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.

[Fibrilación auricular de primera vez en evento vascular cerebral isquémico en el servicio de urgencias]. / Undiagnosed atrial fibrillation in patients with an ischemic cerebral vascular event

Objective: To determine the incidence of undiagnosed atrial fibrillation in patients with an ischemic cerebral vascular event. Methods: A descriptive cross-sectional design was carried out in patients older than 18 years with a diagnosis of ischemic cerebral vascular event, attended in the emergency department. The sample size was made up of the total clinical records of patients with a diagnosis of ischemic cerebral vascular event (n = 199). All patients who underwent electrocardiogram were included. Age and sex were studied; history of diabetes mellitus and history of hypertension. The cerebral vascular event was diagnosed with a computerized axial tomography endorsed by a radiologist; atrial fibrillation was considered when an irregular R-R wave, absence of P wave, and irregular atrial activity were identified on the electrocardiogram. The reading and interpretation was performed by the emergency physician. Statistical analysis included percentages, confidence intervals for percentages and calculation of probability of occurrence of binomial event. Results: The average age of the patients with a cerebral vascular event is 72.37 years (95% CI: 70.91-73.82), the male sex predominates with 57.7% (95% CI: 50.8-64.7). The diagnosis of arterial hypertension is present in 74.8% (95% CI: 68.8-80.9) of the patients. The incidence of first-time atrial fibrillation is 72.36% (95% CI: 66.0-78.6). Conclusion: In the studied population, the incidence of previously undiagnosed atrial fibrillation in patients with ischemic cerebrovascular event is high.

Objetivo: Determinar la incidencia de fibrilación auricular no diagnosticada en pacientes con evento vascular cerebral tipo isquémico. Métodos: Diseño transversal descriptivo en pacientes mayores de 18 años con diagnóstico de evento vascular cerebral de tipo isquémico, atendidos en el servicio de urgencias. El tamaño de la muestra lo integraron el total de expedientes clínicos de pacientes con diagnóstico de evento vascular cerebral isquémico (n = 199). Se incluyeron todos los pacientes a los que se les realizó electrocardiograma. Se estudió edad, sexo, antecedente de diabetes mellitus y antecedente de hipertensión arterial. El evento vascular cerebral se diagnosticó con tomografía axial computarizada avalada por médico radiólogo; se consideró fibrilación auricular cuando en el electrocardiograma se identificó onda R-R irregular, ausencia de onda P y actividad auricular irregular; la lectura e interpretación fue realizada por el médico urgenciólogo. El análisis estadístico incluyó porcentajes, intervalos de confianza para porcentajes y cálculo de probabilidad de ocurrencia de evento binomial. Resultados: El promedio de edad de los pacientes con evento vascular cerebral es 72.37 años (IC 95%: 70.91-73.82), predomina el sexo masculino con un 57.7% (intervalo de confianza del 95% [IC 95%]: 50.8-64.7). El diagnóstico de hipertensión arterial está presente en el 74.8% (IC 95%: 68.8-80.9) de los pacientes. La incidencia de fibrilación auricular de primera es el 72.36% (IC 95%: 66.0-78.6). Conclusión: En la población estudiada la incidencia de fibrilación auricular no diagnosticada previamente en pacientes con evento vascular cerebral isquémico es alta.

Comanejo de la fractura de cadera del anciano en un hospital de tercer nivel: un estudio de cohortes / Hip fracture co-management in the elderly in a tertiary referral hospital: a cohorts study

