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Biomedical subjects

M Flashner

Publications and source records attributed to M Flashner.

At least 19 recordsLinked to original sources
PubMed1998

An in vivo study of the chlorhexidine release profile of the PerioChip in the gingival crevicular fluid, plasma and urine.

The release profile of chlorhexidine from the PerioChip (Chip), a biodegradable local delivery system that contains 2.5 mg of chlorhexidine gluconate (CHX) in a cross-linked hydrolyzed gelatin matrix, into the gingival crevice, was evaluated in an in vivo, open label, single-center, 10-day pharmacokinetic study conducted on 19 volunteers with chronic adult periodontitis. Each volunteer had a single chip inserted into each of 4 selected pockets, with probing pocket depths of between 5-8 mm, at time 0. Gingival crevicular fluid (GCF) samples were collected using filter paper strips prior to Chip placement and at 2 h, 4 h, 24 h and 2, 3, 4, 5, 6, 8, and 9 days post-Chip placement. The GCF volume was measured using a calibrated Periotron 6000. Blood samples were collected at times 0, 1, 4, 8, 12 h and 5 days post-dosing. Urine was collected as a total 24-h specimen immediately post-dosing and 2 single samples at time 0, prior to dosing, and 5 days. The CHX was eluted from the paper strips and the CHX levels in GCF, blood and urine quantified using HPLC. The results indicate an initial peak concentration of CHX in the GCF at 2 h post-Chip insertion (2007 microg/ml) with slightly lower concentrations of between 1300-1900 microg/ml being maintained over the next 96 h. The CHX concentration then progressively decreased until study conclusion with significant CHX concentrations (mean=57 microg/ml) still being detectable at study termination. CHX was not detectable in any of the plasma or urine samples at any time point during the study. These results indicate that the PerioChip can maintain clinically effective levels of CHX in the GCF of periodontal pockets for over 1 week with no detectable systemic absorption.

Adult↗
PubMed1998

Adjunctive use of a subgingival controlled-release chlorhexidine chip reduces probing depth and improves attachment level compared with scaling and root planing alone.

The present studies evaluated the efficacy of a controlled-release biodegradable chlorhexidine (CHX) (2.5 mg) chip when used as an adjunct to scaling and root planing on reducing probing depth (PD) and improving clinical attachment level (CAL) in adult periodontitis. Two double-blind, randomized, placebo-controlled multi-center clinical trials (5 centers each) were conducted; pooled data are reported from all 10 centers (447 patients). At baseline, following 1 hour of scaling and root planing (SRP) in patients free of supragingival calculus, the chip was placed in target sites with PD 5 to 8 mm which bled on probing. Chip placement was repeated at 3 and/or 6 months if PD remained > or = 5 mm. Study sites in active chip subjects received either CHX chip plus SRP or SRP alone (to maintain study blind). Sites in placebo chip subjects received either placebo chip plus SRP or SRP alone. Examinations were performed at baseline; 7 days; 6 weeks; and 3, 6, and 9 months. At 9 months significant reductions from baseline favoring the chlorhexidine chip compared with both control treatments were observed with respect to PD (chlorhexidine chip plus SRP, 0.95 +/- 0.05 mm; SRP alone, 0.65 +/- 0.05 mm, P < 0.001; placebo chip plus SRP, 0.69 +/- 0.05 mm, P < 0.001) and CAL (chlorhexidine chip plus SRP, 0.75 +/- 0.06 mm; SRP alone, 0.58 +/- 0.06 mm, P < 0.05; placebo chip plus SRP, 0.55 +/- 0.06 mm, P < 0.05). The proportion of patients who evidenced a PD reduction from baseline of 2 mm or more at 9 months was significantly greater in the chlorhexidine chip group (19%) compared with SRP controls (8%) (P < 0.05). Adverse effects were minor and transient toothache, including pain, tenderness, aching, throbbing, soreness, discomfort, or sensitivity was the only adverse effect that was higher in the chlorhexidine group as compared to placebo (P = 0.042). These data demonstrate that the adjunctive use of the chlorhexidine chip results in a significant reduction of PD when compared with both SRP alone or the adjunctive use of a placebo chip. These multi-center randomized control trials suggest that the chlorhexidine chip is a safe and effective adjunctive chemotherapy for the treatment of adult periodontitis.

