Cytotoxic Activity of Lepidium virginicum L. Methanolic Extract on Human Colorectal Cancer Cells, Caco-2, through p53-Mediated Apoptosis.

Colorectal cancer (CRC) is the third most common type of cancer worldwide. Its treatment options have had a limited impact on cancer remission prognosis. Therefore, there is an ongoing need to discover novel anti-cancer agents. Medicinal plants have gained recognition as a source of anti-cancer bioactive compounds. Recently, ethanolic extract of L. virginicum stems ameliorated dinitrobenzene sulfonic acid (DNBS)-induced colitis by modulating the intestinal immune response. However, no scientific study has demonstrated this potential cytotoxic impact on colon cancer cells. The objective of this study was to evaluate the cytotoxic effect of the methanolic extract of L. virginicum (ELv) on a human colorectal adenocarcinoma cell line (Caco-2) and to identify and quantify the phenolic compounds present in ELv extracts by liquid chromatography-mass spectrometry analysis. The cytotoxic activity was assessed using cell viability assays by reduction in the compound 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH). MTT and LDH assays revealed that the ELv decreases cell viability in the Caco-2 cell line in a concentration-dependent manner. Cell death was a result of DNA fragmentation and p53-mediated apoptosis. Eight phenolic acids and five flavonoids were identified and quantified in the stems. In conclusion, our findings demonstrate that the extract of L. virginicum possesses cytotoxic properties on Caco-2 cell line, suggesting that it could be a potential source of new drugs against CRC.

Association of DNA Methylation with Infant Birth Weight in Women with Gestational Diabetes.

Offspring exposed to gestational diabetes mellitus (GDM) exhibit greater adiposity at birth. This early-life phenotype may increase offspring risk of developing obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease later in life. Infants born to women with GDM have a dysregulation of several hormones, cytokines, and growth factors related to fetal fat mass growth. One of the molecular mechanisms of GDM influencing these factors is epigenetic alterations, such as DNA methylation (DNAm). This review will examine the role of DNAm as a potential biomarker for monitoring fetal growth during pregnancy in women with GDM. This information is relevant since it may provide useful new biomarkers for the diagnosis, prognosis, and treatment of fetal growth and its later-life health consequences.

Gestational Weight Gain Is Associated with the Expression of Genes Involved in Inflammation in Maternal Visceral Adipose Tissue and Offspring Anthropometric Measures.

BACKGROUND: Adequate gestational weight gain (GWG) is essential for maternal and fetal health. GWG may be a sign of higher visceral adipose tissue (VAT) accretion. A higher proportion of VAT is associated with an inflammatory process that may play a role in the fetal programming of obesity. This study aimed to (1) compare the expression of genes involved in inflammatory responses (TLR2, TLR4, NFκB, IKKß, IL-1RA, IL-1ß, IL-6, IL-10, TNF-α) in the VAT of pregnant women according to GWG and (2) explore whether VAT inflammation and GWG are related to offspring anthropometric measures. MATERIAL AND METHODS: 50 women scheduled for cesarean section who delivered term infants were included in the study. We collected maternal omental VAT, and the expression of genes was examined with RT-qPCR. RESULTS: Women with excessive and with adequate GWG had significantly higher expressions of most inflammatory genes than women with insufficient GWG. Neonates from mothers with excessive GWG had greater birth weight and chest circumference than those from mothers with insufficient GWG. GWG was positively correlated with fetal birth weight. CONCLUSIONS: The VAT expression of most genes associated with inflammatory pathways was higher in excessive and adequate GWG than in pregnant women with insufficient GWG. Moreover, GWG was found to be positively associated with newborn weight.

Excessive Pregestational Weight and Maternal Obstetric Complications: The Role of Adipokines.

There is a high frequency of overweight and obesity in women of reproductive age. Women who start pregnancy with overweight or obesity have an increased risk of developing maternal obstetric complications such as gestational hypertension, pre-eclampsia, gestational diabetes mellitus, postpartum hemorrhage, and requiring C-section to resolve the pregnancy with a higher risk of C-section surgical site infection. Excessive weight in pregnancy is characterized by dysregulation of adipokines, the functions of which partly explain the predisposition of pregnant women with overweight or obesity to these maternal obstetric complications. This review compiles, organizes, and analyzes the most recent studies on adipokines in pregnant women with excess weight and the potential pathophysiological mechanisms favoring the development of maternal pregnancy complications.

