Cellular senescence with SASP in periodontal ligament cells triggers inflammation in aging periodontal tissue.

The direct cause of periodontitis is periodontopathic bacteria, while various environmental factors affect the severity of periodontitis. Previous epidemiological studies have shown positive correlations between aging and periodontitis. However, whether and how aging is linked to periodontal health and disease in biological processes is poorly understood. Aging induces pathological alterations in organs, which promotes systemic senescence associated with age-related disease. Recently, it has become evident that senescence at the cellular level, cellular senescence, is a cause of chronic diseases through production of various secretory factors including proinflammatory cytokines, chemokines, and matrix metalloproteinases (MMPs), which is referred to the senescence-associated secretory phenotype (SASP). In this study, we examined the pathological roles of cellular senescence in periodontitis. We found localization of senescent cells in periodontal tissue, particularly the periodontal ligament (PDL), in aged mice. Senescent human PDL (HPDL) cells showed irreversible cell cycle arrest and SASP-like phenotypes in vitro. Additionally, we observed age-dependent upregulation of microRNA (miR)-34a in HPDL cells. These results suggest that chronic periodontitis is mediated by senescent PDL cells that exacerbate inflammation and destruction of periodontal tissues through production of SASP proteins. Thus, miR-34a and senescent PDL cells might be promising therapeutic targets for periodontitis in elderly people.

Autophagy facilitates type I collagen synthesis in periodontal ligament cells.

Autophagy is a lysosomal protein degradation system in which the cell self-digests its intracellular protein components and organelles. Defects in autophagy contribute to the pathogenesis of age-related chronic diseases, such as myocardial infarction and rheumatoid arthritis, through defects in the extracellular matrix (ECM). However, little is known about autophagy in periodontal diseases characterised by the breakdown of periodontal tissue. Tooth-supportive periodontal ligament (PDL) tissue contains PDL cells that produce various ECM proteins such as collagen to maintain homeostasis in periodontal tissue. In this study, we aimed to clarify the physiological role of autophagy in periodontal tissue. We found that autophagy regulated type I collagen synthesis by elimination of misfolded proteins in human PDL (HPDL) cells. Inhibition of autophagy by E-64d and pepstatin A (PSA) or siATG5 treatment suppressed collagen production in HPDL cells at mRNA and protein levels. Immunoelectron microscopy revealed collagen fragments in autolysosomes. Accumulation of misfolded collagen in HPDL cells was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. E-64d and PSA treatment suppressed and rapamycin treatment accelerated the hard tissue-forming ability of HPDL cells. Our findings suggest that autophagy is a crucial regulatory process that facilitates type I collagen synthesis and partly regulates osteoblastic differentiation of PDL cells.

Splenic mass of uncertain etiology in a 15-year-old male patient: a case report.

BACKGROUND: There are few reports on spleen masses, and solitary splenic abscesses with abdominal pain have not been reported in younger age groups. We report a case of a splenic mass of uncertain etiology in a 15-year-old boy. CASE PRESENTATION: A 15-year-old boy visited the emergency department with abdominal pain. Abdominal ultrasonography revealed a thin-walled multilobular splenic cyst. Computed tomography revealed a cystic shadow and a septate structure in the spleen. Magnetic resonance imaging examination revealed a high-signal region on the T2-weighted image. The neutrophil ratio in the white blood cell count of 8,330/µL was high (80%), and splenic abscess could not be ruled out. Thus, therapy with 2 g/day fosfomycin was initiated. Abdominal pain disappeared on day 3 of hospital stay, and the patient was discharged on day 8. CONCLUSION: Antibiotic therapy can be effective against very acute onset splenic abscesses, although surgical treatment is usually carried out.

Effect of ß-Cyclodextrin on Physicochemical Properties of an Ionic Liquid Electrolyte Composed of N-Methyl-N-Propylpyrrolidinium bis(trifluoromethylsulfonyl)amide.

Ionic liquids (ILs) are promising electrolyte materials for developing next-generation rechargeable batteries. In order to improve their properties, several kinds of additives have been investigated. In this study, ß-cyclodextrin (ß-CD) was chosen as a new additive in IL electrolytes because it can form an inclusion complex with bis(trifluoromethylsulfonyl)amide (TFSA) anions. We prepared the composites by mixing N-methyl-N-propylpyrrolidinium bis(trifluoromethylsulfonyl)amide/LiTFSA and a given amount of triacetyl-ß-cyclodextrin (Acß-CD). The thermal behaviors and electrochemical properties of the composites were analyzed by several techniques. In addition, pulse field gradient NMR measurements were conducted to determine the self-diffusion coefficients of the component ions. The addition of Acß-CD to the IL electrolytes results in the decrease in the conductivity value and the increase in the viscosity value. In contrast, the addition of Acß-CD to the IL electrolytes induced an improvement in the anodic stability because of the formation of an inclusion complex between the Acß-CD and TFSA anions. CDs are potential candidates as additives in IL electrolytes for electrochemical applications.

