Serie de 22 casos de ictus isquémico arterial perinatal: factores de riesgo, manejo clínico y secuelas neurológicas / A series of 22 cases of perinatal arterial ischaemic stroke: risk factors, clinical management and neurological sequelae

Introduction. Perinatal arterial ischaemic stroke (PAIS) is almost as common as in adulthood and causes significant neurological sequelae. Aim. The aim is to describe the risk situations surrounding these neonates, the clinical manifestations, the management, the cost-effectiveness of diagnostic tests and the neurological sequelae. Patients and methods. We conducted an observational study of a cohort of patients consisting of neonates with a gestational age = 35 weeks diagnosed with PAIS in our hospital between 2010 and 2021. Results. Twenty-two cases of PAIS were included, and the incidence in our centre was 1/1,869 live newborns. The data showed that 81.8% had some intrapartum risk factor and 40.9% had a combination of several risk factors. It started with seizures (mean age 27.3 hours) in 77.3% of cases. Patients with a stroke in the left hemisphere had more sequelae (77.8%) than those with a stroke on the right-hand side (16.6%) (p = 0.041), with the exception of infantile cerebral palsy (p = 0.04), while we found no difference between hemispheres in the frequency of language impairment (p = 0.06). The mean follow-up time was 6.13 ± 3.06 years. A total of 63.6% of infants had neurological sequelae: infantile cerebral palsy (40.9%), language disorders (22.7%) and intellectual disability (9%). Moreover, 18.2% developed epilepsy (between 0.25 and 1.8 years) and antiseizure treatment was maintained after discharge in 37.5% of cases in the last years of the study. Conclusions. If a newborn infant presents seizures, it is necessary to rule out the possibility of a stroke. PAIS causes neurological sequelae in over 60% of cases. Early identification is essential to improve the neurological prognosis and avoid the prolonged use of antiseizure drugs where possible. (AU)

Introducción: El ictus cerebral isquémico arterial perinatal (IIAP) es una entidad casi tan frecuente como en la época adulta, que ocasiona secuelas neurológicas importantes.ObjetivoDescribir las situaciones de riesgo que rodean a estos neonatos, la clínica que manifiestan, el manejo, la rentabilidad de las pruebas diagnósticas y las secuelas neurológicas.Pacientes y métodosEstudio observacional de una cohorte de pacientes formada por neonatos = 35 semanas de edad gestacional diagnosticados de IIAP entre 2010 y 2021 en nuestro hospital.ResultadosSe incluyeron 22 casos de IIAP, y su incidencia en nuestro centro fue de 1/1.869 recién nacidos vivos. El 81,8% tuvo algún factor de riesgo intraparto y en el 40,9% se aglutinaron varios. Comenzó con convulsiones (edad media 27,3 horas) el 77,3% de casos. Los pacientes con ictus del hemisferio izquierdo tuvieron más secuelas (77,8%) en comparación con los derechos (16,6%) (p = 0,041), a expensas de la parálisis cerebral infantil (p = 0,04), mientras no encontramos diferencia en la frecuencia de alteraciones del lenguaje (p = 0,06) entre hemisferios. El tiempo medio de seguimiento fue de 6,13 años ± 3,06. El 63,6% de los neonatos tuvo secuelas neurológicas: parálisis cerebral infantil (40,9%), trastornos del lenguaje (22,7%) y discapacidad intelectual (9%). Desarrolló epilepsia el 18,2% (entre 0,25 y 1,8 años) y se mantuvo el tratamiento anticrisis tras el alta en el 37,5% de los casos en los últimos años del estudio.ConclusionesAnte un neonato con convulsiones hay que descartar un ictus cerebral. El IIAP ocasiona secuelas neurológicas en más del 60% de los casos. Su identificación precoz es fundamental para mejorar el pronóstico neurológico y evitar el uso prolongado de fármacos anticrisis cuando resulte posible. (AU)

[A series of 22 cases of perinatal arterial ischaemic stroke: risk factors, clinical management and neurological sequelae]. / Serie de 22 casos de ictus isquémico arterial perinatal: factores de riesgo, manejo clínico y secuelas neurológicas.

