Metabolism of renin-angiotensin and enkephalin in human follicular fluid: An experimental study.

Background: The relationship between the biochemical characteristics of follicular fluid (FF), oocyte quality and embryonic development has not yet been elucidated. We compared samples of FF with a normal metabolic profile against samples with metabolic abnormalities to identify potential predictive biomarkers of reproductive success. Objective: To analyze peptide activity in the FF of women undergoing in vitro fertilization using 3 samples of FF per individual. Materials and Methods: FF samples were obtained by ovum pick-up. Pathological samples were defined as samples of FF obtained from women with a gynecological condition or with infertility. A total of 30 women participated in this study. 3 samples of FF were obtained per individual (90 samples), but 8 samples were excluded because they were hemolyzed. The samples (n = 82 FF) included controls (n = 36, donors without fertility problems), women with endometriosis (n = 15), unexplained infertility (n = 19), and aged > 39 (n = 12). We assessed local encephalinergics: aminopeptidase-N (puromycin sensitive aminopeptidase and neutral endopeptidase; and components of the angiotensin system of the reproductive tract: prolyl-endopeptidase, APN, aspartate-aminopeptidase, and basic-aminopeptidase. Results: No differences were observed in peptide metabolism based on the presence or absence of oocytes in the FF. Women with endometriosis and aged > 39 yr showed alterations in puromycin sensitive aminopeptidase (p = 0.01), aminopeptidase-B (p = 0.01), aspartate-aminopeptidase (p < 0.001) and neutral endopeptidase (p < 0.001). Conclusion: This study reveals alterations in the metabolism of enkephalin and angiotensin in pathological FF, which points to these components as potential diagnostic biomarkers.

Características clínicas y radiológicas de las malformaciones pulmonares congénitas: reporte de cuatro casos en un centro de tercer nivel de la ciudad de México / Clinical and radiological characteristics of congenital lung malformations: report of four cases in a third - level center in Mexico city

Las malformaciones pulmonares congénitas (MPC) conforman un grupo de entidades originadas por alteraciones en la embriogénesis del pulmón y de las vías respiratorias que se producen de acuerdo al nivel del árbol traqueobronquial donde se dé el insulto o el momento de la edad gestacional. Las entidades que en la actualidad forman parte de las MPC son: malformación congénita de la vía aérea, secuestro pulmonar, quiste broncogénico, enfisema lobar congénito, atresia bronquial. Su diagnóstico puede realizarse desde la etapa prenatal, al momento del nacimiento, en la edad pediátrica o adulta por la aparición de síntomas o incidentalmente en pruebas radiológicas. El manejo de estas lesiones depende del tipo de malformación y de la severidad de los síntomas, por lo que se debe individualizar la conducta a seguir en cada caso. Aunque la mayoría de los autores recomienda la resección de la lesión, no existe en la actualidad un consenso sobre la indicación de cirugía, sobre todo en pacientes asintomáticos. Nuestro objetivo es describir los hallazgos clínicos, radiológicos y en algunos casos anatomopatológicos así como el tratamiento empleado de cuatro casos clínicos, atendidos en un hospital de tercer nivel que ejemplifican las presentaciones más frecuentes de las MPC.

Congenital pulmonary malformations (CPM) make up a group of entities caused by alterations in the embryogenesis of the lung and the respiratory tract that occur according to the level of the tracheobronchial tree where the insult occurs or the moment of gestational age. The entities that are currently part of the CPM are: congenital malformation of the airway, pulmonary sequestration, bronchogenic cyst, congenital lobar emphysema, bronchial atresia. Its diagnosis can be made from the prenatal stage, at birth or in pediatric or adult age due to the appearance of symptoms or incidentally in radiological tests. The management of these injuries depends on the type of malformation and the severity of the symptoms, so the conduct to be followed in each case must be individualized. Although most authors recommend resection of the lesion, there is currently no consensus on the indication for surgery, especially in asymptomatic patients. Our objective is to describe the clinical, radiological and in some cases histopathological findings, as well as the treatment used in four clinical cases, treated in a tertiary level hospital that exemplify the most frequent presentations of MPC.

Activated gut-homing CD8+ T cells for coeliac disease diagnosis on a gluten-free diet.

