Effect of Postnatal Epigallocatechin-Gallate Treatment on Cardiac Function in Mice Prenatally Exposed to Alcohol.

Prenatal alcohol exposure affects the cardiovascular health of the offspring. Epigallocatechin-3-gallate (EGCG) may be a protective agent against it, but no data are available regarding its impact on cardiac dysfunction. We investigated the presence of cardiac alterations in mice prenatally exposed to alcohol and the effect of postnatal EGCG treatment on cardiac function and related biochemical pathways. C57BL/6J pregnant mice received 1.5 g/kg/day (Mediterranean pattern), 4.5 g/kg/day (binge pattern) of ethanol, or maltodextrin until Day 19 of pregnancy. Post-delivery, treatment groups received EGCG-supplemented water. At post-natal Day 60, functional echocardiographies were performed. Heart biomarkers of apoptosis, oxidative stress, and cardiac damage were analyzed by Western blot. BNP and Hif1α increased and Nrf2 decreased in mice prenatally exposed to the Mediterranean alcohol pattern. Bcl-2 was downregulated in the binge PAE drinking pattern. Troponin I, glutathione peroxidase, and Bax increased in both ethanol exposure patterns. Prenatal alcohol exposure led to cardiac dysfunction in exposed mice, evidenced by a reduced ejection fraction, left ventricle posterior wall thickness at diastole, and Tei index. EGCG postnatal therapy restored the physiological levels of these biomarkers and improved cardiac dysfunction. These findings suggest that postnatal EGCG treatment attenuates the cardiac damage caused by prenatal alcohol exposure in the offspring.

Effects of Antioxidant Intake on Fetal Development and Maternal/Neonatal Health during Pregnancy.

During pregnancy, cycles of hypoxia and oxidative stress play a key role in the proper development of the fetus. Hypoxia during the first weeks is crucial for placental development, while the increase in oxygen due to the influx of maternal blood stimulates endothelial growth and angiogenesis. However, an imbalance in the number of oxidative molecules due to endogenous or exogenous factors can overwhelm defense systems and lead to excessive production of reactive oxygen species (ROS). Many pregnancy complications, generated by systemic inflammation and placental vasoconstriction, such as preeclampsia (PE), fetal growth restriction (FGR) and preterm birth (PTB), are related to this increase of ROS. Antioxidants may be a promising tool in this population. However, clinical evidence on their use, especially those of natural origin, is scarce and controversial. Following PRISMA methodology, the current review addresses the use of natural antioxidants, such as epigallocatechin gallate (EGCG), melatonin and resveratrol (RESV), as well as other classical antioxidants (vitamin C and E) during the prenatal period as treatment of the above-mentioned complications. We review the effect of antioxidant supplementation on breast milk in lactating mothers.

Therapeutic Effects of Catechins in Less Common Neurological and Neurodegenerative Disorders.

In recent years, neurological and neurodegenerative disorders research has focused on altered molecular mechanisms in search of potential pharmacological targets, e.g., imbalances in mechanisms of response to oxidative stress, inflammation, apoptosis, autophagy, proliferation, differentiation, migration, and neuronal plasticity, which occur in less common neurological and neurodegenerative pathologies (Huntington disease, multiple sclerosis, fetal alcohol spectrum disorders, and Down syndrome). Here, we assess the effects of different catechins (particularly of epigalocatechin-3-gallate, EGCG) on these disorders, as well as their use in attenuating age-related cognitive decline in healthy individuals. Antioxidant and free radical scavenging properties of EGCG -due to their phenolic hydroxyl groups-, as well as its immunomodulatory, neuritogenic, and autophagic characteristics, makes this catechin a promising tool against neuroinflammation and microglia activation, common in these pathologies. Although EGCG promotes the inhibition of protein aggregation in experimental Huntington disease studies and improves the clinical severity in multiple sclerosis in animal models, its efficacy in humans remains controversial. EGCG may normalize DYRK1A (involved in neural plasticity) overproduction in Down syndrome, improving behavioral and neural phenotypes. In neurological pathologies caused by environmental agents, such as FASD, EGCG enhances antioxidant defense and regulates placental angiogenesis and neurodevelopmental processes. As demonstrated in animal models, catechins attenuate age-related cognitive decline, which results in improvements in long-term outcomes and working memory, reduction of hippocampal neuroinflammation, and enhancement of neuronal plasticity; however, further studies are needed. Catechins are valuable compounds for treating and preventing certain neurodegenerative and neurological diseases of genetic and environmental origin. However, the use of different doses of green tea extracts and EGCG makes it difficult to reach consistent conclusions for different populations.

