Cobalamin deficiency with and without neurologic abnormalities: differences in homocysteine and methionine metabolism

Blood ◽  
2003 ◽  
Vol 101 (8) ◽  
pp. 3302-3308 ◽  
Author(s):  
Ralph Carmel ◽  
Stepan Melnyk ◽  
S. Jill James
Keyword(s):  
Pernicious Anemia ◽  
Metabolic Pathways ◽  
Healthy Subjects ◽  
Serum Levels ◽  
Metabolic Changes ◽  
Cobalamin Deficiency ◽  
Methionine Metabolism ◽  
Biochemical Basis ◽  
Neurologic Dysfunction ◽  
Total Homocysteine

AbstractThe unknown biochemical basis for neurologic dysfunction in cobalamin deficiency and the frequent divergence between neurologic and hematologic manifestations led us to study homocysteine metabolism in 22 patients with pernicious anemia. Serum levels of total homocysteine (tHcy), methionine, S-adenosylmethionine (AdoMet), cysteine, cysteinylglycine (cys-gly), and glutathione (GSH) were measured. Only levels of tHcy and cysteine were increased and only GSH was decreased in cobalamin deficiency as a whole, compared with 17 control subjects. AdoMet correlated only with methionine levels (P = .015) and cysteine only with cys-gly (P = .007) in healthy subjects, but in cobalamin-deficient patients AdoMet correlated instead with cysteine, cys-gly, and folate levels only (P = .008,P = .03, and P = .03, respectively). Significant differences appeared in clinically subgrouped cobalamin-deficient patients. The 11 patients with neurologic defects had higher mean levels of folate (27.9 versus 15.4 nM), AdoMet (117.2 versus 78.6 nM), cysteine (462 versus 325 μM), and cys-gly (85.0 versus 54.7 μM) than the 11 neurologically unaffected patients. Cobalamin therapy restored all metabolic changes to normal. The results indicate that changes in several metabolic pathways differ in patients with and without neurologic dysfunction. Cysteine levels were the most significant predictors of neurologic dysfunction, but it is unclear if they are direct or indirect indicators of neurotoxicity. The higher AdoMet levels in neurologically affected patients may result from inhibition of glycine N-methyltransferase by those patients' higher folate levels. The origin of the folate differences is unclear and possibly varied. Low AdoMet and GSH levels were independent predictors of anemia.

scholarly journals Malondialdehyde, glutathione, glutathione peroxidase and homocysteine levels in type 2 diabetic patients with and without microalbuminuria

2005 ◽  
Vol 42 (2) ◽  
pp. 99-104 ◽  
Author(s):  
Gülsen Ozdemır ◽  
Meltem Ozden ◽  
Hale Maral ◽  
Sevinc Kuskay ◽  
Pinar Cetınalp ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Vascular Disease ◽  
Healthy Subjects ◽  
Serum Levels ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Significant Difference ◽  
Total Homocysteine ◽  
Type 2 Diabetic

Background: High levels of homocysteine and oxidative stress are known to be associated with premature vascular disease in type 2 diabetes mellitus (DM). The aim of this study was to estimate homocysteine levels and oxidant-antioxidant status and to determine the relationship between them in type 2 diabetic patients with and without microalbuminuria. Methods: Fasting blood samples were obtained from 48 diabetic patients (17 with and 31 without microalbuminuria) and 20 healthy subjects. Serum total homocysteine (tHcy), plasma malondialdehyde (MDA) erythrocyte glutathione (GSH) and glutathione peroxidase (GPx) activity were measured in these patients and the results were compared with those of controls who were chosen among healthy subjects. Results: MDA levels were found to be significantly lower and GSH levels and GPx activities were found to be significantly higher in control subjects when compared with patients with and without microalbuminuria (MDA: P<0.0001, P<0.0001; GSH: P<0.0001, P<0.0001; GPx: P<0.0001, P<0.001, respectively). MDA levels were found to be significantly higher in patients with microalbuminuria compared with patients without microalbuminuria ( P<0.0001), while similarly GSH levels were found to be significantly lower in patients with microalbuminuria ( P<0.0001). Although there were no significant differences with respect to tHcy levels and GPx activities between the microalbuminuric and normoalbuminuric patients ( P>0.05), there was a significant difference with respect to tHcy levels between healthy controls and patients with microalbuminuria ( P<0.05). The serum levels of tHcy correlated best with plasma MDA and erythrocyte GSH concentrations in all diabetic patients ( r=0.549, P<0.0001; r=0.385, P<0.01). Conclusion: Decreased antioxidant levels, increased lipid peroxidation and increased tHcy levels were observed in patients with microalbuminuria. These changes may contribute to vascular disease, which is particularly prevalent in type 2 DM patients with microalbuminuria.