INTRODUCTION: Perinatal arterial ischaemic stroke (PAIS) is almost as common as in adulthood and causes significant neurological sequelae. AIM: The aim is to describe the risk situations surrounding these neonates, the clinical manifestations, the management, the cost-effectiveness of diagnostic tests and the neurological sequelae. PATIENTS AND METHODS: We conducted an observational study of a cohort of patients consisting of neonates with a gestational age = 35 weeks diagnosed with PAIS in our hospital between 2010 and 2021. RESULTS: Twenty-two cases of PAIS were included, and the incidence in our centre was 1/1,869 live newborns. The data showed that 81.8% had some intrapartum risk factor and 40.9% had a combination of several risk factors. It started with seizures (mean age 27.3 hours) in 77.3% of cases. Patients with a stroke in the left hemisphere had more sequelae (77.8%) than those with a stroke on the right-hand side (16.6%) (p = 0.041), with the exception of infantile cerebral palsy (p = 0.04), while we found no difference between hemispheres in the frequency of language impairment (p = 0.06). The mean follow-up time was 6.13 ± 3.06 years. A total of 63.6% of infants had neurological sequelae: infantile cerebral palsy (40.9%), language disorders (22.7%) and intellectual disability (9%). Moreover, 18.2% developed epilepsy (between 0.25 and 1.8 years) and antiseizure treatment was maintained after discharge in 37.5% of cases in the last years of the study. CONCLUSIONS: If a newborn infant presents seizures, it is necessary to rule out the possibility of a stroke. PAIS causes neurological sequelae in over 60% of cases. Early identification is essential to improve the neurological prognosis and avoid the prolonged use of antiseizure drugs where possible.

TITLE: Serie de 22 casos de ictus isquémico arterial perinatal: factores de riesgo, manejo clínico y secuelas neurológicas.Introducción. El ictus cerebral isquémico arterial perinatal (IIAP) es una entidad casi tan frecuente como en la época adulta, que ocasiona secuelas neurológicas importantes. Objetivo. Describir las situaciones de riesgo que rodean a estos neonatos, la clínica que manifiestan, el manejo, la rentabilidad de las pruebas diagnósticas y las secuelas neurológicas. Pacientes y métodos. Estudio observacional de una cohorte de pacientes formada por neonatos = 35 semanas de edad gestacional diagnosticados de IIAP entre 2010 y 2021 en nuestro hospital. Resultados. Se incluyeron 22 casos de IIAP, y su incidencia en nuestro centro fue de 1/1.869 recién nacidos vivos. El 81,8% tuvo algún factor de riesgo intraparto y en el 40,9% se aglutinaron varios. Comenzó con convulsiones (edad media 27,3 horas) el 77,3% de casos. Los pacientes con ictus del hemisferio izquierdo tuvieron más secuelas (77,8%) en comparación con los derechos (16,6%) (p = 0,041), a expensas de la parálisis cerebral infantil (p = 0,04), mientras no encontramos diferencia en la frecuencia de alteraciones del lenguaje (p = 0,06) entre hemisferios. El tiempo medio de seguimiento fue de 6,13 años ± 3,06. El 63,6% de los neonatos tuvo secuelas neurológicas: parálisis cerebral infantil (40,9%), trastornos del lenguaje (22,7%) y discapacidad intelectual (9%). Desarrolló epilepsia el 18,2% (entre 0,25 y 1,8 años) y se mantuvo el tratamiento anticrisis tras el alta en el 37,5% de los casos en los últimos años del estudio. Conclusiones. Ante un neonato con convulsiones hay que descartar un ictus cerebral. El IIAP ocasiona secuelas neurológicas en más del 60% de los casos. Su identificación precoz es fundamental para mejorar el pronóstico neurológico y evitar el uso prolongado de fármacos anticrisis cuando resulte posible.

Children's physiological and behavioural response evoked by the observation, olfaction, manipulation, and consumption of food textures. Part 1: Liquid products.

Children are thought to prefer homogeneous and simple textures that are easy to manipulate in the mouth. Although scientific research has been done on children's acceptance for food textures, there is a lack of knowledge regarding the emotional response elicited by textures in this group of population. Physiological and behavioural methods could be an appropriate approach to measure food-evoked emotions in children since they require a low cognitive effort and allow a real-time measure. In this regard, a study that combined the measure of skin conductance response (SCR) and facial expressions was conducted: (i) to provide a first insight into food-evoked emotions induced by liquid food products that only vary in texture, (ii) to capture the emotional response evoked by the observation, olfaction, manipulation, and consumption of the products, and (iii) to overcome methodological drawbacks that are frequently associated to these methods. To achieve these goals, 50 children (5-12 yrs old) evaluated three liquids designed to only vary in texture (from slightly thick to extremely thick), following four sensory tasks: observation, olfaction, manipulation, and consumption. After each sample was tasted, children rated liking with a 7-pt hedonic scale. Facial expressions and SCR were monitored during the test, and they were analysed as action units (AUs) and basic emotions as well as changes in SCR. Results showed that the extremely thick liquid was less liked by the children and induced a more negative emotional response, whereas the slightly thick liquid was more liked and evoked a more positive emotional response. The combined method used in this study showed good discrimination ability among the three samples tested, obtaining the best discrimination during the manipulation task. The codification of the AUs located in the upper side of the face allowed us to measure the emotional response evoked by the consumption of the liquids, without the artifacts caused by the oral processing of the products. This study provides a child-friendly approach to be used during the sensory evaluation of food products in a broad range of sensory tasks minimising the methodological drawbacks.

