Hungry brains: A meta-analytical review of brain activation imaging studies on food perception and appetite in obese individuals

The dysregulation of food intake in chronic obesity has been explained by different theories. To assess their explanatory power, we meta-analyzed 22 brain-activation imaging studies. We found that obese individuals exhibit hyper-responsivity of the brain regions involved in taste and reward for food-related stimuli. Consistent with a Reward Surfeit Hypothesis, obese individuals exhibit a ventral striatum hyper-responsivity in response to pure tastes, particularly when fasting. Furthermore, we found that obese subjects display more frequent ventral striatal activation for visual food cues when satiated: this continued processing within the reward system, together with the aforementioned evidence, is compatible with the Incentive Sensitization Theory. On the other hand, we did not find univocal evidence in favor of a Reward Deficit Hypothesis nor for a systematic deficit of inhibitory cognitive control. We conclude that the available brain activation data on the dysregulated food intake and food-related behavior in chronic obesity can be best framed within an Incentive Sensitization Theory. Implications of these findings for a brain-based therapy of obesity are briefly discussed

Penicillamine-related lichenoid dermatitis and utility of zinc acetate in a wilson disease patient with hepatic presentation, anxiety and spect abnormalities

Wilson disease is an autosomal recessive disorder of hepatic copper metabolism with consequent copper accumulation and toxicity in many tissues and consequent hepatic, neurologic and psychiatric disorders. We report a case of Wilson disease with chronic liver disease; moreover, in our patient, presenting also with high levels of state anxiety without depression, 99mTc-ECD- SPECT showed cortical hypoperfusion in frontal lobes, more marked on the left frontal lobe. During the follow-up of our patient, penicillamine was interrupted after the appearance of a lichenoid dermatitis, and zinc acetate permitted to continue the successful treatment of the patient without side-effects. In our case the therapy with zinc acetate represented an effective treatment for a Wilson disease patient in which penicillamine-related side effects appeared. The safety of the zinc acetate allowed us to avoid other potentially toxic chelating drugs; this observation is in line with the growing evidence on the efficacy of the drug in the treatment of Wilson disease. Since most of Wilson disease penicillamine-treated patients do not seem to develop this skin lesion, it could be conceivable that a specific genetic factor is involved in drug response. Further studies are needed for a better clarification of Wilson disease therapy, and in particular to differentiate specific therapies for different Wilson disease phenotypes

Effect of Etidronate and Ibandronate on Cytosolic Ca2+ in HT29 and Parasite Cell Line from Echinococcus Granulosus sensu lato

Background: The bisphosphonates are synthetic analogs of pyrophosphate in which two phosphates are connected through carbon instead of oxygen. They are approved compounds for the treatment of hypercalcemia, bone diseases and they have been proposed to treat infectious diseases. Bisphosphonates’ main mechanisms of action are on calcium metabolism, inhibition of protein prenylation and on ATP synthesis. In a previous work, the antiparasitic activity of bisphosphonates on a cell line from Echinococcus granulosus, sensu lato protoscoleces, 30 µM etidronate and ibandronate have antiproliferative activity after 72 h of incubation, decreasing intracellular ATP and only etidronate increased intracellular total calcium concentration. Objective: This work studied the effect of etidronate and ibandronate on cytoplasmic ionic calcium concentration in parasitic cell line and in HT29, cell line from human colon adenocarcinoma. Methods: Ionic calcium was measured by spectrofluorometric, labeling cells with Fluo-4AM. Cells were suspended in Na+ or K+ rich buffer and two calcium salts were used Cl- or Gluc- , anion permeable and impermeable, respectively. Results: Remarkable differences between cell lines were shown with the effect of bisphosphonates on intracellular ionic calcium concentration in hyperpolarized cells and these differences were smoothed on depolarized cells, in spite of the similar cellular response to calcium salts in absence of bisphosphonates. Conclusion: The bisphosphonates, mainly etidronate, decreased intracellular ionic calcium on parasitic cells explaining other aspects of their antiproliferative effect. Results suggested that other mechanism, such as Cl- and Na+ interchange are differentially affected by bisphosphonates, depending on cell line originFil: Ferrulli, Mariana. Universidad Abierta Interamericana. Secretaría de Investigación. Centro de Altos Estudios En Ciencias Humanas y de la Salud - Sede Buenos Aires; ArgentinaFil: Pérez Rojo, Fernando Gabriel. Universidad Abierta Interamericana. Secretaría de Investigación. Centro de Altos Estudios En Ciencias Humanas y de la Salud - Sede Buenos Aires; ArgentinaFil: Granada Herrera, Lilian Andrea. Universidad Abierta Interamericana. Secretaría de Investigación. Centro de Altos Estudios En Ciencias Humanas y de la Salud - Sede Buenos Aires; ArgentinaFil: Maglioco, Andrea Florencia. Universidad Abierta Interamericana. Secretaría de Investigación. Centro de Altos Estudios En Ciencias Humanas y de la Salud - Sede Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roldán, Emilio A. J.. Universidad Abierta Interamericana. Secretaría de Investigación. Centro de Altos Estudios En Ciencias Humanas y de la Salud - Sede Buenos Aires; ArgentinaFil: Fuchs, Alicia Graciela. Universidad Abierta Interamericana. Secretaría de Investigación. Centro de Altos Estudios En Ciencias Humanas y de la Salud - Sede Buenos Aires; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentin

