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Biomedical subjects

J Hickey

Publications and source records attributed to J Hickey.

At least 19 recordsLinked to original sources

Optimization of cutaneous electrically mediated plasmid DNA delivery using novel electrode.

The easy accessibility of skin makes it an excellent target for gene transfer protocols. To take advantage of skin as a target for gene transfer, it is important to establish an efficient and reproducible delivery system. Electroporation is an established technique for enhancing plasmid delivery to many tissues in vivo. A critical component of this technique is the electrode configuration. Electroporation parameters were optimized for transgene expression with minimal tissue damage with a novel electrode. The highest transgene expression and efficiency of individual cell transformation with minimal damage was produced with eight 150 ms pulses at field strength of 100 V/cm. This electrode design offers the potential for easier and more reproducible electrically mediated cutaneous plasmid delivery than the simple electrodes currently commercially available. This electrode can be a valuable tool in determining the applicability of electrically mediated cutaneous gene transfer.

Animals↗

Characteristics of blast furnace slag leachate produced under reduced and oxidized conditions.

A laboratory study was conducted to determine the environmental conditions necessary to reproduce leachates observed emerging from blast furnace slag acting as the foundation of highways in northwest Indiana. The leachates in the field are often highly alkaline with a pungent sulfur odor, a distinct green or milky-white in color, and sulfate concentrations exceeding 2,000 mg/L. Slag was equilibrated in the laboratory under both oxidized and anoxic environments and at various slag:water ratios. Constant anoxic conditions were required to produce to green colors in the slag, but high sulfate concentrations were observed only when the suspensions were fully oxidized. Leachate from the study site appears to form as a result of a series of complex chemical reactions including fluctuating oxidized and reduced conditions.

Adsorption↗

Genetic aspects of growth of Holstein-Friesian dairy cows from birth to maturity.

In general, genetic selection is applied after first calving to traits that manifest themselves during the animal's productive life, mostly during the early part of productive life. This selection policy has had undesirable correlated responses in other economically important traits, such as health and fertility, and may also have had an effect on the growth of animals both during productive life and before first calving. In this study, we analyzed the growth trajectory of dairy heifers that had been selected for maximum production of combined fat and protein (measured in kg; select line) or for average production (control line) in the United Kingdom. Before first calving, these divergent lines were managed as a single group. Select line heifers grew faster than did control line heifers. They were also heavier at first calving, but by the end of 3 lactations, the lines were not significantly different in live weight. Selection primarily for yield and for other traits has led to heifers that grow faster and reach higher growth rates earlier in life. A genetic analysis of birth, weaning, and calving weights yielded heritability estimates of 0.53 (birth weight), 0.45 (weaning weight), and 0.75 (calving weight). Confidence intervals for the genetic correlations between the traits indicated that these BW traits are not under the same genetic control.

Aging↗

Comparisons of PBDE composition and concentration in fish collected from the Detroit River, MI and Des Plaines River, IL.

Polybrominated diphenyl ethers (PBDEs) were identified in fish collected from the Detroit River, MI and Des Plaines Rivers, IL. In the Detroit River fish, carp and large mouth bass, the congener patterns were dominated by the 2,2',4,4'-tetrabromo (BDE-47) congener, however, in Des Plaines River carp the dominant isomers were the heptabromo congeners BDE-181 and BDE-183 and lesser amounts of another heptabromo congener, BDE-190, and two hexabromo congeners, BDE-154 and BDE-153. Three possible sources exist for these less-commonly identified PBDE congeners: (a) waste discharge from manufacturing or discarded products near the river, (b) public owned treatment work (POTW) effluents which constitute more than 75% of the flow in the Des Plaines River, (c) or formation of these congeners by debromination of in-place deposits of decabromodiphenyl ether. Average concentration totals (sum of concentrations for seven of the dominant PBDE congeners) were similar on a wet weight bases for the carp (5.39 ng/g wet weight) and large mouth bass (5.25 ng/g) in the Detroit River samples; however, the bass were significantly higher, p = 0.01, when compared on a lipid basis (bass--163 ng/g vs. carp--40.5 ng/g lipid weight). Some of the PBDE congeners were positively correlated with increasing lipid levels in both fish species. Average total PBDE concentrations in the carp from the Des Plaines River (12.48 ng/g wet weight) were significantly higher, p = 0.01, than in carp from the Detroit River. The residues were isolated using standard organochlorine methods for fish and analyzed using gas chromatography/mass spectrometry-negative chemical ionization methods.

Animals↗

Toxicity of anticancer agents mediated by electroporation in vitro.

