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Biomedical subjects

J M Tanzer

Publications and source records attributed to J M Tanzer.

At least 37 records · Page 2Linked to original sources
PubMed1992

High-performance liquid chromatographic determination of pilocarpine in plasma.

A high-performance liquid chromatographic procedure requiring neither derivatization nor complex sample work-up is reported for reproducibly and sensitively determining pilocarpine in plasma. Following stabilization of pilocarpine against in vitro hydrolysis using sodium fluoride, plasma samples were extracted and the extracts chromatographed on a 5-microns, low-carbon-load (6%) C18 reversed-phase column. The assay was linear between 10 and 300 ng/ml (r = 0.998). It had sufficient sensitivity to quantitate pilocarpine at concentrations as low as 10 ng/ml (signal-to-noise ratio > or = 4) using a 500-microliters sample. The assay appears to be the first published specifically for plasma determinations and has proven capable of supporting pharmacokinetics studies of pilocarpine disposition in the anesthetized dog.

Animals↗
PubMed1992

Pilocarpine disposition and salivary flow responses following intravenous administration to dogs.

Oral doses of pilocarpine increase salivary flow rates in patients afflicted with xerostomia (dry mouth). This study examined the pharmacokinetics of and a pharmacodynamic response (salivation) to intravenous pilocarpine nitrate administration in dogs. Disposition was linear over a dose range of 225-600 micrograms/kg; plasma concentrations were 10-120 micrograms/L. Elimination was rapid and generally biphasic, with a terminal elimination half-life of approximately 1.3 hr. The systemic clearance of pilocarpine was high (2.22 +/- 0.49 L/kg/hr) and its steady-state volume of distribution (2.30 +/- 0.64 L/kg) was comparable to that of many other basic drugs. All doses of pilocarpine induced measurable submaxillary and parotid salivary flow rates which could be maintained constant over time. Cumulative submaxillary saliva flow was linearly related to total pilocarpine dose. Plasma pilocarpine concentration was linearly related to both steady-state and postinfusion submaxillary salivary flow rates.

Animals↗
PubMed1992

Salivary flow induction by buccal permucosal pilocarpine in anesthetized beagle dogs.

We tested whether permucosal delivery of pilocarpine nitrate could be used to elicit significant salivary secretion. Pilocarpine (pKa 6.6 at 37 degrees C) was applied as solutions (pHs 5.6, 6.6, 7.6; 15 mg/mL) to the buccal mucosa (2.8 cm2) of 6 anesthetized dogs. Saliva was collected continuously from cannulated submandibular and parotid ducts and blood sampled during and after drug administration. Plasma pilocarpine levels were determined by reversed-phase HPLC. Absorption rates were determined by use of data from separate zero-order intravenous infusions to the same dogs. Pilocarpine was buccally absorbed at a constant rate of 72.9 +/- 38.5 micrograms/kg/h following its application at pH 7.6. At this pH of the drug solution, the time to appearance of pilocarpine in blood plasma was 0.31 +/- 0.08 h, and the time to appearance of salivary flow was 0.86 +/- 0.32 h. A threshold dose of 32.9 +/- 7.5 micrograms/kg was required to induce secretion with the pH 7.6 drug, the steady-state submandibular flow rate was 0.14 +/- 0.11 mL/min/gland pair. Salivary flow induction was symmetrical and reached levels as high as 0.35 mL/min/submandibular gland pair without apparent tachyphylaxis. Results at pHs 5.6, 6.6, and 7.6 were consistent with the hypothesis that pilocarpine is primarily absorbed as un-ionized drug. The data indicate that transmucosal delivery of pilocarpine, avoiding "first pass" hepatic loss, may hold promise for the treatment of xerostomia.

Administration, Buccal↗
PubMed1988

Factors influencing cell shape in the mutans group of streptococci.