BACKGROUND: The diagnosis of coeliac disease (CD) in individuals that have started a gluten-free diet (GFD) without an adequate previous diagnostic work-out is a challenge. Several immunological assays such as IFN-γ ELISPOT have been developed to avoid the need of prolonged gluten challenge to induce the intestinal damage. We aimed to evaluate the diagnostic accuracy of activated gut-homing CD8+ and TCRγδ+ T cells in blood after a 3-day gluten challenge and to compare it with the performance of IFN-γ ELISPOT in a HLA-DQ2.5 subsample. METHODS: A total of 22 CD patients and 48 non-CD subjects, all of them following a GFD, underwent a 3-day 10-g gluten challenge. The percentage of two T cell subsets (CD8+ CD103+ ß7hi CD38+/total CD8+ and TCRγδ+ CD103+ ß7hi CD38+/total TCRγδ+) in fresh peripheral blood drawn baseline and 6 days after the challenge was determined by flow cytometry. IFN-γ ELISPOT assays were also performed in HLA-DQ2.5 participants. ROC curve analysis was used to assess the diagnostic performance of the CD8+ T cell response and IFN-γ ELISPOT. RESULTS: Significant differences between the percentage of the two studied subsets of CD8+ and TCRγδ+ cells at days 0 and 6 were found only when considering CD patients (p < 10-3 vs. non-CD subjects). Measuring activated CD8+ T cells provided accurate CD diagnosis with 95% specificity and 97% sensitivity, offering similar results than IFN-γ ELISPOT. CONCLUSIONS: The results provide a highly accurate blood test for CD diagnosis in patients on a GFD of easy implementation in daily clinical practice.

Sentido y significado de vejez de los residentes de la calle Zanja, 2017-2019 / Sense and meaning of old age of residents in Zanja Street, 2017-2019

Introducción: En Cuba, en el 2016, las personas mayores de 60 años constituían el 19,8 por ciento de la población, y La Habana era una de las provincias más envejecidas. En 2018 aumentó a 20,4 por ciento. En la calle Zanja, residen pobladores de distintos grupos étnicos, con herencias y tradiciones culturales diversas y diferentes visiones del sentido y significado de vejez. Objetivo: Caracterizar el sentido de vejez de los adultos mayores y el significado de vejez de los niños, adolescentes, jóvenes y adultos medios, residentes en la calle Zanja. Métodos: Se realizó un estudio exploratorio, a partir de una metodología mixta: cualitativa y cuantitativa. Se utilizó el método observacional y, en consecuencia, se decidió hacer uso de las técnicas de entrevista en profundidad, la observación no participante, con sus correspondientes guías, la técnica porcentual y la triangulación de datos. Resultados: Los adultos mayores manifestaron satisfacción de las necesidades materiales y espirituales en un alto nivel; aunque el 50 por ciento de los jubilados declaró no recibir atención de las organizaciones a las que pertenecían. Un alto porcentaje de adultos medios opinaron que los adultos mayores son personas importantes y útiles, tienen experiencia y constituyen ayuda. Los niños, adolescentes y jóvenes refirieron que lo que más les gusta de sus abuelos es que los quieren y los ayudan y lo que no les gusta es que pelean y se enferman. Conclusiones: Si los adultos mayores son importantes para las familias, comunidad y sociedad, es preciso mejorar las condiciones materiales de su existencia y del entorno y que se sientan reconocidos por sus aportes(AU)

Introduction: In Cuba, in 2016, people over the age of 60 made up 19.8 percent of the population, and Havana was one of the most aged provinces. In 2018 it increased to 20.4 percent. In Zanja Street, people of different ethnic groups reside, with diverse cultural heritage and traditions and different visions of the sense and meaning of old age. Objective: Characterize the sense of old age of older adults and the old-age meaning of children, adolescents, young people and average adults, residing on Zanja Street. Methods: An exploratory study was carried out, based on a mixed methodology: qualitative and quantitative. he observational method was used and, consequently, it was decided to make use of in-depth interview techniques, non-participating observation, with their corresponding guidelines, percentage technique and data triangulation. Results: Older adults expressed satisfaction with material and spiritual needs at a high level; although 50 percent of retirees reported not receiving care from the organizations to which they belonged. A high percentage of average adults said that older adults are important and useful people, they have experience and are helpful. Children, teenagers and young people said that what they love most about their grandparents is that they love and help them and what they don't like is that they argue and get sick. Conclusions: If older adults are important to the families, communities and the society, the material conditions of their life and environment need to be improved, and so they can feel acknowledge for their contributions(AU)

Dolor y analgésicos. Algunas consideraciones oportunas / Pain and painkillers. Some timely considerations

