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Biomedical subjects

M Chasin

Publications and source records attributed to M Chasin.

11 recordsLinked to original sources
PubMed1992

Bone conduction implants: transcutaneous vs. percutaneous.

Clinical experience with transcutaneous bone conduction implants has demonstrated that they are most beneficial for patients with purely conductive hearing loss in at least one ear. Percutaneous bone conduction implants, however, have been reported to provide adequate benefit for patients with mixed hearing loss with bone conduction pure-tone averages up to 45 dB HL (Tjellstrom, 1989). The results of 24 Xomed Audiant osseointegrated bone conduction hearing devices (including a clinical trial on two patients using a new, larger magnet [Neodynium Iron Boron]), plus the results of eleven patients implanted and fitted with the percutaneous bone-anchored hearing aid are reported. Aided results with these devices will be presented. In addition, general comparisons of benefit obtained with the two devices will be made for patients who exhibit similar hearing losses. Finally, a direct comparison will be made on two patients who have undergone both implant procedures.

Adolescent↗
PubMed1992

The intracerebral distribution of BCNU delivered by surgically implanted biodegradable polymers.

The local concentration and distribution of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) within normal brain tissue were studied following surgical implantation of biodegradable polymer containing BCNU in New Zealand White rabbits. Cylindrical discs of poly(bis(p-carboxyphenoxy)-propane:sebacic acid) copolymer in a 20:80 formulation were made containing [3H]-inulin or [3H]-BCNU labeled in the methylene hydrogens of the chloroethyl groups. These were implanted in the brains of 56 New Zealand White rabbits. The animals were sacrificed 3, 7, 14, or 21 days later and the brains were rapidly removed, frozen, and prepared for quantitative autoradiography. Autoradiographs from coronal sections bisecting the polymer were analyzed to determine both the proportion of the brain section exposed to the tracer and the local drug concentrations as a function of distance from the polymer. Tritiated BCNU was also injected directly into the brains of eight additional rabbits, and local brain concentrations were studied over time. The results of this study demonstrate that approximately 50% of the area of the brain sections was exposed to radiolabeled compound 3 days after BCNU-polymer implantation, 15% at 7 days, and less than 10% at 14 and 21 days. Polymer discs containing 600 micrograms BCNU generated 6 mM concentrations of BCNU in brain tissue 10 mm from the polymer at 3 and 7 days. Pharmacological studies demonstrated that approximately 25% of the tritium label was associated with intact BCNU 3 days following polymer implantation. Radiolabeled inulin delivered by polymer remained dispersed throughout the ipsilateral hemisphere for 14 days. Direct injection of [3H]-BCNU into brain parenchyma resulted in widely distributed tracer at 1 and 3 hours with rapid disappearance thereafter. It is concluded that local delivery of BCNU to brain tissue with this polymeric drug delivery system results in sustained high local concentrations of BCNU which may be of value in the treatment of patients with brain tumors.

Animals↗
PubMed1979

Short in vitro half-life of thymopoietin32--36 pentapeptide in human plasma.

Thymopoietin32--36 (TP5) is a synthetic pentapeptide that has the biological activity of its parent molecule, the 49 amino acid thymic hormone thymopoietin. Tritiated thymopoietin32--36 (3 /-TP5) was prepared by reductive tritiation of dibromotyrosyl-TP5. The stability of 3 H-TP5 in human plasma was studied by analyzing samples by thin-layer chromatography at different time points and quantitating the radioactivity associated with TP5 (Arg-Lys-Asp-Val-Tyr) and its tyrosyl-containing breakdown products (Lys-Asp-Val-Tyr, Asp-Val-Tyr, Val-Tyr, Tyr). In plasma (but not in saline) the pentapeptide was rapidly degraded (apparent t1/2 approximately 30 seconds) with the corresponding appearance of radioactivity associated with the other tyrosyl-containing reference compounds. These data imply that the pentapeptide, which is active in vivo, may rapidly trigger changes in responsive cells; sustained circulating levels may not be required for activity.

Adult↗
PubMed1979

A new assay for the measurement of mediator release from rat peritoneal mast cells.

