Search PubMed⌕ Search

Biomedical subjects

C Alling

Publications and source records attributed to C Alling.

At least 109 records · Page 6Linked to original sources

Fatty acid composition of ethanolamine phosphoglycerides in different areas of the gerbil brain after chronic exposure to trichloroethylene.

Exposure of Mongolian gerbils to trichloroethylene (TCE) (320 ppm) in an inhalation chamber continuously for 3 mo resulted in an altered fatty acid pattern of phospholipid in discrete areas of the brain. Lipids were extracted from four brain regions: the cerebral cortex, the hippocampus, the cerebellar vermis posterior, and the brain stem. No changes induced by TCE were found in lipid class distribution among the different regions examined. Whole brain weights and weights of the dissected pieces were also unchanged. In ethanolamine phosphoglycerides from the cerebral cortex and the hippocampus, a decrease was found among long-chain fatty acids derived from linolenic acid with a corresponding increase of the linoleic acid family. The cerebellar vermis and the brain stem were less affected. Since areas rich in gray matter were affected more than those with a high proportion of white matter, it seems reasonable to assume that the fatty acid alterations of ethanolamine phosphoglycerides occur mainly in the gray matter. Furthermore, we suggest that the alterations can be a compensatory mechanism for the membrane fluidizing properties of TCE.

Animals↗

Cellular composition of primary cultures from cerebral cortex, striatum, hippocampus, brainstem and cerebellum.

Primary cultures from newborn rat cerebral cortex, striatum, hippocampus, brainstem and cerebellum were grown for 14 days. There was a linear relationship between the amount of material seeded and the protein content of the respective culture. The amount of tissue material seeded was selected so that the different cultures reached confluence at 6-7 days and contained similar amounts of protein when 7 and 14 days old. The cellular content was evaluated by astroglial markers, such as the glial fibrillary acidic protein (GFAp; alpha-albumin) and the S-100 protein, and by markers for other cells expected to be in the cultures (14-3-2 protein, macrophage acidic protein (MAP), alkaline phosphatase, myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP]. Astroglial-like cells represented 60-70% of the cells present in the different cultures. Quantitation of GFAp (alpha-albumin) showed similar amounts to be present in cultures from cerebral cortex, hippocampus and striatum; however, on lower levels expressed in soluble proteins than in the corresponding brain regions of adult rats. Brainstem of adult rat contained large amounts of GFAp (alpha-albumin), while low levels were found in brainstem culture. Also, phagocytic cells (macrophages), endothelial-like cells, mesenchymal-like cells, ependymal-like cells and oligoblasts were found. Neither mature neurons, nor oligodendroglial cells were observed. It is concluded that although there might be some differences in the degree of maturation or in the cellular composition of the various cultures, they could serve as a good model system for studying the characteristics of astroglial cells from various brain regions.

Animals↗

Phosphatidylethanol formation in rat organs after ethanol treatment.

An abnormal acidic phospholipid was found in high concentration in kidney and brain, and also in other organs of rats exposed to ethanol by i.p. injection or by a liquid diet. The compound could be identified as phosphatidylethanol. Phosphatidylethanol is probably formed in cell membranes by a phospholipase D-catalyzed transphosphatidylation reaction.

Animals↗

Molecular size of myelin basic protein immunoactivity in spinal fluid.

The molecular size of myelin basic protein (MBP) immunoactivity in spinal fluid from patients with multiple sclerosis, acute stroke or who had gone through neurosurgery was determined by gel filtration. Gel filtration fractions were analysed for MBP by radioimmunoassay. Spinal fluid from all patients demonstrated a broad range of MBP immunoactivity. The neurosurgery and stroke cases had high MBP immunoactivity in the higher molecular range, around 67 000 daltons. The spinal fluid from MS patients had increased levels of low molecular size MBP immunoactivity, around 10-13 000 daltons. The results suggest that different forms of demyelinating processes give rise to various kinds of MBP fragments and/or different proteolytic activity on MBP within the spinal fluid space.

Acute Disease↗

Chronic effects of perchloroethylene on the composition of lipid and acyl groups in cerebral cortex and hippocampus of the gerbil.

