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Biomedical subjects

E Ebert

Publications and source records attributed to E Ebert.

At least 19 recordsLinked to original sources

Chronic toxicity and carcinogenicity studies with the insecticide endosulfan in rats and mice.

The insecticide endosulfan was evaluated for chronic toxicity and carcinogenicity in long-term feeding studies in both Sprague-Dawley rats and NMRI mice. Dietary concentrations of the test substance were administered to rats at 0, 3, 7.5, 15 and 75 ppm and to mice at 0, 2, 6 and 18 ppm for 24 months each. In the rat study, only the treatment with the highest dose caused a significant reduction of body weight gains of the males and females at 75 ppm. The increased incidence of enlarged kidneys seen at autopsy at 75 ppm in females, and the slightly increased incidence of progressive glomerulonephrosis and slightly increased incidence of renal aneurysms seen histopathologically in the 75 ppm males, make the kidney the target organ in rats. On the basis of these findings a dietary concentration of 15 ppm is considered to be the no-observed-effect level (NOEL) in rats, equivalent to a daily test substance intake of 0.6 mg/kg body weight in males and 0.7 mg/kg body weight in females. In the mouse study, the treatment with 18 ppm caused a significant increase of mortality in the females and a slight (in the first third of the study, significant) reduction of body weight gain in males. Since there were no other substance-related findings, the dietary concentration of 6 ppm is considered to be the NOEL in mice, equivalent to a daily test substance intake of 0.84 mg/kg body weight in males and 0.97 mg/kg body weight in females. An evaluation of all relevant tumour data gained in both studies revealed no differences between control and treated groups. It was concluded, therefore, that endosulfan has no carcinogenic potential.

Administration, Oral

Composition of TCR-CD3 complex in human intestinal intraepithelial lymphocytes: lack of Fc epsilon RI gamma chain.

Human intestinal intraepithelial lymphocytes (iIEL) are a unique population of predominantly CD8 alpha beta+, TCR alpha beta+ lymphocytes and, to a lesser extent, TCP gamma delta+ lymphocytes that proliferate poorly to anti-CD3 mitogenic signals but display significant cytolytic activity. Studies in mouse model systems have shown that the gamma chain of the high-affinity receptor for IgE (Fc epsilon RI gamma) may substitute for the zeta chain in the TCR-CD3 complex of iIEL. This has suggested that the functional properties of these cells may be associated with an altered composition of the TCR-CD3 complex. We therefore analyzed the TCR-CD3 complex of normal human iIEL. One- and two-dimensional non-reducing/reducing SDS-PAGE analysis of CD3 gamma, CD3 delta, CD3 epsilon, zeta and Fc epsilon RI gamma chain immunoprecipitates of cell surface radiolabeled proteins with subunit-specific antibodies revealed a TCR-CD3 complex without associated Fc epsilon RI gamma chains. Thus, normal human iIEL contain a TCR-CD3 complex that consists predominantly of zeta homodimers in association with the alpha beta TCR and CD3 gamma, delta and epsilon, similar to the majority of peripheral lymphocytes. This indicates that the distinct properties of human iIEL are not associated with substitutions of the Fc epsilon RI gamma chain in the TCR-CD3 complex.

Animals

Glufosinate ammonium--some aspects of its mode of action in mammals.

