PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “FOLIC ACID ANTAGONISTS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources
PubMed1997

Effect of folate deficiency and folate and B12 excess on memory functioning in young chicks.

The results of this series of experiments with chicks trained on a single trial, passive avoidance task, demonstrate that methotrexate-induced folate deficiency, and excess levels of folate and B12 lead to amnesia in these subjects. The amnesia appears only after 50 min following learning, leaving the earlier processing stages of memory formation unaffected. The application of methotrexate resulted in disruption of righting reflex in a dose dependent manner, however the ataxia did not appear to be the cause of the memory deficit. The deficit in memory induced by methotrexate-induced folate deficiency could be ameliorated with methionine. These studies suggest that cellular processes involving folate metabolism may play an important role in the memory formation of the young chick and that the observed disruption of memory may well occur due to its affect on protein synthesis mediated by alterations in methionine metabolism.

Animals↗
PubMedDate not supplied

Folic acid and human malformations: a summary and evaluation.

A large body of evidence gathered over the past 30 or more years has led to the firmly established belief that deficiency of the vitamin folic acid is a cause of congenital malformations of neural tube closure. Beginning with studies showing folic acid levels of mothers of children with such defects to be low, this belief has been solidified by epidemiologic studies revealing that this consequence is prevented by maternal supplements of the vitamin from early pregnancy. The present article reviews this evidence for the purpose of examining the claims of the efficacy of folic acid in this respect. This seems to be an advantageous moment to do so, because no clear impact of folic acid supplementation and fortification on the prevalence of neural tube defects has as yet been documented; and furthermore a pause seems to have been reached in such studies. It is felt that a historical, i.e. a chronologic approach will best describe the findings, and therefore they will be considered as they unfolded.

Abnormalities, Drug-Induced↗
PubMed1995

Effects of folate deficiency on embryonic development.

While there is strong evidence that folate deficiency including the use of anti-folate drugs in early pregnancy is teratogenic and may lead to a range of serious abnormalities of the developing fetus including intrauterine death, the mechanism(s) for these effects have not yet been delineated. In neural tube defects, there is increasing evidence that marginal folate status exacerbates the effect of an underlying genetic defect in the mother, the fetus, or both. An abnormal relationship between the ingestion of folate and the folate levels in red blood cells has been found in women who have given birth to infants with neural tube defects. Periconceptional folate supplementation has been shown to give effective protection against the development of neural tube defects. The mechanism of the prevention is as yet unknown. However, folic acid will not prevent all cases of neural tube defect. Moreover, neither determinations of periconceptional vitamin profiles (Mooij et al, 1993) nor determinations of methylmalonic acid and homocysteine levels will detect all women at risk. Anencephaly and spina bifida can be identified prenatally by detection of excessive levels of alpha-fetoprotein in amniotic fluid and maternal serum and by ultrasonographic scanning (Wilson and Rudd, 1993). Both genetic counselling and prenatal diagnosis should be offered to women who are recognized to be at high risk. Research into the underlying biology of neural tube defects is of major importance. The identification of underlying genetic defects would allow for genetic testing and better counselling of families at risk for the occurrence of a neural tube defect.

Animals↗
PubMed2000

Biological and environmental determinants of plasma homocysteine.

This article gives an overview over common physiological, lifestyle, and pathological conditions that may modulate the homocysteine status. The interplay of several environmental factors, including age, gender, nutrition, smoking, and coffee consumption and physical activity with commonly used drugs and prevalent diseases are described. In most cases, an abnormal homocysteine status is not caused by a single factor alone but often is the result of combined effects. We address these frequently found "clusters" of homocysteine-modulating factors. Finally, we give an overview of likely causes of hyperhomocysteinemia found in an authentic material. This material is based on 2462 routine measurements of plasma total homocysteine carried out at the Haukeland University Hospital. The data represent the total number of combined homocysteine and methylmalonic acid determinations, requested by general practitioners in Norway during February 1998.

