The Uncompetitive N-methyl-D-Aspartate Antagonist Memantine Reduces Binge-Like Eating,Food-Seeking Behavior,and Compulsive Eating: Role of the Nucleus Accumbens Shell

Binge-eating disorder is characterized by excessive, uncontrollable consumption of palatable food within brief periods of time. The role of the glutamatergic N-methyl-D-aspartate (NMDA) receptor system in hedonic feeding is poorly understood. The aim of this study was to characterize the effects of the uncompetitive NMDA receptor antagonist memantine on palatable food-induced behavioral adaptations using a rat model, which mimics the characteristic symptomatology observed in binge-eating disorder. For this purpose, we allowed male Wistar rats to respond to obtain a highly palatable, sugary diet (Palatable group) or a regular chow diet (Chow control group), for 1 h a day, under a fixed-ratio 1 (FR1) schedule of reinforcement. Upon stabilization of food responding, we tested the effects of memantine on the Chow and Palatable food groups'' intake. Then, we tested the effects of memantine on food-seeking behavior, under a second-order schedule of reinforcement. Furthermore, we investigated the effects of memantine on the intake of food when it was offered in an aversive, bright compartment of a light/dark conflict test. Finally, we evaluated the effects of memantine on FR1 responding for food, when microinfused into the nucleus accumbens (NAcc) shell or core. Memantine dose-dependently decreased binge-like eating and fully blocked food-seeking behavior and compulsive eating, selectively in the Palatable food group. The drug treatment did not affect performance of the control Chow food group. Finally, intra-NAcc shell, but not core, microinfusion of memantine decreased binge-like eating. Together, these findings substantiate a role of memantine as a potential pharmacological treatment for binge-eating disorder.     

Direct Current Cardioversion in Atrial Fibrillation Patients on Edoxaban Therapy Versus Vitamin K Antagonists: a Real-world Propensity Score–Matched Study

Cardiovascular Drugs and Therapy - The purpose of the present study was to compare the long-term effectiveness and safety of newly initiated anticoagulation with edoxaban (EDO) versus uninterrupted...     

Akt mediates the cross-talk between beta-adrenergic and insulin receptors in neonatal cardiomyocytes

Upregulation of the sympathetic nervous system plays a key role in the pathogenesis of insulin resistance. Although the heart is a target organ of insulin, few studies have examined the mechanisms by which beta-adrenergic stimulation affects insulin sensitivity in cardiac muscle. In this study, we explored the molecular mechanisms involved in the regulation of the cross-talk between beta adrenergic and insulin receptors in neonatal rat cardiomyocytes and in transgenic mice with cardiac overexpression of a constitutively active mutant of Akt (E40K Tg). The results of this study show that beta-adrenergic receptor stimulation has a biphasic effect on insulin-stimulated glucose uptake. Short-term stimulation induces an additive effect on insulin-induced glucose uptake, and this effect is mediated by phosphorylation of Akt in threonine 308 through PKA/Ca2+-dependent and PI3K-independent pathway, whereas insulin-evoked threonine phosphorylation of Akt is exclusively PI3K-dependent. On the other hand, long-term stimulation of beta-adrenergic receptors inhibits both insulin-stimulated glucose uptake and insulin-induced autophosphorylation of the insulin receptor, and at the same time promotes threonine phosphorylation of the insulin receptor. This is mediated by serine 473 phosphorylation of Akt through PKA/Ca2+ and PI3K-dependent pathways. Under basal conditions, E40K Tg mice show increased levels of threonine phosphorylation of the beta subunit of the insulin receptor and blunted tyrosine autophosphorylation of the beta-subunit of the insulin receptor after insulin stimulation. These results indicate that, in cardiomyocytes, beta-adrenergic receptor stimulation impairs insulin signaling transduction machinery through an Akt-dependent pathway, suggesting that Akt is critically involved in the regulation of insulin sensitivity.     

