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Biomedical subjects

R Strong

Publications and source records attributed to R Strong.

At least 55 records · Page 3Linked to original sources

In vitro effects of ethanol on erythrocyte membrane fluidity of alcoholic patients: an electron spin resonance study.

Chronic ethanol consumption has been shown to affect physical properties of membranes from animals as measured by electron spin resonance (ESR). This study compared for the first time the physical properties of erythrocyte membranes of alcoholic patients and control subjects using ESR procedures. Membrane fluidity was determined in the presence and absence of ethanol using the 5-doxyl stearic acid spin-label. Temperature-dependent phase transition also was determined, as were comparisons between ESR parameters, at the 1st and 5th week after alcohol withdrawal. Ethanol-induced fluidity was significantly greater in membranes of control subjects compared with alcoholic patients. Baseline fluidity did not differ and the temperature at which the phase transition occurred was not significantly different between the two groups. The resistance of membranes of alcoholic patients to fluidization by ethanol was unchanged after 5 weeks of withdrawal. Comparisons between ethanol-induced fluidization at the 1st and 5th week after withdrawal were not significantly different. These studies demonstrate differences in ethanol-induced fluidization between alcoholic patients and control subjects that are consistent with earlier ESR studies using an animal model.

Adult

Effects of ethanol on acetylcholine and GABA release: differences in the role of potassium.

Ethanol inhibited electrically stimulated [3H]ACh release from cortical brain slices, but not when release was stimulated by high potassium. In contrast, ethanol was ineffective on electrically stimulated release of [14]GABA from cortical brain slices, but inhibited potassium-induced release. Ethanol also significantly inhibited potassium-stimulated [14C]GABA release from cortical synaptosomes. These data suggest that ethanol selectively inhibits GABA release from neurons by a specific effect on potassium conductance, and inhibits ACh release by a selective effect on Na+ conductance.

Acetylcholine

Chronic ethanol effect on the acidic phospholipids of synaptosomes isolated from cerebral cortex of C57BL/6NNIA mice--a comparison with age.

A total of six groups of C57BL/6NNIA male mice at 6, 18 and 28 months of age were administered a liquid diet containing either ethanol (8 g/kg body wt/day) or an isocaloric amount of glucose for three weeks. Sixteen hours after the last ethanol feeding, homogenates of cerebral cortices were prepared for isolation of the synaptosome-mitochondrial fraction. Phospholipids were separated by two-dimensional tlc and the level of individual phospholipids was determined by assaying the lipid phosphorus content. Based on protein content, there was a decrease (18%) in the level of phosphatidylserines between samples from 6 and 28 month-old mice; no age difference was observed in other phospholipids. Ethanol consumption resulted in a three-fold increase in poly-phosphoinositide level in the 6 month-old group, but the difference diminished considerably with age. The increase in poly-phosphoinositide level suggests a link between chronic ethanol administration and the receptor-mediated signal transduction mechanism involving phosphoinositide turnover. Results further indicate that animals in the younger age group are more readily influenced by the chronic effect of ethanol than those in the older age group.

Aging

Fluidizing effects of centrophenoxine in vitro on brain and liver membranes from different age groups of mice.

This study examined the effects of different concentrations of centrophenoxine on physical properties of synaptic plasma membranes and liver microsomes using electron spin resonance procedures. Membranes of different age groups of mice were labeled with the 5-doxyl stearic acid spin-label and membrane fluidity determined in the presence and absence of different concentrations of centrophenoxine. Centrophenoxine had a direct effect on membranes as shown by a significant increase in membrane fluidity. This effect was greatest in liver microsomes as compared to synaptic plasma membranes. Age differences were not observed in centrophenoxine-induced fluidization. Effects of centrophenoxine in vivo may be due in part to the drug acting directly on the physical properties of the membrane lipid environment.

Aging

Dolichol alters dynamic and static properties of mouse synaptosomal plasma membranes.

