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Biomedical subjects

J R Trevithick

Publications and source records attributed to J R Trevithick.

At least 55 records · Page 3Linked to original sources
PubMed1987

Effect of X-irradiation and vitamin C on DNA degradation and endogenous DNase in embryonic chick lens cells.

The lens is an organ in which epithelial cells become elongated fibers. During this process, nuclei are transformed and the DNA is degraded. In previous studies, we described an autodigestion of the chromatin in isolated fiber nuclei but not in epithelial nuclei, but the level of DNAase activity was found to be identical in both epithelial and fiber nuclei of lenses at 11 days of development. In this study, we have investigated the possibility that x-irradiation might stimulate the nuclear endogenous activity responsible for chromatin breakdown or epithelial cells to a level comparable to that observed in fiber cells. We have observed that x-irradiation does not increase the nuclear epithelial DNAase activity. Conversely, vitamin C, suspected to prevent cataract formation by protecting DNA against free radical formation, has a damaging effect on the DNA of the lens of chick embryo in vitro.

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PubMed1986

Modelling cortical cataractogenesis VIII: effects of butylated hydroxytoluene (BHT) in reducing protein leakage from lenses in diabetic rats.

Normal and streptozotocin diabetic female Wistar rats were given butylated hydroxytoluene at 0-, 0.067- or 0.50% w/w in the diet. At the end of 10 weeks, the animals were examined for weight gain or loss, general body condition, and cataracts. After death, blood was collected for measurement of serum glucose. gamma-Crystallin was determined in aqueous and vitreous humours using a radioimmunoassay. One lens from each rat was homogenized in 8 M guanidinium chloride for adenosine triphosphate analysis. In normal rats, there is a small amount of gamma-crystallin found in the vitreous humour, and an even smaller amount in the aqueous humour. Diabetes caused a 2.5-fold increase of gamma-crystallin in the aqueous humour and a five-fold increase in the vitreous humour. Diabetes also led to a significant worsening in general body condition, loss of body weight, decrease in lens adenosine triphosphate levels, and formation of cataracts. Addition of butylated hydroxytoluene (BHT) to the diet resulted in improved general body condition, reduction in cataracts, decrease of gamma-crystallin leakage into the vitreous humour, and weight gain. There was no effect of dietary butylated hydroxytoluene on levels of lens adenosine triphosphate. Neither the diabetic state nor treatment with butylated hydroxytoluene affected the weight of the lenses.

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PubMed1985

The use of guanidinium chloride in the preparation of stable cellular homogenates containing ATP.

Rat eye lenses were prepared for ATP determination by homogenization in 8 M guanidinium chloride-0.01 M EDTA. Standards of ATP were made up in the same solution. ATP appears to be quite stable in this solution in both standards and lens homogenates whether storage is at room temperature, 4 degrees C, or -20 degrees C for up to several weeks. ATP was measured using a luciferin-luciferase preparation in Hepes buffer, pH 7.75. The photons of light produced were detected by a bioluminescence counter.

Adenosine Triphosphate↗
PubMed1985

Modelling cortical cataractogenesis VII: Effects of vitamin E treatment on galactose-induced cataracts.

The possibility that vitamin E or other antioxidants might prevent cataracts was tested by incubating rat lenses in vitro in galactose-enriched medium or by treating rats fed a diet containing 50% galactose (w/w). The vitamin E was added to the medium at 2.4 microM, and to the diet at a level of 5 g kg-1 diet. In vitro, lenses incubated with 55.6 mM galactose underwent globular degeneration, which was partially prevented by addition of vitamin E (2.4 microM). Even in such vitamin E-protected lenses, which appeared clear, many small globules could be seen in the region of interdigitation at the 'corners' where hexagonal cells intersected. In vivo, in dietary experiments, a dense nuclear opacity of the lens was observed after approximately 5 weeks; unlike diabetic cataracts, this was not prevented by the addition of vitamin E to the diet. The extensive globular degeneration observed was typical of that found in long-term (21-week diabetic) cataracts. Although no significant difference in cataract incidence was observed, the extent of damage in vitamin E-treated rat lenses appeared to be less. The difference in effectiveness of vitamin E in galactose-induced cataracts, as compared to diabetic cataracts, is tentatively ascribed to (1) the more severe osmotic stress expected from the products of the aldose reductase pathway for galactose and (2) the greater depletion of reduced pyridine nucleotides (NADPH + NADH) expected of galactose as compared to glucose.

