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Biomedical subjects

P C Fox

Publications and source records attributed to P C Fox.

At least 127 records · Page 7Linked to original sources

Fluid secretion rates from mouse and rat parotid glands are markedly different following pilocarpine stimulation.

1. Parotid saliva production in two commonly employed laboratory animals, mouse and rat, was studied following pilocarpine stimulation. 2. When normalized to body wt, average parotid saliva output rates in mice were 3-4-fold greater than those observed in rats. When parotid salivary flow rates were normalized to gland weight, mice still displayed 2-3-fold higher values than rats. 3. The Na+ and K+ content of parotid saliva showed small differences between the two species, while saliva from rats contained 3-fold higher protein levels than observed with mice.

Animals↗

Secretion of antimicrobial proteins from the parotid glands of different aged healthy persons.

The secretion of three antimicrobial proteins from the parotid glands of 82 generally healthy men and women, 22 to 81 years in age, was examined. No change was observed in the levels of secretory IgA, but statistically significant, modest elevations (approximately 50 to 100%) of lactoferrin, in both unstimulated and stimulated secretions, and lysozyme, in unstimulated secretions, were detected when results were expressed as mg antimicrobial protein/100 ml saliva. However, these alterations were not observed if data were expressed as mg antimicrobial protein/g total protein. Also, no change was detected in an acinar cell exocrine product, the anionic proline-rich proteins, as reported previously by our laboratory. The data are consistent with a maintenance of protective functions in parotid saliva during aging.

Adult↗

99mTc-pertechnetate uptake in parotid acinar cells by the Na+/K+/Cl- co-transport system.

99mTc-Pertechnetate (99mTcO4-) has widespread clinical use in the diagnosis and evaluation of dysfunctions in many different tissues. However, despite the broad clinical application of this radionuclide, very little is known about the mechanism by which 99mTcO4- enters a cell. We report evidence here that 99mTcO4- shares the Na+/K+/Cl- co-transport system localized to the basolateral membrane of rat parotid acinar cells. 99mTcO4- uptake by these cells was quite rapid (t1/2 approximately 30 s), was completely inhibited by the loop diuretics furosemide and bumetanide, and was markedly dependent on the presence of Na+, K+, and Cl- in the extracellular medium. Relative to uptake measured in the presence of physiological extracellular salt concentrations (Hanks' salts), 99mTcO4- uptake was inhibited 80% by sodium replacement and 50% by potassium replacement. When Cl- was replaced with the physiologically inert anion gluconate a threefold stimulation in 99mTcO4- uptake resulted. These observations provide strong evidence that 99mTcO4- can substitute for Cl- as a substrate for the Na+/K+/Cl- co-transporter and indicate that 99mTcO4- uptake by salivary glands (e.g., as seen with salivary scintiscans), and possibly by a variety of other tissues, reflects the functional activity of this co-transport mechanism.

Animals↗

Regulatory aspects of N-linked glycoproteins.

Activation of beta-adrenoreceptors in rat parotid acinar cells leads to copious exocrine protein secretion. Additionally, beta-adrenergic stimulation dramatically increases specific secretory protein synthesis and enhances N-linked glycosylation of secretory glycoproteins. Recently, efforts have been directed toward understanding the mechanisms underlying these biosynthetic events. We have been particularly interested in the receptor-mediated regulation of glycosylation. In this report, we evaluate available mechanistic information from the rat parotid gland and present initial data examining the ability of various regulatory agents to modulate N-linked glycosylation in enzymatically-dispersed cell aggregates from surgical specimens of human parotid glands. We conclude that glycosylation of human parotid N-linked glycoproteins may be regulated by extracellular signaling similar to that operative in the rat parotid gland.

Animals↗

Systemic therapy of salivary gland hypofunction.

Salivary gland hypofunction occurs most often as a consequence of numerous drug therapies, anti-neoplastic treatments, or systemic disease. There are no universally accepted means of treating gland dysfunction and the resultant subjective xerostomia. A few studies have suggested that treatment of underlying inflammatory connective tissue disease will improve salivary performance in Sjögren's syndrome. Most of these reports, however, have either been limited to a small number of patients or have failed to include objective measures of salivary gland output. A larger body of literature deals with attempts using many different sialogogues to stimulate salivary function in a variety of conditions. Again, many studies have failed to document salivary improvement objectively. Recently, interest has focused on three drugs: bromhexine, anethole-trithione, and pilocarpine hydrochloride. Studies with these agents are reviewed, and current clinical investigations with pilocarpine are presented in detail.

Anethole Trithione↗

Pilocarpine for the treatment of xerostomia associated with salivary gland dysfunction.

A double-blind placebo-controlled study was conducted to evaluate the efficacy of orally administered pilocarpine in treating oral dryness caused by salivary gland hypofunction. At low dosages, pilocarpine increased the production of saliva by parotid and submandibular and/or sublingual glands and relieved the sensation of oral dryness. The quantity and composition of pilocarpine-stimulated secretions were similar to saliva produced in response to gustatory stimulation with citrate. In appropriate patients, pilocarpine is a safe, easily administered, effective therapy to relieve xerostomia by increasing natural salivary function.

Aged↗

Uptake and secretion of technetium pertechnetate by the rat parotid gland.