Oesophageal candidiasis: clinical and mycological analysis

Oesophageal candidiasis is an epithelial infection which requires an immune deficiency. C. albicans is commonly the cause, although other species may also be responsible. Resistance to fluconazole, drug of choice for treatment, is an emerging problem. The objectives of the current paper were: to determine the frequency of oesophageal candidiasis in patients submitted to upper gastrointestinal endoscopy, analyze risk factors, identify Candida species and determine in vitro susceptibility to fluconazole. During 12 months, 34 patients with oesophageal candidiasis were detected. Out of 1.230 HIV negative and 91 HIV positive patients submitted to upper endoscopy, 11 (0.9%) and 23 (25.3%), respectively, had candidiasis. Risk factors for HIV negative patients were systemic antibiotic therapy in 2, deficient dental cleaning in 2 aged patients, use of proton pump inhibitors in 3, inhaled steroids in 2, malignancy in 1 and oral steroids in 1. The histopathologic diagnosis was confirmed in 48.6% of cases. Cultures were positive in 91.2% C. albicans was prevalent (93.5%), and was associated to other species in 5 cases (16.1%), (3 C. glabrata, 1 C. tropicalis and 1 C. parapsilosis). One case cultured only C. glabrata and 1, only C tropicalis. Out of 31 cultures, 25 were susceptible to fluconazole, 4 dose dependent (1 C. albicans, 3 C. glabrata), and 2 resistant (1 C. albicans, 1 C. glabrata). Frequency of oesophageal candidiasis was low, except for HIV positive patients. The most common etiologic agent was C. albicans, though other Candida species were also found. C. albicans and C. glabrata showed dose dependency and resistance to fluconazole.     

Does current treatment of cardiogenic shock complicating the acute coronary syndromes comply with guidelines?

Background

The purpose of our study was to evaluate the implementation of guidelines for the treatment of cardiogenic shock (CS) complicating the acute coronary syndromes (ACS).

Methods and Results

Of the 10 136 patients in the Euro-Heart-Survey-ACS with complete data, CS occurred in 549 (5.4%), of whom 28.6% had CS upon presentation. We examined the use of coronary angiography (CA), percutaneous (PCI) and surgical (CABG) revascularization, and intra-aortic balloon counterpulsation (IABP) among ACS patients with and without CS. During the hospital course, there were no significant differences between patients with and without CS in referral to CA (52.4% vs 53.3%, respectively) or CABG (4.4% vs 4.5%), but CS patients were more likely to undergo IABP (17.7% vs 0.8%, P < .001) and PCI (40.8% vs 31.8%, P < .001), especially younger (<75 years) patients (52.2% vs 31.8%, P < .001). A similar trend was observed when comparing ST-elevation-ACS patients with (368 [8.5%]) and without CS (3945): CA (58.1% vs 56.2%), CABG (3.6% vs 3.3%), IABP (20.0% vs 0.9%, P < .01), and PCI (47.3% vs 40.6%, P < .01; 54.4% vs. 44.6% for patients <75 years, P < .003). Of the 94 ST-elevation-ACS patients presenting with CS, only 39 (41.4%) received any reperfusion treatment, more often fibrinolysis (64.1%). The in-hospital mortality was 52.1% for all CS pts vs 2.0% for all others (P < .001).

Conclusions

Our contemporary survey demonstrates prohibitively-high mortality rates among ACS patients complicated by CS and poor implementation of recent guidelines advocating an aggressive invasive approach, including low rates of revascularization and IABP. Improved adherence to the guidelines pertaining to ACS patients developing CS may hopefully improve outcomes.     

Systemic inflammatory diseases and silicone breast prostheses: report of a case of adult still disease and review of the literature

There has been a debate about the possibility of a link between silicone breast implants and the onset of systemic connective tissue diseases (eg, scleroderma, systemic lupus erythematosus, rheumatoid arthritis) and other inflammatory pathologies, such as silicone implant associated syndrome and adult Still disease. We report a case of adult Still disease in a patient with a silicone gel breast implant. The disease regressed with steroidal treatment, and the patient is now no longer steroid-dependent, although the implant is still in place.