RESUMEN El dolor ha acompañado a la humanidad desde épocas remotas hasta la actualidad; síntoma muy frecuente observado en todos los niveles de salud, y en que la medicina presenta éxitos y fracasos, por lo que preocupa y ocupa en forma permanente a los investigadores. Su atención desde el punto de vista asistencial se hace complejo por la variedad de factores que lo condicionan. El enfoque terapéutico de ese síntoma debe apoyarse en el conocimiento de la fisiopatología y el empleo de medios que permitan hacer una valoración de su origen y evolución para adecuar las estrategias analgésicas que correspondan. En este trabajo se realiza una revisión sobre los aspectos antes mencionados en relación con el dolor.

ABSTRACT Pain has accompanied humanity from remote times to the present day; this is a very well- frequent symptom in health levels, where medicine presents successes and failures. For this reason it is a permanent researchers´ concern and occupation. Assisting pain is complex due to the variety of factors which conditions it. Therapeutic approach to this symptom must be based on pathophysiology knowledge and the use of means that allow assessing its origin and progress to adapt the corresponding analgesic strategies. In this work, a review is made on the aforementioned aspects in relation to pain.

The Pharmacological Inhibition of Fatty Acid Amide Hydrolase Prevents Excitotoxic Damage in the Rat Striatum: Possible Involvement of CB1 Receptors Regulation.

The endocannabinoid system (ECS) actively participates in several physiological processes within the central nervous system. Among such, its involvement in the downregulation of the N-methyl-D-aspartate receptor (NMDAr) through a modulatory input at the cannabinoid receptors (CBr) has been established. After its production via the kynurenine pathway (KP), quinolinic acid (QUIN) can act as an excitotoxin through the selective overactivation of NMDAr, thus participating in the onset and development of neurological disorders. In this work, we evaluated whether the pharmacological inhibition of fatty acid amide hydrolase (FAAH) by URB597, and the consequent increase in the endogenous levels of anandamide, can prevent the excitotoxic damage induced by QUIN. URB597 (0.3 mg/kg/day × 7 days, administered before, during and after the striatal lesion) exerted protective effects on the QUIN-induced motor (asymmetric behavior) and biochemical (lipid peroxidation and protein carbonylation) alterations in rats. URB597 also preserved the structural integrity of the striatum and prevented the neuronal loss (assessed as microtubule-associated protein-2 and glutamate decarboxylase localization) induced by QUIN (1 µL intrastriatal, 240 nmol/µL), while modified the early localization patterns of CBr1 (CB1) and NMDAr subunit 1 (NR1). Altogether, these findings support the concept that the pharmacological manipulation of the endocannabinoid system plays a neuroprotective role against excitotoxic insults in the central nervous system.

Comparing the Effects of Chlorogenic Acid and Ilex paraguariensis Extracts on Different Markers of Brain Alterations in Rats Subjected to Chronic Restraint Stress.

Positive influence of yerba mate (Ilex paraguariensis) on human health issues has been attributed to its frequent consumption in South American countries and is assumed to be due to its high content of antioxidant compounds, including chlorogenic acid (CGA); however, hard evidence about its positive effects under chronic stress conditions is still required. In this study, the effects of yerba mate extracts (IpE), and its main compound chlorogenic acid (CGA), on behavioral and morphological endpoints of brain damage induced by chronic restraint stress (CRS) to rats were evaluated and compared. CRS sessions were performed during 21 days. IpE (200 mg/mL, p.o.) or CGA (2 mg/mL, p.o.) were administered daily 30 min before stress. Behavioral tests comprised motor skills and anxiety-like activity. Histological (H&E) and histochemical changes were explored in three brain regions: cortex (Cx), hippocampus (Hp), and striatum (S). Rats subjected to CRS exhibited hypoactive patterns of locomotor activity. Rats receiving IpE before CRS preserved the basal locomotor activity. Stressed animals also augmented the anxiety-like activity, whereas IpE normalized exploratory behavior. Stressed animals presented cell damage in all regions. Morphological damage was more effectively prevented by IpE than CGA. Stressed animals also augmented the expression/localization pattern of the tumor necrosis factor alpha in the striatum and the expression of the glial fibrillary acidic protein in the hippocampus (stratum moleculare) and cortex, whereas IpE and CGA reduced the expression of these molecules. In turn, CGA exhibited only moderate protective effects on all markers analyzed. Our findings support a protective role of IpE against CRS, which may be related to the antioxidant and anti-inflammatory properties of its compounds. Since CGA was unable to prevent all the alterations induced by CRS, it is concluded that the protective properties of the whole extract of Ilex paraguariensis are the result of the combined effects of all its natural antioxidant compounds, and not only of the properties of CGA.

