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

Impact of a learning health system on acute care and medical complications after intracerebral hemorrhage

Introduction: Patients with stroke often experience pneumonia during the acute stage after stroke onset. Oral care may be effective in reducing the risk of stroke‐associated pneumonia (SAP). We aimed to determine the changes in oral care, as well as the incidence of SAP, in patients with intracerebral hemorrhage, following implementation of a learning health system in our hospital. Methods: We retrospectively analyzed the data of 1716 patients with intracerebral hemorrhage who were hospitalized at a single stroke center in Japan between January 2012 and December 2018. Data were stratified on the basis of three periods of evolving oral care: period A, during which conventional, empirically driven oral care was provided (n = 725); period B, during which standardized oral care was introduced, with SAP prophylaxis based on known risk factors (n = 469); and period C, during which oral care was risk‐appropriate based on learning health system data (n = 522). Logistic regression analysis was performed to evaluate associations between each of the three treatment approaches and the risk of SAP. Results: Among the included patients, the mean age was 71.3 ± 13.6 years; 52.6% of patients were men. During the course of each period, the frequency of oral care within 24 hours of admission increased (P < .001), as did the adherence rate to oral care ≥3 times per day (P < .001). After adjustment for confounding factors, a change in the risk of SAP was not observed in period B; however, the risk significantly decreased in period C (odds ratio 0.61; 95% confidence interval 0.43‐0.87) compared with period A. These associations were maintained for SAP diagnosed using strict clinical criteria or after exclusion of 174 patients who underwent neurosurgical treatment. Conclusions: Risk‐appropriate care informed by the use of learning health system data could improve care and potentially reduce the risk of SAP in patients with intracerebral hemorrhage in the acute stage

Review of Fabrication and Characterization of Nd–Fe–B Thick Films for Magnetic Micromachines

Isotropic Nd-Fe-B thick film magnets were prepared by a high-speed pulsed laser deposition method followed by a post annealing. The deposition rate of 90 μm/h could be successfully achieved, and a pulse annealing was adopted as the post annealing process in order to enhance coercivity. Use of a substrate heating system under the high deposition rate enabled us to obtain anisotropic thick films with (BH)max of approximately 120 kJ/m3, which show the potential for an improvement in the properties of the micromachines. Novel micromachines comprising the Isotropic films were introduced

Clinical characteristics, management strategies and outcomes of patients with recurrent venous thromboembolism in the real world

There is a paucity of data on management strategies and clinical outcomes after recurrent venous thromboembolism (VTE). In a multicenter registry enrolling 3027 patients with acute symptomatic VTE, the current study population was divided into the following 3 groups: (1) First recurrent VTE during anticoagulation therapy (N = 110); (2) First recurrent VTE after discontinuation of anticoagulation therapy (N = 116); and (3) No recurrent VTE (N = 2801). Patients with first recurrent VTE during anticoagulation therapy more often had active cancer (45, 25 and 22%, P < 0.001). Among 110 patients with first recurrent VTE during anticoagulation therapy, 84 patients (76%) received warfarin at recurrent VTE with the median prothrombin time-international normalized ratio (PT-INR) value at recurrent VTE of 1.6, although patients with active cancer had a significantly higher median PT-INR value at recurrent VTE compared with those without active cancer (2.0 versus 1.4, P < 0.001). Within 90 days after recurrent VTE, 23 patients (20.9%) during anticoagulation therapy and 24 patients (20.7%) after discontinuation of anticoagulation therapy died. Active cancer was a major cause of recurrent VTE during anticoagulation therapy as a patient-related factor, while sub-optimal intensity of anticoagulation therapy was a major cause of recurrent VTE during anticoagulation therapy as a treatment-related factor, particularly in patients without active cancer