INTRODUCCIÓN: La fractura de cadera del anciano es de los diagnósticos más prevalentes en los servicios de Traumatología, con gran impacto en términos clínicos, económicos y sociales. Nuestro objetivo es analizar el impacto clínico de un modelo de comanejo entre Traumatología y Medicina Interna para pacientes ancianos ingresados por fractura de cadera en un hospital de tercer nivel. MATERIAL Y MÉTODOS: Cohortes retrospectivas de pacientes mayores de 65 años ingresados por fractura de cadera entre enero de 2005 y agosto de 2006 (cohorte HIST) sin modelo de comanejo, y entre enero de 2008 y agosto de 2010 (cohorte COFRAC) con dicho modelo. Se analizaron características demográficas, clínicas y quirúrgicas, incidencia de complicaciones, mortalidad y reingreso a los 30 días. RESULTADOS: Se incluyó a 701 pacientes (471 HIST, 230 COFRAC). No hubo diferencias en edad, género, demora quirúrgica, tiempo y tipo de cirugía e intervención, estancia, deambulación al alta, consulta en urgencias ni reingreso o mortalidad a 30 días. Hubo diferencias en identificación de pluripatológicos (16,8 vs. 24,4%; p = 0,02), osteoporosis (3,9 vs. 7,6%; p = 0,03) o déficit motor (3,5 vs. 8,8%; p = 0,03), fármacos del tratamiento (3,7+/-2,5 vs. 4,3+/-3,2; p < 0,01), aparición de delirium (15,6 vs. 20,9%, p = 0,048) e hipomotilidad intestinal (80,3 vs. 74,7%; p < 0,001), seguimiento de anemia (83,3 vs. 97,1%; p > 0,01) y de función renal (44,5 vs. 97,3%; p < 0,01) y mortalidad intrahospitalaria (4,6 vs. 1,3%; p = 0,02). CONCLUSIONES: El comanejo de pacientes ancianos ingresados por fractura de cadera permite mejorar la documentación de los problemas crónicos previos y el control de complicaciones hospitalarias y disminuye la mortalidad intrahospitalaria

INTRODUCTION: Hip fracture in the elderly is one of the most prevalent diagnoses in Orthopedic Surgery Departments. It has a great impact in medical, economic and social terms. Our objective is to analyze clinical impact of a co-management care model between orthopedic surgery and internal medicine departments for elderly patients admitted with hip fracture in a tertiary referral hospital. MATERIAL AND METHODS: Retrospective cohort study of patients older than 65 years old admitted with hip fracture between January 2005-August 2006 (HIST cohort) without a co-management care model, and between January 2008-August 2010 (COFRAC cohort) with a co-manEdadment care model. Analysis of demographic, clinical and surgery characteristics, complications incidence and mortality and re-admissions at 30 days was made. RESULTS: A total of 701 patients were included (471 HIST, 230 COFRAC). There were no differences in sex, gender, time to surgery, type of anesthesia and surgery, length of stay, ambulation at discharge and 30-days emergency room consultation, readmissions or mortality at 30 days. There were differences in identification of polypatological patients (16.8 vs. 24.4%, P=0.02), presence of osteoporosis (3.9 vs. 7.6%, P=0.03), motor deficit (3.5 vs. 8.8%, P=0.03), number of chronic drugs (3.7+/-2.5 vs. 4.3+/-3.2, P<0.01), diagnosis of delirium (15.6 vs. 20.9%, P=0.048), constipation (80.3 vs. 74.7%, p < 0.001), monitoring of anemia (83.3 vs. 97.1%, P>0.01) and renal failure at discharge (44.5 vs. 97.3%, P<0.01) and hospital mortality (4.6 vs. 1.3%, P=0.02). CONCLUSIONS: Co-management for elderly patients admitted with hip fracture provides a better information about previously chronic conditions, a higher control of hospital complications and decreases hospital mortality

Hip fracture co-management in the elderly in a tertiary referral hospital: A cohorts study. / Comanejo de la fractura de cadera del anciano en un hospital de tercer nivel: un estudio de cohortes.

INTRODUCTION: Hip fracture in the elderly is one of the most prevalent diagnoses in Orthopedic Surgery Departments. It has a great impact in medical, economic and social terms. Our objective is to analyze clinical impact of a co-management care model between orthopedic surgery and internal medicine departments for elderly patients admitted with hip fracture in a tertiary referral hospital. MATERIAL AND METHODS: Retrospective cohort study of patients older than 65 years old admitted with hip fracture between January 2005-August 2006 (HIST cohort) without a co-management care model, and between January 2008-August 2010 (COFRAC cohort) with a co-manEdadment care model. Analysis of demographic, clinical and surgery characteristics, complications incidence and mortality and re-admissions at 30 days was made. RESULTS: A total of 701 patients were included (471 HIST, 230 COFRAC). There were no differences in sex, gender, time to surgery, type of anesthesia and surgery, length of stay, ambulation at discharge and 30-days emergency room consultation, readmissions or mortality at 30 days. There were differences in identification of polypatological patients (16.8 vs. 24.4%, P=0.02), presence of osteoporosis (3.9 vs. 7.6%, P=0.03), motor deficit (3.5 vs. 8.8%, P=0.03), number of chronic drugs (3.7±2.5 vs. 4.3±3.2, P<0.01), diagnosis of delirium (15.6 vs. 20.9%, P=0.048), constipation (80.3 vs. 74.7%, p<0.001), monitoring of anemia (83.3 vs. 97.1%, P>0.01) and renal failure at discharge (44.5 vs. 97.3%, P<0.01) and hospital mortality (4.6 vs. 1.3%, P=0.02). CONCLUSIONS: Co-management for elderly patients admitted with hip fracture provides a better information about previously chronic conditions, a higher control of hospital complications and decreases hospital mortality.

