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This article belongs to the Special Issue Coffee and Caffeine Consumption for Human Health., Coffee is one of the most popular beverages consumed worldwide. Roasted coffee is a complex mixture of thousands of bioactive compounds, and some of them have numerous potential health-promoting properties that have been extensively studied in the cardiovascular and central nervous systems, with relatively much less attention given to other body systems, such as the gastrointestinal tract and its particular connection with the brain, known as the brain–gut axis. This narrative review provides an overview of the effect of coffee brew; its by-products; and its components on the gastrointestinal mucosa (mainly involved in permeability, secretion, and proliferation), the neural and non-neural components of the gut wall responsible for its motor function, and the brain–gut axis. Despite in vitro, in vivo, and epidemiological studies having shown that coffee may exert multiple effects on the digestive tract, including antioxidant, anti-inflammatory, and antiproliferative effects on the mucosa, and pro-motility effects on the external muscle layers, much is still surprisingly unknown. Further studies are needed to understand the mechanisms of action of certain health-promoting properties of coffee on the gastrointestinal tract and to transfer this knowledge to the industry to develop functional foods to improve the gastrointestinal and brain–gut axis health., The project “Nuevos conocimientos para la sostenibilidad del sector cafetero” was funded by Consejo Superior de Investigaciones Científicas (CSIC) (201970E117); “Generación de nuevos ingredientes y alimentos beneficiosos dirigidos a condiciones de riesgo y al bienestar global de personas con cáncer colorrectal (TERÁTROFO, IDI-20190960)” and “Novel coffee by-product beverages for an optimal health of the brain-gut axis (COFFEE4BGA)” were funded by the Ministerio de Ciencia e Innovación (PID2019-111510RB-I00).

Introduction Aggressive behavior is commonly associated with epilepsy and can be influenced by the antiepileptic drugs (AEDs) taken. Sodium channel blockers, specifically the carboxamides derivatives such as carbamazepine and oxcarbazepine, are some of the AEDs considered to have a favorable psychiatric effect profile. Objectives We aimed to assess whether the carboxamide analogue eslicarbazepine acetate (ESL) has any effect on the levels of anger in patients with epilepsy. Material and methods We prospectively recruited adult patients with epilepsy on treatment with ≦2 active AEDs, who required AED addition or substitution, excluding patients with active psychiatric disorders. All patients completed anger level (STAXI-2), depression-anxiety (HADS), and quality of life (QOLIE-10) assessments, and were evaluated at baseline and within 3-6 months after treatment initiation. Results Of 78 patients receiving ESL, as add-on therapy or in substitution of a previous AED, were recruited into the ESL group, with an average age of 48 years and 54% men. We used a control group of 58 patients receiving AEDs other than carboxamides. Conclusions Patients overall showed improvements in anger levels, mood, and quality of life during the follow-up. A history of psychiatric disorders was a limiting factor to improve anger levels. As compared to controls, anger levels improved in ESL patients independently from seizure control. Therefore, ESL seems to exert a favorable influence on the anger levels of otherwise healthy patients with epilepsy, including those unresponsive to seizure control. The potential ESL anti-aggressive effect should be studied in patients with epilepsy and active psychiatric disorders.

This article belongs to the Special Issue Dietary Management of Gastrointestinal Diseases and Disorders., Dietary modifications, including those affecting dietary fat and its fatty acid (FA) composition, may be involved in the development of brain–gut axis disorders, with different manifestations in males and females. Our aim was to evaluate the impact of three purified diets with different FA composition on the brain–gut axis in rats of both sexes. Male and female Wistar rats fed a cereal-based standard diet from weaning were used. At young adult age (2–3 months old), animals were divided into three groups and treated each with a different refined diet for 6 weeks: a control group fed on AIN-93G diet containing 7% soy oil (SOY), and two groups fed on AIN-93G modified diets with 3.5% soy oil replaced by 3.5% coconut oil (COCO) or 3.5% evening primrose oil (EP). Different brain–gut axis parameters were evaluated during 4–6 weeks of dietary intervention. Compared with SOY diet (14% saturated FAs, and 58% polyunsaturated FAs), COCO diet (52.2% saturated FAs and 30% polyunsaturated FAs) produced no changes in brain functions and minor gastrointestinal modifications, whereas EP diet (11.1% saturated FAs and 70.56% polyunsaturated FAs) tended to decrease self-care behavior and colonic propulsion in males, and significantly increased exploratory behavior, accelerated gastrointestinal transit, and decreased cecum and fecal pellet density in females. Changes in FA composition, particularly an increase in ω-6 polyunsaturated FAs, seem to facilitate the development of brain–gut axis alterations in a sex-dependent manner, with a relatively higher risk in females., We thank Comunidad Autónoma de Madrid for the technician contract of Lorena Blanco (PEJ15/BIO/TL-0580) and the predoctoral contract of Yolanda López-Tofiño (PEJD-2017-PRE/BMD-3924), and URJC for the predoctoral contracts of Yolanda López-Tofiño and Carlos Gálvez-Robleño (both under PREDOC20-054 call). Damian Jacenik was a recipient of fellowship funded by Faculty of Biology and Environmental Protection, University of Lodz, Poland.

The transforming growth factor β (TGFβ) family plays a role in fibrosis and has been involved in inflammatory bowel disease (IBD), a chronic gastrointestinal (GI) tract disease that can affect both sexes. Importantly, this is increasingly prevalent in industrialized countries due to changes in lifestyle and diets. The family comprises three isoforms: TGFβ1, TGFβ2 and TGFβ3. While TGFβ1 has an established role in fibrosis, the pathophysiological relevance of the two other isoforms is unclear. Here we evaluated the possible functional and structural alterations of the GI tract and sex influence in an experimental model with partial deficiency of TGF-β3, due to lethality of the homozygous null mouse. Wild-type (WT) and heterozygous for TGF-β3 (HZ) mice of both sexes were exposed to control or high fat diet (HFD), as a possible model of IBD. After oral administration of a radiopaque marker, faeces were collected for 4 h, weighed and exposed to X-rays for GI transit evaluation. Body weight, size/length and histology of the GI organs were also evaluated. No typical signs of IBD were detected. WT females presented lower body weight, delayed GI transit and an increased relative size of the GI organs when compared to males. The HZ genotype modified the latency of expulsion of marked faeces, in a sex and diet dependent manner, without producing macroscopic structural alterations in the GI tract. Moreover, submucosa thickness was decreased in HZ male mice under control diet. HFD increased body weight, accelerated GI transit and decreased GI organs size, especially in females. Importantly, HFD partly counteracted the effects of TGF-β3 heterozygosity on the latency of marked faeces expulsion. To conclude, sex, diet and TGF-β3 genotype alter the GI tract motility and structure, with a possible impact on the IBD development associated with obesity, yet to be determined.

Background Cisplatin is an antineoplastic drug known to produce intense vomiting, gastric dysmotility, and peripheral neuropathy. Monosodium glutamate (MSG) is a flavor enhancer with prokinetic properties potentially useful for cancer patients under chemotherapy. Our aim was to test whether MSG may improve gastrointestinal motor dysfunction and other adverse effects induced by repeated cisplatin in rats. Methods Male Wistar rats were exposed or not to MSG (4 g L-1 ) in drinking water from week 0 to 1 week after treatment. On the first day of weeks 1-5, rats were treated with saline or cisplatin (2 mg kg-1 week-1 , ip). Gastrointestinal motility was measured by radiological methods after first and fifth administrations, as well as 1 week after treatment finalization. One week after treatment, the threshold for mechanical somatic sensitivity was recorded. Finally, samples of stomach, terminal ileum and kidneys were evaluated in sections using conventional histology. The myenteric plexus was immunohistochemically evaluated on distal colon whole-mount preparations. Key results Monosodium glutamate prevented the development of cisplatin-induced neuropathy and partially improved intestinal transit after the fifth cisplatin administration with little impact on gastric dysmotility. MSG did not improve the histological damage of gut wall, but prevented the changes induced by cisplatin in the colonic myenteric plexus. Conclusion and inferences Our results suggest that MSG can improve some dysfunctions caused by anticancer chemotherapy in the gut and other systems, associated, at least partially, with neuroprotectant effects. The potentially useful adjuvant role of this food additive to reduce chemotherapy-induced sequelae warrants further evaluation.

