Role of CB2 cannabinoid receptor in the development of food addiction in male mice.

The endocannabinoid system plays an important role in multiple behavioral responses due to its wide distribution in the central nervous system. The cannabinoid CB1 receptor was associated to the loss of behavioral control over food intake occurring during food addiction. The cannabinoid CB2 receptor (CB2R) is expressed in brain areas canonically associated with addictive-like behavior and was linked to drug-addictive properties. In this study, we evaluated for the first time the specific role of the CB2R in food addiction by using a well-validated operant mouse model of long-term training to obtain highly palatable food. We have compared in this model the behavioral responses of wild-type mice, mutant mice constitutively lacking CB2R, and transgenic mice overexpressing CB2R. The lack of CB2R constitutes a protective factor for the development of food addiction and the impulsive and depressive-like behavior associated. In contrast, the overexpression of CB2R induces a vulnerable phenotype toward food addiction after long-term exposure to highly palatable chocolate pellets. Relevant transcriptomic changes were associated to resilience and vulnerability to food addiction depending on the genotype, which provides a mechanistic explanation for these behavioral changes. Therefore, CB2R may constitute a potential therapeutic target for the loss of eating control and the comorbid emotional effects associated to food addiction.

[Hematoma of the rectus abdominis. experience of a primary care hospital]. / Hematoma del recto anterior del abdomen: experiencia en un hospital comarcal.

OBJECTIVE: To describe patients diagnosed with hematoma of the rectus abdominis (HRA) muscle. MATERIAL AND METHODS: A retrospective analysis of patients diagnosed with HRA over the past 8 years in our center. RESULTS: A total of 17 patients (9 women) with mean age of 73 years were included in the study. In 52% of the cases the HRA was the cause of hospitalization. Anticoagulant therapy was documented in 70%. More than half of patients treated with low molecular weight heparin had renal insufficiency. In the group receiving oral anticoagulants (OA), 86% had INR greater than 4. Paroxysmal cough appeared in 13. The most common presentation was abdominal pain and palpable mass. CT scan sensitivity was superior to that of the ultrasound. The most common location was the lower right. Treatment was conservative in all but one. Two patients died. Mean decrease in hemoglobin was 4.7 g/dl. Average stay was 19 days. CONCLUSIONS: In our center, HRA almost equally affects both genders and appears in older people with excessive anticoagulation and cough. The clinical presentation, increased diagnostic sensitivity of CT scan and predominance in the right abdominal involvement are similar to other series. Mortality and hospital stay are higher than described.

Vulnerability to addiction.

Addiction is a chronic brain disease that has dramatic health and socioeconomic consequences worldwide. Multiple approaches have been used for decades to clarify the neurobiological basis of this disease and to identify novel potential treatments. This review summarizes the main brain networks involved in the vulnerability to addiction and specific innovative technological approaches to investigate these neural circuits. First, the evolution of the definition of addiction across the Diagnostic and Statistical Manual of Mental Disorders (DSM) is revised. We next discuss several innovative experimental techniques that, combined with behavioral approaches, have allowed recent critical advances in understanding the neural circuits involved in addiction, including DREADDs, calcium imaging, and electrophysiology. All these techniques have been used to investigate specific neural circuits involved in vulnerability to addiction and have been extremely useful to clarify the neurobiological basis of each specific component of the addictive process. These novel tools targeting specific brain regions are of great interest to further understand the different aspects of this complex disease. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'.

Non-invasive monitoring of stress biomarkers in the newborn period.

The neonatal period is a highly sensitive time span during which stressful experiences may have an influence on later health outcomes. Medical procedures applied to newborn babies during hospitalization are stressors that trigger a physiological and psychological stress response. Stress response has been traditionally evaluated using scores based on behavioural signs such as facial expressions, limb movements, crying, etc., which are subjectively interpreted. Only few studies have employed measurable physiological signs to objectively evaluate the stress response to specific interventions. The aim of this review is to inform of recently developed biochemical methods that allow clinicians to evaluate the stress response to medical procedures performed in the neonatal period in biological samples non-invasively obtained. Stress biomarkers are based on the physiological stress response mediated by the hypophysis-pituitary-adrenal axis and the sympathetic-adreno-medullary systems. Cortisol is at present the most widely employed laboratory determination to measure stress levels. In recent years, sequentially determined salivary cortisol levels have allowed non-invasive monitoring of newborn infants under stressful conditions in the NICU.

Neuropsychological assessment and cortisol levels in biofluids from early Alzheimer's disease patients.