Rotura de pseudoaneurisma de arteria uterina tras cesárea / Uterine artery pseudoaneurysm rupture after cesarean section

RESUMEN El pseudoaneurisma de arteria uterina es una causa de hemorragia puerperal poco frecuente y de gran gravedad cuya principal manifestación es el sangrado puerperal tardío. Esta complicación suele ocurrir de manera tardía tras una cirugía pélvica, aunque también está descrito tras el parto. La prueba de elección para el diagnóstico de esta complicación es la angiografía que permite además su tratamiento en el mismo acto, asociando una menor morbilidad y preservando la fertilidad de la paciente. Presentamos el caso de un pseudoaneurisma de arteria uterina tras cesárea cuya manifestación fue un hemoperitoneo masivo a los 17 días de la cesárea y que se resolvió mediante angiografía con embolización supraselectiva del mismo.

ABSTRACT Uterine artery pseudoaneurysm is a serious complication but an uncommon cause of postpartum haemorrhage which can mainly manifest as a severe bleeding in the late puerperium. This complication usually occurs after pelvic surgery, although it is also described after vaginal delivery. Angiography is the best diagnosis method which joins not only the diagnosis but also the treatment at the same moment, reducing the morbidity and preserving fertility. We report a case of a uterine artery pseudoaneurysm after cesarean delivery whose clinical manifestation was a massive haemoperitoneum after 17 days of the cesarean. It was treated by angiographic selective embolization of uterine artery pseudoaneurysm.

Percepción de valores y antivalores coexistentes en el sector salud / Perception about the existing and coexisting values and anti-values in the health sector

Introducción: se muestran resultados de una investigación realizada en 4 facultades de Ciencias Médicas de La Habana y sus escenarios docentes en el periodo 2012-2014. Objetivo: explorar los valores éticos sociales y profesionales consensuados por docentes, estudiantes, profesionales, directivos y usuarios del sector salud e identificar los antivalores coexistentes. Métodos: se utilizó una metodología cualitativa, seleccionando intencionalmente una muestra correspondiente al 57 por ciento del universo de estudio, con quienes se aplicaron variadas técnicas: grupo focal y proyectiva, observación participante, encuesta y técnica de Delphi. Resultados: existió consenso en la percepción de los valores honestidad y responsabilidad coexistiendo con el antivalor deshonestidad; el valor solidaridad con antivalor egoísmo; valor responsabilidad con antivalor irresponsabilidad y valor humanismo con antivalores desidia e indiferencia. Según los expertos, las principales causas de desmotivación de los profesionales son los bajos salarios, insuficientes condiciones de trabajo y poco reconocimiento social. Conclusiones: se propone fortalecer los valores éticos ciudadanos y profesionales y combatir los antivalores. Corresponde a los decisores trazar estrategias para enfrentar las insuficiencias con la participación de los profesionales comprometidos con una mejor calidad y eficiencia de los servicios y una mayor satisfacción de los usuarios(AU)

Introduction: results are shown of a research carried out in the period from 2012 to 2014 in four Havana School of Medical Sciences and their teaching campuses. Objective: to explore the ethical, social and professional values agreed upon by teachers, students, professionals, managers and users of the health area and to identify the coexisting anti-values. Methods: a qualitative methodology was used, intentionally selecting a sample corresponding to 57 percent of the study total sample, on whom several techniques were applied: projective and focal group, participant observation, survey. and the Delphi technique. Results: there was consensus in the perception of the values of honesty and responsibility, as coexisting with the anti-value dishonesty; the value of solidarity, with anti-value selfishness; the value of responsibility, with anti-value irresponsibility, and the value of humanism with the anti-values apathy and indifference. According to the experts, the main causes of demotivation of professionals are low wages, insufficient working conditions, and little social recognition. Conclusions: the ethical values of citizens and professionals has been proposed to be strengthened, together with confronting anti-values. The decision-makers are in now in charge of drawing up strategies to put up with the shortcomings, by means of the participation of the professionals committed to better quality and efficiency of the services and greater satisfaction of the users(AU)

The Antiepileptic Drug Levetiracetam Protects Against Quinolinic Acid-Induced Toxicity in the Rat Striatum.

