Search for Periodic Time Variations of the Solar

We report a search for time variations of the solar ^{8}B neutrino flux using 5804 live days of Super-Kamiokande data collected between May 31, 1996, and May 30, 2018. Super-Kamiokande measured the precise time of each solar neutrino interaction over 22 calendar years to search for solar neutrino flux modulations with unprecedented precision. Periodic modulations are searched for in a dataset comprising five-day interval solar neutrino flux measurements with a maximum likelihood method. We also applied the Lomb-Scargle method to this dataset to compare it with previous reports. The only significant modulation found is due to the elliptic orbit of the Earth around the Sun. The observed modulation is consistent with astronomical data: we measured an eccentricity of (1.53±0.35)%, and a perihelion shift of (-1.5±13.5) days.

Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande.

We report a search for cosmic-ray boosted dark matter with protons using the 0.37 megaton×years data collected at Super-Kamiokande experiment during the 1996-2018 period (SKI-IV phase). We searched for an excess of proton recoils above the atmospheric neutrino background from the vicinity of the Galactic Center. No such excess is observed, and limits are calculated for two reference models of dark matter with either a constant interaction cross section or through a scalar mediator. This is the first experimental search for boosted dark matter with hadrons using directional information. The results present the most stringent limits on cosmic-ray boosted dark matter and exclude the dark matter-nucleon elastic scattering cross section between 10^{-33}cm^{2} and 10^{-27}cm^{2} for dark matter mass from 1 MeV/c^{2} to 300 MeV/c^{2}.

Erratum: Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande [Phys. Rev. Lett. 130, 031802 (2023)].

This corrects the article DOI: 10.1103/PhysRevLett.130.031802.

Oral environment and taste function of Japanese HIV-infected patients treated with antiretroviral therapy.

The aim of the study was to evaluate the oral environment and the taste function of Japanese HIV-infected patients treated with antiretroviral therapy. Their median age of 73 patients taking anti-HIV drugs was 46 years. The median period of taking anti-HIV drugs was 30 months. The oral condition was evaluated by measurement of oral moisture, amount of saliva secretion, the number of oral bacteria, presence of oral candida, a taste test, and the number of missing teeth. The levels of oral moisture and secreted saliva were significantly lower in the HIV-infected group than in the healthy volunteer (control) group. The HIV-infected group showed a more robust decrease in taste sensation than the control group. The number of missing teeth was significantly higher in the HIV-infected group than in the control group. Furthermore, all of the evaluated oral conditions were worse in the HIV-infected patients whose CD4+ T lymphocyte counts were less than 500/mm3 than in the control group. It became clear that the patients taking anti-HIV drugs, especially the CD4+ count < 500/mm3 group, had a deteriorated oral environment and dysgeusia, suggesting that the management of oral hygiene is necessary to maintain oral health, which leads to systemic health.

Heparin-LL37 complexes are less cytotoxic for human dental pulp cells and have undiminished antimicrobial and LPS-neutralizing abilities.

AIM: To investigate whether glycosaminoglycans (GAGs) binding to high-dose LL37 eliminates its cytotoxicity to dental pulp cells (hDPCs) whilst retaining undiminished antimicrobial and LPS-neutralizing abilities. METHODOLOGY: hDPCs were stimulated with varying concentrations of LL37, and their cell viability was analysed by MTT. Then, high-dose LL37 (10 µmol L-1 ) was bound to varying concentrations of three GAGs, heparin, chondroitin sulphate and hyaluronic acid, and their cytotoxic effects on hDPCs and antimicrobial effects were evaluated and compared. Furthermore, the LPS-neutralizing ability of heparin (5 µg mL-1 )-LL37 (10 µmol L-1 ) complexes, which were found to be less cytotoxic for hDPCs with undiminished antimicrobial ability, was investigated. Statistical analysis was performed using one-way analysis of variance (anova), followed by Dunnett's test. P values below 0.05 were considered significant. RESULTS: LL37 significantly reduced the cell viability of hDPCs in a dose-dependent manner (P < 0.01). LL37 (10 µmol L-1 ) binding to heparin within a limited concentration range (2~6 µg mL-1 ) eliminated the cytotoxicity for hDPCs (P < 0.01) whilst exerting potent antimicrobial effects against Streptococcus mutans, Streptococcus sobrinus, Streptococcus salivarius, Aggegatibacter actinomycetemcomitans and Escherichia coli. LL37 (10 µmol L-1 ) binding to chondroitin sulphate exhibited similar functions (P < 0.01); however, the effective chondroitin sulphate concentration was highly restricted (3 µg mL-1 ). LL37 (10 µmol L-1 ) binding to hyaluronic acid was unable to abrogate the cytotoxicity of LL37 even at higher concentrations (10 and 100 µg mL-1 ). Moreover, exogenous addition of LPS dose-dependently reduced the amount of LL37 precipitated with the heparin-LL37 agarose beads (P < 0.01), and the released LL37 simultaneously neutralized the pro-inflammatory ability of LPS in macrophages (P < 0.01). CONCLUSIONS: Heparin-LL37 complexes generated at suitable concentration ratios are easy to make, are less cytotoxic and are broad-range antimicrobial materials that can neutralize LPS by providing LL37 in accordance with the amount of free LPS. They may be a potential treatment to save dental pulp tissue from the acute inflammation exacerbated by invading bacteria and the LPS they release.

