Effect of Prenatal Care on Perinatal Outcomes of Pregnant Women with Diabetes Mellitus: A Systematic Review.

Objective: to evaluate the effect of prenatal care (PC) on perinatal outcomes of pregnant women with diabetes mellitus (DM). Methods: systematic review developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines and conducted through the population, intervention, control, and outcomes (PICO) strategy. Clinical trials and observational studies were selected, with adult pregnant women, single-fetus pregnancy, diagnosis of DM, or gestational DM and who had received PC and/or nutritional therapy (NT). The search was carried out in PubMed, Scopus, and BIREME databases. The quality of the studies was evaluated using the tools of the National Heart, Lung and Blood Institute-National Institutes of Health (NHLBI-NIH). Results: We identified 5972 records, of which 15 (n=47 420 pregnant women) met the eligibility criteria. The most recurrent outcomes were glycemic control (14 studies; n=9096 participants), hypertensive disorders of pregnancy (2; n=39 282), prematurity (6; n=40 163), large for gestational age newborns (4; n=1556), fetal macrosomia (birth weight >4kg) (6; n=2980) and intensive care unit admission (4; n=2022). Conclusions: The findings suggest that PC interferes with the perinatal outcome, being able to reduce the risks of complications associated with this comorbidity through early intervention, especially when the NT is an integral part of this assistance.

7-Amine-spiro[chromeno[4,3-b]quinoline-6,1'-cycloalkanes]: Synthesis and cholinesterase inhibitory activity of structurally modified tacrines.

Five new examples of 9,10-chloro(bromo)-7-amine-spiro[chromeno[4,3-b]quinoline-6,1'-cycloalkanes] - in which cycloalkanes = cyclopentane, cyclohexane, and cycloheptane - were synthesized at yields of 42-56%, using a sequential one-pot two-step cyclocondensation reaction of three different scaffolds of 2-aminobenzonitriles and the respective spiro[chroman-2,1'-cycloalkan]-4-ones, and using AlCl3 as the catalyst in a solvent-free method. Subsequently, the five new spirochromeno-quinolines and nine quinolines previously published by us (14 modified tacrine scaffolds) were subjected to AChE and BChE inhibitory activity evaluation. The molecule containing a spirocyclopentane derivative had the highest AChE and BChE inhibitory activity (IC50 = 3.60 and 4.40 µM, respectively), and in general, the non-halogenated compounds were better inhibitors of AChE and BChE than the halogenated molecules. However, the inhibitory potency of compounds 3a-n was weaker than that of tacrine. By molecular docking simulations, it was found that the size of the spirocarbocyclic moieties is inversely proportional to the inhibitory activity of the cholinesterases, probably because an increase in the size of the spirocyclic component sterically hindered the interaction of tacrine derivatives with the active site of tested cholinesterases. The findings obtained here may help in the design and development of new anticholinesterase drugs.

Effect of the Dietary Approaches to Stop Hypertension (DASH) diet on the development of preeclampsia and metabolic outcomes in pregnant women with pre-existing diabetes mellitus: a randomised, controlled, single-blind trial.

Preeclampsia (PE) affects up to five times more women with pre-existing diabetes mellitus (PDM) than women without it. The present study aimed to identify the effect of the DASH diet on PE incidence (primary outcome) and blood pressure, glycated haemoglobin (GH), serum lipids, glutathione peroxidase (GP), C-reactive protein (CRP - secondary outcomes) in pregnant with PDM. This randomised, controlled, single-blind trial studied sixty-eight pregnant women with PDM throughout prenatal care until delivery (18 weeks) at a public maternity hospital, Brazil. The standard diet group (SDG) received a diet containing 45-65 % carbohydrates, 15-20 % protein and 25-30 % lipids. The DASH diet group (DDG) received the adapted DASH diet with a similar macronutrient distribution, but with a higher concentration of fibres, unsaturated fats, calcium, magnesium and potassium as well as lower saturated fat. Student's t, Mann-Whitney U and the Chi-square tests were used to compare outcomes. PE incidence was 22⋅9 % in the SDG and 12⋅1 % in the DDG (P = 0⋅25). GP levels significantly increased in the DDG (intra-group analysis; mean difference = 1588 [CI 181, 2994], P = 0⋅03) and tended to be different from the variation in the SDG (mean difference = -29⋅5 [CI -1305; 1⋅365]; v. DDG: 1588 [CI 181; 2994], P = 0⋅09). GH levels decreased significantly and similarly between groups (SDG: -0⋅61 [CI -0⋅26, -0⋅96], P = 0⋅00) v. DDG: -1⋅1 [CI -0⋅57, -1⋅62], P = 0⋅00). There was no evidence of a difference in PE incidence at the end of the intervention between the two diets. The DASH diet seems to favour PE-related biochemical markers.

Influence of the DASH Diet on Gestational Weight Gain and Perinatal Outcomes in Women with Pre-Existing Diabetes Mellitus: A Randomized, Single-Blind, Controlled Clinical Trial.

