			Home About us Contact

Folinic Acid (folinic + acid)

Distribution by Scientific Domains

Medical Sciences	83%
Life Sciences	16%

Distribution within Medical Sciences

General & Internal Medicine	26%
Oncology & Radiotherapy	13%

Selected Abstracts

Folinic acid,responsive seizures are identical to pyridoxine-dependent epilepsy,

ANNALS OF NEUROLOGY, Issue 5 2009
Renata C. Gallagher MD
Objective Folinic acid,responsive seizures and pyridoxine-dependent epilepsy are two treatable causes of neonatal epileptic encephalopathy. The former is diagnosed by characteristic peaks on cerebrospinal fluid (CSF) monoamine metabolite analysis; its genetic basis has remained elusive. The latter is due to ,-aminoadipic semialdehyde (,-AASA) dehydrogenase deficiency, associated with pathogenic mutations in the ALDH7A1 (antiquitin) gene. We report two patients whose CSF showed the marker of folinic acid,responsive seizures, but who responded clinically to pyridoxine. We performed genetic and biochemical testing of samples from these patients, and seven others, to determine the relation between these two disorders. Methods CSF samples were analyzed for the presence of ,-AASA and pipecolic acid. DNA sequencing of the ALDH7A1 gene was performed. Results Both patients reported here had increased CSF ,-AASA, CSF pipecolic acid, and known or likely pathogenic mutations in the ALDH7A1 gene, consistent with ,-AASA dehydrogenase deficiency. Analysis of CSF samples from seven other anonymous individuals diagnosed with folinic acid,responsive seizures showed similar results. Interpretation These results demonstrate that folinic acid,responsive seizures are due to ,-AASA dehydrogenase deficiency and mutations in the ALDH7A1 gene. Thus, folinic acid,responsive seizures are identical to the major form of pyridoxine-dependent epilepsy. We recommend consideration of treatment with both pyridoxine and folinic acid for patients with ,-AASA dehydrogenase deficiency, and consideration of a lysine restricted diet. The evaluation of patients with neonatal epileptic encephalopathy, as well as those with later-onset seizures, should include a measurement of ,-AASA in urine to identify this likely underdiagnosed and treatable disorder. Ann Neurol 2008 [source]

Folinic acid protects against suppression of growth by Methotrexate in mice

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2001
M. Perwaiz Iqbal
Abstract The objective of this study was to investigate whether folinic acid supplementation would protect young mice against suppression of growth by methotrexate (MTX). Four equal groups of Balb/c young male mice (5 animals in each group; mean±SD body weight 9.64±0.85 g, in their rapid growth phase) were subjected to the following drug treatment: One group was given MTX (3.5 mg/kg body weight) intraperitoneally on every 2nd day, another received folinic acid (7.0 mg/kg body weight) intraperitoneally every 2nd day. The third group was given both of these drugs (MTX on every 2nd day and folinic acid 8 h post-MTX injection). The fourth group was injected with physiological saline every other day to serve as a control group. Total body weight, food and water consumption by animals in each group were monitored every second day for a period of 3 weeks. After this period mice were sacrificed and liver, spleen and kidneys were excised, weighed and analyzed for MTX and dihydrofolate reductase activity. A small segment of the proximal part of small intestine and small pieces of liver and kidney were also removed to study morphological changes. Compared to the groups, which received folinic acid alone, folinic acid plus MTX or physiological saline, mean increase in body weight (6.8±0.8 g) of mice over a period of 3 weeks was minimal in the group receiving MTX alone (one-way ANOVA p=0.0001). The mean weights of liver and kidney in this group receiving MTX alone were also found to be significantly less than the mean weights of these organs in the 3 groups (p<0.001). The negative effect on growth of animals appears not only due to malabsorption but inhibition of pathway of de novo DNA synthesis may also be involved. This is supported by loss of villous pattern in small intestine of mice treated with MTX alone and increased accumulation of free MTX and decreased dihydrofolate reductase in the liver of the group receiving MTX alone as compared with the group receiving MTX plus folinic acid. The data indicate that the administration of folinic acid protects mice against suppression of growth by MTX. On the basis of these observations it can be deduced that patients suffering from juvenile rheumatoid arthritis or acute lymphoblastic leukaemia receiving MTX over a long period of time might be at a risk of experiencing short-term suppression of growth, however they could benefit from supplementation with folinic acid. Copyright © 2001 John Wiley & Sons, Ltd. [source]

