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Biomedical subjects

R E Davies

Publications and source records attributed to R E Davies.

At least 19 recordsLinked to original sources
PubMed2006

Neurodegenerative actions of interleukin-1 in the rat brain are mediated through increases in seizure activity.

The cytokine interleukin-1 (IL-1) is an established and important mediator of diverse forms of neuronal injury in experimental animals. However, its mechanisms of action remain largely unknown. We have reported previously that IL-1 markedly enhances excitotoxic injury induced in the rat by striatal administration of the excitotoxin alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), leading to widespread neuronal loss throughout the ipsilateral cortex. Here we tested the hypothesis that IL-1 causes this injury through induction and/or enhancement of seizure activity in the rat. Consistently with this hypothesis, intrastriatal injection of AMPA or AMPA with IL-1 in the rat brain increased c-Fos expression in regions similar to those in which c-Fos has been reported previously in response to seizures. A significant increase in cortical neuronal activity (number of c-Fos positive cells) was observed in response to AMPA with IL-1 compared with AMPA (8 hr after injection). Increased seizure duration [3,522 +/- 660 sec (SEM) vs. 1,415 +/- 301 sec; P < 0.001] and cell death volume (140 +/- 20 mm3 vs. 52 +/- 6 mm3; P < 0.001) were seen in response to coinfusion of AMPA with IL-1 vs. AMPA alone. In addition, the anticonvulsant diazepam (intraperitoneal) significantly reduced cell death (P < 0.001) and seizure duration (P < 0.001) induced by AMPA with IL-1, and a significant correlation was found between seizure duration and cell death volume. These findings support our hypothesis that IL-1 enhances excitotoxic injury by enhancement of seizures, which may be of relevance to IL-1 actions in other forms of neuronal injury, including cerebral ischemia.

Analysis of Variance↗
PubMed1998

A comparison of the effects of capsaicin with inhibitory nerve stimulation in the rat anococcygeus muscle in vitro.

Capsaicin was used to test whether centrifugal activation of sensory fibres in the rat anococcygeus muscle can contribute to non-adrenergic non-cholinergic (NANC) relaxation of the muscle. In a solution containing 0.5 mM Ca2+ and in the presence of carbachol (10 microM) capsaicin evoked a fast concentration-dependent relaxation of the muscle that was usually followed by a smaller, slower, relaxant response. The fast relaxant response was reduced when extracellular Ca2+ was raised to 2.5 mM, desensitized after a single application of capsaicin and was blocked by tetrodotoxin (1 microM) or ruthenium red (10 microM). The fast response was greatly reduced by haemoglobin, by cold storage of the muscles or by N-monomethyl-L-arginine (100 microM) in the absence but not in the presence of L-arginine (100 microM). It is concluded that centrifugal activation of sensory fibres evokes a nitric oxide-mediated relaxation of the anococcygeus muscles that probably contributes to electrically evoked NANC relaxation.

Animals↗
PubMed1998

A selective Pt-CdS photodiode to monitor erythemal flux.

The design and potential benefit of a solar ultraviolet (UV) radiometer reporting a maximum instantaneous flux of erythemally weighted heterogeneous energy is considered. The proposed device is electronically peak detecting; the user would ideally 'point and paint' the sun to find a localized maximum. A projected exposure time can be calculated from an instantaneous reading of erythemally weighted flux for a given minimal erythemal dose (MED) specified by the user. This calculation, though not necessarily providing a true exposure time, may be useful and informative in that it serves as a more 'recognizable' measure of erythemal flux and introduces a custom scale for each individual via their MED. Erythemal flux is calculated as the weighted integral sum [symbol: see text]j(lambda,t) epsilon(lambda) d lambda, where j (lambda, t) is the instantaneous angular integrated spectral irradiance accepted by human skin. This instrument proposal uses a single interference filter over a Pt-CdS photodiode; the interference filter is offered as a nominal design transmittance. The simulated response of the selective photodiode has a near-linear relation to the effective irradiance. Test inputs for evaluation purposes and to elucidate a transducer response are constructed from a spline interpolation of the World Radiation Center (WRC) spectrum and classic transmittance models. Our desired erythemal flux is offered in interconvertible UV Indexes (UVIs) as a function of zenith angle and atmosphere, characterized by elevation, ozone path, and turbidity.

Cadmium Compounds↗
PubMed1993

Wavelength dependence of skin cancer induction by ultraviolet irradiation of albino hairless mice.

