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Biomedical subjects

A Gaiti

Publications and source records attributed to A Gaiti.

At least 37 records · Page 2Linked to original sources
PubMed1991

Choline incorporation into phospholipids in brain areas from spontaneously hypertensive rats: effect of oxiracetam treatment.

It has been demonstrated that spontaneously hypertensive rats (SHR) develop severe hypertension and cerebrovascular lesions on drinking 1% NaCl from weaning. These animals present a learning and memory impairment as well as impairment of both energy metabolism and membrane phospholipid turnover. We tested both choline uptake into the cells and incorporation into choline phosphoglyceride (CPG) by incubating slices from hippocampus and cortex. After 5 min of incubation, a noticeable decrease in free labelled choline content inside the cells as well as its incorporation into phospho-choline (PC) and CPG were found in the brain of SHR, as compared to Wistar-Kyoto (WK) rats. This may indicate that in the SHRs with cerebrovascular lesions there is a reduction in choline uptake which in turn causes a decline in CPG biosynthesis through de novo pathway. Oxiracetam treatment is able to restore the labeled choline content in the cells from SH rats, as well as the incorporation of choline into its derivatives PC and CPG, to the levels found in the WK or more. Tests performed in the presence of such a high affinity choline uptake as hemicholinium (HC) confirmed the capacity of oxiracetam to stimulate choline uptake into the cells even if the results obtained up to now are not sufficient to hypothesize a direct effect of oxiracetam on acetylcholine metabolism. In conclusion, from the results obtained it would seem reasonable to hypothesize that the effects of the drug above mentioned on the cholinergic system may be secondary to its effect on choline phosphoglycerides biosynthesis.

Animals↗
PubMed1990

Synaptic vesicle-bound phospholipase(s) acting on phosphatidylinositol exhibit(s) high susceptibility to brain ischemia.

The activity of phospholipase C acting against [3H]-inositol-phosphatidylinositol (PI) and the activity of arachidonic acid (AA) release from [1-14C]arachidonoyl-phosphatidylinositol by enzyme(s) located in synaptic vesicles (SV) isolated from normoxic and ischemic brains was investigated. Brain ischemia significantly activated phospholipase C (PhLC) by about 90% and AA release by about 50%. PhLC and AA release in SV isolated from brain submitted to ischemia were not further activated by 2 mM CaCl2 contrary to the enzymes from normoxic brain. The activation of PhLC and PhLA2 may produce conformational changes and rearrangement of the SV membranes leading to vesicle-membrane fusion and subsequently to massive neurotransmitter release known to occur during ischemia.

Animals↗
PubMed1990

Is multi-infarct dementia representative of vascular dementias? A retrospective study.

Multi-infarct dementia (MID) indicates a dementia disorder primarily caused by multiple cerebral infarcts. Since other pathogenetic mechanisms cause vascular dementia we evaluated clinical, CT scan and CSF neurochemical parameters of 134 MID and 67 PVD (probable vascular dementia) patients. We found no differences with regard to the presence of major risk factors. Only TIA/stroke episodes and focal neurological signs were significantly more frequent in MID than in PVD cases, an anticipable result on the basis of MID definition. CT scan findings showed a prevalence of subcortical with respect to cortical lesions in both groups, with a higher frequency in MID patients. Subjects with deep infarcts more frequently showed TIA/stroke episodes and diabetes mellitus. No differences were detectable in CSF monoamine metabolite levels. We conclude that in the majority of vascular dementias subcortical damage seems to have a major pathogenetic role.

Aged↗
PubMed1987

Effect of aging on the rate of axonal transport of choline-phosphoglycerides.

The anterograde axonal transport of choline-phosphoglycerides was studied in sciatic nerve motoneurons of adult (3-month-old) and aged (24-month-old) rats. After the spinal cord injection of [2-3H]glycerol, choline-phosphoglycerides; the major phospholipid class was transported along the nerve. The axonal transport rate was determined by plotting the distance covered by the front of transported radioactivity as a function of the time employed. In aged animals the rate of the choline-phosphoglyceride anterograde axonal transport was about 68% lower than that of adults; furthermore, the rate slowed down along the nerve in the proximal-distal direction. This altered axonal transport mechanism might contribute to the degenerative processes observed in distal regions of peripheral nerve fibers of aged animals.