Levetiracetam (LVT) is a relatively novel antiepileptic drug (AED) known to act through binding with the synaptic vesicular 2A (SV2A) protein, thus modulating the presynaptic neurotransmitter release. The tryptophan metabolite quinolinic acid (QUIN) acts as an excitotoxin when its brain concentrations reach toxic levels under pathological conditions. Since increased neuronal excitability induced by QUIN recruits degenerative events in the brain, and novel AED is also expected to exert neuroprotective effects in their pharmacological profiles, in this work the effect of LVT (54 mg/kg, i.p., administered for seven consecutive days) was tested as a pretreatment against the toxicity evoked by the bilateral intrastriatal injection of QUIN (60 nmol/µl) to adult rats. QUIN increased the striatal levels of peroxidized lipids and carbonylated proteins as indexes of oxidative damage 24 h after its infusion. In addition, in synaptosomal fractions isolated from QUIN-lesioned rats 24 h after the toxin infusion, γ-aminobutyric acid (GABA) release was decreased, whereas glutamate (Glu) release was increased. QUIN also decreased motor activity and augmented the rate of cell damage at 7 days post-lesion. All these alterations were significantly prevented by pretreatment of rats with LVT. The results of this study show a neuroprotective role and antioxidant action of LVT against the brain damage induced by excitotoxic events.

A retrospective study on the management of patients with rituximab refractory follicular lymphoma.

Given that there are currently no clear recommendations regarding therapeutic options for rituximab refractory/relapsed follicular lymphoma patients, this study aimed to describe the real-life management of patients with refractory follicular lymphoma after systemic rituximab-containing regimens (rFL), and rFL patient characteristics. In this retrospective, national, multicentre study, descriptive analyses were mainly performed according to rituximab-containing regimen at rFL diagnosis [rituximab monotherapy (R-MONO), rituximab + chemotherapy (R-COMBO), and ongoing rituximab maintenance (R-MAINTAIN)]. The 459 analysed patients experienced rituximab-refractoriness between October 2013 and September 2015: R-MONO: 58 (13%), R-COMBO: 197 (43%), R-MAINTAIN: 204 (44%). Post-refractoriness strategies were heterogeneous: idelalisib ± rituximab (22%), without anti-lymphoma treatment (21%), rituximab-chemotherapy (21%) and stem cell transplantation (18%). Rituximab was continued in combination in 41% of cases. Chosen strategies varied according to patient age (without anti-lymphoma treatment: 28% of patients if ≥65 years vs. 12% if <65 years old; stem-cell transplantation: 4% vs. 38%), treatment line at rFL, FL International Prognostic Index score and prior treatment. This French retrospective study, the first one conducted in a large cohort of rFL patients, showed that further strategies were highly heterogeneous, depending notably on patient characteristics and previous treatment. These data are the basis for a better understanding of rFL management and for the design of clinical trials in these patients.

Neuropharmacological and neuroprotective activities of some metabolites produced by cell suspension culture of Waltheria americana Linn.

Waltheria americana is a plant used in Mexican traditional medicine to treat some nervous system disorders. The aims of the present study were to isolate and determine the neuropharmacological and neurprotective activities of metabolites produced by a cell suspension culture of Waltheria americana. Submerged cultivation of W. americana cells provided biomass. A methanol-soluble extract (WAsc) was obtained from biomass. WAsc was fractionated yielding the chromatographic fractions 4WAsc-H2O and WAsc-CH2Cl2. For the determination of anticonvulsant activity in vivo, seizures were induced in mice by pentylenetetrazol (PTZ). Neuropharmacological activities (release of gamma amino butyric acid (GABA) and neuroprotection) of chromatographic fractions were determined by in vitro histological analysis of brain sections of mice post mortem. Fraction 4WAsc-H2O (containing saccharides) did not produce neuronal damage, neurodegeneration, interstitial tissue edema, astrocytic activation, nor cell death. Pretreatment of animals with 4WAsc-H2O and WAsc-CH2Cl2 from W. americana cell suspensions induced an increase in: GABA release, seizure latency, survival time, neuroprotection, and a decrease in the degree of severity of tonic/tonic-clonic convulsions, preventing PTZ-induced death of up to 100% of animals of study. Bioactive compounds produced in suspension cell culture of W. americana produce neuroprotective and neuropharmacological activities associated with the GABAergic neurotransmission system.

