Advanced glycation end-products increase IL-6 and ICAM-1 expression via RAGE, MAPK and NF-κB pathways in human gingival fibroblasts.

BACKGROUND AND OBJECTIVES: Diabetes mellitus (DM) is a risk factor for periodontal diseases and may exacerbate the progression of the pathogenesis of periodontitis. Advanced glycation end-products (AGEs) cause DM complications relative to levels of glycemic control and larger amounts accumulate in the periodontal tissues of patients with periodontitis and DM. In the present study, we investigated the effects of AGEs on the expression of inflammation-related factors in human gingival fibroblasts (HGFs) to elucidate the impact of AGEs on DM-associated periodontitis. MATERIAL AND METHODS: HGFs were cultured with or without AGEs. Cell viability was examined, and RNA and protein fractions were isolated from AGE-treated cells. The expression of interleukin (IL)-6, intercellular adhesion molecule-1 (ICAM-1), and the receptor for AGE (RAGE) was investigated using reverse transcription-polymerase chain reaction, quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, and reactive oxygen species activity was measured using a kit with 2',7'-dichlorofluorescin diacetate. Human monocytic cells (THP-1) labeled with a fluorescent reagent were co-cultured with HGFs treated with AGEs and IL-6 siRNA, and the adhesive activity of THP-1 cells to HGFs was assessed. The expression of IL-6 and ICAM-1 was examined when HGFs were pretreated with recombinant human IL-6, the siRNAs of RAGE and IL-6, and inhibitors of MAPK and NF-κB, and then cultured with and without AGEs. The phosphorylation of MAPK and NF-κB was assessed using western blotting. RESULTS: AGEs increased the mRNA and protein expressions of RAGE, IL-6, ICAM-1 and reactive oxygen species activity in HGFs, and promoted the adhesion of THP-1 cells to HGFs, but had no effect on cell viability until 72 hours. Recombinant human IL-6 increased ICAM-1 expression in HGFs, while the siRNAs of RAGE and IL-6 inhibited AGE-induced IL6 and ICAM1 mRNA expression, and IL-6 siRNA depressed AGE-induced THP-1 cell adhesion. AGEs increased the phosphorylation of p38 and ERK MAPKs, p65 NF-κB and IκBα, while inhibitors of p38, ERK MAPKs and NF-κB significantly decreased AGE-induced IL-6 and ICAM-1 expression. CONCLUSION: AGEs increase IL-6 and ICAM-1 expression via the RAGE, MAPK and NF-κB pathways in HGFs and may exacerbate the progression of the pathogenesis of periodontal diseases.

Inhibitory effects of advanced glycation end-products and Porphyromonas gingivalis lipopolysaccharide on the expression of osteoblastic markers of rat bone marrow cells in culture.

BACKGROUND AND OBJECTIVES: Diabetes is a major risk factor for periodontitis and there is a close relationship between the degree of hyperglycemia and the severity of periodontitis. Advanced glycation end-products (AGEs) accumulate in various tissues under diabetic conditions. AGEs in the periodontal tissues probably play a role in upregulating periodontal inflammation; however, the association of AGEs with the severity of periodontitis has not been fully clarified. Lipopolysaccharide from Porphyromonas gingivalis (P-LPS) is a potent pathogenic factor in periodontitis. Although the independent effect of AGE or P-LPS on osteoblastic cells has been reported in vitro, the effect of adding both has not been clearly elucidated. In this study, to explore factors aggravating diabetic periodontitis, we investigated the effects of AGE and P-LPS on the expression of osteoblastic markers and the expression of inflammation-related markers in vitro. MATERIAL AND METHODS: Rat bone marrow cells were cultured, and alkaline phosphatase activity and bone nodule formation were evaluated as osteoblastic markers. Reverse transcription-polymerase chain reaction was performed to determine the mRNA expression of molecules associated with bone and inflammation. Protein levels of osteocalcin and interleukin-1ß (IL-1ß) were measured using enzyme-linked immunosorbent assay. RESULTS: AGEs and P-LPS independently reduced alkaline phosphatase activity and bone nodule formation. The addition of both AGE and P-LPS (AGE+P-LPS) further decreased these markers. Reverse transcription-polymerase chain reaction analysis revealed that AGE+P-LPS markedly decreased the mRNA expression of osteoblast-related molecules such as type 1 collagen, osteocalcin and Cbfa1, and markedly increased that of inflammation-related molecules such as IL1ß and S100A8. AGE and P-LPS decreased the protein level of osteocalcin and increased that of IL-1ß, and a further increase of IL-1ß was detected for AGE+P-LPS. CONCLUSION: AGEs and P-LPS inhibited the expression of osteoblastic markers and increased the levels of inflammatory markers in rat bone marrow cells, suggesting that both AGE and P-LPS may be important factors associated with the aggravation of diabetic periodontitis.