Brain-derived neurotrophic factor prevents the endothelial barrier dysfunction induced by interleukin-1ß and tumor necrosis factor-α.

BACKGROUND AND OBJECTIVE: Brain-derived neurotrophic factor (BDNF) promotes the regeneration of periodontal tissue. Although a local inflammatory step is required to initiate the subsequent process of tissue regeneration, excessive inflammation may inhibit or delay tissue regeneration. Therefore, the regulation of inflammation is essential for periodontal tissue regeneration. In the present study, we examined the influence of BDNF on the human microvascular endothelial cell (HMVEC) barrier dysfunction induced by interleukin (IL)-1ß or tumor necrosis factor (TNF)-α to determine the effects of BDNF on the regulation of local inflammation in periodontal tissue regeneration. MATERIAL AND METHODS: Endothelial permeability was analyzed using a Dextran transport assay with transwell plates. The expression of vascular endothelial (VE)-cadherin was assessed by immunoblotting and immunofluorescence microscopy. RESULTS: BDNF (25 ng/mL) inhibited increase induced in endothelial permeability by IL-1ß and TNF-α. IL-1ß and TNF-α decreased VE-cadherin protein levels, while BDNF recovered the reduction in HMVECs. BDNF protected the increase induced in endothelial permeability by IL-1ß and TNF-α through TrkB. The single addition of BDNF into the culture increased the expression of VE-cadherin in HMVECs. CONCLUSION: BDNF played an important role in inhibiting endothelial barrier dysfunction, which suggests that it may assist in enhancing periodontal tissue regeneration.

Interleukin-8 induces DNA synthesis, migration and down-regulation of cleaved caspase-3 in cultured human gingival epithelial cells.

BACKGROUND AND OBJECTIVE: Migration of the junctional epithelium occurs in association with the formation of a periodontal pocket. Although the migration of junctional epithelium is known to be related to the proliferation and migration of gingival junctional epithelial cells, the mechanism has not been clarified. In patients with periodontitis, the levels of interleukin-8 (IL-8) in both gingival tissue and gingival crevicular fluid are dramatically increased. IL-8 has broad bioactive functions. In this study, we examined the role of IL-8 in DNA synthesis, migration and protection against apoptosis in cultured human gingival epithelial cells (HGEC). MATERIAL AND METHODS: DNA synthesis was estimated by measuring the incorporation of bromodeoxyuridine. The migration of gingival epithelial cells was assessed in a wound-healing assay. The expression of integrin beta-1 was analyzed using immunofluorescence confocal microscopy and western blotting. Cleaved caspase-3 was detected using western blotting and a Caspase-Glo assay kit. RESULTS: IL-8 increased the synthesis of DNA in HGEC, and the maximal effect was seen at 25 or 50 ng/mL of IL-8. In addition, 50 ng/mL of IL-8 induced cell migration, and a neutralizing antibody of integrin beta-1 inhibited the migration. IL-8 also activated expression of integrin beta-1. Furthermore, IL-8 reduced the Aggregatibacter actinomycetemcomitans-induced increase in caspase-3 expression in HGEC. CONCLUSION: IL-8 may facilitate the migration of gingival junctional epithelium by enhancing DNA synthesis, migration and preventing apoptosis of gingival epithelial cells.

