Dong-Hoo Han

Translationally controlled tumour protein is associated with podocyte hypertrophy in a mouse model of type 1 diabetes

Aims/hypothesisTranslationally controlled tumour protein (TCTP) is thought to be involved in cell growth by regulating mTOR complex 1 (mTORC1) signalling. As diabetes characteristically induces podocyte hypertrophy and mTORC1 has been implicated in this process, TCTP may have a role in the pathogenesis of diabetes-induced podocyte hypertrophy.MethodsWe investigated the effects and molecular mechanisms of TCTP in diabetic mice and in high glucose-stimulated cultured podocytes. To characterise the role of TCTP, we conducted lentivirus-mediated gene silencing of TCTP both in vivo and in vitro.ResultsGlomerular production of TCTP was significantly higher in streptozotocin induced-diabetic DBA/2J mice than in control animals. Double-immunofluorescence staining for TCTP and synaptopodin revealed that podocyte was the principal cell responsible for this increase. TCTP knockdown attenuated the activation of mTORC1 downstream effectors and the overproduction of cyclin-dependent kinase inhibitors (CKIs) in diabetic glomeruli, along with a reduction in proteinuria and a decrease in the sizes of podocytes as well as glomeruli. In addition, knockdown of TCTP in db/db mice prevented the development of diabetic nephropathy, as indicated by the amelioration of proteinuria, mesangial expansion, podocytopenia and glomerulosclerosis. In accordance with the in vivo data, TCTP inhibition abrogated high glucose-induced hypertrophy in cultured podocytes, which was accompanied by the downregulation of mTORC1 effectors and CKIs.Conclusions/interpretationThese findings suggest that TCTP might play an important role in the process of podocyte hypertrophy under diabetic conditions via the regulation of mTORC1 activity and the induction of cell-cycle arrest.

Influence of a microgrooved collar design on soft and hard tissue healing of immediate implantation in fresh extraction sites in dogs

OBJECTIVE This study compared the alveolar bone reduction after immediate implantation using microgrooved and smooth collar implants in fresh extracted sockets. MATERIAL AND METHODS Four mongrel dogs were used in this study. The full buccal and lingual mucoperiosteal flaps were elevated and the third and fourth premolars of the mandible were removed. The implants were installed in the fresh extracted sockets. The animals were sacrificed after a 3-month healing period. The mandibles were dissected and each implant site was removed and processed for a histological examination. RESULTS During healing, the marginal gaps in both groups, which were present between the implant and the socket walls at implantation, disappeared as a result of bone filling and resorption of the bone crest. The buccal bone crests were located apical of its lingual counterparts. At the 12-week interval, the mean bone-implant contact in the microgrooved group was significantly higher than that of the turned surface group. From the observations in some of the microgrooved groups, we have found bone attachment to the 12 mum microgrooved surface and collagen fibers perpendicular to the long axis of the implants over the 8 mum microgrooved surface. CONCLUSION Within the limitations of this study, microgrooved implants may provide more favorable conditions for the attachment of hard and soft tissues and reduce the level of marginal bone resorption and soft tissue recession.

Morphometric analysis of the anterior region of the maxillary bone for immediate implant placement using micro-CT.

The purpose of this study was to elucidate the relationship between the maxillary incisor roots and surrounding alveolar structures using microscopic computerized tomography (micro‐CT) for the immediate implant placement. Nineteen maxillae from 14 Korean cadavers were used in this study. All specimens were scanned and reconstructed into a three‐dimensional (3D) structure using a micro‐CT system. The roots of the maxillary central and lateral incisors became dramatically narrower from 6 mm above the cementoenamel junctions to the apex. The roots of the maxillary incisors and canine were located at the labial one fifths region of the alveolar bone. The angle formed by the longitudinal root axis and the alveolar bone was greatest at the maxillary canine. On the basis of the results of this study, guidelines for immediate implant placement can be suggested on the implant diameter and drilling angle to minimize damage of the alveolar plate. Clin. Anat. 24:462–468, 2011.

Investigation of Pathogenic Genes in Peri-Implantitis from Implant Clustering Failure Patients: A Whole-Exome Sequencing Pilot Study

Peri-implantitis is a frequently occurring gum disease linked to multi-factorial traits with various environmental and genetic causalities and no known concrete pathogenesis. The varying severity of peri-implantitis among patients with relatively similar environments suggests a genetic aspect which needs to be investigated to understand and regulate the pathogenesis of the disease. Six unrelated individuals with multiple clusterization implant failure due to severe peri-implantitis were chosen for this study. These six individuals had relatively healthy lifestyles, with minimal environmental causalities affecting peri-implantitis. Research was undertaken to investigate pathogenic genes in peri-implantitis albeit with a small number of subjects and incomplete elimination of environmental causalities. Whole-exome sequencing was performed on collected saliva samples via self DNA collection kit. Common variants with minor allele frequencies (MAF) > = 0.05 from all control datasets were eliminated and variants having high and moderate impact and loss of function were used for comparison. Gene set enrichment analysis was performed to reveal functional groups associated with the genetic variants. 2,022 genes were left after filtering against dbSNP, the 1000 Genomes East Asian population, and healthy Korean randomized subsample data (GSK project). 175 (p-value <0.05) out of 927 gene sets were obtained via GSEA (DAVID). The top 10 was chosen (p-value <0.05) from cluster enrichment showing significance of cytoskeleton, cell adhesion, and metal ion binding. Network analysis was applied to find relationships between functional clusters. Among the functional groups, ion metal binding was located in the center of all clusters, indicating dysfunction of regulation in metal ion concentration might affect cell morphology or cell adhesion, resulting in implant failure. This result may demonstrate the feasibility of and provide pilot data for a larger research project aimed at discovering biomarkers for early diagnosis of peri-implantitis.

