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At least 595 records · Page 33Linked to original sources
PubMed2002

Treatment of disseminated granuloma annulare with fumaric acid esters.

BACKGROUND: Granuloma annulare is a granulomatous disease of unknown etiology. Various therapies have been tried in disseminated granuloma annulare (DGA), including corticosteroids, several variants of psoralen plus ultraviolet-A radiation, ultraviolet- A1 radiation, systemic retinoids, and dapsone, with variable success. We report a patient with recalcitrant DGA who was treated with fumaric acid esters (FAE). CASE PRESENTATION: A 40-year old Caucasian woman presented with a 25-year history of recalcitrant DGA. On both legs and the abdomen there were erythematous annular plaques. She was treated with FAE in tablet form using two formulations differing in strength (low strength tablets: 30 mg dimethylfumarate, 67 mg monoethylfumarate Ca salt, 5 mg monoethylfumarate Mg salt, 3 mg monoethylfumarate Zn salt; high strength tablets: 120 mg dimethylfumarate, 87 mg monoethylfumarate Ca salt, 5 mg monoethylfumarate Mg salt, 3 mg monoethylfumarate Zn salt). After three-month therapy, an almost complete clearance of skin lesions was achieved. With the exception of temporary lymphopenia, no adverse effects were observed. The patient remained in remission during a six-month follow up period. CONCLUSIONS: Our observation has demonstrated that FAE is a potentially beneficial therapeutic option for patients with recalcitrant DGA. However controlled trials are necessary to fully explore the efficacy, optimal dosage, and safety of FAE in the management of DGA.

Adult↗
PubMed2001

Asymptomatic QTc prolongation associated with quetiapine fumarate overdose in a patient being treated with risperidone.

We report a patient who ingested a 2000-mg overdose of quetiapine fumarate (Seroquel). Her maintenance medications also included risperidone, venlafaxine, topiramate, and clonazepam. On presentation, she was drowsy, but had no other significant CNS signs and no cardiac symptoms or abnormal physical signs. Approximately 2 h after the quetiapine ingestion, an electrocardiogram (ECG) showed normal sinus rhythm at 95 beats/min with a corrected QT (QTc) interval of 537 ms (upper limit of normal = 440 ms). Plasma quetiapine concentration at that time was 1800 ng/ml. Continuous ECG monitoring for the subsequent 18 h did not reveal any episode of ventricular tachycardia. A 12-lead ECG 18 h post-overdose was normal with a QTc interval of 401 ms and the corresponding plasma quetiapine concentration was 160 ng/ml. She made an uneventful medical recovery from the toxic ingestion. This case suggests that when patients overdose on quetiapine while taking therapeutic doses of risperidone, such overdoses, even if not massive, can cause considerable QTc interval prolongation. We recommend that quetiapine overdose patients undergo continuous ECG monitoring for 12-18 h post-ingestion.

Adult↗
PubMed2006

Adult leydig cell tumors of the testis caused by germline fumarate hydratase mutations.

CONTEXT: Leydig cell tumors (LCTs) are the most common non-germ-cell neoplasms of the testis. LCTs are often hormonally active and can result in precocious virilization or in adult feminization. We identified an LCT in an affected individual from a kindred with hereditary leiomyomatosis and renal cell cancer (HLRCC) and a germline fumarate hydratase (FH) mutation (N64T). OBJECTIVE: Our objective was to investigate the role of FH mutations in predisposition to LCTs. DESIGN: We tested for pathogenic effects of the N64T mutation and screened an additional 29 unselected adult LCTs for FH alterations. We also tested these LCTs for mutations in two genes, the LH/choriogonadotropin receptor (LHCGR) and the guanine nucleotide-binding protein alpha (GNAS) that had been implicated in LCT tumorigenesis. RESULTS: No mutations were found in GNAS, and one tumor had a LHCGR somatic substitution. In addition to the HLRCC case with the N64T germline FH mutation, we identified one other LCT with a previously unreported FH mutation (M411I). Both LCTs from these patients showed loss of the wild-type FH allele. Immunohistochemical and in situ hybridization analyses demonstrated activation of the hypoxia/angiogenesis pathway not only in the tumors belonging to the FH mutation carriers but also in several other mutation-negative LCTs. CONCLUSIONS: Our study shows that some LCTs are caused by FH mutations and represents one of the first reports of germline mutations in any type of adult testicular tumor.