[Neuropsychology of generalized anxiety disorders: a systematic review]. / Neuropsicologia del trastorno de ansiedad generalizada: revision sistematica.

INTRODUCTION: Cognitive symptoms in psychiatric diseases such as schizophrenia, bipolar disorder or major depression have been widely studied and defined; however, despite the frequent subjective cognitive complaints in patients with anxiety disorders, neuropsychology of anxiety disorders has less consistent results in literature. PATIENTS AND METHODS: This study offers a systematic review of controlled studies that evaluate neuropsychological findings in adults diagnosed of generalized anxiety disorders (GAD). Finally, 40 articles were selected for this systematic review, with a total sample of 1098 patients with GAD. RESULTS: Results suggest that subjects with GAD have a worse performance than controls in the following cognitive domains: complex attention (selective attention), executive functions (working memory, cognitive inhibition, decision making), and social cognition (recognizing and processing emotions, attribution bias). Most consistent results report the influence of emotional stimuli (specifically, threatening or anxiety-provoking stimuli) on performance on cognitive task related with complex attention, working memory and cognitive inhibition. CONCLUSION: In our knowledge, there is not any previous systematic review defining the neuropsychological profile of GAD. Due to the clinical and functional consequences of cognitive symptoms in these patients, future studies that allow a better knowledge on this field are needed: including larger samples of patients; controlling variables that could eventually modify the association between cognitive symptoms and GAD, such as pharmacological treatment and comorbid depression; focusing on specific neuropsychological test for GAD; and evaluating the effect of pharmacological and psychological treatment on cognitive symptoms in GAD patients.

TITLE: Neuropsicologia del trastorno de ansiedad generalizada: revision sistematica.Introduccion. Los sintomas cognitivos en enfermedades psiquiatricas como la esquizofrenia, el trastorno bipolar o la depresion mayor se han estudiado y definido ampliamente; sin embargo, a pesar de las frecuentes quejas cognitivas en los pacientes con trastornos de ansiedad, sus hallazgos neuropsicologicos son menos consistentes en la literatura cientifica. Pacientes y metodos. Se realiza una revision sistematica de los estudios controlados que evaluan alteraciones neuropsicologicas en adultos con diagnostico clinico de trastorno de ansiedad generalizada (TAG). Finalmente se seleccionaron 40 articulos para esta revision sistematica, que en total comprendian una muestra de 1.098 pacientes con TAG. Resultados. Los estudios revisados sugieren que los sujetos con TAG tienen peor rendimiento que los controles en los siguientes dominios cognitivos: atencion compleja (atencion selectiva), funciones ejecutivas (memoria de trabajo, inhibicion cognitiva, toma de decisiones) y cognicion social (identificacion y procesamiento de las emociones, sesgo atribucional). Los resultados mas consistentes señalan la influencia de estimulos emocionales (sobre todo los estimulos de caracter amenazante o ansiogeno) en el rendimiento en tareas de atencion, memoria de trabajo e inhibicion cognitiva. Conclusiones. En nuestro conocimiento, no existen revisiones sistematicas previas que definan el perfil neuropsicologico en el TAG. Dada la repercusion clinica y funcional de los sintomas cognitivos en estos pacientes, se necesitan futuros trabajos que incluyan muestras mas amplias de pacientes y controlen posibles variables de confusion, como el tratamiento farmacologico y la comorbilidad depresiva, asi como el desarrollo de instrumentos especificos de evaluacion y el estudio del eventual efecto del tratamiento sobre estos sintomas.