Continuous exposure of Mongolian gerbils to perchloroethylene (PCE) (120 ppm) for 12 months in an inhalation chamber caused no changes in body or brain weights. The protein content, the concentration of lipid phosphorus or cholesterol were unaltered in the cerebral cortex and hippocampus. However, a small change in the fatty acid pattern of phospholipid was observed. In the phosphatidylethanolamine of cerebral cortex and hippocampus a decrease was found among the long-chain, linolenic acid-derived, fatty acids. The ratio 22:4 (N-6)/22:5 (N-3) was increased, indicating a shift towards the corresponding linoleic acid-derived 22-carbon fatty acids. The observed changes among poly-unsaturated fatty acids are similar to those appearing after peroxidation and either protein or essential fatty acid malnutrition. However, an attractive explanation for the changes is that they represent a response to the fluidizing properties of PCE.

Animals↗

Changes in fatty acid composition of major glycerophospholipids in erythrocyte membranes from chronic alcoholics during withdrawal.

Low-degree haemolysis, seen in alcoholics after debauche, may originate from abnormal lipid and fatty acid composition of the erythrocyte membranes. This hypothesis was tested on 13 chronic alcoholics without signs of severe liver disease after an abuse period of more than 7 days. Erythrocytes were analysed at admittance and during withdrawal after 1 and 2 weeks. In order to evaluate the usefulness of whole erythrocytes instead of purified plasma membranes for these analyses a comparison was made. No differences were found with regard to the fatty acid patterns. Reference values of the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine from erythrocytes were also established in control persons. The fatty acid composition of both phosphatidylcholine and phosphatidylethanolamine in the erythrocytes was significantly different from controls at admission. Polyunsaturated fatty acids were decreased and saturated and monounsaturated fatty acids were increased. In phosphatidylcholine, the proportions of the fatty acids of the linoleic acid series were 24% decreased at admittance and 2 weeks later still 19% lower than in controls. The abnormal fatty acid patterns of erythrocytes correlated with similar aberrations in blood plasma phospholipids at admittance. The pathological levels of fatty acids in erythrocytes normalized slower in erythrocytes than in plasma. We conclude that the abnormal fatty acid composition is induced during erythropoiesis.

Adult↗

Tolerance to ethanol in rats bred on essential fatty acid deficient diets.

We bred three generations of Sprague-Dawley rats on a diet deficient in essential fatty acids, low-EFA (0.3 energy %), whereas age matched controls received normal-EFA (3.0 energy %). Subgroups (N = 6) of female rats were given daily IP injections of ethanol (3.0 g/kg) or isocaloric glucose for 23 consecutive days. On days 1 and 22 blood-ethanol profiles, rates of ethanol metabolism and ethanol-induced impairment of motor coordination were measured after the challenge dose of 3.0 g/kg. Rats exposed to ethanol ate and drank more than controls and gained more body weight over the 23 days. Low-EFA rats were slightly more impaired than normal EFA rats after an acute dose of ethanol even though the peak blood ethanol concentrations reached were about the same at 2.9 mg/ml (63 mmol/l). After chronic ethanol treatment a functional tolerance developed in both dietary groups but the degree of tolerance was less clearcut in low EFA rats. Metabolic tolerance was confirmed after chronic treatment in both dietary groups as shown by steeper slopes (19-27%) of the ethanol elimination curves. But no significant differences in the development of metabolic tolerance were apparent in rats on low EFA and normal EFA diets.

Animals↗

Alcohol effects on cell membranes.

The brain has a great cellular heterogeneity. It is one of the most membrane dense organs in the body. There are different kinds of movements within the membranes. These are influenced by the acute effect of ethanol, which gives rise to more fluid membranes. When the lipid milieu in which the proteins are embedded is disturbed, the properties of the enzymes and receptor proteins are altered. Fluid regions are more affected than rigid ones. In chronic alcoholism, selective vulnerability among the cells determines the final outcome and myelin seems to be reduced. Biochemical assays on humans are restricted to spinal fluid, where brain membrance molecules must be searched for.

Alcohol Drinking↗

Chronic exposure to trichloroethylene: lipid and acyl group composition in gerbil cerebral cortex and hippocampus.