Folic acid utilisation related to sulfa drug resistance in Saccharomyces cerevisiae

FEMS MICROBIOLOGY LETTERS, Issue 2 2001
Ann M. Bayly
Abstract Saccharomyces cerevisiae mutants deficient in folate synthesis have been constructed and employed to study the utilisation of exogenous folates in yeast. One mutant specifically lacked dihydropteroate synthase while the second lacked dihydrofolate synthase. Exogenous folinic acid restored optimal growth to both strains. Folic acid did not generally rescue growth but spontaneous isolates capable of utilising folic acid were selected. The folic acid synthesis pathway in the folate utilising isolates was restored via transformation with FOL1 or FOL3 expression plasmids and transformants were tested for resistance to sulfamethoxazole (SMX). The presence of elevated levels of folic acid led to greatly reduced SMX sensitivity regardless of whether strains were folate utilisers or not. [source]

Adjuvant chemotherapy in colon cancer: what is the evidence?

INTERNAL MEDICINE JOURNAL, Issue 3 2003
A. Haydon
Abstract Over the last 12 years, numerous randomized trials have addressed the role of adjuvant chemotherapy in resected colon cancer. Together, these studies give conclusive evidence of the benefit of adjuvant 5-fluorouracil combined with folinic acid in stage III (node positive) disease and this is now considered the standard of care. The chemotherapy appears to be equally effective whether it is given daily for 5 days per month or on a weekly schedule. The overall effect is a relative reduction in tumour recurrence of 25% or an absolute improvement in survival of 10%. However, doubt remains as to the role of adjuvant chemotherapy in stage II colon cancer. To date, most of the randomized trials have demonstrated a relative reduction in tumour recurrence but have not shown any significant impact on survival. It seems likely that this inability to demonstrate a survival benefit from adjuvant chemotherapy in stage II disease relates to the fact that the trials have been underpowered to do so. Nevertheless, the absolute survival advantage is only about 2% and clinicians need to weigh this against the costs and toxicities of the treatment when managing these patients. (Intern Med J 2003; 33: 119,124) [source]

Variability in administration of 5-fluorouracil and folinic acid in standard treatment regimens for advanced colorectal cancer

INTERNAL MEDICINE JOURNAL, Issue 12 2002
J. R. Zalcberg
First page of article [source]

Homocysteine, malondialdehyde and endothelial markers in dialysis patients during low-dose folinic acid therapy

JOURNAL OF INTERNAL MEDICINE, Issue 5 2002
T. Apeland
Abstract. Apeland T, Mansoor MA, Seljeflot I, Brønstad I, Gøransson L, Strandjord RE (Rogaland Central Hospital, Stavanger; and Ullevål University Hospital, Oslo; Norway). Homocysteine, malondialdehyde and endothelial markers in dialysis patients during low-dose folinic acid therapy. J Intern Med 2002; 252: 456,464. Objectives. Haemodialysis patients have elevated levels of the atherogenic amino acid homocysteine. We wanted to assess the effects of small doses of intravenous folinic acid (the active form of folic acid) on some biochemical risk factors of cardiovascular disease. Design. Longitudinal and open intervention study. Setting. Two dialysis units in the County of Rogaland. Subjects. All patients on maintenance haemodialysis were invited, and 32 of 35 patients gave their informed consent. Interventions. After each dialysis session, the patients were given 1.0 mg of folinic acid intravenously thrice a week for a period of 3 months. Prior to and during the study, all patients were on maintenance supplementation with small doses of vitamins B1, B2, B3, B5, B6 and B12. Main outcome measures. Changes in the levels of (i) plasma total homocysteine (p-tHcy) and folate, (ii) circulating endothelium related proteins , markers of endothelial activation and (iii) serum malondialdehyde (S-MDA) , a marker of oxidative stress and lipid peroxidation. Results. The p-tHcy levels were reduced by 37% (P < 0.0001), whilst the serum and erythrocyte folate levels increased by 95 and 104%, respectively (P < 0.0001 for both). The circulating levels of endothelium related cellular adhesion molecules and haemostatic factors remained high and unchanged, except the thrombomodulin (TM) levels increased (P = 0.0004). The high levels of S-MDA were reduced by 26% (P = 0.003). Conclusions. Low doses of folinic acid given intravenously to dialysis patients reduced their levels of p-tHcy and S-MDA and thus improved their cardiovascular risk profile. The concurrent increment in TM levels was unexpected and of unknown clinical significance. [source]