Adult↗
PubMed1980

Nutritional anemia in alcoholism.

Megaloblastic anemia due to folate deficiency, the result of dietary lack and a weak antifolate action of ethanol, is the most common cause of a low hematocrit in hospitalized alcoholics. Alcoholism in the absence of significant folate depletion is more commonly responsible for macrocytosis, however. Neutrophil hypersegmentation, which typically persists or worsens during the first 1 to 2 weeks of folic acid therapy, is a useful sign of folate depletion. Serum folate concentrations, however, are often misleading. During conversion of the megaloblastic marrow following hospitalization, giant bands and metamyelocytes often persist after erythroid cells become normal. Reversible ineffective erythropoiesis due to sideroblastic anemia, often but not invariably in association with folate deficiency, is also common. In about half the patients, siderocytes in the peripheral blood smear, which may transiently increase in number during recovery, provide a useful diagnostic clue. Despite the presence of hypochromic microcytes, the erythrocyte mean corpuscular volume is typically normal or elevated. The chronic administration of alcohol along with a marginal diet has produced ringed sideroblasts in human volunteers. Inhibition of heme synthesis by ethanol and an unidentified nutritional factor probably play major roles in pathogenesis. Current evidence does not clearly implicate vitamin B6 depletion in sideroblastic anemia in alcoholics.

Alcoholism↗
PubMed1972

Toxicity of trimethoprim-sulphamethoxazole in patients with megaloblastic haemopoiesis.

Four consecutive patients with megaloblastic anaemia who also received therapy with trimethoprim-sulphamethoxazole all showed poor responses to specific haematinic therapy. This was attributed to trimethoprim, which suppressed reticulocyte responses in three cases and produced a pancytopenia in two and a falling haemoglobin with neutropenia in a third. A fourth patient, with pernicious anaemia, had a satisfactory reticulocyte response but experienced no clinical benefit until after withdrawal of trimethoprim.Trimethoprim seems not to be a safe form of therapy in patients with a megaloblastic process; many of the toxic reactions reported with this drug may be on the basis of an unrecognized megaloblastic form of haemopoiesis.

Adult↗
PubMed2001

No effect of phenobarbital pretreatment of rats on methotrexate pharmacokinetics in the isolated liver perfused in a single-pass way.

Pretreatment of the rat with phenobarbital (PB) is known to increase gene expression of the canalicular multispecific organic anion transporter (cMOAT) and hepatobiliary transport of its substrates (glutathione, sulfobromophthalein). To determine the effect of PB on the hepatobiliary transport of methotrexate (MTX, another substrate of cMOAT) and its metabolism to 7-hydroxymethotrexate (7-OHMTX) in the rat, we compared the steady-state pharmacokinetics of MTX in the isolated liver of either PB-pretreated (80 mg/day/kg bw for 4 days, i.p.) or nonpretreated rats. The livers were perfused in a single-pass way at a flow rate of 15 ml/min using a perfusate which consisted of Krebs-Henseleit buffer containing glucose, taurocholate, bovine albumin and erythrocytes. During the perfusion with 50 micromol/l MTX, the steady-state biliary clearance (1.26 +/- 0.24 ml/min) in 7 nonpretreated rats accounted for a major proportion of the hepatic clearance (1.30 +/- 0.33 ml/min), metabolism of MTX to 7- OHMTX was minor (partial metabolic clearance = 0.041 +/- 0.023 ml/min). MTX concentrations in bile surpassed those in the input perfusate by approximately 100-fold. Pretreatment of rats (n = 7) with PB did not change significantly the steady-state hepatic, biliary and partial metabolic clearances of 50 micromol/l MTX. An interesting result is a 38% increase in the hepatic vascular resistance of non-pretreated livers caused by MTX. The results suggest that in rats, pretreatment with PB has no effect on the hepatobiliary transport and hydroxylation of MTX.

Animals↗