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Biomedical subjects

J Kost

Publications and source records attributed to J Kost.

At least 37 records · Page 2Linked to original sources
PubMed1998

Mass transport enhancement by ultrasound in non-degradable polymeric controlled release systems.

In this work, an attempt was made to characterize mass transport enhancement in non-erodible polymeric matrices, caused by ultrasound. It was found that drug release rates from polymeric matrices exposed to ultrasound, can be controlled by modifying parameters like: ultrasound frequency, molecular weight of the incorporated drug and structure of the polymeric matrix (size of pores in the network). It is suggested that the enhancing effect of ultrasound on drug release from non-erodible polymers is due to the contribution of a convective term, generated by cavitation, without any destructive effect on morphology of the polymer. This phenomenon was found to be more pronounced in systems which are mass-transport limited.

Drug Carriers↗
PubMed1996

Long-term protection against the effects of tumour necrosis factor by controlled delivery of the soluble p55 TNF receptor.

Chronic inflammatory diseases are associated with increased soluble tumour necrosis factor (TNF) receptor concentrations in serum. To obtain such an increase, we implanted mice with ethylene vinyl-acetate or poly (lactic-co-glycolic) acid copolymers containing human soluble p55 TNF receptor. Copolymers containing rather small amounts of the receptor (about 20 micrograms) maintained prolonged increases in serum receptor concentrations. Mice implanted with these copolymers were effectively protected against lethal wasting and from arthritis resulting from chronic exposure to TNF. These findings suggest that the increased production of soluble TNF receptors in chronic inflammatory diseases counteracts deleterious effects of TNF, and suggest a therapeutic application for the natural forms of the receptors in such diseases.

Animals↗
PubMed1994

Enhanced protein blotting from PhastGel media to membranes by irradiation of low-intensity ultrasound.

A novel approach to protein blotting based on application of ultrasound is proposed. Three minutes of ultrasound exposure (1 MHz, 2.5 W/cm2) was sufficient for a very clear transfer of proteins from a polyacrylamide gel (PhastGel) to nitrocellulose or nylon 66 Biotrans membranes. The proteins evaluated were prestained sodium dodecyl sulfate-polyacrylamide gel electrophoresis standards (18,500-106,000 Da) and 14C-labeled Rainbow protein molecular weight markers (14,300-200,000 Da). In control experiments, which were performed following similar procedures without turning the ultrasonic generator on, no protein blotting could be seen. For comparable blotting results, 30 min for electroelution or 240 min for elution by convection blotting was required.

Electrophoresis, Polyacrylamide Gel↗
PubMed1993

Interleukin 7-induced expression of specific T cell receptor gamma variable region genes in murine fetal liver cultures.

We previously reported that culture of murine fetal liver (FL) cells with interleukin 7 (IL-7) results in expression of high levels of T cell receptor (TCR) gamma transcripts by a population of cells expressing Thy-1 and Pgp-1, suggesting that IL-7 promotes the growth and/or differentiation of pre-T cells. We demonstrate herein that culture of FL cells for 7 d with IL-7 caused the rearrangement and expression of TCR gamma variable (V) region genes V gamma 4 and V gamma 6, but not V gamma 5 or V gamma 7. Since this effect was not blocked by hydroxyurea, it appeared to represent induction of expression of these genes by IL-7 rather than expansion of a preexisting positive population. We also show that IL-7 induced RAG-1 and RAG-2 mRNA expression by FL cells. These data provide evidence that specific TCR gamma/delta V region genes can be rearranged and expressed by T lineage cells before their migration to the thymus, in response to IL-7.

Animals↗
PubMed1993

Glucose-sensitive polymeric matrices for controlled drug delivery.

Hydrogel matrices were prepared by chemical polymerization of solutions containing 2-hydroxyethyl methacrylate, N,N-dimethyl-aminoethyl methacrylate, tetraethylene glycol dimethacrylate, ethylene glycol and water solutions containing glucose oxidase, bacitracin or insulin. The hydrogels displayed faster and higher swelling and release rates at lower pH or at higher glucose concentrations. Swelling and release kinetics were also responsive to step changes in glucose concentration in the physiological range. The kinetics of the soluble and immobilized enzyme followed Michaelis Menten's kinetics. In the soluble state the enzyme was more active than the immobilized one due to mass transfer limitations, which may be overcome by preparation of microbead configuration.

