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Biomedical subjects

J B Stanbury

Publications and source records attributed to J B Stanbury.

At least 19 recordsLinked to original sources

Hydroxychloroquine therapy in patients with primary Sjögren's syndrome may improve salivary gland hypofunction by inhibition of glandular cholinesterase.

OBJECTIVE: To determine whether (i) cholinesterase activity is increased in the saliva of patients with primary Sjogren's syndrome (pSS), (ii) increased levels of cholinesterase of lymphocyte origin could interfere with the secretory activity of submandibular acinar cells, and (iii) hydroxychloroquine at therapeutic doses could interfere with cholinesterase activity. METHODS: The Ellman method was used to determine the levels of salivary cholinesterase activity and the K(i) of both chloroquine and hydroxychloroquine for serum cholinesterase. The ability of lymphocyte cholinesterase to inhibit the acetylcholine (ACh)-evoked rise in [Ca(2+)](i) in mouse submandibular acinar cells was determined using fura-2 microfluorimetry. RESULTS: Patients with pSS had significantly higher levels of cholinesterase activity in both their unstimulated (P < 0.05) and stimulated saliva (P < 0.0001) compared with control subjects. Lymphocyte cholinesterase was capable of inhibiting the ACh-evoked rise in [Ca(2+)](i). The in vitro K(i) for hydroxychloroquine inhibition of cholinesterase was 0.38 +/- 1.4 microM. CONCLUSION: These data suggest that increased levels of cholinesterase present in the salivary glands of patients with pSS may contribute to glandular hypofunction and provide evidence that the therapeutic enhancement of salivary secretion in patients with pSS by hydroxychloroquine may be mediated by inhibition of glandular cholinesterase activity, although further in vivo investigation is needed.

Animals↗

Thyroid function changes related to use of iodinated water in the U.S. Space Program.

BACKGROUND: The National Aeronautics and Space Administration (NASA) has used iodination as a method of microbial disinfection of potable water systems in U.S. spacecraft and long-duration habitability modules. A review of thyroid function tests of NASA astronauts who had consumed iodinated water during spaceflight was conducted. METHODS: Thyroid function tests of all past and present astronauts were reviewed. Medical records of astronauts with a diagnosis of thyroid disease were reviewed. Iodine consumption by space crews from water and food was determined. Serum thyroid-stimulating hormone (TSH) and urinary iodine excretion from space crews were measured following modification of the Space Shuttle potable water system to remove most of the iodine. RESULTS: Mean TSH significantly increased in 134 astronauts who had consumed iodinated water during spaceflight. Serum TSH, and urine iodine levels of Space Shuttle crewmembers who flew following modification of the potable water supply system to remove iodine did not show a statistically significant change. There was no evidence supporting association between clinical thyroid disease and the number of spaceflights, amount of iodine consumed, or duration of iodine exposure. CONCLUSIONS: It is suggested that pharmacological doses of iodine consumed by astronauts transiently decrease thyroid function, as reflected by elevated serum TSH values. Although adverse effects of excess iodine consumption in susceptible individuals are well documented, exposure to high doses of iodine during spaceflight did not result in a statistically significant increase in long-term thyroid disease in the astronaut population.

Astronauts↗

Iodine-induced hyperthyroidism: occurrence and epidemiology.

We have critically reviewed the available information on iodine-induced hyperthyroidism (IIH) from published sources and other reports as well as the experience of the authors in Tasmania, Zaire, Zimbabwe, and Brazil. Administration of iodine in almost any chemical form may induce an episode of thyrotoxicosis (IIH). This has been observed in epidemic incidence in several countries when iodine has been given as prophylaxis in a variety of vehicles, but the attack rate as recorded has been low. IIH is most commonly encountered in older persons with long standing nodular goiter and in regions of chronic iodine deficiency, but instances in the young have been recorded. It customarily occurs after an incremental rise in mean iodine intake in the course of programs for the prevention of iodine deficiency, or when iodine-containing drugs such as radiocontrast media or amiodarone are administered. The biological basis for IIH appears most often to be mutational events in thyroid cells that lead to autonomy of function. When the mass of cells with such an event becomes sufficient and iodine supply is increased, the subject may become thyrotoxic. These changes may occur in localized foci within the gland or in the process of nodule formation. IIH may also occur with an increase in iodine intake in those whose hyperthyroidism (Graves' disease) is not expressed because of iodine deficiency. The risks of IIH are principally to the elderly who may have heart disease, and to those who live in regions where there is limited access to medical care. More information is needed on the long-term health impact of IIH or "subclinical" IIH, especially in the course of prophylaxis programs with iodized salt or iodinated oil in regions where access to health care is limited.

