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Effect of furazolidone and nitrofurazone on egg production, on plasma luteinising hormone and on prolactin concentrations in turkeys.

1. Furazolidone or nitrofurazone were given orally to laying turkeys at doses of 7.5, 15 or 30 mg/kg for 7 d. Plasma concentrations of luteinising hormone (LH), prolactin (PRL) and egg production were measured before, during and after treatment. 2. Both drugs produced dose-dependent decreases in LH concentration which were statistically significant at doses of 15 and 30 mg/kg. Plasma PRL concentration was significantly increased in birds receiving 15 or 30 mg/kg of nitrofurazone, and tended to increase in the other treated groups, but this was not statistically significant. 3. Egg production was lowered in a dose-dependent manner by both drugs. However, nitrofurazone appeared to be more potent in reducing egg production than furazolidone. 4. Birds given 15 mg/kg of either drug were injected intramuscularly with luteinising hormone releasing hormone (LHRH) at a dose of 5 micrograms/kg and blood was collected immediately before and 30 min after LHRH administration. 5. Nitrofurazone significantly reduced the rise in LH induced by LHRH. Seven days after withdrawing the drug, the LHRH-induced LH release was not significantly different when compared to that in the control group or that seen on day 7 of treatment.

Administration, Oral↗

Effect of furazolidone on sister-chromatid exchanges, cell proliferation kinetics, and mitotic index in vivo and in vitro.

Furazolidone is an antimicrobial compound used in human and veterinary medicine. The aim of this investigation was to determine its genotoxic capacity in vitro and in vivo. We used the human lymphocyte culture system to detect the effect of 2.0, 4.0, 6.0, 8.0, or 10.0 micrograms/ml, and the mouse bone marrow assay to determine the effect of 8.6, 30.0, or 75.0 mg/kg furazolidone. In both systems we determined the frequency of sister-chromatid exchanges (SCE), the cell proliferation kinetics (CPK), and the mitotic index (MI). The in vitro results showed a significant SCE increase starting from the second dose tested and a CPK and MI decrease starting from the third dose. The in vivo results showed a SCE increase with the two high doses tested, but no significant modification was found in the CPK and MI with the three doses tested in the experiment.

Animals↗

Furazolidone residues in pigs: criteria to distinguish between treatment and contamination.

The use of furazolidone in food-producing animals has been banned in the EU. The ban can most effectively be enforced by monitoring for bound residues containing the 3-amino-2-oxazolidinone (AOZ) moiety. Unlike the parent drug, AOZ residues are stable and can be detected for prolonged periods after cessation of treatment. However, AOZ can be passed from pig-to-pig following brief exposure of unmedicated animals to housing that previously contained medicated pigs. We describe criteria by which a distinction may be drawn between pigs treated illegally with the drug and pigs that contain detectable AOZ residues as a result of exposure to contaminated housing. These criteria are that illegally treated pigs will have a concentration ratio of AOZ in bile:kidney of less than 0.3; while unmedicated pigs will have a concentration ratio of AOZ in bile:kidney of greater than 3.0. Using this criteria, 12 pigs, either treated with the drug or exposed to contaminated housing were analysed in a blind study. The pigs were classified as 'Treated' or 'Contaminated' on the basis of the criteria described above. All 12 pigs were assigned to the correct group. This shows that it is possible to differentiate between furazolidone abuse and contamination.

Animals↗

Detection of 3-amino-2-oxazolidinone (AOZ), a tissue-bound metabolite of the nitrofuran furazolidone, in prawn tissue by enzyme immunoassay.

