scholarly journals Interrelationship of Rheumatoid Arthritis, Folic Acid, and Aspirin

Blood ◽  
1971 ◽  
Vol 38 (4) ◽  
pp. 405-416 ◽  
Author(s):  
HARVEY J. ALTER ◽  
NATHAN J. ZVAIFLER ◽  
CHARLES E. RATH
Keyword(s):  
Rheumatoid Arthritis ◽  
Folic Acid ◽  
Plasma Clearance ◽  
Normal Subjects ◽  
Serum Levels ◽  
Serum Folate ◽  
Pteroylglutamic Acid ◽  
Apparent Equilibrium ◽  
Low Serum

Abstract Decreased serum folate (FA) levels were detected in 71% of 51 patients with rheumatoid arthritis (RA). Of 11 patients studied more intensively, only one fulfilled the usual hematologic criteria for FA deficiency. All, however, demonstrated an abnormally rapid plasma clearance of tritium-labeled pteroylglutamic acid (3HPGA). "Binding" of 3HPGA was evaluated by dialysis to apparent equilibrium and found to be significantly reduced in the sera of patients with RA. Common to all these patients was the ingestion of aspirin (ASA). Four RA patients not taking ASA had normal 3HPGA "binding". The 3HPGA "binding" of RA sera decreased as these patients were given increased ASA dosage and vice versa. The in vitro addition of ASA to normal sera reduced "binding" to the level detected in RA sera. Progressive increases in ASA resulted in progressive decreases in "binding". Aspirin given to three normal subjects reduced 3HPGA "binding" in all and serum FA in two. Precedents for ASA-induced structural change in binding proteins and for the relation between decreased binding and lowered serum levels are discussed. It is suggested that the low serum FA concentration and rapid plasma clearance of 3HPGA in RA might reflect ASA-induced alterations of FA binding, resulting in a redistribution rather than deficiency of this vitamin.

Oral Contraceptives and Folate Metabolism

1972 ◽  
Vol 42 (4) ◽  
pp. 405-414 ◽  
Author(s):  
M. E. M. Stephens ◽  
I. Craft ◽  
T. J. Peters ◽  
A. V. Hoffbrand
Keyword(s):  
Folic Acid ◽  
Oral Contraceptives ◽  
Significant Variation ◽  
Serum Folate ◽  
Fasting Serum ◽  
Significant Difference ◽  
Pteroylglutamic Acid ◽  
Normal Menstrual Cycle ◽  
Erythrocyte Folate

1. There are conflicting reports regarding the effect of oral contraceptives on serum and erythrocyte folate concentrations and on folate absorption. A detailed study of this problem was therefore undertaken. 2. It was first ascertained that there was no significant variation in serum folate concentrations at different stages in the normal menstrual cycle. 3. No significant difference was found in fasting serum folate concentrations between control subjects and those taking oral contraceptives. 4. Synthetic sex hormones did not inhibit jejunal pteroylpolyglutamate hydrolase in vitro. 5. Tests of absorption of pteroylglutamic acid (folic acid) and pteroylpolyglutamates in controls and women taking oral contraceptives showed no difference between the two groups, provided the subjects were presaturated with pteroylglutamic acid. Without presaturation, the rise in serum folate after oral pteroylpolyglutamates was significantly decreased in the women taking oral contraceptives, suggesting that the latter may alter folate clearance from the blood.

scholarly journals Malabsorption of Folic Acid due to Diphenylhydantoin

Blood ◽  
1967 ◽  
Vol 30 (3) ◽  
pp. 341-351 ◽  
Author(s):  
MIRIAM B. DAHLKE ◽  
ELIZABETH MERTENS-ROESLER
Keyword(s):  
Folic Acid ◽  
Megaloblastic Anemia ◽  
Acid Tolerance ◽  
Test Dose ◽  
Serum Levels ◽  
Folate Deficiency ◽  
Normal Serum ◽  
Serum Folate ◽  
Hematologic Response

Abstract A high incidence of subnormal serum folate levels in pediatric subjects receiving diphenylhydantoin is reported. The effect is observed shortly after the onset of therapy and is not related to dosage of drug. An adult epileptic, who presented with a megaloblastic anemia secondary to a diphenylhydantoin-induced folate deficiency, demonstrated normal serum and erythrocyte folate levels only after folic acid was administered orally in amounts of 600 µg. per day. The folate deficiency was due to malabsorption of folic acid induced by diphenylhydantoin. Folic acid tolerance tests performed at 0, 4, 12, 16 and 20 hours after diphenylhydantoin showed a progressive rise in serum levels as diphenylhydantoin was withheld for longer periods prior to the test dose of folic acid. Further evidence of improved absorption was an associated rise in urinary folates. In addition, the patient demonstrated a convincing hematologic response to ingested conjugase, in the form of chick pancreas. The hematologic response was observed, despite prior demonstration of conjugase activity in the patient’s intestinal secretions. Attempts to show inhibition of chick pancreas conjugase activity by diphenylhydantoin in vitro were unsuccessful. Several explanations for these conflicting observations are offered.

