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Biomedical subjects

J P Kennedy

Publications and source records attributed to J P Kennedy.

At least 19 recordsLinked to original sources

Characterization and performance of membranes designed for macroencapsulation/implantation of pancreatic islet cells.

Amphiphilic polymer membranes were synthesized for macroencapsulation of cells and characterized by select chemical and biological techniques. The membranes were prepared by crosslinking hydrophilic poly(N,N-dimethyl acrylamide) (PDMAAm) main chains with hydrophobic di-, tri-, and octa-methacrylate telechelic polyisobutylene (PIB) stars. The hydrophilic/hydrophobic composition and the molecular weights between crosslink sites (both M(c,hydrophilic) and M(c,hydrophobic)) were controlled by synthesis conditions. Small tubular membranes were made by in situ rotational copolymerization/crosslinking and filled with pancreatic rat islets. The water-swelling behavior, mechanical properties, and oxygen and insulin diffusion were studied. Macroencapsulatory performance of these membranes was investigated in vitro by macroencapsulation of pancreatic rat islets within tubular membranes for up to 1.5 months, and studying the insulin secreting ability of encapsulated islets in culture. The membranes are robust and maintain their integrity for the period of encapsulation. They allow oxygen and insulin diffusion. Macroencapsulated islets maintained their viability and insulin secretion over an extended period (i.e., 45 days).

Animals↗

Synthesis, permeability and biocompatibility of tricomponent membranes containing polyethylene glycol, polydimethylsiloxane and polypentamethylcyclopentasiloxane domains.

The synthesis of "smart" tricomponent amphiphilic membranes containing poly(ethylene glycol) (PEG), polydimethylsiloxane (PDMS) and polypentamethylcyclopentasiloxane (PD(5)) domains is described. Contact angle hysteresis indicates that in air, the surfaces of such PEG/PD(5)/PDMS membranes are enriched by the hydrophobic components, PDMS and PD(5), while in water, the surfaces are rich in the hydrophilic PEG. The oxygen permeability of a series of membranes with varying M(c,hydrophilic) (M(n,PEG)=4600, 10,000 and 20,000 g/mol) and varying PEG/PD(5)/PDMS compositions was studied. Oxygen permeability increased with the amount of PDMS in the membrane. The molecular weight cut-off (MWCO) ranges and permeability coefficients of insulin through a series of PEG/PD(5)/PDMS(=29/14/57) membranes with varying M(c,hydrophilic) were determined. Insulin permeability is directly related to M(c,hydrophilic) of the membrane. MWCO studies show that the membranes are semipermeable to, i.e., allow the transport of smaller proteins such as insulin (M(n)=5733 g/mol, R(s)=1.34 nm) and cytochrome c (M(n)=12,400 g/mol, R(s)=1.63 nm), but are barriers to larger proteins such as albumin (M(n)=66,000 g/mol, R(s)=3.62 nm). Implantation of representative membranes in rats showed them to be biocompatible. According to these studies, PEG/PD(5)/PDMS membranes may be suitable for biological applications, e.g., immunoisolation of cells.

Animals↗

Intellectual ability in adolescents with conduct disorder.

A U.K. population of young offenders show the typical deficits in Verbal IQ reported in conduct disordered populations. Performance IQs are generally lower than those of previous studies from the 1970s, raising a question about decline in intellectual ability.

Adolescent↗

Novel polyisobutylene/polydimethylsiloxane bicomponent networks: III. Tissue compatibility.

The tissue biocompatibility of a series of novel rubbery polyisobutylene (PIB)/polydimethylsiloxane (PDMS) bicomponent networks was investigated by in vivo implantation into rats. Bicomponent networks of varying composition (PIB wt%/PDMS wt% = 70/30, 50/50, 35/65) as well as a standard polyethylene control were implanted intraperitoneally. After eight weeks the implants and surrounding tissue were removed for histological evaluation. In all scoring categories (i.e. collagen thickness, fibrous tissue orientation, collagen deposition in muscle tissue, lymphocyte infiltration, angiogenesis) the PIB/PDMS bicomponent network implants elicited either less or similar tissue and cellular response than polyethylene. To determine which implant elicited the least tissue and cellular response overall, a weighted score including collagen thickness, lymphocyte infiltration, and angiogenesis was calculated for each implant. According to these preliminary investigations, PIB/PDMS bicomponent networks are suitable for implant applications.

