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Biomedical subjects

A Poli

Publications and source records attributed to A Poli.

At least 181 records · Page 10Linked to original sources
PubMed1983

Pharmacological manipulation of GABA system does not protect the goldfish optic tectum from the neuroexcitatory and neurotoxic action of kainic acid.

Inhibition of GABA transaminase which led to a several-fold increase of GABA levels in the goldfish optic tectum or diazepam pre-treatment, were unable to protect tectal neurons from kainic acid neurotoxicity, as judged by light and electron microscopic observations and by the drop of marker enzymes for neurotransmitters. In an in vitro preparation of tectal slices GABA, added to the incubation medium, had no effect on a metabolic parameter (CO2 production from exogenous glucose) related to the excitatory action of kainic acid. It is concluded that, in the goldfish optic tectum, pharmacological manipulation cannot enhance the activity of GABAergic circuits to the extent necessary to block the neuroexcitatory and neurotoxic action of kainic acid.

4-Aminobutyrate Transaminase↗
PubMed1983

Familial lipoprotein lipase and apolipoprotein C-II deficiency. Lipoprotein and apoprotein analysis, adipose tissue and hepatic lipoprotein lipase levels in seven patients and their first degree relatives.

Plasma lipids, lipoproteins, tissue lipoprotein lipase (LPL) and hepatic lipase (H-TGL) were studied in 7 patients with familial hyperchylomicronemia from four different families. Their first-degree relative were also studied. The patients were heterogeneous for the genetic defect; LPL activity was absent in five patients (LPL deficiency) but normal in two. However, these two did not have apo C-II, the physiological activator of LPL (C-II deficiency). There were no significant differences in the clinical picture between patients with LPL deficiency and C-II deficiency. In both mutants, marked hypertriglyceridemia was due to an accumulation of lipoproteins of density less than 1.006 g/ml. The LDL fraction was very reduced and abnormal in composition, presenting a CH/TG ratio of 0.5. The plasma apolipoprotein B (apo B) level was low (67 +/- 5.5 mg/dl) and was transported mainly in the VLDL fraction (26 +/- 3.2 mg/dl) rather than in the LDL fraction (15 +/- 1.4 mg/dl). Very low levels of cholesterol and apolipoprotein A-I in HDL subfractions HDL2 and HDL3 were also recorded. Only 3 out of the 24 first-degree relatives of patients with LPL deficiency showed even a small increase in plasma triglycerides, but 15 had low or low to normal LPL values. H-TGL levels were normal in all subjects. The 4 first-degree relatives of C-II deficiency patients showed normal levels of plasma lipids. LPL and H-TGL, and 2 children of 1 patient showed normal distribution of apo C peptides in their VLDL. A block in chylomicron catabolism, due to the absence of LPL or apo C-II, may lead to a massive accumulation of lipoproteins with a density less than 1.006 g/ml, and a drastic reduction in the LDL and HDL fractions. Low LPL values in the first-degree relatives of LPL deficiency patients might represent a biochemical marker for healthy carriers of LPL deficiency.

Adipose Tissue↗
PubMed1983

Study of differential effects of kainic acid on metabolic rates, utilizing exogenous or endogenous substrates, in rat brain slices.

CO2 production from exogenous glucose of cortical, whole hippocampal, and CA3 region hippocampal slices, as well as O2 consumption of whole hippocampal slices, were measured in the presence of different concentrations of kainic acid. A moderate, significant increase of CO2 production was seen only in the CA3 region hippocampal preparation at kainic acid concentrations of 10(-4)-10(-2) M. The O2 consumption, at the expense of endogenous energy stores of whole hippocampal slices, was substantially increased by 10(-3) M kainic acid when the slices were incubated without exogenous glucose. The effect was partly paralleled by the use of high (50 mM) K+ concentration. Some of the possible factors involved in the differential metabolic responses of brain slices to the action of kainic acid are discussed briefly.

Animals↗
PubMed1982

Characterization of human chylomicrons.