Irsogladine maleate inhibits Porphyromonas gingivalis-mediated expression of toll-like receptor 2 and interleukin-8 in human gingival epithelial cells.

BACKGROUND AND OBJECTIVE: Periodontitis is an infectious disease caused by an interaction between the host and periodontopathogenic bacteria. Regulating the immune response in human gingival epithelial cells (HGEC) may contribute to the prevention of periodontitis. Irsogladine maleate (IM) has previously been shown to regulate inflammation and the cell-cell junctional barrier in HGEC. In addition to these functions, control of bacterial recognition is important for preventing inflammation in periodontal tissue. Innate immunity in gingival epithelium is the first line of defense and plays a crucial role against bacterial challenge. Therefore, the effect of IM on regulating toll-like receptor 2 (TLR2), which is part of the innate immunity, was determined in this study. MATERIAL AND METHODS: OBA-9, an immortalized human gingival epithelial cell line, and primary cultured HGEC were used in this study. Real-time PCR and western blotting were performed in OBA-9 or HGEC stimulated with whole cells of Porphyromonas gingivalis or with lipopolysaccharide (LPS) derived from P. gingivalis (PgLPS) in the presence or absence of IM to determine expression of TLR2 mRNA and production of TLR2 protein. Small interfering RNA (siRNA) against TLR2 was transfected into OBA-9 to clarify the association between the induction of TLR2 and interleukin-8 (IL-8) production. RESULTS: The addition of IM into P. gingivalis or PgLPS-induced OBA-9 suppressed IL-8 production (p < 0.01). The addition of IM also abolished the induction of TLR2 by P. gingivalis or PgLPS in OBA-9 and primary cultured HGEC (p < 0.01). The suppressive effect of IM on the induction of TLR2 was also confirmed by immunohistostaining. Stimulation with peptidoglycan, a specific ligand for TLR2, suppressed the expression of toll-like receptor 4 (TLR4) mRNA in the presence of IM (p < 0.01). However, LPS derived from Escherichia coli, a ligand for TLR4, did not induce the expression of TLR2 mRNA. The PgLPS-induced expression of TLR4 mRNA was abolished by IM. Knockdown of TLR2 by siRNA transfection resulted in a weaker response of induction of IL8 mRNA in P. gingivalis or PgLPS-stimulated OBA-9. CONCLUSION: These results suggest that IM suppresses the induction of IL-8 production by regulating increased levels of TLR2.

The differential expression of mgl mRNA by Porphyromonas gingivalis affects the production of methyl mercaptan.

OBJECTIVE: A large number of individuals have halitosis. The total amount of volatile sulfur compounds, which are the main cause of halitosis, has been correlated with periodontitis following bacterial infection. In this study, Porphyromonas gingivalis (Pg), a major periodontopathogenic bacterium, was isolated from patients with halitosis by the amplification of 16S rRNA, and the ability of isolated Pg to produce methyl mercaptan (CH3 SH) was determined to clarify the relationship between halitosis and Pg infection. MATERIALS AND METHODS: CH3 SH concentrations were measured in patients using Oral Chroma. The production of CH3 SH by Pg standard and clinical strains was also measured in vitro. Real-time PCR was performed to compare the expression of mgl mRNA (which encoded l-methionine-a-deamino-g-mercaptomethane-lyase) among the Pg strains. The production of CH3 SH and the expression of mgl mRNA were also determined to assess the effects of oriental medicine. RESULTS: The production of CH3 SH and the expression of mgl mRNA strongly correlated with each other in the presence of l-methionine. The expression of mgl mRNA by Pg W83 was strongly inhibited by magnoliaceae. CONCLUSION: The production of CH3 SH was correlated with the expression of mgl. Furthermore, the oriental medicine, magnoliaceae, may represent a potential treatment for halitosis.

LL37 induces VEGF expression in dental pulp cells through ERK signalling.