Blood Glucose↗
PubMed1993

Ultrasound for controlled delivery of therapeutics.

Release of substances from polymeric drug delivery systems can be repeatedly modulated at will through ultrasound. Nondegradable-diffusion controlled and degradable-erosion controlled polymeric delivery systems have both been shown to have enhanced kinetics of release when exposed to ultrasonic energy. The effect of ultrasound was also evaluated on skin and synthetic membranes permeability. The main factors contributing to this effect included mixing, temperature, cavitation, acoustic streaming and polymer morphological changes. These phenomena have appealing therapeutic and commercial possibilities, as many drugs may benefit from subtle delivery pattern under temporal control to obtain optimal therapeutic effects.

Animals↗
PubMed1993

Ultrasonically enhanced transdermal drug delivery. Experimental approaches to elucidate the mechanism.

The effect of therapeutic range ultrasound on skin permeability was studied in vitro. Permeating molecule ionization state, pH, ultrasound duration, reversibility of the enhancement phenomenon, and skin structural alterations were evaluated. It was found that ultrasound affects the permeability of both ionized and unionized molecules. No irreversible structural alterations due to the ultrasound exposure were detected in the stratum corneum. Ultrasound enhancing mechanism was discussed.

Administration, Cutaneous↗
PubMed1992

Responsive polymer systems for controlled delivery of therapeutics.

The ideal drug-delivery system should provide therapeutics in response to physiological requirements, having the capacity to 'sense' changes and alter the drug-release process accordingly. Such responsive controlled delivery systems are still at an experimental stage. This review focuses on two basic approaches: (1) externally regulated systems (utilizing triggers such as magnetism, ultrasound, temperature and electricity), and (2) self-regulated systems (utilizing pH-sensitive polymers, enzyme-substrate reactions, competitive binding, and antibody interactions).

Animals↗
PubMed1990

Chemically-modified polysaccharides for enzymatically-controlled oral drug delivery.

Starch polysaccharides were investigated as bioerodible matrices for enzymatically-controlled oral drug delivery. Corn starch was ionically cross-linked with calcium chloride. It was found that the cross-linked starch could be used for entrapment and controlled release of bioactive molecules. The release rate of large molecules was degradation-dependent due to amylase activity, which might target the release to the intestine, when the particles were taken orally. The release of small molecules such as salicylic acid, was mainly by diffusion.

Administration, Oral↗
PubMed1989

Ultrasound-enhanced polymer degradation and release of incorporated substances.

The effect of ultrasound on the degradation of polymers and the release rate of incorporated molecules within those polymers was examined. Up to 5-fold reversible increases in degradation rate and up to 20-fold reversible increases in release rate of incorporated molecules were observed with biodegradable polyanhydrides, polyglycolides, and polylactides. Up to 10-fold reversible increases in release rate of incorporated molecules within nonerodible ethylene/vinyl acetate copolymer were also observed. The release rate increased in proportion to the intensity of ultrasound. Temperature and mixing were relatively unimportant in effecting enhanced polymer degradation, whereas cavitation appeared to play a significant role. Increased release rates were also observed when ultrasound was applied to biodegradable polymers implanted in rats. Histological examination revealed no differences between normal rat skin and rat skin that had been exposed to ultrasonic radiation for 1 hr. With further study, ultrasound may prove useful as a way of externally regulating release rates from polymers in a variety of situations where on-demand release is required.

Animals↗
PubMed1989

Treatment of an influenza A outbreak in a teaching nursing home. Effectiveness of a protocol for prevention and control.

