Microwave-assisted derivatisation and LC-MS/MS determination of nitrofuran metabolites in farm-raised prawns (Penaeus monodon).

A new microwave-assisted derivatisation and LC-MS/MS method has been developed for the analysis of nitrofuran metabolites - 3-amino-5-morpholino-methyl-1,3-oxa-zolidinone (AMOZ), 3-amino-2-oxazolidinone (AOZ), 1-aminohydantoin (AHD) and semicarbazide (SEM) - in farm-raised prawns (Penaeus monodon) from the coastal regions of South India. Analysis was carried out by reverse-phase column (Phenomenex Luna C18) with gradient elution using mobile phase A (0.02% acetic acid in water) and mobile phase B (0.02% acetic acid in acetonitrile), at a flow rate of 200 µl min(-1) and an injection volume of 20 µl. Microwave-assisted derivatisation was achieved in 6 min with good recovery. The results showed that the samples collected from Andhra Pradesh and Karnataka contained residues of nitrofuran metabolites in the range from 5.0 to 40 ng g(-1). This work emphasises the importance of ensuring the safety of seafood and that a new method of derivatisation is applicable for the analysis of nitrofuran metabolites in seafood.

[A comparison of efficacy and tolerance of furamag and norbactin in the treatment of acute cystitis in females].

Efficacy and tolerance of furamag and norbactin were compared in a prospective controlled trial with participation of 82 females aged 18-60 years with acute uncomplicated cystitis. All the women were divided into two groups. Group 1 (n=42) received norbactin (norfloxacin) in a dose 400 mg twice a day for 7 days. Group 2 (n=40) was given furamag in a dose 50 mg 3 times a day for 10 days. The results were evaluated 2 weeks after the treatment. The comparison of the treatment results showed that a new nitrofuranic drug furamag has significantly higher clinical and bacteriological efficacy: acute cystitis was cured in 95% patients, eradication of the infective agent occurred in 96.4% patients, tolerance was good in 97.5% patients. Sensitivity of the agents causing acute cystitis to nitrofurans reached 98.2% while to norbactin--only 86%.

Nifuroxazide-induced acute pancreatitis: a new side-effect for an old drug?

We report the case of a middle-aged woman who developed a typical picture of acute pancreatitis together with systemic features of immunoallergy after the intake of two capsules (200 mg) of nifuroxazide. Even if acute pancreatitis is a rare adverse event of nitrofuran derivative therapy, nifuroxazide-induced pancreatitis as not been previously described. As suggested by associated systemic features, the disease is likely of immunoallergic origin.

Nifuroxazide in acute diarrhoea: OTC preparation. Irrational.

(1) Nifuroxazide, an intestinal antibacterial agent, is now available in France, without a prescription, for the treatment of acute diarrhoea in adults. (2) According to the only available comparative randomised trial, there is no effect on dehydration. Relative to a placebo, the mean number of stools is reduced by about one per day during the first two days of treatment, with no significant difference thereafter.

Malignant, non-Hodgkin's lymphomas in Trypanosoma cruzi-infected rabbits treated with nitroarenes.

Use of 2-nitroimidazole, 5-nitrofuran and 5-nitroimidazole compounds in T. cruzi-infected rabbits resulted in a reduction in duration of parasitaemia in comparison with untreated, infected rabbits. The chronic myocarditis associated with Chagas' disease was not, however, prevented in nitroarene-treated rabbits; lymphocytic infiltrates associated with cardiac cell lysis, in the absence of parasites in situ, were present in both treated and untreated rabbits. The carcinogenic effect of each trypanocidal nitroarene used in this study was also assessed. Administration of nitroarenes to rabbits resulted in the appearance of solid tumours in 37.8 per cent of animals that received drug therapy. Untreated, control rabbits in this series did not show tumour growth. Furthermore, malignant, mixed-cell type, non-Hodgkin's lymphomas were seen in 32.4 per cent of the treated rabbits. It seems that a direct relationship could be present between the presence of the nitro group, the trypanocidal cytotoxicity and the prevalence of tumours. Benznidazole cleared up parasitaemias in the shortest time and was associated with 41.6 per cent of lymphoma growths, whereas MK-436 required twice as much time to clear blood parasites, and showed lymphomas in 25 per cent of experimental rabbits. The demonstration of a high prevalence of malignant tumours in addition to the chronic myocarditis of Chagas' disease in nitroarene-treated rabbits is important since indiscriminate use of such compounds currently used to treat T. cruzi infections in man could increase the risk of lymphoma.

Toxic effects of nifurtimox and benznidazole, two drugs used against American trypanosomiasis (Chagas' disease).