Mast cells are key actors in inflammatory reactions. Upon activation, they release histamine, heparin and nerve growth factor, among many other mediators that modulate immune response and neuron sensitization. One important feature of mast cells is that their population is usually increased in animal models and biopsies from patients with irritable bowel syndrome (IBS). Therefore, mast cells and mast cell mediators are regarded as key components in IBS pathophysiology. IBS is a common functional gastrointestinal disorder affecting the quality of life of up to 20% of the population worldwide. It is characterized by abdominal pain and altered bowel habits, with heterogeneous phenotypes ranging from constipation to diarrhea, with a mixed subtype and even an unclassified form. Nutrient intake is one of the triggering factors of IBS. In this respect, certain components of the daily food, such as fatty acids, amino acids or plant-derived substances like flavonoids, have been described to modulate mast cells’ activity. In this review, we will focus on the effect of these molecules, either stimulatory or inhibitory, on mast cell degranulation, looking for a nutraceutical capable of decreasing IBS symptoms., This research was funded by Ministerio de Ciencia, Innovación y Universidades, grant number PID2019-111510RB-I00.

Objective To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic-clonic seizures (GTCS). Methods This multicenter, retrospective, observational study was conducted in patients aged >= 12 years treated with PER as primary monotherapy or converted to PER monotherapy by progressive reduction of background antiepileptic drugs. Outcomes included retention, responder, and seizure-free rate after 3, 6, and 12 months and tolerability throughout the follow-up. Results A total of 98 patients (mean age = 49.6 +/- 21.7 years, 51% female) with focal seizures and/or GTCS were treated with PER monotherapy for a median exposure of 14 months (range = 1-57) with a median dose of 4 mg (range = 2-10). The retention rates at 3, 6, and 12 months and last follow-up were 93.8%, 89.3%, 80.9%, and 71.4%, respectively. The retention rates according to the type of monotherapy (primary vs conversion) did not differ (log-rank P value = .57). Among the 98 patients, 61.2% patients had seizures throughout the baseline period, with a median seizure frequency of 0.6 seizures per month (range = 0.3-26). Responder rates at 3, 6, and 12 months were 79.6%, 70.1%, and 52.8%, respectively, and seizure freedom rates at the same points were 62.7%, 56.1%, and 41.5%. Regarding the 33 patients who had GTCS in the baseline period, 87.8% were seizure-free at 3 months, 78.1% at 6 months, and 55.1% at 12 months. Over the entire follow-up, PER monotherapy was generally well tolerated, and only 16% of patients discontinued PER due to adverse events (AEs). Female patients were found to be at a higher risk of psychiatric AEs (female vs male odds ratio = 2.85, 95% confidence interval = 1-8.33, P = .046). Significance PER demonstrated good effectiveness and a good safety profile when used as primary therapy or conversion to monotherapy at relatively low doses, in a clinical setting with patients with focal seizures and GTCS.

Irritable bowel syndrome (IBS) is a disorder of the gut-brain interaction, highly prevalent and impactful. Visceral hypersensitivity and alterations of colonic motility and defecation are definitory, but other features (increased intestinal permeability, anxiety, depression) also occur throughout the life of IBS patients. In this chapter, we will first review the different animal models that have been developed in an attempt to mimic IBS and its symptoms, which may vary according to the different underlying etiology. Thereafter, we will review the techniques and models that are used in vitro. Whereas in vivo models constitute the final preclinical step in the search of new effective and safe treatments, in vitro studies offer essential information on molecular mechanisms underlying the disease, which may open the gate to finding new treatment targets. Both approaches are therefore complementary and need to be considered for successful preclinical research on IBS.

Cannabis sp. and their products (marijuana, hashish…), in addition to their recreational, industrial and other uses, have a long history for their use as a remedy for symptoms related with gastrointestinal diseases. After many reports suggesting these beneficial effects, it was not surprising to discover that the gastrointestinal tract expresses endogenous cannabinoids, their receptors, and enzymes for their synthesis and degradation, comprising the so-called endocannabinoid system. This system participates in the control of tissue homeostasis and important intestinal functions like motor and sensory activity, nausea, emesis, the maintenance of the epithelial barrier integrity, and the correct cellular microenvironment. Thus, different cannabinoid-related pharmacological agents may be useful to treat the main digestive pathologies. To name a few examples, in irritable bowel syndrome they may normalize dysmotility and reduce pain, in inflammatory bowel disease they may decrease inflammation, and in colorectal cancer, apart from alleviating some symptoms, they may play a role in the regulation of the cell niche. This review summarizes the main recent findings on the role of cannabinoid receptors, their synthetic or natural ligands and their metabolizing enzymes in normal gastrointestinal function and in disorders including irritable bowel syndrome, inflammatory bowel disease, colon cancer and gastrointestinal chemotherapy-induced adverse effects (nausea/vomiting, constipation, diarrhea).

[Background]: Guanylate cyclase C (GC-C) receptor is a transmembrane receptor, predominantly expressed in intestinal epithelial cells, which is considered to play a main role in homeostasis and function of the digestive tract. The endogenous ligands for this receptor are the paracrine hormones uroguanylin and guanylin. Upon ligand binding, GC-C receptors increase cyclic guanosine monophosphate (cGMP) levels, regulating a variety of key cell-type specific processes such as chloride and bicarbonate secretion, epithelial cell growth, regulation of intestinal barrier integrity and visceral sensitivity. It has been suggested that GC-C acts as an intestinal tumor suppressor with the potential to prevent the initiation and progression of colorectal cancer. In fact, loss of ligand expression is a universal step in sporadic colorectal carcinogenesis. Interestingly, the role of GC-C is not limited to the digestive tract but it has been extended to several other systems such as the cardiovascular system, kidney, and the central nervous system, where it has been involved in a gut-hypothalamus endocrine axis regulating appetite., [Objetive]: In this review we summarize the physiology of the GC-C receptor and its ligands, focusing on newly developed drugs like linaclotide, and their suggested role to reverse/prevent the diseases in which the receptor is involved., [Conclusion]: Available data points toward a relationship between uroguanylin and guanylin and their receptor and pathological processes like gastrointestinal and renal disorders, colorectal cancer, obesity, metabolic syndrome and mental disorders among others. Recent pharmacological developments in the regulation of GC-receptor may involve further improvements in the treatment of relevant diseases.

