scholarly journals Folic acid uptake by the human syncytiotrophoblast is affected by gestational diabetes, hyperleptinemia, and TNF-α

2013 ◽  
Vol 73 (1-4) ◽  
pp. 388-394 ◽  
Author(s):  
João R. Araújo ◽  
Ana Correia-Branco ◽  
Liliana Moreira ◽  
Carla Ramalho ◽  
Fátima Martel ◽  
...  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura K. Cole ◽  
Genevieve C. Sparagna ◽  
Marilyne Vandel ◽  
Bo Xiang ◽  
Vernon W. Dolinsky ◽  
...  

AbstractBerberine (BBR) is an isoquinoline alkaloid from plants known to improve cardiac mitochondrial function in gestational diabetes mellitus (GDM) offspring but the mechanism is poorly understood. We examined the role of the mitochondrial phospholipid cardiolipin (CL) in mediating this cardiac improvement. C57BL/6 female mice were fed either a Lean-inducing low-fat diet or a GDM-inducing high-fat diet for 6 weeks prior to breeding. Lean and GDM-exposed male offspring were randomly assigned a low-fat, high-fat, or high-fat diet containing BBR at weaning for 12 weeks. The content of CL was elevated in the heart of GDM offspring fed a high fat diet containing BBR. The increase in total cardiac CL was due to significant increases in the most abundant and functionally important CL species, tetralinoleoyl-CL and this correlated with an increase in the expression of the CL remodeling enzyme tafazzin. Additionally, BBR treatment increased expression of cardiac enzymes involved in fatty acid uptake and oxidation and electron transport chain subunits in high fat diet fed GDM offspring. Thus, dietary BBR protection from cardiac dysfunction in GDM exposed offspring involves improvement in mitochondrial function mediated through increased synthesis of CL.


Author(s):  
Xinmei Huang ◽  
Bingbing Zha ◽  
Manna Zhang ◽  
Yue Li ◽  
Yueyue Wu ◽  
...  

Abstract Objective The immune system plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). Monocytes, the main innate immune cells, are especially important in the maintenance of a normal pregnancy. Here, we investigated the potential effect of monocytes in GDM. Materials and Methods: Monocyte count was monitored throughout pregnancy in 214 women with GDM and 926 women without in a case-control and cohort study. Circulating levels of inflammatory cytokines, placenta-derived macrophages and their products were measured. Results Throughout pregnancy, monocyte count was significantly decreased in women with GDM, and closely associated with glucose level, insulin resistance and newborn weight. First-trimester monocyte count outperformed that of the second and third trimester as a risk factor and diagnostic predictor of GDM and macrosomia in both the case-control and cohort study. In addition, our cohort study showed that as first-trimester monocyte count decreased, GDM and macrosomia incidence, glucose level and newborn weight increased in a stepwise manner. Risk of GDM started to decrease rapidly when first-trimester monocyte count exceeded 0.48 × 10 9/L. Notably, CD206 and IL-10 were significantly lower, while CD80, CD86, TNF-α and IL-6 were higher in both GDM placental tissue and peripheral blood. First-trimester monocyte count was positively related to IL-10 and CD206, but negatively related to CD80, CD86, TNF-α and IL-6. Conclusions Decreased monocyte count throughout pregnancy was closely-associated with the development of GDM, macrosomia and the chronic inflammatory state of GDM. First-trimester monocyte count has great potential as an early diagnostic marker of GDM.


1987 ◽  
Vol 252 (4) ◽  
pp. F757-F760 ◽  
Author(s):  
J. Selhub ◽  
S. Nakamura ◽  
F. A. Carone