AIM: To examine the in vitro effects of LL37 on the expression of vascular endothelial growth factor (VEGF) in human pulp cells and to identify the intracellular signalling pathway involved. METHODOLOGY: Pulp cells at passage 6 were treated with 10 µg mL(-1) synthesized LL37, and an inhibition assay was performed with MAPK or NF-κB inhibitors to determine the possible signalling pathway. VEGF mRNA, VEGF protein and phosphorylated ERK1/2 levels were determined by real-time PCR, ELISA and Western blot, respectively. Data were analysed using t-tests. RESULTS: LL37 significantly increased both the mRNA and protein levels of VEGF in pulp cells (P < 0.01). However, pre-treatment with an ERK kinase inhibitor suppressed these increases. Furthermore, the inhibitor blocked LL37-induced ERK1/2 phosphorylation. CONCLUSIONS: LL37 activated the ERK pathway to boost VEGF secretion from human pulp cells. Because of this angiogenic effect and its reported induction of pulp cell migration and antimicrobial activity against cariogenic bacteria, LL37 may be applicable as a pulp capping material.

Antimicrobial peptide LL37 promotes vascular endothelial growth factor-A expression in human periodontal ligament cells.

BACKGROUND AND OBJECTIVE: LL37, originally found in the innate immune system, is a robust antimicrobial peptide. LL37 exhibits multiple bio-functions in various cell types, such as migration, cytokine production, apoptosis, and angiogenesis besides its antimicrobial activity Periodontal ligament (PL) cells play a pivotal role in periodontal tissue regeneration. Based on these findings, we hypothesized that LL37 can regulate PL cell function to promote regeneration of periodontal tissue. To prove this hypothesis, we investigated the effect of LL37 on the potent angiogenic inducer vascular endothelial growth factor (VEGF) expression in cultures of human PL (HPL) cells because neovascularization is indispensable for the progress of tissue regeneration. Moreover, we investigated the signaling cascade associated with LL37-induced VEGF expression. MATERIAL AND METHOD: HPL cells were treated with synthesized LL37 in the presence or absence of PD98059, a MEK-ERK inhibitor, or PDTC, an NF-κB inhibitor. VEGF expression levels were assessed by real-time polymerase chain reaction analysis and an enzyme-linked immunoassay. Phosphorylation levels of ERK1/2 or NF-κB p65 were determined by Western blotting. RESULTS: LL37 upregulated VEGF-A expression at the mRNA and protein levels in HPL cells, while VEGF-B mRNA expression was not affected. Both ERK and NF-κB inhibitors clearly abrogated the increase in VEGF-A levels induced by LL37 in HPL cells. Importantly, LL37 increased phosphorylated levels of ERK1/2 and NF-κB p65 in HPL cells. CONCLUSION: LL37 induces VEGF-A production in HPL cells via ERK and NF-κB signaling cascades, which may result in angiogenesis, thereby contributing to periodontal regeneration.

Irsogladine maleate regulates epithelial barrier function in tumor necrosis factor-α-stimulated human gingival epithelial cells.

BACKGROUND AND OBJECTIVE: As epithelial cells function as a mechanical barrier, the permeability of the gingival epithelial cell layer indicates a defensive capability against invasion by periodontal pathogens. We have reported the expression of claudin-1 and E-cadherin, key regulators of permeability, in the gingival junctional epithelium. Irsogladine maleate (IM) is a medication for gastric ulcers and also regulates Aggregatibacter actinomycetemcomitans-stimuated chemokine secretion and E-cadherin expression in gingival epithelium. In this study, we have further investigated the effects of IM on the barrier functions of gingival epithelial cells under inflammatory conditions. MATERIAL AND METHODS: We examined the permeability, and the expression of claudin-1 and E-cadherin, in human gingival epithelial cells (HGECs) stimulated with tumor necrosis factor (TNF)-α, with or without IM. RESULTS: TNF-α increased the permeability of HGECs, and IM abolished the increase. TNF-α reduced the expression of E-cadherin in HGECs, and IM reversed the reduction. In addition, immunofluorescence staining showed that TNF-α disrupted claudin-1 expression in HGECs, and IM reversed this effect. CONCLUSION: The results suggest that IM reverses the TNF-α-induced disruption of the gingival epithelial barrier by regulating E-cadherin and claudin-1.

