[History of child abuse among patients with bipolar disorders]. / El maltrato infantil y su rol en el curso clínico de pacientes con trastorno bipolar.

BACKGROUND: A history of child abuse is common and has a significant impact in the clinical course of patients diagnosed with bipolar disorders (BD). AIMS: To assess the frequency of child abuse experiences in patients BD type I and to evaluate its association with clinical course and cognitive functioning variables. MATERIAL AND METHODS: 117 patients with BD aged 45 ± 14 years (66% women) answered the Childhood Trauma Questionnaire (CTQ). The clinical course (illness onset, history of suicide attempts and number of hospitalizations) was obtained from medical records. Cognitive functioning was evaluated through social and non-social cognition tasks. RESULTS: 64% of participants reported some type of child abuse. This variable was associated with an early onset of the disease (Odds ratio (OR) = 3.3; p < 0.02), increased risk of suicide attempts (OR = 2.4; p < 0.04) and specific disturbances in social cognitive tasks. CONCLUSIONS: Our study supports evidence of a common history of child abuse in patients with BD. Although child abuse predicts a worse clinical course, major clinical practice guidelines, as well as research designs, do not highlight this evidence.

Complement peptide C3a stimulates neural plasticity after experimental brain ischaemia.

Ischaemic stroke induces endogenous repair processes that include proliferation and differentiation of neural stem cells and extensive rewiring of the remaining neural connections, yet about 50% of stroke survivors live with severe long-term disability. There is an unmet need for drug therapies to improve recovery by promoting brain plasticity in the subacute to chronic phase after ischaemic stroke. We previously showed that complement-derived peptide C3a regulates neural progenitor cell migration and differentiation in vitro and that C3a receptor signalling stimulates neurogenesis in unchallenged adult mice. To determine the role of C3a-C3a receptor signalling in ischaemia-induced neural plasticity, we subjected C3a receptor-deficient mice, GFAP-C3a transgenic mice expressing biologically active C3a in the central nervous system, and their respective wild-type controls to photothrombotic stroke. We found that C3a overexpression increased, whereas C3a receptor deficiency decreased post-stroke expression of GAP43 (P < 0.01), a marker of axonal sprouting and plasticity, in the peri-infarct cortex. To verify the translational potential of these findings, we used a pharmacological approach. Daily intranasal treatment of wild-type mice with C3a beginning 7 days after stroke induction robustly increased synaptic density (P < 0.01) and expression of GAP43 in peri-infarct cortex (P < 0.05). Importantly, the C3a treatment led to faster and more complete recovery of forepaw motor function (P < 0.05). We conclude that C3a-C3a receptor signalling stimulates post-ischaemic neural plasticity and intranasal treatment with C3a receptor agonists is an attractive approach to improve functional recovery after ischaemic brain injury.

Effects of Estrogen and Phytoestrogen Treatment on an In Vitro Model of Recurrent Stroke on HT22 Neuronal Cell Line.

An increase of stroke incidence occurs in women with the decline of estrogen levels following menopause. This ischemic damage may recur, especially soon after the first insult has occurred. We evaluated the effects of estrogen and phytoestrogen treatment on an in vitro recurrent stroke model using the HT22 neuronal cell line. HT22 cells were treated with 17ß-estradiol or genistein 1 h after the beginning of the first of two oxygen and glucose deprivation/reoxygenation (OGD/R) cycles. During the second OGD, there was a deterioration of some components of the electron transport chain, such as cytochrome c oxidase subunit 1 with a subsequent increase of reactive oxygen species (ROS) production. Accordingly, there was also an increase of apoptotic phenomena demonstrated by poly(ADP-ribose) polymerase 1 cleavage, Caspase-3 activity, and Annexin V levels. The recurrent ischemic injury also raised the hypoxia-inducible factor 1α and glucose transporter 1 levels, as well as the ratio between the lipidated and cytosolic forms of microtubule-associated protein 1A/1B-light chain 3 (LC3-II/LC3-I). We found a positive effect of estradiol and genistein treatment by partially preserving the impaired cell viability after the recurrent ischemic injury; however, this positive effect does not seem to be mediated neither by blocking apoptosis processes nor by decreasing ROS production. This work contribute to the better understanding of the molecular mechanisms triggered by recurrent ischemic damage in neuronal cells and, therefore, could help with the development of an effective treatment to minimize the consequences of this pathology.

