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Biomedical subjects

A Poole

Publications and source records attributed to A Poole.

At least 55 records · Page 3Linked to original sources

Comparison of the toxicity of orally administered L-triiodothyronine (T3) in rat and cynomolgus monkey.

Oral administration of L-triiodothyronine (L-T3) (0.015-1 mg/kg) for 30 days to mature rats or cynomolgus monkeys resulted in both species in a high mortality at 1 mg/kg (after 2 weeks of treatment) and a progressive loss in body weight. Dose-related elevations in plasma marker enzymes occurred, mainly after 1-2 weeks of treatment. The approximate no-effect dose for these changes was around 0.015-0.020 mg/kg for both rat and primate. The large elevations of leucine aminopeptidase (LAP) at 1 mg/kg L-T3 in monkey indicated hepatocellular toxicity although in the rat such large increases in alanine aminotransferase (ALT) and glutamate dehydrogenase (GLDH) were not seen. L-T3 also showed little toxicity to rat hepatocytes in vitro. High concentrations of L-T3 (7 x 10(-9) to 7 x 10(-7) M) had minimal effects on parameters of cell viability such as lactate dehydrogenase (LDH) leakage, chromium-51 release and [3H]leucine incorporation. Urinary enzymes in the rat showed a similar profile to those in plasma. Large rises in alkaline phosphatase (AKP) and N-acetyl glucosaminidase (NAG) at 1 mg/kg indicated possible proximal tubular damage although this was not supported histologically. Clinically, in both species L-T3 appeared more toxic to males than females but this was not supported histologically. The histological lesions observed were different in the 2 species. In the monkeys there was extensive lipid vacuolation of hepatocytes and changes in thyroid and adrenal cortex. In the rat there was fine, non-lipid vacuolation of hepatocytes and thyroid changes. In the rat, 2 previously unreported lesions were also noted. There were multinucleated cells in the renal distal tubular epithelium, and focal fibroplasia of serosal surfaces of abdominal viscera.

Acetylglucosaminidase↗

Use of general anesthesia in dental care of the child with sickle cell anemia. A case report.

This article reviews the clinical manifestations of sickle cell anemia and describes the dental management, with the use of general anesthesia, of a child affected by the disease and exhibiting some of its complications. The discussion stresses the vital importance of awareness of the possible complications of sickle cell anemia and sickle cell trait in the safe and successful management of patients requiring dental care that includes the use of general anesthesia.

Anemia, Sickle Cell↗

Changes in the morphology and synthetic activity of cultured rat tail tendon.

Isolated single fascicles from tail tendons of young rats were freed of epitenon cells and cultured in vitro for up to 7 days. The tissue remained viable, as judged by the structural integrity of cell organelles and the ability to synthesize DNA and glycosaminoglycans (GAG). The rate of DNA synthesis peaked after 2 days in culture and decreased slowly thereafter. Concomitantly, an increase in cell number was noted at the periphery of the fascicle. GAG production also increased during culture, sulphated GAG being increased proportionately more than hyaluronic acid. Dermatan sulphate was the predominant sulphated GAG in freshly isolated fascicles, but in cultured tissue, the newly synthesized sulphated GAG was more sensitive to degradation by chondroitinase AC and had an increased electrophoretic mobility. fine structural changes were observed in cultured tissues such as the retraction of cell processes. rounding up of cell bodies and the appearance of gaps between collagen fibrils. Cultured tenocytes also frequently contained apparently phagocytized collagen fibrils which were not seen in freshly isolated fascicles, and this appearance was suggestive of collagen degradation occurring in vitro, although no change in the total hydroxyproline content was noted. The data show that when individual fascicles are cultured in vitro they undergo a process of matrix remodelling which has features in common with events occurring in vivo when tendons have been surgically manipulated.

Animals↗

Malignant hyperthermia.

The increasing use of intravenous and inhalation sedation in the dental office has the potential of increasing the incidence of malignant hyperthermia (MH) in susceptible subjects. The object of this article is to present two cases of MH and to discuss its pathophysiology, its clinical picture, and its management in the light of the current literature. Stringent screening procedures should be adopted and maintained in order to channel suspected cases to appropriate centers for expert consultation and management. It is further advocated that a program of education for patients and their families be instituted, as it is an essential prerequisite of effective prophylaxis.