8 figures, 1 table.-- Electronic supplementary information available, If not properly regulated, the inflammatory immune response can promote carcinogenesis, as evident in colorectal cancer (CRC). Aiming to gain mechanistic insight into the link between inflammation and CRC, we perform transcriptomics analysis of human CRC, identifying a strong correlation between expression of the serine protease granzyme A (GzmA) and inflammation. In a dextran sodium sulfate and azoxymethane (DSS/AOM) mouse model, deficiency and pharmacological inhibition of extracellular GzmA both attenuate gut inflammation and prevent CRC development, including the initial steps of cell transformation and epithelial-to-mesenchymal transition. Mechanistically, extracellular GzmA induces NF-κB-dependent IL-6 production in macrophages, which in turn promotes STAT3 activation in cultured CRC cells. Accordingly, colon tissues from DSS/AOM-treated, GzmA-deficient animals present reduced levels of pSTAT3. By identifying GzmA as a proinflammatory protease that promotes CRC development, these findings provide information on mechanisms that link immune cell infiltration to cancer progression and present GzmA as a therapeutic target for CRC., This work was supported in part by FEDER/Gobierno de Aragón (group B29), Ministerio de Economia y Competitividad (SAF2014-54763-C2-1 and SAF2017-83120-C2-1-R to J.P. and SAF2014-54763-C2-2-R to E.M.G.), and Instituto de Salud Carlos III (PI13/00864 to L.M.-L.). Predoctoral grants/contracts from Fundacion Santander/Universidad de Zaragoza (to L.S. and M.A.A.), Gobierno de Aragon (to I.U.-M., L.C., L.S., and P.J.-S.), and FPU/Ministerio de Educación, Cultura y Deportes (to P.M.L.). I.U.-M. was supported by Fondo Garantía Empleo Juvenil/INAEM. M.A.A. has a Juan de la Cierva contract (Ministerio de Ciencia, Innovación y Universidades). J.P. was supported by Fundación Aragon I+D (ARAID).

This article belongs to the Special Issue Dietary Lipids and Human Health., The bioaccessibility, metabolism, and excretion of lipids composing spent coffee grounds (SCGs) were investigated. An analysis of mycotoxins and an acute toxicity study in rats were performed for safety evaluation. Total fat, fatty acids, and diterpenes (cafestol and kahweol) were determined in SCGs and their digests obtained in vitro. A pilot repeated intake study was carried out in Wistar rats using a dose of 1 g SCGs/kg b.w. for 28 days. Fat metabolism was evaluated by analysis of total fat, cholesterol, and histology in liver. The dietary fiber effect of SCGs was measured radiographically. The absence of mycotoxins and toxicity was reported in SCGs. A total of 77% of unsaturated fatty acids and low amounts of kahweol (7.09 µg/g) and cafestol (414.39 µg/g) were bioaccessible after in vitro digestion. A significantly lower (p < 0.1) accumulation of lipids in the liver and a higher excretion of these in feces was found in rats treated with SCGs for 28 days. No lipid droplets or liver damage were observed by histology. SCGs acutely accelerated intestinal motility in rats. SCGs might be considered a sustainable, safe, and healthy food ingredient with potential for preventing hepatic steatosis due to their effect as dietary fiber with a high fat-holding capacity., This research was funded by the SUSCOFFEE (AGL2014-57239-R) Project.

[Background] Cisplatin is a highly emetogenic antineoplastic drug and induces peripheral neuropathy when given in cycles. Granisetron, a 5-HT3 antagonist, is clinically used to prevent chemotherapy-induced nausea/emesis and abdominal pain in irritable bowel syndrome. The effects of cisplatin on visceral sensitivity and those of granisetron in the context of cancer chemotherapy are not well known. [Methods] Adult male Wistar rats received two intraperitoneal injections 30 minutes apart: granisetron (1 mg kg)/vehicle and cisplatin (6 mg kg)/vehicle. Thereafter, nausea-like behavior was measured as bedding intake for 4 hours, and gastric dysmotility was measured radiographically for 8 hours. Gastric weight and size were determined ex vivo and samples of the forestomach, corpus, ileum, and colon were obtained for histological analysis at 4 and 30 hours after cisplatin/vehicle. Visceral sensitivity was measured as abdominal contractions in response to mechanical intracolonic stimulation 2 hours after cisplatin/vehicle. [Key Results] Cisplatin-induced bedding intake and gastric dysmotility, and granisetron blocked these effects, which occurred in the absence of frank mucositis. Visceral sensitivity was reduced to a similar extent by both drugs alone or in combination. [Conclusions and Inferences] Cisplatin-induced bedding intake and gastric dysmotility were blocked by granisetron, confirming the involvement of serotonin acting on 5-HT3 receptors. Unexpectedly, visceral sensitivity to colonic distension was reduced, to the same extent, by cisplatin, granisetron, and their combination, suggesting important mechanistic differences with nausea and gastric dysmotility that warrant further investigation., Ministerio de Ciencia e Innovación (SAF2012‐40075‐C02‐01). L. Blanco had a contract by Consejería de Educación, Juventud y Deporte from Comunidad de Madrid and Fondo Social Europeo (PEJ15/BIO/TL‐0580).

Background: Food and diet are central issues for proper functioning of the cardiovascular (CV) system and gastrointestinal (GI) tract. We hypothesize that different types of dietary FAs affect CV parameters as well as GI motor function and visceral sensitivity. Methods: Male Wistar rats were fed with control diet (CTRL), diet supplemented with 7% soybean oil (SOY), SOY + 3.5% virgin coconut oil (COCO), and SOY + 3.5% evening primrose oil (EP) for 4 weeks. The content of insoluble fiber in CTRL was higher than in SOY, COCO, or EP. Body weight gain and food/water intake were measured. At day 28, biometric, biochemical, CV parameters, GI motor function (X-ray and colon bead expulsion test), and visceral sensitivity were evaluated. Changes in propulsive colonic activity were determined in vitro. The colon and adipose tissue were histologically studied; the number of mast cells (MCs) in the colon was calculated. Results: SOY, COCO, and EP had increased body weight gain but decreased food intake vs CTRL. Water consumption, biometric, biochemical, and CV parameters were comparable between groups. SOY increased the sensitivity to colonic distention. All groups maintained regular propulsive neurogenic contractions; EP delayed colonic motility (P, The funding was supported by the Medical University of Lodz (#50 2‐03/1‐156‐04/502‐14‐343‐17, #502‐03/1‐156‐04/502‐14‐343‐18 to PM and #503/1‐156‐04/503‐11‐001 to JF), Ministerio de Ciencia e Innovación (SAF2012‐40075‐C02‐01 to MIMF), and Ministerio de Ciencia, Innovación y Universidades (RTI2018‐101511‐B‐I00) and GEMD‐Allergan to RA . Universidad Rey Juan Carlos (Programa Propio de Fomento y Desarrollo de la Investigación, 2012) and Ministerio de Educación y Deporte (Subprograma de Movilidad, 2016: PRX17/00373) funded two research leaves to RA enjoyed at Dr Costa's laboratory (Flinders University of South Australia). L. Blanco had a contract by Consejería de Educación, Juventud y Deporte from Comunidad de Madrid and Fondo Social Europeo (PEJ15/BIO/TL‐0580).