Loss of GLUT4 induces metabolic reprogramming and impairs viability of breast cancer cells.

Metabolic reprogramming strategies focus on the normalization of metabolism of cancer cells and constitute promising targets for cancer treatment. Here, we demonstrate that the glucose transporter 4 (GLUT4) has a prominent role in basal glucose uptake in MCF7 and MDA-MB-231 breast cancer cells. We show that shRNA-mediated down-regulation of GLUT4 diminishes glucose uptake and induces metabolic reprogramming by reallocating metabolic flux to oxidative phosphorylation. This reallocation is reflected on an increased activity of the mitochondrial oxidation of pyruvate and lower lactate release. Altogether, GLUT4 inhibition compromises cell proliferation and critically affects cell viability under hypoxic conditions, providing proof-of-principle for the feasibility of using pharmacological approaches to inhibit GLUT4 in order to induce metabolic reprogramming in vivo in breast cancer models.

[Weight control behaviors in dieting adolescent girls and their relation to body dissatisfaction and obsession with thinness]. / Conductas de control de peso en mujeres adolescentes dietantes y su relación con insatisfacción corporal y obsesión por la delgadez.

INTRODUCTION: Obsession with thinness and body dissatisfaction can lead adolescents to follow unsupervised diets, which could result in risky weight control behaviors such as fasting, vomiting, use of diuretics and laxatives. The aim of the current study is to examine weight control behaviors in dieting adolescents and relate them to body dissatisfaction (BD) and obsession with thinness (OT). METHODS: A cross-sectional study was conducted on 439 adolescents from Valparaiso public schools to investigate risky weight control behaviors due to BD and OT scales from the Eating Disorders Inventory-2 (EDI-2), comparing restrained eaters and non-restrained eaters. RESULTS: A total of 43% adolescents had followed a weight loss diet without medical supervision. The dieters had higher BD and OT values. Moderate to severe food restriction, based on expert judgment, was observed in 29.6%, and differences in the presence and severity of purging behaviors were found between the 2 groups. CONCLUSIONS: One third of the adolescents studied followed diets without professional supervision and had higher BD and OT values, as well as risky weight control behaviors. Overweight and obese adolescents followed more restrictive diets and developed riskier weight control behaviors.

Integration of Postbiotics in Food Products through Attenuated Probiotics: A Case Study with Lactic Acid Bacteria in Bread.

The study examines the integration of postbiotics in food products through the use of attenuated probiotics, specifically lactic acid bacteria (LAB) in bread. Postbiotics, non-viable microorganisms or their metabolites, offer health benefits similar to probiotics without the risks associated with live bacteria. This research evaluates the regulatory aspects and safety of LAB in sourdough bread production, highlighting their historical and significant use in Europe before 1997. The study includes microbial quantification and Next-Generation Sequencing (NGS) to identify LAB in traditional sourdough, comparing them with historical and current EFSA Qualified Presumption of Safety (QPS) lists. Findings show that the LAB present in sourdough have been extensively and safely used in bread making, supporting their classification as non-novel foods under EU regulations. The stability and consistency of LAB metabolites in sourdough bread are also confirmed, ensuring quality and safety in each batch. The study concludes that LAB in sourdough, when inactivated through bread-making processes, are not considered novel foods, aligning with historical, scientific, and regulatory evidence.

The interaction of the oxytocin receptor gene and child abuse subtypes on social cognition in euthymic patients with bipolar disorder type I.

Background: Most studies on cognitive impairment in bipolar disorder have neglected the role of early stress, despite the high frequency of childhood maltreatment in this clinical group. The aim of this study was to establish a connection between a history of emotional, physical, and sexual abuse in childhood and social cognition (SC) in patients with bipolar disorder type I (BD-I) in euthymia, and to test a possible moderating effect of the single nucleotide polymorphism rs53576 in the oxytocin receptor gene (OXTR). Methods: One hundred and one participants were included in this study. History of child abuse was evaluated using the Childhood Trauma Questionnaire-Short Form. Cognitive functioning was appraised using The Awareness of Social Inference Test (social cognition). The interaction effect between the independent variables OXTR rs53576 (AA/AG and GG) and the absence or presence of any one type of child maltreatment or a combination of types was analyzed using a generalized linear model regression. Results: BD-I patients who had been victims of physical and emotional abuse in childhood and were carriers of the GG genotype at OXTR rs53576 displayed greater SC alterations, specifically in emotion recognition. Discussion: This gene-environment interaction finding suggests a differential susceptibility model of a genetic variants that can be plausibly associated with SC functioning and might help to identify at-risk clinical subgroups within a diagnostic category. Future research aimed at testing the interlevel impact of early stress constitutes an ethical-clinical duty given the high rates of childhood maltreatment reported in BD-I patients.

