The involvement of mucosal mast cells (MMC) in the pathophysiology of irritable bowel syndrome (IBS) is still controversial. We aimed to re-evaluate the role of MMC in visceral hypersensitivity associated with IBS using a rat IBS model that develops the IBS symptom after a subsidence of acetic acid-induced colitis. No significant difference in the number of MMC was observed between normal rat colon and IBS rat colon. (61.7 +/-2.9/mm 2 in normal vs. 88.7 +/-13.3/mm 2 in IBS, p >0.29). However, the degranulation rate of MMC was significantly higher in IBS rat colon (49.5 +/-2.4% in normal vs. 68.8 +/-3.4% in IBS, p >0.05). Pretreatment of a mast cell stabilizer, doxantrazole (5 mg/kg, i.p.), reduced the degranulation rate of MMC and significantly attenuated visceral hypersensitivity to rectal distension in IBS rat, whereas it had no effect on the visceral sensory responses in normal rat. These results suggest that, although the number of MMC is not significantly changed in IBS rat colon, the higher degranulation rate of MMC is responsible for visceral hypersensitivity in this model IBS.
Acetic Acid/toxicity ; Animals ; Cell Count ; Colitis/chemically induced/*pathology ; Hypersensitivity/*pathology ; Image Processing, Computer-Assisted ; Intestinal Mucosa/*pathology ; Irritable Bowel Syndrome/*pathology ; Male ; Mast Cells/drug effects/*pathology ; Models, Theoretical ; Phosphodiesterase Inhibitors/pharmacology ; Rats ; Rats, Sprague-Dawley ; Thioxanthenes/pharmacology ; Viscera/immunology ; Xanthones/pharmacology

OBJECTIVES: The aim of this study is to evaluate the effect of light intensity variation on the polymerization rate of composite resin using IB system (the experimental equipment designed by Dr. IB Lee) by which real-time volumetric change of composite can be measured. METHODS: Three commercial composite resins [Z100(Z1), AeliteFil(AF), SureFil(SF)] were photopolymerized with Variable Intensity Polymerizer unit (Bisco, U.S.A.) under the variable light intensity (75/150/225/300/375/450mW2) during 20 sec. Polymerization shrinkage of samples was detected continuously by IB system during 110 sec and the rate of polymerization shrinkage was obtained by its shrinkage data. Peak time(P.T.) showing the maximum rate of polymerization shrinkage was used to compare the polymerization rate. RESULTS: Peak time decreased with increasing light intensity(p<0.05). Maximum rate of polymerization shrinkage increased with increasing light intensity(p<0.05). Statistical analysis revealed a significant positive correlation between peak time and inverse square root of the light intensity (AF:R=0.965, Z1:R=0.974, SF:R=0.927). Statistical analysis revealed a significant negative correlation between the maximum rate of polymerization shrinkage and peak time(AF:R=-0.933, Z1:R=-0.892, SF:R=-0.883), and a significant positive correlation between the maximum rate of polymerization shrinkage and square root of the light intensity (AF:R=0.988, Z1:R=0.974, SF:R=0.946). DISCUSSION AND CONCLUSIONS: The polymerization rate of composite resins used in this study was proportional to the square root of light intensity. Maximum rate of polymerization shrinkage as well as peak time can be used to compare the polymerization rate. Real-time volume method using IB system can be a simple, alternative method to obtain the polymerization rate of composite resins.
Composite Resins ; Equipment Design ; Light ; Polymerization ; Polymers

Sjögren syndrome (SS) is a chronic autoimmune disorder that primarily targets the salivary and lacrimal glands. The pathology of these exocrine glands is characterized by periductal focal lymphocytic infiltrates, and both T cell-mediated tissue injury and autoantibodies that interfere with the secretion process underlie glandular hypofunction. In addition to these adaptive mechanisms, multiple innate immune pathways are dysregulated, particularly in the salivary gland epithelium. Our understanding of the pathogenetic mechanisms of SS has substantially improved during the past decade. In contrast to viral infection, bacterial infection has never been considered in the pathogenesis of SS. In this review, oral dysbiosis associated with SS and evidence for bacterial infection of the salivary glands in SS were reviewed. In addition, the potential contributions of bacterial infection to innate activation of ductal epithelial cells, plasmacytoid dendritic cells, and B cells and to the breach of tolerance via bystander activation of autoreactive T cells and molecular mimicry were discussed. The added roles of bacteria may extend our understanding of the pathogenetic mechanisms and therapeutic approaches for this autoimmune exocrinopathy.