Information on the variation in carcinogenicity with wavelength is crucial in risk assessments for skin cancers induced by UV radiation. Until recently the wavelength (lambda) dependencies of other detrimental UV effects, such as sunburn, have been used as substitutes. Direct information on the lambda dependency can only be obtained from animal experiments. To this end we accumulated a large data set on skin tumors induced by chronic UV exposure of albino SKH:HR1 mice (14 different broadband UV sources and about 1100 mice); the data come from the Photobiology Unit of the former Skin and Cancer Hospital in Philadelphia and from the Department of Dermatology of the University of Utrecht. The lambda dependency was extracted from this data set (a statistically satisfactory description with chi 2 = 13.4, df = 7) and represented by the Skin Cancer Utrecht-Philadelphia action spectrum, i.e., a set of factors to weight the exposures at different wavelengths according to their respective effectiveness (inversely proportional to the daily exposure required for a median tumor induction time of 300 days). The fits obtained with other already available action spectra proved to be poor (chi 2 > 60, df = 11). The maximum effectiveness was found at 293 nm, and above 340 nm the effectiveness showed a shoulder at about 10(-4) of the maximum. A sensitivity analysis of the final solution for the lambda dependency showed a large margin of uncertainty above 340 nm and an information gap below 280 nm. The large variation in tumor responses in the present data set can be transformed to a coherent, common dose-response relationship by proper spectral weighting with this single action spectrum.

Animals↗
PubMed1991

All the observed universe has contributed to life.

This paper presents evidence that virtually all electrons and nuclei of the atoms that are or have been part of living matter on Earth came from almost all stars in our and nearby galaxies and even from all other galaxies in the Universe that have produced observed high-energy gamma rays. However, a standard 70 kg human is always making about 7 3He, 600 40Ca, and 3000 14N nuclei every second by radioactive decay of 3H, 40K, and 14C, respectively.

Animals↗
PubMed1991

Breath-by-breath measurement of oxygen consumption and FIO2-FEO2 with increased oxygen demand.

Continuous on-line breath-by-breath measurement of pulmonary gas exchange was used to monitor the increase in oxygen uptake (VO2) and carbon dioxide excretion (VCO2) induced by the oxidative phosphorylation uncoupling agent 2, 4-dinitrophenol (DNP) in 10 dogs. With incremental doses of DNP totaling 5 mg/kg, the continuously monitored VO2 increased within 2-3 min after the first injection of the drug. VCO2 showed a similar response 4-6 min after the first injection. Temperature increase due to the pharmacological oxidative phosphorylation uncoupling required 20-30 min for a discernible change at this dose. This study also demonstrated a modified and compromised response to the drug in dogs where oxygen delivery was limited by mechanical ventilation.

Animals↗
PubMed1989

Fibre types in Limulus telson muscles: morphology and histochemistry.

Using a variety of techniques, we have demonstrated the presence of at least two fibre types in Limulus median telson levator muscle. By light and electron microscopy, large (2,156 microns 2 mean cross-sectional area) fibres have A-bands of 4.1 microns, one-half I bands of 2.15 microns and Z lines less than or equal to 0.5 microns in width. Few mitochondria are found in these fibres, which comprise 54% of those present in a given microscope field and which occupy 82% of the total cross-sectional area. Small fibres (484 microns 2 mean cross-sectional area) have A bands of 6.3 microns, one-half I bands of 3.1 microns and Z lines between 0.5 and 1.0 microns in width and are rich in mitochondria. Although small fibres comprise nearly one-half (46%) of the fibres in a field, they occupy only 18% of the total cross-sectional area. Histochemical staining for alkaline-stable myofibrillar ATPase activity and mitochondrial reduced beta-nicotinamide adenine nucleotide (beta-NADH) tetrazolium reductase activity confirms the presence of two fibre types. The large fibres react positively for the myofibrillar ATPase activity and negatively for the mitochondrial enzyme activity. The reverse is seen with the small fibres. Some fibres of intermediate size, having intermediate staining characteristics, were also observed. Native gel electrophoresis of both myofibrillar and purified myosin preparations supports the observed differences in myofibrillar ATPase activity in that two myosin isozymes are resolved on pyrophosphate gels. Although the thick filaments isolated from unstimulated small fibres are longer (greater than 6.0 microns) than those isolated from unstimulated large fibres (4.26 microns), all have a similar appearance with respect to the arrangement of myosin heads on their surfaces, and similar diameters. The implications of the observed heterogeneity of fibre types is discussed with reference to previously reported phenomena in Limulus telson muscle, including changes in length of thick filaments on fibre stimulation and the shape of the length-tension curve obtained from fibre bundles.

Animals↗
PubMed1989

Narrow-band UV radiation and induction of dermal elastosis and skin cancer.

