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Biomedical subjects

A M Batlle

Publications and source records attributed to A M Batlle.

At least 91 records · Page 5Linked to original sources

S-adenosyl-L-methionine a counter to lead intoxication?

The effect of S-adenosyl-L-methionine (SAM) administration to both acute and chronic lead exposed mice was investigated. SAM was given s.c. at different doses and for different time intervals. The best results were obtained using 20 mg SAM/kg applied daily over a period of 20-22 days. Results obtained in both acute and chronic lead poisoning were quite similar. GSH concentration in blood and liver, reduced in intoxicated animals was increased after SAM administration reaching normal values. Blood, liver and kidney lead content notably increased at the beginning of SAM treatment and decreased rapidly in the group receiving SAM, attaining values near control levels in 2 weeks. A significant recovery of blood, liver, kidney, spleen and brain delta-aminolevulic acid dehydratase (ALA-D) initially reduced in poisoned animals, was clearly produced after SAM administration. A clear and direct correlation between the recovery of both ALA-D activity and GSH levels and the decreased concentration of lead in tissues was observed, reinforcing our proposal that enhancement of thiol content as a result of SAM administration would facilitate the detoxification process and lead removal, consequently reversing the inactivation of the enzyme. We conclude that SAM therapy is beneficial in the treatment of lead intoxication.

Acute Disease↗

[Adaptation of Rhodopseudomonas palustris to changes in atmospheric conditions].

The high level of delta-aminolaevulinate synthetase (ALA-S) in Rhodopseudomonas palustris cells grown under photosynthetic conditions decreased when they were vigorously aerated; moreover, the bacteriochlorophyll synthesis suddenly stopped. When aeration was interrupted, enzymatic level increased notably, but bacteriochlorophyll level did not. Chloramphenicol added to cultures when aeration was interrupted did not affect the increase of enzymic level. When it was added as the aeration started, the enzymic level decayed, but did not increase as notably when the aeration was interrupted. ALA-S in extracts of aerated cells underwent spontaneous activation when homogenates were stored at 4 degrees C. The effect of several activators on different forms of ALA-S is postulated in order to explain these findings.

5-Aminolevulinate Synthetase↗

Enzyme replacement therapy in porphyrias--IV. First successful human clinical trial of delta-aminolevulinate dehydratase-loaded erythrocyte ghosts.

A patient with chronic lead intoxication was treated with only one course of highly purified human blood aminolaevulinate dehydratase entrapped in autologous erythrocyte ghosts given intravenously. No untoward effects were observed during or after infusion. An immediate increase in the patient's erythrocyte dehydratase activity was detected 1 hr after enzyme administration, reaching its maximum and nearly normal level 2 days later, values remained unchanged for a week, to slowly diminish after 2 weeks of initiated the treatment, and finally recovered activity was kept practically leveled off for weeks. This novel therapeutic trial produced complete improvement both clinical and biochemical, showing that enzyme infusion has been beneficial and can be safely and successfully used in the treatment of human lead intoxication.

Adult↗

Porphyrin biosynthesis in parasitic hemoflagellates: functional and defective enzymes in Trypanosoma cruzi.

1. Heme compounds are necessary as a growth factor for Trypanosoma cruzi in culture, this porphyrin requirement being due to the inability of the parasite to synthesize heme. To obtain supporting evidence for this hypothesis, an extensive study of porphyrin biosynthesis in the epimastogote form of T. cruzi (Tulahuén strain) was carried out. 2. Low levels of endogenous delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) were found in extracts of T. cruzi. Free porphyrins and heme contents were practically nil. 3. The activity of succinyl CoA synthetase (Suc. CoA-S) was rather high and therefore non-limiting. 4. Both delta-aminolevulinic acid synthetase (ALA-S) and 4.5, dioxovaleric transaminase (DOVA-T), the two enzymes forming ALA, were readily detected and their activities, although low, were of the same order. 5. delta-Aminolevulinic acid dehydratase (ALA-D) activity was almost negligible and both porphobilinogenase (PBGase) and deaminase were absent or inactive. 6. Heme-Synthetase (Heme-S) was totally functional. 7. It is concluded that T. cruzi has lost part of its heme biosynthetic pathway, possibly due to mutations of several genes involved in the synthesis of the soluble enzymes ALA-D, PBGase, deaminase and probably others preceding Heme-S; while the particulate enzymes Suc CoA-S, ALA-S, DOVA-T and Heme-S are functional. As a consequence, the host should supply the parasite with the porphyrin substrate to form its essential heme compounds.

5-Aminolevulinate Synthetase↗