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A M Goldberg

Publications and source records attributed to A M Goldberg.

At least 19 recordsLinked to original sources
PubMed1992

Status of in vitro ocular irritation testing.

This paper reviews advances in the validation of alternative methods for eye irritation testing since the 1987 publication, A Critical Evaluation of Alternatives to Acute Ocular Irritation Testing (1). We have highlighted details of methods that appear promising and identified the minimum needs and endpoints necessary to develop a battery or batteries of in vitro tests to evaluate eye irritancy. We have recommended a series of workshops to provide identified batteries for specific classes of chemicals or for specific uses of eye irritancy testing. We have also identified the need for consensus meetings and peer-reviewed publication to ensure that the most predictive batteries become parts of validation studies. Finally, we note that academic scientists, industry, government and the animal protection community must work together in order to replace in vivo eye irritancy testing with appropriately validated in vitro methods.

Allantois↗
PubMed1985

An approach to the development of in vitro toxicological methods.

Over the last few years there has been increased societal pressure on the one hand and self-generated scientific pressure on the other to develop new and better in vitro techniques for the evaluation of the safety of commercial products. In vitro methodology addresses four major areas within toxicology. It provides the basic science of the discipline with new information. In acute toxicity testing, it can provide alternatives to current approaches, e.g. the Draize irritation tests. In the area of chronic toxicity testing, it will allow us to define the mechanisms associated with organ specific insults. In the area of risk assessment, the combined knowledge obtained by superior methods will allow us to assess risk more accurately. The results of studies on alternatives to the Draize irritation tests being carried out at or supported by The Johns Hopkins Center for Alternatives to Animal Testing will be reviewed.

Animal Testing Alternatives↗
PubMed1984

Perturbation of a hippocampal zinc-binding pool after postnatal lead exposure in rats.

Morphologic alterations of the hippocampal mossy fiber pathway after postnatal lead exposure have been observed in rats. It is hypothesized that lead might perturb zinc pools found in this pathway. To test this hypothesis, rat pups were exposed to lead indirectly by administering 0.2% lead acetate to dams via the drinking water during lactation for 21 days and control litters were maintained on tap water. To evaluate whether or not the effects of postnatal lead exposure were selective for hippocampal zinc pools, the hippocampus was compared with the cerebellum. There were no significant differences between lead-treated and control rats in total zinc content in either the hippocampus or the cerebellum in rats at 30 and 90 days of age. Furthermore, no differences in the subcellular distribution of zinc were observed between control and lead-treated animals. Because the effects on zinc content may be more subtle, the amounts of cytosolic zinc-binding species, isolated using Ultrogel AcA 34 gel chromatography, were measured in control and lead-treated animals. A striking decrease was observed in the amount of zinc associated with one of the cytosolic zinc-binding species, a putative zinc-glutathione complex, shown in previous studies to be the major hippocampal zinc pool. This effect was observed only in the hippocampus of 30-day-old lead-treated rats. By 90 days of age, the effect was no longer present. These data suggest that lead preferentially affects a zinc pool found in the hippocampus and supports our hypothesis that postnatal lead exposure results in an alteration in hippocampal zinc.

Animals↗
PubMed1984

The Johns Hopkins Center for Alternatives to Animal Testing.

The Center strives to develop new non-whole-animal test methodologies based on understanding mechanisms of toxicity of chemicals, consumer products, and drugs for the evaluation of safety. The Center will strive for scientific excellence, and to provide superior methods which will replace existing strategies.

Animal Testing Alternatives↗
PubMed1984

The distribution and binding of zinc in the hippocampus.

Quantitative and qualitative studies suggest that zinc is concentrated in the mossy fiber boutons of the hippocampus and is believed to exist as a chelatable cytosolic pool. These studies were aimed at testing the hypothesis that a zinc-binding protein(s) or an amino acid pool in the cytosol is responsible for the sequestration of zinc. For comparison with the hippocampus, the cerebellum was chosen as a control region since it has been reported to contain lower levels of zinc both quantitatively and qualitatively. Initially, we confirmed that a quantitative difference in the levels of zinc exists between the hippocampus (12.59 +/- 0.85 micrograms of zinc/gm wet weight tissue, X +/- SD) and that this difference is reflected in cytosolic zinc levels. Using Ultrogel AcA 34 gel permeation chromatography, three major zinc-binding species were resolved. Two of these binding species appeared to account for most of the difference observed in the cytosolic levels of the two brain regions. Molecular weight criteria and differential pulse polarography behavior suggest that one of the species is a metallothionein-like protein. Based upon both molecular weight and ion exchange chromatography criteria, the other binding species may be a zinc-glutathione complex. There are no qualitative differences in the zinc-binding species localized in the cytosol of the hippocampus as compared with the cerebellum. However, the amount of binding species, in particular, the metallothionein-like protein and the putative zinc-glutathione complex, is greater in the hippocampus. These findings support the hypothesis that a cytosolic zinc-binding protein(s) may be responsible for the sequestration of zinc observed in the hippocampus.