Furazolidone, a nitrofuran antibiotic, is banned from use in food animal production within the European Union. Increasingly, compliance with this ban is monitored by use of analytical methods to detect a stable tissue-bound metabolite, 3-amino-2-oxazolidinone (AOZ). Widespread use of furazolidone in poultry and prawns imported into Europe highlighted the urgent need for development of nitrofuran immunoassay screening tests. The first enzyme-linked immunoabsorbant assay for detection of AOZ residues in prawns (shrimps) is now described. Prawn samples were derivatized with o-nitrobenzaldehyde, extracted into ethyl acetate, washed with hexane and applied to a competitive enzyme immunoassay based on a rabbit polyclonal antiserum. Assay limit of detection (LOD) (mean + 3 s) calculated from the analysis of 20 known negative cold and warm water prawn samples was 0.1 microg kg(-1). Intra- and interassay relative standard deviations were determined as 18.8 and 38.2%, respectively, using a negative prawn fortified at 0.7 microg kg(-1). The detection capability (CCbeta), defined as the concentration of AOZ at which 20 different fortified samples yielded results above the LOD, was achieved at fortification between 0.4 and 0.7 microg kg(-1). Incurred prawn samples (n = 8) confirmed by liquid chromatography coupled with tandem mass spectrometry detection to contain AOZ concentrations between 0.4 and 12.7 microg kg(-1) were all screened positive by this enzyme-linked immunoabsorbant assay. Further data are presented and discussed with regard to calculating assay LOD based on accepting a 5% false-positive rate with representative negative prawn samples. Such an acceptance improves the sensitivity of an ELISA and in this case permitted an LOD of 0.05 microg kg(-1) and a CCbeta of below 0.4 microg kg(-1).

Animals↗

Depletion of protein-bound furazolidone metabolites containing the 3-amino-2-oxazolidinone side-chain from liver, kidney and muscle tissues from pigs.

Ten 3-month-old pigs were treated with feed containing 300 mg furazolidone per kg for a period of 7 days, followed by withdrawal periods of 0, 1, 2, 3 or 4 weeks (two per group). The treatment resulted in the formation of protein-bound metabolites containing an intact 3-amino-2-oxazolidinone (AOZ) side-chain that could be chemically released and then detected in liver, kidney and rump muscle tissues even 4 weeks after dosing. In tissues from animals killed at the end of the medication period, 993, 600 and 124 ng of AOZ were released from 1 g of liver, kidney and muscle respectively. In the tissues of the animals killed after a further 4 weeks the corresponding levels were 41, 7 and 10 ng/g respectively. It may be concluded that long withdrawal periods prior to slaughter for human consumption are required for pigs treated with furazolidone, because of the long residence time of protein-bound AOZ and the possibility that it might be released from its protein-bound form in the stomach and subsequently be transformed into a hydrazine.

Animals↗

Furazolidone in multi-resistant childhood typhoid fever.

Multi-drug-resistant Salmonella typhi infection is an emerging public health problem in most developing countries. Fifty children up to the age of 12 years whose blood cultures were positive for S. typhi, mostly drug-resistant ones, were treated with oral furazolidone in a prospective year-long study. Defervescence occurred in 96% of the treated group with a mean duration for response of 5.9 days. No clinically significant side-effects were noted. Furazolidone was found to be efficacious, safe and cost-effective in the treatment of most cases of childhood typhoid fever caused by multi-resistant S. typhi.

Child↗

[Histomorphometric and histological investigations of the morphometric effects of furazolidone on spermatogenesis in mature rats].

The antispermatongenic effects of furazolidone on the testes of mature Wistar rats were investigated using histological and morphometric methods. The sections showed a varying degree of depopulation of the germinal epithelium, a shrinking and a deformation of the Tubuli contorti, and an enlargement of the intertubular lymphatic sinuses. The strain led to a standstill in the spermatogenesis at the primary-spermatocyte stage. After administering furazolidone, the following results could be seen: a weight loss of up to 42.1% and a decrease in testes volume by up to 30.2%; a decrease in the volume of the nuclei of the Leydig-cells by up to 51.6%; a reduction in the diameter, perimeter and area covered by Tubuli seminiferi contorti of up to 33.5%, 30.8%, and 53.4%, respectively; an increase in the number of Tubuli seminiferi contorti per mm2 by up to 44.8%; a decrease in the percentage of Tubuli seminiferi contorti of the total testes tissue by up to 39.1%.

