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PubMedDate not supplied

[Dose-effect of the administration of ferrous fumarate in aged persons with iron deficiency].

BACKGROUND: Anemia is the most prevalent hematological problem in elderly persons, affecting 14% of the males and 6% of the females of the population over 60 years of age in Mexico City. OBJECTIVE: To determine the effect produced by the prolonged administration of ferrous fumarate in elderly persons with iron deficiency. METHOD: In a population of 178 subjects, aged between 65 to 100 years, iron deficiency was diagnosed in 51 (28.6%), who had serum iron concentrations below 80 micrograms/dL for men and 60 micrograms/dL for women, but only 21 patients (11.8%), accepted to participated in the study. The response to a 6 months oral administration of ferrous fumarate were studied with a daily oral dose of 5 mg/kg of elemental iron. The patients were classified in 3 groups according to the abnormal parameters of iron metabolism (group 1 = 10.9% anemia, group 2 = 28.0% and group 3 = 63.0% anemia). RESULTS: The efficacy of treatment was evaluated by quantification of the changes occurred in serum iron concentrations, hemoglobin, ferritin and transferrin saturation index, at 0, 30, 90 and 180 days of treatment. This study showed that the treatment of oral ferrous fumarate in elderly patients with iron deficiency, produces a quantifiable improvement in measures of iron parameters within 6 months. CONCLUSIONS: The results of this study suggest the usefulness of prolonged treatment with ferrous fumarate in elderly patients with iron deficiency, to avoid therapeutic failure as a consequence of non-compliance as is common in elderly patients.

Age Factors↗

PubMed1977

Double-blind, controlled study of clemastine fumarate, chlorpheniramine and placebo in the symptomatic treatment of seasonal allergic rhinitis in desensitized and nondesensitized patients.

In double-blind trials clemastine fumarate 2.68 mg. chlorpheniramine 4 mg and placebo were randomly assigned to two groups of patients with seasonal allergic rhinitis. Thirty-nine desensitized patients were given one of the three test drugs in a parallel design; 67 nondesensitized patients each received two of the three drugs in a crossover design. Assessment of drug activity in each study was by whole body plethysmography and intranasal color photography as well as by subjective methods. Objective measurements showed clemastine fumarate was significantly superior to placebo and often better than chlorpheniramine in decreasing true nasal resistance and relieving nasal congestion. High placebo responses characterized the subjective evaluations, although the active drugs were clearly better. Responses varied somewhat between desensitized and nondesensitized patients. The number of reports of sedative effect, high in all groups, seemed to be more closely related to these antihistamine conditioned patients than to activity of the drugs themselves, based on previous reports of low sedation with clemastine fumarate. The techniques described proved very useful in distinguishing relative activity of antihistamines. Clemastine fumarate, the new antihistamine studied, appears to offer certain advantages over the older drug, chlorpheniramine.

Airway Resistance↗

PubMed1987

Malic enzyme, malate dehydrogenase, fumarate reductase and succinate dehydrogenase in the larvae of Taenia crassiceps (Zeder, 1800).

Malate dehydrogenase, malic enzyme, succinate dehydrogenase, and fumarate reductase activities have been studied in the cytoplasm and mitochondria of Taenia crassiceps larvae. The results show that these larvae contain enzymes for anaerobic acquisition of energy with terminal fumarate reductase, but some facts, as the high ratio of succinate dehydrogenase activity to fumarate reductase activity and the low proportion of fumarate reductase in the whole NADH oxidase activity in mitochondria, suggest that aerobic processes are also involved in the energy acquisition in this parasite.

Aerobiosis↗

PubMedDate not supplied

[Fumarate reductase in the mitochondria of the trematode Calicophoron ijimai].