scholarly journals Vitamin D as a Principal Factor in Mediating Rheumatoid Arthritis-Derived Immune Response

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Muhammad M. Aslam ◽  
Peter John ◽  
Attya Bhatti ◽  
Sidrah Jahangir ◽  
M. I. Kamboh
Keyword(s):  
Rheumatoid Arthritis ◽  
Vitamin D ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Genetic Factors ◽  
Autoimmune Disorder ◽  
Serum Levels ◽  
Principal Factor ◽  
Phosphate Homeostasis ◽  
Low Serum

Rheumatoid arthritis (RA) is a systemic multifactorial autoimmune disorder. The interactions between diverse environmental and genetic factors lead to the onset of this complex autoimmune disorder. Serum levels of vitamin D (VD) are involved in the regulation of various immune responses. Vitamin D is a key signaling molecule in the human body that maintains calcium as well as phosphate homeostasis. It also regulates the functions of the immune system and, thus, can play a substantial role in the etiology of various autoimmune disorders, including RA. Low serum VD levels have been found to be associated with a higher risk of RA, although this finding has not been replicated consistently. The molecular mechanisms by which VD influences autoimmunity need to be further explored to understand how variation in plasma VD levels could affect the pathogenesis of RA. This mini-review focuses on the influence of VD and its serum levels on RA susceptibility, RA-associated complexities, treatment, and transcriptome products of key proinflammatory cytokines, along with other cytokines that are key regulators of inflammation in rheumatoid joints.

scholarly journals Clinical and laboratory observations on serum folate-binding protein

Blood ◽  
1975 ◽  
Vol 46 (4) ◽  
pp. 599-609 ◽  
Author(s):  
ER Eichner ◽  
CJ Paine ◽  
VL Dickson ◽  
MD Jr Hargrove
Keyword(s):  
Binding Protein ◽  
Elevated Serum ◽  
Normal Subjects ◽  
Serum Levels ◽  
Serum Folate ◽  
Folate Level ◽  
Folate Binding Protein ◽  
Serum Folate Level ◽  
Relationship Of ◽  
The Relationship

Abstract We studied the effect of serum folate-binding protein (FBP) on folate radioassays and the relationship of the serum level of unsaturated FBP to the serum folate level in various clinical states. Our modification of a heat-extracted radioassay was compared to a whole serum radioassay. Our results confirmed the existence of elevated serum levels of unsaturated FBP in some normal subjects, in some women taking oral contraceptives, and in most patients with uremia. Elevated levels of unsaturated FBP will produce falsely low results in folate radioassay unless the FBP has been destroyed by heat, as was done in the modified radioassay here presented. In normal and uremic subjects, serum folate and unsaturated FBP levels tended to correlate, whereas in patients taking large doses of folic acid the level of unsaturated FBP fell as the level of serum folate rose.

Folate: In Vitro and in Vivo Effects on VLDL and LDL Oxidation

2007 ◽  
Vol 77 (1) ◽  
pp. 66-72 ◽  
Author(s):  
McEneny ◽  
Couston ◽  
McKibben ◽  
Young ◽  
Woodside
Keyword(s):  
Folic Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Folic Acid Supplementation ◽  
Serum Folate ◽  
Ldl Oxidation ◽  
Low Density ◽  
Acid Supplementation

Raised total homocysteine (tHcy) levels may be involved in the etiology of cardiovascular disease and can lead to damage of vascular endothelial cells and arterial wall matrix. Folic acid supplementation can help negate these detrimental effects by reducing tHcy. Recent evidence has suggested an additional anti-atherogenic property of folate in protecting lipoproteins against oxidation. This study utilized both an in vitro and in vivo approach. In vitro: Very-low-density lipoprotein (VLDL) and low density lipoprotein (LDL) were isolated by rapid ultracentrifugation and then oxidized in the presence of increasing concentrations (0→ μmol/L) of either folic acid or 5-methyltetrahydrofolate (5-MTHF). In vivo: Twelve female subjects were supplemented with folic acid (1 mg/day), and the pre- and post-VLDL and LDL isolates subjected to oxidation. In vitro: 5-MTHF, but not folic acid, significantly increased the resistance of VLDL and LDL to oxidation. In vivo: Following folic acid supplementation, tHcy decreased, serum folate increased, and both VLDL and LDL displayed a significant increase in their resistance to oxidation. These results indicated that in vitro, only the active form of folate, 5-MTHF, had antioxidant properties. In vivo results demonstrated that folic acid supplementation reduced tHcy and protected both VLDL and LDL against oxidation. These findings provide further support for the use of folic acid supplements to aid in the prevention of atherosclerosis.

