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Early clinical and morphologic alterations in the pathogenesis of furazolidone-induced toxicosis in ducklings.

Clinical and pathologic alterations during the development of furazolidone-induced toxicosis were investigated in a group of 35 newly hatched male Pekin ducklings fed a ration containing 700 mg of furazolidone/kg of feed for 27 days. A control group (n = 25) was fed the same ration without added furazolidone. Every 3 days, ducklings were weighted and palpated for ascites and 3 were chosen at random for euthanasia to determine the severity of lesions and to obtain hearts for gross measurements and ultrastructural study. Clinical alterations in treated ducklings consisted of decreased feed consumption with lower weight gain and nervous signs. Gross pathologic alterations included cardiomegaly with dilatation of all chambers and thinning of the myocardium, pericardial effusion, pulmonary edema and congestion, ascites, and testicular enlargement. Gross lesions were not observed before day 8. The earliest lesion (day 9) was cardiac chamber dilatation, with the left ventricle and left atrium most commonly and most severely dilated. Hearts from ducklings euthanatized on days 6, 12, 18, 24, and 27 were examined ultrastructurally. Myofibrillar lysis was first observed on day 12 in 1 duckling (of 3) and in at least 1 duckling from subsequent euthanasia periods. Myofibrillar lysis did not appear to be uniform among the cardiac chambers.

Animal Feed↗

Ultrastructural alterations in furazolidone-induced cystic testicular degeneration in ducklings.

Cystic testicular degeneration was induced in groups of ducklings by feeding furazolidone at 250, 400, 550, or 750 mg per kilogram of feed (ppm) for 4 weeks. In normal ducklings, tall, columnar Sertoli cells predominated in the seminiferous epithelium. In treated ducklings, the mildest ultrastructural alteration was cytoplasmic vacuolation of Sertoli cells. In birds with more severely affected tubules, cytoplasmic vacuolation was more severe and the cells were cuboidal or rounded. The rounded cells desquamated into the tubular lumens, eventually undergoing cytolysis. In birds with the most severely affected tubules, only extensively flattened epithelial cells lined the extremely dilated seminiferous tubules. The interstitium was edematous and compacted between the expanded tubules. Many of the testicular ultrastructural alterations in furazolidone-intoxicated ducklings were similar to those described in the testicles of sodium-intoxicated cockerels.

Animals↗

Liquid chromatography-electrochemical detection of furazolidone and metabolite in extracts of incurred tissues.

One-day-old chicks were raised to maturity on a diet fortified with 0.0055% furazolidone. Analyses of tissue extracts by a liquid chromatographic-electrochemical detection screening procedure for nitro-containing drugs disclosed, in addition to the parent drug, an unidentified metabolite in the liver and breast tissue of the mature birds sacrificed while on the fortified feed. No evidence of residues of the drug or metabolite was found in birds removed from the medicated feed 48 h prior to sacrifice. In view of the rapid in vivo and postmortem metabolism of the parent drug in liver tissue, the metabolite can serve as an alternative means of detecting furazolidone residues in chicken tissues.

Animals↗

Hepatitis, cardiomyopathy and hemodynamics in furazolidone-induced round heart disease of turkeys.

Twenty-five large broad-breasted white turkeys were fed a 22% protein diet supplemented with 500 ppm furazolidone from day 1 to 3.5 weeks of age and the same diet supplemented with 700 ppm furazolidone until 9.5 weeks of age. Following the development of round heart disease as indicated by altered electrocardiograms the 25 turkeys were sacrificed. In the livers of turkeys with biventricular dilatation (72% of cases) there was bile duct hyperlasia, portal fibrosis and intracytoplasmic globules in the hepatocytes. Globules stained pink with hematoxylin-eosin, deep red with PAS and variable with Massons trichrome stains in paraffin-embedded liver sections. Clear intracytoplasmic vacuoles demonstrable in hepatocytes of PAS stained liver sections embedded in paraffin did not stain as lipid in frozen sections but did contain sparse flocculent material in 1 micrometer sections of liver embedded in epoxy resin and stained with toluidine blue. At the subcellular level, the intracytoplasmic globules in hepatocytes were surrounded by a single membrane, contained flocculent material and had enzymatic properties characteristic of lysosomes. Blood pressure, heart rate, dp/dt max, total plasma proteins and plasma trypsin inhibitory capacity of turkeys with round heart disease were lower than corresponding values for control turkeys. Control turkeys did not exhibit the characteristic gross or microscopic lesions of round heart disease.