Systematic review and recommendations for nonodontogenic toothache.

Nonodontogenic toothache is a painful condition that occurs in the absence of a clinically evident cause in the teeth or periodontal tissues. The purpose of this review is to improve the accuracy of diagnosis and the quality of dental treatment regarding nonodontogenic toothache. Electronic databases were searched to gather scientific evidence regarding related primary disorders and the management of nonodontogenic toothache. We evaluated the level of available evidence in scientific literature. There are a number of possible causes of nonodontogenic toothache and they should be treated. Nonodontogenic toothache can be categorised into eight groups according to primary disorders as follows: 1) myofascial pain referred to tooth/teeth, 2) neuropathic toothache, 3) idiopathic toothache, 4) neurovascular toothache, 5) sinus pain referred to tooth/teeth, 6) cardiac pain referred to tooth/teeth, 7) psychogenic toothache or toothache of psychosocial origin and 8) toothache caused by various other disorders. We concluded that unnecessary dental treatment should be avoided.

Metformin prevents liver tumorigenesis induced by high-fat diet in C57Bl/6 mice.

The prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is increasing with the growing epidemics of obesity and diabetes. NAFLD encompasses a clinicopathologic spectrum of disease ranging from isolated hepatic steatosis to NASH, which is a more aggressive form of fatty liver disease, to cirrhosis and, finally, hepatocellular carcinoma (HCC). The exact mechanism behind the development of HCC in NASH remains unclear; however, it has been established that hepatic steatosis is the important risk factor in the development of HCC. Metformin has recently drawn attention because of its potential antitumor effect. Here, we investigated the effects of metformin on high-fat diet (HFD)-induced liver tumorigenesis, using a mouse model of NASH and liver tumor. Metformin prevented long-term HFD-induced liver tumorigenesis in C57Bl/6 mice. Of note, metformin failed to protect against liver tumorigenesis in mice that had already begun to develop NAFLD. Metformin improved short-term HFD-induced fat accumulation in the liver, associated with the suppression of adipose tissue inflammation. Collectively, these results suggest that metformin may prevent liver tumorigenesis via suppression of liver fat accumulation in the early stage, before the onset of NAFLD, which seems to be associated with a delay in the development of inflammation of the adipose tissue.

Preoperative drainage using a transanal tube enables elective laparoscopic colectomy for obstructive distal colorectal cancer.

BACKGROUND AND STUDY AIMS: Acute colorectal obstruction (ACO) often accompanies colorectal cancer (CRC) and requires urgent treatment, but achieving elective laparoscopy-assisted colectomy (LAC) is difficult in this setting. The aim of the current study was to assess the clinical outcomes of a transanal tube (Dennis colorectal tube [DCT]) for CRC with ACO, focusing in particular on the impact of the DCT on subsequent elective LAC. PATIENTS AND METHODS: Among 1142 patients who underwent surgery for CRC between January 2007 and December 2011, 92 patients with ACO were identified retrospectively. Of these 92 patients, the DCT procedure was performed in 66 patients who fulfilled the indications for DCT, and these patients were included in the study. RESULTS: All 66 patients presented with complete obstruction. Technical and clinical success rates for DCT were 93.9 % and 86.4 %, respectively. Perforation after DCT occurred in 4.5 % and the mortality rate was 1.5 %. The rate of LAC was 48.5 %, and the rate of primary stoma was 13.6 %. For curative stage II/III CRC with ACO, DCT resulted in a primary stoma rate of 13.6 %, a one-stage surgery rate of 90.9 %, a LAC rate of 50.0 %, and a 3-year survival rate of 73.1 %. For stage II/III CRC cases with clinical success by DCT, the one-stage surgery rate was 97.4 % and the LAC rate was 56.4 %. CONCLUSIONS: DCT achieved a high rate of clinical success and enabled safe one-stage surgery and LAC for CRC with ACO. DCT followed by LAC is proposed as a promising non-invasive strategy for CRC with ACO.