Frecuencia de tiña del cuerpo en un hospital del estado de Quintana Roo / Frequency of tinea corporis in a hospital in Quintana Roo state

Resumen ANTECEDENTES: las dermatofitosis son micosis superficiales causadas por un grupo de hongos parásitos de la queratina, denominados dermatofitos. Comprenden tres géneros: Trichophyton, Microsporum y Epidermophyton. Son cosmopolitas, predominan en climas cálidos y húmedos, y representan 70 a 80% de todas las micosis. OBJETIVO: identificar la frecuencia de consulta por tiña del cuerpo en una zona urbana tropical. MATERIAL Y MÉTODO: estudio descriptivo, abierto y transversal, en el que durante tres meses en 2015 se registraron todos los pacientes con diagnóstico clínico de tiña del cuerpo que asistieron a la consulta de dermatología de un hospital de segundo nivel de Playa del Carmen, Quintana Roo, México. Se registraron los datos demográficos, tiempo de evolución, topografía y factores predisponentes asociados. Se realizó examen directo en escama con hidróxido de potasio (KOH), cultivo micológico en medio de Sabouraud y examen directo del cultivo con azul de lactofenol para identificar al agente causal. RESULTADOS: de 546 consultas de dermatología general se detectaron 17 pacientes (3%) y se corroboró el diagnóstico con KOH en 14 pacientes (82%, nueve mujeres [64%]), entre éstos hubo crecimiento en el cultivo en 9 muestras (64%). Se aisló Microsporum canis en 4 (44%), Trichophyton rubrum en 4 (44%) y T. mentagrophytes en uno (11%). Los límites de edad fueron 3 y 57 años (4 niños, 28.5%). El tiempo de evolución promedio fue de 15 semanas. La localización más frecuente fueron las extremidades. Los factores predisponentes más comunes fueron el contacto con mascotas infectadas y la administración de corticoesteroides. CONCLUSIONES: la tiña del cuerpo representa 3% de la consulta de dermatología en un hospital de una zona urbana tropical. Fue más frecuente en mujeres, predominó en las extremidades y en 28.5% afectó a población pediátrica. T. rubrum y M. canis fueron los agentes causales más frecuentes.

Abstract BACKGROUND: Dermatophytosis are superficial mycosis caused by dermatophytes, a group of fungi that parasite keratin, and is composed of three genera: Trichophyton, Microsporum and Epidermophyton. They predominate on hot and humid climates, and are responsible of 70-80% of all mycosis. OBJETIVE: To identify the frequency of consultation for tinea corporis. MATERIAL AND METHOD: A descriptive, open and cross-sectional study in which, during three months in 2015, all patients with clinical diagnosis of tinea corporis that attended to the dermatology department in a second level hospital at Playa del Carmen, QR, Mexico, were registered including demographic data, such as progression time, topography and associated predisposing factors; a KOH mount was performed, as well as mycological culture in Sabouraud dextrose agar and microscopic examination of the colony with lactophenol blue to identify the causal agent. RESULTS: Out of 546 visits to the dermatology service, the diagnosis was confirmed in 17 patients (2.5%) and diagnosis was confirmed with a positive KOH mount in 14 patients (82%, nine women [64%]), and in 9 samples there was culture growth (64%). Microsporum canis and Trichophyton rubrum were isolated in 4 cases (44%) each, and Trichophyton mentagrophytes in one case (11%). Age range was 3-57 years, with four children registered (28.5%). The progression time of the disease was 15 weeks in average. The most frequent topography was the extremities. The most common predisposing factors were contact with infected pets and the administration of corticosteroids. CONCLUSIONS: Tinea corporis represents 3% of the dermatology consultation in a second level hospital in urban tropical zone. It is more frequent in female patients, affecting more frequently extremities; 28.5% were children. The isolated causal agents were M. canis and T. rubrum.

Neonatal Treatment with a Pegylated Leptin Antagonist Induces Sexually Dimorphic Effects on Neurones and Glial Cells, and on Markers of Synaptic Plasticity in the Developing Rat Hippocampal Formation.

The present study aimed to better understand the role of the neonatal leptin surge, which peaks on postnatal day (PND)9-10, on the development of the hippocampal formation. Accordingly, male and female rats were administered with a pegylated leptin antagonist on PND9 and the expression of neurones, glial cells and diverse markers of synaptic plasticity was then analysed by immunohistochemistry in the hippocampal formation. Antagonism of the actions of leptin at this specific postnatal stage altered the number of glial fibrillary acidic protein positive cells, and also affected type 1 cannabinoid receptors, synaptophysin and brain-derived neurotrophic factor (BDNF), with the latter effect being sexually dimorphic. The results indicate that the physiological leptin surge occurring around PND 9-10 is critical for hippocampal formation development and that the dynamics of leptin activity might be different in males and females. The data obtained also suggest that some but not all the previously reported effects of maternal deprivation on hippocampal formation development (which markedly reduces leptin levels at PND 9-10) might be mediated by leptin deficiency in these animals.

