The pattern of change in salivary immunoglobulins and antibodies to S. mitis and S. oralis in children undergoing bone marrow transplantation: use of an indirect method of assessment.
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The objective of this study was to assess the pattern of change in salivary immunoglobulins and antibodies to S. mitis and S. oralis in 23 children following allogeneic bone marrow transplantation and their matched controls. To overcome the difficulty of obtaining a sufficient quantity of whole saliva from very young, sick children saliva was collected in a 5-ml oral rinse of sterile normal saline. It was not possible to measure the volume of whole saliva in each rinse and the concentration of the salivary immunoglobulins and bacterial antibodies were estimated from 1 ml of oral rinse. Despite these shortcomings a pattern of change in the mean concentrations of total salivary IgA, secretory IgA, antibodies to S. mitis and S. oralis and total IgG at specific event- related times during the transplantation period has been demonstrated. There was a significant increase in the concentration of salivary IgG 7 days post-transplantation, followed by significant decreases in total salivary IgA, secretory IgA and antibodies to S. mitis after recovery of the peripheral neutrophil count above 0.5 x 10(9). The concentrations of total IgA and antibodies to S. oralis was significantly greater in the transplant group 119 days post-transplantation. (+info)
Passage of immunoglobulins from plasma to the oral cavity in rhesus monkeys.
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The passage of immunoglobulin from plasma to the oral cavity was studied in rhesus monkeys. Immunoglobulins G, A and M were purified from pooled rhesus monkey serum, radiolabelled with 125I and injected intravenously into twelve monkeys. Sequential samples of oral fluids were taken over a 24 h period and were assayed for radioactivity. Radioactivity could be detected in crevicular fluid washings after 0.5 h in monkeys injected with IgG and IgA, and after 2 h in monkeys given IgM. Maximal levels were found after 4 h with each immunoglobulin. Radioactivity in parotid and mixed saliva could be detected in all animals after 30 min, reaching a maximal level after 4 h. Ultracentrifugation on sucrose density gradients revealed that most of the radioactivity in crevicular fluid washings was in the 7S zone in the animals given IgG and IgA, and in a 19S zone in animals given IgM. The radioactivity in partoid saliva did not represent intact immunoglobulin molecules, since all the activity was present in zones of low molecular weight in animals given IgG, IgA or IgM. In mixed saliva a small amount of radioactivity was found in the immunoglobulin zones. The results suggest that intact molecules of IgG, IgA and IgM can pass from plasma to the oral cavity via crevicular fluid, and could contribute to oral defence mechanisms particularly in the crevicular domain. The volume of crevicular fluid in the approximal space of deciduous molars of rhesus monkeys was estimated to be approximately 0.3 microliter. (+info)
Purification and characterization of monkey salivary mucin.
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Highly purified mucin was prepared from monkey (Macaca arctoides) extraparotid saliva by sequential chromatography on Sephadex G-200 (followed by reduction and alkylation of void volume materials), Sepharose CL-2B with 6 M urea, and CM52 cellulose with 6 M urea. Purity was critically ascertained by anion exchange chromatography, ultracentrifugal analysis, isoelectric focusing, sodium dodecyl sulfate-polyacrylamide electrophoresis, and crossed immunoelectrophoresis. Use of crossed immunoelectrophoresis to examine mucin preparations has not been previously reported. This technique was useful for assessing purity and displaying charge and size microheterogeneity in the purified S-carboxymethylated mucin. Threonine and serine comprised 37.8% of the total amino acids while the oligosaccharide moiety contained N-acetyl-glucosamine, N-acetylgalactosamine, fucose, galactose, N-acetylneuraminic acid, and sulfate. Following alkaline borohydride treatment, the carbohydrate chains were found to be linked O-glycosidically between N-acetylgalactosamine and threonine (serine). (+info)
Targeted disruption of the Nhe1 gene prevents muscarinic agonist-induced up-regulation of Na(+)/H(+) exchange in mouse parotid acinar cells.
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The onset of salivary gland fluid secretion in response to muscarinic stimulation is accompanied by up-regulation of Na(+)/H(+) exchanger (NHE) activity. Although multiple NHE isoforms (NHE1, NHE2, and NHE3) have been identified in salivary glands, little is known about their specific function(s) in resting and secreting acinar cells. Mice with targeted disruptions of the Nhe1, Nhe2, and Nhe3 genes were used to investigate the contribution of these proteins to the stimulation-induced up-regulation of NHE activity in mouse parotid acinar cells. The lack of NHE1, but not NHE2 or NHE3, prevented intracellular pH recovery from an acid load in resting acinar cells, in acini stimulated to secrete with the muscarinic agonist carbachol, and in acini shrunken by hypertonic addition of sucrose. In HCO(3)(-)-containing solution, the rate of intracellular pH recovery from a muscarinic agonist-stimulated acid load was significantly inhibited in acinar cells from mice lacking NHE1, but not in cells from NHE2- or NHE3-deficient mice. These data demonstrate that NHE1 is the major regulator of intracellular pH in both resting and muscarinic agonist-stimulated acinar cells and suggest that up-regulation of NHE1 activity has an important role in modulating saliva production in vivo. (+info)
Penetration of moxifloxacin into peripheral compartments in humans.