Prognostic value of serum surfactant protein D level prior to transplant for the development of bronchiolitis obliterans syndrome and idiopathic pneumonia syndrome following allogeneic hematopoietic stem cell transplantation.

Bronchiolitis obliterans syndrome (BOS) and idiopathic pneumonia syndrome (IPS) cause high mortality and impaired survival after allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Early recognition of patients at high risk of developing BOS/IPS may lead to improving the outcome of allo-HSCT. We retrospectively analyzed serum surfactant protein A, D (SP-A, -D) and Kerbs von Lungren 6 Ag (KL-6) levels before allo-HSCT in 56 patients who survived more than 90 days after allo-HSCT and compared values of these serum markers and other transplant factors in BOS/IPS patients with those in non-BOS/IPS patients. Five patients developed BOS and two developed IPS at a median interval of 303 and 117 days (range, 100-452 and 95-153) from transplantation. As a result of univariate analysis, pretransplant serum SP-D levels but not SP-A, KL-6 in BOS/IPS patients were significantly lower than those in non-BOS/IPS patients (P=0.03). In multivariate analysis, the patients with lower pretransplant serum SP-D level had a trend toward frequent development of BOS/IPS (P=0.08). Constitutive serum SP-D level before allo-HSCT may be a useful, noninvasive predictor for the development of BOS/IPS.

Early results of multicenter phase II trial of perioperative oxaliplatin and capecitabine without radiotherapy for high-risk rectal cancer: CORONA I study.

BACKGROUNDS: Perioperative introduction of developed chemotherapy into the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. However, the most prevalent treatment for high-risk LARC remains preoperative chemoradiotherapy (CRT) in Western countries. PATIENTS AND METHODS: A phase II trial was undertaken to evaluate safety and efficacy of perioperative XELOX without radiotherapy (RT) for patients with high-risk LARC. Patients received 4 cycles of XELOX before and after surgery, respectively. Primary endpoint was disease-free survival. RESULTS: We enrolled 41 patients between June 2012 and April 2014. The completion rate of the preoperative XELOX was 90.3%. Twenty-nine patients (70.7%) could start postoperative XELOX, 15 of these patients (51.7%) completed 4 cycles. Allergic reaction to oxaliplatin was experienced by 5 patients (17.2%) during postoperative XELOX. One patient received additional RT after preoperative XELOX. Consequently, the remaining 40 patients underwent primary resection. Major complications occurred in 6 of 40 patients (15.0%). Pathological complete response (pCR) rate was 12.2%, and good tumor regression was exhibited in 31.7%. N down-staging (cN+ to ypN0) and T down-staging were detected in 56.7% and 52.5%, respectively. Clinical T4 tumor was a predictor of poor pathological response (p < 0.001). CONCLUSIONS: We could show the favorable pCR rate after preoperative XELOX alone. However, the T and N down-staging rate was likely to be insufficient. When tumor regression is essential for curative resection, the use of preoperative CRT is likely to be recommended. For patients with massive LN metastasis, the additional Bev to NAC might be a promising option.

Effect of mandibular position on upper airway collapsibility and resistance.

It has been proposed that advancement of the mandible is a useful method for decreasing upper airway collapsibility. We carried out this study to test the hypothesis that mandibular advancement induces changes in upper airway patency during midazolam sedation. To explore its effect, we examined upper airway pressure-flow relationships in each of 4 conditions of mouth position in normal, healthy subjects (n = 9). In the neutral position, Pcrit (i.e., critical closing pressure, an index of upper airway collapsibility) was -4.2 cm H(2)O, and upstream resistance (Rua) was 21.2 cm H(2)O/L/sec. In the centric occlusal position, Pcrit was -7.1 cm H(2)O, and Rua was 16.6 cm H(2)O/L/sec. In the incisor position, Pcrit was significantly reduced to -10.7 cm H(2)O, and Rua was significantly reduced to 14.0 cm H(2)O/L/sec. Mandibular advancement significantly decreased Pcrit to -13.3 cm H(2)O, but did not significantly influence Rua (22.1 cm H(2)O/L/sec). We conclude that the mandibular incisors' position improved airway patency and decreased resistance during midazolam sedation.

