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[effect of bradkinin-potentiating snake venom peptides and c-terminal pentapeptide fragment of bradkinin on carboxypeptidase n and kiniase activities of human blood serum].effects of bradikinin-potentiating peptides (bpp5a and bppb), which are identical to peptides from bothrops jararaca and agkistrodon halys blomhoffii snake venom, and pentapeptide c-terminal bradikinin fragment on carboxypeptidase n and kinase activities in human blood serum are studied. it is found that bpp5a and bppb at concentrations of 5-10(-4) m and 2.5-10(-4) m respectively do not inhibit the hydrolysis of hippuryl-l-lysine and hippuryl-l-argininic acid by carboxypeptidase n and at a conce ...1975173428
the spectrophotometric determination of human serum carboxypolypeptidase with angiotensin converting enzyme-like activity.1. a colorimetric method was developed for the direct chemical assay of human carboxypeptidase a (carboxypolypeptidase; ec 3.4.12.2) with angiotensin converting enzyme-like activity in serum or plasma, with the substrate analogue glycyl-l-histidylglycine and the angiotensin converting enzyme substrate angiotensin i (a-i). this method was based on the spectrophototometric determination of histidylglycine and histidyl-leucine, products of the hydrolysis of glycyl-l-histidylglycine and a-i respecti ...1976179749
role of converting enzyme in the cardiovascular and adrenal cortical responses to (des-asp1)-angiotensin i.(des-asp1)-angiotensin i, angiotensin ii and iii were evaluated for pressor activities in conscious nephrectomized rats and for steroidogenic actions in rat adrenal zona glomerulosa. the pressor effect of this angiotensin nonapeptide was similar to that found with mole-equivalent doses of angiotensin iii (one-third as active as angiotensin ii) and was significantly attenuated by pretreatment with the 0. jararaca nonapeptide converting enzyme inhibitor. hence, (des-asp1)-angiotensin i is a substr ...1976184474
components of the renin-angiotensin system in the plasma of bothrops jararaca.by means of high voltage electrophoresis experiments it could be demonstrated that the dipeptide hydrolase present in the plasma of bothrops jararaca is similar to the angiotensin i converting enzyme of human plasma. therefore, angiotensin i can be considered as a probable natural substrate for this potent snake peptidase in contrast to bradykinin, which is excluded in that case, since this snake plasma was previously found to be deficient in intrinsic kinin releasing system. on the other hand, ...1978205119
inhibition of brain angiotensin-1 converting enzyme by bothrops jararaca nonapeptide (sq 20881) and a prolyl analog (sq 14225). 1978209137
pathogenic factors involved in renovascular hypertension. state of the art.the complex hormonal action of angiotensin ii in the long-term control of blood pressure or sodium metabolism, or in renal hypertension, is not completely understood. structure-activity relations with analogues of angiotensin ii gave information about the functions responsible for pressor and myotropic response in the molecule that led to the synthesis of competitive antagonists of this hormone. these antagonists, however, show variable agonist/antagonist ratios in different species or different ...1977327161
the hydrolysis of biologically active peptides by bovine lung tissue factor (thromboplastin).tissue factor apoprotein and relipidated tissue factor preparations extensively hydrolyze bradykinin, lys-bradykinin, met-lys-bradykinin, substance p, [asp1, ile5]-angiotensin ii, [asp1, ile5]-angiotensin i, and human fibrinopeptide a while acting more slowly on [sar1, ile5]-angiotensin ii, [me2gly1, ile5]-angiotensin ii, bradykinin potentiating pentapeptide from b. jararaca, luteinizing hormone-releasing hormone, melanocyte stimulating hormone-release-inhibiting factor (pro-leu-gly-nh2), and ox ...1976787991
des-asp1-angiotensin i: a metabolite of angiotensin i in the perfused feline adrenal.the administration of radioactive angiotensin i to the retrogradely perfused feline adrenal gland caused a brisk discharge of catecholamines. recovery of the labelled decapeptide and metabolites in the adrenal effluent fluid was complete in 5 min. radioimmunoassay of this perfusate revealed that most of the peptide remained as angiotensin i, but chromatographic and electrophoretic evaluation indicated that greater than 68% of the peptide had been metabolized to des-asp1 -angiotensin i. the abse ...1976954820
synthesis and properties of new bradykinin potentiating peptides.in a study of the relationship between structure and activity of bradykinin potentiating peptides (bpp), six analogs and homologs of peptides occurring in the venoms of bothrops jararaca and agkistrodon halys blomhoffii were synthesized and assayed in the isolated guinea pig ileum and rat uterus. none of the peptides had bradykinin-like activity and their bradykinin potentiating activity was much greater in the guinea pig ileum than in the uterus. the following observations were made with the gu ...19751120978
