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Biomedical subjects

D L Snyder

Publications and source records attributed to D L Snyder.

63 records · Page 4Linked to original sources
PubMedDate not supplied

Interactions of radiofrequency radiation on 2-methoxyethanol teratogenicity in rats.

Concurrent exposures to chemical and physical agents occur in the workplace; exposed workers include those involved with microelectronics industry, plastic sealers and electrosurgical units. Previous animal research indicates that hyperthermia induced by an elevation in ambient temperature can potentiate the toxicity and teratogenicity of some chemical agents. We previously demonstrated that combined exposure to radiofrequency (r.f.; 10 MHz) radiation, which also induces hyperthermia and is teratogenic to exposed animals, and the industrial solvent 2-methoxyethanol (2ME) produces enhanced teratogenicity in rats. A subsequent study replicated and extended that research by investigating the interactive dose-related teratogenicity of r.f. radiation (sham exposure or maintaining colonic temperatures at 42.0 degrees C for 0, 10, 20 or 30 min by r.f. radiation absorption) and 2ME (0, 75, 100, 125 or 150 mg/kg) on gestation days 9 or 13 of rats. The purpose of the present research is to determine the effects of r.f. radiation (sufficient to maintain colonic temperatures at 42.0 degrees C for 10 min) on a range of doses of 2ME (0, 20, 40, 60, 80, 100, 120 and 140 mg kg-1) administered on gestation day 13 of rats. Focusing on characterizing the dose-response pattern of interactions, this research seeks to determine the lowest interactive effect level. Day 20 fetuses were examined for external and skeletal malformations. The results are consistent with previous observations. Dose-related developmental toxicity was observed for 2ME both in the presence and absence of r.f. radiation. However, concurrent RF radiation exposure changed the shape of the dose-effect curve of 2ME. These data indicate that combined exposure effects should be considered when developing exposure guidelines and intervention strategies.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Tolerability of long term therapy with enalapril maleate in patients resistant to other therapies and intolerant to captopril.

Patients with severe hypertension and/or congestive heart failure (n = 281) who were unresponsive to other therapies and intolerant to captopril received enalapril treatment (mean dose 19.5 mg/day) under study conditions as part of a Compassionate Use Program. Many of these patients had serious concurrent disorders known to predispose them to a greater risk of adverse experiences and death. The mean duration of enalapril treatment was 29 weeks, with a range of 1 day to approximately 3.5 years. Enalapril was generally well tolerated, and the estimated long term probability of patients terminating enalapril therapy because of adverse effects was low. 20 patients had discontinued captopril treatment because of low white blood cell counts; during subsequent enalapril treatment these reactions resolved in 14 patients, persisted in 2 patients, and could not be evaluated in 4 patients. Captopril-related proteinuria improved or resolved in 9 and persisted in 2 of 15 patients, taste disturbances resolved in 35 and persisted in 2 of 38 patients; and rash resolved in all but 7 of 178 patients during enalapril treatment. 18 patients (6%) discontinued enalapril treatment because of lack of efficacy; 6 of these 18 patients died due to a progression of heart failure, and another 11 patients died for other reasons. The deaths were considered unrelated to therapy with enalapril. Adverse reactions were the reason for discontinuation of enalapril treatment in 53 patients (19%). The most common adverse experiences that resulted in discontinuation of enalapril were: impairment of renal function (5%), hypotension (2%) and rash (2%). No neutropenia, proteinuria, or new taste disturbances were recorded as reasons for discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Effects of age, dietary restriction and germ-free environment on glutathione-related enzymes in Lobund-Wistar rats.

The effects of age, dietary restriction and germ-free environment on glutathione peroxidase (GP), glutathione reductase (GR) and glutathione-S-transerases (GT) were studied in 48 Lobund-Wistar male rats obtained through the Lobund Aging Study. The treatment design was a 2 x 2 x 3 factorial design (environment x food level x age). Four rats were killed at 6, 18 and 30 months for each of the following groups of rats: conventional ad libitum (CV-A), conventional restricted (CV-R), germ-free ad libitum (GF-A) and germ-free restricted (GF-R). The dietary restriction (DR) was 30%. The activities of the three enzymes in the liver cytosolic fraction were determined. The activities of DR and GT were not affected by age, and were significantly lower in the rats raised in the GF environment than in those raised in the CV environment. DR significantly increased GR in the GF environment. The total GP activity was not affected by age but significantly increased by DR and a GF environment, suggesting that these life prolonging conditions provide greater protection against organic hydroperoxides and low concentrations of hydrogen peroxide.

Journal Article↗
PubMedDate not supplied

Effects of age and dietary restriction on liver glutathione transferase activities in Lobund-Wistar rats.