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PubMed1985

In vitro studies of microwave-induced cataract: reciprocity between exposure duration and dose rate for pulsed microwaves.

Rat ocular lenses exposed to pulsed microwave irradiation were maintained at constant temperature by circulating phosphate buffered saline in a thermostatically-controlled chamber. Irradiations with pulsed radiation (10 musec, 24 kW pulses) of 918 MHz were done at several different specific absorption rates (SAR) for durations up to 1 hr in order to explore a possible reciprocal relationship. The extent of damage was measured by the maximum depth of granular degeneration in the equatorial region of lenses fixed immediately after irradiation. The parameters of the pulses were increased to 20 musec and 48 kW to explore the variation in the biological effects and threshold with respect to average power, as well as pulse parameters (pulse width, peak power and energy per pulse). A total of 47 lenses were used in 3 X 4 factorial experimental design to explore effects observed at different average powers and durations (6, 20 and 60 min). The results were statistically analyzed by ANOVA and multiple regression analysis with logarithmic transformation. The results are summarized as follows. This data showed clear trends towards increasing depth of granular degeneration with increasing duration of exposure and dose rate. There was considerable evidence to confirm such reciprocity suggesting that total dose is an important parameter. A model postulating reciprocity was shown to explain observed variation in depth of damage as well as one allowing for separate effects of duration and dose rate. Lens fibre cell effects were detected by scanning electron microscopy after 6 min irradiation at the SAR values of 40 and 20 mW g-1. Light microscopic evidence of lens fiber cell damage can be detected at an SAR of 10 mW g-1 after a 1 hr exposure.

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PubMed1983

Radiation cataract formation diminished by vitamin E in rat lenses in vitro.

Eye lens cataract is a late effect of exposure to ionizing radiation. Depending on the dose and quality of radiation impinging on the lens, the development of a clinically discernible cataract usually takes several months in animal models, when the lens is irradiated in situ. However, we have developed a rapid in vitro assay with the isolated intact rat lens to study the effect of radiation and influence of antioxidants as protective agents. After only 24 hr of post-irradiation incubation at 35.5 degrees C in complete medium 199 + 10% foetal calf serum, damage in the form of globular degeneration subcapsularly and 'holes' in the cortical fibre cells is detectable. Doses as low as 0.10 Gy seem to be capable of causing some damage, and vitamin E (2.4 microns) in the medium confers some protection to the irradiated lens.

Animals↗
PubMed1983

Modelling cortical cataractogenesis: VI. Induction by glucose in vitro or in diabetic rats: prevention and reversal by glutathione.

Cataractogenesis can be induced by glucose in the rat lens in vitro and in vivo. In vitro, this is done by increasing the amount of glucose in the medium surrounding the isolated lens; within 48 hr considerable globular degeneration is seen subcapsularly, deeper in the equatorial region. In vivo, it is achieved by making the rat diabetic by injecting streptozotocin i.v., which selectively destroys the beta-cells of the pancreas; the blood serum glucose level increases markedly, and thence the aqueous humour level and, in turn, the lens concentration. Globular degeneration occurs as in vitro, but not until 6 weeks is a degree of damage observed comparable to that seen in the lenses incubated in vitro for only 48 hr. Lenticular sorbitol and fructose are also markedly elevated as a result of the high glucose levels. If glutathione (GSH) is present in the medium (0.1 mM) or injected s.c. daily into the diabetic rats, there is no evidence of subcapsular globular degeneration of the cortical fiber cells, even though the lenticular levels of glucose, sorbitol and fructose are the same as when GSH was not given; this is true for either the in vitro or in vivo situation, although individual values in the two situations do differ somewhat from one another. When rats were given GSH beginning several weeks after the diabetic state had been induced, the damage subsequently observed was much less than if the rats had been diabetic without GSH for the same total length of time; it was also much less than damage which should have occurred by the time GSH treatment was instituted. It would thus appear that a certain amount of reversal of the globular degeneration is possible, although damage in the equatorial region (wedge-shaped) seems less amenable to rescue by glutathione. The data indicate that glutathione can prevent or diminish the severity of sugar cataractogenesis, and that there would appear to be more steps in sugar cataractogenesis than simply osmotic damage, although this may be the primary event.