neutralization of the oedematogenic activity of bothrops jararaca venom on the mouse paw by an antibothropic fraction isolated from opossum (didelphis marsupialis) serum.the pharmacological modulation of mice paw oedema produced by bothrops jararaca venom (bjv) has been studied. intraplantar injection of bjv (1-30 micrograms/paw) produced a dose- and time-related oedema, which was maximal 30 min after injection, reduced gradually thereafter and disappeared over 48 h. bjv heated at 100 degrees c for 5 or 15 min blocked local hemorrhage and caused partial inhibition of its oedematogenic activity. the bjv oedema was not inhibited by the anti-histamine meclizine, th ...19921295374
broad substrate specificity of snake venom fibrinolytic enzymes: possible role in haemorrhage.we found previously that two fibrinolytic enzymes (jararafibrases i and ii) purified from bothrops jararaca venom displayed a haemorrhagic activity. to elucidate the mechanisms involved and the role of the enzymatic activity in haemorrhage, the enzymatic properties of the purified enzymes were examined. the substrate specificity of the enzymes was determined using type i collagen, type iv collagen, gelatin, laminin and fibronectin as substrates. the enzymes degraded type iv collagen, gelatin, la ...19921336630
circulating vasotocin in the snake bothrops jararaca.1. there is biochemical and pharmacological evidence to suggest the presence of vasotocin in the blood and plasma of the snake bothrops jararaca (bj). 2. xe-64 extracts from bj blood showed antidiuretic and hypotensive activities in rats and a contractile effect on rat isolated uterus, which was totally dialysable and inhibited by thioglycollate. 3. extracts from bj whole plasma presented an antidiuretic activity which was only partially dialysable. 4. the plasma extracts also showed oxytocic pr ...19921356701
angiogenic activity of paf and inhibition of blood flow by bothrops jararaca venom in a mouse sponge model. 19921377548
purification, cloning, and molecular characterization of a high molecular weight hemorrhagic metalloprotease, jararhagin, from bothrops jararaca venom. insights into the disintegrin gene family.a large hemorrhagin, jararhagin, has been cloned from a bothrops jararaca venom gland cdna expression library. the cdna sequence predicts a 421-amino acid residue molecule with strong amino acid sequence homology and similar domain structure to hr1b, a high molecular weight hemorrhagic metalloprotease isolated from trimeresurus flavoviridis (habu) venom. like hr1b, jararhagin contains enzyme, disintegrin, and cysteine-rich carboxyl-terminal regions. in the disintegrin region, the arg-gly-asp seq ...19921385408
antivenom and biological effects of ar-turmerone isolated from curcuma longa (zingiberaceae)a potent antivenom against snakebite was isolated from curcuma longa, a plant commonly used in traditional brazilian medicine. the fraction consisting of ar-turmerone neutralized both the hemorrhagic activity present in bothrops jararaca venom, and the lethal effect of crotalus durissus terrificus venom in mice. immunological studies demonstrated that this fraction also inhibited the proliferation and the natural killer activity of human lymphocytes.19921440627
neutralization of different activities of venoms from nine species of bothrops snakes by bothrops jararaca antivenom.antivenoms are the usual treatment in cases of systemic envenoming by bothrops snakes. however, the neutralization of each venom component by the antivenom is not well established. bothrops jararaca antivenom, produced in rabbits, recognizes the venoms of nine different bothrops species with high elisa antibody titres. western blot analysis showed that almost all antigens present on both homologous and heterologous venoms are recognized. neutralization tests were performed using whole antivenom ...19921488768
pioneers of anti-venomous serotherapy: dr vital brazil (1865-1950).dr vital brazil was a great humanitarian and pioneer of medical science. his main work arose from his concern with poisonous snakebite accidents to labourers working the land. vital brazil estimated that, at the beginning of this century, deaths due to crotaline snakebites in the state of são paulo, brazil, were nearly 3000 per year, representing a mortality rate of about 25%, the majority being due to bothropic envenomation. after reading a report of calmette's anti-naja serum, vital brazil rai ...19921519249
