Upregulation of mGlu2 receptors via NF-kB p65 acetylation is involved in the proneurogenic and antidepressant effects of acetyl-L-carnitine

Acetyl-L-carnitine (ALC) is a naturally occurring molecule with an important role in cellular bioenergetics and as donor of acetyl groups to proteins, including NF-kappa B p65. In humans, exogenously administered ALC has been shown to be effective in mood disturbances, with a good tolerability profile. No current information is available on the antidepressant effect of ALC in animal models of depression and on the putative mechanism involved in such effect. Here we report that ALC is a proneurogenic molecule, whose effect on neuronal differentiation of adult hippocampal neural progenitors is independent of its neuroprotective activity. The in vitro proneurogenic effects of ALC appear to be mediated by activation of the NF-kappa B pathway, and in particular by p65 acetylation, and subsequent NF-kappa B-mediated upregulation of metabotropic glutamate receptor 2 (mGlu2) expression. When tested in vivo, chronic ALC treatment could revert depressive-like behavior caused by unpredictable chronic mild stress, a rodent model of depression with high face validity and predictivity, and its behavioral effect correlated with upregulated expression of mGlu2 receptor in hippocampi of stressed mice. Moreover, chronic, but not acute or subchronic, drug treatment significantly increased adult born neurons in hippocampi of stressed and unstressed mice. We now propose that this mechanism could be potentially involved in the antidepressant effect of ALC in humans. These results are potentially relevant from a clinical perspective, as for its high tolerability profile ALC may be ideally employed in patient subpopulations who are sensitive to the side effects associated with classical antidepressant

P116 GIANT LEFT ATRIAL MYXOMA CAUSING ACUTE ISCHEMIC STROKE

Abstract Aims Primary cardiac tumours are rare; most are benign, and around half are myxomas, often located in the left atrium. Clinical presentation is variable. Ischaemic stroke is a rare, although real and potentially fatal, complications of cardiac myxomas. Case Report We present a case of a 51–year–old man, ex– smoker, obese, with history of hypertension and COPD, presented to our emergency department with right–sided hemiplegia and aphasia caused by ischaemic stroke. Brain CT revealed cerebral perfusion deficit. The patient was underwent intravenous thrombolytic strategy. TTE showed a large left atrial mass attached to the interatrial septum, with a friable appearance, suggestive of myxoma. The 2D and 3D TEE detected a giant space–occupying mass in the left atrium, coral–like, and the most apical portion prolapsed into the left ventricle during diastole, causing fixed obstruction to flow in the left ventricular inflow tract. In view of the risk of imminent embolization, the emergent surgical excision of the tumour was performed. Subsequent histopathological findings confirmed the diagnosis of myxoma. Symptomatic cardiac myxoma may present with one of the three classic clinical presentations of the Goodwin’s triad, which include intracardiac obstruction, constitutional symptoms, and embolism. The obstructive pattern mimics atrioventricular valve obstruction. Constitutional manifestations include fatigue, fever, weight loss. Systemic embolization from myxoma occurs in around a third of cases. Of these, the most serious is cerebrovascular embolism, which may result in cerebral stroke. The tumour size, location, and macroscopic appearance, along with mean platelet volume and platelet count, are closely associated with embolic events. Echocardiography remains the method of choice for diagnosis and morphological characterization of myxoma. Two patterns have been established by echocardiography: round, with a solid appearance and a firm surface, and polypoid, with an irregular outline and a friable surface. The incidence of systemic embolization is higher in those with an irregular and friable surface and those that prolapse into the ventricle. Once a diagnosis of myxoma is established, surgical resection is the only effective treatment and should be performed immediately, in view of the risk of embolization. Conclusions With this case report, we stress the importance of echocardiography in new onset of neurological deficit to prevent potentially fatal outcomes. </jats:sec

Giant left atrial myxoma causing acute ischemic stroke

Atrial myxomas are primary cardiac tumors which may cause ischemic stroke. The authors present a case of a 51-year-old man admitted to the emergency department with right-sided hemiplegia and aphasia caused by ischemic stroke. 2D and 3D transesophageal echocardiography showed an atrial myxoma described as a large mass in the left atrium attached to the interatrial septum. In the end, surgical excision of the myxoma was performed 48 h after diagnosis. Nowadays, specific guidelines concerning the correct time for surgical excision of the myxoma are lacking. The authors highlight the utmost role of echocardiography to promptly characterize a cardiac mass and the importance of discuss about the timing of cardiac surgery. Plain language summary Atrial myxoma is a rare cardiac tumor that is often located in the left atrium of the heart. Patients with myxoma can have no symptoms, or they can present signs of systemic embolization, where fragments of the tumor have been released into the blood stream and are circulating to different areas of the body. Indeed, if a fragment reaches the brain, it can cause a cerebral acute ischemic stroke, which is a sudden loss of blood circulation to an area of the brain, resulting in a loss of neurologic function. Transesophageal echocardiography, an ultrasound test that produces real-time and detailed images of the heart, is a useful tool that allows physicians to diagnose the presence of an atrial myxoma. In this case report, the authors stress the role of echocardiography in diagnosing patients presenting with sudden neurological symptoms, because it can show a potential mass inside the heart. Once identified, the tumor can be removed surgically as soon as possible to avoid further complications, such as a new stroke. Tweetable abstract The authors describe a case of an ischemic stroke caused by a large atrial myxoma, which was surgically removed 48 h after diagnosis

Scrivere di santi

Il volume, frutto del II Convegno dell'Associazione per lo studio della santità, culti e agiogafia (AISSCA) affronta le varie problemati,che della scrittura dei santi e sui santi dall'antichità all'età contemporane