Lower hepatotoxicity risk in Xelaglifam, a novel GPR40 agonist, compared to Fasiglifam for type 2 diabetes therapy.

Fasiglifam, a candidate targeting GPR40, showed efficacy in clinical trials for type 2 diabetes but exerted liver toxicity. This study investigated the drug-induced liver injury (DILI) risk of Xelaglifam, a new GPR40 agonist, based on the potential toxicity mechanism of Fasiglifam; transporter inhibition, mitochondrial dysfunction, reactive metabolite formation, and covalent binding to proteins. In the hepatobiliary transporter assay, Xelaglifam showed a broader safety margin (>10-fold) against bile acid transporters, suggesting its less likelihood to cause bile acids accumulation, unlike Fasiglifam (<10-fold safety margin).

Xelaglifam, a novel GPR40/FFAR1 agonist, exhibits enhanced β-arrestin recruitment and sustained glycemic control for type 2 diabetes.

Xelaglifam, developed as a GPR40/FFAR1 agonist, induces glucose-dependent insulin secretion and reduces circulating glucose levels for Type 2 diabetes treatment. This study investigated the effects of Xelaglifam in comparison with Fasiglifam on the in vitro/in vivo anti-diabetic efficacy and selectivity, and the mechanistic basis. In vitro studies on downstream targets of Xelaglifam were performed in GPR40-expressing cells.

Prediction of Pharmacokinetics of IDP-73152 in Humans Using Physiologically-Based Pharmacokinetics.

IDP-73152, a novel peptide deformylase inhibitor with an antibacterial effect against Gram-positive bacteria, is in phase I development. The objective of this study was to develop a physiologically-based pharmacokinetic model (PBPK) for IDP-73152 in animals, and to extend the model to humans. Biopharmaceutical properties of IDP-73152 are determined using in vitro/in vivo experimentations for the PBPK model.

Pharmacokinetics and tolerability of IDP-73152 mesylate after a single oral administration under fasted and fed conditions in healthy volunteers.

Background And Objective: IDP-73152 mesylate is a peptide deformylase inhibitor under investigation for the treatment of complicated skin and respiratory tract infections. The objective of this study was to investigate the pharmacokinetic (PK) profile and tolerability of IDP-73152 and the effect of food after a single oral administration.

Methods: A dose block-randomized, double-blind, placebo-controlled, dose-escalation study was conducted.

Identification of novel aminopiperidine derivatives for antibacterial activity against Gram-positive bacteria.

We have previously reported amidopiperidine derivatives as a novel peptide deformylase (PDF) inhibitor and evaluated its antibacterial activity against Gram-positive bacteria, but poor pharmacokinetic profiles have resulted in low efficacy in in vivo mouse models. In order to overcome these weaknesses, we newly synthesized aminopiperidine derivatives with remarkable antimicrobial properties and oral bioavailability, and also identified their in vivo efficacy against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and penicillin-resistant Streptococcus pneumoniae (PRSP).

Comparative histomorphometric analysis of maxillary sinus augmentation with and without bone grafting in rabbit.

Purpose: The aim of this animal study was to evaluate, by histomorphometric analysis, new bone formation in rabbit maxillary sinuses with, and without, bone grafting.

Materials And Methods: Bilateral sinus augmentation procedures were performed in 20 adult male rabbits. Bony windows were made by a saw insert connected with a piezoelectric surgical device in both groups.

Piezoelectric internal sinus elevation (PISE) technique: a new method for internal sinus elevation.

This article reports the surgical procedure of a transalveolar approach for sinus floor elevation using piezoelectric surgery without a mallet, called piezoelectric internal sinus elevation (PISE) technique. PISE is the modified technique of the osteotome-mediated sinus floor elevation. Osteotome-mediated sinus floor elevation uses a mallet to break the sinus floor and to push sinus membrane up.

Efficacy of demineralized bone matrix paste for maxillary sinus augmentation: a histologic and clinical study in humans.

Objectives: The aim of this study is to report the effect of paste type of demineralized bone matrix (DBM) on augmentation of maxillary sinus using clinical parameters.

Study Design: Sinus augmentation with DBM was performed on 5 maxillary sinuses. This study included 5 patients, 4 men and 1 woman, aged from 41 to 67 years (mean age 55 years).

Reconstruction of atrophic anterior mandible using piezoelectric sandwich osteotomy: a case report.

Extensive loss of alveolar bone and teeth in the anterior mandible presents a complex problem for reconstruction. Numerous augmentation techniques are currently in use to create sufficient bone volume for reliable placement of endosseous implants in the case of severely resorbed mandibles. The aim of this report is to assess the efficacy of the piezoelectric sandwich osteotomy for vertical augmentation in the atrophic segment of anterior mandible through clinical and histologic studies.

Histomorphometric evaluation of mineralized cancellous allograft in the maxillary sinus augmentation: a 4 case report.

Purpose: The aim of this article is to report the histomorphometric analysis and clinical study of mineralized cancellous bone allografts in maxillary sinus augmentation procedures in 4 cases.

Materials And Methods: Sinus bone augmentation, using a piezoelectric device and mineralized cancellous allografts, was performed in 3 patients. After an average of about 8 months of healing, a trephine core sample was gained from the lateral windows area for histomorphometric analysis.

Erbium, chromium:yttrium-scandium-gallium-garnet laser-assisted sinus graft procedure.

The possibility of using lasers in the field of dentistry has been a subject of investigation. There are few reports that any laser systems have been used for bony window osteotomy by direct sinus grafting. In this study, erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser of various laser systems was used for 12 sinus bone grafts in ten patients, and the efficiency of the laser was evaluated according to the osteotomy time and the rate of sinus membrane perforation in the clinical results; the mechanism is described.

Fungal infection as a complication of sinus bone grafting and implants: a case report.

Sinus bone grafts have been used successfully to augment atrophic posterior maxilla for dental implant placement. Even though sinus bone grafting is generally considered to be a safe surgical procedure, postoperative maxillary sinus infections can occur and therefore need to be considered. Bacteria, as well as viruses and fungi, have been identified as causative agents.

Minor tooth movements using microimplant anchorage: case reports.

For the treatment of extruded or tipped molars, various conventional techniques have been used. But those methods may lead to undesirable movement of the anchorage units and lengthen treatment time because of limited tooth-borne anchorage potential. Introduction of microimplants as orthodontic anchorage has expanded treatment possibilities because of their advantages.

Immediate loading with mini dental implants in the fully edentulous mandible.

The use of immediate loaded prostheses is not recommended for at least 2 weeks to prevent implants from premature loading. In addition, immediate removable prostheses are negated for at least 4 weeks at the site of guided bone regeneration or bone graft. However, patients are often not pleased with limited diets and the unaesthetic appearance during the healing period without a denture between implant placement and final prosthesis.