Dolichols are isoprenologues that are found in almost all tissues and whose biochemical function, aside from dolichol phosphate precursors, is not known. In addition, an understanding of the organizational and dynamic properties of dolichols in biological membranes has not been forthcoming. The purpose of the experiments reported here were to examine the effects of dolichol on the physical properties of mouse synaptic plasma membranes (SPM). Differential polarized phase fluorometry indicated that dolichol both fluidized and rigidified SPM. Membrane areas detected by diphenylhexatriene and trans-parinaric acid were selectively fluidized and rigidified, respectively. It also was found that the spin label, 5-doxyl stearic acid indicated that dolichol reduced membrane fluidity. These results report for the first time a structural effect of dolichol on a biological membrane.

Animals

Intra-regional variations in the effect of aging on high affinity choline uptake, choline acetyltransferase and muscarinic cholinergic receptors in rat neostriatum.

High affinity sodium-dependent choline uptake (HACU), choline acetyltransferase (ChAT) and quinuclidinyl benzilate binding ([3H]-QNB) are measured in synaptosomal preparations from four areas of the neostriatum of Fischer 344 rats of three different ages (6, 18 and 30 months). There is a marked regional distribution of all three markers, being higher generally in lateral as compared to medial striatal regions. In addition, in the medial neostriatum, all three measures are higher rostrally than caudally. HACU is reduced with age in the rostromedial and the caudolateral neostriatum. Small (usually less than 20%) but significant decreases in muscarinic cholinergic receptors occur in all regions of the neostriatum. There are no significant age-associated differences in ChAT activity in any region. The lack of decrease in ChAT is evidence that the reductions in HACU in striatal subregions are not simply the result of a loss of axon terminal integrity. The changes in HACU may reflect altered activity of cholinergic neurons in specific striatal subregions.

Animals

Chronic ethanol consumption and aging: changes in lipid composition of liver microsomes.

Both aging and chronic ethanol consumption have been found to produce changes in lipid composition. Severity of intoxication, withdrawal and release of gamma-aminobutyric acid following chronic ethanol consumption have been shown to be associated with age. It was predicted in this study that aged mice would differ in response to ethanol-induced changes in lipid composition of liver microsomes as compared to younger mice. Two different age groups of C57BL/6NNIA male mice (6 and 28 months) were administered an ethanol or control liquid diet for 24 days. Liver microsomes were prepared on Day 25. Age and ethanol consumption significantly affected liver weight and the ratio of liver weight to body weight. PC significantly decreased and PE significantly increased in both the young and old ethanol groups. Cholesterol and total phospholipid content were not affected by age or chronic ethanol consumption. Aged animals were able to adapt to the effects of chronic ethanol administration to the same extent as younger animals. These findings differ from studies that have examined effects of chronic ethanol consumption on behavior and neurotransmitter release among different age groups of mice. While the results are specific for liver microsomes, it appears that chronic ethanol consumption has less of an effect on liver function as compared to brain function in aged mice.

Aging

Metabolic characteristics of aorta from spontaneously hypertensive and renal and deoxycorticosterone acetate-salt hypertensive rats.

The purpose of this study was to determine if any changes occurred in the basal and stimulated rates of oxygen consumption and lactate production of thoracic aortas from spontaneously hypertensive rats (SHR) and renal and deoxycorticosterone acetate (DOCA)-salt hypertensive rats, and, if so, whether these changes were similar in these three models of hypertension. Rings of thoracic aorta were placed in an isothermic (37 degrees C) muscle bath, and isometric tension development, oxygen consumption, and lactate production were measured. The results indicated that under basal conditions oxygen consumption, but not lactate production, was higher in aortas from all three hypertensive models; the elevation above control was greatest in the renal model (95%) and smallest in SHR (34%). On stimulation with 60 mM KCl, a significant increase in oxygen consumption above basal value occurred in all aorta samples (p less than 0.05); however, lactate production was increased above basal only in aortas from hypertensive animals. Only in aortas from renal and DOCA-salt models was the rate of oxygen consumption during stimulation significantly greater than that of their normotensive controls (p less than 0.05). Developed active stress in response to KCl was the same in all groups, and when the change in lactate production or oxygen consumption was expressed relative to the amount of active stress developed, no differences were observed. These results suggest that, 1) compared to values in aortas from normotensive animals, only the basal rate of oxygen consumption is higher; 2) this higher level of basal metabolic activity is not associated with an alteration in the metabolic cost of force development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Comparison of the hepatic mixed function oxidase system of young, adult, and old non-human primates (Macaca nemestrina).