Abdominal Muscles↗

Evaluation of extended-release applications for solid dispersion hot-melt fluid bed coatings utilizing hydrophobic coating agents.

A new hot-melt fluid bed coating method was evaluated for potential extended-release applications. Chlorpheniramine maleate (CPM) USP was chosen as a model drug. The assays for drug release and content uniformity were dictated by the USP Official Monograph for a Chlorpheniramine Maleate Extended-Release Capsule. The fluid bed chamber was charged with CPM-loaded nonpareils and hydrophobic coating agents in the solid state. The method consists of four processing stages: (a) warming, (b) preheating, (c) melting-spreading, and (d) cooling-congealing. Various hydrophobic coating agent candidates were evaluated for extended-release potential by a preliminary screen at a coating agent level of 1.5% (w/w). A beeswax coating agent was identified as the most promising candidate of the preliminary screen. After the level of beeswax was increased to 2.0%, the dissolution profile met all of the specifications of the USP Drug Release Test 1 for a CPM Extended-Release Capsule. The potency and content uniformity remained unchanged by the process. Dual coatings demonstrated a cumulative extension of release superior to the capability of a single coat. The new method is a viable alternative to hot-melt spray-coating methodologies. Organic solvents, spraying equipment, steam jackets, and/or heating tape are eliminated from the process. A reduction of equipment costs, setup time, and cleanup time may be realized. The method has demonstrated extended-release capabilities. No excessive attrition of potency or content uniformity has been noted. Additive, multiple coatings that have a cumulative effect on release retardation are feasible.

Evaluation Studies as Topic↗

Amphiphilic networks. X. Diffusion of glucose and insulin (and nondiffusion of albumin) through amphiphilic membranes.

Select semipermeable amphiphilic membranes have been prepared and their diffusional characteristics for glucose, insulin, and albumin investigated. The membranes were prepared by cast copolymerization of a hydrophilic monomer (i.e., N,N-dimethyl acrylamide, or N,N-dimethylaminoethyl methacrylate) with the hydrophobic crosslinker methacrylate-ditelechelic polyisobutylene. The products have sufficient mechanical properties for the fabrication of swollen membranes, sheets, tubes, etc. Membranes have been identified which allowed the rapid simultaneous countercurrent diffusion of glucose (Mn = 180 Da) and insulin (Mn = 5733 Da) but did not allow albumin (Mn approximately 60,000 Da) to pass. Evidently, the effective molecular weight cutoff point of these membranes is in the 6-60-KDa range.

Albumins↗

Preliminary assessment of an image analysis method for the evaluation of pharmaceutical coatings.

This article describes the development and preliminary assessment of an innovative image analysis method for the evaluation of pharmaceutical coatings. Nonpareils previously hot-melt coated with a red water-soluble dye incorporated into polyethylene glycol were employed to develop and evaluate the new method. Digital images of batch samples were acquired and transferred to a PC for evaluation by image analysis software. Standard deviations generated for the optical densities of individual nonpareils in each batch sample were utilized to evaluate coating uniformity. Mean optical densities generated for each batch sample were used to evaluate the mean coating thickness. Method precision determinations, using an average sample size of 221 nonpareils, returned a relative standard deviation of 2.47% for coating uniformity and 1.71% for coating thickness. The new method is rapid, objective, and relatively inexpensive. It proved to be both qualitative and quantitative for coating uniformity, qualitative for coating thickness, and maintained a high degree of precision. The method can be used independently or in conjunction with other methods to eliminate their subjective aspects regarding sample selection.

