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Biomedical subjects

E J Calabrese

Publications and source records attributed to E J Calabrese.

At least 145 records · Page 8Linked to original sources

Gastrointestinal and dermal absorption: interspecies differences.

It has been repeatedly demonstrated that there are considerable interspecies differences with respect to the dermal absorptions of a chemically diverse set of substances, ranging from ionic substances to complex organic molecules, some of which are of great relevance to environmental/occupational health (e.g., the organophosphate insecticides). In general, human skin was found to be much less permeable to the substances evaluated when compared to rabbit and rodent skin; however, the pig and monkey appear to most closely simulate the absorption capabilities of human skin for a variety of substances. Unfortunately, no truly systematic evaluations of numerous classes of compounds have been made via interspecies comparisons. Thus, even though the data derived until now are very consistent, one could argue that strong general conclusions with respect to interspecies differences in dermal absorption cannot yet be made because the substances evaluated thus far may not be sufficiently representative. Clearly, further research along these lines is required.

Animals↗

The effect of in vivo ozone exposure to Dorset sheep, an animal model with low levels of erythrocyte glucose-6-phosphate dehydrogenase activity.

Female Dorset sheep were exposed in vivo to ambient ozone levels of 0.12 ppm, 0.25 ppm, 0.50 ppm, 0.70 ppm for 2.75 hours and the effects of this exposure upon erythrocytes were studied. Ozone exposure induced biochemical evidence of oxidant stress as indicated by decreases in GSH levels (at 0.5 and 0.7 ppm ozone) and ACHE (at 0.7 ppm), increases in MetHb (from 0.12 ppm upward) and decreases in red blood cell counts (from 0.12 ppm upward). However, only the decrease in GSH levels at the 0.5 ppm ozone exposure was statistically significant (p = 0.05).

Acetylcholinesterase↗

The effect of ascorbic acid on sodium nitrite-induced methemoglobin formation in glucose-6-phosphate dehydrogenase-deficient erythrocytes.

Ascorbic acid significantly reduced the occurrence of sodium nitrite-induced methemoglobin (METHB) formation in a dose-dependent manner in erythrocytes from glucose-6-phosphate dehydrogenase (G-6-PD)-deficient humans in vitro. The ascorbic acid treatment, however, also decreased levels of reduced GSH in a dose-dependent manner, a response indicative of oxidant stress to the erythrocyte membrane. The latter findings are inconsistent with the hypothesis that ascorbic acid supplementation in G-6-PD-deficient humans may help compensate for inherently low levels of erythrocyte GSH. Finally, the ascorbic acid-induced reduction of METHB values, while of statistical significance, does not appear to be of clinical significance.

Ascorbic Acid↗

An evaluation of the dorset sheep as a predictive animal model for the response of glucose-6-phosphate dehydrogenase-deficient human erythrocytes to a proposed systemic toxic ozone intermediate, methyl oleate ozonide.

Erythrocytes of both glucose-6-phosphate dehydrogenase (G-6-PD)-deficient humans and Dorset sheep, an animal model with an erythrocyte G-6-PD deficiency, responded in a dose-dependent manner to the oxidant stress of methyl oleate ozonide (MOO) as measured by decreases in G-6-PD activity, increases in methemoglobin (METHB) levels, and decreases in GSH. However, the human G-6-PD-deficient erythrocytes were considerably more sensitive to the formation of METHB than the sheep erythrocytes while the reverse was the case for the GSH parameter. The results suggest a qualitative difference in the response of sheep erythrocytes and human G-6-PD-deficient erythrocytes to MOO that seriously questions the value of the sheep erythrocyte as a quantitatively accurate predictive model.

Animals↗

The effect of methyl oleate hydroperoxide, a possible toxic ozone intermediate, on human normal and glucose-6-phosphate dehydrogenase-deficient erythrocytes.

Erythrocytes of both normal and glucose-6-phosphate dehydrogenase (G-6-PD)-deficient humans responded in a dose-dependent manner to the oxidant stress of methyl oleate hydroperoxide (MOHP) as measured by decreases in G-6-PD activity, increases in methemoglobin (METHB) levels, and decreases in reduced glutathione (GSH). The G-6-PD-deficient erythrocytes displayed a markedly enhanced sensitivity to MOHP-induced decreases in G-6-PD activity and METHB increases while being less sensitive than normal erythrocytes to changes in GSH levels.