Base Sequence↗
PubMed2006

Effects of solvents on skin permeation of formoterol fumarate.

Effects of various chemicals applied as penetration enhancers on the permeation of formoterol fumarate (FF) across excised rat skin were investigated. Remarkable enhancement was noted with terpenes, fatty acid esters, and higher alcohols, whereas no significant influence was observed in the case of lower alcohols, pyrrolidones, and amines. At high concentration, a cineole/N-methyl-2-pyrrolidone (NMP) mixed solvent system slightly enhanced the skin permeation of FF compared with cineole alone, and a l-menthol/NMP mixed solvent system caused significant further increase. Maximum skin permeation of FF was seen when the ratio of l-menthol/NMP was 60/40 w/w. From the present results, l-menthol/NMP and isopropyl myristate (IPM)/NMP mixed solvent systems can be considered effective for augmenting skin permeation of FF, with potential applications in transdermal delivery of the drug.

Administration, Cutaneous↗
PubMed2006

Effects of ethylcellulose and 2-octyldodecanol additives on skin permeation and irritation with ethylene-vinyl acetate copolymer matrix patches containing formoterol fumarate.

Skin permeation of formoterol fumarate (FF) and irritation with ethylene-vinyl acetate (EVA) copolymer matrix patches was investigated using rat and human skin in vitro and different species of experimental animal, respectively. Skin permeation of FF increased remarkably without addition of ethylcellulose (EC) and was remarkably enhanced by incorporation of 2-octyldodecanol (OD) instead of hydrogenated rosin glycerol ester (Ester Gum H). Effects on skin permeation of FF with EVA matrix patches were similar in rat and human skin, but rat skin was 1000 times more permeable than human skin after 24 h. The primary irritation indices for matrix patches without EC and with EC (OD-0), EC and 0.5 mg OD per square centimeter (OD-0.5), and EC and 1.0 mg OD per square centimeter (OD-1) were 1.46, 1.13,1.29 and 1.38. The results suggested that the irritation induced by these patches was rather mild, but significantly greater than the 0.21 observed with the control. No significant effects were noted for either EC or OD alone. Skin irritation intensity with EVA matrix patches was observed to be in the order of rabbits, guinea pigs, rats and miniature swine.

Administration, Cutaneous↗
PubMed2006

Formulation and evaluation of ethylene-vinyl acetate copolymer matrix patches containing formoterol fumarate.

The skin permeability and stability of formoterol fumarate (FF) in matrix patches containing l-menthol as an enhancer and N-methyl-2-pyrrolidone (NMP) as the solvent were investigated. Using a total of 28 matrix patches having a similar composition, containing ethylene-vinyl acetate (EVA) as the forming polymer and hydrogenated rosin glycerol ester (Ester Gum H) as the adhesive, the skin permeation of FF was found to increase with increasing l-menthol and NMP contents. FF in the matrix patches containing NMP in the range of 4.8-7.2% was stable, but stability decreased at higher values. With a standard matrix patch containing FF, the Cmax and AUC(0-24) values were found to be 1.93 ng/ml after 4 h percutaneous application to rats and 25.6 ng x h/ml. The bioavailability after percutaneous exposure was equivalent to 15.2% of the AUC(0-24) after intravenous administration. Percutaneous application proved efficacious with regard to control of simulated asthma at dose levels lower than those with which side effects occurred. Thus an optimized matrix patch containing FF was prepared with potential advantages for control of asthma.

Administration, Cutaneous↗
PubMed1989

Inhibitory effect of fumaric acid on 3'-methyl-4-(dimethylamino)azobenzene-induced hepatocarcinogenesis in rats.