Mouth-opening increases upper-airway collapsibility without changing resistance during midazolam sedation.

Sedative doses of anesthetic agents affect upper-airway function. Oral-maxillofacial surgery is frequently performed on sedated patients whose mouths must be as open as possible if the procedures are to be accomplished successfully. We examined upper-airway pressure-flow relationships in closed mouths, mouths opened moderately, and mouths opened maximally to test the hypothesis that mouth-opening compromises upper-airway patency during midazolam sedation. From these relationships, upper-airway critical pressure (Pcrit) and upstream resistance (Rua) were derived. Maximal mouth-opening increased Pcrit to -3.6 +/- 2.9 cm H2O compared with -8.7 +/- 2.8 (p = 0.002) for closed mouths and -7.2 +/- 4.1 (p = 0.038) for mouths opened moderately. In contrast, Rua was similar in all three conditions (18.4 +/- 6.6 vs. 17.7 +/- 7.6 vs. 21.5 +/- 11.6 cm H2O/L/sec). Moreover, maximum mouth-opening produced an inspiratory airflow limitation at atmosphere that was eliminated when nasal pressure was adjusted to 4.3 +/- 2.7 cm H2O. We conclude that maximal mouth-opening increases upper-airway collapsibility, which contributes to upper-airway obstruction at atmosphere during midazolam sedation.

Concurrent induction of two chiral centers from symmetrical 3, 4-disubstituted and 3,3,4-trisubstituted 4-pentenals using Rh-catalyzed asymmetric cyclizations

Asymmetric cyclization of symmetrical 3,4-disubstituted and 3,3, 4-trisubstituted 4-pentenals was studied using Rh-complexes with chiral ligands. The cyclization of symmetrical 4-pentenals 4a,b by a neutral Rh[(R)-BINAP]Cl afforded cis-3,4-disubstituted (4R)-cyclopentanones 9a,b of >95% ee in 25-31% yields; on the other hand, the cyclization of 4a-c by a cationic Rh[(R)-BINAP]ClO(4) afforded trans-3,4-disubstituted (4S)-cyclopentanones 10a-c of >95% ee in 70-81% yields. All stereoisomers could be stereoselectively made by the selection of a neutral or cationic Rh-complex, and (R)- or (S)-BINAP ligand. The Rh-catalyzed cyclization could be applied to the construction of cyclopentanones 17 and 18 bearing a chiral quaternary carbon. The cyclization by the cationic Rh[(R)-BINAP]ClO(4) afforded the optically active trans-3,3, 4-trisubstituted cyclopentanones 18a-c of 92-95% ee in 75-83% yields. The catalytic cycle was also studied by using deuterium aldehyde, and the tentative mechanisms of the enantio- and diastereoselection were proposed.

Semiquantitative evaluation of alpha1A-adrenoceptor subtype mRNA in human hypertrophied and non-hypertrophied prostates: regional comparison.

The main purpose of this study was to compare semiquantitatively the amount of alpha1a-adrenoceptor subtype mRNA in urethral, central and peripheral areas in benign hypertrophied prostates and non-hypertrophied prostate by the competitive reverse transcriptase polymerase chain reaction (RT-PCR) method. Prostates from twenty cases of men with benign prostatic hypertrophy (BPH) and 5 cases of bladder tumor without BPH were obtained for this study. The mRNA was extracted from the urethral, central and peripheral areas of each prostate, and quantitative RT-PCR was performed using the ratio of PCR product of alpha1a-adrenoceptor mRNA/beta2-microglobulin mRNA. The ratio for the central area of the hypertrophied prostate was significantly greater than that for the same area of the non-hypertrophied prostate (p < 0.05). In contrast, the urethral area showed no significant difference between the two prostate conditions. The central area of the hypertrophied prostate showed the tendency to have an increased alpha1a-adrenoceptor mRNA level compared with the urethral area, though no statistical difference was recognized because of the high standard error. Regional differences in the alpha1a-adrenoceptor mRNA in the non-hypertrophied prostate were rarely observed. The present finding demonstrates that the increased alpha1a-adrenoceptor mRNA content found in the hypertrophied prostate (1) was due to that in the central area.