Child↗

In vitro release of arachidonic acid and in vivo responses to respirable fractions of cotton dust.

It was considered that the fall in lung function seen after exposure to cotton dust may be attributable in part to the activity of arachidonic acid metabolites, such as leucotrienes as well as to the more established release of histamine by cotton dust. However, we found that cotton and barley dusts elicited poor release of arachidonic acid from an established macrophage like cell line compared with that observed with other organic dusts. In the experimental animal, pulmonary cellular responses to both cotton and barley dust were similar to those evoked by moldy hay and pigeon dropping dusts, although after multiple doses a more severe response was seen to cotton and barley. Since both moldy hay and pigeon droppings elicit a greater arachidonic acid release than cotton or barley, a role for arachidonic acid in inducing the cellular response is less likely than other factors. There are limitations to our conclusions using this system, i.e., the arachidonic acid may be released in a nonmetabolized form, although it is noted that the two dusts with the greatest arachidonic acid release produce their clinical responses in humans largely by hypersensitivity mechanisms.

Animals↗

The in vitro activities of a highly carcinogenic mineral fibre--potassium octatitanate.

The in vitro activities of a highly carcinogenic potassium octatitanate fibre (Fybex) have been investigated. This material caused a low level of in vitro transformation in C3H10T1/2 cells and is thus more active in this assay than the UICC amphibole asbestos samples but less active than fibrous erionite. This ranking is in accord with carcinogenicity in vivo. However Fybex had no detectable activity in an assay for DNA damage based on the S1-nuclease sensitivity of the DNA from exposed cells. In that assay crocidolite asbestos was more active than either of the more carcinogenic dusts. It is suggested that the activities of amphibole asbestos in assays for genetic toxicity may depend on the production of free radicals via a catalytic reaction requiring the presence of transition elements which are either not present or only present at low concentrations in erionite or Fybex. This type of reaction may not be related to in vivo carcinogenicity. The action of fibrous dusts against macrophage-like cells, measured in this instance by the release of arachidonic acid, remains one of the best measures of biological activity.

Aluminum Silicates↗

In vitro biological effects of volcanic ash from Mount Sakurajima.

Mount Sakurajima in the south of the Kyushu Island of Japan erupts hundreds of times a year and continuously emits large amounts of ash. More than a million people live under this ash plume, and there is considerable concern about the possible effects of this on their health. We have studied the physicochemical characteristics and in vitro effects of airborne ash collected at 8 km from the crater. More than 30% of the ash was found to be SiO2 (w/w) with most of the particles within the respirable size range. The ash did not inhibit the colony formation of V79-4 cells and failed to activate complement or generate chemotactic factor activity in samples of fresh human serum. It was minimally active in causing the release of lysosomal enzymes from human neutrophile, and did not cause arachidonic acid release from macrophage-like cells. These results were in accord with our epidemiological study, in which very low prevalences of nonspecific respiratory disease were demonstrated even at the area with highest ash exposure.

Air Pollutants↗

Measurements of enzymes of collagen synthesis in rats with experimental silicosis.

The levels of two enzymes of collagen biosynthesis namely lysyl oxidase and prolyl hydroxylase were measured in the lungs of rats 3 and 6 weeks after receiving a single intratracheal instillation of silica or sterile saline. Circulating levels of lysyl oxidase were also estimated. Significant increased lung-enzyme activities were observed in the silica-exposed rats at both time intervals. Plasma levels of lysyl oxidase were also found to be raised in the silica-exposed rats. These changes were not, however, accompanied by profound pathological alterations. These results demonstrate that after exposure to silica histologically detectable fibrosis is preceded by significant changes in the activities of enzymes associated with collagen synthesis.

Amino Acid Oxidoreductases↗

Collagen biosynthesis enzymes in lung tissue and serum of rats with experimental silicosis.

The activities of prolyl 4-hydroxylase, galactosylhydroxylysyl glucosyltransferase (GGT) and lysyl oxidase (three enzymes catalysing post-translational modifications of collagen) were measured in the lungs of rats exposed to silica (DQ12). Circulatory levels of GGT were also estimated. Rats were killed after 24 h and at 6, 12 and 24 weeks after a single intratracheal instillation of either 12.5 or 25 mg of silica (DQ12). Control animals received saline. The total activity of the three enzymes in the lungs of the exposed animals was significantly increased at all times (P less than 0.05). The circulatory levels of GGT were also increased though some differences failed to reach significance. Thus increased activities of enzymes of collagen biosynthesis correlated with the development of silicosis and occurred within 24 h of treatment. This suggests that the changes responsible for the eventual development of fibrosis are operative within hours of dust exposure.

