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Brain lipids in pyridoxine-deficient young rats.

Pyridoxine deficiency produced in rats during the period of development of the central nervous system resulted in a decreased incorporation of (1-14C) acetate into total lipid extracts of brain. It also resulted in a uniform decrease in the incorporation of the labeled precursor into the cholesterol, glycolipid and phospholipid fractions of brain. The specific radioactivity of purified cerebrosides and sulfatides was decreased by 78% in pyridoxine-deficient rats with respect to controls. The decreased incorporation of labeled precursor in the deficient rats was not due to the labeled precursor, since the specific radioactivity of brain acetate and the brain concentrations of acetyl coenzyme A and acetate were similar in both deficient and control rats. The results indicate that in pyridoxine deficiency established in the young rat there is an impaired formation of myelin.

Acetates↗

[Metachromatic leukodystrophy in adult patient initially diagnosed as multiple sclerosis].

The article presents a case of metachromatic leucodystrophy (MLD) of the adult onset type, in which atypical initial course could suggest multiple sclerosis. MLD is an inherited, metabolic, degenerative disease of the nervous system. It is caused by a deficiency of a lysosomal enzyme--arylsulphatase A, with the storage of cerebroside sulphate and demyelination affecting mainly the central and peripheral nervous system. In the reported case of a female aged 21 the clinical onset of the disease was at the age 20. The first neurological symptoms included a mild spastic paraparesis, ataxia of lower limbs, and imbalance. The neurological deterioration has been progressing since the onset. There was no family history of neurological or metabolic diseases, but the patient's parents were near relatives (first cousins). T-2 weighted MRI showed high intensity areas in the white matter, mainly periventricular. The clinical symptoms could suggest multiple sclerosis (of the primary progressive type). The patient was admitted to our Dept. in Oct. 2000, i.e. about a year since the onset. Her increasing spastic triparesis, cerebellar ataxia, neuropathy in lower limbs and cognitive deterioration were confirmed. Re-analysis of the patient's clinical picture and family history, her MRI scans and repeated neurophysiological examinations which demonstrated a damage of the central and peripheral nervous system, suggested metachromatic leucodystrophy. Therefore, it was decided to assay arylsulphatase A activity. The result confirmed the diagnosis of the late onset MLD. Additionally, molecular genetic examination was performed of a DNA sample obtained from the patient.

Adult↗

[Studies on chemical constituents in herba of Lysimachia davurica].

OBJECTIVE: To study the chemical constituents from the whole plant of Lysimachia davurica. METHOD: The constituents were separated and purified by column chromatograph, and identified by spectral analysis and physical data. RESULT: Six compounds were isolated and identified as triacontanoic acid(I), palmitic acid(II), beta-amyrin(III), stigmasterol(IV), oleanolic acid(V), soya-cerebroside I (VI). CONCLUSION: I, III, VI were isolated from this gene for the first time.

Cerebrosides↗

[Late perturbations of the central nervous system compatible with life. 5. Study of learning aptitude of the offspring after administration of anticerebroside serum to pregnant female and newborn rats].

Rabbits are injected with cerebrosids, cholesterol and albumen. Their serum, titrated for anticerebrosids antibodies, was injected into female rats on the 18th, 19th and 20th days of gestation and into the offspring aged 5, 9 and 14 days. The learning ability of the little rats was explored at the age of 1-1/2, 3, 4-1/2 and 6 months. Only the offspring of non-treated mothers and treated themselves present an important alteration of their learning ability, particularly if the injection is on the 5th post-natal day. These results are discussed.

Age Factors↗

[Adult-type Gaucher's disease: an histochemical study of one case (author's transl)].

Spleen of adult-type Gaucher's disease has been investigated by histochemical technics. As usually, an overload of cerebroside (revealed by the PAS reaction for glycolipids) with beta-glucosidase deficiency has been demonstrated. But many particularities must be emphasized in this case: increase of acid MPS, high activities of pentose pathway--and glycolysis enzymes in the overload cells.