Animals↗

Liquid chromatographic method for determination of furazolidone in premixes and complete feeds: collaborative study.

A liquid chromatographic (LC) method for determining furazolidone in finished feeds and premixes was collaboratively studied. Finished feed sample is extracted with acetone-water (93 + 7) on a Goldfisch apparatus, extracting solvent is removed, and the residual material is dissolved in warm DMF. A solution of tetraethylammonium bromide is added, the fat layer is removed, and the sample is clarified by filtration and injected onto a reverse phase LC system with detection at 365 nm. Premixes, extracted by shaking with DMF and diluted so that the final furazolidone concentration is about 55 micrograms/mL, are chromatographed and detected the same as finished feed samples, using a mobile phase of acetonitrile-2% acetic acid (20 + 80). Ten commercial feed samples were preweighed and supplied to 14 collaborators. The 5 matched pairs were chosen to represent the following allowed levels: 0.0055, 0.022, 0.033, 2.2, and 22%. Two familiarization samples at the 0.0055 and 11% levels were also supplied. Instructions called for a single analysis of each sample. Two results were eliminated by the Dixon test. The coefficients of variation, following treatment by the ranking test, ranged from 2.0 at the 22% level to 6.5 at the 0.0055% level. Calculated F-values are not significant (P greater than 0.01) except for the 0.0055% level samples extracted overnight. This method has been adopted official first action.

Animal Feed↗

High pressure liquid chromatographic determination of furazolidone in turkey tissue.

A high pressure liquid chromatographic method for determining furazolidone in turkey tissue has been developed. Tissues are ground with methanol and centrifuged. For lower levels of furazolidone, 2--40 ppb, the supernate is evaporated to dryness and redissolved before it is injected onto the liquid chromatographic column. Using a reverse phase column and an ultraviolet absorption detector set at 365 nm, the assay is linear over the concentration range 2--400 ppb with a coefficient of variation of less than 4%. Average recovery from fortified tissues was 96% with a coefficient of variation of 6% at the 50--400 ppb level, and 105% with a coefficient of variation of 11% at the 2--40 ppb level.

Animals↗

Furazolidone in paediatric cholera.

Tetracycline continues to be an effective antimicrobial agent in the clinical control of cholera but because of its high cost, relatively short shelf-life and recent reports of increased resistance of vibrios to tetracycline in vitro, alternative antimicrobial agents have been tested. Furazolidone, effective against cholera caused by the El Tor biotype in adults, was found to be as effective as tetracycline in reducing the volume and duration of diarrhoea in children with classical cholera and, given over a period of 7 days, only slightly less effective in reducing duration of vibrio excretion.Therapy with an antimicrobial agent over a period of 7 days was associated with a significantly smaller rise in vibriocidal antibody titre (of no clinical significance) in the youngest age-group studied; this was probably due to a diminished antigenic stimulus from the primary infection. Undernourished children showed a poorer response to anti-microbial therapy.The study indicated that furazolidone is a reasonable alternative to tetracycline in the treatment of cholera.

Antibody Formation↗

Chemotherapeutic studies on Litomosoides carinii infection of Mastomys natalensis. 8. The action of furazolidone on adult worms and microfilariae.

After oral administration of furazolidone in doses of 5 x 50 mg/kg and 1 x 100 mg/kg body weight to Litomosoides carinii--infected Mastomys natalensis microfilaraemia decreased continuously and was reduced by more than 98% 42 days after start of treatment. After the 5-day treatment all adult female and male worms were found dead and encapsulated within 2 weeks, whereas after the single dose 100% of the female parasites were encapsulated 28 days after treatment. In untreated animals quantiative examinations of the intrauterine stages showed an average number of 500 x 103 embryos per adult female worm. Following the 5-day treatment the number of embryos per female parasite was reduced after 42 days to 12.5 x 103, and after the single treatment to 26.9 x 103. By classification into 5 different stages (2- and 4-cell stages, Morula stage, "Horse-shoe" stage, "Ring" and "Brezel" stages, and intruterine microfilariae) an embryogram showed a continuous increase in pathologically-altered embryos during the whole observation period. The 2- and 4-cell stages suffered the most damaged. By 16 days after the end of the 5-day treatment and by 28 days after the single treatment all embryonic stages in the uteri were found to be pathologically altered. Furazolidone possessess high macrofilaricidal activity together with a considerable adverse effect on embryognesis and some delayed effect on microfilaraemia.

