[Pesticide poisoning referred to the Poison Center of Milan in 1995-1998]. / Intossicazioni da prodotti antiparassitari rilevate dal Centro Antiveleni di Milano nel periodo 1995-1998.

From 1995 through 1998 the Poison Control Centre of Milan identified 7594 cases of suspected or confirmed cases of acute pesticide poisoning. Domestic use products accounted for 4483 (59%) of the cases. Of these, 84% occurred at home and 48% in children under five. The most frequently reported domestic use products were pyrethrins/pyrethroids (26%), fertilizers (19%) and camphor/naphthalene (12%). Of 3111 cases (41%) due to agricultural products, 10% were children under five and 69% were males. Half of the poisonings from agricultural products occurred at home, the remainder at workplace. The products most frequently reported were organophosphates (26%), pyrethrins/pyrethroids (9%), and carbamates (9%). These preliminary data indicate the importance of implementing prevention programs to reduce pesticide poisonings with particular reference to young children.

Potential coanthracyclinic activity of pyridylmethylene-2-indolinones.

The paper reports the cytotoxic activity of pyridylmethylene-2-indolinones previously described as cardiotonics and the synthesis of three analogs of the most potent cytotoxic agent. Some of these compounds could be useful, when associated with anthracyclines, to reduce the cardiotoxicity of these potent antitumor drugs.

In vivo cardiotonic activity of pyridylmethylene-2-indolinones.

The synthesis of 5-chloro-3-pyridylmethylene-2-indolinone is reported. This compound was subjected to an in vivo cardiotonic assay with 10 analogs whose synthesis and in vitro cardiotonic activity were previously reported. All the compounds tested (except the 5-hydroxyindole derivative) showed significant positive inotropic activity. The 3-pyridyl derivative without substituents at the indole system was the most active of the whole series.

In vivo cardiotonic activity of aryl- and pyridyl-substituted fused imidazoles.

Two new imidazo[2,1-b]thiazoles related to sulmazole were synthesized and subjected to an in vivo cardiotonic assay with 14 analog compounds which gave the best results in previously reported in vitro tests. The data obtained show that three substituents (3-pyridyl, 4-pyridyl and 2,5-dimethoxyphenyl group) are useful pharmacophoric groups in modulating the in vivo cardiotonic activity of the fused imidazoles considered.

Reduction of adriamycin cardiotoxicity by enoximone.

Several non catecholamine, non glycoside cardiotonic drugs have been described recently. New compounds include amrinone, sulmazole, milrinone and pimobendan. In an attempt to alleviate or prevent anthracycline toxicity, we have reported that these compounds reduce the negative effects of adriamycin, 4-epiadriamycin and esorubicin in isolated guinea pig atria. The present study reports the effects of a new cardiotonic agent: enoximone. Enoximone was administered after adriamycin (100 micrograms/ml) on the isolated and spontaneously beating atria, and on electrically driven left atria of guinea pig-in normodynamic and hypodynamic conditions. Exposure for 60 minutes to the antitumor drug causes a depression of contractile force (g) and its derivative versus time (dF/dt, as maximal rate of contractile force). The negative effects of adriamycin are antagonised by enoximone (100, 200 micrograms/ml).

The effects of roxatidine on neuromuscular transmission.

We have investigated the effects of the H2 receptor antagonist roxatidine on the neuromuscular transmission by using the sciatic nerve-gastrocnemius muscle preparation of the rat in vivo. Roxatidine, administered by i.v. injection, potentiates the neuromuscular blockade induced by d-tubocurarine, pancuronium and aminoglycoside antibiotic, kanamycin. Moreover, the drug alone is capable of producing a blockade on the preparation stimulated at high frequency. The neuromuscular blockade induced by roxatidine is partially reversed by 4-aminopyridine but not by dimaprit.

The effect of nizatidine on neuromuscular transmission.

The effect of the H2-receptor antagonist, nizatidine, on neuromuscular transmission was investigated using sciatic nerve-gastrocnemius muscle preparations of rat in vivo. Nizatidine, administered by i.v. injection, potentiates the neuromuscular blockade induced by d-tubocurarine, pancuronium and the aminoglycoside antibiotic, kanamycin. Moreover, the drug alone is capable of producing a blockade on preparations stimulated at high frequency. The neuromuscular blockade induced by nizatidine is reversed by 4-aminopyridine but not by dimaprit.

The effect of H2 receptor antagonists on neuromuscular transmission.

We have reported that the H2 receptor antagonists, cimetidine and ranitidine, interfere with neuromuscular transmission on the isolated phrenic nerve--diaphragm preparation of the rat in vitro and we have suggested that the neuromuscular blockade produced could be ascribed to an action at presynaptic level by competing calcium ions unrelated to their specific effects on H2 histamine receptor: in fact, neuromuscular blockade was reversed by calcium and 4-aminopyridine but not by neostigmine or dimaprit. In the present study these results are confirmed in vivo on the sciatic nerve-gastrocnemius muscle preparation of the rat.

The effect of famotidine on neuromuscular transmission.

We have investigated the effects of the H2 receptor antagonist famotidine on the neuromuscular transmission by using the sciatic nerve--gastrocnemius muscle preparation of rat in vitro. Famotidine, administered by I.V. injection, potentiates the neuromuscular blockade induced by d-tubocurarine, pancuronium and aminoglycoside antibiotics. Moreover, the drug alone is capable of producing a blockade on the preparation stimulated at high frequency. The neuromuscular blockade induced by famotidine is reversed by 4-aminopyridine but not by dimaprit. Similar results have previously been obtained with cimetidine.