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Biomedical subjects

C Alling

Publications and source records attributed to C Alling.

At least 91 records · Page 5Linked to original sources
PubMed1989

Ethanol stimulates basal and serotonin-induced formation of [32P]phosphatidic acid in human platelets.

The addition of serotonin to preparations of 32P-labelled human platelets resulted in a time- and dose-dependent hydrolysis of [32P]phosphatidylinositol 4,5-bisphosphate (PIP2) and formation of [32P]phosphatidic acid (PA). This response was inhibited by the serotonin2 receptor antagonist ritanserin, indicating that the stimulation was mediated via the serotonin2 receptor. The addition of 50-150 mM of ethanol prior to stimulation with 10(-5) M serotonin resulted in an increased accumulation of [32P]PA, but had no effect on [32P]PIP2. Ethanol stimulated [32P]PA formation at all serotonin concentrations studied (10(-7)-10(-5) M). Furthermore, in the absence of serotonin, ethanol increased basal [32P]PA formation.

Blood Platelets↗
PubMed1989

Bradykinin effects on phospholipid metabolism and its relation to arachidonic acid turnover in neuroblastoma x glioma hybrid cells (NG 108-15).

In neuroblastoma x glioma hybrid cells (NG 108-15) labelled with [32P]-trisodium phosphate, [3H]-inositol and [14C]-arachidonic acid, bradykinin stimulated the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) while it had no effect on the release of [14C]-arachidonic acid (AA). The effect on PIP2 was time- and dose-dependent with a maximal effect on [3H]-inositol- and [32P]-labelled cells after 10-30 s of stimulation with 10(-6) M bradykinin. However, the hydrolysis of [14C]-AA labelled PIP2 was delayed compared to the effect on [3H]- and [14C]-PIP2 and was not detectable until after 60 s of stimulation. Bradykinin stimulation resulted in an increased formation of [3H]-inositol phosphates (IP) and [32P]- and [14C]-phosphatidic acid (PA) but the time course for PA formation did not follow the time-course for PIP2 hydrolysis. A reduced labelling of [32P]- and [14C]-phosphatidylcholine was also found in stimulated cells suggesting that PA may derive from other sources than PIP2. In conclusion, our results indicate that bradykinin activates phospholipase C, but not phospholipase A2, in NG 108-15 cells.

Animals↗
PubMed1989

Protein kinase C modulation of the ethanol effect on serotonin2 receptor transduction in astrocytes.

Acute ethanol exposure stimulated serotonin2 receptor signalling in cultured astrocytes. Pretreatment with the protein kinase C inhibitor H7 significantly increased the ethanol-induced potentiation of [3H]-inositol phosphates accumulation. The increase could be explained by an augmented activation of phospholipase C. The results indicate a role of PKC for the modulation of ethanol effects on cellular signalling.

Astrocytes↗
PubMed1989

Increase in synaptosomal acidic phospholipids after intermittent but not continuous ethanol exposure.

The aim of this study was to compare the effects of different ethanol administration procedures on synaptosomal concentrations of acidic phospholipids. The concentrations of phosphatidylinositol and phosphatidylserine were significantly increased after intermittent ethanol exposure for one week but were unaltered after one or three weeks of continuous ethanol administration. The results indicate the importance of drinking pattern for changes in synaptosomal acidic phospholipids.

Alcoholic Intoxication↗
PubMed1988

The 5-hydroxytryptamine stimulated formation of inositol phosphate is inhibited in platelets from alcoholics.

The accumulation of inositol monophosphate (IP1) was measured after stimulation of 5-hydroxytryptamine2 (5-HT2) receptors on platelets from alcoholics and healthy controls. In controls, 5-HT induced a dose-dependent response with an EC50 = 2 x 10(-6) M and a maximal response at 10(-5) M. Ritanserin, a selective 5-HT2 antagonist, markedly reduced the accumulation. The IP1 formation after stimulation by 10(-5) M 5-HT was significantly impaired in platelets from alcoholics as compared to controls. This study indicates that the 5-HT2 receptor function is inhibited in alcoholics. It also illustrates the possibility of using IP1 formation in peripheral cells as a mean of studying receptor function in disease.