The use of SPECT/CT to assess resorptive activity in mandibular condyles.

The aim of this study was to clarify the clinical significance of bone metabolism in the mandibular condyles in determining condylar resorptive changes. Twelve condyles of patients with idiopathic condylar resorption and degenerative joint disease were analysed using 99mTc HMDP SPECT/CT at baseline and subsequent computed tomography during the follow-up period. Twenty-two healthy condyles were enrolled as controls. After generating three-dimensional SPECT/CT images, two independent observers scored the degree of condylar uptake and measured the morphological changes in the condylar height and condylar volume. In the group with positive condylar uptake, the follow-up computed tomography showed significant decreases in condylar height (-1.69 ± 0.93 mm) and condylar volume (-12.51 ± 10.30%) when compared to healthy controls (condylar height, 0.09 ± 0.54 mm; condylar volume, -0.29 ± 4.22%) (P < 0.001). Moreover, the degree of uptake correlated with the changes in condylar height (observer 1, P = 0.012; observer 2, P = 0.039) and condylar volume (observer 1, P = 0.005; observer 2, P = 0.037). These results suggest that condylar bone metabolism is closely related to the resorptive activity. Thus, SPECT/CT would be useful in the prognostic evaluation or determination of treatment strategies for idiopathic condylar resorption and degenerative joint disease.

Loss of IκBζ Drives Dentin Formation via Altered H3K4me3 Status.

Enforced enrichment of the active promoter marks trimethylation of histone H3 lysine 4 (H3K4me3) and acetylation of histone H3 lysine 27 (H3K27ac) by inhibiting histone demethylases and deacetylases is positively associated with hard tissue formation through the induction of osteo/odontogenic differentiation. However, the key endogenous epigenetic modulator of odontoblasts to regulate the expression of genes coding dentin extracellular matrix (ECM) proteins has not been identified. We focused on nuclear factor (NF)-κB inhibitor ζ (IκBζ), which was originally identified as the transcriptional regulator of NF-κB and recently regarded as the NF-κB-independent epigenetic modulator, and found that IκBζ null mice exhibit a thicker dentin width and narrower pulp chamber, with aged mice having more marked phenotypes. At 6 mo of age, dentin fluorescent labeling revealed significantly accelerated dentin synthesis in the incisors of IκBζ null mice. In the molars of IκBζ null mice, marked tertiary dentin formation adjacent to the pulp horn was observed. Mechanistically, the expression of COL1A2 and COL1A1 collagen genes increased more in the odontoblast-rich fraction of IκBζ null mice than in wild type in vivo, similar to human odontoblast-like cells transfected with small interfering RNA for IκBζ compared with cells transfected with control siRNA in vitro. Furthermore, the direct binding of IκBζ to the COL1A2 promoter suppressed COL1A2 expression and the local active chromatin status marked by H3K4me3. Based on whole-genome identification of H3K4me3 enrichment, ECM and ECM organization-related gene loci were selectively activated by the knockdown of IκBζ, which consistently resulted in the upregulation of these genes. Collectively, this study suggested that IκBζ is the key negative regulator of dentin formation in odontoblasts by inhibiting dentin ECM- and ECM organization-related gene expression through an altered local chromatin status marked by H3K4me3. Therefore, IκBζ is a potential target for epigenetically improving the clinical outcomes of dentin regeneration therapies such as pulp capping.

The expressions of claudin-1 and E-cadherin in junctional epithelium.

BACKGROUND AND OBJECTIVE: The epithelium provides an important barrier against microbial invasion. Tight junction structural proteins called claudins are known to contribute to the epithelial cell barrier. Junctional epithelium is located at a strategically important interface between gingival sulcus and is interconnected by desmosomes and gap junctions, but not by tight junctions. Although claudins are tight junction-associated proteins, they are also expressed in the epithelium despite its lack of tight junctions in invertebrates. Therefore, claudins may play an important role in junctional epithelium without tight junctions. E-cadherin is a key molecule in the formation of adherence junctions and desmosomes. In the present study, we aimed to investigate the expressions of claudin-1,claudin-3, claudin-7 and E-cadherin in the junctional epithelium of Fischer 344 rats. MATERIAL AND METHODS: Gingival tissues from Fischer 344 rats were analyzed by immunohistochemical staining for claudin-1, claudin-3, claudin-7, and E-cadherin. RESULTS: Intense staining for claudin-1 and E-cadherin were observed in the junctional epithelium. In contrast to claudin-1, claudin-3 was mainly expressed in oral gingival epithelium and claudin-7 could not be detected on immunohistochemical analysis of the rat gingiva. CONCLUSION: These data suggest that claudin-1 and E-cadherin exist in the junctional epithelium and may play an important role in epithelial barrier function.

