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Biomedical subjects

G Stramentinoli

Publications and source records attributed to G Stramentinoli.

At least 19 recordsLinked to original sources

[The effect of S-adenosyl-L-methionine (SAM) on membrane permeability in the perfused rat liver].

S-adenosilmethionine is present in most human tissues and is an important factor for transmethylation, transulphuration and aminopropylation reactions. The compound improves the biological, morphological and histochemical aspects of rat liver following CCl4 intossication. At the same time has been successfully used during chronic liver disease in man. With the aim to better clarify the action mechanism of SAMe some aspects concerning its effects on cell permeability in rat liver, by using the perfusion technique, have been investigated. In particular the capacity of this compound to prevent the enzymatic loss (GPT and GOT) during liver perfusion has been studied. 30 perfusions without SAMe, as control, and 6 by infusing 2 mg of compound during the perfusion time have been accomplished. Varing the perfusion time from 0 to 120 min it has been observed that at any time the presence of the SAMe reduced by about 50% the loss of GOT. Similarly the activity of GPT ranging from 2 to 6 mU/ml indicate that no appreciable enzyme output occurs in presence of SAMe.

Animals

Methylation hypothesis.

L-Methionine had no behavioral effects in normal humans and failed to increase concentrations of S-adenosylmethionine (methyl donor) in human or rat blood, while increasing rat liver levels more than fivefold. Methionine or S-adenosylmethionine in very high doses had almost no effect on methylation of tritiated levodopa in rodent tissues; various "methyl acceptor" molecules, including nicotinamide, guanidineacetic acid, and estradiol similarly had little effect. In rabbit lung, methionine and S-adenosylmethionine not only failed to increase production of dimethyltryptamine, but actually decreased it, possibly due to end-product inhibition by S-adenosylhomocysteine, which also strongly inhibited methylation of dopa in rat. These results fail to support several predictions of the "methylation hypothesis" concerning the pathophysiology and potential treatment of idiopathic psychotic disorders and leave the consistent clinical worsening effects of methionine in schizophrenia unexplained.

Adult

Localization of S-[methyl-14 C]adenosyl-L-methionine in pregnant mice and fetuses as determined by autoradiography.

The distribution of S-[methyl-14C]Adenosyl-L-methionine has been examined in pregnant mice using an autoradiographic technique. The results indicate that the compound crosses the placental barrier quite slowly and accumulates in some fetal tissues such as intestine, liver, kidney, eye and lung. The highest concentration is reached 12 hours after i.v. administration of the compound. In the placenta the labelling can be detected for a long time after administering the radioactive compound.

Animals

Kinetics of S-adenosyl-L-methionine in isolated perfused rat liver and its effects on microsomal enzyme activity.

S-Adenosyl-L-methionine (SAMe) levels in liver tissue were reduced by 35% after isolation and washing of the organ. The apparent half-life of SAMe (1,75-25 microM) during liver perfusion was between 120 and 460 min; however the uptake of the labelled methyl group by hepatic tissue of fed rats was low (6%). This value increased to 12% in organs isolated from 24-hour fasted animals. Addition of SAMe to the perfusion medium increased tissue levels of ATP. Except for N-demethylation of aminopyrine and cytochrome c reductase, liver microsomal activity was not affected by treatment with SAMe either in vivo or/and in perfused liver.

Adenosine Triphosphate

Intestinal absorption of S-adenosyl-L-methionine.

The gastrointestinal absorption of S-adenosyl-L-methionine (SAMe) is demonstrated by evaluating plasma levels and gastrointestinal content of the unmodified molecule after oral administration. When [methyl-14C]SAMe is given orally, the radioactivity found in the liver is associated both with SAMe and phosphatidylcholine, a compound known to be derived from the methylation of phosphatidylethanolamine with SAMe as a methyl donor. These results and low plasma levels after the oral administration may be suggestive of a first-pass effect of SAMe characterized by an extensive uptake of the drug by the liver where it is rapidly metabolized.

Administration, Oral

Postnatal changes in blood S-adenosylmethionine concentration. Some observations in hyaline membrane disease.

The blood concentration of S-adenosylmethionine in 18 premature neonates affected by hyaline membrane disease did not differ from that found in a control group of healthy premature newborns. However, these values are higher than those found in full-term infants: this fact suggests that the methionine cycle is active in both the fetus and premature neonate with consequent conservation of homocysteine sulfur. These data provide ancillary evidence in support of the hypothesis that in premature babies cyst(e)ine is an essential amino acid. The concentration of S-adenosylmethionine reaches its lowest level 30 days after birth and then stabilizes at the age of 2--5 months with blood levels similar to those of the normal adult.

Adult