Effects of ethyl acetate extract of Kaempferia parviflora on brown adipose tissue.

We have previously reported the effects of Kaempferia parviflora (KP), including anti-obesity, preventing various metabolic diseases, and regulating differentiation of white adipose cells. In this study we used Tsumura, Suzuki, Obese Diabetes (TSOD) mice--an animal model of spontaneous obese type II diabetes--and primary brown preadipocytes to examine the effects of the ethyl acetate extract of KP (KPE) on brown adipose tissue, which is one of the energy expenditure organs. TSOD mice were fed with MF mixed with either KPE 0.3 or 1% for 8 weeks. Computed tomography images showed that whitening of brown adipocytes was suppressed in the interscapular tissue of the KPE group. We also examined mRNA expression of uncoupling protein 1 (UCP-1) and ß3-adrenalin receptor (ß3AR) in brown adipose tissue. As a result, mRNA expression of UCP-1 significantly increased in the KPE 1% treatment group, indicating that KPE activated brown adipose tissue. We then evaluated the direct effects of KPE on brown adipocytes using primary brown preadipocytes isolated from interscapular brown adipocytes in ICR mice. Triacylglycerol (TG) accumulation in primary brown preadipocytes was increased by KPE in a dose-dependent manner. Each mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), UCP-1, and ß3AR exhibited an upward trend compared with the control group. Moreover, some polymethoxyflavonoids (PMFs), the main compound in KP, also increased TG accumulation. This study therefore showed that KPE enhanced the thermogenesis effect of brown adipocytes as well as promoted the differentiation of brown adipocyte cells.

A novel enzyme-based antimicrobial system comprising iodide and a multicopper oxidase isolated from Alphaproteobacterium strain Q-1.

Alphaproteobacterium strain Q-1 produces an extracellular multicopper oxidase (IOX), which catalyzes iodide (I-) oxidation to form molecular iodine (I2). In this study, the antimicrobial activity of the IOX/iodide system was determined. Both Gram-positive and Gram-negative bacteria tested were killed completely within 5 min by 50 mU mL(-1) of IOX and 10 mM iodide. The sporicidal activity of the system was also tested and compared with a common iodophor, povidone-iodine (PVP-I). IOX (300 mU mL(-1)) killed Bacillus cereus, B. subtilis, and Geobacillus stearothermophilus spores with decimal reduction times of 2.58, 7.62, and 40.9 min, respectively. However, 0.1% PVP-I killed these spores with much longer decimal reduction times of 5.46, 38.0, and 260 min, respectively. To evaluate the more superior sporicidal activity of the IOX system over PVP-I, the amount of free iodine (non-complexed I2) was determined by an equilibrium dialysis technique. The IOX system included more than 40 mg L(-1) of free iodine, while PVP-I included at most 25 mg L(-1) free iodine. Our results suggest that the new enzyme-based antimicrobial system is effective against a wide variety of microorganisms and bacterial spores, and that its strong biocidal activity is due to its high free iodine content, which is probably maintained by re-oxidation of iodide released after oxidation of cell components by I2.

Endoscopic diagnosis of early neoplasia of the esophagus with narrow band imaging: correlations among background coloration and iodine staining findings.

BACKGROUND AND AIM: It was previously reported that high-grade intraepithelial neoplasia of the esophagus turns pink within a few minutes after iodine staining (pink-color sign; PCS); however, iodine staining is uncomfortable. By using narrow band imaging (NBI), color change in the area between the intraepithelial papillary capillary loop (background coloration; BGC) is often observed within the brownish area. The diagnostic usefulness of BGC findings for differentiating high-grade intraepithelial neoplasia from low-grade intraepithelial neoplasia was evaluated. METHODS: In a prospective observational study from September 2010 to August 2012, 285 patients who were in a high-risk group for esophageal squamous cell carcinoma underwent endoscopic examination. Lesions with both endoscopic findings of dilated intraepithelial papillary capillary loop on NBI and iodine-unstained areas were studied, in which endoscopic biopsy or endoscopic resection was subsequently performed. The esophageal background mucosa was also evaluated on the basis of the iodine staining pattern (uniform type: Group U, scattered type: Group S). RESULTS: One hundred three esophageal lesions in 87 patients were studied. When BGC was used as the differentiation index, sensitivity was 93.8%, specificity was 88.2%, and accuracy was 91.3%. When PCS was used, sensitivity was 97.9%, specificity was 88.2%, and accuracy was 93.2% (P = 0.79). In Group U (n = 54), BGC had an accuracy of 93.8%, and PCS had an accuracy of 92.3% (P = 1.0). On the other hand, in Group S (n = 33), BGC had an accuracy of 86.8%, while PCS had an accuracy of 94.7% (P = 0.27). CONCLUSIONS: Diagnosis using BGC on NBI may substitute for diagnosis based on PCS in many patients.

