摘要:

Polysomes and their associated ribonucleic acids were extracted from ageing soybean cotyledons. Density gradient analysis showed that the ribosomes of older cotyledons were present largely as monosomes and light polysomes while younger cotyledons possessed a high proportion of heavy polysomes. Increased polysomal and mRNA activities were observed in 3- to 5-day-old and again in 10-day-old cotyledons. The presence of polyadeny-lated mRNA was determined by oligo (dT) cellulose chromatography and confirmed by hybridization with 3H-polyuridylic acid.

ISSN:0304-324X    

DOI:10.1159/000212505

出版商:S. Karger AG    

年代:1982

数据来源: Karger

ISSN:0304-324X    

DOI:10.1159/000212567

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

The biological determinants of drug disposition have been clearly identified and methods are available to quantify what effects altering them will have on drug kinetics. The factors include blood flow and intrinsic clearance of the organ of elimination, drug binding in blood and tissues, and, in the case of drugs eliminated by the liver, the oral route of administration. The effects of these various factors on drug elimination depend on the efficiency of the elimination process. At one end of the spectrum, some drug elimination is very efficient as it is largely flow-dependent, while at the other elimination depends largely on intrinsic clearance. The oral route of elimination may be important for drugs which undergo efficient hepatic extraction, when a large ‘first-pass’ effect results. In addition, that fraction of the drug escaping first-pass elimination is largely dependent on intrinsic clearance and not flow. Finally, plasma drug binding may affect both elimination and drug distribution. The way in which these factors can be affected by the aging process will be discussed and illustrated with examples showing how changes in organ blood flow, intrinsic clearance and plasma drug binding can produce pharmacokinetic changes seen in the elde

ISSN:0304-324X    

DOI:10.1159/000212568

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Insulin and glucagon secretion after glucose load and the hormone-receptor interaction were compared between 6- and 24-month-old Wistar rats. The 24-month-old rats showed a failure to decrease glucagon secretion after glucose load in contrast to 6-month-old rats with a similar degree of glucose tolerance and insulin response. Age-related change of insulin receptor of rat liver was tentatively suggested to be a disappearance of the binding site with higher affinity. Affinity of the glucagon receptor did not differ significantly between the two groups. The hyposuppressibility of glucagon by hyperglycemia and the decrease of insulin affinity might contribute to the glucose intolerance with aging.

ISSN:0304-324X    

DOI:10.1159/000212506

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

The incidence of adverse reaction to drugs and of drug interaction increases with age. The types of interaction which may occur are described. The mechanisms underlining pharmacokinetic and pharmacodynamic interactions are described and examples of common drug interactions which may occur in the elderly are given. It is emphasised that the elderly may need to take several drugs for the maintenance of good health and the potential danger of the part played by interaction must be recognised.

ISSN:0304-324X    

DOI:10.1159/000212570

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Neuron density, volume of the area and total neuron number were measured in the medial preoptic area, supraoptic nucleus, paraventricular nucleus, anterior hypothalamic area, ventromedial nucleus, dorsomedial nucleus and arcuate nucleus of the hypothalamus in young adult male rats (3.5–5 months old) and in old male rats (26–27 months old) of the Sprague-Dawley strain. There is no neuron loss in all measured areas. The results correlate well with the sex difference in the functional changes of the feedback response to sex steroids in old r

ISSN:0304-324X    

DOI:10.1159/000212507

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Measures of body weight change were calculated and examined in relation to the life span of 68 male and 71 female Wistar rats that were maintained either in wheel-cage units or cages without wheels. The analysis revealed the following: (a) sex and wheel exercise accounted for nearly one third of the obtained variation in life span; (b) growth rate, defined as the ratio of peak body weight to growth duration, accounted for over 15% of the variance in life span unattributable to sex and exercise; (c) measures of body weight gain early in the developmental span were virtually unrelated to life span; (d) beyond 9 months of age, measures of body weight gain showed a significant positive relationship with life span. Thus, there was no evidence of a negative relationship between life span and body weight gain during early life.