Cannabinoid CB1 and CB2 Receptors, and Monoacylglycerol Lipase Gene Expression Alterations in the Basal Ganglia of Patients with Parkinson's Disease.

Previous studies suggest that the endocannabinoid system plays an important role in the neuropathological basis of Parkinson's disease (PD). This study was designed to detect potential alterations in the cannabinoid receptors CB1 (CB1r) and CB2 (A isoform, CB2Ar), and in monoacylglycerol lipase (MAGL) gene expression in the substantia nigra (SN) and putamen (PUT) of patients with PD. Immunohistochemical studies were performed to identify precise CB2r cellular localization in the SN of control and PD patients. To ensure the validity and reliability of gene expression data, the RNA integrity number (RIN) was calculated. CB1r, CB2Ar, and MAGL gene expressions were evaluated by real-time polymerase chain reaction (real-time PCR) using Taqman assays. Immunohistochemical experiments with in situ proximity ligation assay (PLA) were used to detect the precise cellular localization of CB2r in neurons, astrocytes, and/or microglia. All RIN values from control and PD postmortem brain samples were > 6. CB1r gene expression was unchanged in the SN but significantly higher in the PUT of patients with PD. CB2Ar gene expression was significantly increased (4-fold) in the SN but decreased in the PUT, whereas MAGL gene expression was decreased in the SN and increased in the PUT. Immunohistochemical analyses revealed that CB2r co-localize with astrocytes but not with neurons or microglial cells in the SN. The results of the present study suggest that CB1r, CB2r, and MAGL are closely related to the neuropathological processes of PD. Therefore, the pharmacological modulation of these targets could represent a new potential therapeutic tool for the management of PD.

Effects of whole-body vibration applied to lower extremity muscles during decline bench press exercise.

OBJECTIVES: To evaluate the effects of whole-body vibration (WBV) on skeletal muscle activity and power performance of the upper body during decline bench press exercise at different loads. METHODS: Forty-seven healthy young and active male students volunteered. Each performed dynamic decline bench press repetitions with and without WBV (50 Hz, 2.2 mm) applied through a hamstring bridge exercise at three different loads of their 1-repetition maximum (1RM): 30%, 50%, and 70% 1RM. Muscle activity of the triceps brachii (TB), biceps brachii (BB), pectoralis major (PM), and biceps femoris (BF) was measured with surface electromyography electrodes and kinetic parameters of the repetitions were measured with a rotary encoder. RESULTS: WBV increased peak power (PP) output during the 70% 1RM condition (p<0.01). Muscle activity was increased with WBV in the TB and BF muscles at all loads (p<0.05). There were no effects of WBV on BB or PM muscles. CONCLUSION: WBV applied through a hamstring bridge exercise increases TB muscle activity during a decline bench press and this augmentation contributes to an increased peak power at higher loads and increased peak acceleration at lower loads.

The addition of synchronous whole-body vibration to battling rope exercise increases skeletal muscle activity.

OBJECTIVES: To evaluate the effects of performing battling rope exercise with and without the addition of whole-body vibration (WBV) on muscle activity of the leg, trunk, and upper body. METHODS: Twenty-eight recreationally active university students completed 20-s of battling rope undulation for 6 separate conditions: 1) alternating arm motion no WBV -Alt_NoWBV; 2) alternating arm motion 30 Hz low amplitude WBV -Alt_30 Hz-L; 3) alternating arm motion 50 Hz high amplitude -Alt_50 Hz-H; 4) double arm motion no WBV -Double_NoWBV; 5) double arm motion 30Hz low amplitude WBV -Double_30Hz-L; 6) double arm motion 50 'Hz high amplitude -Double_50 Hz-H. Electromyography (EMG) was measured for the gastrocnemius medialis (GM), vastus medialis oblique (VMO), vastus lateralis (VL), rectus abdominis (RA), multifidus (MF), biceps brachii (BB), and triceps brachii (TB) muscles. RESULTS: The double arm motion during undulation resulted in greater (p<0.05) muscle activity in the VMO, VL, RA, and MF muscles while the GM was more active during the alternating arm motion. WBV at 50Hz increased EMG in all muscles measured vs NoWBV and the 30 Hz condition. CONCLUSION: These results are the first to demonstrate that the exercise stimulus of performing battling rope exercise can be augmented by completing the exercise while being exposed to WBV from a ground-based platform.