The broad-spectrum herbicide glufosinate ammonium is a structural analogue of glutamate and acts in plants by inhibition of glutamine synthetase leading to a complete breakdown of ammonia metabolism. Owing to the structural analogy of glufosinate ammonium to glutamate, its effect on various glutamate-utilizing systems needed to be investigated in mammals. Although in laboratory animals glufosinate ammonium causes an inhibition of glutamine synthetase activity in different tissues, this inhibition led to slight increases of glutamate and ammonia levels at high sublethal and lethal doses only. After oral administration for 28 days, glufosinate ammonium had no effect on glutathione and carbohydrate metabolism and no effect on biosynthesis of non-essential amino acids in rats and dogs. Glufosinate ammonium does not interfere with various neurotransmitter receptors in vitro and does not influence the catecholamine neurotransmitter tissue concentrations after iv application. The results of these studies show that--in contrast to the plant metabolism--in mammals the inhibition of glutamine synthetase activity in various tissues does not lead to a breakdown of ammonia metabolism. The mammalian metabolism obviously compensates for this inhibition of glutamine synthetase activity by various other metabolic pathways. It is concluded that under the conditions of recommended use of glufosinate ammonium as an active ingredient in herbicides, a detrimental effect on the health of both users and consumers is extremely unlikely.

Administration, Oral

Toxicology and hazard potential of trifluralin.

This paper reviews the results of toxicity studies conducted in laboratory animals to evaluate the safety of the herbicide trifluralin (TFL). The data show that TFL is slightly toxic following single oral exposure. Testing for embryotoxicity in rats and rabbits indicated no teratogenic potential, and many different mutagenicity tests showed that TFL was non-genotoxic. Subchronic and chronic toxicity testing in rats, mice and dogs indicated that TFL was haematotoxic (anaemia and methaemoglobinaemia), particularly in the dog, and slightly hepatotoxic. No-observed-effect levels of 4.8 and 41 mg/kg body weight/day, respectively, were determined in dogs and rats exposed chronically to TFL. Oncogenicity studies in rats and mice revealed no carcinogenic potential. Since the data for TFL indicated no mutagenic or other special toxicological risks, it is suggested that a safety factor of 100 could be used for the determination of the acceptable daily intake of TFL, which would be 0.05 mg/kg body weight/day.

Administration, Oral

Summary of safety evaluation toxicity studies of glufosinate ammonium.

This article reviews the results of toxicity studies to evaluate the safety of the herbicide glufosinate ammonium (GLA) and its formulation (200 g/litre) in laboratory animals. The data show that GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced slight dermal toxicity and eye irritation. Testing for teratogenicity in rats and rabbits indicated no teratogenic potential, and numerous mutagenicity tests showed GLA to be non-genotoxic. Chronic toxicity testing in rats and dogs yielded no-observable-effect levels of 2 and 5 mg/kg body weight/day, respectively. Oncogenicity studies in rats and mice revealed no carcinogenic potential. On the basis of these toxicity data it is concluded that this herbicide is safe under conditions of recommended use.

Aminobutyrates

The dural shunt syndrome. I. Management of glaucoma.

The authors present four cases of the dural shunt syndrome in which shallowing of the anterior chamber or rubeosis developed. All patients were female, ranging in age from 66 to 79 years, exhibiting elevated intraocular pressure (IOP), decreased extraocular movements, injected tortuous episcleral vessels, and proptosis. The authors managed these four cases with laser iridotomy, gonioplasty, panretinal photocoagulation, or medical treatment. It is important to recognize associated findings in patients with shallow anterior chambers and elevated IOPs so that a diagnosis of a dural shunt is considered and appropriately treated. Theories on the mechanisms of increased IOP in the dural shunt syndrome and the management of various types of glaucoma in four different cases are reviewed.

Aged

Increased scleral rigidity and age-related macular degeneration.

The coefficient of scleral rigidity of the eyes of 29 patients with age-related macular degeneration (ARMD) was significantly higher than the rigidity of 25 control patients, frequency matched for age. The data suggest that an increased scleral rigidity may be a significant risk factor for the development of the disorder.

Aged

Growth of abused children. Contrasted with the non-abused in an urban poor community.