Electron and light microscopic and growth studies of representatives of the diverse species of mutans streptococci revealed the cells to be either bacillary or coccoid in shape. Some strains changed from bacillary to coccoid if the HCO3-/K+ ratio of the media was increased and from coccoid to bacillary if the ratio was decreased. Doubling times of rods and cocci were the same despite an HCO3-/K+ ratio change between 0.008 and 2.84. For strain 10449S, no tested anions or cations substituted for HCO3- or K+ to produce this effect, except for B4O7(2-). Strain 10449S grown at a high B4O7(2-)/K+ ratio became ellipsoid, and this phenomenon was associated with slower doubling times. Up to three incomplete septa could be observed in one rod, but no more than one incomplete septum could be observed in either ellipsoid or spherical cells. Interseptal distances were greatest in rods, shorter in spheres, and shortest in ellipses. All of the above differences were statistically significant (P less than 0.001).

Microscopy, Electron↗
PubMed1988

Bicarbonate-based dental powder, fluoride, and saccharin inhibition of dental caries associated with Streptococcus mutans infection of rats.

The effects of NaHCO3-based dental powder containing NaF and sodium saccharin on dental caries and Streptococcus mutans recoveries in rats were studied. Weanling specific-pathogen-free Osborne-Mendel (SPFOM) rats were inoculated with S. mutans NCTC-10449S. Four infected groups were topically treated with either demineralized water (DW), a dental powder suspended such that there was 1 part solid per 2 parts DW, 0.073% NaF, or a combination of 0.073% NaF and 0.5% Na-saccharin (Nas). NaF-supplemented DW (at 10 ppm F-) was provided to a 5th group of infected rats as a positive treatment control, but this group was otherwise untreated. A sixth but uninfected group was topically treated with DW. All topical treatments were given once for 1 min daily per rat, for 5 days per week. Animals' teeth were swabbed for recovery of 10449S and total recoverable flora. Recoveries of 10449S were lower from powder-treated rats than from DW-treated rats. This difference approached but did not reach statistical significance. Total caries scores were 51% lower for the dental powder, 36% lower for the topical NaF, 34% lower for the combined NaF-Nas, and 54% lower for the NaF-supplemented drinking water group, all p less than 0.001. While all of the treatments inhibited smooth-surface caries, the dental powder effects, like those for the combined NaF-Nas, and NaF drinking water, were evident in fissure tooth surfaces as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Bicarbonate and potassium regulation of the shape of Streptococcus mutans NCTC 10449S.

Morphological changes of S. mutans NCTC 10449S associated with growth in modified Jordan medium and FMC medium (Terleckyj et al., Infect. Immun. 11:649-655, 1975) were studied by scanning electron microscopy. The cells were bacillary in Jordan medium, but coccoid and of unequal size in FMC. Transfer of the cells from Jordan medium to FMC and vice versa reversed their shapes, as did salt exchange between these media. Morphological changes could not be ascribed to either medium pH, concentration of P, or Na+/K+ ratio. However, they were growth dependent, since the changes did not occur when the cells were suspended in salt components alone or in media supplemented with protein synthesis inhibitors. Only a high bicarbonate/K+ ratio, as in FMC, produced spherical cells, whereas cells remained bacillary in medium with a low bicarbonate/K+ ratio, as in Jordan medium. Manipulating this ratio in other media resulted in similar shape changes. Thus, the shape of S. mutans 10449S can be dictated by the ratio of bicarbonate to K+ in the growth medium.

Bicarbonates↗
PubMed1987

Effects of bicarbonate-based dental powder, fluoride, and saccharin on dental caries and on Streptococcus sobrinus recoveries in rats.