Animals↗

Contact allergy to furazolidone.

A case of occupational contact allergy to furazolidone, used as an animal feed additive and as an antimicrobial drug in veterinary medicine, is described. The patient did not react to furazolidone 2% pet. Using PEG-400 and alcohol as patch test vehicles resulted in positive patch test reactions. No cross-reactions were observed to other nitrofuran derivatives (nitrofurazone, nitrofurantoin) or to furfural. The literature on contact allergy to nitrofurans is reviewed.

Adult↗

Clinical evaluation of co-trimoxazole and furazolidone in treatment of shigellosis in children.

Co-trimoxazole (trimethoprim-sulphamethoxazole) was compared with furazolidone in the treatment of shigellosis in two groups of 33 and 30 patients respectively. Those treated with co-trimoxazole recovered more quickly; none had shigellae in the faeces four days after the start of treatment, whereas in the group given furazolidone eight still had positive stool cultures seven days after treatment.The susceptibility of 104 shigella strains to seven antimicrobial agents was studied by plate dilution technique. All agents but tetracycline and chloramphenicol were found highly effective against most of the strains tested. All shigella isolates were resistant to sulphamethoxazole, and 63% were sensitive to trimethoprim. Potentiation of trimethoprim by sulphamethoxazole was shown in that all strains tested became sensitive to the combination of trimethoprim and sulphamethoxazole in a ratio of 1:20.

Anti-Bacterial Agents↗

Myocardial calcium cycling defect in furazolidone cardiomyopathy.

We have previously demonstrated that in furazolidone-induced congestive heart failure in turkeys the specific Ca(2+)-ATPase activity of myocardial sarcoplasmic reticulum (SR) is 60% increased in compensation for a 50% depression in net Ca(2+)-sequestration activity. This study tested the hypothesis that SR Ca(2+)-uptake and Ca(2+)-ATPase activities were uncoupled in this cardiomyopathy because of increased Ca(2+)-release channel activity. A novel microassay was used to monitor Ca2+ transport by myocardial homogenates using the fluorescent Ca2+ dye indo 1 to indicate extravesicular ionized Ca2+. The method is applied to cyropreserved biopsy specimens of myocardium and requires only 50 mg tissue. Both SR Ca(2+)-pump and SR Ca(2+)-channel activity were estimated using the channel-inhibitor ruthenium red (RR) and the mitochondrial inhibitor sodium azide. The specificity of the RR inhibition was confirmed using ryanodine. Cardiomyopathy was induced in 2-week-old turkey poults by the addition of 0.07% furazolidone to their feed for 4 weeks. Compared with controls, myocardial maximal Ca(2+)-channel activity relative to maximal Ca(2+)-pump activity was 22% greater and duration of Ca(2+)-channel activity was 100% increased. However, the heart failure birds had 43 and 53% decreases in absolute maximal Ca(2+)-pumping and Ca(2+)-channel activities, respectively. The abnormal Ca(2+)-channel activity resulted in 200% greater time before initiation of net Ca2+ sequestration and 700% greater final myocardial Ca2+ concentrations. For all birds, the Ca(2+)-accumulating activity was highly correlated with Ca(2+)-release activity (all p less than 0.05). These data indicate that in this animal model of congestive heart failure there is defective SR Ca(2+)-channel function resulting in abnormal Ca2+ homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Helicobacter pylori eradication using tetracycline and furazolidone versus amoxicillin and azithromycin in lansoprazole based triple therapy: an open randomized clinical trial.