Age Distribution↗

Influence of nutritional state on the disposal of orally and intramuscularly administered iodized oil to iodine repleted older children and adult women.

Iodinated oil (Ethiodol, 1 or 2 ml) was administered po or by im administration to adult women and older children in rural highland Ecuador who were either well nourished or malnourished to determine the effect of nutritional status on the disposal rate of iodine. These subjects resides in a region previously severely deficient in iodine, but this had been corrected in these subjects by prior administration of iodinated oil or by use of iodized salt or both. Malnutrition as determined by the conventional standards of height for age was associated with a significantly shortened retention time of the administered iodine, whether given po or im. The half life of retention was approximately half in the malourished of that in the well nourished. If these findings can be extrapolated to chronically iodine deficient subjects, then malnourished populations in need of iodine supplementation should either receive higher dosages than those conventionally employed or more frequent dosage.

Adolescent↗

Effects on school children of prophylaxis of mothers with iodized oil in an area of iodine deficiency.

The results of tests of intellectual and psychomotor performance and school performance in a group of school children from a rural impoverished and iodine deficient Andean community whose mothers received injections of iodinated oil prior to the end of the first trimester of pregnancy have been compared with results in children from a neighboring comparable community whose mothers had received no iodinated oil. Subjects between ages 8 and 15 were studied. Statistically significant differences were not observed between the two groups in tests of intellectual function, but children of mothers who had received iodinated oil performed better on tests of psychomotor maturation. The group whose mothers had received oil performed distinctly better when assessed in terms of school drop-out rates, grades achieved, grades repeated, and in overall performance as judged by teacher notes in school records. Performance of both groups on standard tests of intellectual and psychomotor function was lower than standard scores. This may be a result of social and cultural deprivation, the general malnutrition prevailing in the region or other unidentified factors. The improved scoring and school performance exhibited by the children of mothers who received iodinated oil underlines the importance of prophylaxis with iodine in iodine deficient regions as one important contributor to community development.

Adolescent↗

Biochemical changes in periodontal ligament ground substance associated with short-term intrusive loadings in adult monkeys (Macaca Fascicularis).

Proteoglycan-like fractions (PG) were isolated from the ligaments of teeth undergoing various degrees of intrusive loadings. The PG were characterized by their molecular-size profiles on Sepharose 4B, the presence of uronic acid in the separated fractions and by the electrophoretic detection of constituent glycosaminoglycans including heparan sulphate, hyaluronic acid, dermatan sulphate and chondroitin-4-sulphate. The high molecular-weight fraction, peak i (estimated minimum size, 2 X 10(6) daltons) of the normal-functioning (stressed) ligament was reduced approx. 70 per cent, compared with ligament undisturbed for 3 h. There was a decrease in peak-i size between 0.25 and 1 N loadings of approx. 72 per cent. The 4 N loadings produced a further decrease followed by an increase during a 3 h undisturbed recovery phase. Thus changes in the chemistry and properties of the ground-substance components of the periodontal ligament could partly explain changes in tooth mobility.

Animals↗

Studies on the organic polyanionic constituents of human acquired dental pellicle.

Extracts of acquired dental pellicle were obtained by a two-step procedure. Pellicle formed on cleaned teeth was first extracted using 2 M CaCl2, and the remainder then removed by scraping followed by solubilization in 5 per cent (w/v) EDTA. The 2 M CaCl2 extract contained high-molecular-weight glycoprotein which was present in only trace amounts in the EDTA extract. Cellulose-acetate electrophoresis of both extracts revealed low-molecular weight protein which contained phosphate. This protein tentatively identified as a phosphoprotein, disappeared as the pellicle matured. The findings have implications in relation to early bacterial colonization of the tooth surface.