BACKGROUND: This study aimed to investigate the influence of the dietary approaches to stop hypertension (DASH) diet on gestational weight gain and perinatal outcomes in pregnant women with pre-existing diabetes mellitus (PDM). METHODS: A randomized, single-blind, controlled clinical trial was conducted with 68 pregnant women with PDM throughout prenatal care until delivery (18 weeks) at a public maternity hospital in Rio de Janeiro, Brazil (2016-2020). The standard diet adopted by the control group (standard diet group-SDG) contained 45-55% carbohydrates, 15-20% protein, and 25-30% lipids of the total energy intake. An adapted DASH diet, with a similar macronutrient composition, but with higher calcium, potassium, magnesium, fiber, and reduced saturated fat, was prescribed for the intervention group (DASH diet group-DDG). Student's t- or Mann-Whitney U tests were used to compare outcomes between groups. To assess the trajectory of gestational weight gain throughout the intervention between the study groups, linear mixed-effects regression models were used. RESULTS: The DDG had lower gestational weight gain at the fifth (p = 0.03) and seventh appointment (p = 0.04), with no difference in average total gestational weight gain (SDG: 10 kg [SD = 4]; DDG: 9 kg [SD = 5], p = 0.23). There was a trend for a lower length of stay of the newborns (p = 0.08) in the DDG without differences for other perinatal outcomes. CONCLUSIONS: The DASH diet promoted less variation in gestational weight gain without promoting a difference in total gestational weight gain, and there was no difference between the study groups for perinatal outcomes.

Erratum: Effect of the Dietary Approaches to Stop Hypertension (DASH) diet on the development of preeclampsia and metabolic outcomes in pregnant women with pre-existing diabetes mellitus: a randomized, controlled, single-blind trial - CORRIGENDUM.

[This corrects the article DOI: 10.1017/jns.2023.54.].

Hybrid Nanoparticles as an Efficient Porphyrin Delivery System for Cancer Cells to Enhance Photodynamic Therapy.

Photodynamic therapy (PDT) is a potential non-invasive approach for application in oncological diseases, based on the activation of a photosensitizer (PS) by light at a specific wavelength in the presence of molecular oxygen to produce reactive oxygen species (ROS) that trigger the death tumor cells. In this context, porphyrins are interesting PS because they are robust, have high chemical, photo, thermal, and oxidative stability, and can generate singlet oxygen (1O2). However, porphyrins exhibit low solubility and a strong tendency to aggregate in a biological environment which limits their clinical application. To overcome these challenges, we developed hybrid nanostructures to immobilize 5,10,15,20-tetrakis[(4-carboxyphenyl) thio-2,3,5,6-tetrafluorophenyl] (P), a new third-generation PS. The biological effect of this system was evaluated against bladder cancer (BC) cells with or without light exposition. The nanostructure composed of lipid carriers coated by porphyrin-chitosan (P-HNP), presented a size of ca. 130 nm and low polydispersity (ca. 0.25). The presence of the porphyrin-chitosan (P-chitosan) on lipid nanoparticle surfaces increased the nanoparticle size, changed the zeta potential to positive, decreased the recrystallization index, and increased the thermal stability of nanoparticles. Furthermore, P-chitosan incorporation on nanoparticles increased the stability and enhanced the self-organization of the system and the formation of spherical structures, as observed by small-angle X-ray scattering (SAXS) analysis. Furthermore, the immobilization process maintained the P photoactivity and improved the photophysical properties of PS, minimizing its aggregation in the cell culture medium. In the photoinduction assays, the P-HNP displayed high phototoxicity with IC50 3.2-folds lower than free porphyrin. This higher cytotoxic effect can be correlated to the high cellular uptake of porphyrin immobilized, as observed by confocal images. Moreover, the coated nanoparticles showed mucoadhesive properties interesting to its application in vivo. Therefore, the physical and chemical properties of nanoparticles may be relevant to improve the porphyrin photodynamic activity in BC cells.

Assessing the cytotoxic potential of glycoalkaloidic extract in nanoparticles against bladder cancer cells.

OBJECTIVE: This study proposed to use the nanotechnology to deliver glycoalkaloidic extract (AE) to bladder cancer cells, evaluating their activity in 2D and 3D models and the biological mechanism of cell death. METHODS: NPs were prepared by nanoprecipitation method using polylactic acid (PLA) and characterized considering their size, charge, particle concentration and stability. The cytotoxicity was evaluated in 2D and 3D model, and the apoptosis and cell cycle were investigated using flow cytometry. KEY FINDINGS: NPs loading AE (NP-AE) had diameter around 125 ± 6 nm (PdI <0.1) and negative charge. The encapsulation efficiency of SM and SS was higher than 85% for both compounds. The obtained formulation showed a significant in-vitro cytotoxic effect against RT4 cells in a dose-dependent manner with IC50 two fold lower than the free AE. The cytotoxic effect of NP-AE was mediated by apoptosis and cell cycle arrested in the S phase. RT4 cells cultured under 3D conditions exhibited a higher resistance to the treatments (IC50 ~ three fold higher than in 2D cell culture). CONCLUSION: The NP-AE might be a promising nanocarrier to load and deliver glycoalkaloids against bladder cancer.