Apolipoprotein and lipid composition of differently sized chylomicrons from healthy volunteers was determined. During their intravasal catabolism the chylomicrons lose triacylglycerol and apolipoproteins. Decreasing particle size results in a loss of apolipoprotein C and apolipoprotein E peptides and an increase in apolipoproteins B and A-I, which constitutes more than 20% of the moiety of small chylomicrons. The C peptides do not seem to behave as a functional entity. Apolipoprotein C-III, the inhibitor of lipolytic activities, is catabolized independently of the other C peptides. Albumin constitutes about 15-25% of the protein moiety of all chylomicrons. The different chylomicron fractions were incubated with lipolytic activities of lipoprotein lipase and hepatic triacylglycerol lipase. At lower substrate concentrations the reactions were of first-order. Large chylomicrons were the favored substrate for both enzymes with Michaelis Menten constant Km = 1.1 mM for hepatic triacylglycerol lipase and 0.48 mM for lipoprotein lipase. After incubation with hepatic triacylglycerol lipase or lipoprotein lipase the shape of chylomicrons differs from that of control particles as demonstrated by electron microscopy. C peptides were completely dissociated and found in the infranatant. In the enzyme assay with triolein gum arabic substrate several apolipoproteins showed an influence on the activities of hepatic triacylglycerol lipase and lipoprotein lipase. Apolipoprotein C-III peptides were the most effective inhibitors of both enzymes. Also, apolipoprotein A-II, A-I and apolipoprotein C-I inhibited lipoprotein lipase activity, whereas only apolipoprotein A-II was able to decrease hepatic triacylglycerol activity.

Apolipoproteins↗
PubMed1982

Neurotoxic effect of kainic acid on ultrastructure and GABAergic parameters in the goldfish cerebellum.

Kainic acid administration into the cerebellar dorsal lobe of the goldfish causes selective degeneration of some neuronal types. Stellate and Golgi neurons are very sensitive to the neurotoxin and undergo rapid degeneration. On the basis of their differential responses to kainic acid, Purkinje cells can be divided in two distinct sub-populations (i.e. sensitive and insensitive neurons). The degenerative changes of the Purkinje neurons are in addition remarkably slow in comparison with the same cells in mammals or with stellate and Golgi neurons in the goldfish. Granule cells, as well as the cerebellar afferent fiber system, are not significantly affected. Six days after kainic acid administration, the level of glutamate decarboxylase in the cerebellar dorsal lobe drops to about 40% of the control value. This result suggests that the neurons sensitive to kainic acid neurotoxicity are, at least in part, GABAergic. Light- and electron-microscopic autoradiography of cerebellar elements selectively accumulating [3H]GABA, supports this idea. Moderate decreases of acetylcholinesterase and protein content were also noticed in the kainic acid-treated cerebellar dorsal lobe.

Acetylcholinesterase↗
PubMed1982

Effect of kainic acid, glutamate, and aspartate on CO2 production by goldfish tectal slices.

For a study of the excitatory effect of kainate, glutamate, and aspartate in the goldfish optic tectum, these substances were tested on the production of CO2 from radioactive glucose in tectal slices incubated in Krebs-Ringer medium for fish. Kainate increased the rate of CO2 production for up to 30 min in a dose-related manner, the effect being maximum at 0.1 mM concentration and decreasing at higher doses. The effect was blocked by ouabain (1 mM) as well as by the substitution of choline for Na+ in the incubation medium. Glutamate and aspartate exerted a less pronounced excitatory effect on CO2 production at higher concentration than kainate. This effect was also abolished by ouabain. Glutamate, added to the medium at a concentration at least 100-fold higher than kainate, partially reversed the increase in CO2 production induced by kainic acid. No similar effect was noticed for aspartate. The supposed glutamate antagonists glutamic acid diethylester (1 mM) and proline (5 mM) did not affect the excitatory action of kainic acid or exert an antagonistic effect towards glutamate. At higher concentration (10 mM) glutamic acid diethylester increased CO2 production, an effect that was, however, ouabain insensitive. Methyltetrahydrofolic acid (1 mM), a substance reported to compete for the kainate receptor, did not inhibit the effect of kainic acid or increase CO2 production.

Animals↗
PubMed1982

Experimental infection of European wild swine (Sus scrofa L.) with pseudorabies virus.