a nontoxic derivative of bothrops jararaca venom suitable to generate antibodies against the native venom.bothrops jararaca venom was toxoided by stepwise iodination with cold iodine, and doses up to 30 ld50 were non-lethal by i.p. route (bicalho et al., 1990). groups of mice injected chronically with the native, or the iodinated venom, have been subjected to histological examination. in the native group, in the spleen, around the white pulp, an acellular, amorphous eosinophilic substance, metachromatic to methyl violet, pas positive, and dichroic to congo red under polarized light, was present. str ...19921606895
systemic haemorrhage in rats induced by a haemorrhagic fraction from bothrops jararaca venom.the main haemorrhagic fraction of bothrops jararaca venom, showing in vitro fibrinogenolytic activity and an inhibitory effect on platelets aggregation induced by collagan, was studied in rats. development of coagulopathy and/or haemorrhage was studied 2 hr after s.c. injection of batroxobin, b. jararaca whole venom and its haemorrhagic fraction. incoagulable blood, together with low fibrinogen levels, were found only in rats injected with batroxobin and whole venom; thrombocytopenia alone was d ...19911796474
immunological studies with the venom of the scorpion tityus serrulatus.1. we describe a "sandwich" enzyme-linked immunosorbent assay (elisa) sensitive to quantities of scorpion (tityus serrulatus) venom (tsv) in the range of 1-3 ng/ml sample. 2. cross-reactivity with the venom from the rattlesnake crotalus durissus terrificus and with venoms from several snakes of the bothrops genus was detected only at concentrations higher than 1 microgram/ml sample. 3. a conventional elisa is also described for the detection of antibodies against tsv. 4. analysis by western blot ...19911823231
[domain structure of human von willebrand factor, and its modulators involved in the platelet adhesion process in vitro].von willebrand factor (vwf), a macromolecular glycoprotein synthesized in endothelial cells and megakaryocytes circulates in blood as heterogenous multimers and plays a critical role in the formation of platelet plugs. vwf is composed of an identical subunit with a molecular weight (mw) of 270 kda, which is held together by disulfide bonds. functional domains of vwf for factor viii, heparin, platelet glycoprotein (gp) ib, collagen, and gp iib/iiia locate in this order from the n-to c-terminus of ...19911870263
coagulopathy and haemorrhage in human victims of bothrops jararaca envenoming in brazil.thirty-four patients envenomed by bothrops jararaca in brazil were studied. of these, 20 (59%) had incoagulable blood associated with local and/or systemic bleeding and 10 of the 20 were thrombocytopenic. among 14 patients with coagulable blood, 6 (43%) had bleeding symptoms and 3 (21%) were thrombocytopenic. high levels of von willebrand factor (vwf), plasminogen activator inhibitor type 1 (pai-1) and tissue type plasminogen activator (t-pa) antigens were also recorded in some patients with sys ...19911949067
[epidemiology and clinical picture of accidents by adult and young snakes bothrops jararaca].four hundred and fifteen cases of bites by adult bothrops jararaca (group a) were admitted to the hospital vital brasil between 1981 and 1987. these cases were compared to 562 cases of bites by young snakes of the same species (group b) during the same period and at the same hospital. in group b blood incoagulability was more frequent when compared to group a. however in group a bites in the leg, use of tourniquet, tecidual damage (blister, necroses and abscess), were more frequent when compared ...19902135490
the effect of stepwise iodination on biological properties of bothrops jararaca venom.by titrating 5 mg of native venom with aliquots of a 2 x 10(-2) m iodine monochloride solution, neutralization of lethality by the incorporation of iodine was found with 200 +/- 5 microliters of solution, and above, up to 310 +/- 10 microliters, when saturation with iodine was attained. doses up to 1500 micrograms (equivalent to 32 ld50 of native venom), where injected i.p. in mice without lethal effects. proteolytic, phospholipase a2 and esterolytic activities were greatly reduced, but a low ac ...19902187279
hyperosmotic sodium chloride partially blocks the effects induced by bothrops jararaca venom on vascular permeability and hemorrhage in the rat.the effect of the administration of hyperosmotic nacl (2 ml, 7.8% nacl, iv) on hemorrhage and vascular permeability changes induced by bothrops jararaca venom in rats was determined 30 min after venom injection. this treatment given immediately after subcutaneous venom injection significantly reduced the hemorrhagic manifestations by 33%. the increase in vascular permeability was significantly reduced when the animals were pretreated with hyperosmotic saline or mannitol 15 min before receiving t ...19902207444
