Evidence for a role of mast cells in the lung edema induced by Tityus serrulatus venom in rats.

In the most severe cases of human poisoning by Tityus serrulatus, pulmonary edema is a frequent finding and can be the cause of death. Mast cells can release a range of mediators known to be involved in the development of lung edema following T. serrulatus venom injection. The present work was designed to investigate whether mast cells participated in the acute lung injury induced by T. serrulatus scorpion venom and could, thus, be an intermediate between neuropeptide release and activation of the inflammatory cascade. To this end, mast cells were depleted using compound 48/80. Pulmonary edema, as assessed by the levels of extravasation of Evans blue dye in the bronchoalveolar lavage and in the left lung, was completely inhibited in compound 48/80-treated animals. Moreover, the number of animals surviving 60min after injection of venom rose from 20 to 60%. Our results demonstrate an important role for mast cells in the development of lung injury and lethality following the intravenous administration of T. serrulatus venom.

Effects of tachykinin NK1 or PAF receptor blockade on the lung injury induced by scorpion venom in rats.

In cases of severe human scorpion envenoming, lung injury is a common finding and frequently the cause of death. In the rat, two distinct mechanisms account for oedema following the intravenous injection of the venom -- acute left ventricular failure resulting from a massive release of catecholamines and an increase in pulmonary vascular permeability. In the present work, we investigated the effects of a tachykinin NK1 receptor antagonist (CP96,345, the dihydrochloride salt of (2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)methyl)-1-az abicycol[2.2.2]octan-3-amine) and its 2 R-3 R inactive enantiomer (CP96,344) on the acute lung injury induced by the i.v. injection of Tityus serrulatus venom in rats. Lung injury was assessed by evaluating the extravasation of Evans blue dye in the bronchoalveolar lavage fluid and in the lung of venom-treated and control animals. The effects of the platelet-activating factor (PAF) receptor antagonist WEB2170 (2-methyl-1-phenylimidazol[4,5c]pyridine) were evaluated for comparison. The i.v. injection of the venom induced the extravasation of Evans blue in the bronchoalveolar lavage fluid and into the left lung. Pretreament with the tachykinin NK1 receptor antagonist CP96,345, but not CP96,344, inhibited Evans blue dye extravasation in the bronchoalveolar lavage fluid and in the lung by 96% and 86%, respectively. The PAF receptor antagonist WEB2170 inhibited the increase in vascular permeability in the bronchoalveolar lavage fluid by 60% and had no effect on the extravasation to the lung parenchyma of venom-injected animals. In addition to abrogating lung injury, pretreatment of rats with CP96,345, but not CP96,344 or WEB2170, decreased by 70% the mortality induced by the venom. This is the first study to show the relevance of the tachykinin NK1 receptor in mediating lung injury and mortality in animals injected with the neurotoxic T. serrulatus venom. Blockade of the tachykinin NK1 receptor may represent an important strategy in the treatment of patients with signs of severe envenoming and clearly deserves further studies.

Pharmacological evidence that neuropeptides mediate part of the actions of scorpion venom on the guinea pig ileum.

Severe human scorpion envenoming is characterised by instability of several physiological systems and death. These manifestations are explained by the ability of the venom toxins to activate sodium channels in nerve terminals with the subsequent release of neurotransmitters, specially acetylcholine and noradrenaline. However, there is evidence to suggest that other neurotransmitters are also released. We now have sought evidence for a role of the substance P receptor, the tachykinin NK1 receptor, in mediating part of the contractile actions of Tityus serrulatus venom on the isolated guinea pig ileum. Scorpion venom induced a significant elevation of baseline tension with frequent and periodic superimposed contractions on the elevated baseline. Pretreatment with atropine partially blocked the elevation in baseline and in the number of superimposed contractions. These responses were also partially inhibited by the tachykinin NK1 receptor antagonist, CP96,345 (the dihydrochloride salt of (2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)methyl)-1-az abicycol[2.2.2]octan-3-amine), but not by its inactive enantiomer, CP96,344 (the 2R-3R enantiomer of CP96,345). Pretreatment with the combination of atropine and CP96,345 completely inhibited the effects of the venom. Moreover, pretreatment with the combined drugs abolished the effects of toxin gamma, a toxin purified from the venom. Finally, another tachykinin NK1 receptor antagonist, RP67,580 ((3aR, 7ar)-7,7-diphenyl-2-[1-imino-2-(2-methoxy-phenyl)ethyl]perhydro isoindol-4-one), significantly inhibited the venom-induced contractions. These results demonstrate an important role for NK1 receptors in mediating part of the contractile effects of the venom on guinea pig ileum. The release of neuropeptides may play an important role in the systemic manifestations of severe envenoming.