Metabolic Syndrome (MS) is related to increased risk of early death due to cardiovascular complications, among others. Dietary intervention has been suggested as the safest and most cost‐effective alternative for treatment of those alterations in patients with MS. The aim of this study was to investigate the effects of different egg white hydrolysates (HEW1 and HEW2) in obese Zucker rats, focus on the development of cardiovascular complications. Blood pressure, heart rate, basal cardiac function and vascular reactivity in aorta and mesenteric resistance arteries were evaluated. Reactive oxygen species production by dihydroethidium‐emitted fluorescence, NOX‐1 mRNA levels by qRT‐PCR, angiotensin‐converting enzyme activity by fluorimetry and kidney histopathology were also analysed. Both hydrolysates improve the endothelial dysfunction occurring in resistance arteries. Additionally, HEW2 reduced vascular oxidative stress., Ministerio de Ciencia, Innovación y Universidades, Grant/Award Number: AGL2012‐32387 and SAF2015‐69294‐R

Nutritional compounds could be a safe and less expensive treatment for complications associated with obesity and metabolic syndrome (MetS). The aim of this study was to investigate the mechanism of action and the target tissues of a pepsin egg white hydrolysate (EWH) which had previously been demonstrated to improve some obesity-related disorders on a high-fat/high-glucose rat model. Wistar rats were used and divided into 3 groups: Control group (C), High-fat/high-glucose diet (MS) and high-fat/high-glucose diet + EWH (MSH). The rats were fed for 20 weeks and the EWH was administered from the 9th week. At the end of the study, white adipose tissue (WAT), brown adipose tissue (BAT) and muscle samples were collected for RT-qPCR analyses and immunohistochemistry. Our results showed a gene expression enhancement (2-fold basal level) in BAT of genes related to thermogenesis and mitochondrial dynamics. Mitochondrial DNA quantification and immunohistochemistry results also showed an increase of the mitochondrial content in this tissue. In conclusion, our results show the potential metabolic effect of this pepsin EWH by enhancing mitochondrial proliferation and gene expression related to thermogenesis in BAT. The EWH could be used as a functional food ingredient which is able to increase energy expenditure and counteract obesity-related MetS in a chronically obese society., The authors want to acknowledge the financial support from the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) (under the project AGL2012-32387, AGL2017-89213, CSIC – Intramural 201570I028 and under the grant numbers BES-2013-065684 and EEBB-I-16-11349).

Background: Real-world data of current antiepileptic drugs (AEDs) used to treat focal seizures is of importance to understand the efficacy and safety outside of the clinical trial setting. Here we report real-world data from a large series of patients treated with perampanel for 1 year. Methods: FYDATA was a multicentre, retrospective, 1-year observational study assessing the efficacy and safety of adjuvant perampanel in patients >= 12 years of age with focal epilepsy in a real-world setting. At 12 months, the proportion of patients who were seizure free, median percentage seizure reduction, proportion of responders, retention rate and proportion of patients with adverse events (AEs) were assessed. Analyses were also performed to identify any patient-, medication-and disease-related factors associated with a large clinical response or carry a risk for AEs. Results: A total of 464 patients were included in the study with a retention rate of 60.6% at 1 year. The mean number of prior AEDs was 7.8. The median percentage reduction in overall seizures was 33.3% (75% for secondary generalised seizures) after 1 year, with 7.2% of patients achieving seizure freedom. Furthermore, patients on non-enzyme-inducing AEDs were more likely to achieve seizure freedom, and logistic regression revealed that patients aged >= 65 years, those with epilepsy due to a vascular aetiology and those who had received fewer prior AEDs showed a better clinical response to perampanel. A total of 62.9% of the patients experienced AEs at 12 months; dizziness, somnolence and irritability were the most frequent AEs. Patients with prior psychiatric comorbidities (hyperactivity and personality disorder) were more likely to experience psychiatric AEs with perampanel, and slower titration schedules were associated with less AEs overall. Conclusion: Perampanel, for the treatment of focal epilepsy in a real-world setting in a refractory population, over 1 year, demonstrates a similar efficacy and safety profile to that observed in clinical trials. Our results have implications for the optimisation of perampanel use in a clinical setting. (C) 2016 Elsevier B.V. All rights reserved.

[Background] Vincristine is a commonly used chemotherapeutic agent. It is associated with undesirable digestive side effects. However, the impact of vincristine on gastrointestinal structure and motility or its long-term effects have not been deeply studied in animal models. This could be useful in order to develop therapeutic or preventive strategies for cancer patients. The aim of this study was to analyze such effects., [Methods] Rats received saline or vincristine (0.1 mg kg-1 , ip) daily for 10 days. Evaluations were performed during treatment and 2-6 weeks after. Somatic mechano-sensitivity was assessed using von Frey hairs. Gastrointestinal motor function was studied by means of radiographic still images and colonic propulsion of fecal pellets using fluoroscopy videos. Histological assessment of the gut morphology and immunohistochemistry for HuC/D and nNOS were performed in whole-mount myenteric plexus preparations., [Key Results] Peripheral sensitivity was increased in animals treated with vincristine and did not subside 2 weeks after treatment finalization. Vincristine treatment inhibited gastrointestinal motility although this was recovered to normal values with time. Damage in the digestive wall after vincristine treatment was greater in the ileum than in the colon. Villi shortening (in ileum) and large inflammatory nodules still remained 2 weeks after treatment finalization. Finally, the proportion of nNOS-immunoreactive neurons was increased with vincristine and continued to be increased 2 weeks after treatment finalization., [Conclusions and Inferences] Vincristine alters gastrointestinal motility, peripheral sensitivity and mucosal architecture. Vincristine-induced neuropathy (somatic and enteric), intestinal mucosa damage and inflammatory infiltrations are relatively long-lasting., L. Blanco has a contract by Consejería de Educación, Juventud y Deporte from Comunidad de Madrid and Fondo Social Europeo (PEJ15/BIO/TL-0580). This work was supported by Ministerio de Ciencia e Innovación (SAF2012-40075-C02-01), and Comunidad de Madrid (S-SAL/0261/2006; S2010/BMD-2308).

ObjectiveTo analyze the effectiveness and tolerability of perampanel across different seizure types in routine clinical care of patients with idiopathic generalized epilepsy (IGE). MethodsThis multicenter, retrospective, 1-year observational study collected data from patient records at 21 specialist epilepsy units in Spain. All patients who were aged 12 years, prescribed perampanel before December 2016, and had a confirmed diagnosis of IGE were included. ResultsThe population comprised 149 patients with IGE (60 with juvenile myoclonic epilepsy, 51 generalized tonic-clonic seizures [GTCS] only, 21 juvenile absence epilepsy, 10 childhood absence epilepsy, 6 adulthood absence epilepsy, and one Jeavons syndrome). Mean age was 36 years. The retention rate at 12 months was 83% (124/149), and 4 mg was the most common dose. At 12 months, the seizure-free rate was 59% for all seizures (88/149); 63% for GTCS (72/115), 65% for myoclonic seizures (31/48), and 51% for absence seizures (24/47). Seizure frequency was reduced significantly at 12 months relative to baseline for GTCS (78%), myoclonic (65%), and absence seizures (48%). Increase from baseline seizure frequency was seen in 5.2% of patients with GTCS seizures, 6.3% with myoclonic, and 4.3% with absence seizures. Perampanel was effective regardless of epilepsy syndrome, concomitant antiepileptic drugs (AEDs), and prior AEDs, but retention and seizure freedom were significantly higher when used as early add-on (after 2 prior AEDs) than late (3 prior AEDs). Adverse events were reported in 50% of patients over 12 months, mostly mild or moderate, and irritability (23%), somnolence (15%), and dizziness (14%) were most frequent. SignificanceIn routine clinical care of patients with IGE, perampanel improved seizure outcomes for GTCS, myoclonic seizures, and absence seizures, with few discontinuations due to adverse events. This is the first real-world evidence with perampanel across different seizure types in IGE.