Parental personality traits and emotion regulation: Its relationship with infants' socioemotional development during the perinatal period.

Socioemotional development is central throughout life, and it unfolds in an interpersonal context in which each significant caregiver has an impact, particularly during infancy. However, only a relatively small number of studies have investigated associations between mothers and fathers' personality and emotional characteristics with their infant's socioemotional development during the perinatal period. Therefore, the present article examines the relationship between maternal and paternal personality traits and emotion regulation difficulties during the prenatal period with offspring's socioemotional development. This was a non-experimental and longitudinal study that included a community sample of 55 mother-father-baby triads. Parental assessments were carried out between the second and third trimester of pregnancy, and baby's socio-emotional development was assessed during their 2nd month after birth. Results evidenced differences between maternal and paternal personality traits and emotion regulation difficulties during the perinatal period as well as distinct contributions on infant's socioemotional development.

Phycological debriefing in acute traumatic events: Evidence synthesis. / Debriefing psicológico en eventos traumáticos agudos: síntesis de la evidencia secundaria.

Stressful life situations can generate chronic symptomatology, so it is of great concern to analyze preventive strategies. Psychological debriefing is an intervention for acute trauma, which verbalizes perceptions, thoughts, and emotions experienced during a recent traumatic event. The evidence surrounding its efficacy is controversial. This article discusses the efficacy of psychological debriefing based on systematic reviews and clinical practice guidelines. In all, nine systematic reviews were included. Only one of them found that psychological debriefing effectively decreased psychological stress, while the remaining eight found no significant effects for outcomes such stress, depressive and anxious symptoms, or development and severity of post-traumatic stress disorder. Moreover, two clinical trials found that the intervention had a significantly deleterious effect. Another study found a worsening in the symptomatology associated with the event. Of the eight clinical practice guidelines incorporated, none recommended psychological debriefing as an intervention for acute trauma. Some phenomena could explain the lack of success of the intervention in the scientific evidence. The bioethical conditions related to the traumatic scenario hinder its research, and its lack of standardization makes its evaluation in clinical trials problematic. Other variables such as ethnicity, personality, culture, gender, and history of traumatic experiences have been little considered in research. Nevertheless, the intervention may hinder the adequate processing of traumatic memory and emotions. Current evidence is consistent in not recommending psychological debriefing as an intervention for acute trauma, so its management should avoid it. It is suggested to promote research on preventive interventions to develop chronic traumatic symptomatology.

Las situaciones vitales estresantes tienen el potencial de generar sintomatología crónica, por lo que es de gran interés analizar estrategias preventivas. El debriefing psicológico es una intervención para el trauma agudo, que consiste en la verbalización de percepciones, pensamientos y emociones experimentados durante un evento traumático reciente. La evidencia en torno a su eficacia es controvertida. Este artículo describe y discute la eficacia del debriefing psicológico a partir de los resultados de las revisiones sistemáticas y guías de práctica clínica al respecto. Se incluyeron nueve revisiones sistemáticas. Solo una de ellas encontró que el debriefing psicológico fue eficaz en la disminución del estrés psicológico. Las ocho restantes no encontraron efectos significativos para desenlaces como severidad de los síntomas de estrés postraumático, depresivos, ansiosos o desarrollo de trastorno de estrés postraumático. Dos ensayos clínicos incorporados en las revisiones sistemáticas verificaron que la intervención tenía un efecto significativamente deletéreo, y otro estudio corroboró un empeoramiento numérico en la sintomatología asociada al evento. De las ocho guías de práctica clínica incorporadas, ninguna recomendó al debriefing psicológico como intervención para el trauma agudo. Existen algunos fenómenos que explicarían la falta de éxito de la intervención en la evidencia científica. Las condiciones bioéticas relativas al escenario traumático dificultan su investigación. Asimismo, su falta de estandarización problematiza la evaluación en ensayos clínicos. Otras variables como etnia, personalidad, cultura, género y antecedentes de experiencias traumáticas han sido poco consideradas en la investigación. No obstante, la intervención podría entorpecer el procesamiento adecuado de la memoria y las emociones traumáticas. La evidencia actual es consistente en no recomendar el debriefing psicológico como intervención para el trauma agudo, por lo que debe ser una práctica evitada en su manejo. Se sugiere promover la investigación en intervenciones preventivas para el desarrollo de sintomatología traumática crónica.