The presence of active fumarate reductase system in mitochondria of the trematode Calicophoron ijimai was shown. Fumarate reductase activities in different collections of C. ijimai vary considerably. Maximum activity accounts for 47.7 +/- 1.0 nM/min/mg protein whereas minimum--for 15.1 +/- 0.1. Some properties of the enzyme were studied. The effect of thiabendazole, bitionol, oxinid and preparations of G-1026 and G-937 on the fumarate reductase activity was investigated. G-1026, G-937 preparations and bitionol have the strongest inhibitory effect on the enzyme. Thiabendazole inhibited but little the fumarate reductase reaction in C. ijimai. The enzyme activity was not affected by oxinid.

Animals↗

PubMed2004

[Successful treatment of skin and lung sarcoidosis with fumaric acid ester].

A 61-year old female patient with cutaneous sarcoidosis was treated with fumaric acid esters (Fumaderm). After 12 months of therapy, lesions were markedly improved and treatment was discontinued. 18 months later, the cutaneous lesions recurred, angiotensin converting enzyme (ACE) serum levels were increased and a chest X-ray demonstrated pulmonary involvement. Therapy with fumaric acid esters was again started. The skin showed improvement after 2 months and completely cleared within 17 months, within 4 months ACE levels normalized, and within 10 months radiologic changes markedly resolved. This case demonstrates a possible role for fumaric acid esters not only in the treatment of cutaneous but also systemic sarcoidosis.

Dermatologic Agents↗

PubMed2006

Fumaric acid esters are effective in chronic experimental autoimmune encephalomyelitis and suppress macrophage infiltration.

Fumaric acid esters (FAE) have proven their therapeutic efficacy in psoriasis, a Th1 mediated skin disease. More recently, preliminary data have suggested an activity in multiple sclerosis (MS) as well. To investigate further possible mechanisms of action of these compounds in inflammatory diseases, we studied the FAE methyl hydrogen fumarate (MHF) and dimethyl fumarate (DMF) in chronic experimental autoimmune encephalomyelitis (EAE) induced by immunization of C57BL/6 mice with MOG peptide aa 35-55. Preventive treatment with these FAE was delivered twice a day by oral gavage. Both esters had a significant therapeutic effect on the disease course and histology showed a strongly reduced macrophage inflammation in the spinal cord. Multiparameter cytokine analysis from blood detected an increase of IL-10 in the treated animals. We conclude that the underlying biological activity of FAE in EAE is complex and, to elucidate the molecular mechanisms, further investigation is needed.

Animals↗

PubMed1993

Synthesis of 3-arsonoalanine and its action on aspartate aminotransferase and aspartate ammonia-lyase. Comparison with arsenical analogues of malate and fumarate.

DL-3-Arsonoalanine has been synthesized by the Strecker synthesis from the unstable compound arsonoacetaldehyde. It inactivates pig heart cytosolic aspartate aminotransferase and inhibits aspartate ammonia-lyase by competing with aspartate (Ki/Km 0.23). The fumarate analogue (E)-3-arsonoacrylic acid and the malate analogue (RS)-3-arsonolactate also inhibit fumarate hydratase, competing with fumarate (Ki/Km 1.8) and malate (Ki/Km 1.6) respectively. Attempted non-enzymic transamination of 3-arsonoalanine gave elimination of arsenite, in contrast with the transamination of 3-phosphonoalanine, which is either successful or leads to loss of phosphate.

Alanine↗

PubMed1996

Phosphorylation-independent bacterial chemoresponses correlate with changes in the cytoplasmic level of fumarate.

Bacterial chemotaxis is based on modulation of the probability to switch the direction of flagellar rotation. Responses to many stimuli are transduced by a two-component system via reversible phosphorylation of CheY, a small cytoplasmic protein that directly interacts with the switch complex at the flagellar motor. We found that the chemorepellents indole and benzoate induce motor switching in Escherichia coli cells with a disabled phosphorylation cascade. This phosphorylation-independent chemoresponse is explained by reversible inhibition of fumarase by indole or benzoate which leads to an increased level of cellular fumarate, a compound involved in motor switching for bacteria and archaea. Genetic deletion of fumarase increased the intracellular concentration of fumarate and enhanced the switching frequency of the flagellar motors irrespective of the presence or absence of the phosphorylation cascade. These correlations provide evidence for fumarate-dependent metabolic signal transduction in bacterial chemosensing.

