Impacts of Diabetes and an SGLT2 Inhibitor on the Glomerular Number and Volume in db/db Mice, as Estimated by Synchrotron Radiation Micro-CT at SPring-8.

Background: Recent large-scale clinical studies demonstrate that sodium-glucose cotransporter 2 (SGLT2) inhibitors protect the diabetic kidney. However, clinical and animal studies have not shown the changes of the total glomeruli in the whole kidney treated with SGLT2 inhibitors.

Methods: We performed computed tomography (CT) imaging on mice using synchrotron radiation to investigate the impact of luseogliflozin, a SGLT2 inhibitor, on the number and volume of glomeruli in the whole kidney.

Assessment of inhalation flow patterns of soft mist inhaler co-prescribed with dry powder inhaler using inspiratory flow meter for multi inhalation devices.

The patients' inhalation flow pattern is one of the significant determinants for clinical performance of inhalation therapy. However, the development of inhalation flow meters for various inhalation devices has been unable to keep up with the increasing number of newly launched inhalation devices. In the present study, we developed simple attachment orifices for the inhalation flow pattern monitoring system, which are suitable for all commercial inhalers, and investigated the efficacy of the system on the clinical inhalation instruction for patients co-prescribed dry powder inhaler (DPI) and soft mist inhaler (SMI).

Passenger lymphocyte syndrome with hemophagocytic syndrome after peripheral blood stem-cell transplantation from an HLA-matched full biological sibling: case report.

Massive hemolysis due to passenger lymphocyte syndrome (PLS) is rare after peripheral blood stem-cell (PBSC) transplantation with a minor ABO mismatch. We present, in a 16-year-old boy (group A Rh+), PLS with hemophagocytic syndrome (HPS) after PBSC transplantation from his HLA (human leukocyte antigens)-matched biological sister (group O Rh+). Mild-to-moderate hemolysis was evident from day +11 to day +15 after transplantation.

Influence of peak inspiratory flow rates and pressure drops on inhalation performance of dry powder inhalers.

The aim of this study was to reveal the relationship between human inspiratory flow patterns and the concomitant drops in pressure in different inhalation devices, and the influence of the devices on inhalation performance. As a model formulation for inhalers, a physically mixed dry powder composed of salbutamol sulfate and coarse lactose monohydrate was selected. The drops in pressure at 28.

Imaging analysis of osteogenic transformation of Meckel's chondrocytes from green fluorescent protein-transgenic mice during intrasplenic transplantation.

Our previous studies demonstrated that Meckel's chondrocytes, which are derived from ectomesenchyme, have the potential to transform into osteogenic phenotypes. The present study aimed to clarify the role of cell origin in the phenotypic transformation of chondrocytes. Cell pellets from ectomesenchyme-derived Meckel's cartilage and mesoderm-derived costal cartilage from green fluorescent protein (GFP)-transgenic mice were transplanted into the spleen for up to 4 weeks.

Differentiation of induced pluripotent stem cells into dental mesenchymal cells.

Similar to embryonic stem cells, induced pluripotent stem (iPS) cells can differentiate into various cell types upon appropriate induction, and thus, may be valuable cell sources for regenerative medicine. However, iPS cells have not been reported to differentiate into odontogenic cells for tooth regeneration. Here we demonstrated that neural crest-like cells (NCLC) derived from mouse iPS cells have the potential to differentiate into odontogenic mesenchymal cells.

Hepatocyte growth factor stimulates root growth during the development of mouse molar teeth.

Background And Objective: It is well known that tooth root formation is initiated by the development of Hertwig's epithelial root sheath (HERS). However, relatively little is known about the regulatory mechanisms involved in root development. As hepatocyte growth factor (HGF) is one of the mediators of epithelial-mesenchymal interactions in rodent tooth, the objective of this study was to examine the effects of HGF on the root development of mouse molars.

Pioglitazone reduces urinary albumin excretion in renin-angiotensin system inhibitor-treated type 2 diabetic patients with hypertension and microalbuminuria: the APRIME study.