Aging↗
PubMed1986

Turnover of palmitic and arachidonic acids in the phospholipids from different brain areas of adult and aged rats.

[3H]Palmitic acid and [14C]arachidonic acid were injected together into the cerebral ventricle of 4-month and 24-month-old rats. At different time intervals from the injection, the distribution of these fatty acids in the lipids from different brain areas was examined. The fatty acids were rapidly incorporated into the lipids through different mechanisms. The time-specific activity relationship indicate that the utilization of the fatty acid differs according to the different areas and aging decreases the utilization of both the fatty acids. The decline of arachidonic acid incorporation into phospholipids is particularly evident, indicating that aging affects mainly the utilization of polyunsaturated fatty acids.

Aging↗
PubMed1986

Biochemical studies on the nootropic drug, oxiracetam, in brain.

The aim of this work was to study the effects of the nootropic drug oxiracetam, on lipid metabolism in rat brain. Twenty-month-old rats and spontaneous hypertensive (SHR) rats with cerebrovascular lesions were used, which showed an impaired learning and memory rate if challenged with behavioral tests. Oxiracetam improves the in vitro and in vivo synthesis of phosphatidylcholine (PhC) and phosphatidylethanolamine (PhE) impaired by aging, when respectively added to the incubation medium or administered subacutely to animals. SHR rats drinking saline, and with cerebrovascular lesions, have a reduced choline incorporation into cerebral phospholipids and an increase of arachidonic acid release from the same lipids if compared to SHR rats (without cerebrovascular lesions) drinking water. They also show a decreased incorporation rate of arachidonic acid into PhC, PhE, and PhC plasmalogen and PhE plasmalogen. If oxiracetam is chronically administered (200 mg/kg/day for 14 weeks) a significant variation in the incorporation of both precursors takes place. In the first 2 h after the intracerebroventricular (i.c.v.) injection of choline and arachidonic acid the values are comparable to those observed in SHR rats with lesions; at longer time intervals, however, the rates of incorporation are similar and even better than those of SHR rats without lesions. Since the drug does not seem to influence the incorporation of the precursors in the first 2 h after their administration, we may assume that oxiracetam acts on the turnover of the phospholipids more than on their rate of synthesis from injected precursors.

Aging↗
PubMed1985

Effect of chronic treatment with phosphatidyl serine on phospholipase A1 and A2 activities in different brain areas of 4 month and 24 month old rats.

The activities of phospholipase A1 and A2 were tested in mitochondria and microsomes from different cerebral areas of both 4 month and 24 month old rats, after 30 days i.p. treatment with ox Brain Cortex Phosphatidyl Serine (BC-PS). In the brain areas from control animals a rather great decline in its ability to hydrolize the fatty acids of the main phosphoglycerides was found. Taking into account only the effect of treatment with BC-PS on the modification of phospholipase activities caused by aging, we found that the treatment was able to balance the enzymatic functions altered by aging in several of the area examined. The importance of this result on the lipidic metabolism of the aging brain is also discussed.

Aging↗
PubMed1984

Turnover of ethanolamine phosphoglycerides in different brain areas of adult and aged rats.

The turnover of ethanolamine glycerophospholipids (EGP) has been determined in six different cerebral areas of 4-month and 22-month-old rats, by injecting [3H]glycerol together with [14C]ethanolamine into the lateral ventricle of the brain. The areas examined behave quite differently in respect to their utilization of the most simple precursors of phosphoglyceride biosynthesis. The incorporation of both glycerol and ethanolamine is already complete as early as 2-4 hours and then reutilization begins, at least for the so called fast pools of phosphoglycerides. The different slopes of the specific activity of the two precursors in EGP suggest a high degree of variance among catabolic rates in the different brain regions. In aged rats the utilization of the water-soluble precursors of EGP synthesis decreases in all brain areas and these data suggest that aging may have a different effect on the catabolic activities as well as phospholipid biosynthesis.

Age Factors↗
PubMed1982

The synthesis in vivo of choline and ethanolamine phosphoglycerides in different brain areas during aging.

