Chronic hyperglycemia reduces the expression of intercellular adhesion molecules and increases intercellular hyperpermeability in the periodontal epithelium

This is the peer reviewed version of the following article: Narukawa Y., Sugiyama N., Miura J., et al. Chronic hyperglycemia reduces the expression of intercellular adhesion molecules and increases intercellular hyperpermeability in the periodontal epithelium. Journal of Periodontal Research 58, 813 (2023), which has been published in final form at https://doi.org/10.1111/jre.13140 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.Background/Aims: Hyperglycemia in diabetes is closely associated with periodontal disease progression. This study aimed to investigate the effect of hyperglycemia on the barrier function of gingival epithelial cells as a cause of hyperglycemia-exacerbated periodontitis in diabetes mellitus. Methods: The abnormal expression of adhesion molecules in gingival epithelium in diabetes was compared between db/db and control mice. To study the effects of hyperglycemia on interepithelial cell permeability, the mRNA and protein expressions of adhesion molecules were investigated using a human gingival epithelial cell line (epi 4 cells) in the presence of either 5.5 mM glucose (NG) or 30 mM glucose (HG). Immunocytochemical and histological analyses were performed. We also studied HG-related intracellular signaling to assess abnormal adhesion molecule expression in the cultured epi 4 cells. Results: The results of the proteomic analysis implied the abnormal regulation of cell–cell adhesion, and mRNA and protein expression assessments revealed the significant downregulation of Claudin1 expression in the gingival tissues of db/db mice (p <.05 vs control). Similarly, the mRNA and protein expressions of adhesion molecules were lower in epi 4 cells cultured under HG conditions than in those cultured under NG conditions (p <.05). Three-dimensional culture and transmission electron microscopy revealed reduced thickness of the epithelial cell layers with no flattened apical cells and heterogeneously arranged intercellular spaces among adjacent epi 4 cells under the HG. These results were consistent with the increased permeability of epi 4 cells under the HG relative to that of cells under the NG. This abnormal expression of intercellular adhesion molecules under the HG was related to the increased expression of receptors for advanced glycation end products (AGEs) and oxidative stress relative to that seen under the NG, along with stimulation of ERK1/2 phosphorylation in epi 4 cells. Conclusions: High glucose-induced impairment of intercellular adhesion molecule expression in gingival epithelial cells was related to the intercellular permeability of gingival cells, representing a possible link to hyperglycemia-related AGE signaling, oxidative stress, and ERK1/2 activation

Usability of detecting delivery errors during treatment of prostate VMAT with a gantry-mounted transmission detector

Volumetric‐modulated arc therapy (VMAT) requires highly accurate control of multileaf collimator (MLC) movement, rotation speed of linear accelerator gantry, and monitor units during irradiation. Pretreatment validation and monitoring of these factors during irradiation are necessary for appropriate VMAT treatment. Recently, a gantry mounted transmission detector “Delta4 Discover® (D4D)” was developed to detect errors in delivering doses and dose distribution immediately after treatment. In this study, the performance of D4D was evaluated. Simulation plans, in which the MLC position was displaced by 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 mm from the clinically used original plans, were created for ten patients who received VMAT treatment for prostate cancer. Dose deviation (DD), distance‐to‐agreement (DTA), and gamma index analysis (GA) for each plan were evaluated by D4D. These results were compared to the results (DD, DTA and GA) measured by Delta4 Phantom + (D4P). We compared the deviations between the planned and measured values of the MLC stop positions A‐side and B‐side in five clinical cases of prostate VMAT during treatment and measured the GA values. For D4D, when the acceptable errors for DD, DTA, and GA were determined to be ≤3%, ≤2 mm, and ≤3%/2 mm, respectively, the minimum detectable errors in the MLC position were 2.0, 1.5, and 1.5 mm based on DD, DTA, and GA respectively. The corresponding minimum detectable MLC position errors were 2.0, 1.0, and 1.5 mm, respectively, for D4P. The deviation between the planned and measured position of MLC stopping point of prostate VMAT during treatment was stable at an average of −0.09 ± 0.05 mm, and all GA values were above 99.86%. In terms of delivering doses and dose distribution of VMAT, error detectability of D4D was comparable to that of D4P. The transmission‐type detector “D4D” is thus suitable for detecting delivery errors during irradiation