Hirsutism and Polycystic Ovarian Morphology are the Most Frequent Components of Polycystic Ovary Syndrome in Women with Type 1 Diabetes.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. In Mexico, its prevalence in patients with type 1 diabetes (T1D) is unknown. AIM: To evaluate the clinical and biochemical characteristics of patients with T1D with and without PCOS. METHODS: A cross-sectional study was conducted to evaluate women of reproductive age with T1D for the diagnosis of PCOS using the criteria of the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine. Clinical information was obtained from clinical records, and we recorded anthropometric variables and performed a laboratory test during the follicular phase. The estimated glucose disposal rate and visceral adiposity index were also calculated to assess insulin resistance. Subsequently, participants were evaluated based on the presence or absence of PCOS. RESULTS: Thirty-nine percent of patients with T1D had PCOS. The most frequent components of PCOS were polycystic ovary morphology (58.5%), clinical hyperandrogenism (41.5%), oligomenorrhea (29.2%), and biochemical hyperandrogenism (19.5%). Patients with PCOS used more insulin per day (1.04 ± 0.33 vs. 0.71 ± 0.29 IU/kg/d, p = 0.003), had lower fasting glucose (116.4 ± 59.79 vs. 161.16 ± 63.9 mg/dl, p = 0.029) and higher right ovarian volume (11.36 [8.64-15.89] vs. 6.9 [5.55-8.77] cm3, p = 0.005) and Ferriman-Gallwey scores (9.06 ± 2.05 vs. 7.12 ± 3.15 points, p = 0.035) compared to patients without PCOS. The frequency of insulin resistance and metabolic syndrome in women with PCOS was 37.5 and 18.8%, respectively. CONCLUSION: PCOS is a very heterogeneous entity, with a high frequency in women with T1D.

Role of Oxidative Stress and Inflammation in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. It is related to several gestational and fetal adverse outcomes. Moreover, women with GDM and their infants have a high risk of developing type 2 diabetes in the future. The pathogenesis of GDM is not completely understood; nevertheless, two factors that contribute to its development are oxidative stress and inflammation. Oxidative stress and inflammation are related; reactive oxygen species (ROS) production can activate inflammatory cells and enhance the production of inflammatory mediators. Inflammation, in turn, leads to an increased ROS release, causing a vicious circle to ensue. Inflammatory responses can be achieved via the activation of the NF-κB signaling pathway. Herein, we review the English literature regarding oxidative stress and inflammation evaluated simultaneously in the same population, attempting to identify mechanisms through which these factors contribute to the development of GDM. Furthermore, the modulation of oxidative stress and inflammation by different therapies used in women with GDM and in cell models of GDM is included in the review. Probiotics and nutrient supplementations have been shown to reduce biomarkers of inflammation and oxidative stress in vitro and in women with GDM.

Differential Expression of FXR and Genes Involved in Inflammation and lipid Metabolism Indicate Adipose Tissue Dysfunction in Gestational Diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most frequent metabolic alteration in pregnancy. Several abnormalities in visceral adipose tissue (VAT) have been described as part of its pathophysiology including hypertrophy, inflammation and altered lipid metabolism. Farnesoid X receptor (FXR) is involved in adipocyte physiology and inflammation, so its expression may correlate with the expression of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), lipoprotein lipase (LPL), and two fatty acid transporters (SLC27A2, and SLC27A4). AIM: To compare the FXR, LPL, SLC27A2, SLC27A4, TNF-α, and IL-10 mRNA expression in VAT between women with GDM and healthy pregnant (HP) women. Secondarily, to evaluate the potential correlation between these expression levels. MATERIALS AND METHODS: Cross-sectional study of 50 GDM and 50 HP women. Conventional biochemical tests were performed and relative mRNA expression in VAT was measured by RT-qPCR. RESULTS: Gene expression levels of FXR and IL-10 were lower, whereas those of LPL, as well as the TNF-α/IL-10 ratio, were higher in women with GDM compared to HP. Pre-pregnancy BMI was the main significant independent variable for FXR levels in VAT from women with GDM. In all women, LPL expression levels correlated positively with those of SLC27A2. Only in women with GDM, IL-10 expression levels correlated negatively with those of SLC27A2, and SLC27A4. CONCLUSIONS: GDM is associated with decreased expression of FXR and IL-10 and increased expression of LPL, as well as a higher TNF/IL-10 ratio in VAT. These results suggest increased lipid storage and pro-inflammatory state indicating VAT dysfunction in this metabolic disorder.