Background: The aim of his study was to compare the efficacy of pioglitazone with metformin on the reduction of albuminuria in type 2 diabetic patients with hypertension and microalbuminuria treated with renin-angiotensin system inhibitors (RAS-Is).

Methods: The open-label, randomized trial was performed in type 2 diabetic patients with hypertension and microalbuminuria. On the basis of the treatment with RAS-Is, 68 patients with microalbuminuria received either pioglitazone (15-30 mg/day; n = 32) or metformin (500-750 mg/day; n = 31) for 52 weeks.

Functional role of Rho-kinase in ameloblast differentiation.

During tooth development, inner enamel epithelial (IEE) cells differentiate into enamel-secreting ameloblasts, a polarized and elongated cellular population. The molecular underpinnings of this morphogenesis and cytodifferentiation, however, are not well understood. Here, we show that Rho-associated coiled-coil-containing protein kinase (ROCK) regulates ameloblast differentiation and enamel formation.

Establishment of Hertwig's epithelial root sheath cell line from cells involved in epithelial-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) is an important event in the developmental process of various organs. In periodontal development during root formation of a tooth, this EMT has been a subject of controversy. Hertwig's epithelial root sheath (HERS), consisting of two epithelial layers, plays a role of inducing odontogenesis during root development and thereafter becomes fragmented.

Inhalation performance of physically mixed dry powders evaluated with a simple simulator for human inspiratory flow patterns.

Purpose: To construct a simple simulator reproducing human inspiratory flow patterns and use it to evaluate the inhalation performance of active ingredient particle-carrier particle systems (physically mixed dry powders).

Methods: Inspiratory flow patterns were collected and analyzed using a flow recorder. The simulator was constructed using an airtight container, a valve, and a connecting tube.

Expression of osteogenic proteins during the intrasplenic transplantation of Meckel's chondrocytes: A histochemical and immunohistochemical study.

Meckel's chondrocytes, derived from the ectomesenchyme, have the potential to transform into other phenotypes. In this study, we transplanted cell pellets of Meckel's chondrocytes into isogenic mouse spleens and analyzed their phenotypic transformation into osteogenic cells using histological and immunohistochemical methods. With the increasing duration of transplantation, chondrocytes were incorporated into splenic tissues and formed a von Kossa-positive calcified matrix containing calcium and phosphoric acid, similar to that of intact bone.

Reduction of Egf signaling decides transition from crown to root in the development of mouse molars.

Mouse, rat, and human molars begin to form their roots after the completion of crown morphogenesis. Though several signaling pathways and transcription factors have been implicated in the regulation of molar crown development, relatively little is known about the regulatory mechanisms involved in the transition from crown to root development. Tooth root formation is initiated by the development of Hertwig's epithelial root sheath (HERS) from the cervical loop in the enamel organ.

In vitro adipocytic conversion in Meckel's chondrocytes in response to a fatty acid-containing medium.

Chick serum (CKS) contains factors that stimulate adipocytes in Meckel's chondrocytes in vitro. In the present study, we analyzed levels of fatty acids in CKS, and further examined whether these had the potential to convert chondrocytes to adipocytes. Phenotypic changes were evaluated by light and electron microscopies, bromodeoxyuridine (BrdU) incorporation, triglyceride assays, and immunocytochemistry.

Insulin-like growth factor-I stimulates cell proliferation in the outer layer of Hertwig's epithelial root sheath and elongation of the tooth root in mouse molars in vitro.

To elucidate the mechanism of root formation in tooth development, we examined the role of insulin-like growth factor I (IGF-I) on early root formation in mandibular first molar teeth from 5-day-old mice. Immunohistochemistry revealed the specific localization of the IGF-I receptor in Hertwig's epithelial root sheath (HERS) in the tooth root. The effect of IGF-I on root development, especially on HERS, was subsequently examined in vitro.

Induction of adipogenesis by the intrasplenic transplantation of chick serum clots.

Chick serum contains a factor that stimulates adipogenesis in Meckel's chondrocytes in vitro. The present study examined whether chick serum has a capacity for adipogenic induction in vivo, by transplanting serum clots (created by drying chick serum for up to 4 weeks) into mouse spleens. Specimens were harvested for histological analyses, which included light and electron microscopy and immunohistochemistry.