Surface proximal convoluted tubules (PCT) in rats were microinfused in situ with [3H]folic acid to study the role of folate binding protein (FBP) in the kidney brush-border membrane for renal conservation and transport of folate [3H]folic acid absorption was linearly related to tubular length of PCT and occurred largely in this segment of the tubule. Unlabeled folate derivatives inhibited [3H]folic acid absorption, the extent of which was dependent on the type of unlabeled folate used and its concentration. At equivalent concentrations, inhibition was most effective with unlabeled folic acid, slightly lower than with 5-methyltetrahydrofolate and least effective with methotrexate. Comparisons between [3H]folic acid absorption before and after infusion of a saturating dose of unlabeled folic acid or repetitive injections of [3H]folic acid into the same tubular site revealed continuous and rapid regeneration of unsaturated folic acid uptake sites with an apparent half-life of 28.75 +/- 8.75 s. Determination of [3H] retained in the tubule at various periods after microinfusion of [3H]folic acid revealed slow cellular disappearance with an apparent half-life of 47.3 +/- 5.4 min. It is proposed that the brush-border FBP functions as a receptor of infused folic acid and that following the binding of the ligand the folic acid/FBP complex undergoes a rapid change that results in the internalization of folic acid and regeneration of unsaturated binding sites at the membrane surface. Internalized folic acid is slowly released into renal capillaries.


2020 ◽  
Author(s):  
Zhiwei Zhang ◽  
Hui Zhao ◽  
Aixia Wang

Background: Gestational diabetes mellitus (GDM) has a high incidence rate among pregnant women. The objective of the study was to assess the effect of plant-derived oleuropein in attenuating inflammatory and oxidative stress of GDM. Methods: Oleuropein was administered to GDM mice at the doses of 5 or 10 mg/kg/day. Body weight, blood glucose, insulin and hepatic glycogen levels were recorded. To evaluate the effect of oleuropein in reducing oxidative stress, enzyme-linked immunosorbent assay (ELISA) was used to measure the hepatic oxidative stress markers. The inflammation levels of GDM mice were evaluated by measuring serum levels of IL-6 and TNF-α by ELISA, and mRNA levels of IL-1β, TNF-α and IL-6 by real-time PCR (RT-PCR). The AMP-activated protein kinase (AMPK) signaling pathway was assessed by Western blot. Gestational outcome was analyzed through comparing litter size and birth weight. Results: Oleuropein attenuated the elevated body weight of GDM mice, and efficiently reduced blood glucose, insulin and hepatic glycogen levels. Oxidative stress and inflammation were alleviated by oleuropein treatment. The AMPK signaling was activated by oleuropein in GDM mice. Gestational outcome was markedly improved by oleuropein treatment. Conclusions: Our study suggests that oleuropein is effective in alleviating symptoms of GDM and improving gestational outcome in the mouse model. This effect is achieved by attenuating oxidative stress and inflammation, which is mediated by the activation of the AMPK signaling pathway.


2021 ◽  
Vol 15 (5) ◽  
pp. 1270-1275
Author(s):  
S. Ferdousmakan ◽  
Namitha K.B ◽  
M. Etesami

Objective: The present study is aimed at Medication Safety in Obstetrics and Gynecology Ward in Jayanagar General Hospital, Bangalore, India Methodology: It is a prospective observational study, conducted in the inpatient obstetrics and gynecology ward in Jayanagar General Hospital. The study was conducted for 6 months. CRF (Case record form) was designed to record the clinical profile and treatment pattern which contains patient demography, family history, past medication history, obstetric history and follow up and further medication safety was assessed in the patient according to WHO and US-FDA guidelines. The patient demographics and all medically relevant information were noted in a predefined data collection form. Alternatively, these case charts were reviewed for prescription legibility and completeness, unaccepted abbreviations, the capture of relevant information in case sheets, contraindication, drug interactions, and adverse drug events. Result: The data of 150 pregnant women admitted to obstetrics and gynecology ward for delivery related care during the period October 2018 to April 2019 were analyzed. It was observed that 20.67% had Hypertension, 14.67% had Gestational diabetes mellitus, and 8.67% had urinary tract infections as major comorbidities. Among the study population most of them 20.67% had oligohydramnios as a major pregnancy risk factor followed by 12% of preeclampsia and 3.33% of small for gestational age. A total of 1950 drugs were prescribed, and thus the average number of drugs per patient was 13.28. Iron, folic acid, calcium, and vitamins were the most frequently used drugs during the pregnancy. Category A drug constituted 623(54.50%) followed by category B drug 398(34.82%) out of 1950 drugs used in pregnant subjects. Another category C, D and X were 6.99%, 3.5% and 0.1% respectively. The most common drug interaction was found to be between Metronidazole and ondansetron, which may be due to high usage of tramadol and metoclopramide in pregnancy. Conclusion: Among the study patients most them 75.33% were in the age group of 21-30 years. Most of the 20.67% and 14.67% had hypertension and gestational diabetes mellitus as co- morbidities. On the review of 150 prescriptions, the average number of drugs prescribed was found to be 7.62. Iron, folic acid, calcium, and vitamins were the most frequently used drugs during the pregnancy. Most of the used drugs were from Category A (54.50%). Only 0.1% of the drug were from Category X. There were 183 possible risks of major potential drug interactions. The most common interaction was between Metronidazole and ondansetron. The majority of the drugs were prescribed as per FDA category A, the safest category during pregnancy. Keywords: Medication Safety, Obstetrics, Gynecology, pregnancy