Dental Deposits↗

Glycosaminoglycans in human gingival crevicular fluid as indicators of active periodontal disease.

The glycosaminoglycans (GAG) in gingival crevicular fluid (GCF) were investigated by cellulose-acetate electrophoresis of samples from individual sites of defined conditions variously affecting the tissues of the periodontium. The non-sulphated GAG, hyaluronic acid, was present in all samples and was the only major band from sites of chronic gingivitis. An additional sulphated GAG band identified by enzymic digestions as chondroitin-4-sulphate, was detected in GCF from sites of untreated-advanced periodontitis. Initial samples from sites of early periodontitis and juvenile periodontitis yielded a similar additional band which was not detected, however, in samples collected after either surgery to eliminate deep pockets or daily subgingival irrigation with a chlorhexidine solution. Sulphated GAG was also present in fluid from the control situations, i.e. of teeth either undergoing orthodontic movement or showing evidence of trauma from occlusion, and from healing tooth-extraction wounds. Thus the presence of such a component in GCF correlates with those clinical conditions in which degradative changes are occurring in the deeper-periodontal tissues. The electrophoretic profile of GAG in a sample of GCF may be a sensitive laboratory method of indicating active phases of destructive periodontal disease at individual sites.

Chronic Disease↗

Neurological signs in congenital iodine-deficiency disorder (endemic cretinism).

Neurological examinations were made of 67 children and adults with congenital iodine-deficiency disorder (endemic cretinism) in four rural villages in highland Ecuador. There was a distinct and readily identifiable pattern of neurological deficits. These included, to varying degrees: deaf-mutism or lesser degrees of bilateral hearing-loss or dysarthria; spasticity, particularly involving the proximal lower extremities; mental deficiency of a characteristic type; and rigidity and bradykinesia. Not all of these elements were found in all cases. Less common features were strabismus, kyphoscoliosis and frontal-lobe signs. There were exceptional cases with hypotonia. In contrast, cerebellar function was largely spared, as were functions of emotion and attention, vegetative and autonomic functions, social interaction, and probably memory, except in the most severely involved.

Adolescent↗

Promotion of birth spacing on Idjwi Island, Zaire.

Idjwi Island in Lake Kivu in eastern Zaire supports approximately 50,000 largely subsistence farmers, the Bani-Iju. Rapid population growth, a declining economy, and a deteriorating environment have already converged to produce significant malnutrition in this isolated community. The highly structured and traditional social order, particularly regarding reproductive mores, is examined here in its relevance to an intervention program for reducing the demographic pressure by increasing birth spacing. The mean birth interval of approximately three years appears to be shrinking, and is far too brief to prevent rapid population growth. The program, which included films about contraception, did not lead to a longer birth interval among the Bani-Iju, but did succeed in informing women about family planning. It is concluded that no intervention program for promotion of family planning is likely to be effective without substantial improvement in the economy.

Adolescent↗

Interaction of acid glycosaminoglycans (mucopolysaccharides) with hydroxyapatite.

Selected acidic glycosaminoglycans (GAG) have been used as a model series to study some binding properties of hydroxyapatite. The order of binding was heparin, heparin sulfate, dermatan sulfage/chondroitin-4-sulfate/chondroitin-6-sulfate (all similar) and hyaluronic acid, indicating that the negative charge on the molecules is a major determinant in the binding process. Both calcium and saliva pretreatment led to an increase in uptake of selected GAG whereas fluoride even at 1 and 3 parts/106 levels led to a graded reduction in uptake. The clinical significance of these findings may be related to the presence of certain GAG in the dental integuments and to the interaction of a chemically defined group of compounds at a specific solid surface. Such findings may also have an application in studies on endogenous mineralization. The results are in accord with the generally held view that polyanions may interact electrostatically with calcium sites present in the crystal lattice of the hydroxyapatite.

Adsorption↗