Summary
Background
Sublingual immunotherapy (SLIT) has proven to be safe and efficient for the treatment of type I allergies. However, the mechanisms underlying allergen transportation within the ...sublingual compartment, the localization of antigens, and the identities of the cells responsible for this immunization remain incompletely understood.
Objective
In this study, we focused on the sublingual ductal system and analysed the localization and transportation of antigens after their sublingual application.
Methods
In mice given adjuvant‐free antigens sublingually, tissues were removed at 0, 0.5, 1, or 2 h after the application and subjected to immunohistochemistry. Cells isolated from the sublingual duct and mucosa were analysed by flow cytometry.
Results
Substantial immunoreactivity to ovalbumin (OVA) was evident in sublingual ductal epithelial cells at 30 min and 1 h after sublingual administration of OVA, but it had disappeared at 2 h. The ductal epithelial cells incorporated not only OVA, but also particulate antigens such as latex or silica beads and microbes. MHC class II (MHCII)+ antigen‐presenting cells (APCs) were located around the sublingual ductal system, and MHCII+ cells were co‐localized with, and around, antigen‐incorporated sublingual duct cells. CD11b+ CD11c− cells were present among CD45+ MHCII+ cells at greater frequency in the sublingual duct than in the sublingual mucosa, and they were the main contributors to the incorporation of OVA in vitro.
Conclusions and Clinical Relevance
This study reveals that sublingual antigens can be transported across sublingual ductal epithelial cells to the ductal APCs. If the system is the same in humans as in mice, the ductal APCs may prove to be important target cells for SLIT.
Intravenous fluorouracil and leucovorin is the standard adjuvant treatment for stage III colon cancer. However, oral adjuvant chemotherapy is attractive because it has low toxicity and greater ...convenience. We investigated the benefits of oral protein-bound polysaccharide K (PSK) with tegafur/uracil (UFT) as an adjuvant in stage II and III colorectal cancer. Patients were assigned to groups that received either 3 g PSK plus 300 mg UFT, or 300 mg UFT alone orally each day for a 2-year period following intravenous mitomycin C. Of 207 registered patients, 205 with stage II (n=123) or III (n=82) were analysed. The 5-year disease-free survival was 73.0% (95% CI 65.6-80.4%) with PSK (n=137) and 58.8% (95% CI 47.1-70.5%) in the controls (n=68) (P=0.016). Polysaccharide K reduced the recurrence by 43.6% (95% CI 4.5-66.7%) and mortality by 40.2% (95% CI -12.5 to 68.3%). The 5-year survival was 81.8% (95% CI 75.3-88.2%) in the PSK group and 72.1% (95% CI 61.4-82.7%) in the control group (P=0.056). In stage III patients, disease-free and overall survivals in patients receiving PSK were increased significantly: 60.0% (95% CI 47.1-72.9%) and 74.6% (95% CI 63.0-86.1%) in the PSK group as compared with 32.1% (95% CI 14.8-49.4%) and 46.4% (95% CI 28.0-64.9%) in the controls (P=0.002 and 0.003, respectively). Polysaccharide K prevented recurrence, particularly lung metastases (P=0.02; odds ratio 0.27; 95% CI 0.09-0.77). In the models, the presence of regional metastases (relative risk, 2.973; 95% CI 1.712-5.165; P<0.001), omission of PSK (relative risk, 2.106; 95% CI 1.221-3.633; P=0.007), and higher primary tumour (relative risk, 4.398; 95% CI 1.017-19.014; P=0.047) were each significant indicators of recurrence. Adverse effects were mild and compliance was good. Oral PSK with UFT reduced recurrence in stage II and III colorectal cancer, and increased survival in stage III.
Ghrelin is a multifunctional peptide that promotes an increase of food intake and stimulates GH secretion. Ghrelin secretion is regulated by nutritional status and nutrients. Although a high-protein ...(HP) diet increases plasma ghrelin secretion in mammals, the mechanisms and the roles of the elevated ghrelin concentrations due to a HP diet have not been fully established. To clarify the roles of elevated acylated ghrelin upon intake of a HP diet, we investigated the regulation of ghrelin concentrations in plasma and tissues in wethers fed with either the HP diet or the control (CNT) diet for 14 days, and examined the action of the elevated plasma ghrelin by using a ghrelin-receptor antagonist. The HP diet gradually increased the plasma acylated-ghrelin concentrations, but the CNT diet did not. Although the GH concentrations did not vary significantly across the groups, an injection of ghrelin-receptor antagonist enhanced insulin levels in circulation in the HP diet group. In the fundus region of the stomach, the ghrelin levels did not differ between the HP and CNT diet groups, whereas ghrelin O-acyltransferase mRNA levels were higher in the group fed with HP diet than those of the CNT diet group were. These results indicate that the HP diet elevated the plasma ghrelin levels by increasing its synthesis; this elevation strongly suppresses the appearance of insulin in the circulation of wethers, but it is not involved in GH secretion. Overall, our findings indicate a role of endogenous ghrelin action in secretion of insulin, which acts as a regulator after the consumption of a HP diet.