The Importance of Biologically Active Vitamin D for Mineralization by Osteocytes After Parathyroidectomy for Renal Hyperparathyroidism

Hypomineralized matrix is a factor determining bone mineral density. Increased perilacunar hypomineralized bone area is caused by reduced mineralization by osteocytes. The importance of vitamin D in the mineralization by osteocytes was investigated in hemodialysis patients who underwent total parathyroidectomy (PTX) with immediate autotransplantation of diffuse hyperplastic parathyroid tissue. No previous reports on this subject exist. The study was conducted in 19 patients with renal hyperparathyroidism treated with PTX. In 15 patients, the serum calcium levels were maintained by subsequent administration of alfacalcidol (2.0 μg/day), i.v. calcium gluconate, and oral calcium carbonate for 4 weeks after PTX (group I). This was followed in a subset of 4 patients in group I by a reduced dose of 0.5 μg/day until 1 year following PTX; this was defined as group II. In the remaining 4 patients, who were not in group I, the serum calcium (Ca) levels were maintained without subsequent administration of alfacalcidol (group III). Transiliac bone biopsy specimens were obtained in all groups before and 3 or 4 weeks after PTX to evaluate the change of the hypomineralized bone area. In addition, patients from group II underwent a third bone biopsy 1 year following PTX. A significant decrease of perilacunar hypomineralized bone area was observed 3 or 4 weeks after PTX in all group I and II patients. The area was increased again in the group II patients 1 year following PTX. In group III patients, an increase of the hypomineralized bone area was observed 4 weeks after PTX. The maintenance of a proper dose of vitamin D is necessary for mineralization by osteocytes, which is important to increase bone mineral density after PTX for renal hyperparathyroidism

Treatment for secondary hyperparathyroidism focusing on parathyroidectomy

Secondary hyperparathyroidism (SHPT) is a major problem for patients with chronic kidney disease and can cause many complications, including osteodystrophy, fractures, and cardiovascular diseases. Treatment for SHPT has changed radically with the advent of calcimimetics; however, parathyroidectomy (PTx) remains one of the most important treatments. For successful PTx, removing all parathyroid glands (PTGs) without complications is essential to prevent persistent or recurrent SHPT. Preoperative imaging studies for the localization of PTGs, such as ultrasonography, computed tomography, and 99mTc-Sestamibi scintigraphy, and intraoperative evaluation methods to confirm the removal of all PTGs, including, intraoperative intact parathyroid hormone monitoring and frozen section diagnosis, are useful. Functional and anatomical preservation of the recurrent laryngeal nerves can be confirmed via intraoperative nerve monitoring. Total or subtotal PTx with or without transcervical thymectomy and autotransplantation can also be performed. Appropriate operative methods for PTx should be selected according to the patients’ need for kidney transplantation. In the case of persistent or recurrent SHPT after the initial PTx, localization of the causative PTGs with autotransplantation is challenging as causative PTGs can exist in the neck, mediastinum, or autotransplanted areas. Additionally, the efficacy and cost-effectiveness of calcimimetics and PTx are increasingly being discussed. In this review, medical and surgical treatments for SHPT are described

A collaborative approach to head and neck carcinoma for oral surgeons, head and neck surgeons, and plastic surgeons: The role of oral surgeons in two cases

There is a medical team approach used in many hospitals for oral cancer patients. The members are head & neck surgeons and plastic surgeons, or oral surgeons and plastic surgeons. However, in Japan, it is very difficult for oral surgeons to cooperate with head & neck surgeons, except in the case of extractions and oral health care, because both surgeons treat oral carcinomas and there is therefore a conflict in their scope of practice. We believe it desirable for head & neck surgeons to treat oral cancer patients with tumors extending to other regions, and oral surgeons should be in charge of occlusion in head and neck carcinomas. We treated two patients with oral carcinomas in collaboration with head and neck surgeons and plastic surgeons, with head & neck surgeons resecting the tumors, plastic surgeons reconstructing, and oral surgeons (dentists) taking charge of the occlusion for patients in the operating room. This collaboration resulted in patients having good position of the temporomandibular joint and occlusions after the operation. We therefore conclude that this collaborative team approach may be of benefit to the patients