The effects of NaHCO3-based dental powder containing NaF and sodium saccharin on dental caries and Streptococcus sobrinus recoveries in rats were studied. Weanling specific-pathogen-free Osborne-Mendel (SPFOM) rats were inoculated with S. sobrinus 6715-13WT. One of six infected groups was topically treated with either demineralized water (DW), a dental powder suspended such that there was 1 part solid per 2 parts DW, 0.073% NaF, 0.5% Na-saccharin (Nas), or a combination of NaF and Nas at the same concentrations. NaF-supplemented DW (at 10 ppm F-) was provided to the 6th group of infected rats as a positive treatment control, but this group was otherwise untreated. A seventh but uninfected group was topically treated with DW. All topical treatments were given once for one min daily per rat, for five days per week. Animals' teeth were swabbed for recovery of 6715-13WT and total recoverable flora. At 37 days after start of treatment, S. sobrinus recoveries were lower only for those rats topically treated with the dental powder (p less than 0.05) by comparison with recoveries from the infected, topical DW-treated group. Caries scores, however, were 42% lower for the groups receiving the dental powder (p less than 0.005), 30% lower for those treated with the combined NaF-Nas (p less than 0.005), and 47% lower for the NaF-supplemented drinking water group (p less than 0.005). The dental powder effects, like those for the combined NaF-Nas and NaF drinking water, were evident on both smooth and fissure tooth surfaces. Both the 10 ppm F- drinking water and the dental powder significantly (p less than 0.005) reduced fissure caries scores below the level elicited by the indigenous mutans-free flora in the DW-treated uninfected rats; however, these reduction were not significantly different from one another. Thus, the 10 ppm F- drinking water and the dental powder equally inhibited not only the S. sobrinus-attributable component of caries but probably also the component of caries attributable to the indigenous oral flora.

Administration, Topical↗
PubMed1986

Treatment of the periodontal component of Papillon-Lefèvre syndrome.

A 9-year-old girl was treated for the periodontal component of Papillon-Lefèvre syndrome, an autosomal recessive disease characterized by palmarplantar hyperkeratosis and premature loss of teeth. Initially, the patient was found to have a polymorphonuclear leukocyte chemotactic dysfunction, defective leukocyte adherence, and deep periodontal pockets harboring presumptive periodontopathic bacteria. After unsuccessful treatment with combined mechanical therapy and 2 different antibiotics, all of the patient's erupted teeth were extracted in an attempt to minimize the chance of infection of teeth yet to erupt. At age 16 years, the now-erupted teeth have normal gingiva and crevice depths, radiographs show no evidence of periodontal pathology, no periodontopathic bacteria are detected in gingival crevices, and leukocyte function is normal.

Bacteria↗
PubMed1986

In vitro studies of growth and competition between S. salivarius TOVE-R and mutans streptococci.

Streptococcus salivarius TOVE-R has previously been reported as a successful competitor with Streptococcus mutans 10449S and Streptococcus sobrinus 6715-13 WT on the teeth of rats. We studied, in vitro, some possible bases for this competition, including hydrogen peroxide or catalase production, bacteriocin or enocin production, and growth rates. Growth rates were measured spectrophotometrically in both complex and defined media. We studied conditions of aerobic and anaerobic incubation; glucose and sucrose medium supplementation at three concentrations each; various initial pH's; singly- or doubly-inoculated cultures; and half-strength, normal, or double-strength broth used both fresh and as culture filtrates. TOVE-R grew as well as did mutans streptococci at acid pH, decidedly better at alkaline pH, and nearly twice as fast near neutral pH. The average doubling time for TOVE-R was about 0.5 hr, while that for the mutans streptococci was about 1.0 hr. When TOVE-R was grown together with a mutans streptococcus, the growth rate observed for the doubly-inoculated culture was equal to or less than that of TOVE-R alone, never greater. The presence and proportions of both organisms in mixed cultures were confirmed by plate counts, direct specific immunofluorescence, and Nomarski interference microscopy. There was no evidence, by any of the methods employed, to indicate the production of an inhibitory substance against mutans streptococci by TOVE-R, or vice versa. Also, there was no evidence that the faster growth rate of TOVE-R could be attributed to nutrient limitation of the mutans streptococci.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaerobiosis↗
PubMed1985

Competitive displacement of mutans streptococci and inhibition of tooth decay by Streptococcus salivarius TOVE-R.