BACKGROUND: Optimal anti-Helicobacter pylori treatment has not yet been established. AIM: To evaluate H. pylori eradication using tetracycline and furazolidone versus amoxicillin and azithromycin in lansoprazole based triple therapy in northeastern of Brazil. PATIENTS AND METHODS: One hundred and four patients with H. pylori infection, as determined by rapid urease testing and histology, were randomly assigned to receive either: lansoprazole (30 mg q.d.), tetracycline (500 mg q.i.d.), and furazolidone (200 mg t.i.d.) for 7 days (LTF; n = 52); or lansoprazole (30 mg b.i.d.) and amoxicillin (1 g b.i.d.) for 1 week, plus azithromycin (500 mg q.d.) for the first 3 days (LAAz; n = 52). H. pylori eradication was assessed 3 months following completion of therapy by means of rapid urease testing, histology and a 14C-urea breath test. RESULTS: H. pylori eradication was achieved in 46 of 52 (88.4%, 95% CI: 77.5%-95.1%) patients in LTF group and in 14 of 52 (26.9%, 95% CI: 16.2%-40,1%) patients in LAAz group. On a per-protocol analysis, eradication rates were 91.8% (95% CI: 81.4%-97.3%) and 28.5% (95% CI: 17.2%-42.3%), respectively in LTF and LAAz groups. CONCLUSION: The LAAz regimen yielded unacceptably low eradication rates. On the other hand, the LTF scheme represents a suitable alternative for H. pylori eradication.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Omeprazole, furazolidone, and tetracycline: an eradication treatment for resistant H. pylori in Brazilian patients with peptic ulcer disease.

OBJECTIVES: To determine the efficacy of a simple, short-term and low-cost eradication treatment for Helicobacter pylori (H. pylori) using omeprazole, tetracycline, and furazolidone in a Brazilian peptic ulcer population, divided into 2 subgroups: untreated and previously treated for the infection. PATIENTS AND METHODS: Patients with peptic ulcer disease diagnosed by endoscopic examination and infected by H. pylori diagnosed by the rapid urease test (RUT) and histological examination, untreated and previously unsuccessfully treated by macrolides and nitroimidazole, were medicated with omeprazole 20 mg daily dose and tetracycline 500 mg and furazolidone 200 mg given 3 times a day for 7 days. Another endoscopy or a breath test was performed 12 weeks after the end of treatment. Patients were considered cured of the infection if a RUT and histologic examination proved negative or a breath test was negative for the bacterium. RESULTS: Sixty-four patients were included in the study. The women were the predominant sex (58%); the mean age was 46 years. Thirty-three percent of the patients were tobacco users, and duodenal ulcer was identified in 80% of patients. For the 59 patients that underwent follow-up examinations, eradication was verified in 44 (75%). The eradication rate for the intention-to-treat group was 69%. The incidence of severe adverse effects was 15%. CONCLUSION: The treatment provides good efficacy for H. pylori eradication in patients who were previously treated without success, but it causes severe adverse effects that prevented adequate use of the medications in 15% of the patients.

Adolescent↗

Absorption, distribution, metabolism, and excretion of furazolidone. A review of the literature.

Systematic determination of profiles of absorption, distribution, metabolism, and excretion of drugs is standard in the pharmaceutical industry today, and powerful, precise, and specific analytical methods are available to carry out such studies. In the case of furazolidone, developed in the late 1940s, the data were obtained with less precise analytical procedures. This gave rise to the misconception that furazolidone is poorly absorbed and inactivated in the intestine. Newer techniques, such as chromatography and 14C studies, have helped to establish that the drug is indeed well absorbed. Levels of radiolabeled analyte measured in urine indicate that more than 65% of an oral dose is recovered in each animal species tested. Chromatographic methods indicate that little or no intact drug is recovered.

Diarrhea↗

A comparative study of furazolidone and placebo in addition to oral rehydration in the treatment of acute infantile diarrhea.