Backgrond Many patients with epilepsy are treated with antiepileptic drug (AED) polytherapy. Several factors influence the choice of early add-on therapy, and deciding on the most appropriate drug can be difficult. This study aimed to assess the efficacy and tolerability of lacosamide as early add-on therapy in patients with partial-onset seizures. Methods REALLY (REtrospective study of lAcosamide as earLy add-on aLong one Year) was a multicenter, retrospective, 1-year, real-life study. Patients included were aged older than 16 years, had partial-onset seizures, and were treated with lacosamide as add-on therapy after one or two prior AEDs. Data were collected retrospectively from clinical records. The primary study objective was to assess the efficacy of lacosamide over 12 months (seizure-free and responder rates), and the secondary objective was to assess the tolerability of lacosamide at 3, 6, and 12 months [adverse events (AEs) and discontinuation]. Results One hundred and ninety-nine patients were enrolled in the study; 89 patients (44.7 %) had tried one AED and 110 patients (55.3 %) had tried two AEDs before lacosamide. At 12 months, the proportion of patients who were seizure free was 44.9 %, and 76 % of patients were responders. The seizure-free rate at 12 months for patients who had previously received one or two AEDs was 58 and 34.3 %, and the responder rate at 12 months was 83.0 and 70.4 %, respectively. The AE rate was 21.5 % at 3 months, 27.1 % at 6 months, and 31.2 % at 12 months, with 7.0 % of patients discontinuing treatment because of an AE. The most common AE reported was dizziness (11.6 %). Cryptogenic epilepsy, a higher number of prior AEDs, and the use of a sodium channel blocker at onset were associated with a worse outcome. The number of concomitant AEDs decreased over 1 year (Z = 5.89; p < 0.001). Twenty-two patients were converted to lacosamide monotherapy with at least one evaluation a parts per thousand yen6 months from the beginning of monotherapy conversion. Conclusions Lacosamide was effective and well tolerated as early add-on treatment in patients who had received one or two previous AEDs.

[Background]: In different models of paralytic ileus, cannabinoid receptors are overexpressed and endogenous cannabinoids are massively released, contributing to gastrointestinal dysmotility. The antitumoral drug vincristine depresses gastrointestinal motility and a similar mechanism could participate in this effect. Therefore, our aim was to determine, using CB and CB antagonists, whether an increased endocannabinoid tone is involved in vincristine-induced gastrointestinal ileus. [Methods]: First, we confirmed the effects of vincristine on the gut mucosa, by conventional histological techniques, and characterized its effects on motility, by radiographic means. Conscious male Wistar rats received an intraperitoneal injection of vincristine (0.1-0.5 mg/kg), and barium sulfate (2.5 ml; 2 g/ml) was intragastrically administered 0, 24, or 48 h later. Serial X-rays were obtained at different time-points (0-8 h) after contrast. X-rays were used to build motility curves for each gastrointestinal region and determine the size of stomach and caecum. Tissue samples were taken for histology 48 h after saline or vincristine (0.5 mg/kg). Second, AM251 (a CB receptor antagonist) and AM630 (a CB receptor antagonist) were used to determine if CB and/or CB receptors are involved in vincristine-induced gastrointestinal dysmotility. [Key results]: Vincristine induced damage to the mucosa of ileum and colon and reduced gastrointestinal motor function at 0.5 mg/kg. The effect on motor function was particularly evident when the study started 24 h after administration. AM251, but not AM630, significantly prevented vincristine effect, particularly in the small intestine, when administered thrice. AM251 alone did not significantly alter gastrointestinal motility. [Conclusions]: The fact that AM251, but not AM630, is capable of reducing the effect of vincristine suggests that, like in other experimental models of paralytic ileus, an increased cannabinoid tone develops and is at least partially responsible for the alterations induced by the antitumoral drug on gastrointestinal motor function. Thus, CB1 antagonists might be useful to prevent/treat ileus induced by vincristine., This work was supported by Ministerio de Ciencia e Innovación (SAF2009-12422-C02-01, SAF2012-40075-C02-01), Universidad Rey Juan Carlos—Comunidad de Madrid (URJC-CM-2006-BIO-0604) and Comunidad de Madrid (S-SAL/0261/2006; S2010/BMD-2308).

[Background] Gastrointestinal adverse effects occurring during cancer chemotherapy are well known and feared; those persisting once treatment has finished are relatively unknown. We characterized the alterations occurring in the rat small intestine, after repeated treatment with cisplatin., [Methods] Male Wistar rats received saline or cisplatin (2 mg kg−1 week−1, for 5 weeks, ip). Gastric motor function was studied non-invasively throughout treatment (W1- W5) and 1 week after treatment finalization (W6). During W6, upper gastrointestinal motility was also invasively studied and small intestinal samples were collected for histopathological and molecular studies. Structural alterations in the small intestinal wall, mucosa, submucosa, muscle layers, and lymphocytic nodules were histologically studied. Periodic acid-Schiff staining and immunohistochemistry for Ki-67, chromogranin A, and neuronal-specific enolase were used to detect secretory, proliferating, endocrine and neural cells, respectively. The expression of different markers in the tunica muscularis was analyzed by RT/qPCR., [Key Results] Repeated cisplatin induced motility alterations during and after treatment. After treatment (W6), the small intestinal wall showed histopathological alterations in most parameters measured, including a reduction in the thickness of circular and longitudinal muscle layers. Expression of c-KIT (for interstitial cells of Cajal), nNOS (for inhibitory motor neurons), pChAT, and cChAT (for excitatory motor neurons) increased significantly (although both ChATs to a lesser extent)., [Conclusions and Inferences] Repeated cisplatin induces relatively long-lasting gut dysmotility in rat associated with important histopathological and molecular alterations in the small intestinal wall. In cancer survivors, the possible chemotherapy-induced histopathological, molecular, and functional intestinal sequelae should be evaluated., This work was supported by Ministerio de Educación y Ciencia (SAF2009-12422-C02-01, SAF2012-40075-C02-01), Instituto de Salud Carlos III (PI13/01150), Comunidad de Madrid (S2010/BMD-2308), and Fundación Mapfre (convocatoria 2011).

Purpose: Evaluate real-life experience with eslicarbazepine acetate (ESL) after first monotherapy failure in a large series of patients with focal epilepsy. Method: Multicentre, retrospective, 1-year, observational study in patients older than 18 years, with focal epilepsy, who had failed first antiepileptic drug monotherapy and who received ESL. Data from clinical records were analysed at baseline, 3, 6 and 12 months to assess effectiveness and tolerability. Results: Eslicarbazepine acetate was initiated in 253 patients. The 1-year retention rate was 92.9%, and the final median dose of ESL was 800 mg. At 12 months, 62.3% of patients had been seizure free for 6 months; 37.3% had been seizure free for 1 year. During follow-up, 31.6% of the patients reported ESL-related adverse events (AEs), most commonly somnolence (8.7%) and dizziness (5.1%), and 3.6% discontinued due to AEs. Hyponatraemia was observed in seven patients (2.8%). After starting ESL, 137 patients (54.2%) withdrew the prior monotherapy and converted to ESL monotherapy; 75.9% were seizure free, 87.6% were responders, 4.4% worsened, and 23.4% reported ESL-related AEs. Conclusion: Use of ESL after first monotherapy failure was associated with an optimal seizure control and tolerability profile. Over half of patients were converted to ESL monotherapy during follow-up.

The Euro-Esli study was an exploratory pooled analysis of data from 14 European clinical practice studies, which was conducted to audit the real-world effectiveness, safety, and tolerability of eslicarbazepine acetate (ESL) as an adjunctive treatment for partial-onset seizures. Retention and effectiveness were assessed after 3, 6, and 12 months of ESL treatment, and at the final visit. Safety and tolerability were assessed throughout ESL treatment by evaluating adverse events (AEs) and ESL discontinuation due to AEs. Data from 2058 patients (52.1% male; mean age 44.0 years) were included. All 2058 patients were assessed for safety and 1975 (96.0%) patients were assessed for effectiveness. After 12 months, retention, responder (>= 50% seizure frequency reduction), and seizure freedom rates were 73.4, 75.6, and 41.3%, respectively. AEs were reported for 34.0% of patients and led to discontinuation in 13.6% of patients. The most frequently reported AEs were dizziness (6.7% of patients), fatigue (5.4%), and somnolence (5.1%). No unexpected safety signals emerged over a median duration of follow-up of > 5 years. Subgroup analyses revealed that ESL was significantly more effective in patients aged >= 65 versus < 65 years, in patients who were not receiving treatment with other sodium channel blockers versus those who were receiving treatment with other sodium channel blockers, and in patients who were receiving < 2 versus >= 2 concomitant antiepileptic drugs at baseline. Euro-Esli is the largest ESL clinical practice study conducted to date. This study provides strong and reassuring evidence of ESL's safety profile, and complements the data from clinical trials.