A clay permeable reactive barrier to remove Cs-137 from groundwater: Column experiments.

Clay minerals are reputed sorbents for Cs-137 and can be used as a low-permeability material to prevent groundwater flow. Therefore, clay barriers are employed to seal Cs-137 polluted areas and nuclear waste repositories. This work is motivated by cases where groundwater flow cannot be impeded. A permeable and reactive barrier to retain Cs-137 was tested. The trapping mechanism is based on the sorption of cesium on illite-containing clay. The permeability of the reactive material is provided by mixing clay on a matrix of wood shavings. Column tests combined with reactive transport modeling were performed to check both reactivity and permeability. Hydraulic conductivity of the mixture (10(-4) m/s) was sufficient to ensure an adequate hydraulic performance of an eventual barrier excavated in most aquifers. A number of column experiments confirmed Cs retention under different flow rates and inflow solutions. A 1D reactive transport model based on a cation-exchange mechanism was built. It was calibrated with batch experiments for high concentrations of NH4+ and K+ (the main competitors of Cs in the exchange positions). The model predicted satisfactorily the results of the column experiments. Once validated, it was used to investigate the performance and duration of a 2 m thick barrier under different scenarios (flow, clay content, Cs-137 and K concentration).

A comparison of different vibration exercise techniques on neuromuscular performance.

The first purpose of this study was to determine the effects of whole-body vibration (WBV) exercise during an isometric hand-grip exercise. The second purpose was to evaluate whether more than one vibratory focus would evoke an increase in the effects evoked by only one vibratory focus. The present study investigated whether WBV exposure during 10 repetitions of a handgrip dynamometer while standing on a WBV platform. Twenty-eight recreationally active university students completed 3 different test conditions, in random order: 1) grip dynamometer exercise with superimposed WBV and contralateral arm vibration (WBV+AV); 2) superimposed arm vibration only (AV); 3) grip dynamometer exercise without vibration (Control). The hand grip strength was slightly higher in the WBV condition as compared to the Control and AV conditions (1.1% and 3.6%, p>0.05, respectively). A main effect of the EMGrms of extensor digitorum muscle (ED) was observed indicating that the WBV+AV condition produced a lower co-activation of ED during a flexor digital task than the Control and AV (p<0.05) conditions. The application of WBV+AV may acutely increase muscle coordination and decreases the coactivation of ED. Furthermore, the muscle EMGrms showed increases in activation near the vibratory focus in both upper- and lower-body.

Acute unilateral leg vibration exercise improves contralateral neuromuscular performance.

OBJECTIVES: To examine the post-exercise cross-transfer effects of acute whole body vibration (WBV). METHODS: Seventeen healthy male volunteers (20.8 ± 1.2 y) performed three unilateral vibration conditions in a randomized order: 1) WBV-50 Hz [high amplitude]; 2) WBV-30 Hz [low amplitude]; and 3) a control no WBV condition (Sham) applied to the dominant leg. Each condition involved maximal voluntary isometric contractions (MVC) followed by three leg press explosive repetitions (40% MVC) with non-dominant and dominant legs; which were conducted prior to and post vibration (immediately; 2 min and 5 min). Surface electromygraphy (sEMG) of the vastus lateralis (VL) and medial gastrocnemius (MG) were measured throughout each condition. RESULTS: A condition x leg x time interaction effect was detected (p=0.001) where 50 Hz-High in the stimulated leg enhanced mean velocity at post-2 min compared to 30 Hz-Low and Sham, remaining elevated at post-5 min. Similarly, 50 Hz-High in the non-stimulated leg increased mean velocity at post-immediately and post-2 min compared to 30 Hz-Low and Sham. There were no changes in sEMG of VL and GM in the stimulated and non-stimulated post-conditions. CONCLUSION: WBV (50 Hz) can augment cross-transfer in neuromuscular performance. WBV could provide an alternate method of unilateral training to promote cross education explosive strength.

Regulatory role of the cannabinoid CB2 receptor in stress-induced neuroinflammation in mice.