Acute neonatal appendicitis: a diagnosis to consider in abdominal sepsis.

Appendicitis in the neonatal period is extremely rare. Its low incidence together with non-specific clinical symptoms often mean the diagnosis is delayed, leading to increased rates of peritonitis and mortality. We report the case of a 33-week premature infant, small for gestational age (1180 g at birth), clinically stable and receiving exclusive enteral feeding, who presented clinical manifestations of necrotizing enterocolitis at 14 days of life. Acute phase reactants were elevated and abdominal radiography showed pneumoperitoneum. Laparotomy revealed acute perforated appendicitis without intestinal involvement and purulent fluid in the peritoneum, for which appendectomy was performed. Neonatal acute appendicitis should be considered in the differential diagnosis of abdominal sepsis since early diagnosis and treatment significantly reduce associated morbidity and mortality.

[Peri-viability: limits of prematurity in a regional hospital in the last 10 years]. / Periviabilidad: el límite de la prematuridad en un hospital regional de referencia durante los últimos 10 años.

AIM: To determine the preterm viability between 22 and 25 gestational weeks in our hospital in last 10 years. PATIENTS AND METHODS: A descriptive retrospective study was conducted on preterms between 22-25 gestational weeks born between 1-1-2002 and 12-31-2011. RESULTS: There were 121 newborns, 45 (37%) stillbirths and 76 (63%) live births (16 died in delivery room, and 60 admitted to neonatal intensive unit). Among the 60 admitted, 34 died before hospital discharge, and 26 survived (21% of total, 34% of live births and 43% of those admitted to neonatal intensive unit). The causes of death were: 16 therapeutic effort limitation in delivery room, 8 therapeutic effort limitation in neonatal ward, 7 nosocomial sepsis, 7 NEC, 4 respiratory problems, and 8 of unknown cause. There were no survivors below 24 gestational weeks. Of the 26 survivors, 4 had major neurological disorders, and 11 with a normal neurological outcome. No significant statistical differences were found in the mortality between the two five-year periods analysed. CONCLUSIONS: The peri-viability has important clinical and ethical problems for neonatologist.

The endocannabinoid system in critical neurodevelopmental periods: sex differences and neuropsychiatric implications.

This review focuses on the endocannabinoid system as a crucial player during critical periods of brain development, and how its disturbance either by early life stressful events or cannabis consumption may lead to important neuropsychiatric signs and symptoms. First we discuss the advantages and limitations of animal models within the framework of neuropsychiatric research and the crucial role of genetic and environmental factors for the establishment of vulnerable phenotypes. We are becoming aware of important sex differences that have emerged in relation to the psychobiology of cannabinoids. We will discuss sexual dimorphisms observed within the endogenous cannabinoid system, as well as those observed with exogenously administered cannabinoids. We start with how the expression of cannabinoid CB(1) receptors is regulated throughout development. Then, we discuss recent results showing how an experimental model of early maternal deprivation, which induces long-term neuropsychiatric symptoms, interacts in a sex-dependent manner with the brain endocannabinoid system during development. This is followed by a discussion of differential vulnerability to the pathological sequelae stemming from cannabinoid exposure during adolescence. Next we talk about sex differences in the interactions between cannabinoids and other drugs of abuse. Finally, we discuss the potential implications that organizational and activational actions of gonadal steroids may have in establishing and maintaining sex dependence in the neurobiological actions of cannabinoids and their interaction with stress.

Analyzing the effects of a single episode of neonatal maternal deprivation on metabolite profiles in rat brain: a proton nuclear magnetic resonance spectroscopy study.

Animal models have greatly contributed to the understanding of neuropsychiatric disorders and have provided extensive evidence for the "neurodevelopmental hypothesis." In this regard, a single and prolonged episode (24 h) of early maternal deprivation early in life, on postnatal day 9, has been proposed as an animal model for the investigation of certain neuropsychiatric disorders, including schizophrenia. Since metabolic changes in hippocampus (HIP) and prefrontal cortex (PFC) have been described among schizophrenic patients by using ex vivo high-resolution magic angle spinning (HR-MAS) proton ((1)H) nuclear magnetic resonance spectroscopy, in the present study we aimed to investigate the effects of maternal deprivation (MD) on the metabolite profiles of the developing brain by using the HR-MAS technique. MD significantly altered the hippocampal and cortical metabolic profile of neonatal rats (PND 13) in a sex-dependent manner. Glutamine and glutamate (Glx) and taurine of male and female rat pups were altered in both brain areas analyzed. Differences in hippocampal phosphorylethanolamine have also been found as a function of the MD protocol. In addition, MD induced some other region- and sex-dependent effects, including changes in N-acetyl aspartate and total choline signals in the hippocampi of male pups. Present findings indicate a different brain metabolic profile in our animal model of early life stress suggesting its potential utility in the implementation of translational neuropsychiatric research.