Animals↗
PubMed1984

A kinetic study of the in vivo incorporation of 65ZN into the rat hippocampus.

Previous autoradiographical studies utilizing 65Zn demonstrated an apparent concentration of 65Zn in the mossy fiber boutons of the hippocampus. To examine the speciation of the 65Zn pool found in this neuronal pathway, we investigated the in vivo incorporation of systemic 65Zn into rat hippocampus compared with other brain regions. We were especially interested in kinetically assessing the zinc associated with three previously identified cytosolic zinc-binding species found in the hippocampus. The hypothesis that two of these cytosolic zinc-binding species, a metallothionein-like protein and a putative zinc-glutathione complex, may be responsible for the sequestration of zinc in the hippocampus was tested. It was confirmed that the t 1/2 of hippocampal zinc is longer than other brain regions that were studied. Furthermore, we observed that 65Zn is incorporated into three cytosolic zinc-binding species in the hippocampus as resolved using Ultrogel AcA 34 gel permeation chromatography. One of these species, the putative zinc-glutathione complex, accumulates zinc more slowly than the other species. The data suggest that the putative zinc-glutathione complex may represent an important 65Zn pool in the hippocampus. This finding is in accordance with out hypothesis that a zinc-binding species, specifically, the putative zinc-glutathione complex, may be responsible for the sequestration of zinc in the hippocampal mossy boutons.

Animals↗
PubMed1982

Precursor dependence of acetylcholine release from rat brain in vitro.

These experiments were designed to test the extent to which the concentration of extracellular choline affects the synthesis and subsequent release of acetylcholine (ACh) by rat cortex in vitro. We found that the rate of potassium-depolarized ACh release from rat cortical minces was significantly accelerated when choline chloride was added to the incubation medium at concentrations of either 60 or 100 microM. The ACh content of the cortical minces was reduced by prolonged depolarization; this depletion was prevented by incubating minces with choline (100 microM). Raising the extracellular choline concentration of the incubation medium did not elevate the amount of ACh released spontaneously (4.7 mM K+) and had no effect on the accumulation of transmitter that occurs when cortical minces are incubated in physiologic buffer. A single dose of choline chloride administered orally to rats (20 mmol/kg) was without effect on the subsequent release of ACh and choline from cortical minces in vitro. The ACh and choline concentrations of rat cortex in vitro were similarly unaffected by in vivo choline administration. These results indicate that ACh release from rat cortex, in vitro, depends upon the direct availability of extracellular choline under conditions of prolonged neuronal depolarization.

Acetylcholine↗
PubMed1982

The role of chloride in acetylcholine metabolism.

The chloride dependence of acetylcholine (ACh) synthesis and release and of choline uptake was studied in synaptosomal preparations from rat brain. The substitution of propionate for chloride, in the presence of 35 mM-potassium, lowered the ACh content of the synaptosomes. However, in the presence of 5 mM-potassium, the ACh level in synaptosomes was reduced, but significantly less so. Propionate had no effect on choline acetyltransferase (EC 2.3.1.6) activity when measured in a standard chloride-containing medium. In the presence of propionate, the spontaneous release of ACh was unchanged, but potassium-stimulated release of ACh was markedly reduced as compared with a chloride-containing medium. The synthesis of ACh, as measured by the net increase in the amount of ACh in the synaptosomes and that released to the medium, was reduced with propionate at 5 mM-potassium and was totally inhibited when the potassium concentration was increased to 35 mM. Choline uptake studies revealed that with propionate only a low-affinity component of the choline transport system existed. Further, the Vmax was markedly reduced when the potassium concentration was increased to 35 mM. The results suggest that under certain conditions choline transported by a low-affinity system might provide a substantial source of choline for ACh synthesis.

Acetylcholine↗
PubMed1980

Mechanisms of neurotoxicity as studied in tissue culture systems.

This presentation focused on describing the unique aspects of nervous tissue which make it susceptible to toxicological insult. It reviewed the published literature of compounds that have been studied in tissue culture of nerve tissue and compared the data in vivo toxicity studies with that obtained from the tissue culture system. Further, neuronal activity as a determinant of neurotoxicity was discussed as a basic mechanism to understand toxicological outcomes.

Aluminum↗
PubMed1980

The use of spinal cord cell cultures in the study of neurotoxicological agents.

Primary cell cultures of mouse embryo spinal cords were used to study the biological effects of exposure to organophosphate esters and neurotoxic amino acids. The effects of exposure were correlated with markers of cholinergic function. The purpose of this study was to examine the mechanisms whereby xenobiotics produce neurotoxicologic damage.

Animals↗