Purpose: Eslicarbazepine-acetate (ESL) is a third generation antiepileptic drug licensed as adjunctive therapy in adults with focal seizures. Efficacy and safety of ESL have been established in real-life setting. However, data about outcomes in elderly patients are scarce. Primary endpoint was to evaluate outcomes of ESL in elderly patients. Method: This was a retrospective survey that included patients >65 years with focal seizures who started ESL between January 2010 and July 2012 at 12 Spanish Hospitals. ESL was prescribed individually according to real-life practice. Efficacy and safety were evaluated over 1 year. These patients were included within the bigger study ESLIBASE. Results: We included 29 patients, most of them males (18). Mean age was 71.2 year-old and epilepsy evolution was 20 years. Eighteen were pharmacorresistant at baseline. At 12 months, the mean dose was 850 mg/day, the retention rate 69%, the responder rate 62% and 24.1% were seizure-free. At 12 months, 16 patients (55.2%) had >= 1 adverse effect (AE), that led to discontinuation in 7 patients. Dizziness, nausea and ataxia were the most common AEs. The tolerability profile improved in 4/5 patients who switched from carbamazepine (CBZ) or oxcarbazepine (OXC) to ESL due to AEs. Conclusions: ESL was well-tolerated and effective in elderly patients in a real-life setting over 1 year, with a dose around 800 mg/day. AE effects improved in most of who switched from CBZ or OXC to ESL (C) 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Resumen: Introducción: El objetivo del proyecto EPICON es desarrollar una serie de recomendaciones sobre la forma adecuada de realizar el cambio de carbamazepina (CBZ) y oxcarbazepina (OXC) a acetato de eslicarbazepina (ESL) en determinados pacientes con epilepsia. Métodos: Un comité coordinador preparó un cuestionario con 56 preguntas en relación con el cambio de CBZ u OXC a ESL en la práctica clínica (metodología y situaciones del cambio). Posteriormente, se consultó a 54 expertos en epilepsia con el empleo de metodología Delphi (2 rondas de consulta). Se definió un consenso en acuerdo o desacuerdo si las respuestas para el ítem estudiado alcanzaban una mediana ≥ 7 o ≤ 3, respectivamente, y un rango intercuartílico relativo ≤ 0,40. Se analizaron los resultados y se formularon las conclusiones. Resultados: Las recomendaciones fundamentales fueron: el cambio de CBZ a ESL debe ser realizado en 1-3 semanas, con una equivalencia de dosis CBZ:ESL de 1:1.3, siendo recomendado en pacientes con olvidos de medicación, trabajos por turnos, polimedicados, problemas cognitivos, osteoporosis-osteopenia severa, dislipidemia o enfermedad hepática (ausencia de fallo hepático grave), así como en varones con disfunción eréctil causada por CBZ. El cambio de OXC a ESL puede realizarse de un día para otro con una equivalencia de dosis 1:1 y es recomendado en pacientes con olvidos de medicación, trabajos por turnos, polimedicados o problemas cognitivos. Se desaconsejó el cambio en caso de rash con CBZ u OXC. Conclusión: El proyecto EPICON proporciona algunas recomendaciones sobre el manejo clínico del cambio de CBZ u OXC a ESL, mediante el empleo de la metodología Delphi. Abstract: Introduction: The objective of the EPICON Project is to develop a set of recommendations on how to adequately switch from carbamazepine (CBZ) and oxcarbazepine (OXC) to eslicarbazepine acetate (ESL) in some patients with epilepsy. Methods: A steering committee drafted a questionnaire of 56 questions regarding the transition from CBZ or OXC to ESL in clinical practice (methodology and change situation). The questionnaire was then distributed to 54 epilepsy experts in 2 rounds using the Delphi method. An agreement/disagreement consensus was defined when a median ≥ 7 points or ≤ 3 was achieved, respectively, and a relative interquartile range ≤ 0.40. We analysed the results obtained to reach our conclusions. Results: Our main recommendations were the following: switching from CBZ to ESL must be carried out over a period of 1 to 3 weeks with a CBZ:ESL dose ratio of 1:1.3 and is recommended for patients who frequently forget to take their medication, those who work rotating shifts, polymedicated patients, subjects with cognitive problems, severe osteoporosis–osteopaenia, dyslipidaemia, or liver disease other than acute liver failure, as well as for men with erectile dysfunction caused by CBZ. The transition from OXC to ESL can take place overnight with an OXC:ESL dose ratio of 1:1 and it is recommended for patients who frequently forget to take their medication, those who work rotating shifts, polymedicated patients, or those with cognitive problems. The transition was not recommended for patients with prior rash due to CBZ or OXC use. Conclusion: The EPICON Project offers a set of recommendations about the clinical management of switching from CBZ or OXC to ESL, using the Delphi method. Palabras clave: Acetato de eslicarbazepina, Carbamazepina, Oxcarbazepina, Cambio, Metodología, Situaciones, Keywords: Eslicarbazepine acetate, Carbamazepine, Oxcarbazepine, Drug switching, Methodology, Situations

[Background]: The antineoplastic drug 5-fluoruracil (5-FU) is a pirimidine analog, which frequently induces potentially fatal diarrhea and mucositis. Cannabinoids reduce gastrointestinal motility and secretion and might prevent 5-FU-induced gut adverse effects. Here, we asked whether cannabinoids may prevent diarrhea and mucositis induced by 5-FU in the rat. [Methods]: Male Wistar rats received vehicle or the non-selective cannabinoid agonist WIN 55,212-2 (WIN; 0.5 mg kg injection, 1 injection day, 4 consecutive days) by intraperitoneal (ip) route; on the first 2 days, animals received also saline or 5-FU (150 mg kg injection, cumulative dose of 300 mg kg). Gastrointestinal motor function was radiographically studied after barium contrast intragastric administration on experimental days 1 and 4. Structural alterations of the stomach, small intestine and colon were histologically studied on day 4. PAS staining and immunohistochemistry for Ki67, chromogranin A and CD163 were used to detect secretory, proliferating, and endocrine cells, and activated macrophages respectively. [Key Results]: As shown radiographically, 5-FU induced significant gastric emptying delay (on days 1 and 4) and diarrhea (on day 4). WIN did not significantly alter the motility curves obtained for either control or 5-FU-treated animals but tended to reduce the severity of 5-FU-induced diarrhea and increased permanence of barium from day 1 to the beginning of day 4 in 5-FU-treated animals. 5-FU-induced mucositis was severe and not counteracted by WIN. [Conclusions and Inferences]: 5-FU-induced diarrhea, but not mucositis, was partly prevented by WIN at a low dose. Cannabinoids might be useful to prevent chemotherapy-induced diarrhea., This work was supported by Ministerio de Educación y Ciencia (SAF201-40075-C02-01) and Comunidad de Madrid (S2010/BMD-2308).