Bacterial Proteins↗

PubMed1990

Signal transduction in Halobacterium depends on fumarate.

The isolation of a straight-swimming mutant of Halobacterium halobium is reported which has a defect in switching the rotational sense of its flagellar motor. Cells of this mutant strain could be complemented with an extract from wild-type cells by mild sonication and resealing of the cells in fresh medium. The switch factor responsible for restoration of wild-type behaviour was isolated from membrane vesicle preparations. Its chemical nature is proposed to be that of fumarate on the basis of chemical, chromatographic and mass spectrometric analysis. Since the switch factor (fumarate) was released from a membrane-bound state by heat and was accumulated into mutant cells that lack this compound, it is proposed that a membrane-bound protein exists which specifically binds the switch factor. Both the switch factor and fumarate cause stimulus-induced responses in cells at the level of one or few molecules.

Cell Movement↗

PubMed1977

Anaerobic growth of Escherichia coli on formate by reduction of nitrate, fumarate, and trimethylamine N-oxide.

Anaerobic growth of E. coli, strain K-10, depending on formate oxidation by nitrate, fumarate, and trimethylamine N-oxide was followed in a medium containing peptone. The presence of formate and peptone was indispensable for growth with fumarate and trimethylamine N-oxide reduction. While there was no growth in the absence of acceptor, growth was observed in the absence of formate by nitrate reduction though not as much as under aerobic conditions. Per mole consumed formate equimolar succinate or trimethylamine was formed, but 1.2 mole of nitrate was produced, probably depending partly on peptone oxidation. The molar growth yield on formate was found to be 6.5, 7.6, and 7.0 g cells/mole depending on the reduction of nitrate, fumarate, and trimethylamine N-oxide, respectively, suggesting the formation of one mole ATP coupled to the anaerobic electron transfers from formate.

Aerobiosis↗

PubMed1992

An Escherichia coli mutant containing only demethylmenaquinone, but no menaquinone: effects on fumarate, dimethylsulfoxide, trimethylamine N-oxide and nitrate respiration.

The mutant strain AN70 (ubiE) of Escherichia coli which is known to lack ubiquinone (Young IG et al. 1971), was analyzed for menaquinone (MK) and demethylmenaquinone (DMK) contents. In contrast to the wild-type, strain AN70 contained only DMK, but no MK. The mutant strain was able to grow with fumarate, trimethylamine N-oxide (TMAO) and dimethylsulfoxide (DMSO), but not with nitrate as electron acceptor. The membranes catalyzed anaerobic respiration with fumarate and TMAO at 69 and 74% of wild-type rates. DMSO respiration was reduced to 38% of wild-type activities and nitrate respiration was missing (less than or equal to 8% of wild-type), although the respective enzymes were present in wild-type rates. The results complement earlier findings which demonstrated a role for DMK only in TMAO respiration (Wissenbach et al. 1990). It is concluded, that DMK (in addition to MK) can serve as a redox mediator in fumarate, TMAO and to some extent in DMSO respiration, but not in nitrate respiration. In strain AN70 (ubiE) the lack of ubiquinone (Q) is due to a defect in a specific methylation step of Q biosynthesis. Synthesis of MK from DMK appears to depend on the same gene (ubiE).

Anaerobiosis↗

PubMed2005

Enhancement of 1,3-propanediol production by Klebsiella pneumoniae with fumarate addition.

Addition of 5 mM: fumarate to cultures of Klebsiella pneumoniae enhanced the rate of glycerol consumption and the production of 1,3-propanediol (PDO). Compared to the control, the activity of glycerol dehydrogenase increased by 35, 33 and 46%, the activity of glycerol dehydratase increased by 160, 210 and 115%, and the activity of 1,3-propanediol oxidoreductase increased by 25, 39 and 85% when, respectively, 5, 15 and 25 mM: fumarate were provided. At the same time, the ratio of NAD+ to NADH decreased by 20, 23 and 29%. Using a 5 l bioreactor with 5 mM: fumarate addition, the specific rate of glycerol consumption and the productivity of PDO was 30 mmol/l h and 17 mmol/l h, respectively, both increased by 35% over the control.