Single-stage treatment with intraoperative ERCP: management of patients with possible choledocholithiasis and gallbladder in situ in a non-tertiary Spanish hospital.

BACKGROUND: The best way to reduce endoscopic retrograde cholangiopancreatography (ERCP) complications is not to perform it if it is unnecessary. Both intraoperative and postoperative ERCP rely on use of intraoperative cholangiography as a final diagnostic test for choledocholithiasis (CLD) whenever clinical data are unable to rule out CLD. Intraoperative ERCP could become a therapeutic option when a previous preoperative ERCP fails. We present our experience with intraoperative ERCP. PATIENTS AND METHODS: This is a descriptive and prospective study of a cohort of 82 patients with moderate risk of CLD. They were operated on by laparoscopic cholecystectomy with intraoperative cholangiography (IOC). We performed intraoperative ERCP using the rendezvous technique. RESULTS: Thirty-six out of 82 patients had an abnormal IOC study. Mean age was 58.7 years (standard deviation, SD 16.6, 25-83 years), and 60.6% were females. Ultrasound study showed that 51.4% of patients had a dilated bile duct. Magnetic resonance cholangiography (MRC) was performed on three patients (8.3%). The success rate of intraoperative ERCP was 88.2%. Three out of the 36 patients (8.8%) had ERCP complications [2 mild papillary bleeding (5.8%), 1 acute pancreatitis (2.9%)]. The rate of conversion to open surgery was 5% with a surgical complications rate of 4% [one injured duct and two surgical bleeding which required re-operation (2.5%)]. There were no mortalities. Four patients (11.1%) needed post-surgical ERCP, with a residual CLD rate of 5.6% (two patients) in the postoperative period. Mean surgical time was 181 min (SD 60, 75-345 min). Mean hospital stay was 6.2 days (SD 4.7, 2-24 days). CONCLUSIONS: Intraoperative ERCP is an option to prevent performing ERCP unnecessarily on patients with moderate risk of CLD not confirmed using appropriate radiological studies. It can resolve the biliary disease in a single step with a similar success rate to standard ERCP, but with low morbidity, especially of acute pancreatitis. The residual CLD rate is also very low.

Long term sex-dependent psychoneuroendocrine effects of maternal deprivation and juvenile unpredictable stress in rats.

We have analysed the long-term psychoneuroendocrine effects of maternal deprivation (MD) [24 h at postnatal day (PND) 9] and/or exposure to chronic unpredictable stress (CUS) during the periadolescent period (PND 28 to PND 43) in male and female Wistar rats. Animals were tested in the elevated plus maze (EPM, anxiety) at PND 44 and in two memory tests, spontaneous alternation and novel object recognition (NOT) in adulthood. The expression of hippocampal glucocorticoid (GR) and mineralocorticoid (MR) receptors, as well as of synaptophysin, neural cell adhesion molecule and brain-derived neurotrophic factor, was analysed by in situ hybridisation in selected hippocampal regions. Endocrine determinations of leptin, testosterone and oestradiol plasma levels were carried out by radioimmunoassay. Young CUS animals showed decreased anxiety behaviour in the EPM (increased percentage of time and entries in the open arms) irrespective of neonatal treatment. Memory impairments were induced by the two stressful treatments as was revealed by the NOT, with males being most clearly affected. Although each stressful procedure, when considered separately, induced different (always decrements) effects on the three synaptic molecules analysed and affected males and females differently, the combination of MD and CUS induced an unique disruptive effect on the three synaptic plasticity players. MD induced a long-term significant decrease in hippocampal GR only in males, whereas CUS tended to increase MR in males and decrease MR in females. Both neonatal MD and periadolescent CUS induced marked reductions in testosterone and oestradiol in males, whereas MD male animals also showed significantly decreased leptin levels. By contrast, in females, none of the hormones analysed was altered by any of the stressful procedures. Taking our data together in support of the 'two-hit' hypothesis, MD during neonatal life and/or exposure to CUS during the periadolescent period induced a permanent deficit in memory, which was accompanied by a decrement in markers for hippocampal plasticity. The long-term effects on body weight and hormone levels, particularly among males, might reflect sex-dependent lasting metabolic alterations as well as an impaired reproductive function.

