Erzsébet Nagy

Concentration gradients for HVA, 5-HIAA, ascorbic acid, and uric acid in cerebrospinal fluid

Concentrations of HVA, 5-HIAA, ascorbic acid, and uric acid in the lumbar and cisternal cerebrospinal fluid (CSF) were measured in psychiatric and neurologically impaired patients. The concentration of HVA is 6.1 times and of 5-HIAA 2.7 times higher in cisternal than in lumbar samples, the cisternal level of uric acid is half that of the lumbar region, but no significant differences were found in ascorbic acid concentrations. Correlation between lumbar and cisternal metabolite concentrations is high for 5-HIAA and ascorbic acid, and is less for HVA and uric acid. In cisternal CSF there is a significant correlation between levels of HVA-5-HIAA, 5-HIAA-ascorbic acid, and 5-HIAA-uric acid. These correlations disappear in lumbar CSF. These findings indicate that extrapolations to cisternal neurotransmitter metabolite concentration from lumbar measures are unwarranted for HVA, but not for 5-HIAA.

Oxidation of hemoglobin by lipid hydroperoxide associated with low-density lipoprotein (LDL) and increased cytotoxic effect by LDL oxidation in heme oxygenase-1 (HO-1) deficiency

Heme-catalyzed oxidation of low-density lipoprotein (LDL) is one of the relevant mechanisms involved in LDL modification. We previously revealed a substantial oxidation of plasma hemoglobin to methemoglobin and a subsequent heme-catalyzed LDL oxidation generating moieties toxic to endothelium in heme oxygenase-1 (HO-1)-deficiency in human. Drawing upon our previous observation we posited a pathway for oxidation of plasma hemoglobin in the HO-1-deficient child involving LDL-associated lipid hydroperoxide. In support, LDL-associated lipid hydroperoxide oxidized ferrohemoglobin to methemoglobin--known to readily release its heme moieties--in a dose-dependent manner. Repeated heme exposure of the child s LDL further increased its lipid hydroperoxide content within min leading to additional cytotoxic effect on endothelium. Both cytotoxicity and HO-1 inducing ability of the oxidized LDL were strongly dependent on its lipid hydroperoxide content. We wondered if cells of the HO-1-deficient patient were prone to oxidative damage arising from heme-mediated oxidation of LDL. Indeed, we found elevated cytotoxicity induced by heme-catalyzed oxidation of LDL in lymphoblastoid cells derived from the HO-1-deficient patient. We conclude that oxidation of hemoglobin to methemoglobin by LDL-associated lipid hydroperoxide and increased sensitivity of cells of the HO-1-deficient child to stress of oxidized LDL might contribute to the vascular disorders reported earlier.

Amino acid concentrations in cerebrospinal fluid in presenile and senile dementia of Alzheimer type and multi-infarct dementia

Free amino acid levels were measured in cerebrospinal fluid (CSF) from demented patients (D, n = 30) suffering from presenile and senile dementia of Alzheimer type (PDAT, n = 7; SDAT, n = 9), multi-infarct dementia (MID, n = 14) and a reference sample group consisting of young neurotic patients (R, n = 16). Comparing the amino acid levels in the dementia subgroups, significantly higher alanine, methionine, phenylalanine and tyrosine levels were found both in MID and SDAT vs. PDAT. No difference was seen between SDAT and MID. Compared to the reference sample group, higher glycine levels were found in each dementia subgroup; higher alanine, methionine and ornithine levels in MID, and SDAT; and higher phenylalanine levels in MID. In PDAT the level of tyrosine was lower. Coefficients of correlation were calculated between amino acid levels and age, and the findings in the reference sample groups were divergent from those observed in dementia. The differences observed are discussed in terms of amino acid, carbohydrate and neurotransmitter metabolism.

Correlations between cisternal CSF and plasma concentrations of HVA, MHPG, 5-HIAA, DA, and NA

In the present work we compared the levels of HVA, MHPG, 5-HIAA, DA, and NA in cisternal CSF (cCSF) with their plasma concentrations. Our question was whether or not the levels of these substances are in good accordance with the levels in cisternal CSF

Ascorbic acid in cerebrospinal fluid - a possible protection against free radicals in the brain.

The function of ascorbic acid in living organisms is complex. Previous studies emphasize its protective role against harmful effect of free radicals, and its presence is necessary for the function of numerous enzymes. Ascorbic acid is a powerful reducing agent due to its dienol molecular structure, which is not present in the oxidized form, dehydroascorbic acid. The ratio of ascorbic acid and dehydroascorbic acid might be a marker of oxidative-reductive processes. We measured and compared the level of ascorbic acid and dehydroascorbic acid in the plasma of healthy persons and those of senile dementia patients, who represent pathological aging of the brain. In senile dementia patients, ascorbic acid and dehydroascorbic acid levels were also measured in the cerebrospinal fluid. Concentrations were determined by high performance liquid chromatography with electrochemical detection. In the plasma of senile dementia patients, very low ascorbic acid levels were found (ca. 30% of the healthy control). In lumbar cerebrospinal fluid, the concentration of ascorbic acid is 2.7 times higher compared to that of the plasma level. After intravenous infusion of ascorbic acid, a slow but marked increase of the concentration in the cerebrospinal fluid was measured. Our results support an active transport process for ascorbic acid through the blood-CSF barrier. Ascorbic acid level might be an important factor representing the protection of the central nervous system against free radicals.

Dementias, psychological tests, and neurotransmitters

A preliminary investigation was made of data of intelligence quotient, dementia quotients, objective profile analysis of MAWI (Hungarian standardized version of WAIS) in patients suffering from multi infarct, primary degenerative and alcoholic dementia (MID, PDD, Alc. D). Homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) were measured in lumbar cerebrospinal fluid (CSF) from patients with presenile dementia and senile dementia of Alzheimers type (PDAT and SDAT) and multi infarct dementia. They were compared to controls and to each other. Alcoholic dementia can be differentiated from other types of dementia mainly by the values of verbal and practical quotients (VQ/PQ), Hewson Index 5 and by the objective profile analysis. MID can hardly be differentiated from PDD, but the objective profile analysis can help, mainly subtests 1 and 3 of MAWI. No decrease was found in the concentrations of HVA and 5-HIAA in lumbar CSF of demented patients compared to controls, but there was an elevation in 5-HIAA concentration.

Identification of sulfhemoglobinemia after surgical polypectomy

Sulfhemoglobinemia (SHb) is an uncommon cause of cyanosis that is predominantly drug-induced in adults. We report an unusual case of sodium sulfate-induced sulfhemoglobinemia in a 61-year-old woman after surgical polypectomy. Fractional hemoglobin derivates were assayed by spectrophotometry and high-performance liquid chromatography. The SHb ratio was 8.6% in the first sample and 3.77% a month later measured by spectrophotometry. In the blood hemolysate, a new peak was identified as SHb with high-performance liquid chromatography (HPLC). HPLC showed the presence of 9.37% SHb in the first sample and 4.88% a month later. After removing the suspected toxic agent the cyanosis decreased significantly. The findings underline the importance of routine SHb detection in cyanosis of unknown origin especially in emergency cases.