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Biomedical subjects

D L Snyder

Publications and source records attributed to D L Snyder.

At least 19 recordsLinked to original sources

Interactions of radiofrequency radiation-induced hyperthermia and 2-methoxyethanol teratogenicity in rats.

Radiofrequency (RF) radiation is used in a variety of workplaces. In addition to RF radiation, many workers are concurrently exposed to numerous chemicals; exposed workers include those involved with the microelectronics industry, plastic sealers, and electrosurgical units. 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), produces enhanced teratogenicity in rats. The purpose of the present research is to determine the effects of varying the degree and duration of hyperthermia induced by RF radiation (sufficient to maintain colonic temperatures at control [38.5], 39.0, 40.0, or 41.0 degrees C for up to 6 h) and 2ME (100 mg/kg) 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. Significant interactions were observed between 2ME and RF radiation sufficient to maintain colonic temperatures at 41 degrees C for 1 h, but no consistent interactions were seen at lower temperatures even with longer durations. These data indicate that combined exposure effects should be considered when developing both RF radiation and chemical exposure guidelines and intervention strategies.

Abnormalities, Drug-Induced

The effect of age on adenosine A1 receptor function in the rat heart.

Adenosine is an important regulatory metabolite in the heart where it has a cardioprotective function. In the ventricle, the cardioprotective action of adenosine is mediated through the adenosine A1 receptor and inhibition of adenylyl cyclase. In order to investigate the effect of age on adenosine signal transduction in the heart, the effect of specific adenosine A receptor agonists on adenylyl cyclase activity was measured in crude cardiac ventricular membranes isolated from 1-, 6- and 24-month-old Fisher 344 rats. There were no differences in basal cyclase activity with age. Consistent with observations from other laboratories, isoproterenol- and forskolin-stimulated cyclase activity decreased with age. In addition, there was an age-related decline in the capacity of adenosine to inhibit stimulated adenylyl cyclase. The specific A1 adenosine receptor agonists, N6-cyclopentyladenosine (CPA) and N6-p-sulfophenuladenosine (SPA) inhibited isoproterenol- and forskolin-stimulated adenylyl cyclase activity in cardiac membranes from 1-month and 6-month-old rats; however, CPA and SPA did not inhibit adenylyl cyclase in membranes from 24-month-old rats. These data indicate that in addition to the age-related decline in beta-adrenergic receptor function with age, there is also a decrease in adenosine A; receptor-mediated responses. In contrast, carbachol acting through muscarinic receptors, caused the same inhibition of adenylyl cyclase at all ages. Therefore, the age-related decline in inhibitory signal transduction is specific to the adenosine A1 receptor. The age-related defect is probably at the level of the adenosine/receptor interaction and/or the receptor/guanine nucleotide binding protein interaction.

Adenosine

Local computed tomography via iterative deblurring.

X-ray computed tomography is a major imaging modality. An iterative deblurring method is adapted for local reconstruction in parallel-beam and cone-beam geometries, utilizing only x-rays passing through a region of interest. The feasibility is demonstrated in numerical simulation with noise-free and noisy projection data. The iterative deblurring method has the theoretical advantages of maintaining nonnegativity, converging monotonically and minimizing Csiszàr's I-divergence.

Algorithms

Cardiovascular hypertrophy and increased vascular contractile responsiveness following repeated cocaine administration in rabbits.

The effects of repeated cocaine administration on contractile responses were studied in adult rabbits. Repeated cocaine exposure caused a significant increase in the maximal response of the aorta to the agonists norepinephrine and serotonin as well as the receptor- independent stimulus KCl when compared to the saline controls. Cocaine exposure caused a significant increase in the wet weights of both heart and aorta. When the contraction was normalized to the wet weight of the aorta there was no difference between rabbits administered cocaine and saline. Acute cocaine administration caused a time-dependent increase in immunoreactivity of the proto-oncogene c-Fos in the aorta. These results show that repeated cocaine administration leads to the development of cardiovascular hypertrophy.

Animals

Effect of age on cardiac norepinephrine release in the female rat.

