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Biomedical subjects

T Bottiglieri

Publications and source records attributed to T Bottiglieri.

70 records · Page 4Linked to original sources

Short term effect of nitrous oxide on methionine and S-adenosyl methionine concentrations.

Concentrations of methionine and S-adenosyl methionine (SAM) have been measured in various tissues of rats exposed to 50% nitrous oxide for periods up to 80 min, a time by which there is detectable interference with thymidine synthesis in bone marrow. There were no significant changes of either SAM or methionine in plasma, whole blood or brain. Hepatic SAM was unchanged, but there was a highly significant reduction in hepatic methionine, to 62% of control, after 80 min exposure to nitrous oxide.

Animals↗

The switch mechanism and the bipolar/unipolar dichotomy.

During open trials of intravenous and oral S-adenosyl methionine (SAM) and a placebo-controlled trial of intravenous SAM in 29 patients, 25 patients had SAM and four had placebo (27 courses of SAM, two of the patients receiving two trials a piece). Nine of 11 bipolar patients (all SAM-treated) switched into elevated mood state (hypomania, mania and euphoria) and two did not respond. Six endogenous unipolar patients improved and five did not. No non-endogenous patient or placebo patient responded for more than 14 days. No unipolar patient switched into elated mood. In eleven (38%) trials and nine (33%) patients there was a switch from depression to elation. Biochemical data from the cerebrospinal fluid of eight patients suggested that the role of the dopaminergic system should be further explored.

Administration, Oral↗

Demyelination and decreased S-adenosylmethionine in 5,10-methylenetetrahydrofolate reductase deficiency.

We previously described demyelination in the brain and subacute combined degeneration of the spinal cord in a patient with 5,10-methylenetetrahydrofolate reductase deficiency. To assess the role of methionine, S-adenosylmethionine, folate, and neurotransmitter amine metabolism in the demyelination process, we measured these metabolites in CSF from this patient; the findings are compared with those obtained from three patients in whom neurologic deterioration had been halted by the administration of betaine. Folate concentrations were low, and amine and biopterin metabolism were abnormal in all patients. Methionine and S-adenosylmethionine concentrations were undetectable in the first patient. In those receiving betaine, methionine concentrations were proportional to the dose administered and S-adenosylmethionine concentrations were near normal. The results provide the first evidence for an association between defective S-adenosylmethionine metabolism and demyelination in humans.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗

The effect of storage on rat tissues and human plasma amino acid levels determined by HPLC.

Tissue concentrations of the amino acids tryptophan, methionine, valine, phenylalanine, isoleucine and leucine were determined in rat liver, skeletal muscle and brain tissue and human plasma. The effect of storage at -20 degrees C for up to 21 days was examined. Significantly elevated levels after 7 and 21 days of storage were observed in liver and brain tissue but no changes were found in muscle and plasma. Minimal changes occurred in liver tissue stored up to 6 hours at -4 degrees C. This study emphasizes the need for rapid deproteinization of tissues to avoid changes in the free pool of amino acids.

Amino Acids, Essential↗

Effect of short-term administration of nitrous oxide on plasma concentrations of methionine, tryptophan, phenylalanine and S-adenosyl methionine in man.

Plasma concentrations of methionine, tryptophan, phenylalanine and S-adenosyl methionine (SAM) were measured at the beginning and end of general anaesthesia (for routine surgery) lasting between 25 and 217 min which included 60-70% nitrous oxide. Plasma methionine, tryptophan and phenylalanine concentrations in patients prepared for surgery averaged 68 (SD 11.3)% of values in a group of normal control subjects. At the end of administration of nitrous oxide (mean duration 88 min) there were no significant changes in the mean methionine and phenylalanine concentrations, but the mean concentration of tryptophan was reduced by 15% (P = 0.0075). SAM concentrations averaged 40% greater in males than females in all groups, but there were no significant differences between the concentrations in the control subjects and the patients before or after the administration of nitrous oxide.

Adult↗

Affective illness and S-adenosyl methionine: a preliminary report.

S-Adenosyl methionine may well have an antidepressant action beyond a placebo effect but this is virtually confined to endogenous depression. This should be subjected to further study. Our own double-blind placebo-controlled study is still incomplete. The indications are that SAM specifically affects folate, dopamine, and serotonin metabolism as well as activating and switching brain mechanisms. This suggests exciting prospects for further investigations. SAM is a nontoxic physiological metabolite virtually free of side effects.

Adult↗

Decreased homovanilic acid in cerebrospinal fluid correlates with impaired neuropsychologic function in HIV-1-infected patients.

To determine whether dopamine metabolism is abnormal in HIV infected patients and whether dopamine metabolism abnormalities are related to specific neuropsychologic characteristics in HIV-infected patients, we measured cerebrospinal fluid (CSF) levels of homovanilic acid (HVA), the primary dopamine metabolite, in 10 HIV-infected patients and compared it to HVA levels in CSF in a group of 13 healthy control subjects. HIV-infected patients were also assessed with a battery of neuropsychologic tests and HVA levels were then correlated with performance on specific neuropsychologic tests. The mean (+/-SD) HVA level in CSF was 100.9 +/- 29.3 nmol/L in the HIV-infected study group and 230.5 +/- 50.0 nmol/L in the non-HIV-infected control group (p < 0.0001). The decrease in concentrations of HVA in CSF correlated with impairment on performance on neuropsychologic testing (Spearman r = 0.67; p = 0.03). When the relationship between HVA levels and specific cognitive domains was evaluated, we observed trends for positive correlation between HVA levels and tests that measure motor speed (r = 0.59; p = 0.074) and those testing attention, concentration, and executive control (r = 0.54; p = 0.108). There was no relationship between performance on memory tests and CSF HVA levels (r = -0.0061; p = 0.987). These results further support the hypothesis that dopaminergic dysfunction plays an important role in the pathogenesis of AIDS dementia complex (ADC) and suggest that specific motor and cognitive abnormalities may be related to depressed dopaminergic activity. This may have important implications for the development of treatments or preventive strategies for ADC.

Adult↗

Plasma homocysteine levels and folate status in children with sickle cell anemia.

PURPOSE: A sensitive inverse relationship between plasma homocysteine concentration and folate status has been demonstrated. Although children with sickle cell anemia (SCA) are at potential risk for folate deficiency, plasma homocysteine levels have not been reported in such patients. Therefore, a study was designed to assess plasma homocysteine levels as a marker of folate status. DESIGN: Plasma homocysteine concentrations were measured in 120 children with SCA (102 in steady state and 18 during an acute complication) who had never received supplemental folic acid. Folate status was directly assessed in 34 of these patients. RESULTS: Plasma homocysteine levels in the patients with SCA and control subjects were similar. The mean value +/- 1 SD was 5.8+/-2.5 micromol/L (range, 1.6 to 14.1 micromol/L) in the patients with SCA and 6.1+/-2.7 micromol/L (range, 1.7 to 15.3 micromol/L) in 73 pediatric control subjects. In a subpopulation of the study group (34 children), simultaneous serum folate, red cell folate, and total homocysteine concentrations were also measured. Their serum folate and red cell folate concentrations were normal: 12.4+/-10.0 nmol/L (range, 1 to 42 nmol/L) and 604+/-374.7 nmol/L (range, 205 to 1741 nmol/L), respectively. There was no correlation of plasma homocysteine concentration with various clinical or laboratory measures or with red cell folate concentration. CONCLUSION: Folate stores in children with SCA not receiving folic acid supplements are adequate despite an underlying hemolytic anemia.

Adolescent↗