Folinic acid,responsive seizures are identical to pyridoxine-dependent epilepsy,

Methotrexate catabolism to 7-hydroxymethotrexate in rheumatoid arthritis alters drug efficacy and retention and is reduced by folic acid supplementation

ARTHRITIS & RHEUMATISM, Issue 8 2009
Joseph E. Baggott
Objective To assess the catabolism of methotrexate (MTX) to 7-hydroxy-MTX (7-OH-MTX) in patients with rheumatoid arthritis as well as the effect of folic acid and folinic acid on this catabolism. Methods Urinary excretion of MTX and its catabolite, 7-OH-MTX, was measured in 2 24-hour urine specimens collected after MTX therapy. Urine samples were collected from patients after the sixth and seventh weekly doses of MTX. MTX and 7-OH-MTX concentrations were determined by high-performance liquid chromatography mass spectrometry. Swelling and pain/tenderness indices were used to measure symptoms before and at 6 and 7 weeks of therapy. Patients received either folic acid or folinic acid supplements (1 mg/day) from week 6 to week 7. Results Folic acid inhibited aldehyde oxidase (AO), the enzyme that produces 7-OH-MTX, but folinic acid did not. Excretion of 7-OH-MTX (determined as a percentage of the dose of MTX or as mg 7-OH-MTX/gm creatinine) was not normally distributed (n = 39). Patients with marked improvement in swelling and pain/tenderness indices had a lower mean 7-OH-MTX excretion level (P < 0.05). Patients who received folic acid supplements had decreased 7-OH-MTX excretion (P = 0.03). Relatively high 7-OH-MTX excretion was correlated with relatively high MTX excretion and with relatively low MTX retention in vivo (P < 0.05) (n = 35). Conclusion Our findings of a non-normal distribution of 7-OH-MTX excretion suggest that there are at least 2 phenotypes for this catabolism. Decreased 7-OH-MTX formation suggests folic acid inhibition of AO and a better clinical response, while increased 7-OH-MTX formation may interfere with MTX polyglutamylation and binding to enzymes and, therefore, may increase MTX excretion and decrease MTX retention and efficacy in vivo. [source]

Review of case reports of inadvertent intrathecal administration of vincristine: Recommendations to reduce occurrence

ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 2 2007
Peter J GILBAR
Abstract Vincristine has been in clinical use for over 40 years with initial publication of the results from successful trials in 1962. Catastrophic neurotoxicity has been associated with the administration of vincristine directly into the cerebrospinal fluid (CSF). Since the first case in 1968 there have been numerous other instances, of which 23 have been reported in the literature. Of these cases 18 resulted in death. The most prominent damage on autopsy was generally in the spinal cord, brain stem and cerebellum, with severity tending to be greater in the neurons adjacent to the CSF. Fatalities appeared due to a progressive ascending myeloencephalopathy. Early recognition and immediate treatment with CSF drainage and intrathecal exchange appears to be the only intervention that has improved patient survival. The volume of injection, dose and time from the incident until the ventriculo-lumbar washout appear critical, as these factors might contribute to the extent of drug distribution in the CNS. Although several antidotes for vincristine have been suggested, including folinic acid and glutamic acid, supportive evidence for their effectiveness is scant. Several recommendations regarding prevention of this catastrophic event have been proposed. [source]

Persistent trophoblast disease following partial molar pregnancy

AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2006
Sabien WIESMA
Abstract Objective:, Human chorionic gonadotrophin (hCG) follow-up data were analysed retrospectively in all patients registered in the Hydatidiform Mole Registry at the Royal Women's Hospital, Melbourne from January 1992 to January 2001 to determine the risk of persistent trophoblast disease following partial molar pregnancy and to review the present follow-up protocol of patients suffering from partial hydatidiform molar pregnancy (PHM). Methods:, Demographic factors were determined for all 344 cases with a review diagnosis of PHM, included age, history of previous hydatidiform mole, gestation length, hCG levels and compliance with follow-up. Findings:, Six of the 344 patients diagnosed with PHM required treatment with single-agent methotrexate and folinic acid rescue. All six patients achieved and maintained a complete biochemical remission after chemotherapy. hCG regression assays were analysed for 235 patients: 225 patients had at least one normal hCG measurement during follow-up, of whom 152 (64.7%) patients obtained normal values within 2 months after evacuation. All patients obtained normal levels within 32 weeks after evacuation of the partial hydatidiform mole. Only 63 (25.6%) patients completed the recommended follow-up program. No patient who achieved normal hCG levels required chemotherapy because of a recurrent gestational trophoblastic tumour. Recommendations:, This study indicates that 1.7% of all partial mole pregnancy patients needed treatment for malignant sequelae. In contrast, no patient diagnosed with partial mole had a biochemical or clinical relapse after achieving normal levels of hCG, consistent with previous studies. Patients who have had a partial hydatidiform mole should be followed by hCG assays until normal levels are achieved and then follow-up can be safely discontinued. [source]