While the identification of a growth-retarded or otherwise undernourished child suggests a diagnosis of child abuse or neglect, it is not certain that abused children from poor communities are less well nourished than children living in similar environments. The setting of this study--day care centers in an urban poor city--provided an opportunity to make this comparison with appropriate community-based controls. Measures of height, weight, and weight/height (Body Mass Index (BMI] were compared for 196 children, 2 to 6 years of age, 53 of whom were victims of physical abuse. The data was adjusted for age, sex, and ethnicity using logistic regression analysis to determine occurrence of wasting (weight for height less than 5th percentile) and stunting (height for age less than 5th percentile). Significantly more abused children (16.3%) showed wasting as compared to non-abused (0.7%) with abused children 16.6 times more likely to show wasting than non-abused (95% confidence limits on the Odds Ratio 1.9-145.0). While 11.6 percent of abused children showed stunting compared to 5.6 percent of non-abused, this difference was not significant when the data was adjusted for demographic factors. The BMI (15.02 kg/m2) for abused children was significantly less than that (15.9 kg/m2) for non-abused children (F = 8.11; p = 0.0049). In the present study, significant wasting as seen in acute malnutrition was found among abused children at diagnosis, suggesting that within an urban poor community the growth of children so identified does differ from the growth of children who are not abused.

Child

Defective interleukin-2 production and responsiveness by T cells in patients with chronic lymphocytic leukemia of B cell variety.

The present studies were designed to investigate the mechanism(s) of the defective T cell proliferative response to various stimuli in patients with B cell chronic lymphocytic leukemia B-CLL. In 14 patients with advanced B-CLL (stage III or IV) we found the T cell response in the autologous (auto) and allogeneic (allo) mixed lymphocyte reaction (MLR) to be 35.7% and 30% of the controls, respectively. Proliferation in the MLR depends upon the production of and response to interleukin 2 (IL 2), a T cell growth factor. IL 2 production in eight B-CLL patients was 22% of the control. The response to IL 2 was measured by the increase in the T cell proliferation in the MLR with the addition of IL 2. T cell proliferation in both the auto and allo MLR of CLL patients was significantly lower than in the controls after the addition of IL 2. The proliferative response of normal T cells to stimulation by CLL B cells was 50% of the control. This latter response was increased to control levels when cultures were supplemented with exogenous IL 2, suggesting that CLL B cells could stimulate IL 2 receptor generation in normal T cells in an allo MLR, but not IL 2 production. The presence of IL 2 receptors on activated T cells was directly determined using anti-Tac, a monoclonal antibody with specificity for the IL 2 receptor. Of the mitogen- or MLR-activated T cells in CLL patients, 6% and 10%, respectively, expressed Tac antigen, whereas identically stimulated control T cells were 60% and 47% Tac+, respectively. Our findings suggest that T cells in B-CLL are defective in their recognition of self or foreign major histocompatibility antigens as demonstrated by their impaired responsiveness in the MLR. Thus, these cells are unable to produce IL 2 or generate IL 2 receptors.

Antibodies, Monoclonal

[Use of solubilization for the preparation of samples for determination of heavy metals in biological materials using atomic absorption spectrophotometry].

Solubilisation was tested for its suitability to prepare organic samples for metal determination. Flameless atomic-absorption spectrophotometry was used as test method. Copper, manganese, zinc, and chromium levels were determined from various organ systems of Wistar rat, in response to "normal" feeding of pelletised standard feed. A comparison between experimentally established concentrations, on the one hand, and literature data, on the other, suggested that solubilisation was applicable with good success to the preparation of samples from which to determine reliable values, in ppm and ppb, of the above elements.

Animal Feed

[Control of trace elements in the rat using the heavy metal antidote "Unithiol" (sodium-2,3- dimercaptopropane sulfonate)].

The trace element balance in laboratory rats was found to be affected by somewhat lasting application of "Unitiol". Unambiguous decline of manganese, copper, and zinc concentrations was recorded from blood and liver. Complex fixation of copper was stronger than that of the other elements tested. No dose-dependent changes were observed with the experimental arrangement described. The chromium levels in all examined organs were affected but slightly or not at all. The proposal is made that long-term therapeutic use of chelate formers should be accompanied by properly balanced application of essential trace elements.

Animals