Erythrocytes↗

A comparison of how the United States and Canada set drinking water regulations.

How the United States and Canada approach the process and implementation of drinking water standards is critically examined. Despite many similarities in their approaches to regulating drinking water contaminants, there are a number of important differences, including approaches to dealing with genotoxic versus presumed epigenetic carcinogens and selection of biostatistical quantitative risk assessment models. Such international comparisons provide a valuable means to discern how others have attempted to solve similar problems and thereby provide an excellent opportunity to test the validity of one's own methodologies.

Animals↗

The effect of ascorbic acid on copper-induced oxidative changes in the erythrocytes of rats, sheep, and normal humans.

Rats, sheep, and normal humans displayed a comparable sensitivity to copper acetate (3 mM)-induced changes in reduced glutathione (GSH) levels in vitro. However, the human erythrocytes were more sensitive than either animal to methemoglobin (METHB) formation with the rat being least sensitive. Ascorbic acid incubation markedly enhanced the occurrence of copper acetate-induced increases in METHB and decreases in GSH in the sheep and humans. However, ascorbic acid incubation reduced the occurrence of copper acetate-induced increases in METHB, while not effecting changes in GSH in rats.

Animals↗

The effect of ascorbic acid on nitrite-induced methemoglobin formation in rats, sheep, and normal human erythrocytes.

Interspecies differences were demonstrated with respect to the occurrence of sodium nitrite-induced methemoglobin (METHB) in the erythrocytes of rats, dorset sheep, and normal humans, with the rats displaying approximately 25-33% of the sensitivity of sheep and human erythrocytes. Ascorbic acid incubation along with the nitrite was able to significantly reduce METHB formation in a dose-dependent manner in both rats and humans but not in sheep.

Animals↗

Expanded operational concept of high risk groups and its role in standard setting.

The role of the knowledge of high risk groups in the standard-setting process is examined. The overall conclusion is that many potential high risk segments of the population have not been studied adequately and that this deficiency in our knowledge markedly reduces the ability of decision makers to derive appropriate regulatory decisions by either ignoring the potential health effects or applying potentially excessive and expensive safety factors.

Air Pollutants↗

Role of epidemiologic studies in deriving drinking water standards for metals.

Epidemiological investigations are shown to have contributed in a significant way to our understanding of the potential adverse health effects of drinking water with elevated levels of several metals. Particular emphasis is given to an assessment of the epidemiological investigations concerned with characterizing the health effects of exposure to elevated levels of arsenic and sodium in drinking water.

Adult↗

An evaluation of the dorset sheep as a predictive animal model for the response of G-6-PD deficient human erythrocytes to a proposed systemic toxic ozone intermediate, methyl oleate hydroperoxide.

Erythrocytes of both G-6-PD deficient humans and Dorset sheep, an animal model with an erythrocyte G-6-PD deficiency, both responded in a dose dependent manner to the oxidant stress of MOHP as measured by decreases in G-6-PD activity, increases in METHB levels and decreases in GSH. However, the human G-6-PD deficient erythrocytes were considerably more sensitive to the formation of METHB than the sheep erythrocytes while the reverse was the case for the GSH parameter. The results suggest a qualitative difference in the response of sheep erythrocytes and human G-6-PD deficient erythrocytes to MOHP that seriously questions the value of the sheep erythrocyte as a quantitatively accurate predictive model.

Animals↗

Will consumption or oral contraceptives enhance the gastrointestinal absorption of lead.

Consumption of a specific oral contraceptive (OC) preparation resulted in the enhanced gastrointestinal (GI) tract absorption of calcium. Since calcium and lead may compete for the same binding site in the GI mucosa and since lactose enhances the GI uptake of a variety of minerals such as calcium and lead, it is speculated that other agents such as certain OC preparations which facilitate the GI absorption of calcium may also enhance the GI uptake of lead.

Contraceptives, Oral↗

Evolutionary loss of ascorbic acid synthesis: how it may have enhanced the survival interests of man.

It is proposed that the loss of ability by humans to synthesize ascorbic aicd may have markedly enhanced the survival opportunities of early man living in a malarial infested environment. This hypothesis is based on biomedical evidence which indicates that glucose-6-phosphate dehydrogenase (G-6-PD) deficient individuals display enhanced sensitivity to ascorbic acid induced hemolysis which has been fatal at sufficiently high doses and that the G-6-PD deficient trait has been selected for in malarial environments.

Ascorbic Acid↗