Adult↗
PubMed1997

Sustained local delivery of chlorhexidine in the treatment of periodontitis: a multi-center study.

The safety and efficacy of a degradable, subgingivally placed drug delivery system containing 2.5 mg chlorhexidine (CHX) were evaluated in a randomized, blinded, multi-center study of 118 patients with moderate periodontitis. A split-mouth design was used to compare the treatment outcomes of scaling and root planing (SRP) alone with the combined use of SRP and the CHX in pockets with probing depths of 5 to 8 mm. The two maxillary quadrants were used for the two treatment arms of the study. Scaling and root planing was performed at baseline only, while the CHX was inserted both at baseline and at 3 months. Clinical and safety measurements including probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) as well as gingivitis, plaque, and staining indices were recorded at baseline, and at 1, 3, and 6 months. The average PD reduction in the CHX-treated sites was significantly greater than in the sites receiving SRP alone at both 3 and 6 months with a mean difference of 0.42 mm (P < or = 0.01) at 6 months. The reduction in CAL at the treated sites was greater than at the SRP sites, although the difference was statistically significant at the 6-month visit only. An analysis of patients with initial probing depths of 7 to 8 mm (n = 56) revealed a significantly greater reduction in PD and CAL in those pockets treated with CHX compared to SRP at both 3 and 6 months. The mean differences between test and control sites at 6 months were 0.71 mm and 0.56 mm PD and CAL respectively.

Adult↗
PubMed1993

Pharmacodynamics of biological response in vivo after single and multiple doses of interferon-beta.

Interferons (IFNs) induce gene regulation in vivo that may be used to identify effective doses, schedules, and potential correlates of therapeutic response. To critically examine minimum effective dose, duration of response, and cumulative effects of repetitive doses, a range of subcutaneous doses of IFN beta ser was studied in 32 healthy human volunteers. IFN-induced products of gene regulation assessed were beta 2-microglobulin, neopterin, and tryptophan in serum and 2',5'-oligoadenylate (2-5A) synthetase activity in peripheral blood mononuclear cells. Eight subjects per group received 0.09, 0.9, 9, or 45 MU of IFN beta. Responses were measured at 24, 48, and 72 h after single and multiple doses. The lowest biologically effective dose was 0.9 MU; significant (p < 0.02) increases were observed at 24 h in beta 2-microglobulin and cellular 2-5A synthetase activity. At the two higher doses, 9 and 45 MU, changes were observed at 24 h in all products (p < 0.01). A dose response (p < 0.01) over the range of 0.09-45 MU was observed for all these serum and intracellular gene products. Changes in neopterin, beta 2-microglobulin, and cellular 2-5A synthetase correlated significantly with each other. The response to a single dose of IFN beta was as great in magnitude as the response to multiple doses, suggesting an alternate-day schedule would maintain biological response.

2',5'-Oligoadenylate Synthetase↗
PubMed1992

Absence of biological effects of orally administered interferon-beta ser.

To assess biological effectiveness of interferon (IFN) administered orally, we measured serum IFN and several proteins and metabolites induced by IFN after oral administration of 2.5 mg or 7.5 mg of recombinant IFN-beta ser to 6 healthy volunteers. These IFN-induced metabolites, beta 2-microglobulin, and neopterin in serum, and 2',5'-oligoadenylate (2-5A) synthetase in peripheral blood mononuclear cells, are more sensitive to the presence of IFN than bioassay of IFN in serum. Up to 48 h after oral IFN was administered, serum IFN, beta 2-microglobulin, neopterin, or 2-5A synthetase were not generally increased compared to pretreatment levels, indicating that oral IFN had no significant biological effects.

Adenine Nucleotides↗
PubMed1989

Sequential model to describe the nicotinic synaptic current.