The ability of Streptococcus salivarius TOVE-R to displace virulent representatives of the most prevalent human mutans streptococci from the teeth of rats, and thereby to inhibit caries, was studied. Streptococcus mutans 10449S- or Streptococcus sobrinus 6715-13WT-infected specific-pathogen-free rats consuming a high-sucrose diet were inoculated by TOVE-R. The infectants were differentially recovered from swabs of the teeth over the time course of infection and from sonically treated material of extracted teeth and excised tongues. Despite initial colonization of the teeth by the mutans streptococci, TOVE-R colonized the teeth, unlike other essentially nonvirulent plaque formers already described. It did not colonize the tongues of the rats. TOVE-R emerged and persisted as a prominent member of the plaque ecology. There was an associated decline in the mutans streptococci on the teeth, and this decline was associated with significant inhibition of the caries component attributable to 10449S infection (56%) and to 6715-13WT infection (52%). TOVE-R did not reliably inhibit the component of fissure caries attributable to the nonmutans indigenous flora of the rats. TOVE-R itself induced no detectable decay. The data suggest the potential therapeutic utility of TOVE-R to inhibit caries by displacement of mutans streptococci from the teeth. These results supplement the already reported ability of TOVE-R to preempt initial colonization of teeth by the mutans streptococci.

Animals↗
PubMed1985

Inhibition of ecological emergence of mutans streptococci naturally transmitted between rats and consequent caries inhibition by Streptococcus salivarius TOVE-R infection.

The ability of Streptococcus salivarius strain TOVE-R to inhibit the ecological emergence of virulent representatives of the most prevalent human mutans streptococci on the teeth of specific pathogen-free Osborne-Mendel rats was studied. Rats which were infected by TOVE-R, or either S. mutans 10449S or S. sobrinus 6715-13WT, or uninfected were transiently co-caged so as to allow natural fecal transfer of organisms due to coprophagy. The infectants were differentially recovered from swabs of the teeth over the time course of the experiments and from sonified teeth at termination. Data were expressed on both relative (percentage) and absolute (CFU) bases. Initial oral colonization of rats by TOVE-R inhibited the ecological emergence of fecally transmitted S. mutans 10449S and S. sobrinus 6715-13WT. There was a generally inverse relationship between the percentages and absolute numbers of TOVE-R and the mutans streptococci on the teeth, which strongly suggested their competition for tooth sites. Absolute numbers of total recoverable flora from the teeth upon sonification were correlated with caries scores, thus suggesting that total recoverable flora counts substantially reflect cavitation status. TOVE-R itself induced no apparent caries activity and its transmission to rats already infected by 10449S or its colonization of rats before 10449S infection inhibition caries induction by this S. mutans strain; similar anticaries effects were not statistically significant for TOVE-R against 6715-13WT in these experiments. These data on the inhibition of the ecological emergence of the mutans streptococci supplement the already reported ability of TOVE-R to preempt initial colonization of teeth and partially displace the colonization of teeth by the mutans streptococci.

Animals↗
PubMed1984

Glucose-sucrose-potassium tellurite-bacitracin agar, an alternative to mitis salivarius-bacitracin agar for enumeration of Streptococcus mutans.