Clinical Outcomes of Post-exposure Prophylaxis following Occupational Exposure to Human Immunodeficiency Virus at Dental Departments of Hiroshima University Hospital.

BACKGROUND: Dental professionals have so many opportunities to use injection needles and sharp instruments during dental treatment that they face an increased risk of needlestick injuries. This retrospective study reports the utilization and clinical outcomes of occupational post-exposure prophylaxis (PEP) with anti-retroviral agents after being potentially exposed to HIV at the dental departments of Hiroshima University Hospital. OBJECTIVE: This study reports the utilization and clinical outcomes of occupational post-exposure prophylaxis (PEP) with antiretroviral agents after being potentially exposed to HIV at dental departments of Hiroshima University Hospital. METHODS: Data on the clinical status of HIV-infected source patients and information on HIV-exposed dental professionals from 2007 to 2018 were collected. RESULTS: Five dentists with an average experience of 5.6 years (1-15 years) were exposed. The averaged CD4-positive cell number and HIV-RNA load were 1176 (768-1898) /µl and less than 20 copies/ml, respectively, in all the patients. Two of the five HIV exposed dentists received PEP. Three months after the exposures, all of their results were negative in HIV antibody/antigen tests. CONCLUSION: ; These data might support the concept of "undetectable equals untransmittable", although HIV exposure in this study was not through sexual transmission.

A phase I study of full-dose gemcitabine and regional arterial infusion of nafamostat mesilate for advanced pancreatic cancer.

BACKGROUND: The primary end points of this study were to determine the dose-limiting toxic effects (DLTs), maximum tolerated dose, and a recommended phase II dose of a synthetic serine protease inhibitor, nafamostat mesilate, in combination with full-dose gemcitabine in patients with unresectable locally advanced or metastatic pancreatic cancer. The secondary end point was to assess therapeutic response. PATIENTS AND METHODS: Patients with previously untreated pancreatic cancer received gemcitabine (1 000 mg/m(2) i.v. for 30 min) on days 1, 8, and 15, with nafamostat mesilate (continuous regional arterial infusion for 24 h through a port-catheter system) on days 1, 8, and 15; this regimen was repeated at 28-day intervals. The initial dose of nafamostat mesilate was 2.4 mg/kg and was escalated in increments of 1.2 mg/kg until a dose of 4.8 mg/kg was achieved. A standard '3+3' phase I dose-escalation design was used. Therapeutic response and clinical benefit response were assessed. RESULTS: Twelve patients were enrolled in this study. None of the patients experienced DLTs, and nafamostat mesilate was well tolerated at doses up to 4.8 mg/kg in combination with full-dose gemcitabine. This combination chemotherapy yielded a reduction of a high serum level of the tumor marker CA19-9. Pain was reduced in three of seven patients without oral morphine sulfate. Overall survival was 7.1 months for all patients. CONCLUSION: This phase I study was carried out safely. This combination chemotherapy showed beneficial improvement in health-related quality of life. The recommended phase II dose of nafamostat mesilate in combination with full-dose gemcitabine is 4.8 mg/kg.

Eradication of Helicobacter pylori in a Living Donor Liver Transplant Recipient With Immunosuppressive Therapy of Cyclosporine A: A Case Report.