Adult↗

Myelin lipids in ischemic stroke.

Slices of ischemic focus (infarct area) and of the contralateral frontal lobe were submitted to histological and biochemical studies. The obtained results indicate that in stroke cases the necrotic focus as well as contralateral brain hemisphere are characterized by a marked decrease of cholesterol and cerebrosides content and an increase of lysophosphatidylcholine and cholesterol esters in the myelin fraction. We conclude that ischemia as well as the degenerative aging process are both responsible for the abnormal lipid pattern in the myelin of the white matter in stroke cases. The long lasting hypoxia resulting from cerebral vessel atheromatosis contributes to biochemical changes in the myelin of the apparently healthy white matter of the contralateral hemisphere in brain infarction.

Acute Disease↗

Adrenoleukodystrophy. Report of an autopsy case with adrenoleukomyeloneuropathy.

The patient was a 27-year-old man who developed spastic quadriplegia and cerebral disorders. Initial signs were gait disturbance, spastic paraplegia, and sphincter disturbance; these occurred when he was 21. Upon autopsy, the white matter of the brain and spinal cord showed diffuse demyelination, and the adrenal glands and right testis were atrophic. Cytoplasmic striations seen by light microscopy and trilamellar inclusions seen by electron microscopy were found in ballooned adrenocortical cells. Trilamellar inclusions were also observed in macrophages of the affected cerebral white matter. Biochemical analysis disclosed a high ratio (0.27) of hexacosanoic acid (C26:0) to docosanoic acid (C22:0) in cerebrosides and sulfatides of the cerebrum. The histological features as well as the result of biochemical analysis were those of classical adrenoleukodystrophy. However, the time of the onset of clinical signs and the duration of the disease were different in the present case from classical adrenoleukodystrophy. The case presented here was diagnosed as adrenoleukomyeloneuropathy, which is a variant of adrenoleukodystrophy.

Adrenoleukodystrophy↗

[Biochemical and ultrastructural changes in the brain of the rat exposed to the cerebrospinal fluid of schizophrenics].

Using biochemical and ultrastructural methods of examination, the authors studied the brain of rats following the intracysternal injection of spinal fluid from schizophrenic patients. The elicited disorders of the ultrastructure of neurons of the medulla oblongata as well as alterations in the content of lipid peroxidation products, gangliosides and cerebrosides were directly correlated with disorders identified in the brain of schizophrenic patients. It was concluded on the basis of the results obtained that marked neurotoxic properties of schizophrenics' cerebral fluid appeared to be explained by the presence of antibodies to brain antigens.

Animals↗

[Incorporation of 1-6-14C-glucose into lipid fractions of the liver and brain of rats with different alcohol motivation].

Specific radioactivity of total phospholipids, cholesterol and lysophosphatidyl choline was decreased in liver tissue of rats consuming ethanol as compared with the animals preferring water. In brain of rats with alcohol motivation incorporation of 1-6-14C-glucose into cardiolipin was decreased, while the label incorporated into triacylglycerols, sulfatides II and cerebrosides I at the increased rate.

Alcohol Drinking↗

Pre-packed reverse phase columns for isolation of complex lipids synthesized from radioactive precursors.

Pre-packed reverse phase columns (Bond Elut) were used for the separation of complex lipids, such as phosphatidylcholine, cerebrosides, sulfatides, and gangliosides, from their respective water-soluble radioactive precursors after their in vitro biosynthesis. After an incubation in vitro, the entire reaction mixture is passed through the column, where complex lipids are retained and the hydrophilic radioactive precursors are washed away from the column. The retained lipids are then eluted with a more nonpolar organic solvent. The procedure is shown to be simpler and more efficient than the normally used Folch partitioning method or other procedures.

Animals↗

Four-directional-development thin-layer chromatography of lipids using trimethyl borate.