Adult↗
PubMed1988

White matter changes in dementia of Alzheimer's type. Biochemical and neuropathological correlates.

A correlative neuropathological-biochemical study was undertaken in order to characterize the selective incomplete white matter infarctions (SIWI) frequently found in dementia of Alzheimer's type. The brain tissue analysed represented white matter with incomplete infarction, complete infarcts and with histologically normal tissue, in cases with dementia, mainly of Alzheimer and multi-infarct type, in nondemented subjects with cerebral infarcts and in age-matched control cases. The biochemical results verify the existence of the white matter changes and agree on their regional distribution as they appear in the morphological analyses. The increasing severity of SIWI as assessed histologically was reflected in a proportional reduction of several biochemically quantified white matter components. The histological difference between incomplete and complete infarction was also expressed biochemically. Incomplete white matter infarction with and without associated complete infarcts were biochemically similar. The aetiological significance of the loss of different white matter components is discussed. The biochemical data support the concept of SIWI as being an independent white matter disorder of cerebrovascular, hypoperfusional/hypoxic origin.

Aged↗
PubMed1988

Laboratory tests as indicators of alcohol consumption in patients with chronic low back pain.

The use of laboratory screening tests for the detection of heavy drinking in outpatients implies among other things knowledge about their relation to the degree of alcohol consumption. In this study of 95 patients with chronic low back pain, serum gamma-glutamyltransferase demonstrated the best correlation with the mean daily amount of alcohol consumed (r = 0.74). Adding other serological tests, such as high density lipoprotein cholesterol, aminotransferases and linoleic acid content in lecithin, did not improve this correlation, although these tests also correlated well with the alcohol intake.

Adult↗
PubMed1988

Primary astroglial cultures in alcohol and drug research.

Primary cell cultures are a potent tool for studying effects of ethanol and drugs at the cellular and molecular level. Such investigations include effects on proliferating and non-dividing cells. Physiologic mechanisms of drug action can be studied as well as toxic effects. The culture conditions including the rate of cell growth, the cellular composition and the differentiation degree of the cells, must be defined before the results from culture studies can be interpreted and be attached any significance. Changes in cell morphology after addition of the drug can be followed over time and compared with results from electrophysiology and/or drug influences upon cell metabolism including specific biochemical/functional properties on small groups of cells. Interaction between drugs and substances or hormones added to the incubation media can be evaluated. From a physiological point of view it must always be remembered that primary cultures elucidate phenomena which are devoid of integrative function. In that context results from culture models must be confirmed in experimental systems, using the intact organism to prove validity. On the other hand, primary cultures of the nervous system are very suitable model systems for elucidating biochemical mechanisms, especially those at the membrane level. The culture system enables us to study biochemical mechanisms, like the receptor transduction, at a very precise level, avoiding e.g. drawbacks with the blood-brain barrier. Furthermore, specific cells derived either from glial or neuronal origin can be studied separately.

Astrocytes↗
PubMed1987

Formation of phosphatidylethanol in rat brain by phospholipase D.

The mechanism of phosphatidyl [14C]ethanol formation was studied in rat brain microsomal fraction. Phospholipase D and base-exchange enzymes were assayed with [14C]ethanol as substrate. Phospholipase D was found to catalyse the formation of phosphatidylethanol. The reaction was dependent on sodium-oleate as activating factor. Phosphatidylethanol formation by phospholipase D has previously only been reported to occur in plant tissues. Stimulation of base-exchange enzymes with calcium in the presence of [14 C]ethanol did not induce any formation of phosphatidylethanol. These findings indicate that phosphatidylethanol formation in ethanol intoxicated rats is catalysed by phospholipase D.