An analytical formula is derived to describe the synaptic end plate current (epc) at the nicotinic receptor. Various concurrently occurring underlying processes, including (a) diffusion, (b) hydrolysis of acetylcholine, and (c) its binding to the dimeric receptor, were considered in order to develop the equation. Numeric solution of the equations that describe the events underlying the epc showed that these events occur in sequence, rather than concurrently. This sequential occurrence of the processes allowed for simplifications, which were used as the basis for the new description of the epc. The resulting formula serves as a tool for evaluating the relative contribution of the various processes in formation of the natural occurring transient epc.

Animals↗
PubMed1988

Photoaffinity labeling of plasma membrane receptors for cytochalasins in Ehrlich tumor cells.

Treatment of purified Ehrlich ascites cell plasma membranes either with [3H]cytochalasin B or [3H]19-O-acetylchaetoglobosin A under photolytic conditions produced several radioactive polypeptides which were characterized by SDS-PAGE analyses. The major proteins so photolabeled were in the 60,000-80,000 Da range, with less labeling found in polypeptides smaller than 43,000 and greater than 90,000 Da. Immunofluorescent staining failed to identify the major photolabeled component as actin. It is concluded, in keeping with prior investigations using other cell types, that the predominant proteins photolabeled by cytochalasins are affiliated with the glucose-transport system.

Affinity Labels↗
PubMed1987

Anti-sense peptide recognition of sense peptides: direct quantitative characterization with the ribonuclease S-peptide system using analytical high-performance affinity chromatography.

The ability of peptides coded by the anti-sense strand of DNA to interact specifically with peptides coded by the sense strand has been evaluated. The sense peptide examined, ribonuclease S-peptide, was immobilized on a coated silica affinity chromatographic matrix. Anti-sense peptides were synthesized on the basis of the anti-sense DNA sequence for the S-peptide region in native pancreatic ribonuclease A. The interaction of synthetic anti-sense peptides with sense peptide was quantitated from the degree of retardation during chromatographic elution on the sense peptide affinity matrix in buffers with and without soluble competing sense peptide. Sense/anti-sense peptide interactions were found to occur with significant affinities with each of two anti-sense 20-residue peptides of opposite amino-to-carboxyl orientations and to weaken progressively with decreasing length of anti-sense peptide. The substantial chromatographic retardation of anti-sense peptides was specific, since it decreased as expected with increasing concentration of the soluble competing S-peptide, could not be mimicked by the elution of several control peptides (including S-peptide itself) on the S-peptide matrix, and did not occur with a blank chromatographic matrix (no S-peptide attached). The stoichiometry of anti-sense peptide binding to immobilized sense peptide was found to be far greater than 1:1, and at least 4-5:1, for the two 20-mer anti-sense peptides. In sum, the analytical affinity chromatographic experiments have established quantitatively that anti-sense peptide binding to sense peptides occurs in the ribonuclease S-peptide case and have identified some structural elements that govern these interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1984

Structure-activity relationships of cytochalasins in the differentiation of cytolytic T lymphocytes.

Four naturally occurring cytochalasins and three synthetic congeners have been studied for their effects on in vitro sensitization of murine lymphocytes to P815 mastocytoma. The relative order of effectiveness of these secondary fungal metabolites in inhibiting cytotoxic T cell development is as follows: cytochalasin D greater than cytochalasin E greater than cytochalasin A greater than cytochalasin B, 21,22- dihydrocytochalasin A greater than 7- acetylcytochalasin D. The 7,20 diacetylcytochalasin B derivative was inactive at the highest level tested (4 X 10(-6) M). Cytochalasin D is the most effective compound, producing at 5 X 10(-8) M a 50% inhibition of 51Cr release in a 4-hr cytolysis assay. This response pattern is in keeping with other test systems that implicate actin involvement, and underscores the contribution of an unsubstituted 7-hydroxyl drug function in receptor recognition. Inhibition produced by the cytochalasins is reversible if the compounds are removed from the tissue culture medium within the first 24 hr of a 4-day culture period. Delayed addition of cytochalasin D inhibits T cell development only within this first 24 hr of culture. These data suggest that the effects of cytochalasins are at an early step in the sensitization process, possibly antigen recognition.

Animals↗