The ability of acinar cells of the rat parotid gland to transport technetium pertechnetate (99mTcO-4) was examined. After intravenous injection, 99mTcO-4 was rapidly detected in parotid saliva. There was an excellent correlation between saliva and plasma 99mTcO-4 levels. The saliva to plasma ratio was always less than 1, consistent with the inability of rat parotid gland duct cells to concentrate the anion. Output of 99mTcO-4 by the parotid gland closely mimicked fluctuations in parotid saliva flow rate. In vitro, enzymatically dispersed parotid acinar cells accumulated 99mTcO-4 from the incubation medium in a biphasic manner. This uptake was partially blocked by 10(-4) M NaI. Cells which had accumulated 99mTcO-4 showed increased radionuclide efflux after exposure to 10(-5) M carbachol.

Animals↗

Taste and salivary function.

Human taste perception was remarkably unimpaired in eight individuals with severe, chronic failure of all major and minor salivary gland function. Subjective reports of taste experience and objective measures of suprathreshold sensitivity were within normal limits for the overwhelming majority of these individuals. Impairments of threshold sensitivity for at least one quality was common, but normal thresholds for all four qualities were observed in one individual. These data demonstrated that the functional integrity of the taste system is not dependent upon the presence of normal saliva in the mouth. Thus, the suggestion that a salivary factor is responsible for the maintenance of taste receptor end organs can be rejected and attention directed toward other mechanisms, not dependent on saliva, that might account for the unusual resistance of these cells to environmental insult.

Adult↗

Multiple reactivity of monoclonal antibodies.

The reactivity of 31 purified monoclonal antibodies (MAbs) with 10 unrelated protein antigens was determined by an enzyme-linked immunosorbent assay. Twenty-two of the monoclonal antibodies (71%) reacted with at least one of these nonhomologous antigens. Overall, there was positive reactivity in 27% of the tests. A larger incidence of multiple reactivities was observed with increasing concentration of the MAbs. Certain of these antibodies (29%) did not react with any nonhomologous tested antigens, whereas others had reactivity with multiple antigens. Multiple reactivity was observed with 6 of 14 of the hybridomas in a test that measured binding to a cell line. Multiple reactivity was more frequently observed when the MAbs were tested with complex antigens, such as keyhole limpet hemocyanin or a cell surface. These experiments demonstrate that MAbs frequently react with multiple antigens.

Animals↗

Xerostomia.

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Diagnosis, Differential↗

In vitro attachment of bacteria to extracts of cementum.

Cementum is a specialized mineralized tissue providing for the attachment of periodontal fibers to the root surface of a tooth. In periodontal disease this connective tissue attachment to the cemental surface is lost. The ability of bacteria to adhere to the root surface, an initial event in the disease process, may be influenced by the organic matrix of cementum. Therefore, an in vitro assay of cell attachment was modified to study bacterial adherence to protein extracts of cementum. Petri dishes coated with the extracts were pre-incubated in culture media and then bacteria were added. Using this assay, Capnocytophaga-like species, a gram negative bacterium implicated in periodontal disease, attached preferentially to dishes coated with cemental extracts when compared with Type I collagen or uncoated dishes. This assay system should prove beneficial for studying the attachment of various microorganisms to protein extracts of both normal and diseased cementum, as well as providing insight into the unique attachment properties of cementum.

Adhesiveness↗

Xerostomia: evaluation of a symptom with increasing significance.

Xerostomia is the subjective sensation of oral dryness. Although it is most commonly associated with salivary gland dysfunction, it may also occur with normal gland activity. Xerostomia may be an early symptom of several morbid systemic conditions with important implications for the medical and dental management of patients. Oral dryness also has negative effects on an individual's emotional well-being and quality of life. The complaint of xerostomia necessitates a complete evaluation of a patient's general health, salivary gland function, and oral motor and sensory abilities. The salivary gland assessment includes symptom review, analysis of glandular secretions, scintiscanning, and minor labial gland biopsy. No single component is sufficient to adequately diagnose the presence, extent, or cause of salivary dysfunction. Treatment of a dry mouth, to date, is mainly palliative in nature, with the intent of preserving oral structures and functions. Better therapies are essential in the management of xerostomia, whatever the cause. The importance of xerostomia as a symptom is increasingly recognized in medicine and dentistry. The dentist is commonly the first health professional to hear this complaint and may be critical in directing a full and appropriate evaluation.

Adult↗

Suppression of postoperative pain by the combination of a nonsteroidal anti-inflammatory drug, flurbiprofen, and a long-acting local anesthetic, etidocaine.

The analgesic efficacy of the combination of a nonsteroidal anti-inflammatory drug, flurbiprofen, and a long-acting local anesthetic, etidocaine, was evaluated for the suppression of acute postoperative pain. Subjects having two impacted third molars removed at two appointments received either the experimental combination or standard treatment in a randomized, crossover design. The experimental treatment consisted of 100 mg flurbiprofen 30 minutes before surgery, 1.5% etidocaine with 1:200,000 epinephrine five minutes before surgery, and 100 mg flurbiprofen three hours after surgery. Standard treatment consisted of 10 mg oxycodone plus 650 mg acetaminophen 30 minutes before surgery, 2% lidocaine with 1:100,000 epinephrine five minutes before surgery, and a second dose of the oxycodone-acetaminophen combination three hours after surgery. Pain intensity was rated hourly from one to seven hours after surgery, using a variety of ordinal and analog scales. The flurbiprofen-etidocaine combination resulted in significantly less postoperative pain than the oxycodone plus acetaminophen-lidocaine combination on all four analgesic scales used and was preferred by the majority of the patients. This study shows that pretreatment with a nonsteroidal anti-inflammatory drug, flurbiprofen, in combination with a long-acting local analgesic, etidocaine, suppresses pain to a greater extent than a potent opiate mild/analgesic combination and lidocaine without an increase in side-effect liability.

Acetanilides↗