Fumaric acid (FA) suppressed the carcinogenesis in the liver of rats fed 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB), and a study was performed to examine the effect of FA on deoxyribonucleic acid (DNA) synthesis and subcellular structures of hepatocytes under the anticarcinogenic regimens. Male Donryu strain rats were given 3'-Me-DAB by being fed a diet containing 0.06% 3'-Me-DAB for 50 d. They were then given a diet containing 1% FA and drinking water containing 0.025% FA for 53 to 69 weeks. Hepatocytes were isolated from the liver by the collagenase perfusion method and placed in culture, and their activity for DNA synthesis was measured in terms of the incorporation of [3H]dThd into DNA. An enhanced DNA synthesis of hepatocytes was noted in the rats given FA, indicating that FA enhanced the proliferation of hepatocytes to counteract the carcinogenic effect of 3'-Me-DAB. An electron microscopic examination indicated that the distribution of subcellular organella was almost normal in the FA-treated hepatocytes.

Animals↗
PubMed1990

Inhibitory effect of fumaric acid on hepatocarcinogenesis by thioacetamide in mice.

The inhibitory effect of fumaric acid (FA) on hepatocarcinogenesis was examined in mice fed thioacetamide (TAA). A group of male ICR mice was fed TAA at a level of 0.035% in the diet for 40 weeks and then fed a basal diet for 48 weeks. Hepatic tumors developed in 11 of the 24 animals of this group and they were diagnosed as hepatocellular carcinomas. However, cirrhotic lesions and the enlargement of hepatocyte nucleoli were not as marked in mice as in previous findings in rats fed TAA. The effect of FA on the carcinogenesis was examined in a group of mice fed this compound at a level of 1% in a basal diet after ingestion of TAA. The inhibitory effect of FA on TAA carcinogenesis was so marked that no hepatic carcinomas were found in any of the 15 animals fed FA in combination with TAA.

Animals↗
PubMed1989

[Enhanced percutaneous absorption of formoterol fumarate via pulsed iontophoresis. II. Effect of polarity, pulse frequency and duty].

To clarify the effect of polarity, pulse frequency and duty on the iontophoretic transport of formoterol fumarate (FF), in vitro and in vivo studies were performed with guinea pigs. In the in vitro studies, the flux at steady state was enhanced by the factor 7.61 with anodal iontophoresis in comparison with control, whereas, with cathodal iontophoresis it was restrained by the factor 0.79. When pulse frequency was varied from 0 to 40 kHz, the flux at steady state was enhanced with an increase in pulse frequency. In the in vivo studies with varying the duty of pulse potential from 10 to 100%, the maximum plasma concentration of FF was obtained at a 30% duty. In contrast, the plasma concentration of FF achieved at 100% duty was not high. With stripped skin, no significant difference in the plasma concentration of FF was shown between iontophoresis and control. Consequently, it is suggested that iontophoresis contributes to FF penetration across stratum corneum.

Animals↗
PubMed2006

Acute respiratory failure with a single dose of quetiapine fumarate.

OBJECTIVE: To report a case of acute respiratory failure after a single dose of quetiapine fumarate in an elderly patient with a history of chronic obstructive pulmonary disease (COPD). CASE SUMMARY: A 92-year-old woman with a history of COPD was admitted to the hospital with pneumonia. Her symptoms improved with antibiotics. Because of acute agitation and delirium, quetiapine 50 mg twice daily was started. After receiving the first dose, the woman developed acute respiratory failure and severe central nervous system depression. She required mechanical ventilation and supportive care in the intensive care unit (ICU). She had a full recovery within 24 hours. DISCUSSION: Quetiapine is an atypical antipsychotic that has been used successfully for the treatment of schizophrenia and bipolar disorder for many years. Recently, it has also been used to treat delirium and agitation. It has proven to be very safe, even in the elderly. In previously reported cases, serious adverse effects were seen in patients who ingested very high doses of quetiapine. Those patients required intubation and supportive care in the ICU. To our knowledge, as of January 19, 2006, this is the first case report of acute respiratory failure of such severity with one dose of quetiapine. Using the Naranjo probability scale, we conclude that the acute respiratory failure observed in this patient was probably related to quetiapine. CONCLUSIONS: This case suggests that quetiapine can have significant adverse effects even with a single 50 mg dose. Elderly patients, especially those with significant underlying pulmonary pathology, should be monitored closely when started on this medication.