Adolescent exposure to nicotine and/or the cannabinoid agonist CP 55,940 induces gender-dependent long-lasting memory impairments and changes in brain nicotinic and CB(1) cannabinoid receptors.

We have analysed the long-term effects of adolescent (postnatal day 28-43) exposure of male and female rats to nicotine (NIC, 1.4 mg/kg/day) and/or the cannabinoid agonist CP 55,940 (CP, 0.4 mg/kg/day) on the following parameters measured in the adulthood: (1) the memory ability evaluated in the object location task (OL) and in the novel object test (NOT); (2) the anxiety-like behaviour in the elevated plus maze; and (3) nicotinic and CB(1) cannabinoid receptors in cingulated cortex and hippocampus. In the OL, all pharmacological treatments induced significant decreases in the DI of females, whereas no significant effects were found among males. In the NOT, NIC-treated females showed a significantly reduced DI, whereas the effect of the cannabinoid agonist (a decrease in the DI) was only significant in males. The anxiety-related behaviour was not changed by any drug. Both, nicotine and cannabinoid treatments induced a long-lasting increase in CB(1) receptor activity (CP-stimulated GTPγS binding) in male rats, and the nicotine treatment also induced a decrease in nicotinic receptor density in the prefrontal cortex of females. The results show gender-dependent harmful effects of both drugs and long-lasting changes in CB(1) and nicotinic receptors.

Sex-dependent alterations in response to maternal deprivation in rats.

We review here our latest results regarding short- and long-term effects of a neonatal maternal deprivation (MD) stress [24h at postnatal day (PND) 9] on diverse psychoneuroimmunoendocrine parameters, pointing out the existence of numerous sexual dimorphisms. Behavioral changes observed in MD animals might be at least in part attributable to neurodevelopmental effects of MD-induced elevated corticosterone levels. Our findings of short-term effects of MD on hippocampal and cerebellar neurons and glial cells appear to support this hypothesis. However, it is important to note that these cellular effects were more marked in males than in females. Moreover, in analyzing the effects of this neonatal stress on the endocannabinoid system (hippocampal endocannabinoid levels and CB1 receptors) we have also found that males were more affected by MD. Since all these sexual dimorphisms were found at an early neonatal age (PND 13), they are attributable to organizational effects of gonadal steroids. We discuss the potential implications of the elevated corticosterone and decreased leptin levels shown by MD animals in their diverse functional alterations, including the above mentioned neural effects as well as the intriguing persistent deficit in their immunological system. We also emphasize the necessity of analyzing the important influence of sex as regards the specific consequences of early life stress.

Early maternal deprivation in rats: a proposed animal model for the study of developmental neuroimmunoendocrine interactions.

Adult animals that had been subjected to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal day (PND) 9-10] show long-term behavioral alterations that resemble specific symptoms of schizophrenia. Moreover, at adolescence MD rats showed depressive-like behavior and altered motor responses. According to the neurodevelopmental hypothesis, certain behavioral abnormalities observed in MD animals may be related to altered neurodevelopmental processes triggered by MD-induced elevated glucocorticoids in relevant specific brain regions. We review here these neuroendocrine effects and show new data indicating that the MD procedure induces diverse detrimental effects on the immune system that are already revealed in the short term (PND 13) and persist into adulthood. These long-lasting effects might be related to altered hypothalamus-pituitary-adrenal axis activity and to social as well as nutrition-related factors. In fact, MD induces long-lasting decreases in body weight. In view of our findings we propose the present MD procedure as a potentially useful model to analyze developmental interactions between early psychophysiological stress and immunodeficient states.

Neuronal and glial alterations in the cerebellar cortex of maternally deprived rats: gender differences and modulatory effects of two inhibitors of endocannabinoid inactivation.

Adult animals submitted to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal day 9-10] show behavioral alterations that resemble specific symptoms of schizophrenia. Accordingly, this experimental procedure has been proposed as an animal model of schizophrenia based on the neurodevelopmental hypothesis. We have recently reported that MD-induced sex-dependent alterations in the hippocampus of neonatal rats. In view of recent evidence for important implications of the cerebellum in neurodevelopmental psychiatric diseases, we have now addressed possible degenerative changes in the cerebellar cortex of neonatal Wistar rats of both genders. To evaluate the presence of degenerated nerve cells, we used Fluoro-Jade C staining and for the study of astrocytes, we employed glial fibrillary acidic protein. Further, we analyzed the modulatory actions of two inhibitors of endocannabinoids inactivation, the fatty acid amide hydrolase inhibitor N-arachidonoyl-serotonin, AA-5-HT, and the endocannabinoid reuptake inhibitor, OMDM-2 (daily subcutaneous injections during the postnatal period 7-12). The animals were sacrificed at postnatal Day 13. MD induced significant increases in the number of Fluoro-Jade C positive cells (indicative of degenerating neurons) and in the number of glial fibrillary acidic protein positive cells, only in males. The two cannabinoid compounds reversed or attenuated these effects. The present results provide new insights regarding the psychopathological implications of the cerebellum, the role of the endocannabinoid system in neural development, and the possible neurodevelopmental basis of gender differences in schizophrenia.