The Spanish gut microbiome reveals links between microorganisms and Mediterranean diet.

Despite the increasing evidence of links between human gut and health, the number of gut microbiomes that have been studied to date at a country level are surprisingly low. Mediterranean countries, including some of the most long-lived and healthy countries in the world, have not been considered so far in those studies at a large scale. The main objective of this work is to characterize the gut microbiome of a healthy adult population of a Mediterranean, paradigmatically healthy country: Spain. Stool samples from 530 healthy volunteers were collected, total metagenomic DNA extracted, and the microbial profiles determined through 16S rRNA metataxonomic sequencing. Our results confirm the associations between several microbial markers and different variables, including sex, age, BMI and diet choices, and bring new insights into the relationship between microbiome and diet in the Spanish population. Remarkably, some of the associations found, such as the decrease of Faecalibacterium with age or the link of Flavonifractor with less healthy dietary habits, have been barely noticed in other large-scale cohorts. On the other hand, a range of links between microorganisms, diet, and lifestyle coincide with those reported in other populations, thus increasing the robustness of such associations and confirming the importance of these microbial markers across different countries. Overall, this study describes the Spanish "normal" microbiome, providing a solid baseline for future studies investigating the effects of gut microbiome composition and deviations in the adherence to the Mediterranean diet.

Video Intervention Therapy for primary caregivers in a child psychiatry unit: a randomized feasibility trial.

BACKGROUND: During child psychiatry hospitalization, working with the families or attachment figures is a challenge, most of the children who are admitted to these units come from multi-problem families, with limited research in this area. Video feedback (VF) interventions have proved to be a powerful resource to promote parental and child well-being in small children and has been used with parents with a psychiatric condition. Parental Reflective Functioning (PRF) is one of the parental abilities that can be improved with VF and could be especially important in coping with conflict and negative emotions in older children. The aim of this study is to implement Video Intervention Therapy (VIT) to enhance PRF in primary caregivers of inpatient psychiatric children. As there is no published research using VF with parents of children with severe psychopathology in a hospitalized context. This report, then, becomes a much needed pilot study providing evidence for a larger randomized control trial (RCT). METHODS: The study is a single-center, two-arm feasibility randomized control trial with a qualitative component. Block randomization was done to generate a 2:1 allocation, leaving more participants in the intervention group. The intervention comprises four modules; every module has both one video-recorded play session and one VIT session (in a group setting) per week. Evaluation of the caregivers included assessments of PRF and well-being, and child assessment included parent-ratings and clinician-ratings of symptomatology and general functioning. RESULTS: Thirty participants were randomized; eligibility and recruitment rate were 70.6% and 83.3%, respectively. The compliance-to-intervention rate was 85% in the VIT group and 90% in the control group. All participants completed entry evaluation and 90% at the 3-month follow-up. The intervention was acceptable to participants and feasible for therapists to deliver. Outcome data must be treated with caution due to the small numbers involved, yet indicate that the VIT may have a positive effect in improving parental and child mental health outcomes. CONCLUSIONS: VIT for primary caregivers of child inpatient children was feasible to deliver and acceptable for participants, therapist, and the staff unit involved; there is sufficient evidence to undertake a full-scale effectiveness RCT. TRIAL REGISTRATION: ClinicalTrials.gov NCT03374904 . Registered on 14 December 2017.

The subjective experience of psychotherapists during moments of rupture in psychotherapy with adolescents.