Inhalation exposure of Mongolian gerbils to trichloroethylene (50 and 150 ppm) for 12 months caused only small changes in the lipid composition of their cerebral cortex and hippocampus. Total protein content and lipid class distribution were almost unaffected. However, the cholesterol to phospholipid ratio decreased in the cortex of animals exposed to trichloroethylene. This might be due to changes in the relative proportions of different membranes or cellular types. The finding of most interest was among the long-chain polyunsaturated fatty acids where changed ratios were found between long-chain derivatives of the linoleic and the linolenic acid series and a decrease in two minor fatty acids, 20:5 (n-3) and 22:5 (n-3). We think it is likely that such changes occur as a result of peroxidation of polyunsaturated fatty acids or in order to withstand the fluidizing properties of trichloroethylene.

Animals↗

Radioimmunoassay of myelin basic protein. A methodological evaluation.

Three techniques for separating free antigen from antigen-antibody complexes have been applied to radioimmunoassay of myelin basic protein: cold ethanol precipitation of complexes, dextran-coated charcoal precipitation of free antigen, and second antibody precipitation of complexes. After optimization of the incubation and separation steps, the 3 methods were evaluated for precision and accuracy when applied to both spinal fluid and brain tissue homogenates. For determinations in brain tissue all 3 methods showed the same precision and gave largely the same values, though the ethanol method gave slightly lower levels. For spinal fluid the ethanol and dextran-charcoal methods gave the same values, but the double antibody method gave values only 1/3 as high. With spinal fluid, the precision of the dextran-charcoal method was poor compared with that of the other two. The double antibody method proved to be the method of choice for brain tissue samples, when the results of the incubation and separation steps, and the precision and accuracy of the determinations were taken into account. However, for an unknown reason values for spinal fluid were too low by this method. Therefore the ethanol precipitation method is recommended for spinal fluid samples and the double antibody method for brain tissue samples.

Animals↗

Brain primary culture-- a characterization (part II).

Brain primary cultures from newborn rat hemispheres have been further characterized. THe cultures contained the glial fibrillary acidic protein (GFAp; alpha-albumin), as analyzed quantitatively. GFAp (alpha-albumin) increased in concentration during growth of cultures and during maturation of the intact rat brain. FITC-labelled antibodies against GFAp (alpha-albumin) reacted specifically with astrocyte-like cells. Theses cells were also positive after Rio-Hortega's silver carbonate staining for astrocytes. No myelin basic protein (MBP) was detected in cultures, neither by quantitative measurements nor by immunofluorescent histochemistry. Negative results were also obtained for the myelin specific enzyme 2', 3'-cyclic nucleotide 3'-phosphohydrolase (CNP), e. e. the enzyme was at the same level in the cultures of different ages as in 3-day-old rat hemispheres. However, in rat brain increasing concentrations of MBP and CNP were found during maturation. This means that no myelin and thereby probably no or few differentiated oligodendroglial cells were present in the cultures, where the predominate cell type was of astroglial nature.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Serum concentration and protein binding of thioridazine and its metabolites in patients with chronic alcoholism.

The blood chemistry and clinical pharmacokinetics of thioridazine and its metabolites, side-chain sulphoxide, side-chain sulphone and ring sulphoxide, were studied in 31 alcoholics and were compared with values in 17 thioridazine-treated controls without alcoholism. Pathological blood chemistry values, including abnormal liver function and protein concentrations, were common among the alcoholics. In relation to dosage, the majority had a low serum concentration of thioridazine and at a given concentration of thioridazine they had high serum concentrations of its metabolites. Positive intercorrelations were found between pathological liver function tests, prolonged serum half-life and increased serum concentration of thioridazine. The free fractions of thioridazine, side-chain sulphoxide and ring sulphoxide were significantly higher and those of the side-chain sulphone lower in the alcoholics than in the controls. The free fractions of side-chain and ring sulphoxide were significantly increased in patients with a low concentration of alpha 1-acid glycoprotein.

Adult↗

Studies on duration of a late recovery period after chronic abuse of ethanol. A cross-sectional study of biochemical and psychiatric indicators.