The safety and efficacy of current ACIP guidelines for the prevention and control of influenza in nursing home populations are uncertain. An outbreak of influenza A/Sichuan (H3N2) in a teaching nursing home during 1988 gave us the opportunity to evaluate the effectiveness of an influenza vaccination and amantadine prophylaxis protocol. Over 13 days, 12 of 60 residents developed influenza. Prior influenza vaccination had been given to 94% of the residents. Protection from infection occurred in those tested who had antibody levels greater than or equal to 1:16 to the A/Leningrad (H3N2) antigen contained in the standard 1987-88 trivalent vaccine. However, five of 17 vaccinated residents who were tested had antibody levels less than or equal to 1:16 at the start of the outbreak. Amantadine (less than or equal to 100 mg/day) was given to all but one resident starting on the third day of the outbreak, and to employees starting on the sixth day of the outbreaks. Seven residents developed illness after the start of amantadine, although amantadine appeared to ameliorate their symptoms. Although amantadine was generally well tolerated by residents, employees receiving amantadine identified a high incidence of side effects and only 44% of employees took at least 70% of the prescribed amantadine. In our opinion, early detection and protocol-directed intervention probably abated a more severe influenza outbreak. Therefore we support existing recommendations that formal nursing home policies be established to ensure that residents and employees receive annual influenza vaccine and that chemoprophylaxis be used when outbreaks of influenza A are suspected.

Aged↗
PubMed1989

Effect of ultrasound on transdermal drug delivery to rats and guinea pigs.

The effect of therapeutic range ultrasound (1 MHz) on skin permeation of D-mannitol, a highly polar sugar alcohol, inulin, a high molecular weight polysaccharide and physostigmine, a lipophilic anticholinesterase drug was studied in rats and guinea pigs. D-Mannitol and inulin are totally and rapidly excreted, once they have penetrated through the skin into the blood stream, permitting direct in vivo monitoring. For evaluating skin penetration of physostigmine the decrease of whole blood cholinesterase was measured. Ultrasound nearly completely eliminated the lag time usually associated with transdermal delivery of drugs. 3-5 min of ultrasound irradiation (1.5 W/cm2 continuous wave or 3 W/cm2 pulsed wave) increased the transdermal permeation of inulin and mannitol in rats by 5-20-fold within 1-2 h following ultrasound application. Ultrasound treatment also significantly increased (P less than 0.05) the inhibition of cholinesterase during the first hour after application in both physostigmine treated rats and guinea pigs: while in control guinea pigs no significant inhibition of cholinesterase could be detected during the first 2 h after application of physostigmine, the ultrasound treated group showed a 15 +/- 5% (mean +/- SEM) decrease in blood cholinesterase 1 h after ultrasound application. For physostigmine-treated rats the level of cholinesterase inhibition 1 h after ultrasound application was 53 +/- 5% in the ultrasound-treated group and 35 +/- 5% in the controls.

Administration, Cutaneous↗
PubMed1987

Magnetically enhanced insulin release in diabetic rats.

Polymer matrices containing insulin and embedded magnets were implanted subcutaneously in diabetic rats for 51 days. Passive release of insulin from the polymer resulted in a decrease in the blood glucose level. When the diabetic rats were exposed to an oscillating magnetic field, the blood glucose levels were additionally lowered by nearly 30%. No statistically significant effect in blood glucose decrease was observed in four different sets of control animals subjected to the magnetic field. Because of the very small size of the implants, they may, with additional study, provide an alternative to current modes of therapy using programmable implantable infusion pumps.

Animals↗
PubMed1986

Polyanhydrides for controlled release of bioactive agents.

This report is a review of the development of a drug delivery system based on biorodible polyanhydrides. With the water labile anhydride linkage, a wide range of matrix degradation and drug release rates can be obtained from these drug-carriers. In addition to monolithic formulations, the feasibility of an injectable system by microencapsulation is demonstrated. The possibility of enhancing the release externally by an ultrasonic source has also been explored. The polymers tested showed good tissue biocompatibility and their breakdown products showed no adverse toxicological effects. Preliminary in vivo results confirmed the efficacy of these devices.

Anhydrides↗
PubMed1985

Regulation of drug release from polymer matrices by oscillating magnetic fields.

The reproducible regulation of release of a macromolecule (bovine serum albumin) from biocompatible polymer systems has been demonstrated. Small magnetic spheres or cylindrical magnets were embedded within the polymer matrix which was then subjected to an oscillating magnetic field. In this fashion baseline release rates could be increased 5- to 10-fold with 5-10% standard error. Parameters critical to the regulation of this release included the position, orientation, and magnetic strength of the embedded objects and the amplitude and frequency of the applied magnetic field. Scanning electronmicrographs of the polymer matrix surface reveal that a gap, approximately 100/microns wide, is formed between the embedded object and adjacent polymer material after repeated exposure to an oscillating magnetic field.

Biocompatible Materials↗