The biosynthesis of choline and ethanolamine phosphoglycerides was tested in vivo in different brain areas of the rat during aging. Mixtures of [2-3H] glycerol and [Me-14C] choline or [2-3H] glycerol and [2-14C] ethanolamine were injected into lateral ventricle of the brain as lipid precursors and their incorporation into corresponding phospholipid was examined. A significant decrease of synthesis of both phosphoglycerides takes place in cerebral cortex and in the striatum, and is already apparent at 9 months of age with no further decrease or change thereafter. No significant change takes place in the cerebellum. The unchanged absorption of injected water-soluble precursors, together with the lack of any significant change of phospholipid/protein ratio in all examined brain areas, suggests that the incorporation of both glycerol and nitrogen bases are affected by aging.

Aging↗
PubMed1982

Modulation of phospholipase A activity in psoriatic skin.

The activity of phospholipase A2 was tested both in rat skin and human psoriatic skin before and after systemic treatment with a retinoic acid derivative: RO 10-9359. An increase of activity was found in the rat skin homogenates when the animals were treated with 3 mg/kg/day of the drug for 8 days, while no effect was found following treatment with 1.5 mg/kg/day for 10 days. On the contrary a decrease of this activity was found in homogenates from both involved and uninvolved skin of psoriatic patients after systemic treatment with 1-1.5 mg/kg/day for 10 days. These different results are discussed also in the light of the clinical effect of RO 10-9359 on psoriasis.

Adult↗
PubMed1981

Phospholipid metabolism in neuronal and glial cells during aging.

The incorporation of cytidine-containing precursors (CDP-Cho and CDP-Etn) into the main phospholipid classes of cellular fractions enriched in neurons and glial cells from whole rat brains of different ages was examined. The rate of synthesis of choline phosphoglycerides in neuronal homogenates significantly decreased with age up to 18 months; after this time no additional decrease was found. The decrease of CDP-Etn incorporation in neurons was found to be less significantly affected by age up to 18 months, but the enzymic activity decreased after 18 months of age. No changes were found in the corresponding glial activity at any age. Biochemical phenomena that occur in 18-month-old rat brain (aged animals) were compared with phenomena occurring in 2-month-old rat brain (adult animals). No significant variations of lipid composition were found in neurons from either 18-month-old or 2-month-old rat brain. These results, together with some kinetic parameters, suggest that ethanolamine and choline phosphotransferases are affected differently by aging.

Aging↗
PubMed1981

Action of phospholipase A2 of rabbit neuronal and glial cells on 1,2-diacyl-, 2-acyl-1-alk-1'-enyl-, and 2-acyl-1-alkyl-glycerophosphatides.

Pronounced differences in the phospholipase A2 activities were found in neurons and glia, the enzyme activity being two- to threefold higher in neurons than in glial cells. Both phospholipases A2 hydrolyzed the 1,2-diacylglycerophosphatides more rapidly than the acylalkyl and acylalkenyl compounds. Choline plasmalogen and the corresponding alkyl derivative were cleaved at similar rates by the phospholipase A2 from both glia and neurons. There was a tendency by the neuronal phospholipase A2 to release arachidonic acid faster than linolenic acid from both phosphatidylcholine and -ethanolamine, while arachidonic acid was removed less actively from phosphatidylethanolamine by the glial enzyme. The glial phospholipase A2 showed a lag period of 10 or 20 min. Norepinephrine, injection into the lateral ventricle of the rabbit brain, stimulated the hydrolysis of the various 1,2-diacyl-, acylalkyl, and and acylalkenyl-glycerophosphatides by the phospholipase A2 from both glia and neurons.

Animals↗
PubMed1981

Occurrence and properties of phospholipases A1 of plasma membranes prepared from neuronal- and glial-enriched fractions of the rabbit cerebral cortex.

Exogenously added glycerophosphatides, specifically radioactively labelled either in the 1 or in the 2 position, were used to investigate the occurrence and properties of phospholipase A1 in plasma membranes prepared from neuronal- and glial-enriched fractions of rabbit brain. Phospholipase A1 activity was maximal at pH values ranging between 8.0 and 9.0 for the plasma membranes of both cell types. The enzyme activity was most abundant in the microsomal fraction, with a neuronal/glial ratio of about 2. The plasma membranes displayed about half the enzymic activity of the microsomal fraction, whereas only small amounts of phospholipase A1 were present in the neuronal and glial mitochondria. Investigations on the substrate specificity showed a different pattern for the enzyme of neuronal and glial origin. The release of labelled fatty acids from phosphatidylcholine by the neuronal plasma membrane phospholipase A1 decreased with increasing degree of unsaturation of the fatty acids at the 1 position. The presence of plasmalogens and plasmalogen precursors in the incubation mixture appreciably inhibited the hydrolysis of the corresponding diacyl compounds.