Cortisol dysregulation is proposed as a factor in the development of Alzheimer's disease (AD). AD patients can show high cortisol levels in prodromal phases of AD, early enough that neuropsychological alterations exist but activities of daily living remain unimpaired. Nevertheless, it is unknown if biofluid cortisol levels can have some AD predictive power together with neuropsychological assessment in prodromal stages in comparison with other cognitive disorders. In this work, an analytical method based on ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) was applied to determine the cortisol levels in different biofluids (urine, plasma, saliva, cerebrospinal fluid). Early AD patients and non-AD patients recruited at out-patient neurological unit were classified from the standard cerebrospinal fluid biomarkers levels (ß-amyloid, tau, phosphorylated tau), and studied with an extensive neuropsychological assessment including global, neuropsychological, functional and affective scales. We used a logistic regression model to discriminate between the AD and non-AD groups. Higher plasma cortisol levels were found in the AD group than in the non-AD group (p < 0.001). Regarding neuropsychological evaluation, delayed memory was used as representative of the neuropsychological status, and lower scores were obtained in the AD group (p < 0.001). The prediction model, including plasma cortisol levels and delayed memory scores, achieved an AUC of 0.93, as well as a sensitivity of 97% and a specificity of 69.4%. In conclusion, plasma cortisol levels and delayed memory scores were specifically impaired in early AD, allowing the development of a new diagnostic model which could be employed as a very satisfactory screening system.

Gender differences in C-reactive protein and homocysteine modulation of cognitive performance and real-world functioning in bipolar disorder.

BACKGROUND: Cognitive and psychosocial impairment has been associated with increased levels of C-reactive protein (CRP) and homocysteine in bipolar disorder, but gender differences have seldom been studied. METHODS: Two hundred and twenty-four bipolar outpatients were included. Cognitive performance was assessed through the Screen for Cognitive Impairment in Psychiatry (SCIP). Psychosocial functioning was evaluated using the Functioning Assessment Short Test (FAST) and the General Assessment of Functioning (GAF). Homocysteine and CRP levels were determined. Separate analyses were performed by gender. Partial correlations were calculated to test for associations between biomarkers and cognitive and psychosocial functioning. Hierarchical multiple regression was used to assess factors predicting cognitive and psychosocial functioning. Covariates were: age, education, duration of illness, hospital admissions, depressive symptoms, tobacco consumption, and BMI. RESULTS: A better performance was noted in women in delayed verbal learning (p = 0.010), along with better occupational functioning (p = 0.027) and greater leisure time impairment (p = 0.034). In men, CRP and homocysteine levels were associated with psychosocial dysfunction (interpersonal relationships and financial functioning, respectively). In women, CRP levels correlated with cognitive performance (SCIP total raw score, immediate and delayed verbal learning, and verbal fluency). CRP was a predictor of cognitive performance in women only. LIMITATIONS: The choice of the cognitive scale and covariates and the lack of a control group may be the main limitations. CONCLUSIONS: A gender difference was found in biomarker modulation of cognition and psychosocial functioning. A gender-based approach to cognition and real-world functioning should be considered in bipolar disorder to ensure an optimal outcome.

Morphological Changes in a Severe Model of Parkinson's Disease and Its Suitability to Test the Therapeutic Effects of Microencapsulated Neurotrophic Factors.

The unilateral 6-hydroxydopamine (6-OHDA) lesion of medial forebrain bundle (MFB) in rats affords us to study the advanced stages of Parkinson's disease (PD). Numerous evidences suggest synergic effects when various neurotrophic factors are administered in experimental models of PD. The aim of the present work was to assess the morphological changes along the rostro-caudal axis of caudo-putamen complex and substantia nigra (SN) in the referred model in order to test the suitability of a severe model to evaluate new neurorestorative therapies. Administration of 6-OHDA into MFB in addition to a remarkable depletion of dopamine in the nigrostriatal system induced an increase of glial fibrillary acidic protein (GFAP)-positive cells in SN and an intense immunoreactivity for OX-42, vascular endothelial growth factor (VEGF), and Lycopersycum esculentum agglutinin (LEA) in striatum and SN. Tyrosine hydroxylase (TH) immunostaining revealed a significant decrease of the TH-immunopositive striatal volume in 6-OHDA group from rostral to caudal one. The loss of TH-immunoreactive (TH-ir) neurons and axodendritic network (ADN) was higher in caudal sections. Morphological recovery after the implantation of microspheres loaded with VEGF and glial cell line-derived neurotrophic factor (GDNF) in parkinsonized rats was related to the preservation of the TH-ir cell number and ADN in the caudal region of the SN. In addition, these findings support the neurorestorative role of VEGF+GDNF in the dopaminergic system and the synergistic effect between both factors. On the other hand, a topological distribution of the dopaminergic system was noticeable in the severe model, showing a selective vulnerability to 6-OHDA and recovering after treatment.

