Oral health and salivary function in ulcerative colitis patients.

BACKGROUND: Although ulcerative colitis primarily involves the colon, extra-intestinal manifestations are common and oral and dental complaints are no exception. OBJECTIVE: This study aims at evaluating oral and dental health problems and salivary function and composition in ulcerative colitis patients and its correlation with disease activity. METHODS: Xerostomia Inventory score, (unstimulated/stimulated) salivary flow rates, salivary amylase and mucin/ Mucin 5B levels, self-reported oral and dental complaints, the oral health related quality of life, Simple Clinical Colitis Activity Index and inflammatory bowel disease-specific health related quality of life were determined. RESULTS: The cohort consisted of 51 ulcerative colitis patients. Hyposalivation was experienced by 16% of patients under resting conditions and 24% under chewing-stimulated conditions. Xerostomia was not correlated with salivary flow rates. Disease activity did not influence salivary amylase and Mucin 5B concentrations. The Xerostomia Inventory score was correlated with the Simple Clinical Colitis Activity Index (p = 0.042) and inflammatory bowel disease-specific health related quality of life (p = 0.001). Most reported oral health problems were halitosis (29%) and aphthae (28%). Frequently reported dental problems were cavities (35%) and gum problems (31%). Patients with active disease experienced significantly more oral and dental complaints. The number of oral problems was positively correlated with the Simple Clinical Colitis Activity Index (p = 0.045) and negatively correlated with the inflammatory bowel disease-specific health related quality of life (p = 0.005). CONCLUSION: The subjective feeling of a dry mouth (xerostomia) is related to disease activity and disease activity-associated quality of life in ulcerative colitis patients, whereas the objective saliva secretion rate is not. Oral and dental health problems are frequently observed in patients with ulcerative colitis, especially during active disease.

Type I interferon receptor deficiency prevents murine Sjogren's syndrome.

In Sjögren's Syndrome (SS), inherent glandular defects, autoimmunity, and mononuclear cell infiltration within the salivary glands cause reduced salivation leading to xerostomia. Excessive production of type I interferons (IFN), triggered by environmental and genetic factors, is considered pathogenic in this disorder. However, whether type I IFN production is causative or an outcome of the disease process is not known. To address this question, we introduced a deficiency of interferon alpha receptor 1 (Ifnar1) into B6.Aec1Aec2 mice, which are known to have the genetic loci necessary for developing a SS-like disorder. This new mouse strain, B6.Aec1Aec2Ifnar1 (-/-), lacking type I IFN-mediated signaling, was characterized for pilocarpine-induced salivation, the presence of serum autoantibodies, sialoadenitis, and dacryoadenitis. Compared with the B6.Aec1Aec2Ifnar1 (+/+) (wild-type) mice, the B6.Aec1Aec2Ifnar1 (-/-) (knockout) mice had significantly lower mononuclear cell infiltration in the salivary and lacrimal glands. The knockout mice were completely protected from salivary gland dysfunction. Surprisingly, they had a robust autoantibody response comparable with that of the wild-type mice. These findings demonstrate that, in the absence of type I IFN-mediated signaling, systemic autoantibody responses can be dissociated from glandular pathology. Our study suggests that, in genetically susceptible individuals, the type I IFN pathway can instigate certain features of SS.

Local delivery of AAV2-CTLA4IgG decreases sialadenitis and improves gland function in the C57BL/6.NOD-Aec1Aec2 mouse model of Sjögren's syndrome.

INTRODUCTION: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a key negative costimulatory molecule that displays a wide range of anti-inflammatory properties and is currently approved to treat rheumatoid arthritis as a recombinant fusion protein (CTLA4IgG). To better understand the role of CTLA4IgG in primary Sjögren's syndrome (pSS), we generated a recombinant adeno-associated virus vector serotype 2 (AAV2) expressing a chimera of mouse CTLA-4 fused with a human immunoglobulin (AAV2-CTLA4IgG) and observed the effect of this molecule in C57BL/6.NOD-Aec1Aec2 mice, an animal model of pSS. METHODS: A recombinant adeno-associated virus-2 (AAV-2) vector was constructed encoding a CTLA4IgG fusion protein. The AAV2-CTLA4IgG vector and an AAV2 control vector encoding beta galactosidase (LacZ) were administered by retrograde cannulation of the submandibular glands of C57BL/6.NOD-Aec1Aec2 mice. Protein expression was measured by ELISA and salivary glands were assessed for inflammation and activity. RESULTS: Recombinant CTLA4IgG blocked B7 expression on macrophages in vitro. In vivo, localized expression of CTLA4IgG in the salivary glands of C57BL/6.NOD-Aec1Aec2 mice inhibited the loss of salivary gland activity and decreased T and B cell infiltration as well as dendritic cells and macrophages in the glands compared with control mice. In addition a decrease in several proinflammatory cytokines and an increase in transforming growth factor beta-1 (TGF-ß1) expression were also observed. CONCLUSIONS: These data suggest expression of CTLA4IgG in the salivary gland can decrease the inflammation and improve the xerostomia reported in these mice.