Animals↗
PubMed1981

Cyclic GABA-GABOB analogues. III - Synthesis and biochemical activity of new alkyl and acyl derivatives of 4-hydroxy-2-pyrrolidinone.

The synthesis of new N-substituted 4-hydroxy (III) and 4-acyloxy- or 4-alkoxy-2-pyrrolidinones (IV), as analogues of oxiracetam (III c), is reported. For this purpose, a convenient procedure for N-alkylation of the base-labile 4-hydroxy-2-pyrrolidinones (II a, c, d) was developed. Compounds (III) and (IV) were examined on phospholipid synthesis in brain microsomal membranes of rats, both in vivo and in vivo-in vitro, and on protein synthesis in brain slices. Results showed that only oxiracetam (III c), and to a lesser extent piracetam, are active both on phospholipid and brain protein synthesis.

Animals↗
PubMed1979

Activity and subcellular distribution of phospholipase A1 from neuronal cell-enriched fractions of the rabbit cerebral cortex.

Glycerophosphatides, specifically labeled either in the 1 or in the 2 position, were used to measure the activity of neuronal phospholipase A1 and to investigate the subcellular distribution of the enzyme. The microsomes were found to possess the highest phospholipase activity, with a threefold increase as compared to the cell homogenate. A considerable enzymatic activity could still be observed in the plasma membranes isolated from the neuronal-enriched cell fraction. Microsomal phospholipase possessed the highest activity with phosphatidylcholine, whereas phosphatidylserine was cleaved at a much lower rate. The rate of release of labeled fatty acids from the substrates by the microsomal phospholipase decreased with increasing degree of unsaturation of the fatty acids at the 1 position. The presence of plasmalogens and of alkylacyl analogues in the incubation mixture caused an appreciable inhibition of the hydrolysis of the diacyl glycerophosphatides.

Animals↗
PubMed1979

Synthesis of phosphatidylcholine and phosphatidylethanolamine at different ages in the rat brain in vitro.

The de novo synthesis of choline and ethanolamine phosphoglycerides in brain microsomes from 18 month-old male rats was investigated in vitro by using labeled cytidine-5'-diphosphate choline and cytidine-5'-diphosphate ethanolamine as lipid precursors. The rate of synthesis of the two phospholipid classes was found to be noticeably decreased, as compared to that of adult animals. The addition of exogenous diacyl glycerols to microsomes from ageing rat brain brings the rate of synthesis nearly to the adult levels. The synthesis of choline and ethanolamine phosphoglycerides is not affected in the liver microsomes of ageing rats. The molar distribution of fatty acids in brain microsomal diacyl glycerols of ageing rats is noticeably different from that of adult animals. The content of monoenoic and dienoic species is increased, whereas that of the tetraenoic species is decreased. Base exchange reaction for choline and ethanolamine incorporation into respective phospholipids is not affected in the brain microsomes of the aged rats.

Aging↗
PubMed1978

Membrane-bound base-exchange reactions in animal tissues.

The calcium-stimulated incorporation of ethanolamine, L-serine and choline into rabbit synaptosomal phospholipids in vitro has been investigated. The synaptosomal membranes were prelabelled in vitro in their choline-, ethanolamine- or serine-phosphoglycerides by base-exchange and then chasing experiments were performed by displacing the lipid-bound base by ethanolamine, choline or L-serine labelled with a different isotope. The results indicate that membrane phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine are substrates for the exchange with all the three mentioned bases. A very small phospholipid pool (0.5-2% of the total available pool) is active in the calcium-dependent exchange between membrane phosphatidylcholine or phosphatidylethanolamine and free bases, whereas the pool of exchanging phosphatidylserine is sensibly larger (2-9%). In another series of experiments the effect of the base-exchange reaction upon the production of cyclic-AMP at the level of rat brain synaptic membranes has been examined. An exchange with ethanolamine produces a significant decrease of the NaF-stimulated production of the cyclic nucleotide, whereas it increases the noradrenaline-induced production. With some exceptions, the exchange with L-serine produces opposite effects. The possible physiological importance of phospholipid pool at the synaptosomal level is discussed.

Adenylyl Cyclases↗