Effects of Microbiota Imbalance in Anxiety and Eating Disorders: Probiotics as Novel Therapeutic Approaches.

Anxiety and eating disorders produce a physiological imbalance that triggers alterations in the abundance and composition of gut microbiota. Moreover, the gut-brain axis can be altered by several factors such as diet, lifestyle, infections, and antibiotic treatment. Diet alterations generate gut dysbiosis, which affects immune system responses, inflammation mechanisms, the intestinal permeability, as well as the production of short chain fatty acids and neurotransmitters by gut microbiota, which are essential to the correct function of neurological processes. Recent studies indicated that patients with generalized anxiety or eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorders) show a specific profile of gut microbiota, and this imbalance can be partially restored after a single or multi-strain probiotic supplementation. Following the PRISMA methodology, the current review addresses the main microbial signatures observed in patients with generalized anxiety and/or eating disorders as well as the importance of probiotics as a preventive or a therapeutic tool in these pathologies.

Epigallocatechin Gallate Ameliorates the Effects of Prenatal Alcohol Exposure in a Fetal Alcohol Spectrum Disorder-Like Mouse Model.

Fetal alcohol spectrum disorder is the main preventable cause of intellectual disability in the Western world. Although binge drinking is the most studied prenatal alcohol exposure pattern, other types of exposure, such as the Mediterranean, are common in specific geographic areas. In this study, we analyze the effects of prenatal alcohol exposure in binge and Mediterranean human drinking patterns on placenta and brain development in C57BL/6J mice. We also assess the impact of prenatal treatment with the epigallocatechin-3-gallate antioxidant in both groups. Study experimental groups for Mediterranean or binge patterns: (1) control; (2) ethanol; (3) ethanol + epigallocatechin-3-gallate. Brain and placental tissue were collected on gestational Day 19. The molecular pathways studied were fetal and placental growth, placental angiogenesis (VEGF-A, PLGF, VEGF-R), oxidative stress (Nrf2), and neurodevelopmental processes including maturation (NeuN, DCX), differentiation (GFAP) and neural plasticity (BDNF). Prenatal alcohol exposure resulted in fetal growth restriction and produced imbalances of placental angiogenic factors. Moreover, prenatal alcohol exposure increased oxidative stress and caused significant alterations in neuronal maturation and astrocyte differentiation. Epigallocatechin-3-gallate therapy ameliorated fetal growth restriction, attenuated alcohol-induced changes in placental angiogenic factors, and partially rescued neuronal nuclear antigen (NeuN), (doublecortin) DCX, and (glial fibrillary acidic protein) GFAP levels. Any alcohol consumption (Mediterranean or binge) during pregnancy may generate a fetal alcohol spectrum disorder phenotype and the consequences may be partially attenuated by a prenatal treatment with epigallocatechin-3-gallate.

Bioavailability of Epigallocatechin Gallate Administered With Different Nutritional Strategies in Healthy Volunteers.

