Agostino Macri

Clinical and pharmacological profile in a clenbuterol epidemic poisoning of contaminated beef meat in Italy

Long-acting beta adrenergic agonists, such as clenbuterol accumulate in the liver, but not meat of treated farm animals, and result in epidemic poisonings in consumers. We describe an outbreak of poisoning in 15 people, following the consumption of meat. Clinical symptoms (distal tremors, palpitations, headache, tachipnoea-dyspnoea, and also moderate hyperglycaemia, hypokalemia and leucocytosis) were seen in nine hospitalised patients, starting about 0.5-3 h after poisoning, and disappearing within 3-5 days later. Clenbuterol was found in the urine of all the symptomatic patients, at higher levels than pharmacokinetic computing (mean level 28 ng/ml, 36 h after ingestion), based on the levels found in the meat (1140-1480 ng/g edible tissue). Thus, epidemic poisoning can be produced following the consumption of contaminated meat. The need for a better definition of pharmaco- and toxico-kinetics, not only for drugs ingested as parent drug, but also when ingested as residues with animal tissues, is recommended.

Antibiotics of zootechnical use: Effects of acute high and low dose contamination on Daphnia magna Straus

To gather data on the effects of antibiotic pollution in freshwater systems and to determine methodological approaches, aminosidine (A), bacitracin (B), erythromycin (E) and lincomycin (L) were subjected to acute high dose toxicily tests (AHDTT) using Daphnia magna and following the EEC protocol (EEC Commission 84/449, 1984); the lethal effect evaluated at 24, 48 and 72 h determined the sequence of decreasing toxicity to be B > E > A > L. Furthermore, the four antibiotics were tested in acute low dose totoxiciiy teats (ALDTT) using Daplmia magna by studying the alteration of phototactic behaviour. This test showed that L and B depressed phototaxis, while A increased the light induced migration rate. E did not alter the phototactic behaviour.

Acute toxicity of furazolidone onArtemia salina, Daphnia magna, andCulex pipiens molestus larvae

As a result of evidence of the ecotoxicity of nitrofurans, the acute toxicity of furazolidone was tested in vivo on two aquatic organisms, Artemia salina and Daphnia magna, which are both crustaceans. Toxicity studies were also performed on larvae of Culex pipiens molestus. Results indicated a significant toxicity of the compound on Culex pipiens and Daphnia magna, while Artemia salina proved to be the least sensitive.

Toxicological evaluation of nitrofurazone and furaltadone on Selenastrum capricornutum, Daphnia magna, and Musca domestica

Short-term toxicity of nitrofurans, nitrofurazone, furaltadone tartrate, and furaltadone chlorohydrate, was tested in the laboratory on two freshwater organisms, Selenastrum capricornutum (algae) and Daphnia magna (crustaceans). Toxicity studies with nitrofurazone were also carried out on larval development of the house fly Musca domestica L. Nitrofurazone was invariably the most toxic compound (the 96-hr EC50 of algal species was 1.45 mg/liters; the EC50 values for D. magna were 40.04 and 28.67 mg/liter after 24 and 48 hr, respectively) followed by furaltadone tartrate and furaltadone chlorohydrate. This study provides some evidence of the potential ecotoxicity of nitrofurans, indicating the need for further investigations.

Intracerebral administration of Interleukin-12 (IL-12) and IL-18 modifies the course of mouse scrapie

BackgroundPrion diseases are characterised by a neurodegenerative pattern in which the function of immune system remains still elusive. In the present study, we evaluate if an exogenous treatment with Interleukin-12 (IL-12) and IL-18, able to activate microglia, is able to affect scrapie pathogenesis.ResultsCytokines injected intracranially, induced a strong inflammatory response characterised by TNF-α production and microglia activation. Two groups of mice were injected intracerebrally with high dose of ME7 strain of scrapie containing IL-12 and IL-18 or sterile saline. Cytokines-treated mice showed a more pronounced accumulation of PrPSc in brain tissues at 90 days post-inoculation and a shorter mean survival times than untreated mice.ConclusionWe can conclude that intracerebral administration of IL-12 and IL-18 can modulate scrapie pathogenesis possibly through a microglia-mediated pattern.

Relay activity of 17-β oestradiol and diethylstilbestrol in a mouse-rat system

The biological activities of diethylstibestrol (DES) of 17 beta-oestradiol (17 beta E) were initially tested, based on the uterus enlargement induced by different doses given with food to immature female mice. In a second series of experiments, the drugs were given in higher doses per os to rats (relay animals) and after 24 h, the livers of the relay rats were removed. Parts of the livers were freeze-dried and were added (10% w/w) to the food of immature female mice, while the remainder underwent chemical analysis to determine the DES and 17 beta E content. When given directly to mice with their food, DES showed about six times more biological activity than 17 beta E. When given through the livers of relay rats, the biological activity of the livers from DES-and 17 beta E-treated relay rats was of the same magnitude. The content of 17 beta E in the livers of relay rats was 10-20 times higher than the DES. Such concentrations corresponded directly to the biological activity of livers. These data show that the bioavailability and the relative potency of xenobiotic drugs and natural hormones may be profoundly altered after passing through metabolic pathways, and may give useful indications for the evaluation of biological activity of residues and contaminants and their metabolites in the food.

Action in cases of suspected chemical food poisoning

Chemical food poisoning is a periodic menace both for the health of the consumers and for trade. It can be intentional or unintentional. In the latter case, poisoning may have a very large attack rate and it may be caused by sophistication (e.g., the methanol poisoning in Italy in 1985) or by environmental pollution (e.g., the Iraq accident in 1971-1972 due to mercury-contaminated flour). As a general statement, they are acute events, often noticed by outbreaks of unexplained deaths or sickness. The purposed lines for intervention (monitoring and biological testing) and some related problems are briefly described. Emphasis is placed on biological of suspected food items by a sensitive method to detect the presence of a noxious agent of unknown origin. The basic principle is to administer the highest amount possible of the suspected food to two different species of rodents for 5 days. Finally it should be noted that the characteristics and severity of every episode depend on the food and the chemical involved; thus only general suggestions may be given.

Hematotoxic effects of 3,5-dinitro-4-chloro-α,α,α-trifluorotoluene, a water contaminant

Three short-term studies of 7, 14, and 21 days, respectively, were made to investigate the nature of the anemia induced in rats by 3,5-dinitro-4-chloro-alpha,alpha,alpha-trifluorotoluene (DNCTT). This compound is an intermediate in the synthesis of dinitroaniline herbicides and was detected as a contaminant of a water-bearing stratum in northern Italy. DNCTT was mixed in a powdered rodent diet at a level of 2000 ppm and administered to Wistar-derived rats. DNCTT was shown to produce a hemolytic anemia of rapid onset; packed cell volume and hemoglobin concentration were decreased at all three treatment periods. Methemoglobin and reticulocyte count were increased in all the treated groups. The relative organ weights of the spleen and the liver were increased compared to those of the control groups. Spleen enlargement was also evident at the macroscopic examination, whereas the liver appearance was normal. Pearls Prussian blue staining performed on the spleen and liver was highly positive in the spleen of treated rats, but no iron deposition was detected in the liver of treated rats.