ISSN:0304-324X    

DOI:10.1159/000212508

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Considerable attention has been focused on biochemical and behavioral changes that manifest themselves in the basal ganglia of aging rodents. The neurochemical changes include a decline in dopamine levels, reductions in the synthetic enzymes for gamma-amino-butyric acid and for acetylcholine and declines in muscarinic, dopaminergic and noradrener-gic receptors. Some of these changes have also been observed in human basal ganglia, where it is known that there are neuronal losses with age. Neuroreceptor alterations have not been widely studied in the aging human central nervous system. Recent evidence has indicated that certain neuropeptides, including the undecapeptide substance P, may be involved in striato-nigral neurotransmission. In Huntington’s disease, which primarily affects basal ganglia, there is a decrease in striatal muscarinic, serotonergic and dopaminergic receptors which may result from the loss of gamma-aminobutyric acid-, acetylcholine- and neuropeptide-containing striatal neurons in the disease. In aging humans, where there can be signs suggesting basal ganglia dysfunction, or in aging rodents, little attention has been given to central nervous system (CNS) neuropeptides. In Fisher 344 rats (National Institute of Aging colony) 3, 10 or 27 months old, we have observed no age-related change in substance P immunoreactivity in the cortex, limbic system, corpus striatum, substantia nigra, hypothalamus, brain stem or cerebellum. In postmortem human brain tissue, however, there was a marked age-related decline in substance P immunoreactivity (n = 20, slope = -0.58, r = -0.65, p < 0.005) in the putamen but no age relationship in the frontal cortex, thalamus or hypothalamus. No conclusive determination has yet been made in the caudate nucleus, globus pallidus or substantia nigra. There were no major age-related changes in levels of somatostatin or neurotensin in the CNS of the rat. There were highly significant age-related declines in neurotensin levels in the pars compacta and reticulata of the human substantia nigra. These results suggest that there may be differences between rodents and humans in the CNS aging process and that region-specific age-related changes in neuropeptides may occur in the human CNS. These alterations in neuropeptides should be considered in the therapeutics of basal ganglia disorders and in age-related changes in drug responsiveness in the human CN

ISSN:0304-324X    

DOI:10.1159/000212571

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Hepatocytes, endothelial and Kupffer cells were isolated from young adult (3 month) and old (24 month) rat livers and the activities of some plasma membrane, endoplasmic reticulum, mitochondrial, lysosomal and soluble enzymes compared using biochemical and electron microscope cytochemical techniques. Age-associated changes included: a decrease in glucose-6-phosphatase activity both in hepatocytes and sinus lining cells; an increase in alkaline phosphatase in endothelial cells but a decrease in hepatocytes; reduced basal and glucagon-induced adenyl cyclase in hepatocytes and endothelial cells and an increase in the number of hepatocytes with γ-glutamyl transferase reaction. Cytochemistry showed that heterogeneity may also be characteristic of senescence particularly with regard to hepatocyte glucose-6-phosphatase which was absent in some cells, low in many cells but high in some and γ-glutamyl transferase which was normally lacking from hepatocytes but localised as large deposits of reaction product on the plasma membranes of occasional cells isolated from old donor

ISSN:0304-324X    

DOI:10.1159/000212509

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Parkinson’s disease ranks among the most prevalent neurological diseases in the elderly. The disease usually begins after the age of 50 years, and the risk of the disease rises steeply with advancing age. The primary etiology of Parkinson’s disease is still unknown, although the aging process may be an important predisposing factor. There is some overlapping between Parkinson’s disease and senile dementia of Alzheimer’s type, although both seem to be disease entities. In Parkinson’s disease, the most prominent and significant neu-ropathological change is the progressive loss of substantia nigra dopamine neurons. Studies of striatal dopamine receptors showed that the specific binding of 3H-spiroperidol was either significantly increased or reduced in the caudate nucleus and putamen of parkin-sonian patients without levodopa therapy. Scatchard analysis showed that there were corresponding changes in the number of receptors, but no significant changes in the mean dissociation constant. Increased binding of 3H-spiroperidol in the basal ganglia was also found in parkinsonian patients suffering from psychotic episodes and treated with neuroleptic drugs. Normal and low binding of 3H-spiroperidol was found in patients treated with levodopa. The behavior of dopamine receptors in the nucleus accumbens was similar to that of dopamine receptors in the striatum. Clinically, the patients with low binding of 3H-spiroperidol in the striatum were more disabled and had lost the beneficial response to levodopa. Thus in some patients with Parkinson’s disease a denervation supersensitivity seemed to develop and in others a loss of postsynaptic dopamine receptor sites in the neostriatum. The latter alteration may contribute to the decreased response of parkinsonian patients to long-term levodopa therapy. However, in patients with a deteriorating response to levodopa, there seem to be still enough dopamine receptors in the striatum for drugs stimulating the dopamine receptors to alleviate directly the parkinsonian disability. Indeed, dopaminergic agonists seem to be a significant and valuable adjuvant therapy to levodopa for parkinsonian patients with a deteriorating response and/or on-of

ISSN:0304-324X    

DOI:10.1159/000212572

出版商:S. Karger AG    

年代:1982

数据来源: Karger