The flavanol epigallocatechin gallate (EGCG) is being tested for the treatment of several diseases in humans. However, its bioavailability and pharmacokinetic profile needs a better understanding to enable its use in clinical trials. There is no consensus on the most appropriate concentration of EGCG in the body to obtain the maximum therapeutic effects. Therefore, the aim of this study is to analyze the bioavailability of EGCG orally administered alone or with different food supplements after overnight fasting in order to determine its optimal conditions (high concentrations in blood and the lowest interindividual variations) to be used as a pharmacological tool in human trials. Ten healthy volunteers (5 men and 5 women) aged 25 to 35 years were recruited prospectively. Three series of clinical experiments with a washout period of seven days among each were performed: 1) Teavigo® (EGCG extract) alone, 2) Teavigo® with a standard breakfast, and 3) FontUp® (Teavigo® commercially prepared with fats, carbohydrates, proteins, vitamins, and minerals). Blood samples were collected at 0, 30, 60, 90, 120, 180, 240, and 360 min after EGCG intake. Free EGCG in plasma was measured using a liquid chromatography and mass spectrometry UPLC-ESI-MS/MS analytical method. The pharmacokinetic variables analyzed statistically were area under the curve (AUC0-360), Cmax, Cav, Cmin, T1/2, and Tmax,. EGCG (Teavigo®) alone was the group with higher AUC0-360, Cmax, and Cav both in men (3.86 ± 4.11 µg/mL/kg/6 h; 5.95 ng/mL/kg; 2.96 ng/mL/kg) and women (3.33 ± 1.08 µg/mL/kg/6 h; 6.66 ng/mL/kg; 3.66 ng/mL). Moreover, FontUp® was the group with the highest value of T1/2 both in men (192 ± 66 min) and women (133 ± 28 min). Teavigo® intake after fasting overnight revealed the highest concentration of EGCG in plasma according to its pharmacokinetic profile, indicating that this is an excellent alternative of administration if the experimental design requires good absorption in the gastrointestinal tract. Moreover, EGCG taken along with food supplements (FontUp®) improved the stability of the molecule in the body, being the best choice if the experimental design wants to reduce interindividual variation.

Listeria monocytogenes: infecciones materno-fetales en el Hospital Universitario Sant Joan de Déu de Barcelona, España / Listeria monocytogenes: maternal and fetal infections in the Hospital Universitario Sant Joan de Déu in Barcelona, Spain

Objetivo. Estudio retrospectivo de casos de listeriosis en mujeres gestantes diagnosticadas en el Hospital Universitario Sant Joan de Déu de Barcelona los años 2000-2010. Material y métodos. Inclusión de todas aquellas gestantes que consultan por clínica sugestiva de listeriosis y posterior confirmación de la infección mediante cultivos. Análisis descriptivo. Resultados. 18 casos de listeriosis diagnosticados (incidencia 4/10.000). En un 94,5% no se hallan factores de riesgo conocidos. En el 45% el signo guía es la fiebre materna. En los 2 casos diagnosticados prenatalmente y que se realiza tratamiento antibiótico, se produce parto a término sin secuelas neonatales (100%). La morbimortalidad materno-fetal tras la infección por Listeria monocytogenes es del 44,5%, produciéndose secuelas importantes en el 11% de recién nacidos vivos y un 33,5% de éxitus fetales. Conclusiones. A pesar de la baja incidencia de la listeriosis, es importante su diagnóstico precoz, ya que un tratamiento adecuado reduce la morbimortalidad materno-fetal (AU)

Objective. We performed a restrospective study of cases of listeriosis diagnosed in pregnant women in the Hospital Sant Joan de Déu from 2000 to 2010. Material and methods. All pregnant women who consulted for symptoms suggestive of listeriosis and with culture-confirmed infection were included. A descriptive statistical analysis was performed. Results. Eighteen cases of listeriosis were diagnosed (incidence 4/10000). In 94.5%, there were no associated risk factors. In 45% of the patients, the main sign was maternal fever. Two patients who were diagnosed prenatally and who received antibiotic therapy delivered at term without neonatal effects (100%). Maternal and fetal morbidity and mortality after Listeria monocytogenes infection was 44.5%, with important sequelae in 11% of the neonates and fetal exitus in 33.5%. Conclusion. Despite the low incidence of listeriosis, early diagnosis is important, since correct treatment reduces maternal and fetal morbidity and mortality (AU)