scholarly journals Clinical spectrum and diagnosis of cobalamin deficiency [see comments]

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 871-881 ◽  
Author(s):  
SP Stabler ◽  
RH Allen ◽  
DG Savage ◽  
J Lindenbaum
Keyword(s):  
Cell Volume ◽  
Peripheral Blood ◽  
Methylmalonic Acid ◽  
Peripheral Blood Smear ◽  
Normal Subjects ◽  
Lactic Dehydrogenase ◽  
Serum Levels ◽  
Cobalamin Deficiency ◽  
Mean Cell Volume ◽  
Total Homocysteine

To better estimate how frequently patients with low serum cobalamin (Cbl) levels in current clinical practice are truly deficient in Cbl and to determine the incidence of atypical or nonclassic presentations of Cbl deficiency, we prospectively studied 300 unselected consecutive patients with serum Cbl concentrations less than 200 pg/mL seen at two medical centers over a 2-year period. Baseline hematologic, neuropsychiatric, and biochemical measurements were obtained, followed by a course of parenteral Cbl therapy and reassessment. A response to Cbl therapy was defined as one or more of the following: (1) an increase in hematocrit of 0.05 or more; (2) a decrease in mean cell volume of 5 fL or more; (3) a clearing of hypersegmented neutrophilis and macroovalocytes from the peripheral blood smear; and (4) an unequivocal and prompt improvement of neuropsychiatric abnormalities. Of the 300 patients with serum Cbl levels less than 200 pg/mL, 86 had one or more responses to Cbl therapy and 59 had no response. In 155, insufficient data was available. In the Cbl-responsive patients, normal values were found for the following tests: hematocrit, 44%; mean cell volume less than or equal to 100 fL, 36%; white blood cell count, 84%; platelet count, 79%; serum lactic dehydrogenase, 43%; and serum bilirubin, 83%. Peripheral blood smears were nondiagnostic in 6% when reviewed by the investigators, but 33% as reported by routine laboratories. Serum Cbl levels in the 100 to 199 pg/mL range were present in 38%. Neuropsychiatric abnormalities were noted in 28%, often in the absence of anemia, macrocytosis, or both. Serum levels of methylmalonic acid and/or total homocysteine were elevated greater than 3 SDs above the mean for normal subjects in 94% of the Cbl-responsive patients. We conclude that Cbl deficiency should be considered and investigated in patients with unexplained hematologic or neuropsychiatric abnormalities of the kind seen in Cbl deficiency, even if anemia, an elevated mean cell volume, a marked depression of the serum Cbl, or other classic hematologic or biochemical abnormalities are lacking. Levels of serum methylmalonic acid and total homocysteine are useful as ancillary diagnostic tests in the diagnostis of Cbl deficiency.

scholarly journals Clinical spectrum and diagnosis of cobalamin deficiency [see comments]

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 871-881 ◽  
Author(s):  
SP Stabler ◽  
RH Allen ◽  
DG Savage ◽  
J Lindenbaum
Keyword(s):  
Cell Volume ◽  
Peripheral Blood ◽  
Methylmalonic Acid ◽  
Peripheral Blood Smear ◽  
Normal Subjects ◽  
Lactic Dehydrogenase ◽  
Serum Levels ◽  
Cobalamin Deficiency ◽  
Mean Cell Volume ◽  
Total Homocysteine

