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Biomedical subjects

D M White

Publications and source records attributed to D M White.

At least 73 records · Page 4Linked to original sources
PubMed1988

The bradykinin-induced release of substance P from nerve fibre endings in the rat saphenous nerve neuroma is not related to electrophysiological excitation.

It has previously been shown that electrical stimulation of a peripheral nerve induces a release of substance P (SP) from cutaneous nerve terminals. In this study, we investigate whether SP is released from nerve fibre endings in experimentally induced rat saphenous nerve neuromas. The neuromas were induced in pentobarbital anaesthetized rats by ligating and cutting the saphenous nerve 5 weeks prior to the release experiments. The 5-week-old neuromas were desheathed, placed in a perspex chamber, in situ, and superfused with Tyrode solution. The SP-like immunoreactivity (SPLI) content of the superfusate was measured by radioimmunoassay. Addition of 90 microM bradykinin to the superfusate resulted in a calcium-dependent release of SPLI. The other inflammatory mediators, histamine and serotonin, did not induce a release of SPLI. Furthermore, repetitive electrical stimulation of the saphenous nerve (50 V, 5 Hz, 0.5 ms) or superfusion of the neuroma with 50 microM veratridine or 40 mM K+ also failed to induce a release of the peptide. The release of SPLI, induced by bradykinin, from nerve fibre endings in the rat cutaneous nerve neuroma, appears to involve a neurochemical interaction that is independent of electrophysiological excitation.

Animals↗
PubMed1988

Effects of chronic exposure to ozone on collagen in rat lung.

Pulmonary fibrosis is a consequence of severe injury from some toxic agents including high doses of ozone. It is not known, however, whether chronic exposure to low doses of ozone, such as those encountered in polluted ambient atmospheres, could also result in abnormal accumulations of lung collagen. Rats were exposed to ozone for 20 hr per day, 7 days per week for 3, 6, 12, and 18 months at concentrations of 0.12, 0.25, or 0.50 ppm. Controls were exposed under identical conditions to purified air. Upon removal from the chambers, rats were euthanized and lung tissue slices incubated with [14C]proline. The incorporation of 14C into hydroxyproline and the total hydroxyproline content of lung tissue were measured as estimates of lung collagen synthesis and content, respectively. The formation of labeled hydroxyproline tended to decrease significantly with time in controls and at the three ozone doses. There were, however, no significant dose-related changes at any of the time points tested. Total lung hydroxyproline increased with age in all groups, but no dose-related changes were detected at any time point. It was concluded that chronic exposure of rats to ozone at concentrations which approximate ambient urban concentrations did not affect normal age-related changes in either synthesis or accumulation of lung collagen.

Animals↗
PubMed1987

Substance P modulates the release of locally synthesized nerve growth factor from rat saphenous nerve neuroma.

In saphenous nerve neuromata of adult rats a long-term increase of immunoreactive nerve growth factor (irNGF) was detected after nerve transection. The occurrence of messenger RNA encoding NGF (NGF mRNA) in these proximal nerve stumps indicates local biosynthesis of NGF. In situ superfusion of neuromata revealed a constant release of irNGF which was significantly reduced by substance P (SP) but not affected by calcitonin gene related peptide (CGRP). We therefore suggest that SP may modulate the availability of NGF in the microenvironment of the regenerating nerve fiber endings.

Animals↗
PubMed1987

DNA synthesis in pulmonary alveolar macrophages and type II cells: effects of ozone exposure and treatment with alpha-difluoromethylornithine.

An increase in the number of pulmonary alveolar macrophages (AM) can be induced by a number of toxic insults to the lung, including ozone, an important photochemical oxidant air pollutant. This increase could arise from an influx of monocytes from the vascular or interstitial compartments, or from proliferation of AM in situ. While proliferation of alveolar type II cells after oxidant exposure has been well documented, it is not clear whether AM are also capable of this response. Rats were exposed to air or to 0.12, 0.25, or 0.50 ppm ozone for 1, 2, 3, 7, or 14 d, 20 h/d. The labeling index in both AM and type II cells increased about 10-fold after 2 d of exposure to 0.25 and 0.50 ppm of ozone, but returned to control levels by the end of 1 wk of exposure. These changes closely paralleled the temporal and dose-response characteristics of changes in total lung DNA synthesis. alpha-Difluoromethylornithine (DFMO) administered to rats during a 2-d exposure to 0.50 ppm ozone did not inhibit the ozone-induced increase in labeling index in AM or type II cells, although evidence of inhibition of lung ornithine decarboxylase activity was obtained, and the ozone-induced increase in total lung DNA synthesis was inhibited by 23%. These results suggest that, like type II cells, AM are capable of entering the cell cycle and synthesizing new DNA in situ in response to short-term exposure to environmentally relevant doses of ozone, and that the ozone-induced stimulation of DNA synthesis in these cell types was refractory to inhibition by DFMO.