A 54-year-old woman underwent living donor liver transplantation (LDLT) for primary biliary cholangitis (PBC) three years earlier. She took cyclosporine A (CyA) 150 mg/day as immunosuppression for prevention of rejection and PBC recurrence. Routine upper gastrointestinal endoscopy showed chronic atrophic gastritis and hyperplastic polyp, and rapid urease test was positive. Anti-Helicobacter pylori (H. pylori) serum IgG was elevated to 51 U/ml. We performed H. pylori eradication therapy with amoxicillin, clarithromycin and lansoprazole measuring the blood CyA concentration every day. Although the blood CyA concentration reached a peak (the concentration 2 hours after the administration: 818 ng/ml) on the second day, she did not develop renal dysfunction or other obvious adverse effects. Five weeks after the treatment, we confirmed eradication of H. pylori with the urea breath test. We herein reported a case of successful eradication of H. pylori in a LDLT recipient on immunosuppressive therapy with CyA without adverse effects.

Irsogladine maleate abolishes the increase in interleukin-8 levels caused by outer membrane protein 29 from Aggregatibacter (Actinobacillus) actinomycetemcomitans through the ERK pathway in human gingival epithelial cells.

BACKGROUND AND OBJECTIVE: Irsogladine maleate (IM) suppresses the increase in interleukin (IL)-8 production induced by outer membrane protein (OMP) 29 from Aggregatibacter (Actinobacillus) actinomycetemcomitans in cultures of human gingival epithelial cells (HGEC). However, how IM suppresses the OMP29-induced increase in IL-8 expression remains unknown. In this study, we focused on intracellular signaling pathways to elucidate the mechanism behind the suppression. MATERIAL AND METHODS: HGEC, which had been pretreated with inhibitors of intracellular signaling molecules, were exposed to OMP29 (1 microg/mL) with or without IM (1 microM). IL-8 expression at the mRNA and protein levels was examined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Extracellular signal-regulated kinase (ERK) activity was measured with a p44/42 mitogen-activated protein kinase assay kit. RESULTS: An ERK inhibitor, PD98059, as well as IM, obviated the OMP29-induced increase in IL-8 levels in HGEC. A Jun kinase inhibitor, SP600125, and a nuclear factor kappaB inhibitor, PDTC, did not influence the OMP29-induced increase in IL-8 mRNA expression. The OMP29 stimulated phosphorylation of ERK in HGEC. Irsogladine maleate inhibited the phosphorylation. CONCLUSION: The suppression of the phosphorylation of ERK by IM in HGEC culminates in inhibition of the OMP29-induced increase in IL-8.

Irsogladine maleate counters the interleukin-1 beta-induced suppression in gap-junctional intercellular communication but does not affect the interleukin-1 beta-induced zonula occludens protein-1 levels in human gingival epithelial cells.

BACKGROUND AND OBJECTIVE: Irsogladine maleate counters gap junctional intercellular communication reduction induced by interleukin-8 or Actinobacillus actinomycetemcomitans in cultured human gingival epithelial cells. Interleukin-1 beta is involved in periodontal disease. Little is known, however, about the effect of interleukin-1 beta on intercellular junctional complexes in human gingival epithelial cells. Furthermore, irsogladine maleate may affect the actions of interleukin-1 beta. In this study, we examined how interleukin-1 beta affected gap junctional intercellular communication, connexin 43 and zonula occludens protein-1, and how irsogladine maleate modulated the interleukin-1 beta-induced changes in the intercellular junctional complexes in human gingival epithelial cells. MATERIAL AND METHODS: Human gingival epithelial cells were exposed to interleukin-1 beta, with or without irsogladine maleate. Connexin 43 and zonula occludens protein-1 were examined at mRNA and protein levels by real-time polymerase chain reaction and western blotting, respectively. Gap junctional intercellular communication was determined using the dye transfer method. The expression of zonula occludens protein-1 was also confirmed by immunofluorescence. RESULTS: Interleukin-1 beta decreased connexin 43 mRNA levels, but increased zonula occludens protein-1 mRNA levels. Irsogladine maleate countered the interleukin-1 beta-induced reduction in gap junctional intercellular communication and connexin 43 levels. However, irsogladine maleate did not influence the increased zonula occludens protein-1 levels. CONCLUSION: The effect of interleukin-1 beta on gap junctional intercellular communication and tight junctions of human gingival epithelial cells is different. The recovery of gap junctional intercellular communication by irsogladine maleate in the gingival epithelium may be a normal process in gingival epithelial homeostasis.