scholarly journals Vitamin B12 and Folic Acid Metabolism in Hookworm-Infected Patients

Blood ◽  
1959 ◽  
Vol 14 (12) ◽  
pp. 1269-1279 ◽  
Author(s):  
MIGUEL LAYRISSE ◽  
NORMA BLUMENFELD ◽  
IRIS DUGARTE ◽  
MARCEL ROCHE
Keyword(s):  
Folic Acid ◽  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Acid Metabolism ◽  
Marked Decrease ◽  
Normal Subjects ◽  
Deficiency Anemia ◽  
Hookworm Infection ◽  
Folic Acid Metabolism ◽  
Pteroylglutamic Acid

Abstract Studies on the metabolism of B12 and folic acid were performed in patients with heavy hookworm infection and severe iron deficiency anemia, and in patients with light infection, noninfected patients and normal subjects. Patients with heavy hookworm infection showed a marked decrease of the serum B12 as compared with normal subjects. Eight of 21 cases studied showed values of serum B12 below 100 µµg./ml. Twelve of 13 patients with severe hookworm infection showed impairment of the pteroylglutamic acid intestinal absorption; however, none of them exhibited megaloblastic proliferation in the bone marrow. They all recovered with iron therapy alone. The patients with light infection and the noninfected patients with iron deficiency anemia did not demonstrate significant differences from the normal subjects studied.

Radiochemical method for measuring plasma clearance and urinary excretion of pteroylglutamic acid.

1979 ◽  
Vol 25 (10) ◽  
pp. 1783-1786
Author(s):  
M da Costa ◽  
S P Rothenberg ◽  
Z Rosenberg
Keyword(s):  
Urinary Excretion ◽  
Plasma Clearance ◽  
Normal Subjects ◽  
Serum Folate ◽  
Metabolic Clearance ◽  
Folate Binding Protein ◽  
Radiochemical Method ◽  
Baseline Serum ◽  
Distribution Phase

Abstract A radiochemical procedure is described for specific determination of pteroylglutamate in serum and urine. This method depends on denaturation of methyltetrahydrofolate with peroxide and measurement of the residual folate by a ligand-binding radioassay. The binding determinant for the radioassay is a folate-binding protein, partially purified from chronic myelogenous lekemia cells, that has low affinity for the reduced folates and thus will preferentially measure residual pteroylglutamate rather than any nondenatured residual methyltetrahydrofolate. We used this assay to measure the clearance from plasma and the urinary excretion of pteroylglutamate and a small fraction of serum folate that is stable to this oxidation procedure. The plasma clearance after intravenous injection is characterized by an initial rapid distribution phase followed by a second, slower metabolic phase; after about 2 h all of the administered pteroylglutamate has been cleared from the blood. The peak concentration of total folate in serum 1--2 min after administration of pteroylglutamate exceeded the sum of the endogenous stable and baseline serum folate, indicating that a reduced labile folate was released from the liver and perhaps from other tissues. This reduced folate had a slower metabolic clearance rate and was excreted to some extent in urine. Only 2.3 and 7.9% of the pteroylglutamate administered to two normal subjects was excreted as stable folate.

Homocysteine in the Plasma of Renal Transplant Recipients: Effects of Cofactors for Methionine Metabolism

1981 ◽  
Vol 61 (6) ◽  
pp. 743-749 ◽  
Author(s):  
D. E. L. Wilcken ◽  
Vatsala J. Gupta ◽  
A. K. Betts
Keyword(s):  
Folic Acid ◽  
Amino Acid ◽  
Renal Transplant ◽  
Serum Creatinine ◽  
Vitamin B12 ◽  
Normal Subjects ◽  
Serum Folate ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Erythrocyte Folate