Experimental infection with pseudorabies virus was carried out by oral exposure of four young wild swine held in contact with two unexposed controls. No disease was observed but virological procedures indicated that the virus was shed in saliva and, in one case, in the nasal discharge, with subsequent infection of the control animals. After slaughter the virus was reisolated from the tonsils but not from lungs and brain. Virus reisolation from the tonsils was obtained in two animals after the throat swabs became negative. Virus neutralizing antibodies were detected.

Animals↗
PubMed1981

Kainic acid neurotoxicity does not depend on intact retinal input in the goldfish optic tectum.

Kainic acid neurotoxicity has been studied in the optic tectum of the goldfish 4 weeks after eye enucleation. The effect of drug treatment has been tested with respect to both neurochemical and morphological parameters. The neurotransmitter-related enzymes, choline acetyltransferase, acetylcholinesterase and glutamate decarboxylase, show about 50% decrease in the deafferented tectum 6 days after kainic acid administration. Relevant morphological alterations of the tectal structure can also be noticed at the same stage. The neurotoxic effects of kainic acid in the deafferented optic tectum are therefore quite similar to the effects of previously noticed for the intact optic tectum of normal fish. Control experiments on the effect of optic nerve degeneration by itself on the levels of the neurotransmitter-related enzymes in the optic tectum, have shown no significant decrease in glutamate decarboxylase, a slight decrease in acetylcholinesterase and a more marked drop in choline acetyltransferase. The findings are discussed with reference to some of the hypotheses advanced in order to explain kainic acid neurotoxicity. It is proposed that the neurotoxic effect of kainic acid after removal of specific excitatory afferents, may vary in different nervous centers depending on differences of the remaining extrinsic connections and of the intrinsic neural circuits.

Acetylcholinesterase↗
PubMed1981

Energy deposition by proton beams of up to 31 MeV in microscopic volumes.

The frequency distributions of energy deposition in microscopic volumes for proton beams of various energies and energy spreads were determined by means of a "rossi type" proportional counter. Tissue equivalent spherical volumes of 0.6, 0.72, 0.80, 1.00, 1.25, 1.50, 1.75, 2.00 micrometer diameter were simulated. Frequency distributions of energy deposition per unit pathlength are reported and their behavior as a function of the simulated pathlength, beam energy and energy spread is discussed. The results indicate that energy deposition distributions in microscopic volumes for protons in the range 8-31 MeV are skewsymmetric distributions with a tail on the high energy side, and that degraded beams behave differently from monoenergetic ones. Dose mean lineal energy values have been quoted for beams used in radiobiological experiments.

Protons↗
PubMed1981

Effects of insulin and anchorage on hepatocytic protein metabolism and amino acid transport.

Insulin partially inhibits endogenous protein degradation in isolated hepatocytes. The inhibition seems to specifically affect the lysosomal pathway of degradation, since it is not additive to the effects of lysosome inhibitors such as propylamine and leupeptin. The insulin effect is potentiated by intermediate concentrations of amino acids, but is largely abolished at high amino acid concentrations which suppress degradation maximally, suggesting that the hormone may exert its effect indirectly by acting upon the more basal amino acid control mechanism. Glucagon, which stimulates protein degradation, similarly displays its effect only in the presence of intermediate amino acid concentrations. The insulin inhibition is not affected by the aminotransferase inhibitor, aminooxyacetate, indicating that it is not due to interference with amino acid metabolism. Protein synthesis furthermore does not seem to be required, since a significant insulin effect can be seen in the presence of the protein synthesis inhibitor, cycloheximide. The issue is, however, complicated by the fact that cycloheximide itself inhibits protein degradation to approximately the same extent as does insulin. Insulin stimulates uptake of the amino acid alpha-aminoisobutyrate (AIB), but not the uptake of valine, indicating a specific stimulation of 'A'-type transport. Cycloheximide similarly stimulates AIB uptake, without completely obfuscating the transport effect of insulin. Neither protein synthesis, protein degradation, amino acid transport, nor the effects of insulin were affected by cell-to-substratum anchorage (attachment and spreading) in any detectable way.

