Durability of protective effect of dulaglutide on pancreatic ß-cells in diabetic mice: GLP-1 receptor expression is not reduced despite long-term dulaglutide exposure.

AIMS: It is well-known that chronic exposure to large amounts of ligand leads to downregulation of its receptor. It is not known, however, whether a GLP-1R agonist downregulates its receptor. For this reason, our study examined whether GLP-1R expression is reduced after long-term exposure to dulaglutide (Dula) in non-diabetic and diabetic mice. METHODS: Seven-week-old male db/db and db/m mice were given either Dula (0.6mg/kg×2/week) or a control vehicle (CTL) for 17 weeks. Various metabolic parameters, such as glucose-stimulated insulin secretion (GSIS), insulin and TG content in islets, were evaluated after the intervention. ß-cell-related gene expression was also analyzed by real-time RT-PCR. RESULTS: In db/m mice, GLP-1R expression in ß-cells did not decrease, not even after long-term administration of Dula, compared with control mice, while GLP-1R expression in 24-week-old db/db mice treated with Dula was augmented, rather than downregulated, compared with 24-week-old CTL db/db mice. This was probably due to improved glycaemic control. In db/db mice treated with Dula, food intake and blood glucose levels were significantly decreased up to 24 weeks of age compared with CTL db/db mice, and their expression levels of various ß-cell-related genes, insulin content and GSIS were also enhanced. In contrast, oxidative and endoplasmic reticulum stress, inflammation, fibrosis and apoptosis were suppressed with Dula treatment. CONCLUSION: Dula exerts beneficial effects on glycaemic control and has long-lasting protective effects on pancreatic ß-cells. GLP-1R expression levels were not reduced at all in non-diabetic as well as diabetic mice despite long-term dulaglutide exposure.

Six-Year Graft Survival After Partial Pancreas Heterotopic Auto-Transplantation: A Case Report.

BACKGROUND: Long-term graft survival of partial pancreas auto-transplantation after total pancreatectomy has not been clarified. The clinical implications of repeat completion pancreatectomy for locally recurrent pancreatic carcinoma in the remnant pancreas after initial pancreatectomy also have not been clarified. METHODS: We have previously reported a 61-year-old woman presenting with re-sectable carcinoma of the remnant pancreas at 3 years after undergoing a pylorus-preserving pancreaticoduodenectomy for invasive ductal carcinoma of the pancreas head. We also performed distal pancreas auto-transplantation with the use of a part of the resected pancreas to preserve endocrine function. RESULTS: The patient was discharged at 20 days after surgery without any complications. She had been followed regularly in our outpatient clinic. She had been treated with S-1 as adjuvant chemotherapy; 72 months after the completion total pancreatectomy with distal partial pancreas auto-transplantation, the patient was alive without any evidence of the pancreatic carcinoma recurrence. The pancreas graft was still functioning with a blood glucose level of 112 mg/dL, HbA1C of 6.7%, and serum C-peptide of 1.2 ng/mL; and urinary C-peptide was 11.6 µg/d. CONCLUSIONS: Our patient demonstrated that repeated pancreatectomies can provide a chance for survival after a locally recurrent pancreatic carcinoma if the disease is limited to the remnant pancreas. An additional partial pancreas auto-transplantation was successfully performed to preserve endocrine function. However, the indications for pancreas auto-transplantation should be decided carefully in the context of pancreatic carcinoma recurrence.

Abrasion resistance of restorative glass-ionomer cements with a light-cured surface coating.

This is a comparative study of the Knoop hardness number and the toothbrush wear of a surface coating agent applied to the surface of a glass-ionomer restorative cement. A reduction in surface hardness of the coating agent resulted in an increase in brush wear. The light-cured glazing agent (Bellfeel Brightener) proved to be significantly harder than those coated with a light-cured bonding agent (Occlusin). Occlusin bonding agent was removed by comparatively rapid abrasion; however, the Bellfeel Brightener was significantly more resistant to such abrasion. The analysis of the surface hardness and scanning electron microscopy observations of the brushed surfaces of the samples suggested that Bellfeel Brightener was effective as a glazing material for glass-ionomer cement restorations.

Effect of coating materials on restorative glass-ionomer cement surface.

Historically glass-ionomer samples have been coated with a varnish to protect the material from the effect of water on the surface. However, varnishes have been shown to peel from this surface. The set cement matrix may become chalky and can erode rapidly. Light-cured glazing agents may demonstrate the ability to limit water movement across the setting-cement surface. In this in vitro study samples were investigated colorimetrically to evaluate the effect of water contamination. Perceivable differences were not found, particularly when a coating of light-cured bonding or glazing agents was applied. We conclude that the color stability of glass-ionomer cements is enhanced with the use of a protective coating of light-cured bonding or glazing agents.