Association between Galectin Levels and Neurodegenerative Diseases: Systematic Review and Meta-Analysis.

Galectins are a family of proteins with an affinity for ß-galactosides that have roles in neuroprotection and neuroinflammation. Several studies indicate that patients with neurodegenerative diseases have alterations in the concentration of galectins in their blood and brain. However, the results of the studies are contradictory; hence, a meta-analysis is performed to clarify whether patients with neurodegenerative diseases have elevated galectin levels compared to healthy individuals. Related publications are obtained from the databases: PubMed, Central-Conchrane, Web of Science database, OVID-EMBASE, Scope, and EBSCO host until February 2022. A pooled standard mean difference (SMD) with a 95% confidence interval (CI) is calculated by fixed-effect or random-effect model analysis. In total, 17 articles are included in the meta-analysis with a total of 905 patients. Patients with neurodegenerative diseases present a higher level of galectin expression compared to healthy individuals (MDS = 0.70, 95% CI 0.28-1.13, p = 0.001). In the subgroup analysis by galectin type, a higher galectin-3 expression is observed in patients with neurodegenerative diseases. Patients with Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALD), and Parkinson's disease (PD) expressed higher levels of galectin-3. Patients with multiple sclerosis (MS) have higher levels of galectin-9. In conclusion, our meta-analysis shows that patients with neurovegetative diseases have higher galectin levels compared to healthy individuals. Galectin levels are associated with the type of disease, sample, detection technique, and region of origin of the patients.

New Insights into Adipokines in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy and has considerable short- and long-term consequences for the health of both the mother and the newborn. Within its pathophysiology, genetic, nutritional, epigenetic, immunological, and hormonal components have been described. Within the last two items, it is known that different hormones and cytokines secreted by adipose tissue, known collectively as adipokines, are involved in the metabolic alterations underlying GDM. Although the maternal circulating profile of adipokines in GDM has been extensively studied, and there are excellent reviews on the subject, it is in recent years that more progress has been made in the study of their expression in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), placenta, and their concentrations in the umbilical circulation. Thus, this review compiles and organizes the most recent findings on the maternal and umbilical circulating profile and the levels of expression of adipokines in VAT, SAT, and placenta in GDM.

The Genomic Landscape of Corticotroph Tumors: From Silent Adenomas to ACTH-Secreting Carcinomas.

Corticotroph cells give rise to aggressive and rare pituitary neoplasms comprising ACTH-producing adenomas resulting in Cushing disease (CD), clinically silent ACTH adenomas (SCA), Crooke cell adenomas (CCA) and ACTH-producing carcinomas (CA). The molecular pathogenesis of these tumors is still poorly understood. To better understand the genomic landscape of all the lesions of the corticotroph lineage, we sequenced the whole exome of three SCA, one CCA, four ACTH-secreting PA causing CD, one corticotrophinoma occurring in a CD patient who developed Nelson syndrome after adrenalectomy and one patient with an ACTH-producing CA. The ACTH-producing CA was the lesion with the highest number of single nucleotide variants (SNV) in genes such as USP8, TP53, AURKA, EGFR, HSD3B1 and CDKN1A. The USP8 variant was found only in the ACTH-CA and in the corticotrophinoma occurring in a patient with Nelson syndrome. In CCA, SNV in TP53, EGFR, HSD3B1 and CDKN1A SNV were present. HSD3B1 and CDKN1A SNVs were present in all three SCA, whereas in two of these tumors SNV in TP53, AURKA and EGFR were found. None of the analyzed tumors showed SNV in USP48, BRAF, BRG1 or CABLES1. The amplification of 17q12 was found in all tumors, except for the ACTH-producing carcinoma. The four clinically functioning ACTH adenomas and the ACTH-CA shared the amplification of 10q11.22 and showed more copy-number variation (CNV) gains and single-nucleotide variations than the nonfunctioning tumors.