The influence of age on the mixed function oxidase system from a non-human primate was studied. Microsomes were isolated from the livers of female Macaca nemestrina ranging from 2 to 21 years of age. No significant age-related change was observed in either the cytochrome P-450 content or the NADPH cytochrome c reductase activity. In addition, the ability of the microsomes to metabolize benzo [a]pyrene did not change significantly with age. These observations contradict studies with liver tissue from laboratory rodents in which an age-related decline in the mixed function oxidase system is generally observed. The lipid composition of the liver microsomes was studied also. Both the cholesterol and total phospholipid content of the liver microsomes increased significantly with age; however, the ratio of cholesterol to phospholipid remained constant. The percentage of individual phospholipids in the microsomes changed only slightly with age. These results provide new information on the effect of age on the mixed function oxidase system and indicate that one must be cautious in extrapolating from studies with liver tissue from laboratory rodents to primates.

Age Factors

Morbidity and mortality of operative intubation for malignant oesophageal obstruction.

In 33 patients who underwent operative intubation of carcinoma of the oesophagus or gastric cardia, there were nine postoperative deaths (mortality 27%). Only 15 patients (46%) had no further operative procedure or anaesthetics, but their mean survival was only 3.7 months. Nine patients (27%) required a total of 17 procedures after the placement of their original tube. Operative intubation has a similar mortality to resection but the survival times are short. Whenever possible palliative resection or endoscopic intubation is to be recommended.

Aged

Changes in lipid composition of cortical synaptosomes from different age groups of mice.

Lipid composition of cortical synaptosomes differed with age in C57BL/6NNIA mice. Significant age differences were observed for cholesterol and the ratio of cholesterol to total phospholipid phosphorus content. The phospholipid to protein ratio of individual phospholipids also increased with age with diacyl-sn-glycero-3-phosphocholine (PC) increasing the most. Acyl group composition of individual phospholipids, however, showed little age difference. The double bond index for PC decreased significantly with age. Changes in membrane composition may help explain differences in the effects of ethanol on the physical and biochemical properties of membranes from different age groups that have been reported previously.

Aging

Regional analysis of neostriatal cholinergic and dopaminergic receptor binding and tyrosine hydroxylase activity as a function of aging.

Tyrosine hydroxylase (TH) activity, as well as dopaminergic and cholinergic muscarinic receptor binding were measured in discrete regions of the neostriatum of rats 7, 17, and 27 months old. Activity of TH was highest in the rostral neostriatum as compared to the caudal region. Age-related differences in TH were detected in only one region. The density of dopamine receptors was also highest in the rostral neostriatum of all age groups, but there were no significant age-related differences. The distribution of cholinergic muscarinic receptor binding was similar to that of TH and dopaminergic receptors, and showed age-related changes in discrete regions. These results, when considered with previous data, suggest that in selected striatal regions in the Sprague Dawley rat the cholinergic system is more vulnerable than the dopaminergic system to aging effects.

Aging

High-affinity uptake of neurotransmitters in rat neostriatum: effects of aging.

High-affinity uptake of dopamine (DA), glutamate, and gamma-aminobutyric acid (GABA) was determined in crude synaptosomal preparations from neostriatal regions of rats 7, 17, and 27 months of age. Dopamine uptake was highest in rostral neostriatum, but no age-related differences were detected. On the other hand, the high-affinity uptake of both GABA and glutamate was increased with age. This may reflect astrocytic hypertrophy or hyperplasia, which have been reported to occur in the neostriatum during the aging process.