PURPOSE: A variety of biodegradable polymers have been utilized to fabricate matrices for engineering genitourinary tissues, Chitosan is a biosynthetic polysaccharide that is the deacetylated derivative of chitin. The aims were to investigate the characteristics of the newly developed porous chitosan-based biodegradable scaffolds and to reconstruct cavernosal smooth muscle structure in vivo. MATERIALS AND METHODS: To study the cytotoxicity of the newly developed scaffolds, cultured L929 murine fibroblasts were stained with PKH-26 and then cultured on culture plate or loaded in chitosan/hyaluronic acid polymers. For in vivo study, human corpus cavernosal smooth muscle cells were seeded on the scaffolds at concentration of 20*106 cells per cm3 .A total of 24 polymer scaffolds were implanted subcutaneously with cells in one side and without cells in the other side, respectively, in 12 athymic mice, Mice were scarificed 7, 14, 28 days after implantation, respectively. H-E stain and monoclonal anti-alpha smooth muscle actin stain were performed. RESULTS: Scanning electron micrographs of chitosan and 0.03% hyaluronic acid based scaffolds showed sheet-like porous structure. The cell division numbers of L929 murine fibroblasts sere significantly increased in scaffolds by chitosan/hyaluronic acid compared with chitosan alone, Histologically the retrieved polymers seeded with cavernosal smooth muscle cells showed organized smooth muscle structure 28 days after implantation. immunohistochemical analysis confirmed the smooth muscle phenotype. CONCLUSION: These results show that porous chitosan-based biodegradable scaffolds are new biomaterials for the reconstruction of cavernosal smooth muscle structure. However, further studies are needed to make cavernosal sinusoidal structure using this new scaffolds.
Actins ; Animals ; Biocompatible Materials ; Cell Division ; Chitin ; Chitosan ; Fibroblasts ; Humans ; Hyaluronic Acid ; Male ; Mice ; Mice, Nude ; Muscle, Smooth* ; Myocytes, Smooth Muscle ; Penis ; Phenotype ; Polymers ; Tissue Engineering

BACKGROUND: To determine the molecular structure of type II collagen-specific T-cell receptors associated with rheumatoid arthritis (RA). METHODS: We generated CII-specific T-cell lines of 8 RA patient s by prolonged in vitro culture with bovine CII (bCII) and the immunogenic peptide (256-270) of human CII. The proliferation response towards CII stimulation was measured from the uptake of 3 H-thymidine. Changes in the secretion of Th 1 and Th2 cytokines in the culture supernatent were measured by ELISA. The TCR clonotypes of these T-cells were examined by RT-PCR/ SSCP analyses of all 22 V beta chains. RESULTS: T-cells from patients' tissue exhibited strong proliferation index upon CII stimulation, which was maintained up to 6 months in the culture. The secretion of INF-gamma from these T-cells increased along with the duration of culture time, while the amount of IL-4 production did not show significant changes. The SSCP band patterns of patients' T-cells appear as discrete bands unlike the smeary streak produced from normal samples. Some SSCP bands, each representing selected expansion of a TCR containing certain subtype of V beta peptides, appeared to be identical in more than one patients. Among these, the expansion of SSCP band representing the V beta 14 CDR3 region persisted after switching the antigen to the immunogenic human peptide (256-270). CONCLUSION: CII-reactive T-cells expressing distinct CDR3 motifs are selectively expanded in the peripheral blood and synovial fluid of RA patients, and their persistent proliferation upon CII stimulation, as well as the production Th 1-type cytokines, may play pivotal roles in RA pathogenesis.
Arthritis, Rheumatoid* ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-4 ; Molecular Structure ; Peptides ; Polymorphism, Single-Stranded Conformational ; Receptors, Antigen, T-Cell ; Synovial Fluid ; T-Lymphocytes*

Congenital anomalies occur in 2-3% of neonates and have unknown and variable causes. It's occurance rate is higher in twin gestations than in singleton gestations, especially in monozygotic twins. In most cases of twin anomalies, one fetus is normal and the other fetus is not. When an anomaly is found in one fetus, various tests, such as chorionic villus sampling, amniocentesis, and umbilical cord aspiration are strongly recommended in high risk groups of chromosmal anomaly for accurate diagnosis and proper treatments. A case of congenital anomalies in both twins diagnosed in a 35 year old multiparous woman is presented with brief review of literatures.
Adult ; Amniocentesis ; Anencephaly ; Chorionic Villi Sampling ; Diagnosis ; Down Syndrome ; Female ; Fetus ; Humans ; Infant, Newborn ; Pregnancy ; Twins* ; Twins, Monozygotic ; Umbilical Cord