[A case of AFP (alpha-fetoprotein) producing gastric cancer successfully treated with EAP (etoposide, adriamycin, cisplatin) therapy].

A case of AFP producing gastric cancer successfully treated with EAP therapy is reported with a review of the literature. A 56-year-old male was admitted complaining of epigastralgia and back pain. He was diagnosed as having a gastric cancer with multiple liver metastases by endoscopy and computed tomography. Serum AFP level was 2,791,000 ng/ml and biopsy specimen showed AFP-positive tumor cells by PAP (peroxidase-antiperoxidase) method in hepatoid structure. Preoperative combination chemotherapy with etoposide, adriamycin and cisplatin resulted in a remarkable decrease in serum AFP level. Subtotal gastrectomy (R3) with hepatic artery cannulation was performed. The therapeutic effect by histological examination showed Grade 3 in the primary site and Grade 2 in both resional lymph nodes and liver metastasis.

[Measurement of bile CEA levels in patients with colorectal cancer: is it of value for diagnosis of occult liver metastases aiming at prophylactic regional hepatic chemotherapy?].

A preliminary study was conducted to determine whether the measurement of CEA levels in gallbladder bile would be of value for diagnosis of occult liver metastases aiming at prophylactic regional hepatic chemotherapy in patients with colorectal cancer. Forty-fold dilution by normal human sera was necessary to measure CEA levels of gallbladder bile by the enzyme immunoassay (EIA). Bile CEA levels were 27.2 +/- 30.4 (M +/- SD) ng/ml in patients with benign biliary diseases (control), 248.5 +/- 426.3 ng/ml (p < 0.05, vs. control) in Dukes B, C patients, and 3,331.5 +/- 4,473.3 ng/ml (p < 0.01 vs. control, p < 0.05 vs. Dukes B, C) in patients with hepatic metastases from colorectal cancer, respectively. Bile CEA tended to demonstrate the existence of hepatic metastases more accurately than serum CEA. Our results obtained from a small number of patients suggest that patients with either elevation of bile CEA level or with a high ratio of bile CEA/serum CEA may be candidates for hepatic recurrence that requires prophylactic hepatic chemotherapy. However, it may be difficult to determine the bile CEA level at which occult liver metastases are demonstrated.

Total pancreatectomy combined with partial pancreas autotransplantation for recurrent pancreatic cancer: a case report.

We describe a patient presenting with a resectable carcinoma of the remnant pancreas at 3 years after undergoing a pylorus-preserving pancreaticoduodenectomy for invasive ductal carcinoma of the pancreatic head. We also performed a distal pancreas autotransplantation using a part of the resected pancreas to preserve endocrine function. Final histologic findings showed the second tumor to be an invasive ductal carcinoma consisting of a well-differentiated tubular adenocarcinoma with similar histopathologic findings as the first tumor. There were no microscopic lymph node metastases and no evidence of microvascular invasion (pStage IA [pT1, pN0, M0] and R0 according to the International Union Against Cancer TNM classification). The patient was discharged at 20 days after surgery without any trouble and followed by adjuvant chemotherapy with S-1. The carbohydrate antigen 19-9 value was again normalized after the second surgery. Twenty months after the second operation, the patient is alive without cancer recurrence. The pancreas graft is functioning with a blood glucose of 108 mg/dL, HbA1C of 6.2%, and serum C-peptide of 1.4 ng/mL.

The effect of glaze on restorative glass-ionomer cements.

The surface texture changes of three kinds of glass-ionomer cements were compared with various glazed and polished cement surfaces after the initial finishing. Method 1--the glazing agent--was used, and method 2 consisted of four different Shofu Super Snap discs. In method 3 specimens were compressed with a glass plate. The glazed and polished surfaces were used for investigating various properties such as the surface roughness, colour change, gloss, hardness, toothbrush wear, and were also subject to SEM (scanning electron microscope) observation in the laboratory. The period of 48 h after mixing was chosen for the various testing data. The smoothest surface was formed after compression with a glass plate, however, the glazing agent gave the highest gloss surface for glass-ionomer cement. The lower roughness generally observed was for glazing compared to polishing. The glazed surface is effective as a glass-ionomer cement restoration.

The effect of glaze on restorative glass-ionomer cements: evaluation of environmental durability in lactic acid solution.

The surface texture changes of three kinds of glass-ionomer cements were compared with glazed and polished cement surfaces after thermal cycling in a storage media [lactic acid solution (pH 4.0)]. The changes were measured with regard to the surface roughness, colour-change, gloss, hardness, toothbrush wear, and SEM (scanning electron microscope) observation in the laboratory. The glazed cement surface was not affected after thermal cycling in the lactic acid solution.