Aging

Membrane properties and aging: in vivo and in vitro effects of ethanol on synaptosomal gamma-aminobutyric acid (GABA) release.

It has been reported previously that biological membranes from aged mice are disordered less by ethanol as compared with membranes from younger animals. The purpose of this study was to determine whether those age differences would be associated with changes in membrane transport as measured by release of gamma-aminobutyric acid (GABA). GABA release in the presence and absence of ethanol was measured in synaptosomes from young (4 months), middle (14 months) and aged (28 months) C57BL/ 6NNIA male mice. In addition, the effects of chronic ethanol administration on GABA release was examined in young and aged mice. GABA release was inhibited more by ethanol in synaptosomes from young mice as compared with older mice. The IC50 for ethanol was significantly lower for the younger mice than for the older mice. GABA release in the presence of ethanol was affected by chronic ethanol administration. Inhibition of release was significantly less for young ethanol-tolerant as compared with young control animals. Release did not differ significantly between the old ethanol and old control groups. Inhibition of GABA release was found to be highly related to the membrane/buffer partition coefficient of n-alcohols. The results of the present study are consistent with our earlier finding that membranes from aged mice are disordered less by ethanol as compared with younger mice.

Aging

The cholinergic system in rat striatum during morphine tolerance and dependence.

Male Sprague-Dawley rats were used in the present study to assess the effects of chronic treatment of morphine on the striatal cholinergic system. The results demonstrate that neither short nor long-term morphine treatment had an effect on choline acetyltransferase (ChAT) activity or 3H-quinuclidinylbenzilate (3HQNB) binding in discrete striatal regions of the rat brain.

Acetylcholine

Ethanol-induced disordering of membranes from different age groups of C57BL/6NNIA mice.

In previous studies, we have shown that many of the pharmacological effects of ethanol administered in vivo are greater in older mice compared to younger mice. This study determined if there are age-related differences in membrane order when ethanol is administered in vitro. Synaptic plasma membranes, brain microsomal membranes and erythrocyte membranes were isolated from young (3-5 month), middle (11-13 months), and old (22-24 months) C57BL/6NNIA mice. The order parameter of each age group was measured using a 5-nitroxide stearic acid spin label in the presence of 0, 250 and 500 mM ethanol added in vitro. No age-related differences in order parameter were seen in the absence of ethanol. However, membranes from young animals were disordered to the greatest degree by ethanol. The synaptic plasma and erythrocyte membranes from young mice were disordered by both 250 and 500 mM ethanol. Membranes from old mice were disordered significantly by 500 mM ethanol only and the disordering was not as great as was seen in the membranes from the young mice. In the microsomal membrane preparation, 500 mM ethanol significantly disordered the membranes from the young animals, but it had no effect on membranes from old animals. Age differences were also observed generally for cholesterol and total phospholipid which both increased with increasing age for synaptic plasma and brain microsomes. Membrane disorder induced by ethanol differs with age and is associated with cholesterol and phospholipid content of membranes.

Age Factors

Regional mapping of neostriatal neurotransmitter systems as a function of aging.

The purpose of the present investigation was to map chemically the distribution of certain neurotransmitter systems in the neostriatum of rats aged 6, 16, and 26 months. This mapping was carried out by microdissection of discrete striatal regions coupled with radiometric assays for choline acetyltransferase (ChAT), glutamate decarboxylase (GAD), dopamine (DA), and norepinephrine (NA). In all age groups, ChAT, DA, and NA were highest in the rostral relative to the caudal neostriatum. Additionally, ChAT was higher in the lateral than in the medial region, whereas GAD was more homogeneously distributed within the striatum. ChAT activity was decreased significantly primarily in the caudal regions in rats aged 16 and 26 months. DA levels were decreased in the caudal striatum in rats aged 26 months. NA levels were found to be significantly decreased primarily in the rostral neostriatal regions of the oldest rats. GAD activity remained unchanged in all age groups. These regional changes in selected neurotransmitter systems may underlie specific motor and cognitive deficits that often occur during aging.

Aging