In this report, we describe a new in vitro experimental system for monitoring the release, and inhibition of release, of [3H]-serotonin from rat peritoneal mast cells, which can be used as a novel screen for evaluation of compounds effective in immediate hypersensitivity reactions. This assay is an improvement on existing assays since the cells are not required to be exposed to hormones at any time during the procedure. In this assay, 1 microgram/ml of compound 48/80 consistently produced a 6- to 8-fold-increase in release of serotonin with a low background release of 4-5%. Disodium chromoglycate (DSCG), a standard inhibitor of histamine release, effectively inhibited compound-48/80-stimulated serotonin release with an average I50 of 2.1 X 10(-4) M. Several other potential antiasthmatic agents were far more potent than DSCG.

5-Hydroxytryptophan↗
PubMed1977

Dissociation of lipolysis from the levels of cyclic AMP in rat epididymal fat cells.

Two compounds, theophylline and 8-aza-9-furfuryl-adenine (SQ 4665), were found to maximally stimulate lipolysis in preparations of rat epididymal fat cells in the absence of exogenous hormones. Cyclic AMP levels in lipocytes maximally stimulated by either agent alone were unchanged from control levels. In contrast, lipolysis stimulated by either epinephrine alone or in combination with several cyclic nucleotide phosphodiesterase inhibitors correlated well with increases in the levels of cyclic AMP observed. These results suggest the presence of a non-cyclic AMP dependent pathway for the stimulation of lipolysis in rat epididymal fat cells.

Adenine↗
PubMed1975

Lack of steroidogenic response to cyclic AMP and ACTH in adrenal cells from rats bearing the MtTF4 tumor.

Adrenal cell suspensions prepared from rats bearing the MtTF4 tumor failed to increase corticosterone production when exposed to adenosine 3', 5'-cyclic monophosphate (cyclic AMP) or ACTH, placing the defect in these adrenals beyond the ACTH receptor site. Adrenal cells from normal rats responded well to these stimuli. Adrenal cyclic AMP phosphodiesterase prepared from the tumor bearing rats appeared normal both with respect to its specific activity and inhibition profile with theophylline. Exposure of the MtTF4 adrenal cells to 1,2-3H-cholesterol in the presence of either cyclic AMP or ACTH did not result in an increase in radioactively labeled corticosterone, whereas increased label could be demonstrated in adrenal cells from normal rats similarly treated.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1975

Modulators of cyclic AMP systems.

On the basis of the data reported here, one may conclude that although many agents that act in the central nervous system are modulators of the action of cyclic AMP, it is difficult to establish a direct connection between the pharmacologic activity and the levels of cyclic AMP in the brain. This lack of interrelation applies to the benzodiazepines as well as to the pyrazolopyridines. The data for members of the latter group are somewhat frustrating in this regard, since an excellent correlation has been shown to exist between the potency of inhibition of PDE and activity in the antianxiety test. In measurements of steroidogenesis in the isolated adrenal cell, the correlation between activity in vito and the conflict assay is even better. The data presented here and reported elsewhere (Shimizu et al., 1974; Kelly et al., 1974; Mayer and King, 1974; King and Mayer, 1974) provide evidence that agents that act as inhibitors of PDE in cell-free systems exert their influence on cyclic AMP in tissue slices of the brain of guinea pigs by mechanisms that seem not to be related to an effect on PDE. Papaverine, and possibly chlordiazepoxide, may act by releasing agonists that, in turn, stimulate the accumulation of cyclic AMP. This activity is blocked bo other inhibitors of PDE, such as theophyline. Results obtained by the use of platelets are refreshingly clear. Inhibition of aggregation has been shown to occur when the level of cyclic AMP is raised, and a suggestive exists that the most potent inhibitors of platelet PDE are the best potentiators of the action of PGE1 in blocking aggregation. The study utilizing drugs collected from a large number of therapeutic classes makes clear that it is difficult to attribute the mechanism of action for any of the classes studied to modulation of cyclic AMP. An unexpected finding of this study, however, was the fact that pharmacologic agents include an unusually large number of inhibitors of PDE as compared with agents chosen at random. This finding provides a powerful tool for the biochemical pharmacologist who is examining large numbers of compounds in the search for potential drugs.

Adenylyl Cyclase Inhibitors↗