Alteración del perfil materno de adipocinas circulantes en preeclampsia / Altered maternal adipokine profile in preeclampsia

Resumen OBJETIVOS: Evaluar las concentraciones séricas maternas de las adipocinas: adiponectina, adipsina, leptina, lipocalina-2, proteína quimioatrayente de monocitos-1, factor de crecimiento nervioso, resistina y factor de necrosis tumoral alfa y su relación con el índice de masa corporal previo al embarazo y la ganancia de peso gestacional en mujeres con preeclampsia comparadas con mujeres sanas, y hacer un análisis de la clasificación de preeclampsia en temprana y tardía. MATERIALES Y MÉTODOS: Estudio transversal, comparativo, retrolectivo, con muestreo no probabilístico por conveniencia efectuado en pacientes atendidas en el Hospital de Gineco-Obstetricia 3, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS). En el preoperatorio se tomó una muestra de sangre para determinar las concentraciones séricas de las adipocinas mediante ensayos multianalito. RESULTADOS: Se estudió una muestra de 75 mujeres con embarazo sano y 44 con preeclampsia (temprana n = 20, tardía n = 24). Solo las concentraciones de adipsina, leptina y factor de necrosis tumoral alfa fueron mayores en preeclampsia que en el embarazo sano [mediana (rango intercuartílico): 3.9 µg/mL (2.9-5.4) vs 2.5 µg/mL (1.9-3.1), 10.6 ng/mL (6.0-19.1) en comparación con 7.1 ng/mL (3.8-12.4), 3.6 pg/mL (2.7-5.8) vs 2.9 (2.3-3.5), respectivamente]. Las concentraciones de las adipocinas no se correlacionaron con el índice de masa corporal previo al embarazo ni con la ganancia de peso gestacional. No hubo diferencias significativas en las concentraciones entre los subtipos de preeclampsia. CONCLUSIÓN: En el tercer trimestre del embarazo la preeclampsia se asocia con un perfil sérico de adipocinas alterado, caracterizado por concentraciones elevadas de adipsina, leptina y factor de necrosis tumoral alfa, que no se relaciona con el índice de masa corporal previo al embarazo, la ganancia de peso gestacional y el subtipo de preeclampsia.

Abstract OBJECTIVES: To evaluate maternal serum concentrations of adipokines: adiponectin, adipsin, leptin, lipocalin-2, monocyte chemoattractant protein-1, nerve growth factor, resistin and tumor necrosis factor-alpha and their relationship with pre-pregnancy body mass index and gestational weight gain in women with preeclampsia compared with healthy women, and to perform an analysis classifying preeclampsia as early and late. MATERIALS AND METHODS: Cross-sectional, comparative, retrolective, non-probabilistic convenience sampling study carried out in patients attended at the Hospital de Gineco-Obstetricia 3, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS). Preoperatively, a blood sample was taken to determine serum adipokine concentrations by multianalyte assays. RESULTS: A sample of 75 women with healthy pregnancy and 44 with preeclampsia (early n = 20, late n = 24) was studied. Only adipsin, leptin, and tumor necrosis factor-alpha concentrations were higher in preeclampsia than in healthy pregnancy [median (interquartile range): 3. 9 µg/mL (2.9-5.4) vs. 2.5 µg/mL (1.9-3.1), 10.6 ng/mL (6.0-19.1) compared to 7.1 ng/mL (3.8-12.4), 3.6 pg/mL (2.7-5.8) vs. 2.9 (2.3-3.5), respectively]. Adipokine concentrations did not correlate with pre-pregnancy body mass index and gestational weight gain. There were no significant differences in concentrations between preeclampsia subtypes. CONCLUSION: In the third trimester of pregnancy, preeclampsia is associated with an altered serum adipokine profile, characterized by elevated concentrations of adipsin, leptin, and tumor necrosis factor-alpha, which is not related to prepregnancy body mass index, gestational weight gain, and preeclampsia subtype.

Epigenetic Alterations Related to Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic complication in pregnancy, which affects the future health of both the mother and the newborn. Its pathophysiology involves nutritional, hormonal, immunological, genetic and epigenetic factors. Among the latter, it has been observed that alterations in DNA (deoxyribonucleic acid) methylation patterns and in the levels of certain micro RNAs, whether in placenta or adipose tissue, are related to well-known characteristics of the disease, such as hyperglycemia, insulin resistance, inflammation and excessive placental growth. Furthermore, epigenetic alterations of gestational diabetes mellitus are observable in maternal blood, although their pathophysiological roles are completely unknown. Despite this, it has not been possible to determine the causes of the epigenetic characteristics of GDM, highlighting the need for integral and longitudinal studies. Based on this, this article summarizes the most relevant and recent studies on epigenetic alterations in placenta, adipose tissue and maternal blood associated with GDM in order to provide the reader with a general overview of the subject and indicate future research topics.

