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[Bites by snakes in the genus Bothrops: a series of 3,139 cases].

Medical records of 3,139 patients bitten by Bothrops snakes and attended at Vital Brazil Hospital (HVB) from 1981 to 1990 were reviewed. They were more frequent in males (75.7%). In 1,412 cases (45.0%) the snake was classified by species, and 1,376 were B. jararaca, 20 B. jararacussu, 11 B. neuwiedi, 2 B. moojeni, 2 B. alternatus e 1 B. pradoi. The most frequent bitten anatomic regions were: foot (47.5%) and hand (21.3%). Tourniquet was used in 38.2% of the cases and its frequency fell down during the study period (p < 0.05). The clinical features at the bite site were: pain (95.6%), swelling (95.4%), ecchymosis (56.1%), blisters (13.8%), necrosis (16.5%), and abscess (11.0%). Systemic manifestations were: bleeding (12.3%), acute renal failure (1.6%), and shock (0.7%). There were blood coagulation disorders in 1,730 (57.9%) of the 2,990 cases. There were 21 amputations (0.7%) and 9 deaths (0.3%). The average serum dose that was used in treatment fell down during the study period (p < 0.001).

Adolescent↗

Sites and mechanisms of antibiotic-induced neuromuscular block: a pharmacological analysis using quantal content, voltage clamped end-plate currents and single channel analysis.

Since the original observation of Vital Brazil and Corrado (1957) concerning the antibiotic induced neuromuscular block produced by streptomycin, there has been considerable interest in the mechanisms responsible for not only neuromuscular block but also the effects of antibiotics on different systems. We used the voltage clamped end-plate of transacted skeletal muscle to examine the concentration-dependent actions of several groups of antibiotics. The aminoglycoside antibiotics, neomycin and streptomycin, were both more effective at reducing quantal release of acetylcholine (ACh) than interacting with the postjunctional ACh receptor-channel complex. Neomycin was approximately 10 X more potent prejunctionally than streptomycin and the prejunctional effects of each antibiotic were reversed competitively by raising extracellular calcium. Both neomycin and streptomycin also had postjunctional actions at higher concentrations. Neomycin interacted with the open state of the ACh receptor ion channel complex while streptomycin blocks the ACh receptor. The lincosamide antibiotics, lincomycin and clindamycin produced their neuromuscular block postjunctionally by interacting with the open state of the ACh-receptor channel complex. Clindamycin is approximately 20 X more effective at blocking the open channel than was lincomycin. Using cell attached patch clamp recordings in cultured rat myotubes, we demonstrated a lincosamide-induced block of open ion channels with clindamycin having a much slower unblocking rate than lincomycin. Using epimers of the lincosamides, we demonstrated that lipophilicity of the molecule, rather than stereochemical considerations, is important for open channel blockade affecting primarily the "off" rate of channel blocking. This mechanism appears important for not only the lincosamide antibiotics but also for the postjunctional actions of the aminoglycoside antibiotics, particularly neomycin.

Animals↗

Aminoglycoside antibiotics as a tool for the study of the biological role of calcium ions. Historical overview.

Beginning with the pioneering work of Vital-Brazil and Corrado (1957), which suggested a possible interaction between aminoglycoside antibiotics (AGA) and calcium ions at the neuromuscular junction, the authors review the studies that demonstrated the existence of a competitive antagonism between AGA and calcium ions. In view of the low liposolubility of AGA and their inability to cross biological membranes, this antagonism seems to occur exclusively at calcium-binding sites at the level of the outer opening of calcium channels of the N-subtype, which are also the sites of interaction of omega-conotoxin. Being highly water soluble, AGA are easily removed from their binding sites with a consequent rapid reversal of their effects, a factor of primary importance to explain their wide use as tools in the pharmacological analysis of the study of the biological role of calcium ion on the membrane's outer surface. This use has advantages over the use of inorganic di- and trivalent cations such as Mg2+, Mn2+, Cd2+, Ni2+, La3+, etc., since the latter, though they are considered to be the most specific competitive antagonists of calcium ions, may induce biphasic effects due to their ability to cross the membranes and replace calcium and/or increase intracellular calcium concentration. The performance of AGA is also superior when compared with the so-called "specific" organic calcium antagonists--verapamil and nifedipine derivatives--since the latter, in addition to inducing possible biphasic effects, antagonize calcium in a non-competitive manner. Finally, the authors remark that AGA-Ca2+ antagonism relevance is not limited only to basic aspects and that it may have therapeutic implications since it provides alternatives for reducing the toxic adverse effects of this important group of antibiotics.

Aminoglycosides↗

[Changes in blood coagulation time in patients bitten by young and adult Bothrops jararaca snakes].