Primary mesenteric liposarcoma of jejunum: presentation like a cystic mass.

This report describes a rare case of intra-abdominal liposarcoma in a 67-year-old woman. The patient presented at Internal Medicine Unit in May 2004, to study of thyroid pathology. The clinical examination was normal, except for the finding of an asymptomatic mass in the abdomen. The patient knew the existence of tumor since time ago, but she confesses to have only occasional discomfort. In the abdominal ultrasonography a solid mass with large cystic component was detected but relation with other organs was not clear. Computed tomography revealed the presence of a mass with solid and cystic components, in contact with small intestine in the left side of abdomen. A complete resection of tumor arising from mesentery of jejunum was performed successfully with end to end anastomosis. The gross specimen was lobulated and measured 8.5 x 7.5 cm. The histopathology analysis showed proliferating lipoblasts with irregular nuclei on a myxoid background, with plexiform vascular pattern, characteristics belongs to myxoid type liposarcoma. The patient is alive and well one year after removal of tumor. The uncommon site and the exceptional cystic morphology of tumor are discussed, and so it must be included the primary mesenteric liposarcoma in the differential diagnosis of intra-abdominal tumors with cystic large areas.

Topographical Distribution of Morphological Changes in a Partial Model of Parkinson's Disease--Effects of Nanoencapsulated Neurotrophic Factors Administration.

Administration of various neurotrophic factors is a promising strategy against Parkinson's disease (PD). An intrastriatal infusion of 6-hydroxidopamine (6-OHDA) in rats is a suitable model to study PD. This work aims to describe stereological parameters regarding rostro-caudal gradient, in order to characterize the model and verify its suitability for elucidating the benefits of therapeutic strategies. Administration of 6-OHDA induced a reduction in tyrosine hidroxylase (TH) reactivity in the dorsolateral part of the striatum, being higher in the caudal section than in the rostral one. Loss of TH-positive neurons and axodendritic network was highly significant in the external third of substantia nigra (e-SN) in the 6-OHDA group versus the saline one. After the administration of nanospheres loaded with neurotrophic factors (NTF: vascular endothelial growth factor (VEGF) + glial cell line-derived neurotrophic factor (GDNF)), parkinsonized rats showed more TH-positive fibers than those of control groups; this recovery taking place chiefly in the rostral sections. Neuronal density and axodendritic network in e-SN was more significant than in the entire SN; the topographical analysis showed that the highest difference between NTF versus control group was attained in the middle section. A high number of bromodeoxyuridine (BrdU)-positive cells were found in sub- and periventricular areas in the group receiving NTF, where most of them co-expressed doublecortin. Measurements on the e-SN achieved more specific and significant results than in the entire SN. This difference in rostro-caudal gradients underpins the usefulness of a topological approach to the assessment of the lesion and therapeutic strategies. Findings confirmed the neurorestorative, neurogenic, and synergistic effects of VEGF+GDNF administration.

Tuning the target composition of amine-grafted CPO-27-Mg for capture of CO2 under post-combustion and air filtering conditions: a combined experimental and computational study.

A computational and experimental screening of hypothetical and real compounds exhibiting different degrees of ethylenediamine grafted to the CPO-27-Mg or Mg-DOBDC skeleton is performed in order to determine the target composition that optimizes the CO2 adsorption properties under flue gas and air filtering conditions. On the basis of the [Mg2(dobdc)] formula, eighteen hypothetical models involving 15-100% of functionalization of the coordinatively unsaturated sites (CUS) were considered by means of Grand Canonical Monte Carlo simulations to evaluate the CO2 adsorption at 298 K. In addition, post-synthesis modification was applied to CPO-27-Mg leading to three kinds of samples exhibiting 15, 50, and 60% of CUS functionalization with ethylenediamine, named CPO-27-Mg-a, CPO-27-Mg-b and CPO-27-Mg-c. Compounds were characterized using elemental analysis, TGA, FTIR spectroscopy, PXRD and DSC. Finally, bare and functionalized CPO-27-Mg materials were evaluated using gas adsorption and microcalorimetry in the 0.001-1 bar range, which is pertinent for the mentioned applications. Valuable information related to design criteria for synthesis of tuned CO2 adsorbents is derived through this computational and experimental investigation.