Maternal serum adipokines and inflammatory markers at late gestation and newborn weight in mothers with and without gestational diabetes mellitus.

OBJECTIVES: Maternal obesity increases the risk of gestational diabetes mellitus (GDM) and is positively correlated with neonatal obesity increasing the risk of adiposity in both young and adult offspring. Maternal secreted factors from adipose tissue such as adipokines and inflammatory cytokines may regulate fetal growth. This study investigated associations between maternal adipokines and inflammatory markers at late gestation, and neonatal anthropometric characteristics in mothers with and without GDM. MATERIAL AND METHODS: The study included 65 women with GDM and 65 pregnant women with normal glucose tolerance evaluated at the time of term elective Caesarean section. Adiponectin, leptin, resistin, adipsin, neutrophil gelatinase-associated lipocalin (NGAL), nerve growth factor (NGF), monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) concentrations were measured in maternal serum by the multiplex immunoassay using Magpix technology. C-reactive protein (CRP) was measured with a particle-enhanced turbidimetric immunoassay and neonatal anthropometric variables were assessed. The association of birthweight with individual biomarkers was analyzed using multivariate logistic regression adjusted for maternal factors. RESULTS: Adiponectin, leptin, resistin, adipsin, NGAL and NGF were not significantly associated with higher birthweight. The maternal factors in association with higher birthweight observed in GDM were CRP, MCP-1 and TNF-alpha levels. Regression analysis showed that TNF-alpha was an independent risk factor for higher birthweight (p = 0.046). CONCLUSIONS: These results suggest an involvement of maternal inflammatory markers at late gestation and fetal growth in mothers with GDM, and that TNF-alpha could play a major role.

Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients.

BACKGROUND: COVID-19 counts 46 million people infected and killed more than 1.2 million. Hypoxaemia is one of the main clinical manifestations, especially in severe cases. HIF1α is a master transcription factor involved in the cellular response to oxygen levels. The immunopathogenesis of this severe form of COVID-19 is poorly understood. METHODS: We performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α and its transcriptionally regulated genes. Also performed metanalysis from the publicly available RNAseq data from COVID-19 bronchoalveolar cells. RESULTS: Critically-ill COVID-19 patients show a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, together with mature monocytes and segmented neutrophils. May be the result of a physiological response known as emergency myelopoiesis. These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2). CONCLUSIONS: The up-regulation and participation of HIF1α in events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy. Key messages Critically ill COVID-19 patients show emergency myelopoiesis. HIF1α and its transcriptionally regulated genes are expressed in immature myeloid cells which could serve as molecular targets. HIF1α and its transcriptionally regulated genes is also expressed in lung cells from critically ill COVID-19 patients which may partially explain the hypoxia related events.

Immune tolerance at the maternal-placental interface in healthy pregnancy and pre-eclampsia.

AIM: The objective of this review is to describe the immunological mechanisms which facilitate maternal tolerance at the maternal-placental interface, and to discuss how these mechanisms are disrupted in pre-eclampsia. METHODS: A literature review was performed based on the analysis of papers available on PubMed. The most important and relevant studies regarding the immunological mechanisms which facilitate maternal tolerance in healthy pregnancy and pre-eclampsia are presented in this article. RESULTS: The maternal-placental interface is the site where the immune tolerance begins and develops. Within the innate immunity, natural killer cells, macrophages and dendritic cells play a pivotal role in tolerance through regulation of inflammation. On the other hand, within the adaptive immunity, the correct increase of regulatory T cells is crucial for ensuring immune tolerance toward placental cells. Disturbances in maternal tolerance can lead to the appearance of pregnancy complications such as pre-eclampsia, which has a considerable impact on perinatal morbidity and mortality. CONCLUSION: Our partial knowledge of immunological mechanisms involved in tolerance at the maternal-placental interface indicates that pre-eclampsia is characterized by alterations of this maternal immune tolerance, which could represent the origin of the disease.

Deregulated microRNAs and Adiponectin in Postmenopausal Women with Breast Cancer.

