Recent studies have suggested that complexation hydrogels poly(methacrylic acid-g-ethylene glycol) (henceforth designated as P(MAA-g-EG)) exhibit high insulin incorporation efficiency, rapid insulin release in the intestine based on their pH-dependent complexation properties, enzyme-inhibiting effects and mucoadhesive characteristics. Therefore, they are promising carriers for insulin delivery via an oral route. As we designed these hydrogels as carriers suitable for oral administration of various peptide/protein drugs, in this study we aimed at investigating the applicability of P(MAA-g-EG) hydrogels to improving the intestinal absorption of various peptide/protein drugs. High incorporation efficiency into hydrogels was observed for insulin, calcitonin, and interferon β. In addition, polymer microparticles loaded with calcitonin and interferon β exhibited complexation/decomplexation and pH-sensitive release behavior. The molecular weight and chemical structure appeared to affect the efficiency of incorporation and release depending on the peptides and proteins. Furthermore, a drastic reduction of plasma calcium concentration accompanied by calcium absorption and a dose-dependent enhancement of plasma interferon β concentration were observed after the administration of particles loaded with calcitonin or interferon β into closed rat ileal segments. These findings indicate that P(MAA-g-EG) hydrogels are promising carriers for administration of various peptides and proteins via an oral route.
Gestational diabetes mellitus (GDM) is characterized by glucose intolerance that is caused by metabolic changes during pregnancy, and is considered a risk factor for the occurrence of DM in future. There are studies that reported changes in the cytokine in women with GDM. The concentration of serum IFN-γ and adiponectin decreased, while serum leptin, IL-6, IL-10, and TNF-α increased in GDM women when compared to that in healthy pregnant women. 16 17 Placenta and adipose tissues from patients with GDM released higher amounts of TNF-α in response to high glucose than that from normal pregnant women.18 Plasma TNF-α were reported to be low during the first and second trimester, but it increased during late pregnancy, and was inversely correlated with the insulin sensitivity. 19, 20 However, the relationship between GDM and the functions of NK cells in pregnant women has not been clarified so far. The purpose of this study was to evaluate the expression of peripheral blood NK (pNK) cell surface markers (CD16, NKp46, and NKp30) and the percentage of cytokine (IFN-γ, TNF-α, TGF-β, and VEGF) producing pNK cells in women with / without GDM at 12 weeks of pregnancy. 2 Materials and Methods Study SubjectsWe designed a prospective study and patients from Hirosaki University Hospital were recruited for this study between July 2014 and March 2015. This study was approved by the local ethics committee, and signed informed consent forms were obtained from all study subjects. Blood samples were collected during routine blood tests for prenatal check-up at 12weeks of gestation.Thirty-four Japanese women (GDM (n=7), non-GDM (n=27)) with singleton pregnancy were included. All GDM patients were diagnosed at 12 to 16 weeks of gestation. Pregnant women with multi-fetal gestations, pre-gestational diabetes, and overt diabetes were excluded, while pregnant women with impaired glucose tolerance before the onset of pregnancy were included in this study. Maternal and neonatal characteristics are shown in Table 1. Two-hour-glucose level of 75-g OGTT in GDM group was significantly higher than that in the non-GDM group.There were no complications reported in the newborn infants (such as macrosomia, shoulder dystocia, and hypoglycemia) in both the GDM and non-GDM groups and there were no pregnant women suffering from PE in both the GDM and non-GDM groups. Screening of GDMAll pregnant women were subjected to a two-step screening method for GDM. This screening method is based on the Guideline for Obstetrical Practice in Japan 2014. 21 Briefly, women who had a random plasma glucose level of ≥95mg/dl at 12 weeks of gestation were subjected to 75-g OGTT after fasting overnight. Diagnosis of GDM was based on the criteria of one or more abnormal values [fasting ≥92mg/dl (5.1mmol/l), such as 1 hour ≥180mg/dl (10.0mmol/l) or 2 hour ≥153mg / dl (8.5mmol/l)] reported for the subjects. Pregnant women, not diagnosed as GDM at 12 weeks of screening, were again subjected to random blood glucose measurement at 3 28 weeks of gestation. Women with random...
The psychology of infertile women was investigated with a battery of psychological tests consisting of a semistructured interview, State Trait Anxiety Inventory (STAI), Center for Epidemiologic Studies Depression Scale (CES-D), and Cornell Medical Index (CMI). The subjects were 107 infertile women being treated for infertility. The semistructured interviews revealed that the stress factor for infertile women changes with the length of infertility. In the early states, the main stress is related to a physical inferiority complex, while later it changes into stress about what others outside the family say. According to STAI, CES-D and CMI, infertile women are considered to become more depressive the longer treatment persists. Therefore, counseling for infertile women should be adapted to long-term treatment.
Endometrial NK22 cells are differently regulated in women with URPL and UI. Women with URPL have higher level of NK22 cells with a potential to induce NK2 shift than women with UI.
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