Chemistry, Pharmaceutical↗

Development and optimization of a solid dispersion hot-melt fluid bed coating method.

A new hot-melt fluid bed coating process has been developed, characterized, and optimized. Polyethylene glycol served as the model coating agent and was charged with substrate into the fluid bed chamber in the solid state. The processing stages included: (A) warm-up, (B) preheating, (C) melting-spreading, and (D) cooling-congealing. A central composite design was utilized to characterize and optimize the process. Substrate porosity and density evaluations were conducted by mercury intrusion. The method proved capable of coating nonpareils from 10 to 35 mesh (0.500 to 2.00 mm) and tablets up to 1 g. The nonpareils were coated as individual particles, while particle sizes significantly smaller than 40 mesh (0.420 mm) tended to agglomerate. The porosity and density values of dissimilar nonpareil batches showed a large degree of variation, affecting the method's reproducibility. Additive coatings were achieved by sequential runs using coating agents of diminishing melting points. The method is a viable alternative to hot-melt spray-coating processes. Organic solvents, spraying equipment, steam jackets, and/or heating tape are eliminated from the process.

Drug Compounding↗

Polyisobutylene-toughened poly(methyl methacrylate): III. PMMA-l-PIB networks as bone cements.

A series of novel polyisobutylene (PIB)-toughened poly(methyl methacrylate) (PMMA) networks consist of rubbery PIB domains covalently bonded to a glassy PMMA matrix. Materials containing 8.5-17 wt.% PIB (Mn = 18,000 g/mol) in a PMMA matrix (PIB/PMMA) were evaluated to assess their feasibility as the powder component along with methyl methacrylate (MMA) as the liquid component in a standard powder/liquid bone cement formulation. A standard ISO four-point bend test, commonly used for testing bone cements, was employed to investigate flexural properties. The mixing time and powder/liquid (P/L) ratio were studied to formulate novel PIB/PMMA cements for optimum toughness. Appropriate formulations led to improved toughness while adequate flexural strength and modulus were maintained. An experimental PIB/PMMA-system exhibited approximately 57 MPa flexural strength and approximately 2000 MPa flexural modulus.

Biocompatible Materials↗

A comparison of two insecticidal shampoos in the treatment of head louse infection.

The efficacy and tolerability of a phenothrin liquid shampoo was compared with a carbaryl shampoo in 50 children with head lice infection. Twenty-five children were treated with a phenothrin liquid shampoo and 25 with a carbaryl shampoo. Each treatment was applied on three occasions at three-day intervals. Reinspection two weeks after initiation of treatment revealed two apparent treatment failures in the carbaryl group and one in the phenothrin group. No side effects were reported for either treatment. It is concluded that phenothrin liquid shampoo is a safe and effective treatment for head louse infection and is therefore a useful addition to those insecticides currently employed.

Carbaryl↗

Trapping sheep blowflies using bait-bins.

A bait-bin designed to attract and kill sheep blowflies is described. It is composed of a garbage bin plus lid, attractant and insecticide-treated offal. Fly entry holes are covered with differentiator wire to increase selectivity of kill. Placing bait-bins in preferred habitats of blowflies to optimise kill is outlined and temporal insecticide strategies to increase effectiveness of kill and reduce blowfly resistance are suggested. Preliminary data supporting the effectiveness of bait-bins in reducing blowfly numbers and flystrike in combination with good management practices to reduce sheep susceptibility to flystrike in the arid zone of New South Wales are presented and cost-effectiveness of bait-bins is analysed.

Animals↗

Amphiphilic networks: II. Biocompatibility and controlled drug release of poly[isobutylene-co-2-(dimethylamino)ethyl methacrylate].