Three hundred and forty eight cases of bites by adult Bothrops jararaca (group A) were admitted to the Hospital Vital Brazil between 1975 and 1984. These cases were compared to 623 cases of bites by young snakes of the same species (group B) during the same period and at the same hospital. There was no difference between groups regarding age or time between bite and admittance to the hospital. However in group B blood incoagulability was more frequent when compared to group A. We conclude that bites caused by young Bothrops jararaca are more likely to cause blood incoagulability in humans than bites caused by adult Bothrops jararaca.

Adolescent↗

[Vital Brasil].

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Brazil↗

[Vital Brasil].

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Brazil↗

Mode of action of Phoneutria nigriventer spider venom at the isolated phrenic nerve-diaphragm of the rat.

The effects of Phoneutria nigriventer venom on muscle contraction and bioelectrical potentials were investigated in the rat phrenic nerve-diaphragm muscle preparation. The venom caused a non-uniform depolarization of the diaphragm muscle fiber membrane. This effect was abolished by tetrodotoxin or reduction of the sodium concentration in the bath fluid. The increase in the frequency of miniature end-plate potentials induced by the venom was also suppressed by tetrodotoxin. These results indicate that the venom activates the voltage-dependent sodium channel in muscle and nerve cell membranes. All the effects of the venom on the phrenic nerve-diaphragm muscle preparation (i.e. increase in twitch tension, delay in twitch relaxation, initial tonic contraction of short duration, spontaneous small phasic contractions, blockade of neuromuscular transmission, repetitive firing in nerve and muscle fiber membranes) can be explained on the basis of its action in the sodium channel. Nearly all of these effects are caused by discharges of repetitive action potentials in the nerve and/or muscle fiber membranes.

Action Potentials↗

Prevalence of virulence-associated genes in clinical and environmental Vibrio cholerae strains isolated in Brazil between 1991 and 1999.

Genes located on the CTX element and the Vibrio cholerae pathogenicity island (VPI) were investigated in 297 clinical V. cholerae O1 and 76 environmental O1 and non-O1 isolates from Brazil between 1991 and 1999. RAPD analysis suggested that serogroup O1 strains regardless of clinical or environmental source were clonal while non-O1 strains showed greater diversity. PCR analysis showed that 71% of O1 clinical isolates had a complete set of CTX element target genes (ctxA, ctxB, zot and ace) and 68% a complete set of the VPI genes studied (orf1, aldA, tagA, tcpA, toxT and int genes). The results also showed that 72.4% of environmental O1 isolates possessed ctxA, ctxB, zot and ace genes while environmental non-O1 strains rarely possessed virulence genes. Our data are consistent with the hypothesis that the CTX element and the VPI can have a mosaic structure in some V. cholerae strains, genotype diversity is due to the circulation of virulence genes which are more commonly found in O1 strains in Brazil. This study also shows that the aquatic environment is a potential source for virulence genes and toxigenic V. cholerae during epidemic periods.

Bacterial Outer Membrane Proteins↗

Neostigmine in the treatment of snake accidents caused by Micrurus frontalis: report of two cases (1).

Antivenom in order to be effective in the treatment of coral snake accidents must be injected very soon after the bite owing to the rapid rate of absorption of the venom neurotoxins. As this is not always possible, other forms of treatment besides serotherapy must be employed to avoid asphyxia and death. Neostigmine and artificial respiration are used for this purpose. Neostigmine restores neuromuscular transmission if the venom-induced blockade results from a reversible interaction of its neurotoxins with the end-plate receptors. This is the mechanism of the neuromuscular blockade produced by the venom of M. frontalis snakes from centereastern and southern Brazil, and Argentine. Neostigmine is able, therefore, to antagonize the blockade, and has been shown to be very effective in the treatment of the experimental envenomation of dogs and monkeys. In the present communication, two cases of M. frontalis accidents treated with antivenom and neostigmine are reported. In both, neostigmine was successful in producing regression of the paralysis, confirming the effectiveness shown in the treatment of the poisoning induced in animals by M. frontalis venom.

Adult↗

Effect of 4-aminopyridine on end-plate receptor desensitization caused by carbachol.

The effect of 4-aminopyridine on receptor desensitization was investigated in the isolated rat diaphragm by measuring transmembrane potential in the end-plate region. When 4-aminopyridine was added to the bath before carbachol, the depolarization produced by the agonist was permanent, that is 4-aminopyridine completely inhibited the receptor desensitization produced by prolonged exposure of the receptors to carbachol. When it was added after carbachol in the phase in which the membrane had already repolarized, the end-plate region depolarized. Therefore, 4-aminopyridine was also able to reverse the receptors from the desensitized state to the resting non-desensitized one. The effect of 4-aminopyridine was concentration-dependent. Calcium antagonized the effect of 4-aminopyridine. 4-Aminopyridine also reversed the receptors from their desensitized state to the resting one in the isolated and chronically denervated rat hemidiaphragm. The known action of the aminopyridines cannot explain the effect of 4-aminopyridine described here. It is suggested that it is caused by an action on either the receptor-ionic channel complex or the lipids of the postjunctional membrane surrounding it.

4-Aminopyridine↗