Two-stage treatment with preoperative endoscopic retrograde cholangiopancreatography (ERCP) compared with single-stage treatment with intraoperative ERCP for patients with symptomatic cholelithiasis with possible choledocholithiasis.

BACKGROUND AND STUDY AIMS: An ideal treatment for choledocholithiasis in the laparoscopic era has not been established. The objective of this study was to elucidate whether a treatment strategy of performing intraoperative endoscopic retrograde cholangiopancreatography (ERCP) during laparascopic cholecystectomy (when choledocholithiasis is confirmed by intraoperative cholangiography) is better for patients with suspected common bile duct stones than the current strategy (preoperative ERCP followed by laparoscopic cholecystectomy). PATIENTS AND METHODS: This was a prospective randomized study to evaluate which of these two approaches was most benefit- and cost-effective for patients with intermediate risk of choledocholithiasis. Patients underwent either preoperative ERCP followed by a laparoscopic cholecystectomy a few weeks later (the "preoperative ERCP" group) or intraoperative ERCP (the "intraoperative ERCP" group). Intraoperative ERCP was performed using the rendezvous technique. RESULTS: There were 64 patients in the preoperative ERCP group and 59 patients in the intraoperative ERCP group. The demographic and clinical characteristics of the two groups were similar, except that the bilirubin and gamma-glutamyl transferase (GGT) levels and the number of patients treated on an inpatient basis were higher in the preoperative ERCP group. Success rates were similar (96.6 % in the preoperative ERCP group vs. 90.2 % in the intraoperative ERCP group in the per-protocol study). Total morbidity, post-ERCP morbidity, and post-ERCP acute pancreatitis rates were higher in the preoperative ERCP group, but there were no differences between the two groups in the frequency of residual common bile duct stones, the conversion rate to open cholecystectomy, or surgical morbidity. The length of hospital stay and costs were lower in the intraoperative ERCP group despite the longer surgical times in this group. Univariate analysis did not find any relationship between morbidity and total bilirubin or GGT. Logistic regression analysis confirmed that morbidity was related only to the treatment group and the time spent in the operating room: the relative risk (RR) was 4.37 for morbidity and 1.015 for the time spent in the operating room); the RR for papillotomy was 5.49. CONCLUSIONS: Both treatment approaches were equally effective but the intraoperative ERCP group had less morbidity, a shorter hospital stay, and reduced costs. The lower morbidity in the intraoperative ERCP group resulted from the lower rate of papillotomy and lower rates of post-ERCP pancreatitis and cholecystitis. Total morbidity was principally related to the type of treatment approach used.

Adolescent exposure to nicotine modifies acute functional responses to cannabinoid agonists in rats.

We have studied functional interactions between nicotine and the cannabinoid receptor agonist CP 55,940 (CP) in the modulation of behavioural and corticosterone responses of male and female adolescent Wistar rats. The animals underwent a subchronic nicotine treatment (0.4 mg/kg i.p., once daily) during the periadolescent period (postnatal days 34-43). Twenty-four hours after the last injection of nicotine an acute dose of CP (1 or 100 microg/kg i.p.) was administered. Thirty minutes after the cannabinoid injection, the animals were tested individually in the holeboard immediately followed by the elevated plus-maze. We also measured corticosterone levels by radioimmunoassay. In males, neither CP (1 microg/kg) nor nicotine induced any modification in anxiety when administered alone. However, the combination of the two drugs resulted in a significant anxiogenic-like effect. In females, the lower dose of CP was anxiogenic and nicotine, which did not induce any effect per se, prevented this response. In the holeboard, subchronic nicotine and the acute cannabinoid treatment interacted in the modulation of horizontal activity and the nature of this interaction also showed a clear sexual dimorphism. Both, the cannabinoid agonist and nicotine increased corticosterone concentrations and the animals receiving the two drugs showed higher levels than the animals receiving the cannabinoid alone. The data provide evidence for the existence of functional interactions between nicotine and cannabinoids in the modulation of behavioural responses and adrenocortical activity in adolescent rats.