BACKGROUND: Obesity is a risk factor for breast cancer (BC). Some mechanisms through which obesity can lead to cancer development are insulin-like growth factors (IGFs), adipokines, and microRNAs (miRs). The objective of the study was to determine whether miR-17-5p, miR-195-5p, and miR-221-3p expressions were deregulated in serum samples of obese and nonobese postmenopausal women with BC. In addition, insulin, adiponectin, leptin and IGFs were analyzed. METHODS: Fifty postmenopausal women with newly diagnosed BC and 50 postmenopausal healthy women were evaluated. Differences in miRs between BC and healthy cases and between obese and lean participants were analyzed. Receiver operating characteristic curves for miRs for discriminating patients with or without BC were established, and relationships between the miRs, adipokines, and breast tumor characteristics were also investigated. RESULTS: miR-17-5p and miR-195-5p were higher in patients with BC in comparison to the controls, while miR-221-3p and adiponectin were significantly lower. Increased levels of miR-195-5p allowed the differentiation of BC from controls with a sensitivity of 83.3 and a specificity of 78.3%, and were associated with lobular and poorly differentiated cancer. There was no difference in miRs levels between obese and lean groups. CONCLUSIONS: Circulating miRs and adiponectin were deregulated in postmenopausal women with BC.

Placental Proinflammatory State and Maternal Endothelial Dysfunction in Preeclampsia.

OBJECTIVE: To evaluate the placental and decidual gene expression and maternal and umbilical serum concentrations of tumor necrosis factor alpha, interleukin 6 (IL-6), IL-8, IL-10, IL-1 receptor antagonist (IL-1RA), intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (VCAM-1), along with the proinflammatory/anti-inflammatory cytokine ratios in women with preeclampsia (PE) vs. women with normal pregnancy (NP), and to analyze PE classified as early- (EO) and late-onset (LO). METHODS: This cross-sectional study was performed with 50 women with PE (EO n = 30, LO n = 20) and 50 women with NP. Tissue gene expression levels were measured by real-time RT-PCR. Cytokines and adhesion molecules serum concentrations were measured by immunoassays. RESULTS: In PE, placental expression of IL-10 and IL-1RA was lower, while placental IL-8/IL-1RA ratio and maternal concentrations of VCAM-1 were higher vs. NP. In EO, placental expression of IL-10 was lower, while placental IL-8/IL-10 and IL-8/IL-1RA ratios were higher than LO and NP. Maternal concentrations of IL-6 were higher in LO than EO and NP. Throughout PE, maternal VCAM-1 concentrations were higher vs. NP. No significant differences were observed in the decidual expression and umbilical concentrations of the markers between the groups. CONCLUSION: PE associates with a proinflammatory placental state; however, EO associates with a proinflammatory placental state, while LO associates with systemic maternal inflammation. Both subtypes associated with maternal endothelial dysfunction.

Relación entre ácido úrico y composición corporal, perfil metabólico, leptina y adiponectina en mujeres posmenopáusicas / Relationship between uric acid and body composition, metabolic profile, leptin and adiponectin in postmenopausal women

Resumen OBJETIVO: Evaluar la relación del ácido úrico con los parámetros metabólicos, antropométricos, leptina y adiponectina, en mujeres posmenopáusicas en quienes se incrementa el riesgo de enfermedad cardiovascular. MATERIALES Y MÉTODOS: Estudio transversal y descriptivo efectuado en mujeres posmenopáusicas. Parámetros de estudio: mediciones antropométricas (bioimpedancia eléctrica), concentraciones de glucosa, colesterol total, LDL-colesterol, HDL-colesterol, triglicéridos (por métodos enzimáticos), adiponectina, leptina e insulina (por radioinmunoensayo). Cálculo de la resistencia a la insulina por el método HOMA-IR. Descripción de variables con promedio y desviación estándar. Análisis estadístico, con prueba de correlación de Pearson, para determinación de la relación entre el ácido úrico y las variables de estudio y regresión múltiple para determinación de los parámetros con mayor influencia en el ácido úrico. RESULTADOS: Se estudiaron 90 mujeres posmenopáusicas de 55 a 84 años, con edad promedio de 63.7 años. La concentración promedio de ácido úrico de las participantes fue de 4.9 mg/dL. En el análisis bivariado los parámetros antropométricos, el LDL-c, los triglicéridos y la leptina se asociaron positivamente con el ácido úrico y el HDL-c y la adiponectina de forma negativa. En el análisis multivariado la grasa corporal se asoció con el ácido úrico, independientemente del peso corporal (beta = 0.592; p = 0.037). CONCLUSIONES: En mujeres posmenopáusicas, las concentraciones anormales de ácido úrico se relacionan con un perfil cardiometabólico adverso.