Manejo anestésico de atresia esofágica y fistula traqueoesofágica. Presentación de un caso / Anesthesia management of esophageal atresia and tracheoesophageal fistula in neonates. Case presentation

La atresia esofágica es una malformación congénita infrecuente incompatible con la vida y una urgencia quirúrgica neonatal. La presentación más común es la atresia esofágica con fístula traqueoesofágica distal (80-90 % de los casos). Tiene una frecuencia de presentación de uno por cada 3000 nacimientos. Por estas razones se presenta el caso de un neonato pretérmino, femenina, de 48 horas de nacimiento, 1245 gramos de peso, APGAR 8/9, con diagnóstico de atresia esofágica y fístula traqueoesofágica tipo lllb/C. Fue diagnosticada al nacimiento, ante la presencia de vómito en proyectil, distrés respiratorio e imposibilidad de introducir una sonda nasogástrica y confirmada al observarse en una radiografía de tórax. Fue anunciada para cirugía en la cual se efectuó reparación de la fistula. Se exponen las consideraciones anestésicas a seguir en el manejo de este caso, relacionadas con: los fármacos anestésicos, reposición de volumen y la estrategia de ventilación mecánica. Se obtuvieron resultados favorables.

Esophageal atresia is an infrequent congenital malformation incompatible with life and a neonatal surgical urgency. The most common presentation is esophageal atresia with distal tracheoesophageal fistula (80-90 % of cases). It presents in one of every 3000 births. For these reasons, the case of a preterm infant, 48 hours of birth, 1245 grams weight, APGAR 8/9, with diagnosis of esophageal atresia and tracheo-esophageal fistula type lllb / C is presented. She was diagnosed at birth, due to the presence of projectile vomiting, respiratory distress and the impossibility of introducing a naso-gastric tube and confirmed when seen on a chest x-ray. It was announced for surgery in which fistula repair was performed. We present the anesthetic considerations to be followed in the management of this case, related to: anesthetic drugs, volume replacement and mechanical ventilation strategy. Favorable results were obtained.

Estudiantes de la facultad de ciencias médicas "General Calixto García" crean situaciones problémicas com sus experiencias / Students of the faculty of medical sciences "General Calixto García" create problematic situations with their experiences

la motivación y participación de los estudiantes desde el inicio de la actividad docente de forma que los atrape y los convierta en protagonistas del proceso. Diseñar una estrategia de aprendizaje con la construcción de un pensamiento analítico que permita contemplar el paso del desarrollo polémico emocional al cognitivo fue el propósito del estudio. Utilizar las vivencias de los estudiantes para motivarlos e introducir aspectos nuevos de la conferencia. Se elaboró en el colectivo una guía para dirigir la creación por los estudiantes de escenarios donde ellos fueran los protagonistas del hacer. El algoritmo de trabajo era: Seleccionar una enfermedad en base a la experiencia vivida en cada grupo orientándolo en dependencia de la especialidad o pudiera ser una enfermedad adquirida en el trabajo. Con la caracterización humana del paciente sus sueños, gustos, aspiraciones, edad. Primeros síntomas, cómo se diagnosticó, repercusión en su vida social, afectiva y desenlace. Para construir la triada ecológica, clasificación, variabilidad de respuesta, conceptos específicos y medidas de prevención. El resultado principal obtenido es a través de sus emociones lograr la participación activa de los estudiantes y arribar al conocimiento deseado.(AU)

Neuroprotective effect of WIN55,212-2 against 3-nitropropionic acid-induced toxicity in the rat brain: involvement of CB1 and NMDA receptors.

The endocannabinoid system (ECS), and agonists acting on cannabinoid receptors (CBr), are known to regulate several physiological events in the brain, including modulatory actions on excitatory events probably through N-methyl-D-aspartate receptor (NMDAr) activity. Actually, CBr agonists can be neuroprotective. The synthetic CBr agonist WIN55,212-2 acts mainly on CB1 receptor. In turn, the mitochondrial toxin 3-nitropropionic acid (3-NP) produces striatal alterations in rats similar to those observed in the brain of Huntington's disease patients. Herein, the effects of WIN55,212-2 were tested on different endpoints of the 3-NP-induced toxicity in rat brain synaptosomes and striatal tissue. Motor activity was also evaluated. The 3-NP (1 mM)-induced mitochondrial dysfunction and lipid peroxidation was attenuated by WIN55,212-2 (1 µM) in synaptosomal fractions. The intrastriatal bilateral injection of 3-NP (500 nmol/µL) to rats increased lipid peroxidation and locomotor activity, augmented the rate of cell damage, and decreased the striatal density of neuronal cells. These alterations were accompanied by transcriptional changes in the NMDA (NR1 subunit) content. The administration of WIN55212-2 (1 mg/kg, i.p.) to rats for six consecutive days, before the 3-NP injection, exerted preventive effects on all alterations elicited by the toxin. The prevention of the 3-NP-induced NR1 transcriptional alterations by the CBr agonist together with the increase of CB1 content suggest an early reduction of the excitotoxic process via CBr activation. Our results demonstrate a protective role of WIN55,212-2 on the 3-NP-induced striatal neurotoxicity that could be partially related to the ECS stimulation and induction of NMDAr hypofunction, representing an effective therapeutic strategy at the experimental level for further studies.