The collaborative role of oral surgery with plastic as well as head & neck surgery in head and neck cancers : Preoperative plate-bending method in cases with mandibular reconstruction using plaster 3D models

The collaboration of various medical teams is crucial for the appropriate treatment of cancer patients. However, in Japan, it is very difficult for oral surgeons to cooperate with head and neck surgeons due to conflicts in the treatment of those patients. There have been few studies on this subject. In the current work, we report on the collaboration of head and neck surgeons, plastic surgeons and oral surgeons in operations on two patients with gingival carcinomas in the mandible. We first prepared plaster 3D models of the patients'mouths by means of ink-jet from CT data. We pre-bent the reconstruction plates using the preoperative 3D models. Therefore, we could save the time required to bend the plate. Plaster models are cheaper than resin models. It is also easy to model the surgery using the plate. During the operation, head and neck surgeons resected the tumors, plastic surgeons performed reconstruction with vascularized bone or skin graft, and oral surgeons (dentists) did plate fixation and took charge of the patients'occlusion. This method resulted in patients having good occlusion after the operation

Advanced Clinical Usefulness of Ultrasonography for Diseases in Oral and Maxillofacial Regions

Various kinds of diseases may be found in the oral and maxillofacial regions and various modalities may be applied for their diagnosis, including intra-oral radiography, panoramic radiography, ultrasonography, computed tomography, magnetic resonance imaging, and nuclear medicine methods such as positron emission tomography. Of these modalities, ultrasound imaging is easy to use for the detection of noninvasive and soft tissue-related diseases. Doppler ultrasound images taken in the B-mode can provide vascular information associated with the morphology of soft tissues. Thus, ultrasound imaging plays an important role in confirming the diagnosis of many kinds of diseases in such oral and maxillofacial regions as the tongue, lymph nodes, salivary glands, and masticatory muscles. In the present article, we introduce three new applications of ultrasonography: guided fine-needle aspiration, measurement of tongue cancer thickness, and diagnosis of metastasis to cervical lymph nodes

Evaluation of complex physical therapy for lymphedema of the unilateral lower limbs

We evaluated the effectiveness of the complex physical therapy (CPT) for lymphedema of the unilateral lower limbs of eleven patients who had been admitted to Tokushima Rehabilitation Hospital. Ten patients were of secondary lymphedema, nine of which were after treatment of uterine cancer and one was of primary lymphedema. Our CPT consited of skin care, manual lymph drainage (MLD), compression therapy with elastic bandages or elastic stockings, and exercise therapy under compression. MLD functionally operates to enhance the lymph drainage more proximally in both contralateral and ipsilateral truncal quadrants of the torso, then in the proximal limb, and only thereafter from the distal to proximal portion of the edematous extremity. Swelling ratio of all patients on admission was 26.9± 11.8% and that at discharge was 16.8±9.4%. Edema reduction ratio (ERR) of the entire patients was 41.5± 16.5%, and 81.8% of cases were recognized as effective, in which ERR showed more than 30% at discharge. In a consensus document about the diagnosis and treatment of peripheral lymphedema in 1995, the International Society of Lymphology Executive Committee reported that most operations designed to alleviate peripheral lymphedema have not as yet been perfected or usually are still inferior to combined physiotherapy. At present lymphedema should be accurately diagnosed in the early stage and be treated with CPT correctly by clinicians who understand lymphedema thoroughly and are well trained

An Association Analysis between Mitochondrial DNA A10398G Polymorphism and Temperament in Japanese Young Adults

The mitochondrial (mt) DNA C5178A and A10398G polymorphisms have been reported to be associated with mental disorders such as bipolar disorder. However, the effects of these polymorphisms on temperament in healthy people are poorly understood. Evaluating healthy subjects can have the advantage of providing new strategies for maintaining psychological health and preventing mental illness. We examined the association between mtDNA polymorphisms and temperament in Japanese students. There was no significant difference in examined temperament when analysed by genotypes, 5178–10398 haplotypes, or sex. The subgroup analysis based on sex indicated that there was an interactive effect of the mtDNA A10398G polymorphism and sex on anxiety and obsession. This finding is preliminary and cannot exclude the possibility of false-positive due to small sample size (144 subjects) and multiple statistical testing. Further studies involving a larger sample size or other ethnic groups are necessary to confirm that mtDNA A10398G polymorphism can be a genetic factor for temperament