Abstract To better estimate how frequently patients with low serum cobalamin (Cbl) levels in current clinical practice are truly deficient in Cbl and to determine the incidence of atypical or nonclassic presentations of Cbl deficiency, we prospectively studied 300 unselected consecutive patients with serum Cbl concentrations less than 200 pg/mL seen at two medical centers over a 2-year period. Baseline hematologic, neuropsychiatric, and biochemical measurements were obtained, followed by a course of parenteral Cbl therapy and reassessment. A response to Cbl therapy was defined as one or more of the following: (1) an increase in hematocrit of 0.05 or more; (2) a decrease in mean cell volume of 5 fL or more; (3) a clearing of hypersegmented neutrophilis and macroovalocytes from the peripheral blood smear; and (4) an unequivocal and prompt improvement of neuropsychiatric abnormalities. Of the 300 patients with serum Cbl levels less than 200 pg/mL, 86 had one or more responses to Cbl therapy and 59 had no response. In 155, insufficient data was available. In the Cbl-responsive patients, normal values were found for the following tests: hematocrit, 44%; mean cell volume less than or equal to 100 fL, 36%; white blood cell count, 84%; platelet count, 79%; serum lactic dehydrogenase, 43%; and serum bilirubin, 83%. Peripheral blood smears were nondiagnostic in 6% when reviewed by the investigators, but 33% as reported by routine laboratories. Serum Cbl levels in the 100 to 199 pg/mL range were present in 38%. Neuropsychiatric abnormalities were noted in 28%, often in the absence of anemia, macrocytosis, or both. Serum levels of methylmalonic acid and/or total homocysteine were elevated greater than 3 SDs above the mean for normal subjects in 94% of the Cbl-responsive patients. We conclude that Cbl deficiency should be considered and investigated in patients with unexplained hematologic or neuropsychiatric abnormalities of the kind seen in Cbl deficiency, even if anemia, an elevated mean cell volume, a marked depression of the serum Cbl, or other classic hematologic or biochemical abnormalities are lacking. Levels of serum methylmalonic acid and total homocysteine are useful as ancillary diagnostic tests in the diagnostis of Cbl deficiency.

Detection and Quantification of 7-Hydroxydehydroepiandrosterone Epimers in Three Body Fluids

2002 ◽  
Vol 67 (1) ◽  
pp. 10-18 ◽  
Author(s):  
Richard Hampl ◽  
Martin Hill ◽  
Luboslav Stárka
Keyword(s):  
Healthy Subjects ◽  
Serum Levels ◽  
Body Fluids ◽  
Gas Chromatography Mass Spectrometry ◽  
Specific Radioimmunoassay ◽  
Order Of Magnitude ◽  
Three Body ◽  
First Time ◽  
Nanomolar Range ◽  
Detection And Quantification

3β,7α-Dihydroxyandrost-5-en-17-one (1) (7α-OH-DHEA) and its 7β-hydroxy epimer 2 (7β-OH-DHEA) - 7α- and 7β-hydroxydehydroepiandrosterone - were detected and quantified in three human body fluids: in blood serum, saliva and ejaculate. Specific radioimmunoassay and gas chromatography-mass spectrometry have been used. For the first time the data on changes of these dehydroepiandrosterone metabolites are reported for a representative group of healthy subjects of both sexes (172 females and 217 males) during the life span. The serum levels of both 7-hydroxydehydroepiandrosterone epimers in serum and also in semen were in the low nanomolar range, while concentrations by one order of magnitude lower were found in saliva, but still within the detection limit. The results will serve as a basis for comparative studies of 7-hydroxydehydroepiandrosterone levels under various pathophysiological conditions, with a particular respect to autoimmune disorders.

scholarly journals Lipocalin 2 serum levels correlate with age and bone turnover biomarkers in healthy subjects but not in postmenopausal osteoporotic women

Bone Reports ◽  
2021 ◽  
pp. 101059
Author(s):  
Antonio Maurizi ◽  
Marco Ponzetti ◽  
Kaare M. Gautvik ◽  
Sjur Reppe ◽  
Anna Teti ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Healthy Subjects ◽  
Serum Levels ◽  
Lipocalin 2 ◽  
Bone Turnover Biomarkers

scholarly journals The Effect of Bilateral Nephrectomy on Renalase and Catecholamines in Hemodialysis Patients

2021 ◽  
Vol 18 (12) ◽  
pp. 6282
Author(s):  
Magda Wiśniewska ◽  
Natalia Serwin ◽  
Violetta Dziedziejko ◽  
Małgorzata Marchelek-Myśliwiec ◽  
Barbara Dołęgowska ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Plasma Concentrations ◽  
Serum Levels ◽  
Hemodialysis Patients ◽  
Pressure Regulation ◽  
Serum Concentrations ◽  
Monoamine Oxidase Activity ◽  
Normal Kidney ◽  
Bilateral Nephrectomy ◽  
Arterial Blood