A fatal case of COVID-19 pneumonia due to possible pulmonary thrombosis

The relationship between the severity of COVID-19, hyperinflammation, and intravascular oagulopathy is of critical importance. We report on a case of severe COVID-19 pneumonia treated with favipiravir during the earliest phase of the pandemic. The present case showed improvement in SARS-CoV-2 viral load and the presence of SARS-CoV-2 IgG with decreased radiological evidence of pulmonary infiltration. Moreover, the levels of serum IL-6 and TNF-α did not increase markedly. However, the hypoxia failed to recover, leading to the patient’s death due to possible pulmonary thrombosis, because D-dimer was markedly elevated, and an electrocardiogram showed typical changes. At present, the fact that some COVID-19 patients with mild to moderate symptoms suddenly die at home has become a major issue in Japan. These findings suggest that additional treatment with anti-coagulants should be considered in some COVID-19 patients at risk of ypercoagulation to prevent sudden death from pulmonary thrombosis

Applicability of radiocolloids, blue dyes and fluorescent indocyanine green to sentinel node biopsy in melanoma

Patients with primary cutaneous melanoma underwent sentinel node (SN) mapping and biopsy at 25 facilities in Japan by the combination of radiocolloid with gamma probe and dye. Technetium-99m (99mTc)-tin colloid, 99mTc-phytate, 2% patent blue violet (PBV) and 0.4% indigo carmine were used as tracers. In some hospitals, 0.5% fluorescent indocyanine green, which allows visualization of the SN with an infrared camera, was concomitantly used and examined. A total of 673 patients were enrolled, and 562 cases were eligible. The detection rates of SN were 95.5% (147/154) with the combination of tin colloid and PBV, 98.9% (368/372) with the combination of phytate and PBV, and 97.2% (35/36) with the combination of tin colloid or phytate and indigo carmine. SN was not detected in 12 cases by the combination method, and the primary tumor was in the head and neck in six of those 12 cases. In eight of 526 cases (1.5%), SN was detected by PBV but not by radiocolloid. There were 13 cases (2.5%) in which SN was detected by radiocolloid but not by PBV. In 18 of 36 cases (50%), SN was detected by radiocolloid but not by indigo carmine. Concomitantly used fluorescent indocyanine green detected SN in all of 67 cases. Interference with transcutaneous oximetry by PVB was observed in some cases, although it caused no clinical trouble. Allergic reactions were not reported with any of the tracers. 99mTc-tin colloid, 99mTc-phytate, PBV and indocyanine green are useful tracers for SN mapping.ArticleJOURNAL OF DERMATOLOGY. 39(4):336-338 (2012)journal articl

A variant Philadelphia chromosome (Ph1) positive chronic myelocytic leukemia.

A rare case of variant Philadelphia (Ph1) chromosome positive [46, XX, t (9; 22) (q34; q11), inv (9) (9q22; 22q13)] chronic myelocytic leukemia (CML) was described. The patient, 73 years old female, was hospitalized to our hospital because of leukocytosis. Hematological findings corresponded to those of CMLs. However, this case lacked hepatosplenomegaly. Southern blot analysis using a 3 breakpoint cluster region (bcr) probe revealed a bcr rearrangement. The patient has been in the chronic phase for sixteen months without treatment. Clinical and chromosomal changes are under observation in order to get accumulate data for a pathophysiological analysis of variant Ph1 positive CMLs.</p

A human T cell leukemia virus type-I carrier with recurrent thrombocytopenia and various autoantibodies.

A 34-year-old woman infected with human T cell leukemia virus type-I(HTLV-I) with recurrent thrombocytopenia and various autoantibodies is described. The platelet counts fluctuated between 1.3 x 10(4)/microliters and 14.8 x 10(4)/microliters without any medical treatment, and thrombocytopenia improved with a decrease of platelet-associated IgG (PA-IgG). Autoantibodies such as rheumatoid factor, antinuclear factor, anti-Sm, anti-RNP and anti-SSA antibodies were also recognized. Marker analysis of peripheral mononuclear cells showed an increase in the proportion of CD 25+ cells, CD 3+ HLA-DR+ cells, CD4+ HLA-DR+ cells and CD8+ HLA-DR+ cells. The recurrent thrombocytopenia and development of various autoantibodies in this HTLV-I carrier are speculated to be due to the alteration of B cell functions by T cells infected with HTLV-I.</p