Animals↗
PubMed1986

Diet-induced alterations in theobromine disposition and toxicity in the rat.

To assess the potential influence of diet on theobromine (TBR) disposition and the development of TBR-induced thymic and testicular toxicity, male Sprague-Dawley rats were given the following diets ad libitum for 28 days: (1) semipurified (S); (2) commercial chow (Ch); (3) semipurified + 0.6% TBR (S + TBR); or (4) commercial chow + 0.6% TBR (Ch + TBR). Toxicity endpoints determined in each TBR group indicated that Ch + TBR-treated animals did not exhibit the marked reduction in body weight or testicular atrophy induced by the S + TBR diet, although thymic weight was lower regardless of diet. Metabolic studies performed after the 28-day feeding period using 5 mg/kg TBR + 10 microCi [8-14C]TBR revealed an overall inductive effect of Ch on TBR metabolism as shown by increased urinary excretion (0-24 hr) of the major TBR metabolite, 6-amino-5[N-methylformylamino]-1-methyluracil (6-AMMU), as well as 7-methylxanthine + 3-methylxanthine (7-MX + 3-MX) and 3,7-dimethyluric acid (3,7-DMU). Consumption of 0.6% TBR for 28 days in either S or Ch diets also induced its own metabolism, as shown by decreased urinary excretion of unchanged TBR and increased conversion primarily to 3,7-DMU. Fecal 14C elimination (0-24 hr) was similar between animals fed S and Ch diets, indicating no effect of control diet on TBR bioavailability. Since serum TBR concentrations and overall toxicity were lower in Ch + TBR-treated animals than in S + TBR treated animals, yet TBR bioavailability was similar, this effect was attributed to the inducing potential of the Ch diet on TBR metabolism and clearance. Investigators are cautioned to consider the potential effect of diet on metabolism when performing and evaluating toxicological studies.

Animals↗
PubMed1985

Release of substance P from peripheral nerve terminals following electrical stimulation of the sciatic nerve.

Substance P is a putative mediator of neurogenic inflammation, where it is postulated to be released from nerve terminals in the skin in response to noxious and electrical stimulation. To demonstrate release of substance P from cutaneous nerve terminals a blister model has been established. Electrical stimulation of the sciatic nerve for 20 min at 50 V, 15 Hz, 0.5 ms, resulted in a significant increase in substance P-like immunoreactivity (SPLI) in blister fluid, which was abolished after neonatal pretreatment of rats with capsaicin. There was no increase of SPLI, following stimulation of the sciatic nerve at 4 V. There was a corresponding decrease in skin SPLI following nerve stimulation at 50 V. Characterization of blister fluid SPLI after stimulation at 50 V demonstrated a peak of immunoreactivity, which co-eluted with synthetic substance P and SPLI from rat skin. These results confirm the hypothesis that electrical stimulation results in release of substance P from nerve terminals in the skin, and therefore fulfils an important criterion of its role as a mediator of neurogenic inflammation.

Animals↗
PubMed1985

Neurogenic inflammation in skin blisters.

The histology of blisters induced in rats using dry-ice or vacuum applied to the hind limb footpad has been examined by light microscopy and indirect fluorescence immunohistochemistry for substance P like immunoreactivity. The effects of sciatic nerve stimulation on plasma extravasation as determined by estimation of Evans Blue content of blister fluid has been examined. Plasma extravasation occurs in both blister types following nerve stimulation. Plasma extravasation may be induced by substance P released from nerve terminals in the blister wall. Vacuum induced blisters have less tissue and nerve damage and therefore less of an inflammatory response, but plasma extravasation is greater in thermal blisters. Blisters serve as a useful model for the study of neurogenic inflammation.

Animals↗
PubMed1984

Dominant lethal testing of theobromine in rats.

Theobromine (TBR) 3,7-dimethylxanthine, the major purine alkaloid present in chocolate and cocoa products, was evaluated for dominant lethality in male Sprague-Dawley rats after administration of subacute oral doses of 0, 50, 150 and 450 mg/kg. Dominant lethal mutations were assessed weekly for a 10-week period by killing the females 13 days after the midweek of presumptive mating with treated males and counting total implants (living and dead), corpora lutea and number of pregnant females. Dead implants per total implants and preimplantation loss per total corpora lutea were evaluated statistically. No significant dose-dependent effects were observed in the % dead implants of preimplantation loss throughout the study; pregnancy rate averaged 94%. These results indicated no induction of dominant lethal mutations or adverse effects on pregnancy rate after TBR doses equivalent to 25-225 times the maximum human consumption level.

Animals↗