[bacterial flora of the oral cavity, fangs and venom of bothrops jararaca: possible source of infection at the site of bite].culture of fang, fang sheath and venom of fifteen healthy freshly captured bothrops jararaca were analyzed. the bacteria most frequently encountered were group d streptococci (12 snakes), enterobacter sp. (6), providencia rettgeri (6), providencia sp. (4), escherichia coli (4), morganella morganii (3) and clostridium sp. (5). the bacteria observed are similar to those found in the abscesses from bothrops bitten patients. since these snake mouth bacteria may be inoculated during the snake bite, b ...19902259834
enzyme-linked immunosorbent assay for the detection of bothrops jararaca venom.this study reports an enzyme-linked immunosorbent assay for detecting bothrops jararaca venom in fluids, employing the sandwich method with biotin/avidin amplification. the assay exhibits high accuracy in correlating optical densities with venom concentrations (r = 0.98), high reproducibility, low background and limited cross-reactivity with venom from other snake genera. nevertheless, it was unable to distinguish among venoms from different bothropic species. using this method we evaluated the ...19902260103
isolation and characterization of hemorrhagic, myonecrotic and edema-inducing toxins from bothrops insularis (jararaca ilhoa) snake venom.bothrops insularis snake venom was fractionated by gel filtration on sephadex g-150 followed by ion-exchange chromatography on sp-sephadex c-25. two active fractions were purified to homogeneity: (1) siii-spi, approximate mol. wt 32,000 and n-terminal amino acid residue val. this fraction showed esterase activity on tame, edema-inducing activity on the rat hind paw and contractile activity on the isolated guinea pig ileum. the latter two activities were antagonized by benadryl plus methysergide; ...19902343462
bothrops jararaca snake venom: effects on platelet aggregation.crude venom from bothrops jararaca has procoagulant, platelet aggregating and phospholipase a2 (pla2) activities. by chromatographic fractionation of the venom on sephacryl s-200 it was possible to separate these three activities and to show that distinct protein components are involved. the procoagulant activity appears to involve the synergistic action of several components and was not further studied in the present work. the aggregating activity results from the action of two components: 1) a ...19902353342
studies on blood coagulation and fibrinolysis in patients bitten by bothrops jararaca (jararaca).the blood coagulation and the fibrinolytic systems of nine patients envenomed by bothrops jararaca in são paulo (brazil) were studied. five of the accidents were caused by young snakes (less than 50 cm). on admission, four patients had non-clotting and three partially-clotting blood. fibrinogen levels were decreased due to the thrombin-like activity of the venom as expected. consequent secondary activation of the fibrinolytic system was evident from the low levels of alpha-2-antiplasmin and the ...19902402749
the humoral immune responses of patients bitten by the snake bothrops jararaca (jararaca).the isotype and specificity of antibodies produced by patients bitten by b. jararaca and submitted to serum therapy were studied. the igg anti-b. jararaca antibodies have large individual dispersion, starting to appear 10 days after the first bite and increasing to at least 80 days after the bite. igm antibodies appeared sooner than igg antibodies but disappeared about 20 days after the bite. secondary responses induced by an additional bite were characterized by a fast and higher igg antibody r ...19902402767
new aspects on inflammatory reactions and cough following inhibiton of angiotensin converting enzyme.the first inhibitor of angiotensin converting enzyme (ace) was found in and isolated from the venom of the south american pit viper bothrops jararaca. this was done after it was discovered that bites of the pit viper inhibit the breakdown of a proinflammatory peptide, bradykinin, in prey. treatment with newly developed orally active ace-inhibitors has been reported to cause symptoms such as adverse skin reactions, angioneurotic oedema, coughs and, in asthmatics, rapidly decreasing lung function. ...19882466391
purification of botrocetin from bothrops jararaca venom. analysis of the botrocetin-mediated interaction between von willebrand factor and the human platelet membrane glycoprotein ib-ix complex.interaction of von willebrand factor (vwf) with its platelet receptor only occurs in vitro in the presence of a modulator such as ristocetin. we have recently confirmed that the human platelet membrane glycoprotein (gp) ib-ix complex is the receptor involved in the ristocetin-dependent binding of vwf by reconstitution with the purified components [berndt, m.c., du, x., & booth, w.j. (1988) biochemistry 27, 633-640]. we have now developed a similar solid-phase reconstitution assay using an altern ...19892557900