BACKGROUND/AIMS: Abnormal visceral sensitivity and disordered motility are common in patients with diabetes mellitus. The purpose of the present study was to investigate whether visceral sensation and bowel motility were altered in a rat model of type 2 diabetes mellitus accompanied by weight loss. METHODS: A type 2 diabetic rat model in adulthood was developed by administrating streptozotocin (STZ; 90 mg/kg, i.p.) to neonatal rats. Eight weeks after STZ administration, rats with blood glucose level of 200 mg/dL or higher were selected and used as diabetic group (n = 35) in this study. Abdominal withdrawal reflex and arterial pulse rate were measured to examine visceral nociception induced by colorectal distension (0.1-1.0 mL). The amplitude, frequency, and area under the curve (AUC) of spontaneous phasic contractions of colonic circular muscles were recorded in vitro to examine colonic motility. RESULTS: STZ-treated diabetic rats gained significantly less weight for 8 weeks than control (P < 0.01). Forty-eight percent of the diabetic rats showed enhanced visceral nociceptive response to colorectal distension. Diabetic rats did not differ from control rats in colorectal compliance. However, the frequency and AUC, not the amplitude, of colonic spontaneous contraction in vitro was significantly decreased in diabetic rats compared to control rats (P < 0.01 in frequency and P < 0.05 in AUC). CONCLUSIONS: These results demonstrate visceral hypersensitivity and colonic dysmotility in a rat model of type 2 diabetes mellitus accompanied by weight loss.
Animals ; Area Under Curve ; Blood Glucose ; Colon* ; Compliance ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Heart Rate ; Humans ; Hypersensitivity* ; Models, Animal ; Muscles ; Nociception ; Rats* ; Reflex ; Sensation ; Streptozocin ; Weight Loss

Nitric oxide (NO) is a non-adrenergic, non-cholinergic neurotransmitter found in the enteric nervous system that plays a role in a variety of enteropathies, including inflammatory bowel disease. Alteration of nitrergic neurons has been reported to be dependent on the manner by which inflammation is caused. However, this observed alteration has not been reported with acetic acid-induced colitis. Therefore, the purpose of the current study was to investigate changes in nitrergic neuromuscular transmission in experimental colitis in a rat model. Distal colitis was induced by intracolonic administration of 4% acetic acid in the rat. Animals were sacrificed at 4 h and 48 h postacetic acid treatment. Myeloperoxidase activity was significantly increased in the acetic acid-treated groups. However, the response to 60 mM KCl was not significantly different in the three groups studied. The amplitude of phasic contractions was increased by Nomega-nitro-L-arginine methyl ester (L-NAME) in the normal control group, but not in the acetic acid-treated groups. Spontaneous contractions disappeared during electrical field stimulation (EFS) in normal group. However, for the colitis groups, these contractions initially disappeared, and then reappeared during EFS. Moreover, the observed disappearance was diminished by L-NAME; this suggests that these responses were NO-mediated. In addition, the number of NADPH-diaphorase positive nerve cell bodies, in the myenteric plexus, was not altered in the distal colon; whereas the area of NADPH-diaphorase positive fibers, in the circular muscle layer, was decreased in the acetic acidtreated groups. These results suggest that NO-mediated inhibitory neural input, to the circular muscle, was decreased in the acetic acid-treated groups.
Acetic Acid/toxicity ; Animals ; Colitis/chemically induced/*pathology/*physiopathology ; Colon/drug effects/enzymology/*innervation/pathology ; Indicators and Reagents/toxicity ; Male ; Muscle Contraction/drug effects ; Muscle, Smooth/drug effects/metabolism ; Myenteric Plexus/pathology ; NADPH Dehydrogenase/metabolism ; NG-Nitroarginine Methyl Ester/pharmacology ; Neuromuscular Junction/drug effects/*metabolism ; Nitrergic Neurons/drug effects/*metabolism ; Nitric Oxide/*metabolism ; Peroxidase/metabolism ; Potassium Chloride/pharmacology ; Rats ; Rats, Sprague-Dawley

