Gestational Diabetes Mellitus Remodels the Fetal Brain Fatty Acid Profile Through Placenta-Brain Lipid Axis in C57BL/6J Mice.

BACKGROUND: Polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal-fetal fatty acid metabolism. OBJECTIVE: This study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/ß-catenin/MFSD2a) of the placenta and fetal brain using western blotting. RESULTS: GDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n-3 PUFA and n-6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n-3 PUFA in the fetal brain. GDM downregulated the Wnt3/ß-catenin/MFSD2a signaling pathway, which transfers n-3 PUFA in the placenta and fetal brain. The HF diet increased n-6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n-6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental ß-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). CONCLUSIONS: Maternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/ß-catenin/MFSD2a pathway of the placental-fetal barrier and by affecting maternal fatty acid metabolism.

Delivery of Local Anesthesia: Current Strategies, Safety, and Future Prospects.

BACKGROUND: The systemic administration of anesthesia is associated with severe and undesirable side effects such as sedation, vomiting, nausea, allergies, respiratory problems, and neutrophil dysfunction. With the increase in the procedures of limb surgery, cosmetics, facial, skin, and cancer reconstruction, the demand for local anesthesia has increased multifold during the last one decade. Therefore, novel, safe, and cost-effective methods are being developed to deliver local anesthetics by the surgeons. METHOD: To prepare a comprehensive research report on anesthesia, we performed a structured literature search of bibliographic databases for peer-reviewed articles published recently. The studies of different articles were summarized and a deductive qualitative and quantitative data analysis was applied. Subsequently, a comprehensive summary of the analysis was used to frame this review article with ample examples. RESULTS: A thorough analysis of the reports suggested that there have been tremendous developments of synthesizing nanoparticle-based local anesthesia drugs. The active targeting ability of nanoparticle-based drug delivery strategy can further help to deliver the desired anesthetic drug locally. It was also found that different local anesthetic drugs are developed into liposome form and show better efficacy in patients receiving anesthesia. CONCLUSION: The findings of this review article endorse that safe delivery of anesthesia drugs are essential for the safety of patients. Further, nanotechnology-based strategies are extremely useful for targeted delivery of anesthetic drugs at the required dose without affecting the neighboring tissues.

[Meta-analysis of effect of n-3 long-chain polyunsaturated fatty acid supplementation of pregnant women on head circumference of newborn infants].

OBJECTIVE: To evaluate systematically the effect of n-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA) supplementation of pregnant women on head circumference of newborn infants. METHODS: A thorough literature search was done for full texts which studied the effect of n-3 LC-PUFA supplementation of pregnant women on head circumference of newborn infants among PubMed, Cochrane Library, Chinese periodical full text database and Wanfang database using the mesh terms as n-3, long chain polyunsaturated fatty acids, DHA, EPA, docosahexaenoic acid, eicosapentaenoic acid, fish oil, pregnancy, infant. Only randomized controlled trials were chosen for analysis. A total of 74 relevant articles were selected. RevMan 5.0 software was used to perform the Meta analysis on those valid studies. Weighted mean difference was calculated with inverse variance method. The sensitivity analysis was also performed. RESULTS: Eight articles met the inclusion criteria, among which 6 literatures were from developing countries and the other 2 from developed countries. All of them were written in English. These studies were reported from 2001 to 2011. Intervention group included 871 objects with n-3 LC-PUFA supplementation, whereas control group included 894 objects with placebo or no supplementation. Supplementation was associated with significantly greater head circumference of the infants in the intervention group than that of the control group (weighted mean difference was 0.17 cm, 95%confidence interval (CI) was 0.01 - 0.32 cm, P < 0.05). But the difference was no long significant according to the sensitivity analysis (weighted mean difference was 0.16 cm, 95%CI was -0.01 - 0.34 cm, P = 0.07). The funnel plot was symmetrical, indicating there was no publication bias between the eight studies. CONCLUSION: It can't be confirmed whether supplementation with n-3 LC-PUFA of pregnant women can increase the infants' head circumference at birth from present data acquired.

Effects of acute hypoglycemia on the orexin system in rat.

OBJECTIVE: To evaluate the effects of acute glucose level changes on expression of prepro-orexin, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) mRNA in rat hypothalamus tissue and pancreatic islets cells. METHODS: Thirty adult male Wistar rats were randomly divided into three equal groups (n = 10). The acute hypoglycemia rat model was induced by a single subcutaneous injection of insulin. Twenty acute hypoglycemia rats were divided into group B and group C. Group B was allowed to eat freely, while group C was food-deprived. Control rats were injected the same volume of saline. The effect of glucose levels (2.8 mmol/L and 8.3 mmol/L) on pancreatic islet cell orexin system was detected in pancreas islet cell cultured in vitro. The expression of prepro-orexin and OXR mRNA was examined in rat hypothalamus tissue and pancreatic islets cell cultured in vitro using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Expression of orexin mRNA increased about 150% for the food-deprived hypoglycemia rats in comparison with control group (P < 0.01), whereas expression of OX1R mRNA decreased up to 30% (P < 0.01). However, expression of OX2R mRNA was unchanged in comparison with control group. In vitro, after incubation with 2.8 mmol/L glucose for 6 hours, the expression of prepro-orexin mRNA increased 2 times in rat pancreas islet cells in comparison with 8.3 mmol/L glucose group (P < 0.01). But the expression of OX1R mRNA was not sensitive to acute glucose fluctuation. CONCLUSIONS: Orexin in rat hypothalamus is stimulated by decline in blood glucose and inhibited by signals related to feeding. Moreover, glucose plays a role in modulating the gene expression of prepro-orexin in rat pancreatic islet cells.