Psychological stress and its influence on salivary flow rate, total protein concentration and IgA, IgG and IgM titers.

UNLABELLED: The hypothalamic-pituitary-adrenal and sympathetic-adrenomedullary axes are the main systems activated in response to stress. Alterations in salivary components and flow rate have been associated with oral health problems and psychological stress. OBJECTIVES: The aim of the present study was to investigate the influence of psychological stress on salivary flow, total protein concentration and IgG, IgM and IgA concentrations. METHODS: Thirty-eight medical students, average age of 21.4 +/- 2.1 years and enrolled in the 2nd to 5th years of their course, took part voluntarily in the study which involved two different periods: the first after vacations and the second during the final exams (a gap of 4 months). An Oral Health Questionnaire and the Lipp Inventory of Stress Symptoms for Adults (ISSL) were applied during both these periods. The flow rate, total protein concentration and immunoglobulin titers of saliva samples, collected after stimulation and stored in a container with protease inhibitor, were measured. RESULTS: Analysis of the ISSL showed that 42.1% (n = 16) of the students had stress during the post-vacation period, and 44.7% (n = 17) during the final exams. The students' salivary flow rate was significantly lower during the latter period than during the post-vacation period (p < 0.0001), regardless of the presence or absence of psychological stress as measured by the ISSL. There was a reduction in salivary flow rate and a consequent reduction in total protein concentration during the exam period (p = 0.0058). However, during both periods of the study there was no significant difference in total salivary protein concentration between the groups of students with or without psychological stress according to the ISSL (p > 0.05). IgG predominated over IgA and IgM (p < 0.001) during both study periods, regardless of the presence or absence of psychological stress. The study period and the presence of stress influenced the secretion of salivary immunoglobulins. IgM titers during the post-vacation period (p = 0.0044), and IgA (p = 0.028), IgG (p = 0.022) and IgM (p = 0.0075) titers during the final exams were higher in students with symptoms of psychological stress. CONCLUSIONS: Although the immunoglobulin titers were high, there was a reduction in the students' salivary flow rates and a consequent reduction in total protein concentrations.

Detection of HCV RNA in saliva does not correlate with salivary flow or xerostomia in patients with chronic hepatitis C.

OBJECTIVE: The objective of this study was to investigate the prevalence of hepatitis C virus (HCV) RNA in saliva and its possible association with xerostomia and hyposalivation in patients with chronic hepatitis C. STUDY DESIGN: One hundred and thirty-six patients with confirmed diagnosis of chronic hepatitis C were prospectively analyzed before HCV treatment. The prevalence of xerostomia and hyposalivation was clinically evaluated. HCV RNA was investigated in saliva samples by qualitative PCR test. Univariate and multivariate analyses were used to verify associations. RESULTS: Xerostomia was reported by 48 (35.3%) patients, whereas hyposalivation was observed in 26 (19.1%). HCV RNA was positive in the saliva of 53 (39.0%) patients. An association among HCV RNA-positive saliva with xerostomia or hyposalivation was not observed. CONCLUSION: Our results demonstrate that the detection of HCV in saliva does not correlate with salivary flow or xerostomia in patients with chronic hepatitis C.

Salivary secretory immunoglobulin a response of elite speed skaters during a competition period.