1986 ◽  
Vol 251 (2) ◽  
pp. G218-G222 ◽  
Author(s):  
J. Zimmerman ◽  
J. Selhub ◽  
I. H. Rosenberg

The effect of sodium on folate transport across the intestinal luminal membrane was analyzed using two techniques: the "influx" chamber and isolated brush-border membrane vesicles. Preincubation of tissue in Na+-free medium did not have a consistent effect on folic acid influx provided that Na+ was present in the test solution. Replacement of Na+ in the test solution by choline+ resulted in a significant reduction of folic acid influx. However, when intestinal sheets that had been equilibrated in Na+-free solution were exposed to test solution containing either Na+, Li+, K+, Rb+, Cs+, Tris+, or guanidinium+ as main cations, folic acid influx was not significantly decreased. Concentration-dependence studies showed that replacement of Na+ by Rb+ did not affect the saturable mechanism of folate transport. Rather, a decrease in nonsaturable folic acid uptake accounted for the slightly reduced influx observed in the presence of Rb+. Experiments with brush-border membrane vesicles revealed that methotrexate uptake was significantly higher in the presence of external Na+ than in the presence of K+, but was not different from uptake in the presence of K+ plus valinomycin. These data suggest that the saturable component of folate transport is not Na+ dependent, and nonsaturable transport of folic acid across the luminal membrane occurs in part through a conductive pathway that involves a negatively charged species of folate and a cation whose membrane permeability affects the rate of folate transport. The importance of Na+ in this process in vivo derives from the fact that Na+ is the most permeant cation available at the absorptive site in the small intestine.


2006 ◽  
Vol 84 (2) ◽  
pp. 247-255 ◽  
Author(s):  
Elisa Keating ◽  
Clara Lemos ◽  
Isabel Azevedo ◽  
Fátima Martel

The aim of this work was to characterize the placental uptake of folic acid from the maternal circulation. Using 2 human trophoblast cell lines (BeWo and JAR), we verified that uptake of 3H-folic acid was pH-dependent, increasing significantly with decreasing extracellular pH. In BeWo cells, uptake of 3H-folic acid at pH 5.5 was (i) Na+-independent; (ii) inhibited by folic acid, 5-methyltetrahydrofolate (5-MTHF), and methotrexate (MTX); (iii) inhibited by the anion transport inhibitors 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS) and 4-acetamido-4′-isothiocyano-2,2′-disulfonic acid stilbene (SITS); (iv) inhibited by the proton ionophore carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP); (v) not inhibited by blockers of receptor-mediated endocytosis (cytochalasin D and monensin); (vi) trans-inhibited by MTX and folic acid; and (vii) not affected by an anti-reduced folate transporter-1 (RFC) antibody. At pH 7.5, uptake of 3H-folic acid was (i) Na+-independent; (ii) inhibited by folic acid and MTX, but not by 5-MTHF; (iii) inhibited by SITS, but not by DIDS; (iv) not affected by FCCP; (v) inhibited by monensin (but not by cytochalasin D); (vi) trans-inhibited by folic acid (but not by MTX); and (vii) inhibited by an anti-RFC antibody. In conclusion, in BeWo cells, both RFC and receptor-mediated endocytosis seem to be involved in 3H-folic acid uptake at pH 7.5, whereas at pH 5.5, RFC and (or) a low pH-operating transporter distinct from RFC are involved.


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