We previously demonstrated an age-related decline in K(+)-induced norepinephrine (NE) release from cardiac synaptosomes prepared from 6- and 24-month-old male F344 rats. The purpose of the present study was to determine if the age-related decrease in NE release seen in male F344 rats is also present in female F344 rats. K(+)-induced NE release was assessed in cardiac synaptosomes prepared from 6-, 12-, 18-, and 24-month-old male and female F344 rats. NE release was significantly greater in young male rats, compared to old male rats. However, no age-related decrease in NE release was observed in the female rats. In contrast to previous observations in male rats, raising extracellular [Mg2+], an inorganic Ca2+ channel blocker, reduced NE release to the same extent in all female ages. Omega-conotoxin, an organic Ca2+ channel blocker, also decreased NE release to the same extent in all female ages. These studies suggest that in contrast to aging male rats, cardiac adrenergic nerve terminals of aging female rats maintain their capacity to release NE.

Aging

Prenatal cocaine exposure alters norepinephrine release from cardiac adrenergic nerve terminals.

The effect of prenatal cocaine exposure on the development of the cardiac adrenergic nervous system was assessed in neonatal rabbits. Pregnant does received cocaine (4 mg/kg, i.v., bid) or saline during gestational days 8 to 29. Hearts were obtained on postnatal days 10, 20, 30, and 50. Adrenergic nerve function was assessed by measuring 3H-norepinephrine (NE) uptake and 3H-NE release from cardiac synaptosomes. NE uptake increased with postnatal age and was not affected by cocaine exposure. K(+)-induced NE release increased with age, was significantly less in cocaine exposed rabbits compared to saline exposed rabbits at days 10, and 20, but was similar at days 30 and 50. NE release induced by ionomycin, a Ca2+ ionophore, did not change with age, was significantly greater in cocaine exposed rabbits compared to saline exposed rabbits at days 10, 20, and 30, but was similar at day 50. Wet heart weight, heart weight per body weight, and NE content of the hearts were not affected by cocaine exposure. These results suggest that prenatal cocaine exposure delays the development of the mechanisms responsible for Ca2+ influx during K(+)-induced depolarization and increases the neurosecretory response to intracellular Ca2+.

Adrenergic Fibers

Age-related changes in cardiac norepinephrine release: role of calcium movement.

The purpose of this study was to determine if the age-related decrease in norepinephrine (NE) release from cardiac adrenergic nerve terminals is due to a defect in Ca2+ movement into the nerve terminal or to an alteration in Ca2+ activation of intracellular events leading to NE release. NE release was assessed in cardiac synaptosomes prepared from 6- and 24-month-old male F344 rats. K(+)-induced NE release was significantly greater in young vs old rats. Raising extracellular [Ca2+] increased NE release, but NE release always remained higher in the younger animals. Ionomycin, a Ca2+ ionophore, induced NE release from cardiac synaptosomes, and there was no age difference in the response. The age-related reduction in NE release induced by K+ and the capacity of ionomycin to induce similar NE release in young and old cardiac synaptosomes points to a reduction in Ca2+ movement during depolarization.

Aging

Prenatal cocaine exposure affects the development of aortic adrenergic innervation and contractile responses.

This study examines the effects of prenatal cocaine administration on the development of vascular sympathetic innervation and contractile responsiveness. Rabbits received cocaine (4 mg/kg, iv, bid) or saline during gestational days 8 to 29. Aortas were obtained on postnatal days 10, 20, 30 and 50. Vascular smooth muscle responsiveness was assessed by measuring aortic contractile responses to norepinephrine (NE) and to other vasoconstrictors. Vascular adrenergic innervation was evaluated by measuring desipramine sensitive [3H]-NE uptake into aortic ring segments and aortic NE content. [3H]-NE uptake and NE content were reduced at postnatal days 10 and 20 in the rabbits exposed prenatally to cocaine. Differences were not observed at postnatal days 30 or 50. The contractile response to NE was reduced in rabbits exposed to cocaine prenatally. Maximal response and potency were decreased at postnatal day 10 and potency was still decreased at day 20, but not at the older ages. Contractile responses to serotonin (5-HT) and angiotensin II (AII) were not affected by prenatal cocaine exposure. These results suggest that prenatal cocaine exposure delays the development of aortic adrenergic innervation and alpha adrenoceptor responsiveness.