Animals↗

[A comparison of the effectiveness of furazolidone and apramycin in the control of colibacillosis in weaned piglets].

To compare the effectiveness of furazolidone and apramycin (Apralan) in the treatment of oedema disease in pigs, a trial was made on a commercial farm on which colibacillosis was a recurrent problem. Medicated feed containing 100 ppm of apramycin and 400 ppm of furazolidone respectively was given for three weeks after weaning. 112 Piglets were distributed over 10 battery houses at random. Results are summarized in Figure 1.

Animals↗

[Chronic furazolidone poisoning in swine? Practical problems and legal consequences].

Long-term treatment (eighteen months) with a medicated feed containing 400 ppm of furazolidone gave rise to side-effects on a pig farm on which the animals were affected with persistent oedema disease. These side-effects disappeared on discontinuation of the medication. In view of this suspected case of chronic furazolidone intoxication the court formulated several questions for a panel of experts. The questions and the replies given are stated.

Animal Feed↗

Toxicity of furazolidone to Nubian goats.

Male Nubian goats were given furazlidone orally at daily doses of 40, 80, 160 and 320 mg/kg for up to 10 days. Animals given 160 and 320 mg/kg became anemic, and showed anorexia, hyperexcitability, uneasiness , backward walking, locomotory disturbances and circling. These animals died within 5 to 7 days of treatment. Postmortem examination showed mild congestion in brain, and fatty change in liver and kidneys. There was histopathological evidence of hepatic and renal damage, and some necrosis in brain and adrenals. Biochemical examination of serum confirmed the presence of hepatic and renal damage. Goats given furazolidone at daily doses of 40 and 80 mg/kg showed similar signs as above, but to a lesser degree. They were killed at the end of the experiment (10 days). The signs of furazolidone intoxication resembled those of cerebrocortical necrosis (thiamine deficiency in ruminants). Therefore, thiamine (100 mg/animal) was injected iv daily to goats receiving 320 mg furazolidone/kg. The vitamin ameliorated the severity of the drug toxicity.

Animals↗

[L-transforming effect of furazolidone on Shigella flexneri cells].

The capacity of furazolidone for L-transformation of Shigella flexneri was studied with its incubation on 1.3 per cent placenta serum salt Difco agar. It was found that a single exposure of Shigella cells to 0.05 microgram/ml of furazolidone resulted in transformation of some of them to the elements characteristic of the L-forms, i.e. spherical and granular forms capable of reproduction on routine nutrient media and possessing pronounced sensitivity to penicillin.

Dose-Response Relationship, Drug↗

Chemotherapeutic studies on Litomosoides carinii infection of Mastomys natalensis. 7. Filaricidal activity of furazolidone.

Investigations were carried out on the filaricidal activity of furazolidone against Litomosoides carinii infection in Mastomys natalensis. Oral administration of the drug in daily doses of 25, 50, 75, and 150 mg/kg body weight on 5 consecutive days revealed respectively 96,4, 99,3 and, with the two later doses, 100% reduction of macrofilariae in the pleural cavities, and produced a continuing dose-dependant decrease of microfilaraemia in the circulating blood. After oral doses of 5 x 50 mg/kg, all the adult parasites were killed within two weeks of the start of treatment and were found encapsulated in fibrinous masses in the pleural cavities. Deformed and degenerated embryonic stages could be seen in female worms as early as 3 days after the end of treatment. Furazolidone possesses a considerable chemotherapeutic index.

Administration, Oral↗

[Sensitivity of Pseudomonas aeruginosa strains isolated from frozen bull seminal fluid to antibiotics, sulfamides and furazolidone].

A total of 66 Pseudomonas aeruginosa strains isolated from frozen bull semen were studied with regard to their sensitivity to antibiotics, sulfamides, and furazolidone with the employment of the disk method after Anderson. All strains were found resistant to penicillin, erythromycin, tetracycline, novobiocin, neomycin, kanamycin, chloramphenicol, streptomycin, oleandomycin, spectam, furazolidone, borgal, tylan, oxacillin, and sulfathiazole. Experiments are carried out to find antibiotics that would have good activity against this species of bacteria. The attention is focused on gentamycin, carbenicillin, and rimactan which inhibit the growth of these strains at a minimal suppressive concentration ranging from 1.5 up to 50 microgram/cm3. Regressive lines have been drawn for these antibiotics. It is suggested to use the graphs of the same lines in the rapid determination of the minimal suppressive concentration of gentamycin, carbenicillin, and rimactan against Ps. aeruginosa strains contaminating the semen of bulls.