Electroporation is a physical event that temporarily reduces cell membrane barrier properties. Diminished membrane barrier properties are achieved by exposing cells to pulsed electric fields. When a cell has been treated with electric fields it is possible for extracellular agents to gain access to the cell interior. This process has been used in vivo to increase the uptake of chemotherapeutic agents by tumor cells which results in dramatically higher response rates than when drug is used alone. This type of treatment is called electrochemotherapy (ECT); bleomycin is most often used as the drug for this type of treatment. It was hypothesized that electroporation could be used to augment the cytotoxicity of other anticancer agents. Therefore, this study was performed in order to screen 44 different combinations of drug and cell type in vitro to identify drugs that may have higher cytotoxicity when combined with electroporation. Results from seven cell types indicate that the IC50 of bleomycin can be reduced by a factor of 100-5000 when electroporation is used to facilitate internalization. The IC50 values of cisplatin and carboplatin could be reduced by factors ranging from 3 to 13 in six different cell lines as a result of electroporation. These IC50 reductions in multiple cell lines suggest that cisplatin and carboplatin may be effective in vivo as part of ECT treatment.

Antineoplastic Agents↗

Properties of an enzyme-based low-level iodine disinfectant.

An enzyme-based iodine (EBI) disinfectant that continuously generates free molecular iodine in a controlled fashion was developed and evaluated for use in disinfecting flexible fibreoptic endoscopes (FFEs). EBI is a powder concentrate that produces iodine from sodium iodide and calcium peroxide when catalyzed by horseradish peroxidase. After dissolution in water, it delivers relatively high concentrations of free molecular iodine (> 15 ppm) at relatively low concentrations of total iodine (30-40 ppm). It demonstrates the ability to function as an effective low level iodine disinfectant by rapidly inactivating bacteria, fungi and viruses. A unique feature of the EBI system is the ability to reoxidize reduced iodine which results in a constant level of active (free molecular) iodine during use. EBI inactivates Mycobacterium bovis var BCG more rapidly than 2% glutaraldehyde (Cidex-7). Its sporicidal activity, however, was found to be slower than the aldehyde formulation. The qualification of EBI for use as a practical disinfectant was shown by its negligible toxicity in dermal, ocular, oral and inhalation studies on animals, which is attributed to the low level of total iodine in the solution.

Animals↗

Control of the amount of free molecular iodine in iodine germicides.

Horseradish peroxidase has been used to generate iodine compositions that comprised principally free molecular iodine. The concentration of free molecular iodine in these enzyme-based compositions ranged from 44 to 63% of the thiosulphate titratable iodine; this is substantially higher than the corresponding value for the povidone-iodine preparation betadine. The biocidal efficacy of these compositions was proportional to the concentration of free molecular iodine. Iodine compositions with relatively low total iodine concentrations but high levels of free molecular iodine (20-175 ppm) killed Staphylococcus aureus and spores of Bacillus subtilis more rapidly than betadine. The effects of normal saline and these enzyme-based iodine compositions on the rate of epidermal regeneration in superficial swine wounds were comparable. These results suggest that an effective germicide containing a high level of molecular iodine need not be irritating or toxic.

Animals↗

Derbyshire thirteen working together.

A group of 13 practices from Derbyshire saw the QDAs as a chance to improve upon their total service quality. Working in groups, and with their FHSA, they succeeded in improving their service and empowering their practice teams.

Adult↗

The dosimetry of iodine-123-labeled TISCH: a SPECT imaging agent for the D1 dopamine receptor.

TISCH is an iodinated D1 specific dopamine receptor antagonist that may be useful as a SPECT imaging agent. This report documents its pharmacological safety in animals and its radiation dosimetry in humans. The dose of radiation that 123I-TISCH delivered to seven healthy subjects was estimated with the absorbed fraction technique. Conjugate images of the body were serially acquired for up to 24 hr after the administration of a known amount of activity. The count rates in the organs that could be visualized were measured on each image. These count rates were corrected for attenuation with 123I transmission scans. The doses to the other organs that did not take up enough activity to be visualized on the images were estimated with established models. The dosimetry was calculated for each subject individually before the results were averaged. Rapid biological washout minimizes the radiation exposure to most organs. The dose to the large bowel is limiting in healthy volunteers. The proximal colon receives about 0.67 rad/mCi (180 microGy/MBq) or about 5 rads for every 7.5 mCi of TISCH injected. This low radiation burden should make it feasible to study the D1 dopamine receptor in patients who have neuropsychiatric disorders before and after treatment.

Adult↗