Folinic acid protects against suppression of growth by Methotrexate in mice

Cardiovascular abnormalities in Folr1 knockout mice and folate rescue,

BIRTH DEFECTS RESEARCH, Issue 4 2007
Huiping Zhu
Abstract BACKGROUND: Periconceptional folic acid supplementation is widely believed to aid in the prevention of neural tube defects (NTDs), orofacial clefts, and congenital heart defects. Folate-binding proteins or receptors serve to bind folic acid and 5-methyltetrahydrofolate, representing one of the two major mechanisms of cellular folate uptake. METHODS: We herein describe abnormal cardiovascular development in mouse fetuses lacking a functional folate-binding protein gene (Folr1). We also performed a dose-response study with folinic acid and determined the impact of maternal folate supplementation on Folr1 nullizygous cardiac development. RESULTS: Partially rescued preterm Folr1,/, (formerly referred to as Folbp1) fetuses were found to have outflow tract defects, aortic arch artery abnormalities, and isolated dextracardia. Maternal supplementation with folinic acid rescued the embryonic lethality and the observed cardiovascular phenotypes in a dose-dependant manner. Maternal genotype exhibited significant impact on the rescue efficiency, suggesting an important role of in utero folate status in embryonic development. Abnormal heart looping was observed during early development of Folr1,/, embryos partially rescued by maternal folinic acid supplementation. Migration pattern of cardiac neural crest cells, genetic signals in pharyngeal arches, and the secondary heart field were also found to be affected in the mutant embryos. CONCLUSIONS: Our observations suggest that the beneficial effect of folic acid for congenital heart defects might be mediated via its impact on neural crest cells and by gene regulation of signaling pathways involved in the development of the pharyngeal arches and the secondary heart field. Birth Defects Research (Part A) 2007. © 2007 Wiley-Liss, Inc. [source]

Neural and orofacial defects in Folbp1 knockout mice ,

BIRTH DEFECTS RESEARCH, Issue 4 2003
Louisa S. Tang
Abstract BACKGROUND Folic acid is essential for the development of the nervous system and other associated structures. Mice deficient in the folic acid-binding protein one (Folbp1) gene display multiple developmental abnormalities, including neural and craniofacial defects. To better understand potential interactions between Folbp1 gene and selected genes involved in neural and craniofacial morphogenesis, we evaluated the expression patterns of a panel of crucial differentiation markers (Pax-3, En-2, Hox-a1, Shh, Bmp-4, Wnt-1, and Pax-1). METHODS Folbp1 mice were supplemented with low dosages of folinic acid to rescue nullizygotes from dying in utero before gestational day 10. The gene marker analyses were carried out by in situ hybridization. RESULTS In nullizygote embryos with open cranial neural tube defects, the downregulation of Pax-3 and En-2 in the impaired midbrain, along with an observed upregulation of the ventralizing marker Shh in the expanded floor plate, suggested an important regulatory interaction among these three genes. Moreover, the nullizygotes also exhibit craniofacial abnormalities, such as cleft lip and palate. Pax-3 signals in the impaired medial nasal primordia were significantly increased, whereas Pax-1 showed no expression in the undeveloped lateral nasal processes. Although Shh was downregulated, Bmp-4 was strongly expressed in the medial and lateral nasal processes, highlighting the antagonistic activities of these molecules. CONCLUSIONS Impairment of Folbp1 gene function adversely impacts the expression of several critical signaling molecules. Mis-expression of these molecules, perhaps mediated by Shh, may potentially contribute to the observed failure of neural tube closure and the development of craniofacial defects in the mutant mice. Birth Defects Research (Part A) 67:209,218, 2003. © 2003 Wiley-Liss, Inc. [source]