Aim: To examine the efficacy, safety and tolerability of rivoglitazone, a novel thiazolidinedione (TZD), and explore its effects on glucose and lipid control compared to placebo and pioglitazone in ...Chinese type 2 diabetic patients who are treatment naÏve or treated with a single oral blood glucose‐lowering drug.
Methods: This was a double‐blind, randomized, placebo‐ and active‐controlled study. A total of 287 Chinese type 2 diabetic patients with suboptimal glycaemic control (defined as HbA1c ≥6.5 to <10% and fasting plasma glucose ≥7 to ≤15 mmol/l) were enrolled. One hundred and seventy‐four eligible patients were randomized into one of the five treatment arms for 12 weeks: placebo, pioglitazone 30 mg daily, rivoglitazone of dose 0.5, 1.0 or 1.5 mg daily. In a full set analysis, we used analysis of covariance to compare the primary endpoint defined as change in HbA1c from baseline to week 12/last observation carried forward in the rivoglitazone group at each dose level with the placebo group.
Results: Changes in HbA1c were −0.11% in the 0.5‐mg group; −0.22% in the 1‐mg group and −0.17% in the 1.5‐mg rivoglitazone group; −0.06% in the 30‐mg pioglitazone group and 0.61% in the placebo group. Compared to placebo, changes were significant in all active treatment groups (all p < 0.05). Increase in high‐density lipoprotein cholesterol and decrease in triglyceride were observed in the rivoglitazone 1 and 1.5 mg groups, respectively, compared to placebo from baseline to week 12 (p < 0.05). Drug‐related oedema was reported in eight patients (7.7%) in all rivoglitazone groups compared to six patients (16.2%) in the pioglitazone group and one patient (3.0%) in the placebo group.
Conclusions: Rivoglitazone is an efficacious, safe and well‐tolerated TZD which improved glycaemic control in Chinese type 2 diabetic patients up to 3 months.
We measured infrared and visible light absorption spectra and EXAFS for Ag–Au core/shell particles. The shell thickness and core diameter can be evaluated from the EXAFS results, which are almost ...consistent with those obtained using TEM. The influence of a thinner shell only slightly appeared in the visible absorption spectra, whereas the influence appeared strongly in the infrared absorption spectra. The spectra of the material in the vicinity of the particle surface appear in the infrared spectra. On the other hand, the spectra of the rather more internal material are observed in the visible spectra. It is thought that the influence of the core metal is different in the visible spectra from the infrared spectra. By considering the penetration depth, this phenomenon can be explained.
In the anterior pituitary gland, inflammatory mediators regulate cell function through an immuno‐endocrine pathway. Recent studies have shown that undifferentiated stem cells act as immunomodulators. ...These studies prompted us to establish a progenitor cell line from the bovine anterior pituitary gland and to detail its function. First, we localised interleukin (IL)‐18 by immunohistochemistry to the marginal cell layer of Rathke’s pouch that is assumed to embody a stem/progenitor cell compartment of the postnatal pituitary gland. A cloned anterior pituitary‐derived cell line from the bovine anterior pituitary gland was established from single cell clone by the limiting dilution method and was designated as bovine anterior pituitary‐derived cell line (BAPC)‐1. BAPC‐1 cells constantly expressed mRNAs for IL‐18 and IL‐18 receptor, and grew steadily and rapidly in the medium containing epidermal growth factor and basic fibroblast growth factor. The cell line also expressed the mRNAs for the stem/progenitor cell‐ related factors such as Nanog, Oct‐4, Ptch1, Nestin, Notch1, Hes1, Lrp and Fzd4, and the mRNAs for embryonic pituitary‐related factors, such as Lhx3, PitX1 and Pit‐1. The nuclei of BAPC‐1 were immunostained positively for Pit‐1, Hes1 and β‐catenin antibodies. Furthermore, BAPC‐1 cells expressed mRNAs for cytokine such as IL‐1α, IL‐6, IL‐7, IL‐12 and IL‐15. Stimulation of BAPC‐1 cells with IL‐18 increased expression of mRNAs for IL‐1α, IL‐6, IL‐1β and IL‐8. At day 6 in culture, BAPC‐1 cells also express growth hormone mRNA. These results strongly suggest that BAPC‐1 is a stem/progenitor cell line and modulates the immuno‐endocrine function of the anterior pituitary cells through its cytokine production.
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