Aging↗

Arachidonic acid release and prostaglandin synthesis in a macrophage-like cell line exposed to asbestos.

A macrophage-like cell line (P388D1) has been treated with asbestos and the release of arachidonic acid and its metabolites has been studied using two methods. In the first monolayer cultures of the cells were labelled with tritiated arachidonic acid and the release of label into the medium was quantified: secondly the synthesis and release of prostaglandins E2 and F2 alpha were followed using radioimmune assay. Crocidolite asbestos caused the greatest release of tritium while the medium from chrysotile-treated cultures contained more of both prostaglandins. Both of the fibrous dusts were significantly more active in both test systems than were the two 'inert' materials--titanium dioxide and milled sample of crocidolite. It is suggested that these phenomena are due to the effect of mineral dusts on phospholipase activity and that differences in this activity are associated with differences in the pathogenicity of various mineral dusts.

Arachidonic Acid↗

The metabolism of benzo(a)pyrene by the lungs of asbestos exposed rats.

A group of Fischer F344 rats were exposed to an aerosol of crocidolite asbestos for 36 d. Short-term organ cultures were established from the lungs of these animals and from a similar control group. The ability of these cultures to metabolise benzo(a)pyrene to water-soluble and ether-soluble forms was measured. Crocidolite treatment reduced the lungs ability to produce both types of metabolite although only the reduction in water-soluble forms was significant. DNA binding increased in cultures from treated rats, though this was not statistically significant. The possible relationship of these results to asbestos pathogenesis is discussed.

Animals↗

The influence of asbestos dust on the oncogenic transformation of C3H10T 1/2 cells.

The cell transforming ability of asbestos dust was investigated using C3H10T 1/2 murine fibroblasts. In a series of experiments both crocidolite and amosite caused no increase in the number of transformed foci over that seen in cultures from untreated cells. The dusts, were, however, capable of augmenting the oncogenic effect of benzo[a]pyrene (BP). This putative synergistic effect was evident when fibres and chemicals were added to cultures as simple mixtures and when BP was adsorbed to the surface of the fibres.

Animals↗

In vitro genotoxic activities of fibrous erionite.

A high incidence of mesothelioma has been reported from some villages in Cappadocia, Turkey. This type of cancer is usually associated with the inhalation of asbestos, but on the basis of the most prevalent fibre in the dust from these villages, the Turkish outbreak has been attributed to the inhalation of zeolite fibres. A counter hypothesis, based on the detection of very small quantities of chrysotile and tremolite in strata samples and human lung tissue, postulates a significant role of these minerals as one of several factors contributing to pleural disease. A respirable fraction of erionite, (from Oregon, USA, but with similar characteristics to the fibres found in Turkey), has some in vitro genotoxic properties associated with many conventional carcinogens. In this study these fibres caused an increase in morphological transformation and unscheduled DNA repair synthesis (UDS) in C3H10T1/2 cells and UDS in the human lung cell line--A549. It is therefore suggested that exposure to fibrous erionite alone may be sufficient to cause the high incidence of pleural tumours observed in Turkey.

Aluminum Silicates↗

Study of the cell-transforming ability of amosite and crocidolite asbestos and the ability to induce changes in the metabolism and macromolecular binding of benzo(a)pyrene in C3H10T1/2 cells.

The cell transforming ability of asbestos dusts was investigated using C3H10T1/2 murine fibroblasts. In a series of experiments, crocidolite and amosite caused no increase in the number of transformed colonies over that seen in cultures from untreated cells. The dusts were, however, capable of augmenting the oncogenic effect of benzo(a)pyrene. This synergistic effect was evident when fibers and chemicals were added to cultures as simple mixtures and when benzo(a)pyrene was adsorbed to the surface of fibers. Asbestos dust did not, however, appear to exert its oncogenic enhancing effect by modifying the metabolism of benzo(a)pyrene in C3H10T1/2 cells.

Animals↗