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T F McNamara

Publications and source records attributed to T F McNamara.

35 records · Page 2Linked to original sources

Tetracyclines inhibit human synovial collagenase in vivo and in vitro.

To determine if tetracyclines can inhibit human synovial collagenase from rheumatoid tissue, paired synovial tissue (or synovial fluid) was collected from 7 patients before and after oral administration of minocycline (100 mg BID) for 10 days. With each patient serving as his own control, the postminocycline collagenase activities fell an average of 67% from pretreatment values. Qualitative SDS-PAGE revealed decreased loss of alpha collagen components and reduced formation of alpha A digestion fragments. Addition of minocycline or a chemically modified tetracycline to synovial culture media in vitro profoundly inhibited collagenase activity. Further study of this action of tetracyclines could serve as a probe of the role of collagenase in rheumatoid arthritis and lead to development of agents capable of modifying the tissue destructive actions of collagenase.

Arthritis, Rheumatoid↗

Tetracyclines inhibit tissue collagenases. Effects of ingested low-dose and local delivery systems.

In a series of experiments, Golub et al. demonstrated that tetracyclines, but not other antibiotics, can inhibit mammalian collagenases and proposed that this property could be useful in treating diseases, such as periodontal disease (but also included certain medical conditions, e.g., corneal ulcers) characterized by excessive collagen degradation (J Periodont Res 1983, 1984 and 1985; Experientia 1984; Cornea 1984). One effect was the dramatic reduction of tissue collagenase activity within the gingival crevicular fluid (GCF) of periodontal pockets after administering a standard regimen of a tetracycline (e.g., 200 mg minocycline or 1000 mg tetracycline/day). The preliminary studies described below determined the effect of (1) low-dose (LD; 40-80 mg/day) orally administered minocycline on GCF collagenase activity and on the subgingival microflora (Exp. I), and (2) tetracycline-loaded monolithic fibers (TF) on collagenase activity in vitro (Exp. II). In Exp. I, GCF collagenase activity was reduced by 45 to 80% 2 weeks after initiating LD minocycline therapy, an effect that lasted for at least several weeks after stopping drug treatment. No consistent change in the relative proportions of G(+), G(-) and motile subgingival microorganisms was detected as a result of LD treatment suggesting that the reduction in GCF collagenase activity was a direct inhibition of the enzyme by the drug. In Exp. II, 3- and 6-mm lengths of TF in vitro established tetracycline concentrations in 250 microliters of 132 micrograms/ml, from 3-mm lengths, and 265 micrograms/ml, from 6-mm lengths, after an 18-hour incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

In vitro and in vivo studies of cellular lysis of oral bacteria by a lysozyme-protease-inorganic monovalent anion antibacterial system.

Compared with anion-activated cell lysis of oral bacteria damaged with either lysozyme or trypsin, cells which were treated with both of these enzymes showed a far greater degree of lysis. This was true regardless of whether turbidimetric, DNA release, or electron microscopic assays were used to monitor the lytic process. At an acidic pH of 5.2 and an NaHCO3 concentration of 100 mM, the kinetics of lysis for two different serotype c strains of Streptococcus mutans were similar. At 0 to 100 mM bicarbonate, however, differences in the lytic susceptibilities of the two strains were evident. At pH 5.2, NaHCO3, but not NaSCN, NaCl, or NaF, was effective in promoting cell lysis of the oral bacteria. At apparent sublytic concentrations of NaHCO3, lysis was achieved by adding appropriate concentrations of NaSCN, NaCl, or NaF to the lysozyme-protease-damaged cells. In in vivo studies, hamsters given a combination of NaHCO3, NaCl, and NaSCN were found to have significantly reduced levels of S. mutans on their molar teeth compared with that found in controls or animals exposed to any one of the salts alone or to a combination of chloride and thiocyanate only. The results suggest that bicarbonate is an essential anion which, together with the other major salivary inorganic monovalent anions, plays an active role in the lysis and ultimate elimination of cariogenic bacteria.

Actinomyces↗

The development of an altered gingival crevicular microflora in the alloxan-diabetic rat.

The microflora of the rat gingival crevice were examined at various time intervals after inducing experimental diabetes. A variety of Gram-positive and Gram-negative cocci and short rods were isolated from the normal rat crevice. Within a week after alloxan administration, Leptotrichia buccalis was detected for the first time. Other features in the diabetic animals included an increased frequency of isolation of Proteus spp., Lactobacillus spp. and decrease of Escherichia coli. Occasionally, a decrease was also observed in Bacteroides spp. and Streptococcus spp. No difference was observed between diabetic and non-diabetic animals in the isolation of Selonomonas, Campylobacter, Bifidobacterium and Actinomyces. Plaque accumulation was markedly increased in the diabetic rats. It was concluded that the change in gingival microflora resulted from diabetes-induced alterations in the sulcular environment (such as increased substrate levels, e.g. glucose and urea, and decreased oxygen) and that the microbiological changes preceded the depending of the periodontal pocket.

Alloxan↗

The role of C. albicans in denture stomatitis.

Denture stomatitis is an erythematous disorder of the denture-bearing tissues, especially the maxillary hard palate. Frequently it mimics many oral lesions. Early diagnosis of the lesion is essential to assure rational therapy. A diagnostic procedure based upon the enumeration of Candida albicans appeared to be feasible. A control group of twenty fully dentate subjects with no clinical evidence of stomatitis was sampled to establish normal concentrations of C. albicans in the oral flora. Samples were taken from a triangular area of the hard palate, serially diluted in broth, and all dilutions were incubated aerobically. In the control population, C. albicans never exceeded 100 organisms per square centimeter per subject sample. A population of edentulous patients with denture stomatitis, prior to any therapy, was similarly sampled. In many of these patients the concentration of C. albicans always exceeded 10,000 organisms per square centimeter per patient. The patients received denture replacements and antimycotic antibiotic therapy. Follow-up cultures were taken 4 to 6 weeks after completion of therapy. All patients were found to be free of denture stomatitis.

Antifungal Agents↗

Cariostatic activity of calcium glycerophosphate in hamsters: topical vs dietary administration.

Two experiments were conducted to determine if calcium glycerophosphate administered continuously in a diet or intermittently as a single daily topical application to teeth had an anticaries potential in young hamsters that were fed a cariogenic diet. The hamsters were inoculated with a caries-conductive streptococcal strain. Within the 60-day experimental period, results of these evaluations indicated calcium glycerophosphate significantly reduces caries when fed in the diet at levels of 1% and higher, and significantly reduces caries when applied topically at levels of 2% and higher. There were no observable differences in plaque formation among treatments.

Administration, Topical↗