BACKGROUND AND PURPOSE: Stress exposure produces excitotoxicity and neuroinflammation, contributing to the cellular damage observed in stress-related neuropathologies. The endocannabinoids provide a homeostatic system, present in stress-responsive neural circuits. Here, we have assessed the possible regulatory role of cannabinoid CB2 receptors in stress-induced excitotoxicity and neuroinflammation. EXPERIMENTAL APPROACH: We used wild type (WT), transgenic overexpressing CB2 receptors (CB2xP) and CB2 receptor knockout (CB2-KO) mice exposed to immobilization and acoustic stress (2 h·day(-1) for 4 days). The CB2 receptor agonist JWH-133 was administered daily (2 mg·kg(-1), i.p.) to WT and CB2-KO animals. Glutamate uptake was measured in synaptosomes from frontal cortex; Western blots and RT-PCR were used to measure proinflammatory cytokines, enzymes and mediators in homogenates of frontal cortex. KEY RESULTS: Increased plasma corticosterone induced by stress was not modified by manipulating CB2 receptors. JWH-133 treatment or overexpression of CB2 receptors increased control levels of glutamate uptake, which were reduced by stress back to control levels. JWH-133 prevented the stress-induced increase in proinflammatory cytokines (TNF-α and CCL2), in NF-κB, and in NOS-2 and COX-2 and in the consequent cellular oxidative and nitrosative damage (lipid peroxidation). CB2xP mice exhibited anti-inflammatory or neuroprotective actions similar to those in JWH-133 pretreated animals. Conversely, lack of CB2 receptors (CB2-KO mice) exacerbated stress-induced neuroinflammatory responses and confirmed that effects of JWH-133 were mediated through CB2 receptors. CONCLUSIONS AND IMPLICATIONS: Pharmacological manipulation of CB2 receptors is a potential therapeutic strategy for the treatment of stress-related pathologies with a neuroinflammatory component, such as depression.

Adalimumab (tumor necrosis factor-blocker) reduces the expression of glial fibrillary acidic protein immunoreactivity increased by exogenous tumor necrosis factor alpha in an organotypic culture of porcine neuroretina.

PURPOSE: To determine if exogenous addition of tumor necrosis factor alpha (TNFα) exacerbates retinal reactive gliosis in an organotypic culture of porcine neuroretina and to evaluate if concomitant adalimumab, a TNF-blocker, diminishes it. METHODS: Porcine retinal explants from 20 eyeballs were cultured. Cultures with 100 pg/ml TNFα, 10 µg/ml adalimumab, 100 pg/ml TNFα plus 10 µg/ml adalimumab, or controls without additives were maintained for 9 days. Freshly detached retinas were processed in parallel. TNFα levels in control culture supernatants were quantified with enzyme-linked immunosorbent assay. Cryostat sections were doubly immunostained for glial fibrillary acidic protein (GFAP), a marker for reactive gliosis, and cellular retinaldehyde-binding protein (CRALBP), a marker for Müller cells. Sections were also labeled with the isolectin IB4, a label for microglia/macrophages. RESULTS: TNFα in control culture supernatants was detected only at day 1. Compared to the fresh neuroretinal samples, upregulation of GFAP and downregulation of CRALBP occurred during the 9 days of culture. Exogenous TNFα stimulated glial cells to upregulate GFAP and downregulate CRALBP immunoreactivity. TNFα-treated cultures also initiated the growth of gliotic membranes and underwent retinal disorganization. Adalimumab inhibited the spontaneous increases in GFAP and maintained CRALBP. In combination with TNFα, adalimumab reduced GFAP expression and conserved CRALBP, with only slight retinal disorganization. No appreciable changes in IB4 labeling were observed under the different culture conditions. CONCLUSIONS: In cultured porcine neuroretina, spontaneous reactive gliosis and retinal disorganization were exacerbated by exogenous TNFα. Adalimumab reduced spontaneous changes and those induced by TNFα. Therefore, inhibiting TNFα may represent a novel approach to controlling retinal fibrosis observed in some human diseases.

Accumbal dopamine, noradrenaline and serotonin activity after naloxone-conditioned place aversion in morphine-dependent mice.

