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G Zanchin

Publications and source records attributed to G Zanchin.

At least 55 records · Page 3Linked to original sources

Cerebral amino acid levels and transport after portocaval shunt in the rat: effects of liver arterialization.

Altered plasmatic and cerebral amino acid patterns have been observed after portocaval shunt in the rat. Similar alterations have been found in plasma and in cerebrospinal fluid of cirrhotic patients and are likely to play an important role in the pathogenesis of hepatic encephalopathy. Impaired liver blood flow could contribute to these biochemical abnormalities. Therefore we wondered whether liver arterialization, by improving liver perfusion, could have any beneficial effects on the altered amino acid levels occurring in the rat after portocaval shunt. Amino acid concentrations were determined in four cerebral regions and in the plasma of shunted rats with or without liver arterialization, 4 weeks after surgery. Blood-brain barrier transport was studied with the Oldendorf's technique. After portocaval shunt, we observed lower plasma levels of the branched chain amino acids valine, isoleucine, leucine, and net higher levels of the aromatic tyrosine and phenylalanine and of glutamine. In the cerebral regions, we observed a slight increase of branched chain amino acids and an enormous increase of tyrosine, phenylalanine, tryptophan, histidine, and glutamine. Arterialization of the liver made no difference to the postportocaval shunt plasma levels of branched chain amino acids, while it almost normalized those of aromatics. In the cerebral regions, we observed a marked improvement in the level of tyrosine, phenylalanine, tryptophan, and histidine. The enhancement of blood-brain barrier transport for the neutral amino acid class, observed after portocaval shunt, was not influenced by liver arterialization. We conclude that, in our model, liver arterialization improves the pathologic amino acid levels following portocaval shunt. This would be in agreement with clinical reports suggesting that hepatic encephalopathy is less frequent after portocaval shunt when associated with arterialization of the liver.

Amino Acids↗

[Pharmacological influences on the brain level and transport of GABA. II) Effect of various psychoactive drugs on brain level and uptake of GABA].

The effects of some psychoactive drugs on the level and uptake of GABA in the mouse brain was studied using well standardized procedures, mainely the silica-gel cromatography for determining the GABA content and the brain slices for measuring GABA uptake. It was found that levomepromazine, sulpiride, haloperidol and amytryptiline were without effects on the cerebral level of GABA; it was also found that these drugs do not influence the rates of uptake of GABA by mouse brain slices. Such results do indicate that the psychoactive drugs studied are without effects on the level and uptake of GABA in the brain.

Amitriptyline↗

Effect of L-dopa treatment on cerebral amino acid levels in rats after portocaval anastomosis.

L-Dopa therapy has been suggested as effective in the reversal of hepatic coma both in humans and in animals. Beneficial effects have been reported also in chronic hepatic encephalopathy. There are many possible mechanisms through which L-dopa could ameliorate this pathological state. The present study was carried out to clarify whether the L-dopa effect could be mediated through an improvement of the brain neutral amino acid patterns, since it competes for the same transport carrier at the blood-brain barrier. A first group of rats was orally administered L-dopa (10 mg/100 g body weight daily) for 1 month following portocaval anastomosis. A second group was intraperitoneally injected (1.5 mg/100 g body weight daily) for 1 week, a month after portocaval shunt. Amino acid levels were determined in plasma and in four cerebral regions. No beneficial effects were observed clinically (in general condition, body weight, or hypertonic posture) in rats receiving L-dopa compared to controls. The large increase of tyrosine, phenylalanine, tryptophan, histidine, and glutamine that occurs in the cerebral tissue after portocaval shunt was also not affected by L-dopa administration. In conclusion, in this experimental condition we had no clinical improvement in shunted animals receiving L-dopa. Moreover, this compound did not seem to influence the pathological increase of aromatic amino acids in the brain, which is considered to play an important role in hepatic encephalopathy.

Amino Acids↗

Effect of antiepileptic drugs on the cerebral amino acid uptake in vitro.

The effects of four commonly used antiepileptic drugs (phenobarbital, diphenylhydantoin, clonazepam and dipropylacetate) on the uptake of amino acids were investigated in mouse cerebral slices. Phenobarbital and diphenylhydantoin showed a net influence on the transport of the neutral amino acids that are also precursors of monoamine neurotransmitters, increasing their uptake. A similar effect was observed for diphenylhydantoin on GABA uptake. The increase in phenylalanine and valine uptake induced by phenobarbital was at least partly due to a decreased release of these metabolites. No major effects were observed for clonazepam and dipropylacetate. Our findings seem to indicate that some antiepileptic drugs may influence cerebral transport of neurotransmitter substances; further investigations are needed to find out whether these effects play a role in the antiepileptic action of these drugs.

Absorption↗

Cerebral amino acid levels and uptake in rats after portocaval anastomosis: I. Regional studies in vitro.

