre son suficientemente resolutivas. En general, la combinación de pruebas que evalúan distintos mecanismos de control hipofisoadrenal es imprescindible. El rigor metodológico se presenta como un elemento primordial para obtener resultados fiables que permitan llevar a cabo diagnósticos precisos y mejorar el rendimiento diagnóstico y terapéutico de esta devastadora enfermedad (AU)

Because of the variability in the clinical expression of Cushing¿s syndrome, different biochemical tests and imaging techniques must be used for effective diagnosis and treatment. The clinical history is important to assess the general impact of hypercortisolism on organs and systems, as well as to guide suspicion toward more aggressive entities such as overt ectopic ACTH syndrome or to detect an iatrogenic etiology of Cushing¿s syndrome. The screening phase relies on tests that are sensitive but not specific, such as urinary free cortisol, nocturnal salivary cortisol and 1 mg dexamethasone suppression, which still require established assessment criteria. Confirmation can be obtained by repeating urinary cortisol, 2 mg/day dexamethasone suppression, both alone and combined with corticotropin releasing hormone (CRH), to exclude pseudoCushing states. ACTH dependency can be easily explored by ACTH measurements, but the differential diagnosis between pituitary and ectopic Cushing¿s disease is difficult and may require invasive procedures such as inferior petrosal sinus sampling. Sophisticated imaging and isotopic techniques play a significant role in locating the source of ACTH in ectopic syndromes but are not always effective. In general, biochemical and imaging tests should be combined in order to assess different mechanisms and perspectives of the syndrome. Rigorous methodology is essential to obtain accurate results, allowing a correct diagnosis and improving therapeutic performance in this devastating disease (AU)

Hiperplasia tímica en una paciente con enfermedad de Graves / Thymic hyperplasia in a patient with Graves¿ disease

Existe una relación conocida entre hiperplasia tímica (HT) e hipertiroidismo. En la mayor parte de los casos el agrandamiento del timo es mínimo; sin embargo, de forma infrecuente se puede presentar como una masa mediastínica anterior. Es importante conocer la naturaleza benigna de la HT en este contexto y su regresión tras tratar el hipertiroidismo para evitar una intervención quirúrgica innecesaria. Presentamos el caso de una paciente con HT e hipertiroidismo por enfermedad de Graves (AU)

Benign thymic hyperplasia (TH) is a known feature of hyperthyroidism. In most cases, thymic enlargement is minimal; however, this syndrome may occasionally appear as an appreciable anterior mediastinal mass. Recognition of the benign nature of TH and its regression following treatment of the hyperthyroidism is important to prevent unnecessary surgical procedures. We present a case of TH associated with hyperthyroidism due to Graves¿ disease (AU)

Hiperandrogenismo en una mujer posmenopáusica / Hyperandrogenism in a postmenopausal woman

La hipersecreción ovárica de andrógenos es una causa conocida de hirsutismo y virilización en la posmenopausia. La hipertecosis ovárica posmenopáusica es una alteración funcional originada por una regulación anormal de la esteroidogénesis ovárica. Presentamos a una paciente con hiperandrogenismo posmenopáusico ocasionado por una hipertecosisovárica (AU)

Ovarian androgen hypersecretion is a wellrecognized cause of hirsutism and virilization in postmenopausal women. Postmenopausal ovarian hyperthecosis is anonneoplastic functional disorder, which results from abnormal regulation of ovarian steroidogenesis. We present a patient with postmenopausal hyperandrogenism due to ovarian hyperthecosis (AU)

Hyperandrogenism in a postmenopausal woman.

Ovarian androgen hypersecretion is a wellrecognized cause of hirsutism and virilization in postmenopausal women. Postmenopausal ovarian hyperthecosis is a nonneoplastic functional disorder, which results from abnormal regulation of ovarian steroidogenesis. We present a patient with postmenopausal hyperandrogenism due to ovarian hyperthecosis.

Pancreatitis aguda grave en una embarazada con hiperparatiroidismo primario / Severe acute pancreatitis in a pregnant woman with primary hyperparathyroidism

La incidencia del hiperparatiroidismo primario en el embarazo es muy baja. El 80% de las pacientes están asintomáticas, y es extremadamente infrecuente su asociación a pancreatitis aguda. Cuando se diagnostica durante la gestación, el manejo depende de la gravedad de la hipercalcemia, la edad gestacional y la aparición de complicaciones. Presentamos el caso de una mujer embarazada que desarrolló fallo multiorgánico secundario a pancreatitis aguda grave por hiperparatiroidismo primario (AU)

The incidence of primary hyperparathyroidism during pregnancy is very low. Eighty percent of patients area symptomatic and an association with acute pancreatitis is fairly uncommon. When hyperparathyroidism is discovered during pregnancy, management is influenced by the degree of hypercalcemia, gestational age, and the presence of complications. We present a pregnant woman who developed multiorgan failure with severe acute pancreatitis due to primary hyperparathyroidism (AU)