Radioimmunotherapy of small-volume disease of metastatic colorectal cancer

CANCER, Issue S4 2002
Results of a phase II trial with the iodine-13, carcinoembryonic antigen antibody hMN-1, labeled humanized anti
Abstract BACKGROUND Whereas radioimmunotherapy (RIT) has shown disappointing results in bulky, solid tumors, preclinical results in small-volume disease and in an adjuvant setting are promising. In a previous Phase I study, the authors had encouraging results with the iodine-131 (131I),labeled humanized anti,carcinoembryonic antigen (anti-CEA) antibody (MAb) hMN-14 in small-volume disease of colorectal cancer. The aim of this study was to evaluate, in a subsequent Phase II trial, the therapeutic efficacy of this 131I-labeled humanized anti-CEA antibody in colorectal cancer patients with small-volume disease or in an adjuvant setting. METHODS Thirty colorectal cancer patients, with small-volume metastatic disease (n = 21; all lesions , 3.0 cm, and chemorefractory to 5-fluorouracil and folinic acid) or in an adjuvant setting (n = 9), 4,6 weeks after surgical resection of liver metastases with curative intention, were studied. The patients were given a single injection of 131I-hMN-14 immunoglobulin G at a 60 mCi/m2 dose level, which was shown to be the maximum tolerated dose in the previous Phase I study. Follow-up was obtained at 3-month intervals for as long as 36 months. RESULTS At a mean blood-based red marrow dose of 1.8 ± 0.8 Gy, myelotoxicity was the only toxicity observed, but only 1 of 28 assessable patients developed transient Grade 4 thrombocytopenia. Of the 21 patients with radiologically documented lesions, 19 were assessable. Three experienced partial remission and eight showed minor responses up to 15 months in duration (corresponding to an objective response rate of 16% and an overall response rate of 58%; the mean duration of response was 9 months). At the time this article was written, seven of nine patients in the adjuvant setting had remained free of disease for up to 36 months (one patient relapsed after 6 months and another after 30 months), whereas the relapse rate in a historical control group receiving chemotherapy was 67% over the same time period. Five patients with radiologically documented lesions, having experienced at least disease stabilization as a consequence of RIT, were retreated at the same 60-mCi/m2 dose level at 8,16 months after the first therapy. No evidence of increased toxicity was observed (no hematologic toxicity was higher than Grade 3). Two of four assessable retreated patients experienced partial remissions; one of these four again experienced disease stabilization as a consequence of the second radioantibody therapy injection. CONCLUSIONS These data suggest that RIT is a safe and effective form of therapy for small-volume colorectal cancer and has potential as treatment for colorectal cancer in an adjuvant setting. Toxicity is restricted to mild and transient leuko- and thrombocytopenia. Retreatment seems to be a feasible option. A prospective randomized comparison with standard chemotherapy is indicated. Cancer 2002;94:1373,81. © 2002 American Cancer Society. DOI 10.1002/cncr.10308 [source]

The impact of pre- or postoperative radiochemotherapy on complication following anterior resection with en bloc excision of female genitalia for T4 rectal cancer

COLORECTAL DISEASE, Issue 4 2009
B. Szynglarewicz
Abstract Objective, The aim of the study was to assess the mortality and morbidity following extended anterior resection with excision of internal female genitalia combined with pre- or postoperative chemoradiotherapy in women with extensive rectal cancer. Method, The study included a consecutive series of 21 women with T4 adenocarcinoma of the rectum infiltrating the reproductive organs treated with curative intent between 1997 and 2003. All patients had an extended anterior sphincter preserving resection of the rectum (total mesorectal excision) and hysterectomy with or without posterior vaginal wall excision. In all patients, surgery was combined with adjuvant radiochemotherapy. Ten patients received preoperative radiotherapy (50.4 Gy) concurrently with two courses of chemotherapy [fluorouracil with folinic acid (FA)] followed by surgery within 6,8 weeks and subsequently four courses of postoperative chemotherapy. Eleven received postoperative chemoradiotherapy (50.4 Gy plus fluorouracil with FA). Results, There was no postoperative mortality. Postoperative complications were observed in 57% patients (early in 14% and late in 52%). These included: anterior resection syndrome with anorectal dysfunction in 52% (requiring proximal diversion in 5%), urinary complications in 24% (complete incontinence requiring a permanent catheter in 5%). In addition, postoperative acute bleeding requiring relaparotomy, delayed wound healing caused by superficial infection, anastomotic leakage, prolonged bowel paralysis, benign rectovaginal fistula and anastomotic stricture occurred (5% each). The risk of postoperative morbidity (52%) was similar for patients with or without preoperative radiochemotherapy. Conclusion, Despite this aggressive therapeutic approach, most postoperative complications were transient or could be treated. Preoperative radiochemotherapy did not increase the risk of morbidity. [source]