Novel Leptin-Cardiac TRH pathway responsible for the cardiac alterations in the Hyperleptinemic obesity.

The association between hypertension and obesity-induced cardiac damage is usually accepted. However, no studies have been focused on cardiac alterations in obesity, independently of blood pressure increase. It is well known that Cardiac TRH induces Left Ventricular Hypertrophy (LVH) and fibrosis, and its inhibition prevents the development of hypertrophy. Also, it has been described that the adiponectin leptin induces TRH expression. Thus, we hypothesized that in obesity, the increase in TRH induced by hyperleptinemia is responsible for LVH, until now mostly attributed to pressure load. We studied obese Agouti mice suffering from hypertension with hyperleptinemia and found a significant LVH development with increased TRH gene expression. Consequently, we found higher fibrotic (collagens and TGF-ß) and hypertrophic markers (BNP and ß-MHC) expression vs lean black controls. As pressure could explain these results, we treated obese mice with diuretic (hydrochlorothiazide 20 mg/kg/day) since weaning. Diuretic treatment was successful as the diuretic group was normotensive in contrast to control obese mice. Nevertheless, both groups showed LVH development, higher cardiac precursor TRH gene and peptide expressions and elevated fibrotic and hypertrophic markers expression, pointing out that obesity-induced LVH is not due to hypertension. In addition, we performed Cardiac TRH inhibition by specific siRNA injection compared to control siRNA treatment and evaluated cardiac damage. As expected, expressions and protein increase in hypertrophic and fibrotic markers observed in the AG mouse with the native cTRH system were not seen in the AG mouse with the cTRH silencing. Indeed, the AG + TRH-siRNA group showed hypertrophic markers expression and fibrosis measurements similar to the lean BL mice. On the whole, these results point out that the novel Leptin-Cardiac TRH pathway is responsible for the cardiac alterations present in hyperleptinemic obesity, independent of blood pressure, and cTRH long-term silencing since early stages totally prevent LVH development and cardiac fibrosis.

Síndrome del seno carotídeo asociado a linfoma B cervical / Carotid sinus syndrome associated to cervical B-cell lymphoma

Resumen Se describe el caso de un varón de 75 años con tumoración submaxilar derecha de 5 meses de evolución sin diagnóstico etiológico, que consultó por episodios de síncope precedidos por disnea y sudoración profusa de instalación súbita. Durante su internación se detectaron, en el monitoreo electrocardiográ fico, pausas mayores a 3 segundos luego de la lateralización cervical reproduciendo los síntomas mencionados y asociadas a sensación de pérdida inminente de la conciencia, por lo que se implantó marcapasos transitorio. Se realizó biopsia de la masa tumoral cervical, consistente con linfoma B difuso de células grandes no centro germinal, y se inició quimioterapia. Luego de dicho tratamiento quimioterápico se observó reducción significativa de la masa tumoral con abolición de los síntomas asociados a las maniobras cervicales. El diagnóstico definitivo fue síndrome del seno carotídeo maligno asociado a linfoma cervical.

Abstract We present the case of a 75-year-old male with history of 5 months of right submaxillary tumor, with no clear etiology, who consulted for episodes of syncope preceded by dyspnea and sudden onset of profuse sweating. During his stay at the hospital, electrocardiographic records showed more than 3-second-long pauses after head movements, with a sensation of imminent loss of consciousness associated. A temporary pacemaker was required. Biopsy showed a diffuse non-germinal large B-cell B lymphoma, which required chemotherapy. After the first chemotherapy session, a significant reduction of the tumoral mass was observed, with abolition of the symptoms associated to cervical movements. The definitive diagnosis was malignant carotid sinus syndrome associated with cervical lymphoma.

[Carotid sinus syndrome associated to cervical B-cell lymphoma]. / Síndrome del seno carotídeo asociado a linfoma B cervical.

We present the case of a 75-year-old male with history of 5 months of right submaxillary tumor, with no clear etiology, who consulted for episodes of syncope preceded by dyspnea and sudden onset of profuse sweating. During his stay at the hospital, electrocardiographic records showed more than 3-second-long pauses after head movements, with a sensation of imminent loss of consciousness associated. A temporary pacemaker was required. Biopsy showed a diffuse non-germinal large B-cell B lymphoma, which required chemotherapy. After the first chemotherapy session, a significant reduction of the tumoral mass was observed, with abolition of the symptoms associated to cervical movements. The definitive diagnosis was malignant carotid sinus syndrome associated with cervical lymphoma.

Se describe el caso de un varón de 75 años con tumoración submaxilar derecha de 5 meses de evolución sin diagnóstico etiológico, que consultó por episodios de síncope precedidos por disnea y sudoración profusa de instalación súbita. Durante su internación se detectaron, en el monitoreo electrocardiográfico, pausas mayores a 3 segundos luego de la lateralización cervical reproduciendo los síntomas mencionados y asociadas a sensación de pérdida inminente de la conciencia, por lo que se implantó marcapasos transitorio. Se realizó biopsia de la masa tumoral cervical, consistente con linfoma B difuso de células grandes no centrogerminal, y se inició quimioterapia. Luego de dicho tratamiento quimioterápico se observó reducción significativa de la masa tumoral con abolición de los síntomas asociados a las maniobras cervicales. El diagnóstico definitivo fue síndrome del seno carotídeo maligno asociado a linfoma cervical.