American trypanosomiasis (Chagas' disease) is an endemic parasitic disease afflicting more than 20 million persons in Latin America. Two drugs are currently being used for treatment of the acute phase of Chagas' disease: 4-[(5-nitrofurfurylidene)amino-3-methylthiomorpholine-1,1-di oxide] (Nifurtimox; Nfx) and (N-benzl-2-nitro-1-imidazole acetamide) (Benznidazole; Bz). Nfx and Bz have serious undesirable effects, which have been reported during their clinical use, including anorexia and weight loss, nausea and vomiting, nervous excitation, insomnia, psyche depressions, convulsions, vertigo, headache, sleepiness, myalgias, arthralgias, loss of balance, disorientation, forgetfulness, paresthesias, adynamia, acoustic phenomena, peripheral neuropathies, gastralgia, mucosal edema, hepatic intolerance, skin manifestations, and intolerance to drinking alcohol. Effects in the central and peripheral nervous system of Nfx were also reproduced in animals. Signs of testicular and ovarian injury were reported for both Nfx and Bz, the effects of Bz being in general less intense than those of Nfx. Both drugs evidenced mutagenicity. In light of the present knowledge about the toxicity of Nfx and Bz, further studies on the mutagenic, teratogenic, carcinogenic, and reproductive effects of both drugs are recommended. Lack of information is particularly serious for Bz. Studies on Nfx and Bz biotransformation, activation to reactive metabolites, and potential mechanisms for their toxic effects were analyzed. Risk-benefit considerations of the use of Nfx and Bz were made and an analysis of the need for research on Chagas' disease chemotherapy was also performed.

Hepatic injury associated with the use of nitrofurans: a clinicopathological study of 52 reported cases.

Fifty cases of nitrofurantoin-associated hepatic injury and two cases of nifurtoinol (hydroxymethylnitrofurantoin)-associated hepatic injury reported to the Netherlands Centre for Monitoring of Adverse Reactions to Drugs were analyzed in detail. In 38 cases, a causal relationship was considered likely [i.e., "highly probable" (n = 4), "probable" (n = 23) or "possible" (n = 11)]. In 25 cases, hepatic injury was of the acute type whereas 13 cases presented a chronic type of reaction. Both types were more common in the elderly. Eighty per cent of the acute reactions appeared within the first 6 weeks of treatment and were sometimes accompanied by fever (28%), rash (12%) and eosinophilia (16%). Biochemically, the pattern was mainly hepatocellular (32%), whereas mixed cholestatic-hepatocellular (4%) and cholestatic (4%) patterns were uncommon. Although mild to moderate liver enzyme elevations (60%) were common, these were primarily symptomatic. The reaction was fatal in one "acute" and one "chronic" case. In the chronic cases, nuclear (82%) and smooth muscle (73%) antibodies and LE cells (50%) were frequently present. HLA typing showed no increase of the HLA B8 or HLA DRw3 haplotype. HLA DR2 (56%) and HLA DRw6 (56%) were more frequent than in controls (both 29%), but this was not statistically significant. Histology showed mainly necrosis, varying from spotty to massive, in the acute cases and a pattern consistent with chronic active hepatitis in the chronic cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Granulomatous lung disease in children by aspiration of medications.

Post mortem examinations of 8 infants, 11 d to 5 months old and one 12 year old girl, demonstrated foreign bodies in the lungs which could be identified as orally administered drugs: cholestyramine (Questran) and phenobarbital (Luminal, Gardenal) or phenydantin-components. The microscopic changes caused by such deposits and the histologic methods of identifying medicines are presented. The authors point to the role of aspiration in deposit formation and to the pseudomiliary granulomatous nature of subsequent changes. It is proposed to define the alterations as a separate form of aspiratory lesion in children.

Genotoxic activities of 2-nitronaphthofurans and related molecules.

The genotoxic activities of 63, 2-nitronaphthofurans and related molecules were examined using two bacterial short-term tests, the Salmonella mammalian microsome assay test or Mutatest, a mutagenesis assay, and/or the SOS Chromotest, an assay for induction of an SOS function in Escherichia coli. Seven compounds were also investigated in the Chinese hamster ovary cells/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) test, a mammalian gene mutation assay. Our main conclusions are the following: (a) Simple empirical rules relating structure to mutagenic activity in the Mutatest can be derived for some of the compounds. In particular, they account for the extremely high Mutagenic Potency of 7-methoxy-1-methyl-2-nitronaphtho[2,1-b]furan (R7372), approximately 2 X 10(6) mutants/nmol on strain TA100. (b) There is a good quantitative correlation between the Mutagenic Potency in the Salmonella/mammalian microsomes assay and the SOS-inducing potency in the SOS Chromotest. This, and previous evidence, suggests strongly that the 2-nitronaphthofurans derivatives are essentially recA and thus probably umuDC-dependent mutagens. (c) Four out of seven compounds tested in the CHO/HGPRT assay gave responses correlated with the bacterial responses. One of them, 7-methoxy-2-nitronaphtho[2,1-b]furan (R7000), is among, or is, the strongest mutagen described for mammalian cells. We briefly discuss the practical and theoretical implications of these results.