Glutathione-S-transferases (GST) are a group of enzymes which detoxify electrophilic xenobiotics (including drugs, carcinogens and their metabolites), and thus may be involved in the age-related pathologic process. Effects of a 30% dietary restriction on liver GST activities toward seven substrates were studied in male Lobund-Wistar (L-W) rats at 6, 12, 18, 24 and 30 months of age. The enzyme activities in the ad libitum (AL) group toward 1-chloro-2,4-dinitrobenzene (CDNB), bromosulfophthalein (BSP), 4-nitropyridine-N-oxide (NPNO), p-nitrobenzyl chloride (NBC), trans-4-phenyl-3-buten-2-one (PBO) and styrene oxide (STOX) did not change with age, while those toward 1,2-dicholoro-4-nitrobenzene (DCNB) decreased after middle age. The enzyme activities in the dietary restricted (DR) group toward CDNB and STOX did not change with age, while those toward DCNB, BSP, NPNO, NBC and PBO decreased after middle age. The DR group had significantly higher GST activities than the AL group, especially at 18 months, when BSP, NPNO, NBC and PBO were used as the substrates. Dietary restriction did not affect GST activities toward all seven substrates at old age. These results are substrate-specific, indicating that isozyme-specific changes in GST activities occur with dietary restriction and aging. The results suggest that dietary restriction enhances liver detoxification capability associated with GSH conjugation in middle age, which may contribute to the delaying of the age-related pathologic process until a later point in life in this animal model.

Journal Article↗
PubMedDate not supplied

Developmental toxicity interactions of salicylic acid and radiofrequency radiation or 2-methoxyethanol in rats.

Radiofrequency (RF) radiation is used in a variety of workplaces where workers are concurrently exposed to chemicals. Combined exposure to RF radiation (10 MHz) and the industrial solvent, 2-methoxyethanol (2ME), produces enhanced teratogenicity in rats. The purpose of the present research was to determine if the synergistic effects noted for RF radiation and 2ME are generalizable to other chemicals. Since salicylic acid (SA) is widely used as an analgesic and is teratogenic in animals, SA was selected to address generalizability. Based on the literature and our pilot studies, 0, 250, or 350 mg/kg SA were administered by gavage on gestation Day 9 or 13 to rats. Concurrently rats given SA on Day 9 were exposed to RF radiation sufficient to maintain colonic temperature at 41 degrees C for 60 min (or sham). Those given SA on Day 13 were also given 0 or 100 mg/kg 2ME (gavage). Dams were sacrificed on gestation Day 20, and the fetuses were examined for external malformations. The data provide no evidence of synergistic interactions between RF radiation and salicylic acid (resorptions and malformations). Limited evidence of antagonism was observed between 2ME and salicylic acid (fetal weights). This investigation highlights the importance of additional research on interactions in developmental toxicology, and emphasizes the need to consider combined exposure effects when developing both physical agent and chemical agent exposure guidelines and intervention strategies.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Developmental toxicity interactions of methanol and radiofrequency radiation or 2-methoxyethanol in rats.

This research was undertaken to determine potential interactions among chemical and physical agents. Radiofrequency (RF) radiation is used in numerous workplaces, and many workers are concurrently exposed to RF radiation and various chemicals. The developmental toxicity of RF radiation is associated with the degree and duration of hyperthermia induced by the exposure. Previous animal research indicates that hyperthermia induced by an elevation in ambient temperature can potentiate the toxicity and teratogenicity of some chemical agents. We previously demonstrated that combined exposure to RF radiation (10 MHz) and the industrial solvent, 2-methoxyethanol (2ME), enhanced teratogenicity in rats. Interactions were noted at even the lowest levels of 2ME tested, but only at hyperthermic levels of RF radiation. The purpose of the present research is to investigate if the interactive effects noted for RF radiation and 2ME are unique to these agents, or if similar interactions might be seen with other chemicals. Because methanol is widely used as a solvent as well as fuel additive, and, at high levels, is teratogenic in animals, we selected methanol as a chemical to address generalizability. Based on the literature and our pilot studies, 0, 2, or 3 g/kg methanol (twice, at 6-hour intervals) were administered on gestation day 9 or 13 to groups of 10 Sprague-Dawley rats. Dams treated on day 9 were given methanol and exposed to RF radiation sufficient to maintain colonic temperature at 41 degrees C for 60 minutes (or sham). Those treated on day 13 were given methanol plus either 0 or 100 mg/kg 2ME. Because we observed that methanol produced hypothermia, some groups were given the initial dose of methanol concurrently with the RF or 2ME, and others were given the first dose of methanol 1.5 hours prior to RF or 2ME. Dams were sacrificed on gestation day 20, and the fetuses were examined for external malformations. The results indicate that RF radiation or methanol on day 9 increased the incidence of resorbed fetuses, but no interactive effects were observed. The resorptions were highest in groups given the experimental treatments 1.5 hours apart. The higher dose of methanol also reduced fetal weights. Administration of 2ME or methanol on day 13 increased the rate of malformations, and there was evidence of a positive interaction between 2ME and methanol. Fetal weights were reduced by 2ME and methanol alone, but no interaction was observed. Also, separation of the dosing with the teratogens did not affect the results. These results point out that interactions in developmental toxicology, such as those of RF radiation, 2ME, and methanol that we have studied, are complex, and such interactions cannot be fully understood or predicted without more research. It is important that combined exposure effects be considered when developing both physical agent and chemical agent exposure guidelines and intervention strategies.

Abnormalities, Drug-Induced↗