Amino Acids↗
PubMed1981

Inhibitors and pathways of hepatocytic protein degradation.

On the basis of experiments using amino acids and various inhibitors (lysosomotropic amines, leupeptin, chymostatin, vanadate, vinblastine, anoxia, methylaminopurines), five different modes of endogenous protein degradation in isolated rat hepatocytes can be distinguished. The two non-lysosomal (amine-resistant) mechanisms preferentially degrade relatively labile (short-lived) proteins: one of these mechanisms is energy-dependent and chymostatin-sensitive, the other is not. Of the three lysosomal (amine-sensitive) mechanisms, one--quantitatively minor--is amino acid-resistant and preferentially degrades labile proteins. The two amino acid-sensitive mechanisms each seen account for about one-half of the degradation of relatively stable (long-lived) proteins; one of them is suppressed by leucine and apparently corresponds to the formation of electron microscopically visible autophagosomes; the other may represent a different type of autophagy, inhibited by asparagine and glutamine. A new class of inhibitors, the purine derivatives (methylated 6-aminopurines, and 6-mercaptopurines) appear to specifically suppress autophagic/lysosomal protein degradation, and may help to further elucidate the mechanisms of autophagy.

Adenine↗
PubMed1980

Amino acid inhibition of the autophagic/lysosomal pathway of protein degradation in isolated rat hepatocytes.

Protein degradation in isolated rat hepatocytes, as measured by the release of [14C]valine from pre-labelled protein, is partly inhibited by a physiologically balanced mixture of amino acids. The inhibition is largely due to the seven amino acids leucine, phenylalanine, tyrosine, tryptophan, histidine, asparagine and glutamine. When the amino acids are tested individually at different concentrations, asparagine and glutamine are the strongest inhibitors. However, when various combinations are tested, a mixture of the first five amino acids as well as a combination of leucine and asparagine inhibit protein degradation particularly strongly. The inhibition brought about by asparagine plus leucine is not additive to the inhibition by propylamine, a lysosomotropic inhibitor; thus indicating that the amino acids act exclusively upon the lysosomal pathway of protein degradation. Following a lag of about 15 min the effect of asparagine plus leucine is maximal and equal to the effect of propylamine, suggesting that their inhibition of the lysosomal pathway is complete as well as specific. Degradation of endocytosed 125I-labelled asialofetuin is not affected by asparagine plus leucine, indicating that the amino acids do not affect lysosomes directly, but rather inhibit autophagy at a step prior to the fusion of autophagic vacuoles with lysosomes. The aminotransferase inhibitor, aminooxyacetate, does not prevent the inhibitory effect of any of the amino acids, i.e. amino acid metabolites are apparently not involved.

Amino Acids↗
PubMed1980

Multinucleate cells and micronucleus formation in cultured human cells exposed to 12 MeV protons and gamma-rays.

Cultured human cells of the EUE line were exposed to different doses of 12 MeV protons, plated and allowed to grow for 8 days; colonies were then scored for the presences of multinucleate cells and micronuclei. The frequency of both effects is an increasing function of the dose; the evaluated exponents of the dose-response equation (e = bDn) are n = 1.0 %/- 0.1 for multinucleate cells and n = 1.6 +/- 0.1 for micronuclei. By comparison with the results obtained with gamma irradiations, r.b.e. values were obtained for both effects. The correlation between the logarithm of the surviving fraction and the yield of the studied effects has been proved to be statiscally significant.

Cell Count↗
PubMed1979

[Acute granulomatous appendicitis. (Contribution to preventive appendectomy in acute ileitis)].

Starting with one case of acute granulomatous appendicitis of their own observation, the authors review the scant literature on the subject (only 23 published cases to date) and advocate systematic appendicectomy in all isolated appendicular localizations of Crohn's disease. On the grounds that no post-appendicectomy fistulization has ever been reported in such patients, the authors recommend prophylactic appendicectomy also in the far more frequent cases of acute ileitis, to forestall the possibility of evolution into chronic Crohn's disease and the risk of missing a nongranulomatous acute appendicitis appearing with the same clinical symptoms.

Adult↗