The study of the ruptures of the therapeutic alliance has impacted research in psychotherapy by highlighting the relational nature of this phenomenon. Despite ruptures are frequent and relevant during adolescent psychotherapy, most of the empirical evidence in this field has been carried out with adults. Understanding the subjective experience of the therapist during ruptures while working with adolescent is proposed as a starting point for the study of this type of interactional scenarios. The study examined the meanings that emerge from the therapists' experience in terms of their explanations about the causes and effects of ruptures with adolescents. Eight psychotherapists were interviewed about their experiences during ruptures with young patients. The data was qualitatively analyzed through the Interpretive Phenomenological Analysis method. Four categories emerged: the failure to recognize the adolescent's experience, the intensity of the affective experience of adolescents in psychotherapy, therapeutic boundaries as an articulator of the therapeutic purpose and, the obstacles that family generates during the therapeutic process. This study concurs with the literature on the need to make explicit with the family about the meaning, roles and limits of the therapy, and to prevent the exercise of control from an adultcentered position. It is concluded that in order to avoid and repair ruptures with adolescents in psychotherapy, an approach that integrates a sensitive attitude, an ecological point of view and mentalizing about the origin of the rupture is needed.

Validation of the Geriatric Anxiety Inventory in Chilean older people.

OBJECTIVE: Currently in Chile there is a lack of validated tools for measuring anxiety in the elderly population. Considering this, the purpose of this study was to validate the Geriatric Anxiety Inventory (GAI) in the country. METHOD: An analysis of the psychometric properties of the GAI was carried out, using a non-clinical sample of 301 older adults in the Metropolitan and Valparaíso regions of Chile. Older people were asked about anxiety, rumination, depression, well-being and sociodemographic data. RESULTS: An excellent internal reliability was obtained with a Cronbach score of 0.931. An adequate convergent validity was observed with the Depression scales (CES-D) (Rho = 0.549, p < .01), Rumination (RSS) (Rho = 0.618; p < 0.01) and Experiential avoiding (Rho = 0.485; p < 0.01). On the other hand, the discriminant validity of the psychological well-being scale presented a negative correlation of Rho = -0.699 (p < 0.01). Finally, and Exploratory Factor Analysis was made, revealing a one-dimensional model of the instrument. CONCLUSION: The Geriatric Anxiety Inventory has very good psychometric properties measuring anxiety in elderly people, being an adequate instrument for the screening of anxiety on this population.

Intranasal C3a treatment ameliorates cognitive impairment in a mouse model of neonatal hypoxic-ischemic brain injury.

Perinatal asphyxia-induced brain injury is often associated with irreversible neurological complications such as intellectual disability and cerebral palsy but available therapies are limited. Novel neuroprotective therapies as well as approaches stimulating neural plasticity mechanism that can compensate for cell death after hypoxia-ischemia (HI) are urgently needed. We previously reported that single i.c.v. injection of complement-derived peptide C3a 1h after HI induction prevented HI-induced cognitive impairment when mice were tested as adults. Here, we tested the effects of intranasal treatment with C3a on HI-induced cognitive deficit. Using the object recognition test, we found that intranasal C3a treated mice were protected from HI-induced impairment of memory function assessed 6weeks after HI induction. C3a treatment ameliorated HI-induced reactive gliosis in the hippocampus, while it did not affect the extent of hippocampal tissue loss, neuronal cell density, expression of the pan-synaptic marker synapsin I or the expression of growth associated protein 43. In conclusion, our results reveal that brief pharmacological treatment with C3a using a clinically feasible non-invasive mode of administration ameliorates HI-induced cognitive impairment. Intranasal administration is a plausible route to deliver C3a into the brain of asphyxiated infants at high risk of developing hypoxic-ischemic encephalopathy.

Cartilage Oligomeric Matrix Protein Levels in Synovial Fluid in Patients With Primary Knee Osteoarthritis And Healthy Controls: A Preliminary Comparative Analysis With Serum Cartilage Oligomeric Matrix Protein.