Cutaneous manifestations in celiac disease

Celiac disease (CD) is an autoimmune gluten-dependent enteropathy characterized by atrophy of intestinal villi that improves after gluten-free diet (GFD). CD is often associated with extra-intestinal manifestations; among them, several skin diseases are described in CD patients. The present review reports all CD-associated skin manifestations described in the literature and tries to analyze the possible mechanisms involved in this association. The opportunity to evaluate the possible presence of CD in patients affected by skin disorders is discussed

In vivo treatment with calcilytic of CaSR knock-in mice ameliorates renal phenotype reversing downregulation of the vasopressin-AQP2 pathway

Abstract: High concentrations of urinary calcium counteract vasopressin action via the activation of the Calcium-Sensing Receptor (CaSR) expressed in the luminal membrane of the collecting duct cells, which impairs the trafficking of aquaporin-2 (AQP2). In line with these findings, we provide evidence that, with respect to wild-type mice, CaSR knock-in (KI) mice mimicking autosomal dominant hypocalcaemia, display a significant decrease in the total content of AQP2 associated with significantly higher levels of AQP2 phosphorylation at Ser261, a phosphorylation site involved in AQP2 degradation. Interestingly, KI mice also had significantly higher levels of phosphorylated p38MAPK, a downstream effector of CaSR and known to phosphorylate AQP2 at Ser261. Moreover, ATF1 phosphorylated at Ser63, a transcription factor downstream of p38MAPK, was significantly higher in KI. In addition, KI mice had significantly higher levels of AQP2-targeting miRNA137 consistent with a post-transcriptional downregulation of AQP2. In vivo treatment of KI mice with the calcilytic JTT-305, a CaSR antagonist, increased AQP2 expression and reduced AQP2-targeting miRNA137 levels in KI mice. Together, these results provide direct evidence for a critical role of CaSR in impairing both short-term vasopressin response by increasing AQP2-pS261, as well as AQP2 abundance, via the p38MAPK-ATF1-miR137 pathway. (Figure presented.). Key points: Calcium-Sensing Receptor (CaSR) activating mutations are the main cause of autosomal dominant hypocalcaemia (ADH) characterized by inappropriate renal calcium excretion leading to hypocalcaemia and hypercalciuria. Current treatments of ADH patients with parathyroid hormone, although improving hypocalcaemia, do not improve hypercalciuria or nephrocalcinosis. In vivo treatment with calcilytic JTT-305/MK-5442 ameliorates most of the ADH phenotypes of the CaSR knock-in mice including hypercalciuria or nephrocalcinosis and reverses the downregulation of the vasopressin-sensitive aquaporin-2 (AQP2) expression, providing direct evidence for a critical role of CaSR in impairing vasopressin response. The beneficial effect of calcilytic in reducing the risk of renal calcification may occur in a parathyroid hormone-independent action through vasopressin-dependent inhibition of cAMP synthesis in the thick ascending limb and in the collecting duct. The amelioration of most of the abnormalities in calcium metabolism including hypercalciuria, renal calcification, and AQP2-mediated osmotic water reabsorption makes calcilytic a good candidate as a novel therapeutic agent for ADH