Aged, 80 and over↗
PubMed2001

Characterization of bioconversion of fumarate to succinate by alginate immobilized Enterococcus faecalis RKY1.

In this study, the immobilization characteristics of Enterococcus faecalis RKY1 for succinate production were examined. At first, three natural polymers--agar, kappa-carrageenan, and sodium alginate--were tried as immobilizing matrices. Among these, sodium alginate was selected as the best gel for immobilization of E. faecalis RKY1. Efficient conditions for immobilization were established to be with a 2% (w/v) sodium alginate solution and 2-mm-diameter bead. The bioconversion characteristics of the immobilized cells at various pH values and temperatures were examined and compared with those of free cells. The optimum pH and temperature of the immobilized cells were the same as for free cells, 7.0 and 38 degrees C respectively, but the conversion ratio was higher by immobilization for all the other pH and temperature conditions tested. When the seed volume of the immobilized cells was adjusted to 10% (v/v), 30 g/L of fumarate was completely converted to succinate (0.973 g/g conversion ratio) after 12 h. In addition, the immobilized cells maintained a conversion ratio of >0.95 g/g during 4 wk of storage at 4 degrees C in a 2% (w/v) CaCl2 solution. In repetitive bioconversion experiments, the activity of the immobilized cells decreased linearly according to the number of times of reuse.

Alginates↗
PubMed2004

Emtricitabine/tenofovir disoproxil fumarate.

The nucleoside analogue reverse transcriptase inhibitor (RTI) emtricitabine and the nucleotide analogue RTI tenofovir disoproxil fumarate (tenofovir DF) have each shown antiviral activity against a number of HIV clinical isolates and cell lines. HIV variants with reduced susceptibility to emtricitabine and tenofovir have been selected for in vitro and have also been isolated from patients receiving the agents. Low rates of these variants have been observed in patients experiencing virological failure in large studies of emtricitabine- or tenofovir DF-containing therapy. Co-formulated oral emtricitabine/tenofovir DF was bioequivalent to the two agents as separate formulations in a pharmacokinetic trial in healthy volunteers. There are no published data on the clinical antiviral efficacy of co-formulated oral emtricitabine/tenofovir DF. However, each agent is effective in combination regimens with other drugs. Ongoing studies in antiretroviral-naive patients are evaluating the efficacy of the individual formulations given together in combination with efavirenz or lopinavir/ritonavir. In the latter trial, HIV RNA levels were reduced and CD4+ cell counts were increased at 24 and 48 weeks. Emtricitabine and tenofovir DF are generally well tolerated. Diarrhoea, nausea and vomiting were the most common adverse events reported with coadministered emtricitabine and tenofovir DF as separate formulations as part of combination therapy.

Anti-HIV Agents↗
PubMed2003

Response of early-weaned pigs to an enterotoxigenic Escherichia coli (K88) challenge when fed diets containing spray-dried porcine plasma or pea protein isolate plus egg yolk antibody, zinc oxide, fumaric acid, or antibiotic.