Inflammatory bowel diseases (ulcerative colitis; Crohn's disease) are debilitating relapsing inflammatory disorders affecting the gastrointestinal tract, with deleterious effect on quality of life, and increasing incidence and prevalence. Mucosal inflammation, due to altered microbiota, increased intestinal permeability and immune system dysfunction underlies the symptoms and may be caused in susceptible individuals by different factors (or a combination of them), including dietary habits and components. In this review we describe the influence of the Western diet, obesity, and different nutraceuticals/functional foods (bioactive peptides, phytochemicals, omega 3-polyunsaturated fatty acids, vitamin D, probiotics and prebiotics) on the course of IBD, and provide some hints that could be useful for nutritional guidance. Hopefully, research will soon offer enough reliable data to slow down the spread of the disease and to make diet a cornerstone in IBD therapy.

Introduction: The objective of the EPICON Project is to develop a set of recommendations on how to adequately switch from carbamazepine (CBZ) and oxcarbazepine (OXC) to eslicarbazepine acetate (ESL) in some patients with epilepsy. Methods: A steering committee drafted a questionnaire of 56 questions regarding the transition from CBZ or OXC to ESL in clinical practice (methodology and change situation). The questionnaire was then distributed to 54 epilepsy experts in 2 rounds using the Delphi method. An agreement/disagreement consensus was defined when a median ≥ 7 points or ≤ 3 was achieved, respectively, and a relative interquartile range ≤ 0.40. We analysed the results obtained to reach our conclusions. Results: Our main recommendations were the following: switching from CBZ to ESL must be carried out over a period of 1 to 3 weeks with a CBZ:ESL dose ratio of 1:1.3 and is recommended for patients who frequently forget to take their medication, those who work rotating shifts, polymedicated patients, subjects with cognitive problems, severe osteoporosis–osteopaenia, dyslipidaemia, or liver disease other than acute liver failure, as well as for men with erectile dysfunction caused by CBZ. The transition from OXC to ESL can take place overnight with an OXC:ESL dose ratio of 1:1 and it is recommended for patients who frequently forget to take their medication, those who work rotating shifts, polymedicated patients, or those with cognitive problems. The transition was not recommended for patients with prior rash due to CBZ or OXC use. Conclusion: The EPICON Project offers a set of recommendations about the clinical management of switching from CBZ or OXC to ESL, using the Delphi method. Resumen: Introducción: El objetivo del proyecto EPICON es desarrollar una serie de recomendaciones sobre la forma adecuada de realizar el cambio de carbamazepina (CBZ) y oxcarbazepina (OXC) a acetato de eslicarbazepina (ESL) en determinados pacientes con epilepsia. Métodos: Un comité coordinador preparó un cuestionario con 56 preguntas en relación con el cambio de CBZ u OXC a ESL en la práctica clínica (metodología y situaciones del cambio). Posteriormente, se consultó a 54 expertos en epilepsia con el empleo de metodología Delphi (2 rondas de consulta). Se definió un consenso en acuerdo o desacuerdo si las respuestas para el ítem estudiado alcanzaban una mediana ≥ 7 o ≤ 3, respectivamente, y un rango intercuartílico relativo ≤ 0,40. Se analizaron los resultados y se formularon las conclusiones. Resultados: Las recomendaciones fundamentales fueron: el cambio de CBZ a ESL debe ser realizado en 1-3 semanas, con una equivalencia de dosis CBZ:ESL de 1:1.3, siendo recomendado en pacientes con olvidos de medicación, trabajos por turnos, polimedicados, problemas cognitivos, osteoporosis-osteopenia severa, dislipidemia o enfermedad hepática (ausencia de fallo hepático grave), así como en varones con disfunción eréctil causada por CBZ. El cambio de OXC a ESL puede realizarse de un día para otro con una equivalencia de dosis 1:1 y es recomendado en pacientes con olvidos de medicación, trabajos por turnos, polimedicados o problemas cognitivos. Se desaconsejó el cambio en caso de rash con CBZ u OXC. Conclusión: El proyecto EPICON proporciona algunas recomendaciones sobre el manejo clínico del cambio de CBZ u OXC a ESL, mediante el empleo de la metodología Delphi. Keywords: Eslicarbazepine acetate, Carbamazepine, Oxcarbazepine, Drug switching, Methodology, Situations, Palabras clave: Acetato de eslicarbazepina, Carbamazepina, Oxcarbazepina, Cambio, Metodología, Situaciones

The aim of this work was to evaluate the effect of the administration of egg white hydrolysates on obesity-related disorders, with a focus on lipid metabolism, inflammation and oxidative stress, in Zucker fatty rats. Obese Zucker rats received water, pepsin egg white hydrolysate (750 mg/kg/day) or Rhizopus aminopeptidase egg white hydrolysate (750 mg/kg/day) for 12 weeks. Lean Zucker rats received water. Body weight, solid and liquid intakes were weekly measured. At the end of the study, urine, faeces, different organs and blood samples were collected. The consumption of egg white hydrolysed with pepsin significantly decreased the epididymal adipose tissue, improved hepatic steatosis, and lowered plasmatic concentration of free fatty acids in the obese animals. It also decreased plasma levels of tumor necrosis factor-alpha and reduced oxidative stress. Pepsin egg white hydrolysate could be used as a tool to improve obesity-related complications., This study has received financial support from the project AGL2012-32387 and SAF2012-40075-C02-01 from the Spanish Ministry of Economy and Competitiveness (MINECO).

Background: The choice of antiepileptic drug (AED) therapy in patients with brain tumor-related epilepsy (BTRE) is complicated, and there are a lack of robust clinical trial data to date. Methods: The NEOPLASM (Neuroncologic Patients treated with LAcoSaMide) study was a 6-month, multicenter, retrospective, observational study in patients with BTRE treated with lacosamide. Patients were started on lacosamide because of a lack of efficacy or adverse events (AEs) with prior AEDs or suitability versus other AEDs, according to clinical practice. The primary efficacy variable was the seizure-free rate at 6 months. Safety variables included the proportion of patients with an AE and the proportion with an AE that led to discontinuation. Results: Overall, 105 patients from 14 hospital centers were included in the analysis. Treatment with lacosamide for 6 months resulted in a 30.8% seizure-free rate, and 663% of patients had a >= 50% seizure reduction (responders). In the subset of patients included because of a lack of efficacy with prior AEDs, seizure-free rates were 28.0%, and 66.7% of patients were responders. No statistically significant differences in efficacy were observed according to the mechanism of action or enzyme-inducing properties of concomitant AEDs. Adverse events were reported by 41.9% of patients at 6 months, and 4.7% of them led to discontinuation. The most common AEs were somnolence/fatigue and dizziness. Notably, 57.1% of the patients who were switched to lacosamide because of AEs with their previous therapy did not report any AE at 6-month follow-up. Conclusions: In this open-label, observational study, lacosamide appeared to be effective and well tolerated in a large population of patients with BTRE. Lacosamide may therefore be a promising option for the treatment of patients with BTRE. (C) 2016 Elsevier Inc. All rights reserved.

Purpose Real-life experience with eslicarbazepine acetate (ESL) after first monotherapy failure in a large series of patients with partial epilepsy Method Multicenter, retrospective, 1 year, observational study. Inclusion criteria: 1) patients older than 18 years; 2) partial-onset seizures; 3) Failure of first monotherapy for any reason (efficacy, tolerability, compliance). Time-points for revision were at 3, 6 and 12 months. Main objectives were to assess efficacy and tolerability. Results A total of 253 patients were collected. The one-year retention rate was 92.9%. The mean dose after 12 months was 903.6±267 mg (range 400–1600). At 12 months, the percentage of seizure-free patients was 62.3%, 82.5% were responders and 5.6% did worse. Along the follow-up 31.6% of the patients reported adverse events and 3.6% discontinued for that reason. The main side effects were somnolence (8.7%) and dizziness (5.1%). A total of 127 patients (50.2%) were converted to monotherapy for at least 6 months. In this group, 77.2% were seizure-free and 29.1% of the patients reported AE after 1 year. Conclusion ESL outcome along 1 year follow-up after first monotherapy failure showed an optimal efficacy and tolerability profile. Half of patients were converted to monotherapy and followed for at least 6 months.