A case of intrahepatic stones with an anomalous intrahepatic portal venous system.

A 64-year-old woman who had undergone surgery for gallstones twice was admitted with epigastric pain and fever. Ultrasonography revealed gallstones in the dilated left lateral intrahepatic bile ducts. Abdominal computed tomography disclosed atrophy of the left lateral segment and the right lobe of the liver, and hypertrophy of the left medial segment and the caudate lobe. Percutaneous transhepatic cholangiography demonstrated that the stones were localized in the left lateral intrahepatic bile ducts, and that the choledochoduodenostomy previously established was patent. Percutaneous transhepatic portography revealed that the left portal vein was absent and the left medial segment was supplied by the right portal vein. Left lateral hepatic segmentectomy and release of the choledochoduodenostomy were performed. Postoperative recovery was good, and the patient is now well without any complaint. This report discusses the surgical treatment for intrahepatic stones under very complicated conditions and the relationship between intrahepatic stones and anomalous portal venous system.

Case of bile duct carcinoma of the hepatic hilus with segmental obstructive cholangitis.

Cholangitis is a risk factor for posthepatectomy liver failure and therefore should be treated aggressively by urgent biliary drainage before definitive liver surgery for bile duct carcinoma. We present a case of bile duct carcinoma of the hepatic hilus with segmental cholangitis. The patient was a 38-year-old man. Percutaneous transhepatic biliary drainage (PTBD) was performed in the left anterior, right anterior, and right posterior segmental ducts to alleviate jaundice and to evaluate the biliary system. One month after PTBD, the patient developed high fever with leukocytosis, suggesting the onset of segmental cholangitis. An urgent repeat PTBD was carried out at the caudate and left medial segmental bile ducts. The bile juice was purulent, and the tube cholangiogram revealed miliary abscesses. After PTBD, cholangitis was subsided, and extended left hepatic lobectomy with caudate lobectomy was performed. The postoperative recovery was uneventful and the patient has been well for 13 months. We conclude that the onset of fever in patients with hilar bile duct cancer, PTBD catheters, and undrained biliary segments suggests the presence of segmental cholangitis.

Determination of vitamin B6 derivatives in foods and biological materials by reversed-phase HPLC.

Through use of a simplified analyzing system, seven vitamin B6 derivatives were determined with a satisfactory sensitivity and precision. This system consisted of a single reversed-phase ODS column with a fluorescence detector employing an isocratic solvent system. Each vitamin B6 derivative in some foods and biological materials was determined, based on the measurement of the integrated peak area. The data obtained by this method were compared with those obtained from a bioassay by Saccharomyces uvarum ATCC 9080, after acid hydrolysis of these materials.

Serious postextraction hemorrhage into the submandibular space: report of case.

A 47-year-old woman had a swelling in the floor of the mouth and in the submandibular area on the left side. About four hours earlier, a dentist had extracted the mandibular left second premolar and first molar. The rate and degree of the distension were alarming; the floor of the mouth was at a level with the incisal edges of the mandibular incisors. Five hours later, the floor of the mouth was elevated about 1 1/2 cm above the incisal edges of the teeth. Treatment of the patient and her unusual sensitivity to meperidine and promethazine that caused a depression into Cheyne-Stokes respiration and hypotension are described.

Cleidocranial dysostosis: a multidisciplinary approach to treatment.

To ensure eruption of the dentition in patients with cleidocranial dysostosis, close collatoration between the oral surgeon and the orthodontist is essential to determine the sequence of extraction, the teeth to be ligated, the preferred technique of ligation, and the approach for surgical exposure.

[Clinical study on ceftezole in oral surgery. Clinical effect of ceftezole used jointly with gamma-globulin (Gamma-Venin) (author's transl)].