Restricción del ductus arterioso fetal en gestante de tercer trimestre por consumo de paracetamol / Fetal Ductus Arteriosus Restriction in the Final Third of Pregnancy Due To Acetaminophen Consumption

Se presenta el caso de una paciente que desde la semana 20 de gestación fue diagnosticada de cólico renal con la necesidad de varios ingresos y colocación de catéter doble J por parte de Urología. La paciente recibió tratamiento con paracetamol intravenoso y oral. Los controles ecográficos obstétricos -a los largo de la gestación- fueron normales hasta que en la semana 32, cuando ingresó de nuevo por cuadro sospechoso de cólico renal tratado con Paracetamol. Se objetivan en ecografía con hallazgos compatibles con restricción precoz del ductus arterioso. Se indicó la suspensión del paracetamol y los cambios se redujeron en las 48 horas posteriores y casi desaparecieron por completo una semana tras la retirada de la medicación. La gestación llegó a término y el recién nacido presentó un ecocardiograma posnatal normal. Recomendamos la restricción de los analgésicos no opiáceos en el tercer trimestre y el seguimiento con Doppler del conducto arterioso en los casos en que se requiriera usarlos(AU)

A case is reported of a pregnant woman who was diagnosed with renal colic at 20 weeks of gestation. She needed various admissions in hospital and double J stent placement by Urology Service and she was treated with acetaminophen by both intravenous and oral ways. Obstetric ultrasound scans were normal throughout gestation until week 32, when she was admitted to hospital again for suspected renal colic. She was treated with acetaminophen. In that moment, ultrasound findings are consisted with early ductus arteriosus constriction. Acetaminophen was decided to be stopped and changes reduced in the first 48 hours and they almost disappeared after one week of medication withdrawal. Pregnancy came to term and the child was born normal. Restricting non-opioid analgesics was recommended in the third quarter, as well as following up with ductus arteriosus doppler in cases in which it is required to use them(AU)

URB597 reduces biochemical, behavioral and morphological alterations in two neurotoxic models in rats.

BACKGROUND: URB597 is a compound largely linked to the inhibition of fatty acid amide hydrolase (FAAH), an enzyme responsible for the metabolic degradation of the endocannabinoid anandamide (AEA). Despite this pharmacological property accounts for its modulatory profile demonstrated in some neurotoxic paradigms, the possible protective properties of this agent have been poorly investigated, and deserve exploration in different neurotoxic models. In this study, we explored the effects of URB597 on oxidative damage to lipids and other major endpoints of toxicity in two neurotoxic models in vivo in rats (the first one produced by the mitochondrial neurotoxin 3-nitropropionic acid [3-NP], and the other generated by the striatal injection of the pro-oxidant toxin 6-hydroxidopamine [6-OHDA]) in order to provide further supporting evidence of its modulatory profile. METHODS: Male Wistar adult rats were treated for 5 or 7 consecutive days with URB597 (0.3mg/kg, i.p.) and simultaneously exposed to three injections of 3-NP (30mg/kg, i.p.) or a single intrastriatal infusion of 6-OHDA (0.02mg/2µl), respectively. Twenty four hours after all treatments were administered, lipid peroxidation was measured in the striatum of 3-NP-treated rats, and in the midbrain of 6-OHDA-treated rats. Motor skills and histological assessment in the striatum were also evaluated in 3-NP-treated rats 6 and 7days after the last drug administration, respectively; whereas apomorphine-induced circling behavior and tyrosine hydroxylase immunolocalization in the striatum and substantia nigra were investigated 21 and 22days after the last drug infusion, respectively. RESULTS: URB597 prevented the oxidative damage to lipids induced by 3-NP in the striatum, and this effect could account for the attenuation of motor deficits in this model. Attenuation of motor disturbances induced by URB597 in both models was associated with the morphological preservation of the striatum in the 3-NP model and the partial preservation of tyrosine hydroxylase in the 6-OHDA model in the SNpc and striatum. CONCLUSION: The modulatory actions exerted by URB597 in both toxic models support its potential against toxic conditions implying motor and neurochemical alterations linked to energy depletion, excitotoxicity and oxidative stress. Although most of these effects could be attributable to its action on FAAH and further AEA accumulation, in light of our present findings other properties are suggested.