Between July and October 1987 an outpatient study of 191 children with acute diarrhea was undertaken in two rural communities in Mexico. Through a double-blind randomization we compared the efficacy of a combination therapy of furazolidone, 7.5 mg/kg/day, plus standard oral rehydration therapy (ORT) (96 patients) versus a placebo plus ORT (95 patients), each given for 5 days. Diarrheal stool samples were collected from all patients before therapy. By means of a two-vial transport media system the samples were sent to a university laboratory and examined for viral, bacterial, and parasitic organisms. The most commonly isolated organisms were enterotoxigenic Escherichia coli (13%) and Giardia lamblia (13%). Patients who received furazolidone plus ORT showed a greater reduction in duration of diarrhea when compared with those receiving placebo plus ORT (63.4 h versus 71.44 h). There was also a trend toward shorter duration of diarrhea in patients with Giardia who were treated with furazolidone/ORT compared with Giardia patients in the placebo/ORT group. When fecal leukocytes were present in the stool, the furazolidone/ORT-treated patients had a significantly higher percentage of clinical cures (79% versus 54%, p = 0.03) and an overall shorter duration of diarrhea (62.0 h versus 80.6 h, p = 0.055) at the end of 5 days of therapy than did the placebo/ORT-treated group.

Diarrhea, Infantile↗

Serum sickness with furazolidone.

Two cases of serum sickness from furazolidone (Furoxona), prescribed for giardiasis in Latin America, are described. No previous case of serum sickness related to this drug has been reported in the United States. Tartrazine (yellow dye number 5), a component of furazolidone tablets (Furoxona) manufactured in Latin America countries but no longer included in the drug (Furoxone) in the United States is suggested as a possible cause of serum sickness.

Adult↗

Eradication of Helicobacter pylori in duodenal ulcer disease tetracycline & furazolidone vs. metronidazole & amoxicillin in omeprazole based triple therapy.

BACKGROUND: The object of the study was to study the efficacy and safety of furazolidone and tetracycline compared to metronidazole and amoxicillin in an omeprazole based triple therapy in a prospective randomized-blind-clinical trial. MATERIAL/METHODS: Patients with endoscopically verified active duodenal ulcer disease in the presence of Helicobacter pylori infection were eligible to enter the study. Endoscopy was performed a day before and 6-8 weeks after the cessation of treatment. H. pylori status was assessed by histologic examination (Giemsa stain) of biopsy specimens were taken from the antrum and corpus. H. pylori eradication was defined as absence in histology of the biopsy specimens at the second endoscopy. Ulcer healing was considered as decrease in ulcer size to less than 20% of its primary size. Patients were randomly assigned to receive omeprazole 20 mg, amoxicillin 1000 mg and metronidazole 500 mg (OAM group) or omeprazole 20 mg, tetracycline 500 mg and furazolidone 200 mg (OTF group). All medications were taken twice daily, for 2 weeks. RESULTS: Out of 111 patients enrolled in the study, 108 completed a course of treatment and underwent a follow-up endoscopy, with 54 patients in each group. H. pylori eradication was achieved in 52 patients (96.3% - 95% CI: 91.27-100) in OTF group and 45 patients (83.3% - 95% CI: 73.35-93.25) in OAM group (P=0.015). Our study showed the superiority of OTF vs. OAM regimen with a 13% increment in eradication rate, with only occasional severe side effect. CONCLUSIONS: In conclusion OTF regimen is a safe, cheaper and effective alternative for OTF regimen and we recommend it to be used especially in developing countries.

Amoxicillin↗

[New ultrashort scheme for helicobacter pylori infection eradication using tetracyline, furazolidone and colloidal bismuth subcitrate in dyspeptic patients with or without peptic ulceration in the National Hospital Cayetano Heredia].