Objetivos La trombosis venosa cerebral (TVC) es una patologia poco frecuente. Su presentacion clinica es inespecifica y variable, lo que ocasiona retrasos en el diagnostico. Analizamos la validez de las diferentes pruebas de neuroimagen, tomografia computarizada (TC), resonancia magnetica (RM), angio-resonancia magnetica (RMV) y angiografia, en el diagnostico de TVC. Material y metodos Estudio retrospectivo sobre 12 pacientes con diagnostico final de TVC. Se realizo TC, que fue la prueba inicial, y RM a todos los pacientes, a 11 RMV y en 4 ocasiones se hizo angiografia. Se valoraron como signos directos la visualizacion del trombo o defectos de replecion en el vaso afecto y como signo indirecto la identificacion de hallazgos compatibles con infarto venoso. Resultados De las 12 TC, 4 mostraron signos directos, 2 indirectos y 6 fueron normales; de estas, en 3 pacientes se objetivaron signos indirectos en TC evolutivos. No mostro la extension real del proceso salvo en un caso de afectacion localizada de una vena cortical. En la RM se objetivo ocupacion de los vasos del territorio venosos afecto en 6 casos, en 2 se aprecio el signo del delta vacio y en 8 signos de infartovenoso. En una ocasion no fue diagnostica. En todas las RMV se visualizaron signos directos de TVC, incluso sin contraste intravenoso. Los resultados fueron similares a los de las angiografias. Once pacientes presentaban afectacion de mas de 2 localizaciones. Conclusiones La TC pone de manifiesto signos indirectos, a veces de modo tardio, y signos directos tan sutiles que requieren experiencia para ser interpretados. Ademas no valora la extension real del proceso. De todos modos debe utilizarse como tecnica de primer nivel, con contraste intravenoso, dada su disponibilidad en la mayoria de los centros, para excluir otras causas y servir para la indicacion de otras pruebas de neuroimagen, en este caso RM y RMV. Los resultados obtenidos con la realizacion simultanea de ambas son equiparables a los de la angiografia, evita los riesgos de esta tecnica, no expone al paciente a radiacionesionizantes y es diagnostica incluso sin la administracion de contraste.

A Spanish family is reported with dystrophinopathy of myalgia and cramps syndrome type. There were five affected males and three females, and also six asymptomatic carriers. Muscle biopsy showed a dystrophic pattern, but immunohistochemistry carried out with three anti-dystrophin antibodies was normal. Dystrophin analysis by western blot revealed a dystrophin of reduced quantity and molecular weight. DNA analysis showed a deletion of the dystrophin gene involving exons 45-52. The natural history of this disorder and the large intrafamilial clinical variability are discussed.

We present an analysis regarding Information and communication technologies (TIC) and their relation with indicators of academic results in bachelor’s degree programs offered in state public universities in Mexico. This work is non experimental, cross-sectional, and correlational. The goal is to determine significant relations between variables: educational programs that incorporate telematics in their programs and courses of study, qualifications, withholding rates, completion rates, professional integration, along with graduates and employers satisfaction. The data is formed by 58 universities that presented their Program of Quality Strengthening in Education Institutions (PROFOCIE) projects before Ministry of Public Education (SEP) in 2015; and were processed in the statistic package SPSS, obtaining correlation coefficients. These results showed significant relation to withholding rates and student and graduates satisfaction, even though a significant relation wasn’t found in degree indicators, completion rates, and professional integration.

Background: Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED) licensed as adjunctive therapy in adults with partial-onset or focal seizures. Objective: To evaluate in a clinical practice setting the long-term efficacy and safety of ESL in patients with focal seizures. Methods: ESLIBASE was a retrospective study that included all patients with focal seizures who started ESL between January 2010 and July 2012 at 12 hospitals. ESL was prescribed individually according to real-life practice. Efficacy and safety were evaluated over 1 year. Switching from carbamazepine (CBZ) and oxcarbazepine (OXC) was assessed. Results: Three hundred and twenty-seven patients were included; 78% of patients were taking >= 2 other AEDs at baseline. Most (87%) began ESL because of poor seizure control and13% because of adverse events (AEs) with CBZ or OXC. After 1 year, 237 patients (72.4%) remained on ESL. At 3, 6 and 12 months, the responder rate was 46.3%, 57.9%, and 52.5%, and 21.0%, 28.0%, and 25.3% of patients were seizure free. The responder rate significantly increased when ESL was combined with a non-sodium channel-targeting drug (non-SC drug) (66.7%) versus an SC drug (47.7%; p < 0.001). At 12 months, 40.7% of patients had >= 1 AE; AEs led to treatment discontinuation in 16.2%. Dizziness, nausea, and somnolence were the most common AEs. The tolerability profile improved in >50% of the patients who switched from CBZ or OXC to ESL because of AEs. Conclusions: ESL was well tolerated and effective in a real-world setting over 1 year. Side-effect profile improved when OXC and CBZ recipients were switched to ESL. (C) 2014 Elsevier B.V. All rights reserved.

Background Parthenogenetic and androgenetic embryos fail to develop to term, possibly because of genomic imprinting, an epigenetic alteration of certain genes, depending on the parent of origin. The effect of this phenomenon has been studied mainly in mid-gestation embryos, without morphological abnormalities detected during the preimplantation period. Nevertheless, parthenogenetic mouse embryos never develop to the blastocyst stage in the same numbers as do fertilized ones, and up to 50% fail to implant, suggesting that genomic imprinting may be responsible for this lack of viability. Methods We have made a quantitative and morphometric analysis of the cell proliferation capacity at the end of the preimplantation period in parthenogenetic mice to study if such parameter is affected by the monoparental constitution of the embryos. Results and conclusions:We have found that, apart from the different morphology and cell number induced by culture conditions, parthenogenetic mouse blastocysts have a significantly smaller cell number than do fertilized control embryos. Our interpretation of these results is that the monoparental constitution of these embryos may be responsible for the lack of some factor required to sustain cell proliferation after the morula stage. Anat. Rec. 247:243-247, 1997. © 1997 Wiley-Liss, Inc.

Culture media for mouse preimplantation development are usually derived from two basic solutions: Krebs-Ringer and Tyrode. We have used outbred mice (OF1) to make a comparative analysis of derived media of both types and their success in sustaining development from the one-cell to the blastocyst stage. The best results (up to 50%), in terms of overcoming the two-cell block and sustaining development to expanded blastocyst, were obtained with media derived from Tyrode's solution and with Krebs-Ringer-based media in which the high concentrations of certain metabolites (Cl-, K+, Mg2+ and PO(4)3+) were reduced to the values present in the Tyrode-derived media. Interestingly, medium T6 (based on Tyrode and incapable of avoiding developmental block on its own), yielded the best development rate with the addition of ethylenediaminetetraacetic acid (EDTA). The addition of glutamine to medium T6 did not have any effect. We further developed T7, a medium based on T6 but incorporating the concentrations of nutrients present in the oviduct. This medium also proved better than its Krebs-Ringer counterpart (MTF), but not better than T6, probably due to the different nutritive requirements in the transition from morula to blastocyst. The two most significant findings were: i) that Tyrode-based formulations were superior to media based on Krebs-Ringer solution, and ii) that medium T6 with EDTA was as effective for mouse egg culture as the recently developed KSOM medium.