Animals↗
PubMed1987

5-Hydroxytryptamine stimulates the formation of inositol phosphate in astrocytes from different regions of the brain.

5-Hydroxytryptamine (5-HT) stimulated the turnover of phosphoinositide in primary cultures of astroglia from the cerebral cortex, striatum, hippocampus and brain stem. Ketanserin and ritanserin, selective antagonists for the central 5-HT2 receptor, inhibited the 5-HT-stimulated formation of inositol monophosphate. In contrast, there was no statistically significant accumulation of cyclic AMP after incubation with different concentrations of 5-HT in any of the cultures studied. The results indicate that astrocytes from various regions of the brain possess 5-HT2 receptors coupled to the formation of inositol phosphates.

Animals↗
PubMed1987

CSF-amine metabolites in depression, dementia and in controls.

Lumbar CSF concentration of 5-HIAA, MHPG, and HVA were measured in patients with depression, dementia due to normal pressure hydrocephalus (NPH) and in controls. Moreover, ventricular concentrations of the metabolites were measured in patients with NPH. It was aimed to match patients and controls for age, sex, and body height. Non-parametric statistics were used throughout the study. No differences in lumbar concentrations of CSF 5-HIAA, MHPG and HVA were found between the different diagnostic groups. A ventriculo-lumbar gradient of 5-HIAA and HVA being 4:1 and 5:1, respectively, was found in patients with NPH. No correlation between the difference in ventricular and lumbar concentrations and body height was found, suggesting that body height may be an inaccurate measure for the rostro-caudal gradient. Moreover, no correlation between ventricular and lumbar levels of 5-HIAA and HVA was seen.

Biogenic Amines↗
PubMed1986

Lipids and fatty acids in membranes from astroglial cells cultured in ethanol-containing media.

A study was undertaken to evaluate the usefulness of a primary brain cell culture for the assessment of general membrane phenomena caused by ethanol. The major aim was to study the inertness versus vulnerability of membrane lipids for 8 days of ethanol exposure. Since brain cells in cultures could be more easily influenced by nutrition than in vivo, effects of varying levels of essential fatty acids in the medium were also studied. Astroglial cells from cerebral hemispheres of newborn rats had a fatty acid composition of major phospholipids resembling that of whole brain. Addition of essential fatty acids to the medium profoundly altered the composition of cell membranes, contrary to what is found in whole animal experiments. Ethanol, in graded levels up to 75 mmol/l and added daily up to 8 days, did not significantly change the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine. The ratio between neutral and acidic phospholipids diminished, which was more pronounced after 8 days of ethanol exposure than after 3 days. This study on ethanol exposure on glial cells focuses on the importance of nutritional composition of culture media and on the role of dynamics among phospholipid classes.

Animals↗
PubMed1986

Anionic glycerophospholipids in platelets from alcoholics.

Studies on ethanol-exposed animals have revealed changes in anionic phospholipids in brain membranes. The intention of this study was to investigate whether there was a similar effect on man. Assuming platelets to be an adequate model for CNS synaptosomes, concentration and fatty acid composition of anionic phospholipids, phosphatidylserine (PS) and phosphatidylositol (PI) in the platelet membrane from alcoholics after a debauche period were examined and compared to controls. Ethanol effects on neutral lipids were also analysed in order to obtain a comprehensive view. No quantitative difference was found in anionic phospholipids between alcoholics and controls. Fatty acid composition of individual phospholipids revealed significant changes which were more obvious in neutral phospholipids than in anionic. Oleic acid was increased and linoleic and arachidonic acids were decreased. After 1 week of detoxification, the abnormalities did not decrease, on the contrary they increased and total phospholipid concentration per platelet was significantly higher than in controls. It is concluded that the ethanol toxicity on bone marrow hampers the use of platelets as a model for synaptosomes but that the observed lipid abnormalities might play a major role in the impairment of platelet function in alcoholics.