Restricción del ductus arterioso fetal en gestante del tercer trimestre por consumo de paracetamol / Fetal ductus arteriosus constriction in the final third of pregnancy due to paracetamol comsumption

El ductus arterioso es una derivación que conecta la arteria pulmonar con el arco aórtico el que permite la descarga del ventrículo derecho sin pasar por la alta resistencia de los pulmones. La permeabilidad del conducto arterioso se mantiene durante la gestación por las prostaglandinas producidas especialmente PGE2, que circulan a nivel local, especialmente PGE2, y la baja saturación de oxígeno fetal. Se trata de una paciente que desde la semana 20 de gestación es diagnosticada de cólico renal con la necesidad de varios ingresos y colocación de catéter doble J por parte de Urología y la cual recibió tratamiento con paracetamol intravenoso y oral. Los controles ecográficos obstétricos a los largo de la gestación fueron normales hasta que en semana 32, cuando ingresa de nuevo por cuadro sospechoso de cólico renal tratado con Paracetamol, se objetivan en ecografía hallazgos compatibles con restricción precoz del ductus arterioso. Se indicó suspender el paracetamol y los cambios se redujeron en las 48 horas posteriores y casi desaparecieron por completo una semana tras la retirada de la medicación. La gestación llegó a término y el recién nacido presentó un ecocardiograma postnatal normal. Recomendamos la restricción de los analgésicos no opiáceos en el tercer trimestre y el seguimiento con Doppler del conducto arterioso en los casos en que se requiriera usarlos(AU)

Ductus arteriosus is a derivation that connects the pulmonary artery with the aortic arch and allows the discharge from the right ventricle without passing the high resistance of lungs. Permeability of the ductus arteriosus is kept during gestation because of the production of prostaglandins, particularly PGE2, which circulates locally, and the low fetal oxygen saturation. Here is a pregnant woman who, since her 20th week of gestation was diagnosed as a renal colic case. She required several admissions to hospital and placement of double J stent in the urology service and she was treated with intravenous and oral paracetamol. Obstetric ultrasound scans throughout gestation were normal until week 32, when she was admitted to hospital again for suspected renal colic and treated again with paracetamol. At that moment, findings compatible with early ductus arteriosus constriction were observed in ultrasound. It was then decided to stop the paracetamol treatment, the changes declined in the following 48 hours and they almost disappeared completely after one week after the medication withdrawal. It was finally a term pregnancy and the postnatal echocardiogram of the newborn was normal. Restricting non-opioid analgesics in the third pregnancy trimester and the follow up of the ductus arteriosus with Doppler technique when required(AU)

The N-Methyl-d-Aspartate Receptor Antagonist MK-801 Prevents Thallium-Induced Behavioral and Biochemical Alterations in the Rat Brain.

Thallium (Tl(+)) is a toxic heavy metal capable of increasing oxidative damage and disrupting antioxidant defense systems. Thallium invades the brain cells through potassium channels, increasing neuronal excitability, although until now the possible role of glutamatergic transmission in this event has not been investigated. Here, we explored the possible involvement of a glutamatergic component in the Tl(+)-induced toxicity through the N-methyl-d-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) in rats. The effects of MK-801 (1 mg/kg, intraperitoneally [ip]) on early (24 hours) motor alterations, lipid peroxidation, reduced glutathione (GSH) levels, and GSH peroxidase activity induced by Tl(+) acetate (32 mg/kg, ip) were evaluated in adult rats. MK-801 attenuated the Tl(+)-induced hyperactivity and lipid peroxidation in the rat striatum, hippocampus and midbrain, and produced mild effects on other end points. Our findings suggest that glutamatergic transmission via NMDA receptors might be involved in the Tl(+)-induced altered regional brain redox activity and motor performance in rats.