Inflammatory mediators has been recognized as an important role in the pathogenesis of rheumatoid arthritis (RA). IL-17 is increasingly recognized as an important regulator of immune and inflammatory responses, including induction of proinflammatory cytokines and osteoclastic bone resorption. Evidence of the expression and proinflammatory activity of IL-17 has been demonstrated in RA synovium and in animal models of RA. However, the signaling pathways that regulate IL-17 production remain unknown. In the present study, we investigated the role of the phosphatidylinositol 3 kinase (PI3K)-Akt pathway in the regulation of IL-17 production in RA. PBMC were separated from RA (n=24) patients, and stimulated with various agents (anti CD3, anti CD28, PHA, ConA, IL-15). IL-17 levels were determined by sandwich ELISA and RT-PCR. The production of IL-17 was significantly increased in cells treated with anti-CD3 antibody, PHA, IL-15 or MCP-1 (P<0.05). ConA also strongly induced IL-17 production (P<0.001), whereas TNF-alpha, IL-1beta, IL-18 or TGF-beta did not. IL-17 was detected in the PBMC of patients with osteoarthritis (OA) but their expression levels were much lower than those of RA PBMC. Anti-CD3 antibody activated the PI3K-Akt pathway and activation of the PI3K-Akt pathway resulted in a pronounced augmentation of nuclear factor kappaB (NF-kappaB). IL-17 production by activated PBMC in RA is completely or partially blocked in the presence of NF-kappaB inhibitor PDTC and PI3K- Akt inhibitor, wortmannin and LY294002, respectively. Whereas the inhibition of AP-1 and extracellular signal-regulated kinase (ERK)1/2 did not affect IL-17 production. These results provide new insight into that PI3K/Akt and NF-kappaB dependent signal transduction pathway could be involved in the overproduction of key inflammatory cytokine, IL-17 in rheumatoid arthritis.
Arthritis, Rheumatoid* ; Bone Resorption ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-15 ; Interleukin-17* ; Interleukin-18 ; Models, Animal ; NF-kappa B ; Osteoarthritis ; Osteoclasts ; Phosphatidylinositol 3-Kinase ; Phosphotransferases ; Signal Transduction* ; Synovial Membrane ; Transcription Factor AP-1 ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha

PURPOSE: In cases of locally advanced non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy (CCRT) is the leading therapeutic modality. However, much controversy exists about the chemotherapeutic regimens and radiation methods. MATERIALS AND METHODS: During concurrent chemoradiotherapy, three or four cycles of gemcitabine (500 mg/m2) and cisplatin (30 mg/m2) were administered every two weeks while 50.4 Gy of irradiation was administered in 28 fractions (once/day, 5 treatment days/week) to the tumor site, mediastinum, and the involved lymph node region. In addition, a booster irradiation dose of 18 Gy in 10 fractions was administered to the primary tumor site unless the disease progressed. Two or three cycles of consolidation chemotherapy were performed with gemcitabine (1,200 mg/m2, 1st and 8th day) and cisplatin (60 mg/m2) every three weeks. RESULTS: A total of 29 patients were evaluable for modality response. Response and treatment toxicities were assessed after concurrent chemoradiotherapy and consolidation chemotherapy, respectively. One patient (4%) achieved a complete response; whereas 20 patients (69%) achieved a partial response after concurrent chemoradiotherapy. Following the consolidation chemotherapy, three patients (10.3%) achieved complete responses and 21 patients (72.4%) achieved partial responses. The median follow-up period was 20 months (range 3m39 months) and the median survival time was 16 months (95% CI; 2.4m39.2 months). The survival rates in one, two, and three years after the completion of treatment were 62.7%, 43.9%, and 20%, respectively. Complications associated to this treatment modality included grade 3 or 4 esophagitis, which occurred in 15 patients (51.7%). In addition, an incidence of 24% for grade 3 and 14% for grade 4 neutropenia. Lastly, grade 2 radiation pneumonitis occurred in 6 patients (22%). CONCLUSION: The response rate and survival time of concurrent chemoradiotherapy with biweekly gemcitabine (500 mg/m2) and cisplatin (30 mg/m2) were encouraging in patients with locally advanced NSCLC. However, treatment related toxicities were significant, indicating that further modification of therapy seems to be warranted.
Incidence ; Chemoradiotherapy ; Lung Neoplasms