1. Homocysteine which is formed during the metabolism of methionine is readily oxidized and is measured by the amino acid analyser as cysteine—homocysteine mixed disulphide and homocystine. We measured plasma amino acid concentrations after an overnight fast in 27 stable long-term renal transplant recipients and 25 age-and sex-matched normal subjects with particular emphasis on sulphur-containing amino acids. 2. Plasma cysteine—homocysteine mixed disulphide was increased in the patients (mean 6.0 ± sd 3.2 μmol/l; normal 3.1 ± 0.9 μmol/l, P < 0.001) and homocystine was detectable in low concentration (< 1.0 μmol/l) in 24; the elevation in cysteine—homocysteine was related to serum creatinine (r = 0.60, P < 0.002). Cystine was also increased (91.6 ± 29.3 μmol/l; normal subjects 64.0 ± 16.7 μmol/l, P < 0.001), but methionine concentrations were normal. 3. When pyridoxine, folic acid and vitamin B12, cofactors for homocysteine metabolism, were administered sequentially to 11 arbitrarily selected transplant recipients cysteine—homocysteine decreased from 7.3 ± 2.1 to 4.3 ± 0.8 μmol/l (P < 0.001) and homocystine became undetectable. the response coincided with the giving of folic acid and occurred without alteration in serum creatinine and with normal serum folate and vitamin B12 concentrations. 4. in eight patients in whom pretreatment erythrocyte folate was measured, folic acid therapy reduced cysteine—homocysteine from 9.0 ± 3.1 to 5.4 ± 1.6 μmol/l over a 4 week period (P < 0.001), the largest response being in the one patient with subnormal erythrocyte folate; values were in the low-normal or normal range in the other seven. 5. We conclude that plasma homocysteine is increased in renal transplant recipients when serum creatinine is only moderately elevated and that the homocysteine concentrations are decreased by treatment with folic acid, suggesting that both reduced homocysteine excretion and relative shortages of folic acid are responsible.

scholarly journals Synthesis of cobalamin coenzymes by human lymphocytes in vitro and the effect of folates and metabolic inhibitors

Blood ◽  
1976 ◽  
Vol 48 (4) ◽  
pp. 609-619
Author(s):  
EV Quadros ◽  
DM Matthews ◽  
AV Hoffbrand ◽  
JC Linnell
Keyword(s):  
Folic Acid ◽  
Pernicious Anemia ◽  
Human Lymphocytes ◽  
Normal Subjects ◽  
Metabolic Inhibitors ◽  
Normal Cells ◽  
Folate Cycle

The uptake of 57Co-cyanocobalamin (CN-Cbl) and its conversion to 5- deoxyadenosylcobalamin (Ado-Cbl), methylcobalamin (Me-Cbl), and hydroxocobalamin (OH-Cbl) has been studied in phytohemagglutinin (PHA)- transformed lymphocytes from normal subjects and patients with patients with pernicious anemia. Uptake and conversion were much greater by PHA- stimulated lymphocytes than by mature non-transformed lymphocytes. In normal cells, uptake of 57Co-CN-Cbl and synthesis of the cobalamin coenzymes were approximately linear between 3 and 48 hr incubation. Ado- Cbl was the major cobalamin formed, and after 72 hr the cells contained about twice as much Ado-Cbl as Me-Cbl. Uptake by lymphocytes from patients with untreated pernicious anemia (PA) was greater than that by normal lymphocytes, but the proportions of Ado-Cbl and Me-Cbl synthesized by each were similar. Folic acid and methyltetrahydrofolate enhanced synthesis of Me-Cbl both in normal and in PA cells, while methotrexate and 5-fluorouracil depressed it. This depression was overcome by 5-formyltetrahydrofolate, suggesting that an uninterrupted folate cycle may play an important role in Me-Cbl synthesis.

The influence of folate serum levels on depressive mood and mental processing in patients with epilepsy treated with enzyme-inducing anti-epileptic drugs

2003 ◽  
Vol 15 (2) ◽  
pp. 63-67 ◽  
Author(s):  
J. Rösche ◽  
C. Uhlmann ◽  
R. Weber ◽  
W. Fröscher
Keyword(s):  
Depression Scale ◽  
Serum Levels ◽  
Folate Deficiency ◽  
Significant Negative Correlation ◽  
Depressive Mood ◽  
Serum Folate ◽  
Bedside Test ◽  
Patients With Epilepsy ◽  
The Impact ◽  
Low Serum

Background:Folate deficiency is common in patients with epilepsy and also occurs in patients with depression or cognitive deficits.Objective:This study investigates whether low serum folate levels may contribute to depressive mood and difficulties in mental processing in patients with epilepsy treated with anti-epileptic drugs inducing the cytochrome P450.Methods:We analysed the serum folate levels, the score in the Self Rating Depression Scale (SDS) and the results of a bedside test in mental processing in 54 patients with epilepsy.Results:There was a significant negative correlation between the serum folate levels and the score in SDS and significant positive correlations between the score in SDS and the time needed to process an interference task or a letter-reading task.Conclusions:Low serum folate levels may contribute to depressive mood and therefore to difficulties in mental processing. Further studies utilizing total plasma homocysteine as a sensitive measure of functional folate deficiency and more elaborate tests of mental processing are required to elucidate the impact of folate metabolism on depressive mood and cognitive function in patients with epilepsy.

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