Effect of N-benzyl-D-glucamine dithiocarbamate on lipid peroxidation in testes of rats treated with cadmium.

The effect of N-benzyl-D-glucamine dithiocarbamate (BGD) on lipid peroxidation in testes, liver, and kidney of rats after cadmium injection was studied. Rats were injected subcutaneously with 5 mg CdCl2/kg and 30 min later they were injected intraperitoneally with BGD (400 mumol/kg). Cadmium treatment resulted in a significant increase in the lipid peroxidation in these organs, with a particularly remarkable increase in the testes. The increased lipid peroxidation in these organs was decreased to the control level by BGD injection after cadmium treatment. The lipid peroxidation in microsomes in testes was significantly increased compared to that of the control. BGD treatment significantly decreased the cadmium concentration in the microsomes in testes of cadmium-treated rats. The lipid peroxidation in liver and kidney microsomes was little changed. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the testes, liver, and kidney were little changed by cadmium treatment. The catalase activity in the testes was increased after cadmium injection and BGD treatment significantly decreased the increased enzyme activity. These results suggest relatively small contribution of SOD, GSH-Px, and catalase in cadmium-induced lipid peroxidation in the testes. The depressive effect of BGD on the increased lipid peroxidation in the testes of rats treated with cadmium may be in part related to the decrease in the cadmium concentration in the microsomes in testes.

Colour changes of light-cured composite resin after exposure to water and photographic wetting agent.

Light-cured composite resins were investigated colourimetrically under the three different conditions, dry and exposed to water and photographic wetting agent. As a result, perceivable differences were found, particularly in photographic wetting agent. We conclude that the colour changes of composite resins seems to be affected by the lower surface tension of a liquid.

Effects of dithiocarbamates on testicular toxicity in rats caused by acute exposure to cadmium.

N-Benzyl-D-glucamine dithiocarbamate (BGD), N-p-isopropylbenzyl-D-glucamine dithiocarbamate (PBGD), and diethyl-dithiocarbamate (DED) were compared for their protective effects against the testicular toxicity in rats induced by acute exposure to cadmium. Rats were injected subcutaneously with 109CdCl2 (3 mg Cd and 74 kBq of 109Cd/kg) and 30 min later, they were injected intraperitoneally with the chelating agents (0.4 or 3 mmol/kg). Cadmium injection increased lipid peroxidation and concentrations of hemoglobin and Ca in the testes, decreased the testicular weight, and caused sterility. The treatment with BGD (0.4 mmol/kg) did not satisfactorily protect against the testicular toxicity of cadmium. The administration of PBGD or DED at a dose of 3 mmol/kg significantly prevented the increase in the lipid peroxidation and hemoglobin concentration in the testes, the decrease in the testicular weight, and the sterility caused by cadmium. PBGD and DED significantly decreased the cadmium concentration in the testes, but DED increased the cadmium concentration in the kidney and brain. Only DED significantly prevented the increase in the testicular Ca concentration after cadmium. These results indicate that PBGD and DED protect against the sterility caused by cadmium in rats and that the effect of DED to increase the brain level of cadmium is more dangerous than the lack of effect of PBGD to prevent the increase in the testicular Ca level. The protective effects of PBGD and DED against the cadmium-induced testicular toxicity presumably result from a decrease in the cadmium concentration in the testes.

[In vitro cytotoxicity of Palfique Bonding Agent].

Cytotoxicity of Palfiqu Bonding agent including Universal and Catalyst was examined by a cell culture study using HeLa cells. The Catalyst was cytotoxic to the cell, but Universal revealed no such cytotoxicity. This depended on time and concentration of materials immersed in culture medium.

[Color change by thickness and background color on visible light-cured composite resins].

The effects of thickness and background color on the color of five commercial light-cured composite resins were studied by a dental color meter using the CIE 1976 L*a*b* color system. As thickness increased from 1.0 to 4.0 mm, values of L*a*b* decreased for white and dentin color background but showed no obvious difference in color for a black background. the color of composite resins were not in fluenced by background color in a thickness of 4.0 mm. The values of color difference for 1.0 and 2.0 mm thick samples have a larger value than the same 4.0 mm samples. The color difference was recognized even for the same shade name in five representative kinds of composite resins.

Origin of lymphocytic-choriomeningitis-virus-bearing mice in Japan.

Mice found in the port areas in Japan, where antibody to lymphocytic choriomeningitis virus (LCMV) was detected, may have originated or partially originated from a southern Asian subspecies, Mus musculus castaneus.