Identification of a high risk gastric cancer group using serum pepsinogen after successful eradication of Helicobacter pylori.

BACKGROUND AND AIM: Pepsinogen (PG) method is widely used to identify high risk groups of gastric cancer. It is very useful before Helicobacter pylori eradication, but after eradication the method becomes useless because the PGI, PGII, PGI/II ratios change. Therefore, we aimed to identify a high risk group for gastric cancer using serum pepsinogen after successful eradication of H. pylori. METHODS: A total of 261 participants were enrolled after successful eradication of H. pylori in Hokkaido University Hospital from 1995 to 2010. Participants with renal failure, taking proton pump inhibitors, and those with advanced gastric cancer were excluded. Serum levels of PGI and II were measured using chemiluminescent immunoassay method. RESULTS: Receiver operating characteristic curves using cancerous and non-cancerous data in post-eradication determined the optimal cut-off value of PGI/II as 4.5. The sensitivity and the specificity were 65.9% and 79.3%, respectively. The usual PG method includes 48.9% of cancer cases, and the PGI/II ≤ 4.5 in post-eradication includes 65.9% of them, and it includes approximately half of the high risk group of diffuse type cancer. PGI/II ≤ 4.5 in post-eradication included many gastric cancer cases detected after eradication (12/16 = 75%). CONCLUSION: In the identification of a high risk group for gastric cancer, we suggest that the optimal cut-off value of PGI/II after successful eradication of H. pylori is 4.5. PGI/II ≤ 4.5 in post-eradication includes more gastric cancer cases compared with the traditional PG method, and 75% of gastric cancer cases detected after eradication.

Frequency of Helicobacter pylori -negative gastric cancer and gastric mucosal atrophy in a Japanese endoscopic submucosal dissection series including histological, endoscopic and serological atrophy.

BACKGROUND: The definition of Helicobacter pylori-negative gastric cancer depends on the accuracy of diagnosis of H. pylori infection. The aim of this study was to determine the frequency of H. pylori-negative gastric cancer and to clarify relationships with histological atrophy, endoscopic atrophy, and serological atrophy. METHODS: A total of 240 early gastric cancers were included in this study. The status of H. pylori infection was determined from the rapid urease test, (13)C-urea breath test, H. pylori culture, histopathological examination and examination of IgG antibodies. In H. pylori-negative gastric cancer, histological atrophy and intestinal metaplasia, endoscopic atrophy and serological atrophy were assessed by pepsinogen. RESULTS: The rate of H. pylori infection was 77.9% and 19 patients (7.9%) had a history of eradication. 34 patients (14.2%) were diagnosed with H. pylori-negative gastric cancer using diagnostic tools of H. pylori. However, most of the patients with H. pylori-negative gastric cancer had histological atrophy and intestinal metaplasia. Only 1 gastric cancer (0.42%) occurred in the mucosa without histological atrophy, endoscopic atrophy or serological atrophy. CONCLUSION: Early gastric cancers in the Japanese endoscopic submucosal dissection series were strongly related to current or past infection with H. pylori and to gastric mucosal atrophy.

Iodide oxidation by a novel multicopper oxidase from the alphaproteobacterium strain Q-1.

Alphaproteobacterium strain Q-1 is able to oxidize iodide (I(-)) to molecular iodine (I(2)) by an oxidase-like enzyme. One of the two isoforms of the iodide-oxidizing enzyme (IOE-II) produced by this strain was excised from a native polyacrylamide gel, eluted, and purified. IOE-II appeared as a single band (51 kDa) and showed significant in-gel iodide-oxidizing activity in sodium dodecyl sulfate-polyacrylamide gel electrophoresis without heat treatment. However, at least two bands with much higher molecular masses (150 and 230 kDa) were observed with heat treatment (95°C, 3 min). IOE-II was inhibited by NaN(3), KCN, EDTA, and a copper chelator, o-phenanthroline. In addition to iodide, IOE-II showed significant activities toward phenolic compounds such as syringaldazine, 2,6-dimethoxy phenol, and p-phenylenediamine. IOE-II contained copper atoms as prosthetic groups and had UV/VIS absorption peaks at 320 and 590 nm. Comparison of several internal amino acid sequences obtained from trypsin-digested IOE-II with a draft genome sequence of strain Q-1 revealed that the products of two open reading frames (IoxA and IoxC), with predicted molecular masses of 62 and 71 kDa, are involved in iodide oxidation. Furthermore, subsequent tandem mass spectrometric analysis repeatedly detected peptides from IoxA and IoxC with high sequence coverage (32 to 40%). IoxA showed homology with the family of multicopper oxidases and included four copper-binding regions that are highly conserved among various multicopper oxidases. These results suggest that IOE-II is a multicopper oxidase and that it may occur as a multimeric complex in which at least two proteins (IoxA and IoxC) are associated.