Dopamine (DA) neurons not only show a pattern signaling the magnitude, delay and probability of rewards but also code negative motivation and aversive events. Beside DA, other systems such as noradrenaline (NA) and serotonin (5-HT) may also be implicated in naloxone-induced conditioned place aversion (CPA; an index of the aversive consequences of withdrawal). The purpose of the present study was to evaluate: (i) the turnover of DA, NA and 5-HT in the nucleus accumbens (NAc), one of the most important substrates for aversive states, (ii) the changes in tyrosine hydroxylase (TH) gene expression in the ventral tegmental area, and (iii) total TH protein levels and TH phosphorylation in the NAc after naloxone-induced morphine withdrawal. DA, NA and 5-HT turnover was evaluated by high-performance liquid chromatography (HPLC). TH gene expression was determined by real time quantitative PCR (RT-PCR) and total TH and TH phosphorylated at Ser31 and Ser40 were analyzed by Western blot. Present results show that the aversion for environmental cues paired with opioid withdrawal was higher than that observed in the saline group treated with naloxone, which indicates that morphine pretreatment potentiated the ability of naloxone to produce place aversion. In addition, present data show that naloxone-induced CPA positively correlated with an increase of DA and NA turnover in the NAc, which paralleled an increase in TH gene expression in the VTA and TH phosphorylation and enhanced TH protein levels in the NAc. Thus, the present study indicates that naloxone-induced aversion in morphine-dependent mice enhances DA and NA activity in the NAc and suggests that transcriptional and post-transcriptional regulation of TH could be involved in the hyperactivity of mesolimbic dopaminergic system observed in morphine-withdrawn mice.

Overexpression of cannabinoid CB2 receptor in the brain induces hyperglycaemia and a lean phenotype in adult mice.

It is well known that the endocannabinoid system, through cannabinoid CB1 receptor activation, has an important role in the main aspects of energy balance (i.e. food intake, energy expenditure and glucose and fat metabolism), orchestrating all the machinery involved in body weight control and energy homeostasis. A number of studies have revealed a crucial role of brain CB1 receptors in these processes. However, functional cannabinoid CB2 receptors have also been described in the brain, with no studies addressing their putative role in body weight control and glucose homeostasis. We have tested this hypothesis by analysing fasting-induced feeding, body weight, some hypothalamic neuropeptides, glucose tolerance and plasma hormones in an animal model specifically overexpressing CB2 receptors in the central nervous system. We found that specific overexpression of CB2 receptors in the brain promoted higher basal glucose levels, decreased fasting-induced feeding and, eventually, led to a lean phenotype and glucose intolerance. These findings could not be attributed to decreased locomotor activity, increased anxiety or depressive-like behaviours. The expression of relevant neuropeptides such as pro-opiomelanocortin and galanin in the arcuate nucleus of the hypothalamus was altered but not those of the CB1 receptor. Indeed, no changes in CB1 expression were found in the liver, skeletal muscle and adipose tissue. However, cannabinoid CB1 and CB2 receptor expression in the endocrine pancreas and glucagon plasma levels were decreased. No changes in plasma adiponectin, leptin, insulin and somatostatin were found. Taken together, these results suggest a role for central cannabinoid CB2 receptors in body weight control and glucose homeostasis.

Laser-induced periodic surface structures nanofabricated on poly(trimethylene terephthalate) spin-coated films.

Here we present a precise morphological description of laser-induced periodic surface structures (LIPSS) nanofabricated on spin-coated poly(trimethylene terephthalate) (PTT) films by irradiation with 266 nm, 6 ns laser pulses and by using a broad range of fluences and number of pulses. By accomplishing real and reciprocal space measurements by means of atomic force microscopy and grazing incidence wide- and small-angle X-ray scattering respectively on LIPSS samples, the range of optimum structural order has been established. For a given fluence, an increase in the number of pulses tends to improve LIPSS in PTT. However, as the pulse doses increase above a certain limit, a distortion of the structures is observed and a droplet-like morphology appears. It is proposed that this effect could be related to a plausible decrease of the molecular weight of PTT due to laser-induced chain photo-oxidation by irradiation with a high number of pulses. A concurrent decrease in viscosity enables destabilization of LIPSS by the formation of droplets in a process similar to surface-limited dewetting.

Flat-on lamellae in spin-coated, stable films of poly(propylene azelate).