Cell Culture Techniques↗

PubMed2006

Fumaric aciduria: mild phenotype in a 8-year-old girl with novel mutations.

Fumaric aciduria is a rare, autosomal recessive disorder caused by deficient activity of fumarate hydratase (FH). Common clinical features are hypotonia, failure to thrive, severe psychomotor retardation and seizures. Facial dysmorphism and brain malformations are frequent. Recently, some FH gene mutations have been associated with inherited cutaneous and uterine leiomyomas and papillary renal cell cancer. Our patient had a relatively mild phenotype, a previously not reported genotype and familial tumour predisposition. The mother and grandmother had uterine myomas. The paternal grandfather and his two brothers died from lung and laryngeal cancers. The pregnancy was complicated by bleeding and intrauterine growth retardation. Delivery was after 35 weeks, with normal Apgar score. The girl was hypotonic since birth. At age 2 months the parents noticed short apnoeic crises. She could sit at age 1.5 years, and walk with assistance at 4 years. At age 8 years highly increased excretion of fumaric acid was found twice (217 and 445 mmol/mol creatinine). Shortly before that the girl started to have leg and arm spasms. Grand mal seizures occurred twice. Facial dysmorphism included depressed nasal bridge, anteverted ears, hypertelorism and microcephaly. Speech was limited to few disyllables. She was atactic with spastic paraparesis. Brain MRI showed slight ventriculomegaly, white-matter atrophy and hypoplasia of corpus callosum. Activity of FH in fibroblasts was 1.9 nmol/min/mg protein (controls 40-80). Analysis of the FH gene revealed the maternally derived c.1029_1031delAGT mutation, resulting in Val deletion and substitution of Gln by His, and paternally derived c.976C > T mutation, resulting in substitution of Pro by Ser.

Brain↗

PubMed1983

Structural properties of the proteoliposomes catalyzing electron transport from formate to fumarate.

The electron-transport chain catalyzing fumarate reduction by formate has recently been reconstituted from the formate dehydrogenase complex and the fumarate reductase complex from Vibrio succinogenes, in a liposomal preparation containing vitamin K-1 (Unden, G. and Kröger, A. (1982) Biochim. Biophys. Acta 682, 258-263). We have now investigated the structural properties of this preparation. The preparation was found to consist of a homogeneous population of unilamellar proteoliposomes with an average diameter of about 100 nm and an internal volume of 2-4 ml/g phospholipid. The buoyant density (1.07 g/ml) was consistent with the protein/phospholipid ratio (0.2 g/g) of the preparation. Leakage of glucose from the internal spaces of the proteoliposomes was negligibly slow. Proteoliposomes prepared with either of the enzyme complexes showed peripheral projections mainly on the outer surface, when examined by electron microscopy after negative staining. The size, orientation and surface density of the projections were consistent with those of the enzymes. Most of the substrate and dye-reactive sites (70-90%) of the enzymes in the proteoliposomes were accessible to external non-permeant substrates. The proteoliposomes catalyzing electron transport were formed by freeze-thawing a mixture of liposomes and protein-phospholipid complexes which did not perform electron transport from formate to fumarate. Nearly the entire amount of the enzymes supplied (0.2 g protein/g phospholipid) was incorporated into the liposomes by this procedure. The transformation of liposomes into proteoliposomes was accompanied by exchange of the internal solutes with the external medium.

Aldehyde Oxidoreductases↗

PubMed1983

Fumaric aciduria: a new organic aciduria, associated with mental retardation and speech impairment.

Two siblings are described who present with fumaric aciduria, a hitherto unreported organic aciduria. The results of our analytical investigations using gas chromatography/mass spectrometry, and the clinical presentation of the patients, are consistent with the notion that the fumaric aciduria is caused by an inherited defect which leads to a net secretion of fumaric acid by the renal tubules.