Angiotensin II

Effect of aging and dietary restriction on matrix Gla protein and other components of rat tracheal cartilage.

Age-related changes in connective tissues can alter their functions of elasticity, compressibility and support. Matrix Gla protein (MGP) is a vitamin K-dependent connective tissue component of unknown function. We have purified bovine MGP, and developed a specific radioimmunoassay for it. Since it is found in highest concentration in cartilage, we have developed quantitative extraction methods for MGP, and examined the age-related changes of MGP relative to other components found in the cartilage matrix. The ratio of hydroxyproline to MGP increases with age, while the ratio of glycosaminoglycan to MGP is constant. No effect is seen for MGP in the dietary restricted rat with prolonged lifespan, while both hydroxyproline and glycosaminoglycan contents of tracheal cartilage are significantly increased by dietary restriction (p < or = .05). These data show that MGP and glycosaminoglycan concentration are relatively constant in rats from 6 to 30 months of age, while hydroxyproline concentration increases with age.

Aging

Image recovery from data acquired with a charge-coupled-device camera.

A model for data acquired with the use of a charge-coupled-device camera is given and is then used for developing a new iterative method for restoring intensities of objects observed with such a camera. The model includes the effects of point spread, photoconversion noise, readout noise, nonuniform flat-field response, nonuniform spectral response, and extraneous charge carriers resulting from bias, dark current, and both internal and external background radiation. An iterative algorithm is identified that produces a sequence of estimates converging toward a constrained maximum-likelihood estimate of the intensity distribution of an imaged object. An example is given for restoring images from data acquired with the use of the Hubble Space Telescope.

Algorithms

Effect of age on potassium- and tyramine-induced release of norepinephrine from cardiac synaptosomes in male F344 rats.

Potassium (K+)-induced norepinephrine (NE) release was examined in preparations of cardiac synaptosomes and sliced atria from 6-, 24-, and 26-mo-old male F344 rats. Cardiac synaptosomes were prepared from rat hearts by collagenase digestion followed by homogenization in 0.32 M sucrose and centrifugation. The synaptosome preparations and the sliced atria were labeled with 3H-NE and then placed in a superfusion system. K(+)-induced net fractional release of NE from synaptosomes prepared from 24- and 26-mo-old rats (4.3% and 3.0%, respectively) was significantly reduced when compared to NE release from synaptosomes from 6-mo-old rats (5.2%). K(+)-induced NE release from sliced atria from 24-mo-old rats (4.7%) was also significantly reduced when compared to NE release from atria from 6-mo-old rats (6.3%). Perfusion of cardiac synaptosomes with buffer prepared without calcium (CA++free, < 5 microM) reduced K(+)-induced release by 50% in all age groups studied. Perfusion with tyramine induced identical rates of NE release from cardiac synaptosomes prepared from 6- and 24-mo-old rats. These results confirm that depolarization-induced NE release from cardiac sympathetic nerves is reduced in the old male F344 rat.

Adrenergic Fibers

Serum zinc in aging germ-free and conventional rats.

Zinc nutritional status appears to decline with age in humans and rodents. Since germ-free rats outlive their conventional counterparts in better health, serum Zn levels were determined in male germ-free and conventional Lobund Wistar rats in samples originating from the Lobund Aging Study. Starting at 5 months of age, germ-free rats showed significantly higher serum Zn levels than did their conventional counterparts. In conventional rats sacrificed up to 30 months of age in apparently good health, serum Zn levels showed no effect of age, while a slight but significant increase with age was observed in the germ-free rats. In healthy germ-free adults (6-24 months of age), serum Zn concentrations were approximately 25% higher than those in comparable conventional animals. In conventional rats 18-30 months of age (average, 24.5 months), sacrificed because of an obvious moribund condition, serum Zn levels were significantly lower than those in rats of the same age range (average, 24.9 months) that were obviously healthy. Results suggest that the often observed higher absorptive capacity of the germ-free gut might have contributed to higher serum Zn levels, and that a decline in serum Zn concentration with age may be a consequence, rather than a causative factor, of declining health.