Background/Aims: Renalase is an enzyme with monoamine oxidase activity that metabolizes catecholamines; therefore, it has a significant influence on arterial blood pressure regulation and the development of cardiovascular diseases. Renalase is mainly produced in the kidneys. Nephrectomy and hemodialysis (HD) may alter the production and metabolism of renalase. The aim of this study was to examine the effect of bilateral nephrectomy on renalase levels in the serum and erythrocytes of hemodialysis patients. Methods: This study included 27 hemodialysis patients post-bilateral nephrectomy, 46 hemodialysis patients without nephrectomy but with chronic kidney disease and anuria and 30 healthy subjects with normal kidney function. Renalase levels in the serum and erythrocytes were measured using an ELISA kit. Results: Serum concentrations of renalase were significantly higher in post-bilateral nephrectomy patients when compared with those of control subjects (101.1 ± 65.5 vs. 19.6 ± 5.0; p < 0.01). Additionally, renalase concentrations, calculated per gram of hemoglobin, were significantly higher in patients after bilateral nephrectomy in comparison with those of healthy subjects (994.9 ± 345.5 vs. 697.6 ± 273.4, p = 0.015). There were no statistically significant differences in plasma concentrations of noradrenaline or adrenaline. In contrast, the concentration of dopamine was significantly lower in post-nephrectomy patients when compared with those of healthy subjects (116.8 ± 147.7 vs. 440.9 ± 343.2, p < 0.01). Conclusions: Increased serum levels of renalase in post-bilateral nephrectomy hemodialysis patients are likely related to production in extra-renal organs as a result of changes in the cardiovascular system and hypertension.

scholarly journals The holding temperature of blood during a delay to processing can affect serum and plasma protein measurements

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Milton Ashworth ◽  
Benjamin Small ◽  
Lucy Oldfield ◽  
Anthony Evans ◽  
William Greenhalf ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Room Temperature ◽  
Serum Levels ◽  
Data Interpretation ◽  
Blood Samples ◽  
Specific Manner ◽  
Associated Proteins ◽  
Holding Temperature ◽  
Pai 1 ◽  
Meaningful Data

AbstractAccurate blood-borne biomarkers are sought for diagnosis, prognosis and treatment stratification. Consistent handling of blood is essential for meaningful data interpretation, however, delays during processing are occasionally unavoidable. We investigated the effects of immediately placing blood samples on ice versus room temperature for 1 h (reference protocol), and holding samples on ice versus room temperature during a 3 h delay to processing. Using Luminex multi-plex assays to assess cytokines (n = 29) and diabetes-associated proteins (n = 15) in healthy subjects, we observed that placing blood samples immediately on ice decreased the serum levels of several cytokines, including PAI-1, MIP1-β, IL-9, RANTES and IL-8. During a delay to processing, some analytes, e.g. leptin and insulin, showed little change in serum or plasma values. However, for approximately half of the analytes studied, a delay, regardless of the holding temperature, altered the measured levels compared to the reference protocol. Effects differed between serum and plasma and for some analytes the direction of change in level varied across individuals. The optimal holding temperature for samples during a delay was analyte-specific. In conclusion, deviations from protocol can lead to significant changes in blood analyte levels. Where possible, protocols for blood handling should be pre-determined in an analyte-specific manner.

P0031AURINE METABOLOMICS: AN EMERGING TOOL FOR DISSECTING BIOLOGICAL ABERRATIONS UNDERLYING RENAL DYSFUNCTION IN BARDET-BIEDL SYNDROME

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Miriam Zacchia ◽  
Emanuela Marchese ◽  
Marianna Caterino ◽  
Margherita Ruoppolo ◽  
Giovambattista Capasso
Keyword(s):  
Lactic Acid ◽  
Kidney Disease ◽  
Renal Disease ◽  
Renal Dysfunction ◽  
Metabolic Pathways ◽  
Healthy Subjects ◽  
Hexadecenoic Acid ◽  
Kidney Dysfunction ◽  
Bardet Biedl Syndrome ◽  
Wide Range

