Folic acid serum

Hydroxymethyl-6-methyluracil (1043) was prepared many years ago from 6-methyl-uracil and formaldehyde, or in other ways. Since 1956 it has received much attention in the USSR under the (transliterated) name pentoxyl or pentoxil. It is used in several anaemic and disease conditions. For example, a mixture of folic acid and pentoxyl quickly reduces the anaemia resulting from lead poisoning pentoxyl stimulates the supply of serum protein after massive blood loss it stimulates wound healing it stimulates the immune response in typhus infection and it potentiates the action of sulfonamides in pneumococcus infections (70MI21300). 

With investigations of phytochemicals and functional foods, the outcome measure is generally going to be a biomarker of disease, such as serum cholesterol level as a marker of heart disease risk, or indicators of bone turnover as markers of osteoporosis risk. Alternatively, markers of exposure may also indicate the benefit from a functional food by demonstrating bioavailability, such as increased serum levels of vitamins or carotenoids. Some components will be measurable in both ways. For instance, effects of a folic acid-fortified food could be measured via decrease in plasma homocysteine levels, or increase in red blood cell folate. 

Growing clinical data also points to the importance of IL-8 in atherogenesis. IL-8 has been found in atheromatous lesions from patients with atherosclerotic disease including carotid artery stenosis (103), CAD (118), abdominal aortic aneurysms (AAA) (103,104,114), and peripheral vascular disease (PVD) (104). Furthermore, studies using plaque explant samples have yielded more direct evidence for IL-8 involvement. Media from cultured AAA tissue induced IL-8-dependent human aortic endothelial cell (HAEC) chemotaxis (122). Homocysteine, implicated as a possible biomarker for CAD, is also capable of inducing IL-8 (123-125) by direct stimulation of endothelial cells (123,124) and monocytes (125). When patients with hyperhomocysteinemia were treated with low-dose folic acid, decreases in homocysteine levels correlated with decreases in IL-8 levels (126). Statins significantly decrease serum levels of IL-6, IL-8, and MCP-1, as well as expression of IL-6, IL-8, and MCP-1 mRNA by peripheral blood monocytes and HUVECs (127). Thus, IL-8 may be an underappreciated factor in the pathogenesis of atherosclerosis. 

Anaemia often becomes a characteristic feature of several chronic diseases, such as rheumatoid arthritis. In most instances this can be linked to lower than normal endogenous serum EPO levels (although in some cases a deficiency of iron or folic acid can also represent a contributory factor). Several small clinical trials have confirmed that administration of EPO increases haematocrit and serum haemoglobin levels in patients suffering from rheumatoid arthritis. A satisfactory response in some patients, however, required a high-dose therapy that could render this therapeutic approach unattractive from a cost benefit perspective. 

Patients sustain convulsions and neurological deterioration. The urine contains low levels of the metabolites of serotonin, norepinephrine and dopamine. The reductase also plays a role in the maintenance of tetrahydrofolate levels in brain, and some patients have had low folate levels in the serum and CNS. Treatment has been attempted with tryptophan and carbidopa to improve serotonin homeostasis and with folinic acid to replete diminished stores of reduced folic acid. This therapy is sometimes effective. Diagnosis involves assay of DHPR in skin fibroblasts or amniotic cells. Phenylalanine hydroxylase activity is normal. 

Serum uric acid and folic acid concentrations should be monitored yearly in patients prone to hyperuricemia or folic acid deficiency. Blood glucose must be monitored carefully in diabetic patients. 

J. M. Cooperman, Microbiological assay of folic acid activity in serum and whole blood. In Methods in Enzymology, XVIII, Part B (eds. D. G. McCormick and... 

Nearly all microbiologic assays for folic acid activity have used Streptococcus faecalis and Lactobacillus casei. Earlier it appeared that these organisms could not detect folic acid deficiency in man (C2, L8) for example, in one study using S. faecalis there was no detectable activity in the fasting serum of humans (C3). Administration of a loading dose of folic acid with subsequent assay by S. faecalis (G9) has served as a workable means of determining folic acid deficiency (C6), a technique having definite drawbacks (G10). 

A microbiologic assay for folic acid activity in human serum was devised (B12). It agrees with the clinical folic acid status (W4). 

Because of the multiplicity of folic acid factors reported in whole blood (Ul), the microbiologic assay for folic acid in whole blood and serum was regarded as valueless (C2, L8, W9) results based on S. faecalis methods (C2, C3) did not contradict this view. Streptococcus faecalis is inferior to L. casei in its utilization of the PGA polyglutamates... 

For correlation with the serum folic acid, FIGlu determinations were carried out using two methods (L9, S6). Both proved insensitive, notably where no urinary FIGlu was excreted despite clinical proof of PGA deficiency. 