Active Subjects with Autoimmune Type 1 Diabetes Have Better Metabolic Profiles than Sedentary Controls

Previous studies in humans with type 1 diabetes (T1D) and in non-obese diabetic mice have investigated the beneficial immunomodulatory potential of aerobic physical activity. Performing high volume of aerobic exercise may favorably regulate autoimmunity in diabetes. We tested whether increased physical activity is a self-sufficient positive factor in T1D subjects. During a 3-month observational period, active (6M; 40.5\ub16.1 years; BMI 24.5\ub12.1) and sedentary (4M, 3F; 35.9\ub18.9 years; BMI 25.7\ub13.8) T1D individuals on insulin pump therapy were studied for metabolic, inflammatory and autoimmune parameters. At baseline and at the end of a 3-month period, glycosylated hemoglobin (HbA1c), auto-antibodies (anti-GAD, anti-ZnT8, anti-IA2, ICA) and pro-inflammatory cytokines (IL-6 and TNF-\u3b1) were evaluated. During the 3rd month of the period, physically active T1D patients showed a significant reduction in the average glucose levels (-9%, p=0.025, by CGM) compared to the 1st-month values, and even their hyperglycemic episodes (>180mg/dL) diminished significantly (-24.2%, p=0.032 vs 1st month). Moreover, active T1D subjects exhibited an improved body composition with respect to sedentary controls. No significant changes were detected as to the autoimmune and inflammatory profiles. This study confirms the beneficial role of physical exercise associated with insulin pump therapy in order to improve metabolic control in individuals with T1D. These preliminary positive observations need to be challenged in a prolonged interventional follow-up

Effect of Sugar versus Mixed Breakfast on Metabolic and Neurofunctional Responses in Healthy Individuals

We investigated the effects of glucose and diverse breakfasts on glucose increment and ghrelin suppression and cognitive processing of sensory information assessed by frontal P300 evoked potentials. In a randomized crossover design, 12 healthy individuals (6M/6F; BMI 22.2\u2009\ub1\u20090.4\u2009kg/m2; 27\u2009\ub1\u20091.3 years, mean\u2009\ub1\u2009SEM) underwent 50\u2009g OGTT (A) and 3 breakfasts (B1: milk and cereals; B2: milk, apple, and chocolate cream-filled sponge cake; B3: milk, apple, bread, and hazelnut chocolate cream) to assess plasma glucose-, insulin-, and ghrelin excursions. An electroencephalography was performed before and 100\u2009min after consumption of each load to measure the latency of frontal P300 evoked potentials as index of cognitive performance. Breakfasts B1 and B2 exhibited significantly lower glycemic and insulinemic responses as compared to A. Breakfast B3 exhibited significantly lower glycemic, but not insulinemic response, as compared to A. Final plasma ghrelin inhibition was more pronounced, albeit not significantly, in all breakfasts with respect to A. P300 latency tended to decrease following each of the three breakfasts, but B3 was the only breakfast capable to elicit a statistically significant reduction in P300 latency with respect to A (), suggesting ameliorated cognitive performance. Such amelioration was correlated with the 2-hour final inhibition of plasma ghrelin concentration (r = 0.61, p = 0.01)

To Vladimir Maz'ya with respect and admiration

We derive some bounds on the location of complex eigenvalues for a family of Schrödinger operators H0,ν defined on the positive half line and subject to integrable complex potential. We generalise the results obtained in [14] where the operator does not have a Hardy term and also include the analysis for potentials belonging to weighted Lp spaces. Some information on the geometry of the complex region which bounds the eigenvalues of the radial Schrödinger multidimensional operator are then recovered

Eigenvalues of the bilayer graphene operator with a complex valued potential

We study the spectrum of a system of second order differential operator Dm perturbed by a non-selfadjoint matrix valued potential V. We prove that eigenvalues of Dm+V are located near the edges of the spectrum of the unperturbed operator Dm