We aimed to determine the responses of salivary secretory immunoglobulin A (SIgA) and the incidence of upper respiratory tract infections (URTI) symptoms among elite speed skaters during an actual competition period. The subjects were 8 international-class elite speed skaters. Saliva samples were obtained 3, 2, and 1 days before the race, the day of the race, and 1 day after the race. Salivary secretory immunoglobulin A concentration was measured by enzyme immunoassay, and SIgA secretion rate was calculated. A visual analogue scale was used to subjectively assess fatigue and tension. Daily URTI symptoms were recorded by using a questionnaire. There was no statistically significant difference in the saliva flow rate (p = 0.69), SIgA concentration (p = 0.07), and subjective fatigue (p = 0.07) during the competition period. The SIgA secretion rate recorded for the day of the race was significantly high compared with that of 3 and 2 days before and 1 day after the race (p < 0.05). The subjective tension recorded on the race day was significantly high compared with that for 3, 2, and 1 days before the race (p < 0.05). Two subjects exhibited URTI symptoms after the race. These findings suggest that salivary SIgA in elite speed skaters increased after a tapering period and that an actual high-intensity speed skating race decreased salivary SIgA in elite speed skaters. These data also suggest that the incidence of URTI symptoms might be related to the SIgA level. Coaches may need to take precautions after competitions to minimize their athletes' contact with cold viruses and adjust training load for a few days after competition to improve the decreased mucosal immune function.

Negative correlation of anti-U1RNP antibody titers and the amount of salivary secretion with age correction.

OBJECTIVE: The aim of this study was to reveal whether or not the presence of anti-U1RNP antibodies is associated with a low amount of salivary secretion (ASS). SUBJECTS AND METHODS: Twenty females (mean age 49+/-12 years) who had anti-U1RNP but not ACA, anti-Ro, or anti-La antibodies (anti-U1RNP-positive group), and 65 control females (mean age 50+/-12 years) were included in this study. The saxon test was performed to measure the ASS. RESULTS: After a correction for age by ANCOVA, ASS in the anti-U1RNP-positive group was significantly lower than ASS in the control group (p <0.001). In the control group, ASS was not significantly decreased with advanced age (r=-0.140, p=0.211). In the anti-U1RNP-positive group, ASS was decreased with age, without a significant difference (r=-0.379, p=0.100). In the next analysis, we introduced 'ASS with age correction', assuming that all subjects in the anti-U1RNP-positive group were 49 years of age. A negative correlation between the titers of anti-U1RNP antibodies and the ASS with the age correction in the anti-U1RNP-positive group was noted (r=-0.520, p=0.019). The log of the antinuclear antibodies titers, or titers of rheumatoid factor was significantly correlated with the titers of anti-U1RNP antibodies, respectively (r=0.466, p=0.038 and r=0.595, p=0.006; respectively). The pathological findings of minor salivary gland biopsy in 2 subjects were compatible with Sjögren's syndrome; one subject showed moderate lymphocytic infiltration. CONCLUSION: The presence of anti-U1RNP antibodies is associated with reduced ASS.

Absence of soluble CD14 in saliva of young patients with dental caries.

It is generally accepted that salivary components are important for dental health, but to date no clear correlation has been found between one or more of these components and the outcome of dental caries. The identification of salivary factors preventing, favoring or signaling dental caries might help to control the disease. In the present study, western blotting analysis of whole saliva from 20 healthy caries-free children showed the presence of the soluble form of CD14, a bacterial pattern-recognition receptor for many bacterial components that is involved in the innate immune response. The identity of the protein was confirmed through N-terminal sequencing by Edman degradation, and by partial sequencing with mass spectrometry of tryptic peptides. Conversely, CD14 was completely absent in the saliva of 20 age-matched patients affected by two to eight carious lesions, but appeared in their saliva a few weeks after dental restoration. These results suggest that the absence of salivary soluble CD14 could represent an useful index of caries activity, and might be used to detect early carious lesions not visible by oral inspection.

Salivary IgA response to intermittent and continuous exercise.

