Biomedical subjects

P Rigotti

Publications and source records attributed to P Rigotti.

At least 73 records · Page 4Linked to original sources

PubMed1985

Infusion of branched-chain amino acids and ammonium salts in rats with portacaval shunts.

During infusion into rats with a portacaval shunt of either ammonium (NH4+) salts alone or NH4+ salts combined with the three branched-chain amino acids (BCAAs) in equimolar quantities, we assessed neurologic function and measured plasma and brain ammonia and amino acid levels and the brain content of amine neurotransmitters and their metabolites. Survival was lengthened and neurologic function was preserved longer in rats receiving BCAAs. Infusion of BCAAs resulted in lower plasma and brain ammonia concentrations compared with rats receiving NH4+ salts alone. Plasma glutamine and alanine levels were higher in rats receiving BCAAs, suggesting increased ammonia detoxification. Loss of neurologic function, regardless of which solution was infused, eventually occurred and corresponded with decreased brain norepinephrine and increased brain alanine levels. These results suggest that BCAAs can protect against hyperammonemia by stimulating the peripheral detoxification of ammonia.

Amino Acids, Branched-Chain↗

PubMed1984

Methionine sulfoximine prevents the accumulation of large neutral amino acids in brain of hyperammonemic rats.

Accumulation of neutral amino acids in the brain due to altered transport across the blood-brain barrier appears to be a consequence of portal-systemic shunting and hyperammonemia. It has been suggested that high brain concentrations of glutamine, a product of cerebral ammonia detoxification, accelerates the transport of other neutral amino acids from blood to brain. To test this hypothesis, normal rats were infused with ammonium salts with or without pretreatment with L-methionine-dl-sulfoximine (MSO), an inhibitor of glutamine synthesis. Pretreatment with MSO prevented most ammonium salt-induced changes in the concentrations of the neutral amino acids in brain, suggesting that hyperammonemia alters the transport of neutral amino acids across the blood-brain barrier by causing the brain glutamine level to rise.

Amino Acids↗

PubMed1984

Functional evaluation of distal esophagus and lower esophageal sphincter after esophagogastric devascularization, esophageal transection and antireflux procedure for bleeding esophageal varices.

Distal esophageal function and LES competence were evaluated in 21 patients by means of esophageal manometry and standard pHmetry after Sujura mod. operation for bleeding esophageal varices. This operation involves complete devascularization of 10-12 cm. of distal esophagus, disruption of anatomic anti-reflux mechanism, excision of nearly one cm. of muscular tissue at lower esophageal sphincter level. Intraoperative manometry was performed in 8 patients and demonstrated a significant shortening of high pressure zone, while lower esophageal sphincter pressure did not show significant variations. Postoperatively gastroesophageal reflux at pHmetry was not observed (five patients had pathological reflux preoperatively). No significant variations of resting lower esophageal sphincter pressure and no peristaltic alterations were observed. In conclusion despite the marked anatomic alterations related to this procedure, sphincter dynamics and distal esophageal function remain nearly normal.

Adult↗

PubMed1982

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↗

PubMed1981

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↗

PubMed1980

Does liver arterialization improve the altered cerebral amino acid pattern in the rat after portacaval shunt?

Altered plasma and brain amino acid patterns have been observed in the rat after portacaval shunt. Similar alterations are likely to play an important role in hepatic encephalopathy in humans. In our model, liver arterialization remarkably improves the pathologic amino acid levels following portacaval shunt.

Amino Acids↗

PubMed1979

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↗

PubMed1979

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↗

PubMed1976

Investigations on the turnover of adrenocortical mitochondria. IV. A stereological study of the effect of chronic treatment with ACTH on the size and number of rat zona reticularis mitochondria.

The effects of chronic administration of of ACTH (up to 36 consecutive days) on the mitochondria of the zona reticularis of the rat adrenal cortex were investigated by stereologic techniques. It was found that ACTH induces two phases of hypertrophy of mitochondria alternating with two proliferative stages, which are associated with a significant decrease in the average volume of the organelles. It is suggested that, as in the zona fasciculata, ACTH controls the processes of growth and division of mitochondria in the zona reticularis. The mechanism underlying this action of ACTH as well as the differences between the responses to ACTH of the mitochondrial population of the two adrenal zones are discussed in the light of evidence indicating that mitochondria contain a complete genetic apparatus largely independent of nuclear control.

Adrenal Cortex↗

PubMed1976

Effect of ACTH on the zona reticularis of the rat adrenal cortex: an ultrastructural stereologic study.

The effects of ACTH on the rat adrenal zona reticularis were investigated by stereologic methods. It was found that the zona reticularis cell responsiveness to ACTH is similar to that of the zona fasciculata elements. This excludes that the zona reticularis of the adult rat can only function as the site of destruction of worn-out elements migrating from the adrenal outer zones.

Adrenal Cortex↗

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