Abstract OBJECTIVE: To determine the relation between uric acid and metabolic and anthropometric parameters and adipokines leptin and adiponectin in post-menopausal women. MATERIALS AND METHODS: A descriptive cross-sectional study was performed in post-menopausal women. Anthropometric measurements were taken by electric bioimpedance, and fasting venous blood samples were taken to determine glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides by enzyme techniques, and levels of adiponectin, leptin and insulin were measured by radioimmunoassay. Insulin resistance was calculated using HOMA-IR. The variables were described with mean and standard deviation. Statistical analysis was performed by Pearson correlation test to evaluate the relation between uric acid and the study variables, and a multiple regression was performed to determine the parameters with greatest influence on uric acid. RESULTS: The study included 90 post-menopausal women aged 55 to 84 years. The average age of the participants was 63.7 years, and the average concentration of uric acid was 4.9 mg/dL. In bivariate analysis, anthropometric parameters, LDL-cholesterol, triglycerides and leptin showed positive association with uric acid, and HDL-cholesterol and adiponectin had a negative one. In multiple regression analysis, body fat associated with uric acid independent of body weight (beta=0.592, p=0.037). CONCLUSIONS: Uric acid relates with an adverse cardio-metabolic profile in post-menopausal women.

Similar to Adiponectin, Serum Levels of Osteocalcin are Associated with Mammographic Breast Density in Postmenopausal Women.

OBJECTIVE: Breast cancer is the most common type of cancer in Canadian women and worldwide. Mammographic density is a well-established breast cancer risk. Recent evidence suggested inverse correlations among adiponectin, osteocalcin, and the risk developing breast cancer. The objective of the study was to evaluate the relationship between breast density and adiponectin and osteocalcin concentrations. METHODS: A cross-sectional study was performed in 239 women, age range 40 to 60. Mammographic density, serum adiponectin, and osteocalcin levels were measured. According to the Wolfe method, participants were divided into those with low-risk and high-risk pattern mammograms. RESULTS: The study population included 107 premenopausal and 132 postmenopausal women. Parameters were no different between women with low-risk and high-risk patterns. In obese postmenopausal women, the high-risk pattern mammogram group had significantly higher values of adiponectin and osteocalcin compared with the low-risk pattern group. Multiple linear regression analyses showed that adiponectin and osteocalcin levels were associated with high-risk pattern mammograms. CONCLUSION: Adiponectin and osteocalcin levels were directly associated with high-risk pattern mammograms in obese postmenopausal women. These results do not support the use of adipokines as biomarkers; nevertheless, the most important factor is to assess the risk through breast density.

[Persists the controversy concerning the rutinary use of diagnostic tests in asymptomatic persons]. / Persiste la controversia acerca del uso rutinario de pruebas de detección en personas asintomáticas.

Currently, in medicine there is an environment replete with controversy and debate, partially due to the popular concept Evidence-Based Medicine, and to the development of technological advances and, apparently, better therapeutic resources. This has led to the establishment of an over-diagnosis epidemic and to an excess of therapeutic interventions, which do not necessarily lead to a longer life expectancy. Some medical controversies, which have called the attention of physicians and even of common people are those related with dislipoproteinemias, pre-diabetes and detection of cancer in asymptomatic persons. The debate and the controversy will surely continue and that is why it is very important to emphasize that clinical practice should be personalized, taking into account risks and implied benefits.

En la actualidad existe en medicina un ambiente repleto de controversias y debates, en parte generado por la popularidad del concepto de medicina basada en evidencia y por la aparición de avances tecnológicos y aparentemente mejores recursos terapéuticos. Esto ha llevado a la instalación de una epidemia diagnóstica y a una excesiva politerapéutica que no se traducen en una más larga expectativa de vida. Algunas controversias médicas que han llamado la atención de los médicos e incluso del público en general son las relacionadas con los tópicos de dislipoproteinemia, prediabetes y detección de cáncer en personas asintomáticas. El debate y la controversia seguramente continuarán y por ello resalta la importancia de la práctica médica en la individualidad, tomando en cuenta los riesgos y los beneficios implicados.