Origin-associated features of chondrocytes in mouse Meckel's cartilage and costal cartilage: an in vitro study.

Using a cell culture method, we histochemically and immunohistochemically investigated whether chondrocytes deriving from different origins, such as Meckel's or costal cartilages, express similar phenotypic characteristics. Chondrocytes isolated enzymatically from Meckel's and costal cartilages of 17-day embryonic mice both actively proliferated and formed cartilage nodules consisting of toluidine blue-positive proteoglycans and type II collagen. Both deposited calcified cartilaginous matrix as revealed by alkaline phosphatase (ALPase) activity and alizarin red staining throughout 3 weeks in culture.

Insulin lispro reduces insulin antibodies in a patient with type 2 diabetes with immunological insulin resistance.

We describe a 54-year-old Japanese female with type 2 diabetes admitted to our hospital with poor metabolic control. On admission the patient's HbA1c was 9.1% despite having taken over 60 U of human insulin per day for the previous 10 years.

Phenotypic switching of in vitro mandibular condylar cartilage during matrix mineralization.

In order to analyze the phenotypic conversion of chondrocytes, mandibular condyles of mice and rabbits were cultured under cell and organ culture systems, and then examined by a combination of morphological and biochemical procedures. In organ culture, mandibular condylar cartilage (MCC) obtained from newborn mice began to mineralize from the central zone and then progressively widened towards the peripheral zone. Electron microscopic observations showed that with the increasing duration of the organ culture, chondrocytes at the central zone converted into spindle-shaped osteoblastic cells accompanying the formation of the bone type of thick-banded collagen fibrils.

Phenotypic characteristics of adipocytes generated from Meckel's chondrocytes in response to chick serum in vitro.

When present in the culture medium, chick serum (CKS) modulated the phenotypic change from chondrocytes of Meckel's cartilage to adipocytes in vitro, as revealed by light and electron microscopy, the incorporation of BrdU, and immunocytochemistry. CKS inhibited DNA synthesis in chondrocytes and the proliferation of these cells, while it facilitated the differentiation to adipocytes. CKS contributed to phenotypic changes in undifferentiated chondrocytes, but did not affect the characteristics of differentiated chondrocytes.

Impaired vascular invasion of Cbfa1-deficient cartilage engrafted in the spleen.

Chondrocyte maturation and vascular invasion of cartilage are essential in the process of endochondral ossification. Cbfal-deficient (Cbfa1-/-) mice displayed a complete absence of osteoblast and osteoclast maturation as well as severely inhibited chondrocyte maturation in most parts of the skeleton. Although chondrocyte maturation and mineralization were observed in restricted areas of Cbfa1-/- mouse skeleton, vascular invasion of calcified cartilage was never noted.

Formation of the sphenomandibular ligament by Meckel's cartilage in the mouse: possible involvement of epidermal growth factor as revealed by studies in vivo and in vitro.

In mammals, the midportion of the soft tissue of Meckel's cartilage at the degenerating stage forms a ligament known as the sphenomandibular ligament. To clarify the mechanism of formation of this ligament by Meckel's cartilage in mouse, we examined the effects of epidermal growth factor (EGF) on the chondrocytes in terms of the proliferation and differentiation of cells and calcification of the matrix in vivo and in vitro. The effects of EGF were examined by immunohistochemical staining, with EGF-soaked beads, by electron microscopy, and by general histochemical analysis of proteoglycans and calcification.

Further evidence for secretion of matrix metalloproteinase-1 by Meckel's chondrocytes during degradation of the extracellular matrix.

We examined the possibility that chondrocytes in Meckel's cartilage might secrete matrix metalloproteinase-1 (MMP-1) during degradation of the extracellular matrix. Evidence for the secretion of MMP-1 was obtained by immunohistochemical staining and immunoelectron microscopy, in addition to general histochemical staining for proteoglycans. Not only staining with toluidine blue and alcian blue but also immunostaining for chondroitin sulfate proteoglycan (CSPG) revealed that levels of glycoproteins are rapidly reduced at the late stage of degradation.