RESUMO
INTRODUCTION: Bites by Phoneutria spp. spiders are common in Brazil, although only 0.5-1% result in severe envenomation, with most of these occurring in children. Cases of systemic envenomation in adults are very unusual, and no serum venom levels have been previously quantified in these cases. CASE REPORT: A 52-year-old man was bitten on the neck by an adult female Phoneutria nigriventer. Immediately after the bite, there was intense local pain followed by blurred vision, profuse sweating, tremors, and an episode of vomiting; 1-2 h post bite the patient showed agitation and a blood pressure of 200/130 mmHg, and was given captopril and meperidine. Upon admission to our service 4 h post bite (time zero - T0), his blood pressure was 130/80 mmHg with a heart rate of 150 beats/min, mild tachypnea, agitation, cold extremities, profuse sweating, generalized tremors, and priapism. The patient was treated with antivenom, local anesthetic, and fluid replacement. Most of the systemic manifestations disappeared within 1 h after antivenom. Laboratory blood analyses at T0, T1, T6, T24, and T48 detected circulating venom by ELISA only at T0, before antivenom infusion (47.5 ng/mL; cut-off, 17.1 ng/mL); his serum blood sugar was 163 mg/dL at T0. The patient was discharged on the second day with a normal arterial blood pressure and a follow-up evaluation revealed no sequelae. CONCLUSION: This is the first report of confirmed moderate/severe envenoming in an adult caused by P. nigriventer with the quantification of circulating venom.
Assuntos
Antivenenos/uso terapêutico , Picada de Aranha/fisiopatologia , Venenos de Aranha/intoxicação , Anestésicos Locais/uso terapêutico , Animais , Brasil/epidemiologia , Captopril/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Hipertensão/etiologia , Masculino , Meperidina/uso terapêutico , Pessoa de Meia-Idade , Picada de Aranha/tratamento farmacológico , Venenos de Aranha/farmacocinética , Aranhas , Fatores de TempoRESUMO
The blood-brain barrier (BBB) is responsible for selective flux of substances between blood and brain. The selective permeability of the BBB is crucial for the maintenance of the brain microenvironment homeostasis, and alterations in the barrier may be involved in many pathophysiological processes. Phoneutria nigriventer armed spider venom produces excitatory signals and symptoms in humans, and its recognized neurotoxic action suggests a potential ability to alter BBB permeability. The aim of the present study was to investigate the capacity of P. nigriventer venom (PNV) in promoting BBB breakdown in adult rats. After intravenous injection of 850 micro g/kg of the whole venom, BBB lesions were evaluated after 18 h to 9 days by ultrastructural methods using the extracellular tracer lanthanum nitrate. Clinical signs and symptoms of rats showed acute neurotoxicity, with some of the animals presenting convulsions, but which were clinically resolved by 12 h post-envenoming. The results showed that PNV is able to increase BBB permeability, particularly in the hippocampus. Changes were first detected in arterioles and post-capillary venules 18 h to 5 days after venom inoculation. The increased permeation of the extracellular tracer peaked on day 1, representing about 42% of the examined vessels (P<0.01). This appeared to occur by both transendothelial and intercellular routes, i.e., by pinocytic transport and through interendothelial junctions. Concomitantly, the surrounding tissue showed vasogenic edema and swollen astrocytic processes, without inflammatory infiltrates. The peak of the edema occurrence was observed on day 3, in about 60% of the vessels (P<0.001). Enhanced capillary permeability was observed on day 9, and affected 36% of all capillaries (P<0.05). The affected capillaries were characterized by increased number of pinocytotic vesicles, which, in addition, were filled with the extracellular tracer, but without visible transport through the interendothelial pathway. This study demonstrates that systemic PNV inoculation induces BBB breakdown through trans- and paracellular routes. It is concluded that BBB breakdown is an event not associated with the acute neurotoxicity exhibited by the rats.
Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/irrigação sanguínea , Encéfalo/efeitos dos fármacos , Permeabilidade Capilar/efeitos dos fármacos , Venenos de Aranha/farmacocinética , Animais , Encéfalo/patologia , Encéfalo/fisiopatologia , Encéfalo/ultraestrutura , Edema Encefálico/induzido quimicamente , Espaço Extracelular , Masculino , Microscopia Eletrônica , Síndromes Neurotóxicas/patologia , Síndromes Neurotóxicas/fisiopatologia , Ratos , Ratos WistarRESUMO
We have recently shown that the sphingomyelinase toxins P1 and P2 from the venom of the spider Loxosceles intermedia induce complement (C)-dependent lysis of autologous erythrocytes by induction of the cleavage of cell surface glycophorins through activation of an endogenous metalloproteinase facilitating the activation of the alternative pathway of C. Phospholipase D (PLD) from Corynebacterium pseudotuberculosis shows some degree of homology with the spider sphingomyelinases and can induce similar clinical symptoms to those observed after spider envenomation. The aim of this study was to investigate if the bacterial PLD-induced haemolysis of human erythrocytes was C dependent and if cleavage of glycophorins occurred. We show here that haemolysis of both PLD- and P1-treated human erythrocytes was C dependent, but while PLD-mediated haemolysis was dependent on activation of the classical pathway of C, P1 induced lysis via both the classical and alternative pathways. P1, but not PLD, induced cleavage of glycophorins and no change in expression of complement regulators was induced by either of the toxins. In both cases, annexin V binding sites were exposed, suggesting that the membrane asymmetry had been disturbed causing exposure of phosphatidylserine to the cell surface. Our results suggest that C susceptibility induced by L. intermedia and C. pseudotuberculosis PLD is a result of exposure of phosphatidylserine, and the higher potency of P1 toxin can be explained by its additional effect of cleavage of glycophorins.
Assuntos
Animais , Aranhas/classificação , Venenos de Aranha/farmacocinética , Intoxicação , Fosfolipase D/análise , Fosfolipase D/toxicidadeRESUMO
Tx1, a neurotoxin isolated from the venom of the South American spider Phoneutria nigriventer, produces tail elevation, behavioral excitation and spastic paralysis of the hind limbs after intracerebroventricular injection in mice. Since Tx1 contracts isolated guinea pig ileum, we have investigated the effect of this toxin on acetylcholine release, as well as its binding to myenteric plexus-longitudinal muscle membranes from the guinea pig ileum. [125I]-Tx1 binds specifically and with high affinity (Kd = 0.36 +/- 0.02 nM) to a single, non-interacting (nH = 1.1), low capacity (Bmax 1.1 pmol/mg protein) binding site. In competition experiments using several compounds (including ion channel ligands), only PhTx2 and PhTx3 competed with [125I]-Tx1 for specific binding sites (K0.5 apparent = 7.50 x 10(-4) g/l and 1.85 x 10(-5) g/l, respectively). PhTx2 and PhTx3, fractions from P. nigriventer venom, contain toxins acting on sodium and calcium channels, respectively. However, the neurotoxin PhTx2-6, one of the isoforms found in the PhTx2 pool, did not affect [125I]-Tx1 binding. Tx1 reduced the [3H]-ACh release evoked by the PhTx2 pool by 33%, but did not affect basal or KCl-induced [3H]-ACh release. Based on these results, as well as on the homology of Tx1 with toxins acting on calcium channels (omega-Aga IA and IB) and its competition with [125I]-omega-Cono GVIA in the central nervous system, we suggest that the target site for Tx1 may be calcium channels.