Lung oedema induced by Tityus serrulatus scorpion venom in the rat.

The effects of drugs were investigated on the induction of acute lung oedema by scorpion Tityus serrulatus venom in male Wistar rats (200-230 g) anaesthetized with sodium pentobarbital (40 mg/kg, i.p.). Intravenous (i.v.) injection of scorpion venom (0.5 mg/kg) into 12 rats induced arterial hypertension and severe lung oedema, whereas i.v. injection of scorpion venom into 16 rats previously injected with commercial heparin induced arterial hypertension, but only a slight lung oedema. It is suggested that the inhibitory effect of commercial heparin on the genesis of lung oedema may be due to a decrease in vascular permeability in the lungs. Previous i.v. injection of aprotinin did not prevent the arterial hypertension and the lung oedema induced by scorpion venom. Previous injections of platelet-activating factor antagonists (BN-52021 and WEB-2170) or of an inhibitor of lipo- and cyclooxygenase (Nordihydroguaiaretic acid) did not prevent the arterial hypertension induced by scorpion venom, but decreased the magnitude of the lung oedema elicited by the venom. Previous injections of inhibitors of 5-lipoxygenase (MK-886) or cyclooxygenase (aspirin or indomethacin) significantly decreased the magnitude of the lung oedema induced by scorpion venom. It is concluded that the release of vascular permeability factors, such as platelet-activating factors, leukotrienes, and prostaglandins may play a role in the induction of acute lung oedema by scorpion venom in rats.

Heparin or a PAF antagonist (BN-52021) prevents the acute pulmonary edema induced by Tityus serrulatus scorpion venom in the rat.

Experiments were performed in pentobarbital-anesthetized rats, to study the mechanism of the acute pulmonary edema induced by Tityus serrulatus scorpion venom. In control rats injection of venom (50 micrograms/100 g, i.v.) induced arterial hypertension and lung edema (lung/body index or LBI equal to 1.01 +/- 0.09). In rats pretreated with heparin (100 IU/100 g 30 min previously) the venom induced similar hypertensive effects, but no edema was detected (LBI = 0.63 +/- 0.06, P > 0.05). Similarly, in rats pretreated with the PAF antagonist BN-52021 (0.5 mg/100 g, i.v., 30 min previously), the venom-induced hypertension was not modified but the acute pulmonary edema was prevented (LBI = 0.67 +/- 0.08, P > 0.05). It is concluded that PAF plays an important role on the genesis of pulmonary edema induced by scorpion venom in the rat. It is suggested that the inhibitory action of heparin could be related to a decrease in the vascular permeability in the lungs.

[Dyslipidemia and some risk factors in the population outside of the metropolitan region of São Paulo, SP-Brazil. A pilot study]. / Dislipidemias e alguns fatores de risco associados em uma população periférica da Região Metropolitana de São Paulo, SP-Brasil. Um estudo piloto.

A survey of the prevalence of lipemic disorders and some risk factors associated with them (obesity, hypertension and alcoholism), in a representative sample of the population of 20 years of age and over in a locality typical of the peripheral zone of the Greater S. Paulo Region, Brazil, both in terms of the poverty of the population and with regard to the lack of public sources such as sewage, transport and housing, is undertaken. The following results were obtained: a) the prevalence of one risk factor was about 55%, and of two or more associated risk factors was of approximately 9% in the age group from 20 to 39. There was found to be a prevalence of about 51% and 57%, respectively of two or more associated risk factors for the age groups from 40 to 59 and 60 years of age and over; b) the prevalence of lipemic disorders proper was of about 49%, 58% and 57% respectively, for the age groups of 20 to 39, 40 to 59 and 60 years of age and over. In these cases the most prevalent risk factors among men were alcoholism and hypertension, either isolatedly or associated with obesity, and among women the most prevalent was obesity, alone or associated with hypertension; c) the most prevalent lipemic disorder was due to HDL-cholesterol, mainly among the younger people. The prevalence lower-than-normal HDL-cholesterol, was of about 28% and of "other lipemic disorders" was of 22% in the age group between 20 and 39 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)