A narrow-band UV light source with emission peaks at 292, 300, 307, 317, and 336 nm was developed and used to irradiate whole cages of hairless mice. The purpose was to obtain experimental information on the action spectrum for photocarcinogenesis and dermal elastosis. Groups of 20 mice were irradiated with 500 J/m2 daily, 5 times per week during one year. The total dose was 130 kJ/m2. All mice irradiated with 292 nm and 300 nm developed squamous cell carcinomas. None in the other groups developed malignant skin tumors. Elastosis was estimated quantitatively. The elastic fibers covered 3% of a representative microscopic section of dermis in the control group. In the groups irradiated with peaks at 336 nm, 317 nm, 307 nm, 300 nm, and 292 nm the corresponding percentages were 6%, 13%, 28%, 32%, and 36%, respectively. The shorter the wavelengths the more pronounced was a subepidermal zone replacing the elastotic tissue to the deeper dermis. This zone stained corresponding to a content of glycosaminoglycans (GAG), sulphated GAG, hyaluronic acid, mature collagen, and new reticulin.

Animals↗
PubMed1987

Toxicity of 8-methoxypsoralen, 5-methoxypsoralen, 3-carbethoxypsoralen, or 5-methylisopsoralen with ultraviolet radiation in the hairless (HRA/Skh) mouse.

An experimental design to simulate PUVA therapy (oral 8-methoxypsoralen followed by uv radiation) has been tested in a 13-week subchronic study to determine the relative toxicities of 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), 5-methylisopsoralen (5-MIP), and 3-carbethoxypsoralen (3-CEP) in inbred hairless mice (HRA/Skh). Drug was administered by 1-hr pulse feedings three times a week after mice were fasted overnight; individually housed animals were then exposed to uv radiation (320-400 nm; less than 2% output less than 320 nm). 8-MOP or 5-MOP administered orally (at doses of approximately 240 or 480 mg/m2 body surface area per week) followed one-half hour later with uv radiation of 2 J/cm2 for 13 weeks were found to cause skin toxicity including inflammation, hyperplasia, ulceration, and cellular atypia. Dose-related toxicity was not seen in other organ systems. Corresponding levels of 5-MIP or 3-CEP with uv radiation did not produce skin toxicity. These studies show that the psoralens with two potential DNA-binding sites (8-MOP and 5-MOP) were more toxic than psoralens with only one photoreactive site (5-MIP and 3-CEP).

5-Methoxypsoralen↗
PubMed1986

Ocular effects of treatment with various psoralen derivatives and ultraviolet-A (UVA) radiation in HRA/Skh hairless mice.

Hairless (HRA/Skh) mice were administered one of four dietary concentrations (50, 100, 625 or 1250 ppm) of 8-methoxypsoralen (8-MOP) or 5-methoxypsoralen (5-MOP), or molar equivalent concentrations of 5-methylisopsoralen (5-MIP) or 3-carbethoxypsoralen (3-CPS) by 'pulse feeding' technique, 3 days per week for 13 weeks. For the final 11 weeks psoralen derivative administration was followed by exposure to 0.2 or 48 J/cm2 of unfiltered ultraviolet-A (UVA) radiant energy from FR74T12PUVA lamps. At 0 and 13 weeks eyes were dilated with 0.2% atropine solution and were examined using a binocular indirect ophthalmoscope with a +20.0 D condensing lens. The lids, cornea, anterior chamber and the lens were evaluated for pathological changes. Ocular damage consisting of dense central corneal opacification was seen at significant levels in animals given 8-MOP or 5-MOP and exposed to UVA. In addition, opacities in the area of the posterior lens were seen in all experimental groups and appeared to be related to drug treatment, independent of light exposure, and therefore appeared not to be related to drug-light interaction. Some corneal and lenticular opacification was seen at non-significant levels in all experimental and control groups.

5-Methoxypsoralen↗
PubMed1985

Effect of indoor lighting on normal skin.

A small but measurable component of some indoor lighting is ultraviolet radiation (UVR); whether it is sufficient to modify the indoor worker's risk for chronic skin changes is not directly answerable with available technology. A first approach to this question involves a) estimating a range of annual background solar exposure for indoor workers currently at risk; b) determining whether, and at what levels, UVR exposure is a part of specified indoor lighting; and c) calculating the increment in risk implied by a and b. This algorithm predicts that some lighting conditions that meet NIOSH recommended standards would still result in significant increases in the risk of cumulative UVR damage, including skin cancer. More information concerning actual exposure conditions, the relation of spectral effectiveness for luminosity and UVR production, and dose-time reciprocity are required to improve our predictions of long-term cutaneous effects of indoor lighting.

Erythema↗