Ceftezole, an antibiotic of cephalosporin C derivative was applied to treatment in 39 patients with odontogenic inflammation or postoperative infections. The drug was administered intravenously (1-5 g/day) for the period of 5-10 days. Twenty of them were administered jointly with gamma-globulin (Gamma-Venin). Therefore, we compared clinically between the group of ceftezole with Gamma-Venin and the other group without it. But no difference was noticed statistically between these groups. No side effect was observed with throughout all the cases.

[Evaluation of polymerase chain reaction method for monitoring of fungal infection in compromised hosts].

Diagnosis of fungal infections in compromised hosts has been difficult because of insufficient sensitivity and specificity of conventional methods such as culturing and serum testing. Therefore, antifungal agents are usually started in febrile patients who are resistant to antibiotics even if these monitoring tests were negative. In this study, therefore, in order to increase the reliability of these monitoring, polymerase chain reaction (PCR) methods for detection of blood fungus were also performed in compromised hosts including 14 patients with hematological malignancies and one with solid tumor who were undergoing chemotherapies. From these patients, total of 56 peripheral blood samples was collected periodically, irrespective of the presence of infectious signs. At each time point of venopuncture, status of the patient was allocated to one of the followings: A, receiving an intravenous antifungal therapy because of sustaining fever which had not responded to prior antibiotic therapies and also positive for culturing and/or serum beta-D-glucan tests; B, receiving an additional intravenous antifungal therapy but negative for culturing and serum-tests; C, febrile but not yet receiving any intravenous fungal therapy; D, afebrile status. During the study, 10 blood samples from 3 patients were allocated in group A, and one sample of them was positive while remaining 9 were all negative for PCR. Six samples from 4 patients were in group B, and one was PCR positive while remaining 5 were negative. Fifteen samples from 7 patients were in group C, and 3 were positive and 12 were negative for PCR. Twenty-five samples were in group D, and 5 were positive and 20 were negative for PCR. Thus, the results from fungal PCR in these patients were in some case showed discrepancies from those expected from the clinical course and/or conventional monitoring tests. Further evaluation of fungal PCR may gain insight into the more precise diagnosis of fungal infection in these patients.

[An analysis of 30 patients with renal trauma: diagnostic value of radiographic examinations].

To evaluate the diagnostic value of radiographic examinations in renal trauma, 30 patients treated between April, 1985 and March, 1988 were examined. The 25 male and 5 female patients ranged in age from 10 to 74 years, with 17 (57%) less than 30 years of age. Causes of injuries were traffic accidents in 19 patients (63%), falls in 5 (17%), sports in 2 (7%), and others in 4 (13%). Twenty-nine patients (97%) had hematuria and 3 (10%) had shock due to renal injury. The presence of shock indicated severe renal injury, but the degree of hematuria did not correlate to severity of injury. Of the 30 patients, 18 (60%) had renal contusions, 7 (23%) had minor lacerations, 4 (13%) had major lacerations and one had vascular injury. One patient had penetrating trauma and the other 29 had blunt trauma. Two patients (7%) had pre-existing renal anomalies. Associated injuries were present in 16 patients (53%). The presence of associated injuries had no relation to the severity of the renal injury. Computerized tomography (CT) with contrast medium was more sensitive to abnormal findings, especially subcapsular and perirenal hematoma, than excretory pyelography. Findings of renal angiography provided additional anatomical information for deciding immediate surgical treatment and for selecting operative methods for salvage of the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of internal hernia through a defect in the falciform ligament treated with laparoscopic surgery].

A 22-year-old male was admitted to our hospital with abrupt onset of upper abdominal pain. Abdominal US and CT revealed dilatation of the small intestine between the abdominal wall and a lateral segment of the liver. After a diagnosis of an internal hernia through a defect in the falciform ligament, emergency surgery was performed. Laparoscopic investigation showed incarceration of the small intestine in a defect of the falciform ligament. After releasing an incarceration, the hernia orifice was opened to prevent relapse. He was discharged on the 4th postoperative day. Internal hernia through a defect in the falciform ligament is extremely rare, with six reported cases including our own in Japan. Characteristic images of abdominal US and CT enable preoperative diagnosis of this condition. Surgery should be performed at an early stage after onset. In patients with no prior history of surgery, laparoscopic techniques may be useful.