The effect of feeding diets containing either spray-dried porcine plasma (SDPP) or pea protein-isolate (PPI) supplemented with either egg yolk antibodies (EYA) from hens immunized with enterotoxigenic Escherichia coli (ETEC) (K88 and F18) antigens, ZnO, fumaric acid (FA), or carbadox (AB) on pig performance, incidence of scours, and gut morphology was studied in a 14-d experiment. Ninety 10-d-old weaned pigs were assigned to six dietary treatments in a completely randomized design to give five pens per treatment with three pigs per pen. The diets were SDPP without EYA (SDPP - EYA), PPI without EYA (PPI - EYA), PPI with EYA (PPI + EYA), PPI with ZnO (PPI + ZnO), PPI with FA (PPI + FA), or PPI with AB (PPI + AB). Diets were formulated to similar nutrient levels, with AB, EYA, FA, and ZnO at 0.25, 0.5, 2.0, and 0.4% of the diet, respectively. Pigs were weighed and bled on d 0, 7, and 14 to determine plasma urea N (PUN). Pigs were orally challenged with a 6-mL dose of 10(10) cfu/mL ETEC (K88) on d 7. On d 14, three pigs per treatment were killed to obtain sections of the small intestine for histological measurements. Weekly feed intake, BW changes, and gain:feed were determined. Incidence of scours and scour scores were monitored and fecal swabs were taken before and after ETEC challenge for PCR test to detect ETEC (K88). Feeding SDPP or supplementing PPI-based diets with EYA, ZnO, FA, or AB did not affect (P > 0.05) ADG, ADFI (as-fed basis), or gain:feed throughout the study. However, pigs fed PPI - EYA tended to have lower (P = 0.08) ADFI during wk 2 (137.9 g/d) and lower (P < 0.10) ADG from d 0 to 14 (100.1 g/d) than those fed the SDPP - EYA (156.6 g/d), PPI + EYA (151.2 g/d), PPI + ZnO (158.9 g/ d), PPI + FA (155.4 g/d), and PPI + AB (152.6 g/d) diets. Although scours was evident in all pigs 8 h after the ETEC challenge, it lasted only 3 to 5 d in pigs fed SDPP or PPI supplemented with EYA, ZnO, FA, or AB. Pigs fed PPI - EYA continued to have severe diarrhea, resulting in 40% mortality vs. 13% or less in the other groups. The PCR results showed that 81% of PPI-fed pigs continued to shed ETEC K88 7 d after ETEC challenge. Pigs fed PPI-EYA had shorter villi (P < 0.05), reduced villi:crypt ratio (P < 0.003), and higher intestinal pH (P < 0.001) and PUN (P < 0.001) than those fed SDPP or PPI supplemented with EYA, ZnO, FA, and AB. In conclusion, SDPP, EYA, ZnO, FA, and AB may have provided passive control to ETEC (K88) infection and potentially enabled young pigs to efficiently utilize a PPI-based diet.

Animal Feed↗
PubMed1988

Fumaric and citric acids as feed additives in starter pig diets: effect on performance and nutrient balance.

The effect of dietary citric acid (CA) and fumaric acid (FA) on pig weight gain (ADG) and gain/feed (G/F) was studied in two trials using 192 crossbred, 4-wk-old weaning pigs. Three dietary levels (0, 1.5 or 3.0%) of either FA (Trial 1) or CA (Trial 2) with or without an antibiotic supplement (110 mg chlortetracycline, 110 mg sulfamethazine and 55 mg penicillin/kg diet) formed six treatment combinations in each trial. These six diets were fed to two replicate pens of eight pigs each for a 4-wk period. In Trial 1, ADG was improved (P less than .01) during wk 1, and G/F was improved during wk 1 (P less than .01) as well as during wk 1 to 2 (P less than .05) for pigs consuming FA-supplemented diets. In Trial 2, CA had no beneficial influence on ADG during the 4-wk trial. However, feed intake during wk 1 was depressed (P less than .05) by adding CA, as was G/F during wk 1 to 2 (P less than .05). Based on these results, FA was selected to be used in a nutrient balance study. Twelve 4-wk-old weanling pigs were fed one of three diets: control (C), C + 1.5% FA, or C + antibiotic supplement (A). Diet digestible energy (DE), ME and N-corrected ME (MEN) were not different among treatments. Nitrogen balance, percentage N retained and apparent N digestibility were not affected by dietary treatment. Calcium balance and percentage of Ca retained were unaffected by diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1997

Fumaric acid, anti-thrombin substance from Rhizopus javanicus.