Solvent mixtures containing trimethyl borate virtually eliminated the pronounced interconversion of 1,2- and 1,3-dipalmitins during their resolution by thin-layer chromatography on Silica Gel G. With trimethyl borate, an average of 1-2% of 1,2-dipalmitin was converted to 1,3-dipalmitin. A four-directional-development TLC procedure incorporating trimethyl borate resolves cholesteryl glucoside, ceramides, monogalactosyl diglyceride, 1- and 2-monopalmitin, palmitic acid, cholesterol, 1,2- and 1,3-dipalmitin, tripalmitin, methyl palmitate, cholesteryl palmitate, beta-carotene and some of its degradation products, squalene, and tetracosane. Digalactosyl diglyceride, phosphatidic acid, phosphatidylglucose, cerebrosides, and other phospholipids remain near the origin. A mixture containing triolein, 1,2- and 1,3-diolein, 1- and 2- monoolein, oleic acid, and cholesterol was resolved in one dimension. A similar series of palmitic-containing neutral lipids was also resolvable in one dimension. These procedures were applied to the TLC of human sera lipids.

Acetates↗

Thin-layer chromatographic analysis of phospholipids in Echinostoma revolutum (Trematoda) adults.

Thin-layer chromatographic analyses were made of phospholipids extracted from adult Echinostoma revolutum (Trematoda) and from the nonnutrient medium in which worms were maintained. Identity of phospholipids was based on comparison with authentic lipid standards and on specific chemical detection tests. The most abundant phospholipids in the extract were phosphatidyl choline, phosphatidyl ethanolamine and phosphatidyl serine; lesser amounts of cerebrosides and lysophosphatidyl choline were detected also. Phospholipids detected in the incubation medium were essentially as described for extracts.

Animals↗

Metabolism of sphingolipids by normal and atherosclerotic aorta of squirrel monkeys.

We studied the synthesis and hydrolysis of sphingomyelin by homogenates of aortic intima plus inner media from normal squirrel monkeys and from monkeys with nutritionally-induced atherosclerosis (6-10 mo on a semi-purified diet containing butter and cholesterol). The concentrations of sphingomyelin in the aortas and plasmas of the atherosclerotic monkeys were higher than those for the normal monkeys. Palmitoyl-1-(14)C coenzyme A was actively utilized for the synthesis of ceramide (N-palmitoyl sphingosine). The addition of sphingosylphosphorylcholine increased the utilization of palmitoyl CoA in sphingomyelin synthesis, and the addition of psychosine (sphingosyl galactoside) increased the incorporation of palmitate into cerebrosides. Rates of sphingomyelin and ceramide synthesis were significantly higher in the atherosclerotic than in the control aortas. Hydrolysis of labeled sphingomyelin to ceramide was also increased in homogenates of the atherosclerotic aortas. Labeled sphingomyelin was taken up from plasma by everted carotid arteries, and this process was also enhanced by atherosclerosis. Increased rates of synthesis and of uptake from plasma of sphingomyelin may account for the increased concentrations of sphingomyelin in the atherosclerotic arteries, even though the ability to degrade sphingomyelin is also enhanced in the atherosclerotic aorta.

Animals↗

Structure of sulfatides biosynthesized in vitro.

Starting from galactose-(14)C-labeled phrenosine and 3'-phosphoadenosine-5'-phosphosulfate, radioactive sulfatides have been obtained in vitro with a biosynthetic system similar to the one described by McKhann and Ho (Ref. 6). It has thus been proved that exogenous cerebrosides can act as acceptors of sulfate. The specific radioactivity of the synthetic phrenosine used as precursor was sufficiently high to permit the proof of the structure of the resulting sulfatides to be done by methylation on an amount estimated at 0.1 micro g. The sulfate group was found only at C-3 of galactose, the position at which it is located in sulfatides isolated from tissues. This observation indicates the specificity of the sulfotransferase involved in the in vivo synthesis of sulfatides.

Adenine Nucleotides↗

Lipid components of sialosylgalactosylceramide of human brain.