Aging

Influence of aging, environmental antigens, and dietary restriction on expression of lymphocyte subsets in germ-free and conventional Lobund-Wistar rats.

Lymphocyte subsets from four groups of Lobund-Wistar (L-W) rats were quantitated to determine the influence of diet restriction (DR) and exposure to environmental antigens on the development of these cells. The following effects were found from 6 to 30 months of age: The number of Ts/c and Ts cells were higher in germ-free (GF) vs conventional (CV) rats, whereas B-cell numbers were lower. W3/13 T cells, Ts, and NK cell numbers were higher in DR vs full-fed rats, whereas B-cell numbers were lower. OX19 and W3/13 T cell numbers decreased from 6 months to 30 months in each group, whereas NK cell numbers increased. Also, OX6+ B cell numbers increased with age, and Ts/c numbers decreased. These data may reflect a relationship between enhanced T-cell function and the extended life span and lower tumor incidence observed in DR L-W rats.

Aging

The influence of dietary restriction, germ-free status, and aging on adrenal catecholamines in Lobund-Wistar rats.

Adrenal catecholamines (CA) were measured in 6-, 18-, and 30-mo Lobund-Wistar rats (LWR) maintained under germ-free or conventional conditions and fed either ad libitum or a restricted (70% of adult ad libitum) diet. Levels of dopamine (DA), norepinephrine (NE), epinephrine (E), and dihydroxymandelic acid (DHMA) were determined by HPLC-EC. Compared with values from 6- and 18-mo rats, mean adrenal weight, DA and NE content and concentration, and E content were increased in the 30-mo rats; E concentration was not. The ratio of E:NE declined in the 30-mo group. Germ-free status and dietary restriction had little effect in modulating these age-related changes. Reanalysis of adrenal weights of 30-mo rats revealed two clear subgroups, hyperplastic and non-hyperplastic; the data from hyperplastic adrenals revealed an exaggerated form of the "aged" CA profile, whereas data from the nonhyperplastic adrenals more closely resembled that of younger rats. Thus, aging in LWR is associated with adrenal hyperplasia and a tendency toward elevated adrenomedullary stores of DA and NE, while E stores are maintained near levels found in young rats.

Adrenal Glands

Myocardial fibrosis in aging germ-free and conventional Lobund-Wistar rats: the protective effect of diet restriction.

The influences of diet restriction and germ-free environment on aging were studied in 127 male Lobund-Wistar rats ranging in age from 7 to 48 months. There was an age-related increase in collagen deposition of the heart, particularly involving the left ventricle. The degree of fibrosis was significantly less extensive in middle and old age rats (18 mo, 30 mo, 32+ mo) maintained on a restricted diet. No clear-cut influence of germ-free environment was apparent. No amyloid was detected in 175 tissue sections examined from hearts, lungs, and livers.

Aging

Effect of somidobove sustained release administration on the lactation performance of dairy cows.

Lactation performance was determined on 190 multiparous Holsteins from five herds supplemented with 0, 320, 640, or 960 mg of somidobove every 28 d. The experiment consisted of 21 d of pretreatment and treatment periods of various lengths, depending upon stage of lactation of animals at first administration. Somidobove beginning in early (28 to 45 d in milk), mid (111 to 166 d in milk), or late (166 to 334 d in milk) stages of lactation consisted of 9, 6, or 3 administrations. Milk and 3.5% FCM yields were increased by each dose of somidobove in all stages. Milk composition and dry matter and energy intakes were similar among treatments within stage. Milk to DMI ratio and milk energy to net energy intake ratio were improved by somidobove. Gain was positive for all treatments, but less in somidobove-supplemented cows. Lower body weight and condition score at the completion of somidobove treatment resulted. For early cows, days to first estrus and days to first breeding were similar; however, total number of inseminations for cows receiving somidobove was twofold greater than control, resulting in a longer calving interval. Results demonstrated efficacy of somidobove administered every 28 d to lactating dairy cattle for increased milk yield.

Animals