Biocompatibility and diffusional characteristics of recently synthesized unique amphiphilic networks, i.e., copolymers of methacryloyl-capped polyisobutylene (MA-PIB-MA) with 2-(dimethylamino)-ethyl methacrylate (DMAEMA) have been examined. Excellent biocompatibility and biostability were obtained after 7 weeks with films containing 53-58% MA-PIB-MA implanted dorsally or abdominally in rats. In contrast, networks with higher or lower MA-PIB-MA contents showed decreased biocompatibility. These amphiphilic networks were also studied as potential implantable drug release systems. Bromophenol blue and folic acid were used as model compounds for drug release. Diffusion of these chemicals from loaded networks into water showed a marked pH dependence. Under specific well-defined conditions (MA-PIB-MA/DMAEMA content, pH, time range) release was observed to be independent of time (zero-order release).

Acrylates↗

The oestrogenicity of equol in sheep.

The effects of intramuscular injection of synthetic racemic equol (+/- 3-(4-hydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-7-ol) into wethers have been examined with respect to maintenance of plasma level, teat growth rate and the activity of the respiratory enzyme glucose-6-phosphate dehydrogenase. At a dose rate of 1.03 mmol/day a steady rise in 'total' (free plus conjugated) equol in plasma occurred to 1.78 mumol/l in 4 days. A dose rate of 2.07 mmol/day produced only a further slight increase in plasma equol. At a lower dose rate of 0.52 mmol/day the plasma concentration reached 0.62 mumol/l in 2 days and this was not exceeded thereafter. At the dose rate of 1.03 mmol/day over 7 days significant increases in teat length and glucose-6-phosphate dehydrogenase activity occurred but no significant changes were observed at the dose rate of 0.52 mmol/day. It appears that threshold levels of intake of equol which maintain a plasma level of about 1.65 mumol/l are needed for oestrogenic effects to become apparent within a relatively short time. Administration of 1.03 mmol/day over 5 days to ovariectomized ewes produced significant increases in uterine weight equivalent to those produced by 92 nmol stilboestrol dipropionate. Thus stilboestrol was apparently 56 000 times more potent than racemic equol.

Animals↗

Fertility studies in young and mature merino ewes 1. Cervical mucus production.

The production of cervical mucus was determined at six-hour intervals during oestrus in young (1(1/2) years old) and mature (3 to 7 years old) Merino ewes. The length of the cervix and the length of the cervical epithelium was also measured in similar ewes. Total weight of mucus secreted as well as secretion rate per unit of time was greater in mature ewes than young ewes. Production was maximal during the first six hours of oestrus and declined considerably after 12 hours in young and 18 hours in mature ewes. The cervix was significantly shorter in young ewes while the length of the cervical epithelium was not significantly different in young and mature. It was concluded that lower mucus production in young ewes is not related to lower mucus output per unit area.

Journal Article↗

Fertility studies in young and mature merino ewes 2. Sperm transport.

Samples of cervical mucus were collected from young and mature ewes at different stages of oestrus. The migration rate of spermatozoa (time taken to travel 410 mm) was not different in samples of mucus from young and mature ewes. Spermatozoa were unable to penetrate the mucus in 7 27 samples, five of which were collected about 16 hours after onset of oestrus. Migration rate in samples collected between 10 and 16 hours after onset of oestrus was significantly slower than in samples collected in the first five hours of oestrus. The transport of spermatozoa in young and mature ewes was also studied by observing distribution of spermatozoa in the female genital tract 26 to 27 hours after hand-mating. There were no significant differences between young and mature ewes either in mean sperm count or in variation of mean sperm numbers in all sections of the tract.

Journal Article↗

Ovarian follicles of new-born Merino lambs from genetic lines which differ in fecundity.

Ovaries were obtained from 78 new-born lambs (12 singletons, 25 twins, 28 triplets, 10 quadruplets and 3 quintuplets) from flocks selected for (T902, T903 and Booroola) or against (O) multiple births. Sections of the ovaries were examined with a projection microscope and the numbers of all types of follicles were estimated. There were no differences between genetic lines in the number of primordial follicles, after adjustment for litter size and sire; however, there were significantly more of these follicles in single-born lambs than in lambs born in litters of two or more within genetic lines. The number of vesicular follicles was lower in Booroola than in O lambs.

Animals↗