OBJECTIVES: This study aims (i) to compare synovial fluid and serum cartilage oligomeric matrix protein levels in patients with primary knee osteoarthritis and healthy controls, (ii) compare variations of synovial fluid and serum cartilage oligomeric matrix protein levels according to sex, Kellgren-Lawrence grades, and daytime sampling, and (iii) correlate the synovial fluid and serum cartilage oligomeric matrix protein levels with age, severity of disease, and daytime sampling. PATIENTS AND METHODS: One hundred and twenty-four individuals (44 males, 80 females; median age 66 years; range 42 to 87 years) were diagnosed with primary knee osteoarthritis according to the American College of Rheumatology guidelines. Additionally, 105 healthy healthy individuals (49 males, 56 females; median age 50 years; range 30 to 75 years) were included as the control group. For both groups, a thorough clinical history and physical examination were performed. Moreover, weight-bearing anteroposterior and lateral bending 30 degrees knee X-rays were collected. Cartilage oligomeric matrix protein in serum and synovial fluid was measured by enzyme-linked immunosorbent assay. RESULTS: Total synovial fluid cartilage oligomeric matrix protein levels were considerably higher than total serum levels for both groups. Levels of cartilage oligomeric matrix protein in synovial fluid and serum were higher in patients than in controls for both sexes. However, only cartilage oligomeric matrix protein levels in synovial fluid were higher in female patients. The levels of synovial fluid cartilage oligomeric matrix protein were significantly higher when sampling after 12 pm. A positive correlation was found between synovial fluid and serum cartilage oligomeric matrix protein levels, age, and daytime sampling. CONCLUSION: These findings may suggest a possible role for synovial fluid and serum cartilage oligomeric matrix protein as a measure for primary knee osteoarthritis. However, more studies need to be performed to address other factors that may influence the levels of cartilage oligomeric matrix protein in synovial fluid and serum.

Effects of resveratrol on ovarian response to controlled ovarian hyperstimulation in ob/ob mice.

OBJECTIVE: To evaluate antidiabetic and anti-inflammatory effects of resveratrol on the ovarian response to controlled ovarian hyperstimulation (COH) in obesity-related infertility. DESIGN: Experimental. SETTING: University laboratory. ANIMAL(S): Sixteen female ob/ob mice and 16 female C57BL/6J mice undergoing COH. INTERVENTION(S): Wild-type placebo group; wild-type resveratrol group; ob/ob mice placebo group; ob/ob mice resveratrol group. Resveratrol 3.75 mg/kg daily for 20 days and undergoing COH protocol. MAIN OUTCOME MEASURE(S): Body and reproductive system weight, food intake, fasting blood glucose, plasma insulin and T levels, and Homeostatic Index of Insulin Resistance; interleukin-6 and tumor necrosis factor-α levels in adipose tissue by Western blot; assessment of quality and quantity of oocytes retrieved; and quantitative analysis of ovarian follicles. RESULT(S): Plasma insulin and T levels decreased and Homeostatic Index of Insulin Resistance improved in ob/ob mice treated with resveratrol. Interleukin-6 and tumor necrosis factor-α levels were significantly reverted back to near normalcy after resveratrol treatment in obese mice. Administration of resveratrol resulted in a significantly higher number of oocytes collected in wild-type mice. The number of primary, growing, preovulatory, and atretic follicles was found to be decreased in the group of obese mice treated with resveratrol when compared with the obese control group. CONCLUSION(S): Resveratrol administration could exert benefits against loss of ovarian follicles, and these actions may be mediated, at least in part, via anti-inflammatory, insulin-sensitizing, and antihyperandrogenism effects. These observations further validate the therapeutic potential of resveratrol to preserve ovarian reserve in conditions associated with obesity. Our results suggest the possible clinical use of resveratrol to enhance the ovarian response to COH in normal-weight females.

El maltrato infantil y su rol en el curso clínico de pacientes con trastorno bipolar / History of child abuse among patients with bipolar disorders

Background: A history of child abuse is common and has a significant impact in the clinical course of patients diagnosed with bipolar disorders (BD). Aims: To assess the frequency of child abuse experiences in patients BD type I and to evaluate its association with clinical course and cognitive functioning variables. Material and Methods: 117 patients with BD aged 45 ± 14 years (66% women) answered the Childhood Trauma Questionnaire (CTQ). The clinical course (illness onset, history of suicide attempts and number of hospitalizations) was obtained from medical records. Cognitive functioning was evaluated through social and non-social cognition tasks. Results: 64% of participants reported some type of child abuse. This variable was associated with an early onset of the disease (Odds ratio (OR) = 3.3; p < 0.02), increased risk of suicide attempts (OR = 2.4; p < 0.04) and specific disturbances in social cognitive tasks. Conclusions: Our study supports evidence of a common history of child abuse in patients with BD. Although child abuse predicts a worse clinical course, major clinical practice guidelines, as well as research designs, do not highlight this evidence.

Effects of estradiol and genistein on the insulin signaling pathway in the cerebral cortex of aged female rats.