A ganglioside, previously designated HG-B in our laboratory, was isolated from mixed human brain ganglioside preparations and shown to contain equimolar quantities of sialic acid, galactose, and sphingosine. Treatment of this material with neuraminidase yielded a galactosylceramide. The ganglioside, now referred to as sialosylgalactosylceramide, thus appears to be identical with G(gal) reported by Kuhn and Wiegandt. The fatty acids and long-chain bases of this material were analyzed by gas-liquid chromatography. Approximately equal amounts of normal and hydroxy acids were found. Oleic, palmitic, and stearic acids were the only normal fatty acids present. In the hydroxy series, the C(24) and C(23) saturated acids were the major components. The ratio of C(20) to C(18) long-chain base was approximately 5:3. These data suggest that sialosylgalactosylceramide has no direct metabolic relationship with either the major brain gangliosides or adult brain cerebroside.

Brain Chemistry↗

Splenic lipids in Gaucher's disease.

Column chromatography (on cellulose, silicic acid, and Florisil) and thin-layer chromatography were employed for the separation and purification of lipid fractions from normal and Gaucher spleens. A new hydrolysis procedure, followed by paper chromatography, was used for identification of sugar moieties. A nonhydrolytic combined colorimetric procedure, with anthrone and orcinol, was used for the estimation of glucose and galactose separately in glycolipids. The limitations of this method were examined. Spleens from two control subjects and three patients with Gaucher's disease have been examined in detail. In all Gaucher spleens, the predominant feature was the massive acccumulation of glucocerebroside; neutral ceramide oligohexoside levels were probably within the normal range, as were other neutral lipids and phospholipids. In one case examined for gangliosides, these were increased twentyfold. One Gaucher spleen, in which others had reported that the stored "cerebroside" contained predominantly lactose as the saccharide moiety, has been examined in detail and it has been established that the stored material was, in fact, glucocerebroside, ceramide lactoside levels not being significantly elevated. In a further nine cases glucose was the major sugar detected in the splenic lipids.

Adolescent↗

New sialic acid-containing sulfolipid: "ungulic acid".

Human epidermis, hair, nails, and kidney as well as bovine and horses' hooves were found to contain a lipid fraction, which on thin-layer chromatography migrated slightly ahead of the cerebroside sulfate esters and gave the color reaction specific for sialic acid. This fraction was isolated from horse hoof, in which it constituted nearly half of the total lipids. The purified fraction contained sulfur, but no phosphorus. The IR spectrum revealed the presence of a sulfate group, which was also determined by the benzidine method. Thin-layer and gas-liquid chromatography of the products of acid hydrolysis revealed the presence of sphingosine, galactose, galactosamine, and sialic acid. Fatty acid analysis showed that stearic acid was the major component, with minor amounts of palmitic and arachidic acids. The fraction isolated contained ceramide, sialic acid, galactose, galactosamine, and sulfate in equimolar amounts. We conclude that the new lipid is a ganglioside sulfate, which we have called "ungulic acid" because it was first separated and identified from a horse's hoof (Latin, ungula).

Amino Alcohols↗

Studies on autoimmune encephalomyelitis in the guinea pig. II. An in vitro investigation on the nature, properties, and specificity of the serum-demyelinating factor.

Complement-dependent demyelinating activity of whole brain homogenate (WBH)-induced experimental allergic encephalomyelitis (EAE) sera was tested on long term tissue cultures of in vitro myelinated fetal guinea pig cerebellum. Complement-fixing (CF) auto-antibodies were shown to be the responsible agents, as demonstrated in experiments where all reagents belonged to the same species: guinea pigs of outbred (Hartley) and even of inbred (S2 or S13) strains. These antibodies were of the IgG2 class as shown by Sephadex G-200 and DEAE cellulose fractionation experiments. The corresponding auto-antigen was present in the homogenate and myelin of the central nervous system (CNS) tissue. It was different from the encephalitogenic basic protein of CNS myelin (BP), as shown in experiments where the demyelinating auto-antibodies were induced, detected, and absorbed by WBH or by CNS myelin but not by BP. They were neither induced by nor cross-reacting with cerebroside and peripheral nervous system (PNS) tissue.

Animals↗