A modification of the above serum folic assay method was recently described (W4). The investigators confirmed the validity of this technique as a practical means of differentiating patients with folic acid from vitamin B12 megaloblastic anemias. Another modification of this method was also described (C4). These investigators reduced the over-all sensitivity by high serum dilutions and thus made the assay, as they used it, valueless as a diagnostic tool. 

The nature of folic acid activity in serum is still obscure despite many clues. Perhaps the best lead has been furnished by the isolation of the previously mentioned N5-methyltetrahydrofolic acid. This is a newly isolated intermediate which is involved in the synthesis of methionine via the reaction in Scheme 1 (L2). This intermediate supports... 

H12. Hoogstraten, B., Baker, H., and Reizenstein, P., Correlation between serum folic acid activity and response to antifolate therapy. Blood 17, 787 (1961). 

Figure 22.6 How various factors increase the risk of atherosclerosis, thrombosis and myocardial infarction. The diagram provides suggestions as to how various factors increase the risk of development of the trio of cardiovascular problems. The factors include an excessive intake of total fat, which increases activity of clotting factors, especially factor VIII an excessive intake of saturated or trans fatty acids that change the structure of the plasma membrane of cells, such as endothelial cells, which increases the risk of platelet aggregation or susceptibility of the membrane to injury excessive intake of salt - which increases blood pressure, as does smoking and low physical activity a high intake of fat or cholesterol or a low intake of antioxidants, vitamin 6 2 and folic acid, which can lead either to direct chemical damage (e.g. oxidation) to the structure of LDL or an increase in the serum level of LDL, which also increases the risk of chemical damage to LDL. A low intake of folate and vitamin B12 also decreases metabolism of homocysteine, so that the plasma concentration increases, which can damage the endothelial membrane due to formation of thiolactone.

Folic acid appears in the plasma approximately 15 to 30 minutes after an oral dose peak levels are generally reached within 1 hour. After IV administration, the drug is rapidly cleared from the plasma. Folic acid is metabolized in the liver. Normal serum levels of total folate have been reported to be 5 to 15 ng/mL normal CSF levels are approximately 16 to 21 ng/mL. In general, folate serum levels less than 5 ng/mL indicate folate deficiency, and levels less than 2 ng/mL usually result in megaloblastic anemia. A majority of the metabolic products appeared in the urine after 6 hours excretion was generally complete within 24 hours. 

Reduced folate Reduction of serum or red cell folate has been reported over long-term administration of cholestyramine. Consider supplementation with folic acid. 

CBC serum folate concentrations <0.005 mcg/ml indicate folic acid deficiency and concentrations <0.002 mcg/ml usually result in megaloblastic anemia... 

A daily multivitamin supplement may prevent reduction in serum levels of vitamins D, E, K, and folic acid... 

Folic acid Macrocytic, normochromic with MCV > 100 fL and normal or elevated MCHC Low serum folic acid (< 4 ng/mL)... 

Once a diagnosis of megaloblastic anemia is made, it must be determined whether vitamin B12 or folic acid deficiency is the cause. (Other causes of megaloblastic anemia are very rare.) This can usually be accomplished by measuring serum levels of the vitamins. The Schilling test, which measures absorption and urinary excretion of radioactively labeled vitamin B12, can be used to further define the mechanism of vitamin Bi2 malabsorption when this is found to be the cause of the megaloblastic anemia. 

Parenteral administration of folic acid is rarely necessary, since oral folic acid is well absorbed even in patients with malabsorption syndromes. A dose of 1 mg folic acid orally daily is sufficient to reverse megaloblastic anemia, restore normal serum folate levels, and replenish body stores of folates in almost all patients. Therapy should be continued until the underlying cause of the deficiency is removed or corrected. Therapy may be required indefinitely for patients with malabsorption or dietary inadequacy. Folic acid supplementation to prevent folic acid deficiency should be considered in high-risk patients, including pregnant women, patients with alcohol dependence, hemolytic anemia, liver disease, or certain skin diseases, and patients on renal dialysis. 

Nausea and mucosal ulcers are the most common toxicities. Progressive dose-related hepatotoxicity in the form of enzyme elevation occurs frequently, but cirrhosis is rare (< 1%). Liver toxicity is not related to serum methotrexate concentrations, and liver biopsy follow-up is only recommended every 5 years. A rare hypersensitivity-like lung reaction with acute shortness of breath is documented, as are pseudolymphomatous reactions. The incidence of gastrointestinal and liver function test abnormalities can be reduced by the use of leucovorin 24 hours after each weekly dose or by the use of daily folic acid, although this may decrease the efficacy of the methotrexate. This drug is contraindicated in pregnancy. 

Deficiencies of folic acid and vitamin B1 are relatively common. Whenever macrocytic anemia is present, evaluation of these two vitamins is necessary 10 determine the cause of the condition, The standard method of measuring folic acid has been the microbiological assay (Bailey et al.. 19821. which can be used to measure folic acid in serum, blood, tissues, and foods. Improved high performance liquid chromatography (HPLC) methods have... 

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