A cross-sectional study on patients with different abstinence time was performed to describe long-time biochemical and psychiatric changes due to withdrawal from heavy alcohol abuse. Physical, neurological, psychiatric and biochemical parameters were measured in 70 patients with a withdrawal period ranging from 2-90 days. The various parameters changed over time in different manners. Fatigability, reduced sleep, reduced sexual interest, apparent sadness, hostility and global ratings of abstinence improved significantly with the duration of the recovery period. Symptoms related to brain hyperexcitability such as fatigability, inner tension, insomnia and pains persisted for approximately 5 weeks. Of the biochemical parameters, the transaminases were normal in patients with more than 10 days of abstinence, while the levels of gamma-glutamyltransferase and HDL-cholesterol remained high for longer periods. The essential fatty acid status, measured by the fatty acid composition of serum lecithin, appeared to be normal only in patients with long recovery time. MAO in platelets was significantly lower than in the controls. The highest values were seen in the early recovery phase, which may indicate a temporary increase. Since polyunsaturated fatty acids are important constituents of synaptic membranes and since platelet MAO may reflect brain MAO, we consider these co-existing findings important in the interpretation of the psychiatric symptoms. The study demonstrated the existence of a subacute withdrawal syndrome lasting for 4-6 weeks.

Adult↗

Impairment of the blood-brain barrier as an aetiological factor in paranoid psychosis.

Possible psychiatric implications of impairment of the blood-brain barrier were studied in 25 patients with paranoid psychosis. Determination of the ratio between the albumin concentrations in cerebrospinal fluid and serum showed increased, indicating impairment of the blood-brain barrier, in seven patients and normal values in 18. The two groups were compared for clinical, pharmacokinetic, neurophysiological and anamnestic variables. The highly significant finding that onset of psychosis had occurred, on average, 20 years earlier in the patients with impairment of the blood-brain barrier than in those without suggests that such impairment might influence the development of psychosis in predisposed individuals.

Adolescent↗

Impairment of renal function in patients on long-term lithium treatment.

A survey of the renal function in 278 patients on long-term lithium treatment maintained on plasma lithium concentration of 0.7-1.2 mmoles/l was conducted. The extent of renal damage were studied with urinary concentration tests, beta-2-microglobulin excretion and measurement of glomerular filtration rate. The mean treatment time was 6.5 years and the longest treatment time was 15 years. Forty-nine per cent of the patients could not concentrate their urine to above 800 mOsm/kg of water, which did not correlate with the presence of polyuria. The urine concentration capacity decreased as a function of time in the lithium treated group, and it was also influenced by the type of tablet administration (readily soluble or sustained release), but not by combination with other drugs, such as neuroleptics. Beta-2-microglobulin excretion was not increased. A reduced glomerular filtration rate was found in 17% and the filtration rate in the whole group of patients was clustered around the lower limit of normal. The filtration rate decreased as a function of the duration of treatment. It was found that the concentrating capacity and the filtration rate decreased in parallel and that there was no selective impairment of the concentrating capacity. We conclude that severe impairment of renal function is uncommon in well controlled patients. Urinary concentration tests are shown to be the most suitable test for detection of kidney damage in long-term lithium treatment.

Adult↗

The effect of chronic ethanol administration on lipids and fatty acids in subcellular fractions of rat brain.

In this study we have investigated the proportion of lipids and of fatty acids in brain membranes and blood serum from rats which received ethanol over a long period. Nine Sprague-Dawley rats were given ethanol in their drinking water for five months. Nine age-matched rats given pure water served as controls. Subcellular fractions (myelin, synaptosomes and mitochondria) were prepared in a discontinuous gradient of sucrose from each of the 18 rats. Blood serum was collected at decapitation. The fractions were assayed for their concentrations of protein, cholesterol, phospholipids and for the proportions of fatty acids in individual phosphoglycerides. No significant differences in the concentration of the major lipids were obtained between the ethanol-exposed rats and the control rats. In the synaptosomal fraction from ethanol-exposed rats, the proportion of oleic acid in phosphatidylcholine was increased and that of arachidonic acid in phosphatidylethanolamine decreased. These two fatty acids were also changed in the blood serum and there was a significant correlation between the changes in the brain and blood serum. The results suggest that during ethanol exposure there is an increased disposition toward modification of synaptosomal membranes by changes in the blood plasma fatty acid pattern.

Animals↗