An agar medium for selective recovery and enumeration of Streptococcus mutans was developed as an alternative to mitis salivarius-bacitracin (MSB) agar. Combinations of dyes, antibiotics, and tellurite were added to a nonselective medium which, because of its sucrose content, allowed easy recognition of S. mutans colonies. Candle jar incubation for 2 days, by comparison with anaerobic incubation, reduced background flora but did not diminish S. mutans recoveries from clinical samples. Quantitative comparisons were made of the simultaneous recoveries of a number of authentic S. mutans serotype representatives and fresh clinical isolates, using various glucose-sucrose-potassium tellurite-bacitracin (GSTB) formulations and mitis salivarius, MSB, and blood agars. Mitis salivarius counts were not detectably different from blood counts, but counts on MSB were distinctly lower. A formulation of the new medium containing 5% glucose 5% sucrose, 0.001% potassium tellurite, 0.3 U of bacitracin per ml (hence GSTB), and 2% agar gave recoveries nearly equal to those on mitis salivarius agar and much greater than those on MSB. The medium yielded readily recognized S. mutans colonies and facilitated detection of intracellular polysaccharide formers upon flooding with I2 reagent. Freshly isolated serotype c, E, and f colonies could often be distinguished from serotype d and g colonies, a distinction made reliable by testing for intracellular polysaccharide. A study of 300 salivary samples revealed GSTB to give significantly higher recoveries than MSB. About 72% of all samples were substantially underestimated for S. mutans with MSB, and 6.7% of samples were falsely negative for S. mutans with MSB. Recovery of background flora on GSTB was as low or lower than on MSB, and both types of agar could be stored for at least 9 weeks without notable change of selectivity. Thus, GSTB agar appears to be simple and reliable to use and requires no anaerobic incubation. Caution is voiced about interpretation of data previously reported which evaluated S. mutans on MSB agar.

Agar↗
PubMed1983

The repressible metabolism of sorbitol (D-glucitol) by intact cells of the oral plaque-forming bacterium Streptococcus mutans.

Sorbitol metabolism of Streptococcus mutans was studied. Cocci adapted to growth in sorbitol, glucose or both were challenged to grow on and to ferment those carbohydrates in pH-controlled defined media with intact cells capable of metabolic inductions and regulations. Glucose degradation when in high concentration did not depend upon induction of glucose-specific phosphoenolpyruvate-dependent phosphotransferase activity, as it did at low glucose concentrations. Sorbitol utilization was signalled by the induction of sorbitol-specific phosphoenolpyruvate-dependent phosphotransferase and sorbitol-6-phosphate dehydrogenase activities which persisted throughout the growth cycle. However, when even low levels of glucose were present, sorbitol transport and catabolic activities were rapidly repressed and they were not de-repressed until essentially all glucose had been utilized. Metabolism of sorbitol thus relies on the sorbitol phosphotransferase/sorbitol-6-phosphate dehydrogenase pathway whose activity is sensitively repressed in the presence of glucose.

Enzyme Repression↗
PubMed1982

Sucrose transport by Streptococcus mutans. Evidence for multiple transport systems.

The transport of sucrose by selected mutant and wild-type cells of Streptococcus mutans was studied using washed cocci harvested at appropriate phases of growth, incubated in the presence of fluoride and appropriately labelled substrates. The rapid sucrose uptake observed cannot be ascribed to possible extracellular formation of hexoses from sucrose and their subsequent transport, formation of intracellular glycogen-like polysaccharide, or binding of sucrose or extracellular glucans to the cocci. Rather, there are at least three discrete transport systems for sucrose, two of which are phosphoenolpyruvate-dependent phosphotransferases with relatively low apparent Km values and the other a non-phosphotransferase (non-PTS) third transport system (termed TTS) with a relatively high apparent Km. For strain 6715-13 mutant 33, the Km values are 6.25 X 10(-5) M, 2.4 X 10(-4) M, and 3.0 X 10(-3) M, respectively: strain NCTC-10449, the Km values are 7.1 X 10(-5) M, 2.5 X 10(-4) M and 3.3 X 10(-3) M, respectively. The two lower Km systems could not be demonstrated in mid-log phase glucose-adapted cocci, a condition known to repress sucrose-specific phosphotransferase activity, but under these conditions the highest Km system persists. Also, a mutant devoid of sucrose-specific phosphotransferase activity fails to evidence the two high affinity (low apparent Km) systems, but still has the lowest affinity (highest Km) system. There was essentially no uptake at 4 degrees C indicating these processes are energy dependent. The third transport system, whose nature is unknown, appears to function under conditions of sucrose abundance and rapid growth which are known to repress phosphoenolpyruvate-dependent sucrose-specific phosphotransferase activity in S. mutans. These multiple transport systems seem well-adapted to S. mutans which is faced with fluctuating supplies of sucrose in its natural habitat on the surfaces of teeth.

Biological Transport↗