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PubMed1983

Modeling cortical cataractogenesis. V. Steroid cataracts induced by solumedrol partially prevented by vitamin E in vitro.

Rat lenses incubated in tissue culture medium (M 199) maintain their transparency for a long period of time. The soluble corticosteroid, solumedrol (methyl prednisolone sodium succinate) was added to the medium, at concentrations including the range expected during rejection episodes following organ transplantation (3.8 X 10(-9) M-3.8 X 10(-6) M). At the lowest level used (3.8 X 10(-9) M), five lenses of 12 became opaque following a 48 hr incubation, while at higher concentrations of solumedrol almost all lenses developed opacities. Addition of vitamin E to the medium resulted in partial prevention of the cataract as judged by the smaller proportion of lenses becoming opaque. Examination of the lenses by scanning and transmission electron microscopy (SEM and TEM, respectively), indicated that in untreated lenses the initial location of the cataract is at the anterior pole of the lens where a deepening area of degeneration formed, followed by a uniform subcapsular layer of degeneration spreading over the remainder of the lens. Damage at this location is not typical of most in vitro cortical cataracts. In the presence of vitamin E the extent of damage was less, involving, initially, an equatorial wedge of globular degeneration and spreading anteriorly and posteriorly in a thinner subcapsular layer. This type of damage was more typical of that seen previously for cataracts induced by cytochalasin D, elevated glucose and hygromycin B.

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PubMed1982

Modelling cortical cataractogenesis: 3. In vivo effects of vitamin E on cataractogenesis in diabetic rats.

Adult rats, some pretreated for 2 weeks with daily injections of vitamin E (961 IU/kg) were made diabetic by an intravenous injection of streptozotocin. The glucose levels in the serum rose to about five times normal in both groups. In the animals that had not been treated with vitamin E, changes appeared in the lenses that worsened as the hyperglycemia continued: by 4 days, irregular structure of the fibre cells at the equator; by 1 week, twisted ends and irregular undulations of these cells; by 2 weeks, jagged protrusions from the cell surfaces and twisting of the entire cell; by 3 weeks, flakiness of the surfaces of the equatorial epithelial cells, and disorganized and jagged fibre cells in a large area at the equator; and by 6 weeks, extensive subcapsular globular degeneration of the cortical fibre cells. In contrast, the lenses of the diabetic animals that continued to receive vitamin E showed minimal changes: after 6 weeks the equatorial fibre cells displayed the structural irregularities found after 4 days in the diabetic control animals. The protective effect of vitamin E could not be ascribed to the effect on aldose reductase, for at 6 weeks the levels of fructose and glucose in the lenses of the diabetic animals treated with the vitamin, although increased, were not significantly different from those in the lenses of the untreated diabetic rats, and the sorbitol levels were significantly higher in the treated animals. These results are discussed in terms of a multistep mechanism of cortical cataractogenesis.

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PubMed1980

Modelling cortical cataractogenesis: 1. In vitro effects of glucose, sorbitol and fructose on intact rat lenses in medium 199.

After 2 days, lenses with intact capsules from adults rats remained clear when incubated in medium 199 with a normal glucose concentration but showed opacities when the level of glucose was increased up to 10 times normal. Scanning electron microscopy of the fixed lenses demonstrate globular degeneration in the visibly opaque lenses. The depth of degeneration increased as a function of the glucose concentration in the medium, as did the opacity. Thus, in glucose-induced cataracts, as in other types of cortical cataracts, opacity and globular degeneration of the lens appear to be associated. Sorbitol (but not fructose) also induced globular degeneration and lens opacities, indicating that there may be a mechanism of cataractogenesis other than osmosis. The high risk of cataracts in persons with controlled diabetes may be related to the observation that, in vitro, a lower concentration of glucose in medium 199, 8.9 mM (1.6 times the normal level), with 96 hours of incubation was as effective as the minimum concentration capable of causing cataracts, 11.1 mM (2 times the normal level), with 24 hours of incubation.

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