Current evidence would support a view that intense exercise increases whereas moderate exercise reduces the susceptibility to illness, predominately upper respiratory tract infections. Concentrations of IgA and cortisol in saliva may be used to reflect changes in immune function. The aim of this study was to determine if the type of exercise (soccer-specific intermittent or continuous exercise at the same average work-rate and duration) affects salivary IgA (s-IgA) and cortisol responses. In a randomized, counterbalanced design, eight healthy males completed two trials one week apart at the same time of day on a motorized treadmill. One session entailed soccer-specific intermittent exercise, the other involved continuous exercise at the same overall work-rate. Diet and activity were standardized for 48 hours prior to and following each trial. Unstimulated saliva samples were collected via passive expectoration during the week prior to commencement of exercise, before, at half-time, immediately post-exercise, and 6 hours, 24 hours, and 48 hours post-exercise. No significant difference was observed in heart rate between the two exercise conditions (Intermittent: 142 +/- 14; Continuous: 141 +/- 16 beats x min (-1)). Average rating of perceived exertion was higher (p < 0.05) in intermittent exercise (11.9 +/- 0.8) than during continuous exercise (10.8 +/- 1.2). The pattern of change in salivary responses, including solute secretion rate, IgA concentration, IgA secretion rate, IgA to osmolality ratio, cortisol, and cortisol secretion rate did not differ between the two trials (p > 0.05). Concentrations of s-IgA for the intermittent and continuous protocols were 131.6 +/- 61.2 vs. 146.4 +/- 107.6 before, 148.4 +/- 82.5 vs. 229.2 +/- 159.6 after, and 125 +/- 78.7 vs. 131.1 +/- 80.7 48 h post-exercise, respectively. Saliva flow rate decreased and osmolality increased significantly across all time points (p < 0.05). In conclusion, soccer-specific intermittent exercise did not suppress the salivary IgA response or alter cortisol secretion compared to continuous exercise performed at the same overall work-rate.

Oral manifestations in selective IgA deficiency.

Selective immunoglobulin A (IgA) deficiency is the most common of the primary immunodeficiencies with a frequency of 1/300-1/3000, depending on the screened population. As secretory IgA (SIgA) has a protective role in mucosal surfaces from invasion of microorganisms, it is thought that IgA-deficient subjects are susceptible to periodontal diseases and oral manifestations. Previous studies show contradictory results, concerning the involvement of the individuals' periodontium with IgA deficiency. The aim of this study was to investigate and compare the oral manifestations in IgA-deficient subjects with controls. Eleven selective IgA-deficient subjects aged 3-18 years with serum IgA levels <10 mg dl(-1) and 11 age-sex-matched healthy children as the controls entered the study. Oral mucosal investigation, dental caries, plaque accumulation and periodontal status were assessed. Serum immunoglobulin levels were measured by single radial immunodiffusion (SRID) method. Saliva immunoglobulins and secretory component levels were measured by enzyme linked immunosorbent assay (ELISA) methods. IgA-deficient patients had serum and saliva IgA levels less than 10 mg dl(-1) and 10 microg ml(-1), respectively, but other serum immunoglobulin levels were normal and saliva immunoglobulin M (IgM) levels were increased, compared with controls. There were no significant differences in oral manifestations between IgA-deficient subjects and controls, which may be a result of compensatory increase of saliva IgM or other non-immunological defence factors in saliva. Thus, it is not necessary to evaluate IgA and SIgA in all the patients with oral and dental lesions and it is thought that it is better to investigate other factors.

Cyclosporin A: effects on the secretory process and noradrenergic activity in the submandibular gland of the rat.

OBJECTIVES: The aim of the present work was to study the effect of long-term cyclosporine (CSA) administration on norepinephrine (NE) metabolism and adrenergic-evoked secretion in the rat submandibular gland (SMG). METHODS: Dose-response curves to adrenergic agonists (methoxamine, isoproterenol, NE) were performed in control and CSA (10 and 30 mg/kg every 2 days for 1 month)-treated rats after SMG duct cannulation. In SMG tissue neuronal NE uptake, release, synthesis and endogenous content were determined. In addition phosphoinositide intracellular signaling was also investigated. RESULTS: CSA administration caused an increase in salivary secretion evoked by methoxamine (alpha-adrenergic agonist) and NE but failed to modify salivation evoked by beta-adrenergic stimulation (isoproterenol). Long-term CSA administration decreased NE release and synthesis whereas it enhanced the amine uptake and phosphoinositide hydrolysis in the SMG. CONCLUSIONS: The administration of CSA for 30 days induced salivary gland sensitization likely mediated by diminished adrenergic input. Present results suggest that the decreased sympathetic activity evoked by long-term CSA administration in the rat SMG may lead to sensitization of the gland supported by increased phosphoinositide hydrolysis and enhanced adrenergic-evoked salivation.