Genetic investigation of bisphosphonate-related osteonecrosis of jaw (BRONJ) via whole exome sequencing and bioinformatics.

Complications associated with the use of bisphosphonate (BP) have risen over the years due to an increase in the prescription of BP. BP-related osteonecrosis of jaw (BRONJ), one of the complications linked to the consumption of BP, greatly affects patients with minor dental trauma, incurring a long healing period. While BRONJ afflicts only a minority of patients prescribed with BP, BRONJ is a multigenic disease affected both by environmental and genetic factors having a distinctive phenotype. This study aims to discover genetic biomarkers associated with BRONJ via whole exome sequencing (WES) followed by statistical analysis. Sixteen individuals who had been prescribed with bisphosphonate medication and diagnosed as BRONJ were chosen and each individual’s saliva sample was collected for WES. 126 randomized subsamples from the GSK project representing 109 male and 17 female Koreans were used as a control data set. Fisher’s exact test was carried out to assess the significance of genetic variants in BRONJ patients. Gene set enrichment analysis (GSEA) (DAVID Bioinformatics Resource 6.7) was used to perform a cluster analysis of variants found from Fisher‘s exact test. The results from this study suggest that BRONJ-inducing factors are genetically associated and BRONJ occurs due to the malfunctioning of post-translational modification in osteoclast leading to the impairment of cell morphology and adhesion.

Is It Beneficial to Convert to a Neutral-pH Bicarbonate/Lactate-Buffered PD Solution in Long-Term CAPD Patients? A Single-Center Prospective Study.

We assumed that hydrothorax was due to the malpositioned peritoneal catheter. Peritoneal dialysis was stopped and the right peritoneal catheter was removed and a new left-sided catheter was inserted at the same time. Peritoneal dialysis was restarted after 1 month of catheter replacement with progressive increase of volume exchange. The chest X-ray did not show any recurrence of the pleural effusion up to 2 months later. Hydrotorax is an infrequent PD mechanical complication of PD (1). It usually occurs early after starting PD treatment (less than 30 days), and it is associated with an increase in intra-abdominal pressure in patients with congenital defects of the diaphragm muscle. It appears more commonly in females and in the r ight hemithorax. On very rare occasions, it has been related to peritonitis episodes (2–3). Treatment consists of peritoneal rest, temporary or definitive transference to HD, pleurodesis or surgical repair of the diaphragm defect (4). Our patient developed a late-onset right peritoneal-pleural leak in clear temporal relationship with a right malpositioned catheter which resolved after removing it. There has been no recurrence of pleural effusion since resuming PD and no surgical repair was required. We propose catheter malposition as a new cause of hydrothorax in PD.

A case of acute phosphate nephropathy in a patient with nephrotic syndrome and decreased serum fetuin-A

We report a case of APN after OSP use in a patient with nephrotic syndrome (NS). Renal biopsy revealed minimal change disease with multifocal calcium phosphate deposits within the tubules and in the interstitium. The serum level of fetuin-A, a systemic calcification inhibitor, was low during severely proteinuric state but normalized after remission of NS. To verify whether fetuin-A levels are low in NS patients, serum fetuin-A levels were determined in 10 patients with NS and 10 with asymptomatic microscopic hematuria (H). The mean serum fetuin-A levels were significantly lower in the NS group compared to the H group (p < 0.01). This finding suggests that a lower serum fetuin-A level may be associated with APN after OSP use in patients with NS, thus careful attention should be paid when colonoscopy using OSP is scheduled in this population.

Alveolar regions of the mandible for the installation of immediate-implant fixtures and bone screws of alveolar distractors.

The purposes of this study were to elucidate the anatomic relationship between the dental roots and surrounding tissues and to identify the optimal sites at which to install dental surgical devices including immediate-implant fixtures and alveolar distractors. We made 5 types of measurements on horizontal cross sections obtained at 1-mm intervals from 20 Korean mandibles. The following results were obtained: (1) the mandibular facial plate was thinnest at the canine (0.5-0.7 mm) and became thicker toward the molar region; (2) the thicknesses of the facial and lingual cortical bone in the interdental region increased from anterior to posterior and from coronal to apical aspects; (3) in each section, the buccolingual root was narrower than 4 mm at depths greater than 8 and 9 mm in the central and lateral incisors, respectively, and the maximum mesiodistal root widths were 3.0 and 3.3 mm; (4) the interroot distance increased from anterior to posterior and from coronal to apical aspects; and (5) on the sections of the first and second molars, the diameter of the septal bone ranged from 4.2 to 7.9 mm buccolingually and from 1.3 to 3.3 mm mesiodistally. Achieving successful placements of implant fixtures and bone screws requires an accurate understanding of the anatomic structure at the installation site. The reported anatomic data might facilitate successful treatments and provide crucial information for use when planning and performing placements of dental surgical devices.