Abstract Background and Aims Bardet Biedl Syndrome (BBS) is a rare genetic disorder characterized by a wide range of organ dysfunction, including kidney disease. The severity of renal dysfunction is highly variable in this setting, ranging from tubular defects to the end stage renal disease, with poor genotype-phenotype correlation. Proteomics and metabolomics are powerful tools able to contribute to the better understanding of molecular basis of disease conditions. Our previous studies demonstrated that the urinary proteomic pattern of BBS patients differed from that of healthy subjects, with a set of deregulated proteins including cell adhesion and extracellular matrix organization proteins (1). The present study aims to characterize urine metabolomic profile of BBS patients, in order to identify both 1) potential disease biomarkers and 2) aberrant metabolic pathways underlying renal disease Method To this end, in the pilot study urine samples have been collected from 14 adult BBS patients and have been compared with healthy volunteers, using an untargeted strategy. In the confirmation study, 24 BBS patients with wide range of kidney dysfunction have been enrolled, and additional control groups, besides healthy subjects, were included: 1) age-gender-matched chronic kidney disease patients by other causes and 2) obese individuals. Results Several metabolites were de-regulated in BBS patients compared with normal subjects (lactic acid, glycolic acid,3-Hydroxypropionic acid, pyruvic acid, 3-hydroxyisobutyric acid, 2-ethyl-3-hydroxy-propionic acid, succinic acid, fumaric acid, erythropentonic acid, 2-hydroxyglutaric acid, 4-hydroxyphenyllactic acid, 3,4-pyridinedicarboxylic acid, retinoic acid, 4-hydroxyphenylacetic acid, palmitic acid, 9-Hexadecenoic acid, oleic acid and 9-Octadecenoic acid). The clusterization performed by MetaboAnalyst tool, revealed a possible deregulation of different metabolic pathways, including glycolysis, TCA cycle, pyruvate metabolism, lipids biosynthesis and glutamate metabolism (p-value &lt;0.01) (figure 1); some of these pathways were described as de-regulated in other ciliopathies (2). In the confirmation study (on-going studies) some metabolites, including lactic acid and intermediates of Krebs cycle, correlated with kidney dysfunction only in the BBS group. Conclusion These findings suggest that urine metabolomic fingerprint of BBS patients is different from that of healthy subjects and indicate a possible deregulation of several metabolic pathways; some urinary molecules correlated with kidney dysfunction only in BBS patients, suggesting the specificity of these results.

scholarly journals Trace elements in patients with aortic valve sclerosis

2021 ◽  
Vol 15 ◽  
pp. 175394472098598
Author(s):  
Hataw Al-Taesh ◽  
Abuzer Çelekli ◽  
Murat Sucu ◽  
Seyithan Taysi
Keyword(s):  
Trace Elements ◽  
Aortic Valve ◽  
Inductively Coupled Plasma ◽  
Healthy Subjects ◽  
Serum Zinc ◽  
Serum Levels ◽  
Control Group ◽  
Aortic Valve Sclerosis ◽  
Inductively Coupled ◽  
Significant Difference

Background: Aortic valve sclerosis (AVSc) is defined as the thickening and calcification of aortic valve cusps, in the absence of obstruction of ventricular outflow. AVSc is linked with a clear imbalance in some trace elements. Aims: The objective of this study was to investigate the relationship between AVSc and serum levels of iron (Fe), zinc (Zn), selenium (Se), and copper (Cu). Additionally, this research aimed to explore the clinical significance of human serum zinc, selenium, copper, and iron concentrations as a potential new biomarker for AVSc patients and to clarify the pathophysiological role in individuals at risk of developing AVSc. Patients and methods: The study included 40 subjects with AVSc (25% male and 75% female) who were compared with a healthy control group with the same gender ratio. AVSc was based on comprehensive echocardiographic assessments. Blood samples were taken and Zn and Cu concentrations were determined through the use of atomic absorption spectroscopy. Se was measured using an inductively coupled plasma mass spectrometry device and Fe was measured using a Beckman Coulter instrument. Results: There was a significant difference in the prevalence of diabetes, blood pressure levels, and body mass index between the patients and the healthy subjects ( p < 0.05). The differences between the serum Fe, Se, and Cu levels of the AVSc patients and the healthy subjects ( p > 0.05) were recorded. The serum Zn of AVSc patients when compared was significantly lower compared with that of the control group ( p < 0.01). Conclusion: Patients with AVSc had an imbalance in some of the trace elements in their blood. The patient group’s valves had higher serum Cu levels and lower serum Se, Zn, and Fe concentrations compared with the healthy group’s valves. In the valve patients as compared, AVSc had a high prevalence of obesity, hypertension, and diabetes.

Sign in / Sign up

Export Citation Format

Share Document