BACKGROUND: Helicobacter pylori (Hp) infection has been associated with the presence of duodenal ulcer, gastric ulcer and chronic active gastritis. It is also speculated that Hp may have a major role in gastric cancer development. Due to rising antibiotic resistance, probably lack of compliance and the expense of the currently used antimicrobial regimens, it's important to develop efficacious, short-duration and low cost therapies, especially for the treatment of low-income populations from underdeveloped countries. The goal of the present study is to asses the efficacy of two ultrashort antibiotic schemes against Hp infection. METHODS: Patients with diagnosis of Hp infection, found in antral gastric biopsies, were included. They were randomly assigned to receive one of the following therapeutic schemes: tetracycline 500 mg qid, furazolidone 100 mg qid and colloidal bismuth subcitrate 120 mg qid for 3 days (Scheme I) or 4 days (Scheme II). Patients were instructed to come back for follow-up at least 8 weeks after starting medication. At the control visit, an upper endoscopy was performed and an average of 3 antral biopsies was taken. Biopsies were stained with hematoxylin-eosin for histological assessment and with Warthin-Starry silver staining for Hp diagnosis. A single experienced pathologist read all biopsies. In both, the initial biopsy and the control one, we evaluated: presence of Hp; presence, depth and grade of chronic gastritis; presence and grade of inflammatory activity; presence, grade and extent of mucinous damage; presence of glandular atrophy, intestinal metaplasia and lymphoid follicles. We also evaluated dyspeptic symptoms prior and after the treatment, and the presence of adverse events. RESULTS: 80 patients were enrolled, 2 were excluded because of intense nausea and vomits, 4 patients didn't follow the indications properly and 8 patients couldn't be contacted for the control visit. From the remaining 66 patients, 32 were assigned to Scheme I and 34 to Scheme II, both groups were comparable. Eradication rate was 68.8% (22/32) (CI = 52.1% - 82.7%) for Scheme I and 88.2% (30/34) (CI = 74.9% - 96.2%), significant higher, for Scheme II. There was decrease of dyspeptic symptoms and significant improvement of the histological pattern for both groups, except for presence of chronic gastritis, intestinal metaplasia, glandular atrophy and lymphoid follicles. Hp eradication was associated with significant symptoms decrease, normal endoscopy raising and improvement of all the histological parameters, except for presence of intestinal metaplasia and glandular atrophy. Treatment was well tolerated, 57.6% of the patients reported only mild adverse events, nausea was the most frequent (19.7%) and there was no difference between schemes. CONCLUSIONS: The triple ultrashort duration scheme including tetracycline, furazolidone and bismuth for 4 days is efficacious against Hp, with a high eradication rate (88.2%). The Hp disappearance is followed by improvement in every histological parameter that we evaluated, except for glandular atrophy and intestinal metaplasia; and it's also accompanied by a decrease in dyspeptic symptoms.

Adolescent↗

Influence of exogenous T4 on body weight, feed consumption, T4 levels, and myocardial glycogen in furazolidone-fed turkey poults.

Ten turkey poults each were placed in one of four groups: control, thyroxine (T4), furazolidone (FZ), and FZ + T4. Thyroxine (T4), at a concentration of 1 ppm, was included in the ration of poults fed T4 and FZ + T4, and furazolidone (FZ), at a concentration of 700 ppm, was included in the ration of poults fed FZ and FZ + T4 from 2 to 5 weeks of age. Levels of plasma T4 decreased significantly (P less than or equal to 0.05) between 2 and 5 weeks in control and FZ poults. At 5 weeks, plasma T4 levels were significantly (P less than or equal to 0.05) lower in FZ poults than in control poults and significantly (P less than or equal to 0.05) lower in the FZ + T4 poults than in the T4 poults. Exogenous administration of T4 had no effect on development of the round heart syndrome or on body weight, but significantly increased feed consumption in FZ-fed poults during weeks 4 (P less than or equal to 0.05) and 5 (P less than or equal to 0.01). Inclusion of T4 in the ration increased plasma levels of the hormone 12x in both T4 and FZ + T4 poults and significantly (P less than or equal to 0.05) increased myocardial glycogen content in T4 poults but not in FZ + T4 poults.

Animals↗