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To characterize the penetration of moxifloxacin (BAY 12-8039) into peripheral target sites, the present study aimed at measuring unbound moxifloxacin concentrations in the interstitial space fluid by means of microdialysis, an innovative clinical sampling technique. In addition, moxifloxacin concentrations were measured in cantharides-induced skin blisters, saliva, and capillary plasma and compared to total- and free-drug concentrations in venous plasma. For this purpose, 12 healthy volunteers received moxifloxacin in an open randomized crossover fashion either as a single oral dose of 400 mg or as a single intravenous infusion of 400 mg over 60 min. An almost-complete equilibration of the free unbound plasma fraction of moxifloxacin with the interstitial space fluid was observed, with mean area under the concentration-time curve (AUC)(interstitial fluid)/AUC(total-plasma) ratios ranging from 0.38 to 0.55 and mean AUC(interstitial fluid)/AUC(free-plasma) ratios ranging from 0.81 to 0.86. The skin blister concentration/plasma concentration ratio reached values above 1.5 after 24 h, indicating a preferential penetration of moxifloxacin into inflamed lesions. The moxifloxacin concentrations in saliva and capillary blood were similar to the corresponding levels in plasma. Our data show that moxifloxacin concentrations attained in the interstitial space fluid in humans and in skin blister fluid following single doses of 400 mg exceed the values for the MIC at which 90% of isolates are inhibited for most clinically relevant bacterial strains, notably including penicillin-resistant Streptococcus pneumoniae. These findings support the use of moxifloxacin for the treatment of soft tissue and respiratory tract infections in humans. (+info)
Absence of epithelial immunoglobulin A transport, with increased mucosal leakiness, in polymeric immunoglobulin receptor/secretory component-deficient mice.
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Mucosal surfaces are protected specifically by secretory immunoglobulin A (SIgA) and SIgM generated through external translocation of locally produced dimeric IgA and pentameric IgM. Their active transport is mediated by the epithelial polymeric Ig receptor (pIgR), also called the transmembrane secretory component. Paracellular passive external transfer of systemic and locally produced antibodies also provides mucosal protection, making the biological importance of secretory immunity difficult to assess. Here we report complete lack of active external IgA and IgM translocation in pIgR knockout mice, indicating no redundancy in epithelial transport mechanisms. The knockout mice were of normal size and fertility but had increased serum IgG levels, including antibodies to Escherichia coli, suggesting undue triggering of systemic immunity. Deterioration of their epithelial barrier function in the absence of SIgA (and SIgM) was further attested to by elevated levels of albumin in their saliva and feces, reflecting leakage of serum proteins. Thus, SIgA did not appear to be essential for health under the antigen exposure conditions of these experimental animals. Nevertheless, our results showed that SIgA contributes to maintenance of mucosal homeostasis. Production of SIgA might therefore be a variable in the initiation of human immunopathology such as inflammatory bowel disease or gluten-sensitive enteropathy. (+info)
Correlation of saliva codeine concentrations with plasma concentrations after oral codeine administration.
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A clinical study was designed to determine if there was a predictable relationship between saliva and plasma codeine concentrations. Drug-free volunteers (n = 17) were administered a 30-mg dose of liquid codeine phosphate. Plasma and saliva specimens were collected at various times for 24 h after administration. Plasma and saliva were analyzed for codeine and morphine by positive-ion chemical ionization gas chromatography-mass spectrometry. The plasma codeine concentrations peaked between 30 min and 2 h after administration and ranged from 19 to 74 ng/mL with a mean of 46 ng/mL. Despite decontamination procedures, elevated saliva codeine concentrations were detected at the early collection times because of contamination of the oral cavity from the liquid codeine. Codeine concentrations in the 15 min specimens ranged from 690 ng/mL to over 15,000 ng/mL. After the initial 2-h period, the mean codeine saliva concentrations declined at a rate similar to that observed in the plasma, but remained 3 to 4 times greater than the plasma concentrations. During the elimination phase, half-life estimates for codeine in plasma and saliva were found to be equivalent, 2.6 and 2.9 h, respectively. However, the area under the curve (AUC) estimate for codeine in saliva was 13 times greater than the plasma AUC. Contamination of the saliva resulted in elevated saliva/plasma (S/P) concentration ratios for the first 1 to 2 h after drug administration. Consequently, S/P ratios in specimens collected in the first 15 to 30 min ranged from 75 to 2580. However, after the absorption phase, a significant correlation between saliva and plasma concentrations was observed (r = 0.809, p < 0.05) and mean S/P ratios remained constant (mean = 3.7). Although small changes in saliva pH were predicted to produce profound changes in the S/P ratios for codeine, this was not observed in the current study. Therefore, saliva codeine concentrations could be used to estimate plasma concentrations through the use of the S/P ratio once the oral contamination has been eliminated. However, these estimates should be made cautiously. One must ensure that oral contamination is not a factor. Also, as with blood-drug concentrations, considerable intersubject variability was observed. (+info)
Salivary carbonic anhydrase isoenzyme VI.
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The carbonic anhydrases (CAs) participate in the maintenance of pH homeostasis in various tissues and biological fluids of the human body by catalysing the reversible reaction CO2 + H2O HCO3- + H+ (Davenport & Fisher, 1938; Davenport, 1939; Maren, 1967). Carbonic anhydrase isoenzyme VI (CA VI) is the only secretory isoenzyme of the mammalian CA gene family. It is exclusively expressed in the serous acinar cells of the parotid and submandibular glands, from where it is secreted into the saliva. In this review, we will discuss recent advances in research focused on the physiological role of salivary CA VI in the oral cavity and upper alimentary canal. (+info)