Non-polymeric Microspheres for the Therapeutic Use of Estrogens: An Innovative Technology

Non-polymeric microspheres are stable-shaped particles constituted by crystalline organic compounds. This technology allows controlled release of parental products that has its prime value on estrogen therapy. The structure is a non-polymeric crystalline microsphere that uses a low solubility fatty acid, cholesterol as a carrier. Cholesterol is a waxy lipid, a substance that is insoluble in water and has been recognized as safe as excipient by FDA for the manufacturing of drugs. Cholesterol is a lipid present in the cell membrane and subcellular organelles of tissues and serves as the building block for all steroid hormones including cortisol, aldosterone, estrogen, and testosterone; therefore, this fatty acid provides better biocompatibility than polymers. The use of cholesterol as a low solubility carrier was used to develop a first of its kind, parental HT product for the management of menopausal symptoms carrying estrogen microspheres in an aqueous suspension, which would allow an extended estrogen release maintaining plasmatic therapeutic concentrations. Estradiol doses would be up to 30 times lower than that provided by oral and transdermal routes fulfilling current recommendations regarding the use of a low dose and the nonoral route. Both intramuscular monthly administered formulations of E/P non-polymeric microspheres had favorable pharmacokinetic and safety profiles, suggesting this route as an interesting, novel, and suitable way of treating menopause-related symptoms

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Weter consumption during pregnancy and lactation

During pregnancy, water is retained partially owing to an increase in vasopressin production. Ingested water is used to produce amniotic fluid. Climate conditions and physical activity, gestational nausea and vomit, and a higher caloric intake, increases water needs; during lactation, more water is needed to produce milk. Dehydration during pregnancy is especially dangerous; it must be avoided. Physiological changes during pregnancy modify water metabolism: blood volume and glomerular filtration rate increase; more water is lost trhough sweating and respiration. Placenta con- tains up to 500 mL of water, and there are between 500-1,200 mL of amniotic fluid. Different studies recommend a total water intake of 2,700-4,800 mL/day during pregnancy, of which 1,470-2,370 should be beverages and water. For the Mexican population, the recommendation is 3,000 mL/day. Based on energy intake and the rule of 1-1.5 mL of water per kcal, water intake must increase in at least 300 mL/day at the beginning of the third pregnancy trimester. During lactation the recommended intake is of 3-3.6 L/ day, depending on age. Obesity and overweight during pregnancy are a major health problem, to which sugary beverages contribute. Water must be considered the best choice for hydration during pregnancy and lactation

New Insights into the Role of Matrix Metalloproteinases in Preeclampsia

Preeclampsia is a severe pregnancy complication globally, characterized by poor placentation triggering vascular dysfunction. Matrix metalloproteinases (MMPs) exhibit proteolytic activity implicated in the efficiency of trophoblast invasion to the uterine wall, and a dysregulation of these enzymes has been linked to preeclampsia. A decrease in MMP-2 and MMP-9 interferes with the normal remodeling of spiral arteries at early pregnancy stages, leading to the initial pathophysiological changes observed in preeclampsia. Later in pregnancy, an elevation in MMP-2 and MMP-9 induces abnormal release of vasoactive factors conditioning hypertension. Although these two enzymes lead the scene, other MMPs like MMP-1 and MMP-14 seem to have a role in this pathology. This review gathers published recent evidence about the implications of different MMPs in preeclampsia, and the potential use of these enzymes as emergent biomarkers and biological therapeutic targets, focusing on studies involving human subjects

Metabolic markers during pregnancy and their association with maternal and newborn weight status