Adult↗

PubMed2005

Preparation of biodegradable networks by photo-crosslinking lactide, epsilon-caprolactone and trimethylene carbonate-based oligomers functionalized with fumaric acid monoethyl ester.

Biodegradable polymer networks were prepared from fumaric acid derivatives of oligomeric esters. Photo-crosslinkable macromers were prepared by reacting star-shaped hydroxyl-group terminated lactide, epsilon-caprolactone and trimethylene carbonate based oligomers and fumaric acid monoethyl ester in the presence of N,N-dicyclohexylcarbodiimide and 4-dimethylamino pyridine at room temperature. The functionalization method is facile and suited for many hydroxyl-terminated oligomers. The reactivity of the fumarate end groups is such that, upon crosslinking by UV radical polymerization, networks with high gel contents (up to 96%) can be obtained without the addition of reactive diluents. The physical properties of the networks can be tuned by adjusting the composition, architecture and molecular weight of the oligomeric precursors. Such networks, built up of non-toxic compounds and designed to release benign degradation products, may find wide application in tissue engineering and other areas of biomedical research.

4-Aminopyridine↗

PubMed2004

High-performance liquid chromatographic method for the bioequivalence evaluation of desloratadine fumarate tablets in dogs.

A simple HPLC method was developed for the determination of desloratadine in dog plasma and was used for evaluating the bioequivalence of desloratadine fumarate tablets and desloratadine tablets in dogs. Chromatographic separation was performed on a Hypersil CN column (150 mm x 5.0 mm, 5 microm) using a mixture of methanol, acetonitrile and phosphate buffer (pH 5.5; 0.01 mol/l) (35:35:30, v/v/v) as mobile phase delivered at a flow rate of 0.8 ml/min. The detection was set at 241 nm. The limit of quantitation was 5.0 ng/ml. The calibration range was from 5.0 to 800.0 ng/ml. Inter- and intra-day precision ranged from 1.8 to 3.8% and from 2.2 to 9.0%, respectively. The recovery of desloratadine from dog plasma ranged from 78.8 to 82.0%. The developed method was applied to the bioequivalence studies of desloratadine fumarate tablets (test preparation) and desloratadine tablets (reference preparation) in five dogs. Pharmacokinetic parameters t(max), C(max), AUC(0-t), AUC(0- infinity ), t(1/2) were determined from plasma concentration-time profiles of both preparations. The analysis of variance (ANOVA) did not show any significant difference between the two preparations and 90% confidence intervals fell within the acceptable range for bioequivalence. Based on these statistical inferences it was concluded that the two preparations exhibited comparable pharmacokinetic profiles and that desloratadine fumarate tablets was bioequivalent to desloratadine tablets.

Animals↗

PubMed2000

Voltammetry of a flavocytochrome c(3): the lowest potential heme modulates fumarate reduction rates.

Iron-induced flavocytochrome c(3), Ifc(3), from Shewanella frigidimarina NCIMB400, derivatized with a 2-pyridyl disulfide label, self-assembles on gold electrodes as a functional array whose fumarate reductase activity as viewed by direct electrochemistry is indistinguishable from that of Ifc(3) adsorbed on gold or graphite electrodes. The enhanced stability of the labeled protein's array permits analysis at a rotating electrode and limiting catalytic currents fit well to a Michaelis-Menten description of enzyme kinetics with K(M) = 56 +/- 20 microM, pH 7.5, comparable to that obtained in solution assays. At fumarate concentrations above 145 microM cyclic voltammetry shows the catalytic response to contain two features. The position and width of the lower potential component centered on -290 mV and corresponding to a one-electron wave implicates the oxidation state of the lowest potential heme of Ifc(3) as a defining feature in the mechanism of fumarate reduction at high turnover rates. We propose the operation of dual pathways for electron transfer to the active site of Ifc(3) with the lowest potential heme acting as an electron relay on one of these pathways.

Binding Sites↗