An anti-thrombin substance (M2) was isolated from a culture broth of Rhizopus javanicus. Accumulation of M2 reached a maximum peak after 14 to 15 days of incubation and then decreased. The yield of M2 was 500 mg from 1 L of culture broth. M2 inhibited thrombin activity, and its 50% inhibition concentration in a reaction mixture containing 50 microL of 12.5 NIH unit/mL thrombin and 200 microL of 0.33% bovine fibrinogen was 63 microM. M2 had a specific activity for thrombin, but it was less responsive to plasmin, tissue-type plasminogen activator, urokinase, plasma kallikrein and glandular kallikrein. The structure of M2 was identified as fumaric acid by elementary analysis, FAB/MS, 1H-NMR, 13C-NMR and IR spectra.

Animals↗
PubMed2000

Pharmacokinetics, tolerability, and clinical effectiveness of quetiapine fumarate: an open-label trial in adolescents with psychotic disorders.

BACKGROUND: This is the first investigation of the pharmacokinetics, tolerability, and efficacy of quetiapine fumarate in adolescents with chronic or intermittent psychotic disorders. METHOD: Ten patients with DSM-IV chronic or intermittent psychotic disorders (ages 12.3 through 15.9 years) participated in an open-label, rising-dose trial and received oral doses of quetiapine twice daily (b.i.d.), starting at 25 mg b.i.d. and reaching 400 mg b.i.d. by day 20. The trial ended on day 23. Key assessments were pharmacokinetic analysis of plasma quetiapine concentrations and neurologic, safety, and efficacy evaluations. RESULTS: No statistically significant differences were observed between 100-mg b.i.d. and 400-mg b.i.d. quetiapine regimens for total body clearance, dose-normalized area under the plasma concentration-time curve, or dose-normalized premorning- or postmorning-dose trough plasma values obtained under steady-state conditions after multiple-dose regimens. No unexpected side effects occurred with quetiapine therapy, and no statistically significant changes from baseline were observed for the UKU Side Effect Rating Scale items that were rated. No serious adverse events or clinically important changes in hematology or clinical chemistry variables were reported. The most common adverse events were postural tachycardia and insomnia. Extrapyramidal side effects improved, as evidenced by significant (p < .05) decreases from baseline to endpoint in the mean Simpson-Angus Scale total scores and Barnes Akathisia Scale scores. Quetiapine improved positive and negative symptoms, as shown by significant (p < .05) decreases from baseline to endpoint in the mean Brief Psychiatric Rating Scale total score, the Clinical Global Impressions-Severity of Illness scale, and the Modified Scale for the Assessment of Negative Symptoms summary score. CONCLUSION: Quetiapine pharmacokinetics were dose proportional in adolescents and were similar to those previously reported for adults. Quetiapine was well tolerated and effective in the small number of adolescents studied.

Adolescent↗
PubMed1999

Augmentation of osteoinduction with a biodegradable poly(propylene glycol-co-fumaric acid) bone graft extender. A histologic and histomorphometric study in rats.

We investigated the feasibility of enhancing the regeneration of skeletal tissues by augmenting bone grafts with a composite biodegradable bone graft extender material based on the polymer poly(propylene fumarate), PPF. The material was mixed with autograft and allograft and placed directly into a cylindrical metaphyseal defect made in the rat tibia. These formulations were compared to defects without any graft material, autografts, allografts and PPF alone. Nine animals were included in each group. Animals were sacrificed at 1 and 4 weeks postoperatively. Implantation sites were then evaluated using histologic and histomorphometric methods. Results of this study showed that defects did not heal in sham operated animals. In the experimental groups, there was early new woven bone formation in the autograft group with near complete healing of the defect at four weeks. When PPF was used alone, gradual ingrowth of new bone was seen. Mixing of the PPF bone graft extender with either allograft or autograft material resulted in enhancement of new bone formation with both allo- and autograft. However, significantly more new bone formation than in the autograft group was only seen when the PPF bone graft extender was mixed with fresh autograft. Histomorphometry corroborated these findings. Results of this study suggest that a PPF-based material may be used to increase the volume of smaller amounts of bone grafts supporting the concept of "bone graft extenders" by application of engineered biodegradable porous scaffolds.

Absorbable Implants↗