Menopause leads to a decrease in estrogen production that increases central insulin resistance, contributing to the development of neurodegenerative diseases. We have evaluated the influence of aging and estradiol or genistein treatments on some key stages of the insulin signaling pathway in the cerebral cortex. Young and aged female Wistar rats were ovariectomized and treated acutely with 17ß-estradiol (1.4µg/kg body weight), two doses of genistein (10 or 40mg/kg body weight), or vehicle. The cortical expression of several key insulin signaling pathway components was analyzed by western blotting. Our results showed an age-related deterioration in the interactions between the regulatory subunit of phosphatidylinositol 3-kinase (p85α) and the activated form of insulin receptor substrate 1 (p-IRS1tyr612), as well as between p85α and the 46kDa isoform of the estrogen receptor α (ERα46). Moreover, aging also decreased the translocation of glucose transporter-4 (GLUT4) to the plasma membrane. 17ß-Estradiol but not genistein reduced the negative impact of aging on central insulin sensitivity by favoring this GLUT4 translocation, and therefore could be neuroprotective against the associated neurodegenerative diseases. However, protein kinase B (Akt) activation by genistein suggests that other possible mechanisms are involved in the neuroprotective effects of this phytoestrogen during the aging process.

Immune modulating capability of two exopolysaccharide-producing Bifidobacterium strains in a Wistar rat model.

Fermented dairy products are the usual carriers for the delivery of probiotics to humans, Bifidobacterium and Lactobacillus being the most frequently used bacteria. In this work, the strains Bifidobacterium animalis subsp. lactis IPLA R1 and Bifidobacterium longum IPLA E44 were tested for their capability to modulate immune response and the insulin-dependent glucose homeostasis using male Wistar rats fed with a standard diet. Three intervention groups were fed daily for 24 days with 10% skimmed milk, or with 10(9) cfu of the corresponding strain suspended in the same vehicle. A significant increase of the suppressor-regulatory TGF- ß cytokine occurred with both strains in comparison with a control (no intervention) group of rats; the highest levels were reached in rats fed IPLA R1. This strain presented an immune protective profile, as it was able to reduce the production of the proinflammatory IL-6. Moreover, phosphorylated Akt kinase decreased in gastroctemius muscle of rats fed the strain IPLA R1, without affecting the glucose, insulin, and HOMA index in blood, or levels of Glut-4 located in the membrane of muscle and adipose tissue cells. Therefore, the strain B. animalis subsp. lactis IPLA R1 is a probiotic candidate to be tested in mild grade inflammation animal models.

17ß-Estradiol and genistein acute treatments improve some cerebral cortex homeostasis aspects deteriorated by aging in female rats.

Aging is associated with decreased insulin sensitivity and impaired cerebral glucose homeostasis. These changes increase neural sensitivity to metabolic damage contributing to cognitive decline, being the decrease in plasma estrogen following menopause one of the main factors involved in aged females. Phytoestrogens as genistein are structurally similar to 17ß-estradiol, bind to estrogen receptors, and can evoke both estrogenic and anti-estrogenic effects. Estrogens and phytoestrogens have neuroprotective potential, but the physiological mechanisms are not fully understood. Young and aged female Wistar rats were ovariectomized and treated acutely with 17ß-estradiol (1.4µg/kg body weight), genistein (10 or 40 mg/kg body weight), or vehicle. Cortical expression of glucose transporter-3 (GLUT-3) and -4 (GLUT-4), cytochrome c oxidase (CO), estrogen receptor-α (ERα) and -ß (ERß) was measured by Western blotting. There was an age-related decline in GLUT-4, CO and ERß levels. Both drugs, estradiol and genistein, were able to reverse GLUT-3 downregulation in the cortex following late ovariectomy. However, genistein was the only treatment able to restore completely GLUT-4 levels in aged rats. In contrast, estradiol was more potent than genistein at increasing CO, a marker of cerebral oxidative metabolism. As regards ER levels, estradiol increased the ERα67 quantity diminished by late ovariectomy, while genistein did the same with the other ERα isoform, ERα46, highlighting drug-specific differences in expression changes for both isoforms. On the other hand, no treatment-related differences were found regarding ERß levels. Therefore, genistein like estradiol could be suitable treatments against cortical metabolic dysfunction caused by aging. These treatments may hold promise as neuroprotective strategies against diabetes and age-related neurodegenerative diseases.