[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%.

Carcinogenic activity of 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide, a food additive, in mice and rats.

The carcinogenicity of a food additive, 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2), was studied in Wistar rats and CDF1 mice. The rats developed mammary tumors; the first appearing 9 months after the start of the experiment. In mice fed AF-2 diet, squamous cell carcinoma of the forestomach was observed in the 11th month. Some mice had metastases in the liver, spleen, lymph nodes and peritoneal cavity.

Mutagenic effect of orally given AF-2 on embryonic cells in pregnant Syrian hamsters.

Pregnant hamsters were given various doses of AF-2 by stomach tube; then the cells of their embryos were isolated and cultured in normal medium. Chromosome preparations were made within 24 h after the start of primary culture, and examined for chromosomal aberrations. Marked chromosomal abnormalities were observed in cells of embryos of animals treated with AF-2 at over 20 mg/kg. Samples of surviving cells were also cultured in normal medium for 48 h, and then selected in medium containing 8AG or 6TG. This treatment with AF-2 caused marked dose-dependent induction of 8AG- or 6TG-resistant mutations: mutant colonies were even obtained after a single treatment with 2 mg of AF-2 per kg. These results show that this is a sensitive and useful mammalian system for detecting environmental mutagens.

The 'dying back' process. A common denominator in many naturally occurring and toxic neuropathies.

The "dying back" process can be defined as a pathological changes affecting certain neurons in a number of systematized degenerative conditions. Examples exist to illustrate the nature of this process, which is unique to nervous tissue, and there is an association of this process with certain chronic vitamin-deficiency syndromes and some important neurotoxic chemicals. Albeit largely speculative, one can attempt to group the conditions showing the dying back process in terms of putative metabolic lesions. Although this attempt is admittedly only a first approximation, it enables us to look ahead to a future understanding of the metabolic problems of long neurons and how their selective degeneration comes about.

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.

Vaginal medications as a cause for varied widespread dermatitides.

Widespread dermatitis developed in three women after use of vaginal preparations. Besides allergic contact dermatitis, these cases involved erythema multiforme and a photosensitive eruption. Antigen absorption into the general circulation through the vaginal wall, and its deposition at distant skin sites, appeared to account for the spread of the eruption. This type of eruption is akin to the systemic, eczematous, contact-type dermatitis mediated by a systemically given drug in a primarily cutaneously sensitized person.

Clinical trial on furapyrimidone in filariasis.

A clinical trial was carried out with furapyrimidone in treating 51 patients with B. malayi, 159 with W. bancrofti and eight with D. perstans using different dosage schedules. Two hundred and fifty-seven cases of Malayan and bancroftian filariasis were treated with hetrazan for comparison. The results based on the microfilaricidal effects suggest that furapyrimidone possesses similar therapeutic effects of hetrazan on Malayan filariasis at eight-month follow-up, and higher incidences of microfilarial disappearance of W. bancrofti infection (81.3%) at six-month follow-up. The drug was also effective against D. perstans. The side effects consisted of fever and irritation of the digestive tract. Fever may be related to allergic reaction of foreign protein from the dead or dying parasites. The side reactions are similar to those of hetrazan and usually not serious. Comparing the efficacies and side effects of furapyrimidone with different dosage schedules the authors recommend regimens of 15 to 20 mg/kg/day for six days in treating Malayan filariasis and 20 mg/kg/day for seven days in treating bancroftian filariasis.

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.

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.