<div><p>Background/Aims</p><p>Obesity during pregnancy increases the risk of adverse clinical outcomes and is associated with low-grade chronic inflammation. We describe maternal metabolic risk and inflammation by maternal weight status, and evaluate the association of metabolic and inflammatory markers with birthweight in a group of pregnant Mexican women.</p><p>Methods</p><p>This study derived from a prospective cohort of healthy pregnant women <14 weeks of gestation, receiving prenatal care at National Institute of Perinatology (Mexico, 2009–2013). Metabolic and inflammatory markers were measured in maternal serum in all three pregnancy trimesters (1st: 11.42±1.7; 2nd: 21.06±2.4; 3rd: 32.74±2.3 weeks). Pregestational weight was self-reported, and body mass index (BMI) was calculated. Gestational weight gain was evaluated in the third trimester. Newborn´s weight was measured at birth. We carried out correlations, general mixed linear model and regression analyses, based on pregestational weight (self-reported), body mass index (BMI), gestational weight gain (evaluated in the third trimester) and newborn weight (measured at birth).</p><p>Results</p><p>Of the 177 women included in the study (mean age = 26.93±8.49), thirty-eight percent (n = 67) were overweight or had obesity, and 32.8% (n = 58) showed excessive gestational weight gain. We found insulin, lipids (including total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides-TG), leptin and interleukin 1b (IL-1b) all increased significantly (p<0.05) during pregnancy. Pregestational maternal weight status altered longitudinal concentrations of insulin, leptin, adiponectin, TG and C reactive protein. Excessive gestational weight gain was associated with higher maternal insulin in the third trimester (p<0.05). Early pregnancy leptin and TNFα were determinants of birthweight in women with normal weight, but not in overweight or obese women.</p><p>Conclusions</p><p>Maternal weight status affected the concentrations of insulin, leptin, adiponectin, triglycerides and C reactive protein throughout pregnancy. The role of early leptin and TNFα in fetal growth need further study given the association was only observed in normal weight women. This study presents data distribution of metabolic and inflammatory markers of normal weight and overweight/obese women that did not develop GDM, preeclampsia nor macrosomia.</p></div

Influential Serum Kinases (Non-sFlt-1) and Phosphatases in Preeclampsia—Systemic Review and Metanalysis

The early identification of women with an increased risk of preeclampsia (PE) is desirable, but apart from soluble fms-like tyrosine kinase-1 (sFlt-1), few biomarkers have previously been identified as relevant for predicting preeclampsia. Since kinases and phosphatases regulate critical biological processes and previous evidence suggests a potential role of these molecules in preeclampsia, we performed this systematic review and metanalysis. The objective was to determine if there are kinases and phosphatases whose serum levels are different between women with and without PE, being relevant biomarkers of PE. We followed the recommendations of Cochrane and the Preferred Reported Items for Systematic Reviews and Metanalysis (PRISMA) to perform this study. The MESH terms preeclampsia, kinases, phosphatases, angiopoietins, soluble tyrosine protein kinase receptor (sTIE2), and cellular-mesenchymal-epithelial transition factor (c-MET) were combined to find relevant articles in the PubMed, PROSPERO, and Cochrane databases. Then, a qualitative and quantitative analysis was performed in R Studio software. From 580 abstracts identified, 37 were included in the final analysis, which comprised 24,211 pregnant women (2879 with PE and 21,332 women without PE [HP]. The pooled analysis showed that serum creatine kinase (CK) (SMD: 2.43, CI 95% 0.25–4.62) was significantly higher in PE, whereas sTIE2 and anti-angiogenic factor soluble c-Met (sMet)were significantly lower in PE than in HP (SMD: −0.23, CI95% −0.37 to −0.09; and SMD:0.24, CI95% 0.01–0.47, respectively). Adenosine monophosphate-activated protein kinase (AMPK), angiopoietin-1 (ANG-1), angiopoietin-2 (ANG-2), the ratio angiopoietin-1/angiopoietin-2, acid phosphatase, and alkaline phosphatase were not different between women with PE and HP. In summary CK, sTIE2, and c-MET are relevant biomarkers of PE. It is desirable to incorporate them into current models for PE prediction to evaluate their utility as biomarkers

Metabolic and inflammatory markers during pregnancy and by pregestational weight status.

<p>Metabolic and inflammatory markers during pregnancy and by pregestational weight status.</p

Significant correlation coefficients of the association between metabolic and inflammatory markers and between maternal and newborn weight with metabolic and inflammatory markers.

<p>Significant correlation coefficients of the association between metabolic and inflammatory markers and between maternal and newborn weight with metabolic and inflammatory markers.</p

General mixed linear models evaluating the effect of pregnancy and pregestational overweight/obesity on metabolic and inflammatory markers.

<p>General mixed linear models evaluating the effect of pregnancy and pregestational overweight/obesity on metabolic and inflammatory markers.</p