Uptake of various amino acids was studied in slices from brain regions of rats four weeks after portocaval anastomosis. No differences of the inulin compartment were observed between control and experimental animals. After 60-minutes incubation, uptake showed an overall pattern of diminution. This was more evident for some amino acids: valine, methionine, and lysine exhibited a lowering of about 30%, which was fairly uniform in the four tested regions; others showed a regional decrease-- alanine in pons-medulla, phenylalanine in cerebellum, histidine and GABA in mesodiencephalon. This decrease did not seen to be related to transport classes. The restricted entry of amino acids into brain cells in portocaval encephalopathy is somewhat difficult to explain; a decreased rate of protein synthesis may be of some importance, but other factors, such as a "carrier" impairment, effects on release and on amino acid metabolism, may also be involved.

Amino Acids↗

Cerebral amino acid levels and uptake in rats after portocaval anastomosis: II. Regional studies in vivo.

Amino acid levels have been determined in plasma and in four cerebral regions of rats one month after portocaval shunt. Many plasma amino acids are significantly lowered (asparagine, glutamine, theonine, serine, alanine, valine, leucine, isoleucine, cystine, lysine), while others remain unchanged (taurine, glycine, proline, tryptophan, ornithine, histidine, arginine). Asparagine and glutamine levels are significantly higher than in normal rats, and a net increase of tyrosine (100%), phenylalanine (50%) and citrulline (50%) is evident. In the shunted rat brain the most prominent feature is a very large rise (up to fivefold) of tyrosine, phenylalanine, histidine, citrulline, tryptophan, and glutamine uniformly in the tested regions. Other neutral amino acids are slightly increased. Lysine and arginine are decreased in cerebellum and pons-medulla; taurine, in forebrain and cerebellum. Cerebral permeability to L-amino acids was studied in vivo. Neutral amino acid permeability is greatly increased, whereas basic amino acids show a net decrease in their rate of passage from blood to the brain. No changes are observed for GABA and glutamic acid. These data suggest an altered permeability of the cerebral capillary membranes, which seems to be selective for the different amino acid transport classes. Competitive inhibition experiments demonstrated that the increased brain permeability to neutral amino acids after portocaval shunt is due to an enhancement of the saturable transport. The sharp rise in the brain of some essential neutral amino acids (phenylalanine, tyrosine, trytophan, histidine), largely exceeding their changes in plasma, and the slight cerebral increase of other neutral amino acids despite their lowered level and the rise of competing amino acids in the plasma, is consistent with our observation of enhanced transport for the neutral class. In hepatic encephalopathy, correction of the altered plasma amino acid levels has been reported to improve the clinical status. If this result is connected to the concomitant correction of the brain amino acid levels, carefully selected competitive inhibition among various plasma amino acids could be a useful therapeutic tool in this pathologic condition. However, the increased activity of the neutral amino acid transport system adds a new factor to the problem, since it probably implies that the competing amino acids will accumulate to unphysiological levels in the brain.

Amino Acids↗

Decrease in cerebral protein synthesis on a low protein diet.

When rats are put on a diet that is low in protein or contains no protein, decrease in brain weight can be observed. Changes in adults are minimal. In the young there is a 10--30% decrease in cell number and protein content; the cell size (protein per cell) does not change significantly. The change is greater, the earlier the diet is started and the more severe the protein dificiency is. The longer the malnutrition period lasts, the smaller is the recovery to normal values on subsequent control diets. Amino acid incorporation in the brain decreased 10--30% under these experimental conditions; it seems the decrease was to a great extent in the more slowly metabolized protein pool. Changes in other organs were greater; for example, in liver the decrease was up to 75% under similar conditions. The changes in the brain were heterogeneous; there were regional differences, and not all proteins were affected to the same degree; choline acetyltransferase was not affected. Cellular amino acid transport as studied with incubated slices of brain was not altered under these conditions.

Animals↗

[Some historical considerations on the inflammatory theory of atherosclerosis].

In the past 20 years several clinical and experimental observations have led to the hypothesis that an inflammatory response can trigger some key processes during the development of atherosclerosis. Here we briefly review, from the historical viewpoint, the inflammatory theory of atherosclerosis, as proposed by the Berliner pathologist Rudolf Virchow in the XIX century. Contrary to this hypothesis, in the same period the Viennese Karl von Rokitansky recognized blood dyscrasia (particularly fibrin-induced alterations) as the promoting factor in the process of atherogenesis. Moreover, we outline the relationship between atherosclerosis and arthritis, by reporting some passages from two scientific works published in the late XIX century, the former by the Italian Achille De Giovanni ("Sull'arterite. Sue forme cliniche e sua patogenesi", 1882) and the latter by the French Theophile Guyot ("L'arthritis. Maladie Constitutionnelle", 1890).

Arteriosclerosis↗

[Not Available].

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History, Ancient↗

[Accumulation of glutamic acid and glycine in human cerebral tumors in vitro].

Preliminary results are given on transport of glycine and L-glutamate into human cerebral tissue, normal and tumoral. In comparison with normal tissue, glycine transport is diminished in meningioma and oligodendroblastoma, unaffected in neurinoma, sharply increased in medulloblastoma. Glutamic acid transport is lowered in neurinoma and oligodendroblastoma; increased in medulloblastoma. Such preliminary observations are briefly discussed.

Brain↗