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Biomedical subjects

D L Snyder

Publications and source records attributed to D L Snyder.

At least 37 records · Page 2Linked to original sources
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

Life span, morphology, and pathology of diet-restricted germ-free and conventional Lobund-Wistar rats.

The effect of germ-free life and dietary restriction (DR) on life span and pathology was investigated in isolator housed germ-free (GF) and conventional (CV) Lobund-Wistar rats fed either ad libitum or restricted to 12 grams per day (70% of adult ad libitum intake) of a natural ingredient diet from weaning. The median length of life of ad libitum CV and GF rats was 31.0 and 33.6 months respectively, while DR increased the median length of life of CV and GF rats to 38.6 and 37.8 months respectively. DR reduced the frequency or postponed the occurrence of diseases which eventually lead to death in the Lobund-Wistar rat. This was especially true of prostate adenocarcinoma, prostatitis, and mammary fibroma. The reduced early food intake and smaller body weight of adult GF rats may be the reason ad libitum fed GF rats live slightly longer than their CV counterparts, but GF life was without additional effect on life span when food intake was restricted.

Adrenal Gland Neoplasms↗
PubMed1990

The effect of food restriction and germ-free environment on age-related changes in bone matrix.

Studies were performed to determine the effects of food restriction or a germ-free environment on age-related changes in bone. Four groups of male Lobund-Wistar rats were examined at 6 months, 18 months, and 30 months of age. Conventional-free-fed rats were housed in routine laboratory cages and fed ad libitum. Conventional-restricted diet rats were fed 12 grams a day, which becomes restrictive at 8 weeks of age. Germ-free rats were maintained using gnotobiotic procedures and were free of pathogens. The germ-free rats were maintained on either the full-fed or restricted diet regimens. Serum bone Gla protein and matrix concentrations of calcium, magnesium, and hydroxyproline (reflecting collagen content) and bone Gla protein were not significantly different between the four treatment groups. All of these parameters except hydroxyproline, however, showed age-related declines in all four treatment groups. We conclude that prolongation of rat life span by dietary restriction and/or a germ-free environment did not alter the measured parameters in each age group, and did not alter or slow the age-related changes in the bone matrix.

Aging↗
PubMed1989

The promotional effect of testosterone on induction of prostate-cancer in MNU-sensitized L-W rats.

Large metastasizing prostate adenocarcinomas (PAs) were induced in L-W rats by a single intravenous (i.v.) inoculation of methylnitrosourea (MNU) and then single subcutaneous implants of testosterone propionate (TP) at intervals of 2 months. This procedure induced PAs in approximately 90% of rats in an average of 11 months. PAs did not develop spontaneously in L-W rats under age 20 months. With this model system, it was demonstrated that within a 14-month observation period, significant numbers of PAs were elicited by TP implants in L-W rats after intervals of 1 week, 1 month and 2 months following the inoculation of MNU. A direct relationship was also demonstrated between amount of TP administered to L-W rats and the resulting incidence of PAs. TP is characterized as a prostate-directed promoter of PA, following a single inoculation of MNU which served as the tumor initiator.

Adenocarcinoma↗
PubMed1989

Role of intestinal microflora in the metabolism of vitamin B-6 and 4'-deoxypyridoxine examined using germfree guinea pigs and rats.

In previous work identification of urinary metabolites of 4'-deoxypyridoxine which had been oxidized in the 5'-position and long-term dilution of labeled urinary metabolites with unlabeled molecules suggested possible microbial contributions. In the current studies germfree guinea pigs were able to convert 4'-deoxypyridoxine to 4'-deoxy-5-pyridoxic acid demonstrating that the ability to oxidize the 5'-position is not restricted to microorganisms. Labelling curves for urinary pyridoxic acid in rats continuously fed [14C]pyridoxine since weaning were similar in conventional and germfree animals indicating that any vitamin B-6 synthesized in the intestinal tract was not readily absorbed and metabolized. Therefore, coprophagy did not make a detectable contribution to vitamin B-6 metabolism in rats receiving a nutritionally complete diet. The difficulty in achieving comparable labeling in adult animals is probably due to very slow turnover of portions of the vitamin B-6 pool and not to microbial production of vitamin B-6. The total pool calculated from the radioactivity in the germ-free rats averaged 16.2 +/- 0.8 nmol vitamin B-6 compounds/g body wt. Only 10% of the ingested label was recovered in the feces. In addition, only about 50% of the label excreted in the urine appeared as 4-pyridoxic acid in rats. These observations suggest that it may be difficult to quantitate the total urinary and fecal excretion of ingested vitamin B-6 without using tracers.

Animals↗
PubMed1989

Spontaneous pituitary gonadotroph nodules in aging male Lobund-Wistar rats.

Spontaneous pituitary changes with aging were studied in 130 male Lobund-Wistar rats by light and electron microscopy and immunohistochemistry. These 69 healthy rats (6, 18, and 30 months) and 61 moribund rats (17-50 months) had been maintained in four different groups with the following environmental conditions: conventional full fed, convention food restricted, germ free-full fed, and germ free-food restricted. Gonadotroph nodules were the most frequent proliferative lesions (27 rats). It was difficult to determine whether these nodules were hyperplastic or neoplastic. They were found in aging rats (26 months or older) and their development was delayed by food restriction and germ-free status parallel to prolongation of life-span. No significant difference in incidence of gonadotroph nodules was demonstrated among the four groups. Six lactotroph adenomas, a thyrotroph nodule, and a mixed thyrotroph and lactotroph nodule were also noted in aging rats (30 months or older). In extranodular adenohypophyses, variable numbers of hyperactive gonadotrophs histologically similar to those in gonadotroph nodules were observed in almost all rats including 6-month rats, suggesting that gonadotrophs were continuously hyperactive during their lifetime from an early stage. The mechanism accounting for the development of gonadotroph nodules remain to be established. It can be concluded that food restriction and germ-free status may have a retarding effect but no preventative role in the development of gonadotroph nodules, which are the most common age-associated pituitary lesions of male Lobund-Wistar rats.

Aging↗