Thin films (5-500 nm thick) of the linear aliphatic polyester (3,7) poly(propylene azelate) (PPAz) were prepared by spin-coating of CHCl(3) polymer solutions with different polymer concentrations. The morphology and structure of the spin-coated thin films were investigated by atomic force microscopy (AFM) and by grazing incidence wide-angle X-ray scattering (GIWAXS) techniques. AFM revealed the continuous nature of the flat, spherulitic films which are stable against dewetting even for polymer coatings as thin as 15 nm. GIWAXS patterns revealed a high crystal orientation of the films. A sharp reflection on the meridian whose spacing is related to the polymer chain unit length (c-axis) supports the presence of flat-on lamellae morphology in the whole range of film thicknesses investigated. The flat-on lamellae morphology is also supported by AFM images. A triclinic unit cell with the c*-axis perpendicular to the substrate is proposed for PPAz. The repulsion of the long aliphatic spacer by the Si-substrate is invoked as the main reason for the flat-on morphology observed.

Comparison of laboratory methodologies for evaluating radiostrontium diffusion in soils: planar-source versus half-cell methods.

A planar-source method, initially designed to obtain diffusion coefficients in compacted clay, is adapted here to determine the apparent diffusion coefficient (D(a)) of radiostrontium in soils representative of the Spanish territory. Experiments were carried out by varying the moisture content (F(moist)), and bulk dry density (ρ(bulk)) of the soil samples, in order to study the influence of these soil packing parameters on D(a) values. The moisture in the soil samples was established as the percentage of occupancy of each soil's field capacity (OFC). For a similar OFC, D(a) values in the examined soils ranged by approximately one order of magnitude (e.g. from 6.2 × 10(-)(11) to 6.5 × 10(-)(12)m(2)s(-)(1), at 100% of OFC; from 3.0 × 10(-)(11) to 3.8 × 10(-)(12)m(2)s(-)(1), at 60% of OFC). For a given soil, D(a) values increased when water content was increased. F(moist), and tortuosity (τ) explained D(a) variability, with R(2) values usually over 0.9. However, no good simple or multiple regressions between the soil packing parameters and D(a) were obtained with the whole dataset of all soils, which indicated that soil sorption capacity affects the diffusion of reactive radionuclides in soils. The inclusion of calculated K(d) values in the multiple regressions improved the correlations in all cases. Finally, D(a) values were compared with those obtained by the application of a half-cell method. The values of D(a) obtained by the planar-source methods were systematically lower than the half-cell ones, with a good correlation between the D(a) derived from both methods (R(2)=0.98).

Regulation of Fas receptor/Fas-associated protein with death domain apoptotic complex and associated signalling systems by cannabinoid receptors in the mouse brain.

BACKGROUND AND PURPOSE: Natural and synthetic cannabinoids (CBs) induce deleterious or beneficial actions on neuronal survival. The Fas-associated protein with death domain (FADD) promotes apoptosis, and its phosphorylated form (p-FADD) mediates non-apoptotic actions. The regulation of Fas/FADD, mitochondrial apoptotic proteins and other pathways by CB receptors was investigated in the mouse brain. EXPERIMENTAL APPROACH: Wild-type, CB(1) and CB(2) receptor knock-out (KO) mice were used to assess differences in receptor genotypes. CD1 mice were used to evaluate the effects of CB drugs on canonical apoptotic pathways and associated signalling systems. Target proteins were quantified by Western blot analysis. KEY RESULTS: In brain regions of CB(1) receptor KO mice, Fas/FADD was reduced, but p-Ser191 FADD and the p-FADD/FADD ratio were increased. In CB(2) receptor KO mice, Fas/FADD was increased, but the p-FADD/FADD ratio was not modified. In mutant mice, cleavage of poly(ADP-ribose)-polymerase (PARP) did not indicate alterations in brain cell death. In CD1 mice, acute WIN55212-2 (CB(1) receptor agonist), but not JWH133 (CB(2) receptor agonist), inversely modulated brain FADD and p-FADD. Chronic WIN55212-2 induced FADD down-regulation and p-FADD up-regulation. Acute and chronic WIN55212-2 did not alter mitochondrial proteins or PARP cleavage. Acute, but not chronic, WIN55212-2 stimulated activation of anti-apoptotic (ERK, Akt) and pro-apoptotic (JNK, p38 kinase) pathways. CONCLUSIONS AND IMPLICATIONS: CB(1) receptors appear to exert a modest tonic activation of Fas/FADD complexes in brain. However, chronic CB(1) receptor stimulation decreased pro-apoptotic FADD and increased non-apoptotic p-FADD. The multifunctional protein FADD could participate in the mechanisms of neuroprotection induced by CBs.