Myelodysplastic syndrome of del 20q with plasma cell dysplasia.

Deletion of the long arm of chromosome 20 (del 20q) has been observed in patients with myelodysplastic syndrome (MDS) or myeloid malignancies. We experienced an MDS female case of del 20q accompanied by clusters of plasmacytic cells in bone marrow. Her bone marrow cells showed morphological abnormalities in three lineages and the chromosomal abnormality of 46, XX, del (20) (q11.2q13.3). Although the percentage of plasma cells was low in free cells, such cells showed nuclear abnormalities. In bone marrow clots, we also observed clusters of anti-CD38 and anti-CD138 antibody-positive cells. According to the FAB or WHO classification, the diagnosis was unclear. Therefore, we were obliged to term this case as MDS with plasma cell dysplasia. This patient was considered to be a rare case of MDS related to abnormalities in myeloid and B-lymphoid cells.

[Repetition of Helicobacter cinaedi infections during chemotherapy for malignant lymphoma].

A 70-year-old male, who had undergone resection of gastric malignant lymphoma in 1992, presented with cervical lymph node swelling in January 2008. Pathological examination of the lymph node biopsy demonstrated recurrence of malignant lymphoma, and he was treated with the R-CHOP regimen. Although he did not develop fever during the first through third course of R-CHOP, from the fourth course, he repeatedly demonstrated fever over 38°C for about one week after each course of chemotherapy, despite the absence of neutropenia. Helicobacter cinaedi infection was confirmed by blood culture each time. Although it is difficult to diagnose Helicobacter cinaedi infection by the standard culture method, increased numbers of recent reports especially in immunocompromised patients have emphasized the importance of diagnosing Helicobacter cinaedi infection.

POEMS syndrome complicated by follicular lymphoma.

A 59-year-old woman presented with ascites and intraperitoneal lymph node swelling. Pathological examination of the lymph node revealed follicular lymphoma. After a lymph node biopsy, she developed atypical genital bleeding, multiple endocrine disorders, polyneuropathy with a high plasma level of vascular endothelial growth factor (VEGF), and was diagnosed with POEMS syndrome. Following administration of methyl prednisolone, ascites immediately decreased and her performance status improved; however, about 18 months later, renal failure occurred, and she died despite increased steroid dosage. Lymph node swelling is often found in POEMS syndrome; however, its histological appearance is not well known, and it is very rare to be concomitant with malignant lymphoma. Therefore, it is important to perform a lymph node biopsy and investigate it in relation with VEGF.

[A case of primary adenocarcinoma of small intestine with multiple liver metastases successfully treated with mFOLFOX6].

A 60-year-old man was referred to our hospital since his stool examination was positive for occult blood. Colonoscopy showed a tumor of Bauhin's valve and terminal ileum. Biopsy of the tumor was performed and pathological examination revealed adenocarcinoma. No other lesions were detected by gastroduodenoscopy and double-balloon enteroscopy. CT also showed multiple liver metastases. Ileocecal resection was performed because of severe stenosis of the terminal ileum. Histopathological examination revealed moderately-differentiated adenocarcinoma of Bauhin's valve and the terminal ileum, and no adenocarcinoma was found in the cecum and ascending colon. He was diagnosed with primary adenocarcinoma of the ileum with multiple liver metastases. Chemotherapy with mFOLFOX6 was performed after surgical resection. After 5 courses of chemotherapy, abdominal CT showed marked regression of the liver metastases, and tumor marker (CA19-9) was normalized from 1,100 U/mL to 36 U/mL. Effectiveness of mFOLFOX6 for primary adenocarcinoma of small intestine is suggested.

Diffuse large B-cell lymphoma with massive portal vein tumor thrombosis in a patient with alcoholic cirrhosis: a case report and literature review.

We describe a case of diffuse large B-cell lymphoma with massive portal vein tumor thrombosis in a patient with alcoholic cirrhosis. The tumor was detected only in the intrahepatic portal vein and the spermatic cord by FDG-PET/CT. Percutaneous liver biopsy and orchiectomy were performed and histological examination revealed diffuse large B-cell lymphoma. The tumor showed complete response after six courses of the combination chemotherapy. Portal vein tumor thrombosis of malignant lymphoma is extremely rare; moreover, it is possible that this is the first case of malignant lymphoma originating from the spermatic cord producing portal vein tumor thrombosis.