Adult↗
PubMed1986

Haematological findings in chronic alcoholics after heavy drinking with special reference to haemolysis.

Haematological abnormalities are frequently found in heavy-drinking chronic alcoholics, but anaemia is generally a rare complication. When present, haemolysis is considered to be one of the most common causes. However, little is known about mild haemolysis without anaemia. The present report on eighteen male chronic alcoholics with a recent heavy debauche but without signs of severe liver disease gave support for the occurrence of a reversible low-degree haemolysis without concomitant gross changes of the erythrocytes. Thus the bone marrow showed an increased erythropoiesis in the absence of iron deficiency and known blood losses. Further, increased reticulocyte counts and low levels of haemopexin were noted in the early abstinence. Finally, during the withdrawal phase haptoglobin and haemopexin increased concomitantly with diminishing values of unconjugated bilirubin. The most likely cause of the proposed diminished red cell survival before the withdrawal is supposed to be a reduced membrane stability.

Adult↗
PubMed1986

Pharmacokinetics of zimeldine in male alcoholics.

The pharmacokinetics of zimeldine, a 5-HT reuptake blocker with antidepressive effects, was studied after a single oral dose and after multiple oral administration in 19 alcoholic males, 10 with and 9 without chronic liver damage. The average plasma concentration of zimeldine as assessed by the AUC values (area under the plasma concentration-time curve) was significantly higher in the chronically liver damaged patients than in the patients without chronic liver damage. The plasma half-life of zimeldine was also significantly longer in the chronically liver damaged patients. There were no differences in the obtained pharmacokinetic parameters between the patients having nonchronic liver damage and healthy control subjects. The pharmacokinetics of the active metabolite norzimeldine (resulting from N-demethylation of zimeldine) showed no differences between the two groups of alcoholics and the healthy controls. The IgA values were significantly correlated to both the AUC and plasma half-life of zimeldine. No other correlation between clinical chemistry parameters and pharmacokinetic parameters of zimeldine and norzimeldine were found.

Adult↗
PubMed1985

Formation of phosphatidylethanol in frozen kidneys from ethanol-treated rats.

We recently identified phosphatidylethanol (Pet) in tissues from ethanol-treated rats. Since phosphatidyl esters are formed artefactually during freezing in plants we wanted to examine if PE was elevated during freezing in animal tissues. Rats were treated with 3 g/kg of ethanol, killed after 3 h and PE was isolated from kidneys at once or after storage at 0, -5, -10, -15, -20 and -80 degrees C for 7 days. Kidneys analyzed at once or after storage at -80 degrees C had Pet equivalent to 0.02 mumol Pet/g. Storage at -10 degrees C and -15 degrees C resulted in increases of Pet to 1.5 mumol Pet/g and 1.2 mumol Pet/g, respectively. Thus, Pet is artefactually elevated during storage of tissues from ethanol-treated rats at lower freezing temperatures, reflecting considerable changes in composition of acidic phospholipids.

Animals↗
PubMed1985

Changes in dopamine receptor sensitivity in humans after heavy alcohol intake.

Dopamine (DA) sensitivity, assessed through maximal growth hormone (GH) response to stimulation by apomorphine (APO) (0.18-0.24 mg iv) was studied in 16 chronic alcoholics newly admitted after a period of heavy alcohol intake. Repeated hormonal tests were thereafter performed during a 2-month period under strictly controlled conditions to avoid relapse into alcohol consumption. Eight healthy volunteers with alcohol consumption slightly less than that of the general population were used as controls. It was found that DA sensitivity in the early abstinence phase was higher than later in the 2-month recovery period but not significantly different from control values. The relatively higher DA sensitivity in the early abstinence phase might be responsible for a lower threshold for psychotic symptoms and neuroleptic-induced extrapyramidal side effects. The results of this study give further evidence of a prolonged recovery phase after heavy alcohol intake.

Adult↗