Animals↗

Congestive cardiomyopathy induced in ducklings fed graded amounts of furazolidone.

Newly hatched male White Pekin ducklings (n = 119) were allotted to 7 groups of 17 each and fed furazolidone (FZ) at dose levels of 0, 100, 250, 500, 750, 1,000, and 1,250 mg/kg of feed for 4 weeks. The frequency and severity of clinical signs of FZ toxicosis, including growth retardation, ascites, and mortality, were dose related. At necropsy, the affected ducklings had ascites, hydropericardium, and biventricular dilatation. The frequencies of cardiomyopathy, ascites, and mortality, respectively, for the several dose levels of drug were as follows: 0, 100, and 250 mg of FZ/kg of feed--0%, 0%, 0%; for the 500 mg/kg level--35%, 12%, 0%; for the 750 mg/kg level--100%, 53%, 18%; for the 1,000 mg/level--79%, 57%, 57%; and for the 1,250 mg/kg level--33%, 20%, 73%. Ducklings with FZ-induced congestive cardiomyopathy had decreased left ventricular free wall and ventricular septal thickness, increased left ventricular chamber diameter, increased left ventricular dilatation score, decreased absolute heart weight, and increased relative heart weight. Cardiac histopathologic changes were minimal; some ducklings had myocytolysis. Liver and lungs were congested. Furazolidone-induced cardiomyopathy in ducklings offers a model for studies of congestive cardiomyopathy in a species that is free from the hereditary cardiomyopathy ("round heart disease") seen in turkeys.

Animals↗

Ultra trace determination of furazolidone in turkey tissues by liquid partitioning and high performance liquid chromatography.

A simple and sensitive procedure is presented for the determination of furazolidone in turkey tissues, using liquid partitioning followed by high performance liquid chromatography (HPLC). Fat, liver, kidney, skin, and muscle tissues are ground with methylene chloride in a Polytron homogenizer, followed by solvent removal, partitioning in hexane-0.01M acetic acid, and back-partitioning the 0.01M acetic acid with methylene chloride. The determination by HPLC used a reverse phase Ultrasphere-ODS 5 micrometer column. The method is sensitive to 0.5 ppb, with a standard deviation of 6.39% at the 2 ppb fortification level. Recovery from fortified tissues averaged 84% from samples fortified with 0.5-10 ppb furazolidone. An alternative cleanup procedure using a Sep-Pak C18 cartridge is also presented.

Animals↗

[Therapeutic effectiveness of furazolidone and difuracil (PAP-49) in experimental staphylococcal and Escherichia septicemia].

The therapeutic efficacy of a new nitrofuran, N-(5-nitrofurilidene)-5-nitrofuran-2-(N'-acetyl)carboxamidra zone (difuracil or PAP-49) in experimental staphylococcal and Coli septicemia was stated and compared to that of furazolidone. It was shown in the models of staphylococcal and Coli septicemia of albino mice that by its therapeutic efficacy difuracil (PAP-49) was 1.3 times more active as furazolidone and by 1-2 days earlier eradicated the pathogens in the host.

Animals↗

[The effect of nitrofurazone and furazolidone on induction of cytochrome P-450 in the CYPIA test].

The double CYPIA-TEST (cytochrome P-450) induction assay) was used to discriminate between the forms of cytochrome P-450 (the 3-methylcholantrene type (3-MC) or phenobarbital type (PB)) induced by nitrofurans; nitrofurazone and furazolidone. The test consisted of the studies by the technique of Ames of the ability of the S9 preparation obtained from livers of rats induced by nitrofurans to cause the metabolic activation of ethidium bromide (EtBr)--for induction of 3-MC type or cyclophosphamide (CPA) for PB type of cytochrome P-450. The mutagenicity of activated EtBr and CPA was checked with TA98 and TA100 of S. typhimurium respectively. It was found that only furazolidone at cumulative dose 3 x 80 mg/kg of body weight induce the 3-MC-type of cytochrome P-450.

Animals↗