effect of the substance(s) released in vitro by the interaction of bothrops jararaca (bj) venom or trypsin and bj plasma on bj blood pressure and uterus. 19892558513
a bothrops jararaca plasma cysteine-proteinase inhibitor related to mammalian kininogen.a kininogen-like protein was purified from bothrops jararaca plasma by deae-sephadex ion-exchange and carboxy-methyl-papain-sepharose affinity chromatography. the molecular weight, estimated by sds-gel electrophoresis, is about 100,000 and a species of about 75,000 is formed after incubation with horse urinary kallikrein. after incubation with trypsin, only traces of biological activity were detected in tests on guinea pig ileum. the purified protein inhibits papain and bromelain, does not corre ...19892633847
pharmacological evaluation of rat paw oedema induced by bothrops jararaca venom.the mechanism involved in the genesis of the rat paw oedema caused by intraplantar (ipl) injection of bothrops jararaca venom (bjv) has been investigated. ipl injection of bjv (1 to 30 micrograms/paw) caused a dose- and time-related oedematogenic effect. oedema was maximal within 1 h after bjv injection, was partially reduced at 6 h and disappeared completely within 24 h. no systemic effect was observed. previous heating of bjv at 100 degrees c for 3 to 30 min caused a significant inhibition (25 ...19892660497
carrageenan-induced acute inflammatory response in chicks.carrageenan from two commercial sources was used in varying concentrations to evoke an acute inflammatory response in the foot pad of chickens. oedema formation and increased vascular permeability were less severe using this experimental model than with turpentine-induced injury. inflammation was monophasic, of short duration and apparently mediated by histamine and serotonin as their respective antagonists diminished the response. prostaglandins seemed to play only a minor role as indomethacin ...19892704884
immunological comparison of hemorrhagic principles present in venoms of the crotalinae and viperinae subfamilies.antibodies were raised against hemorrhagic factors hf1, hf2 and hf3 isolated from the venom of bothrops jararaca and nhfa,b from the venom of bothrops neuwiedi. crude venoms of different species of snakes were assayed with the rabbit antisera specific for the hemorrhagic factors. results of immunodiffusion, neutralization of hemorrhagic activity and micro-complement fixation indicated that there is an immunological relationship between the venom hemorrhagic components of the bothrops species and ...19892718188
intraocular infusate with hemocoagulase for the control of bleeding during vitreous surgery.the effects of hemocoagulase in injectable form (hemocoagulating enzymatic fraction of south american snake bothrops jararaca venom provided by ravizza) on the control of intraocular bleeding during vitreous surgery were evaluated in rabbit eyes. intraocular infusion solution with hemocoagulase (1 nih thrombin unit/100 ml of bss plus) significantly reduced the bleeding time. electroretinogram b-wave and electroretinogram c-wave showed no abnormality. infusate with hemocoagulase (1 nih thrombin u ...19892795941
functional and histopathological renal changes induced in rats by bothrops jararaca venom.1. ninety-eight adult female rats were injected with 14 micrograms/g b. jararaca venom intraperitoneally to determine functional and histopathological renal changes. 2. glomerular filtration rate, renal plasma flow, filtration fraction, osmolar clearance, water transportation in collecting ducts, urinary sodium excretion, fractional sodium excretion, albuminuria, urinalysis, plasma creatinine, urinary output and mean arterial pressure were studied before and 24 and 48 h after venom administratio ...19892804475
kallikrein-kinin system in the plasma of the snake bothrops jararaca.1. bothrops jararaca venom (bjv) caused a fall in the carotid artery blood pressure of the anaesthetized snake. this effect was tachyphylactic and was potentiated by captopril, a kininase ii inhibitor; it was partially antagonized by promethazine plus cimetidine and was not affected by atropine. 2. similar hypotensive effects were obtained by administration of trypsin or a partially purified bjv kininogenase to the snake. 3. incubation of bothrops jararaca plasma (bjp) with trypsin released a su ...19892804549
[human erythrocyte prolyl endopeptidase ii hydrolysing teprotid, an inhibitor of peptidyl peptidase from snake venom].the paper is concerned with the action of 1200-fold purified prolylendopeptidase ii (pe-e) from human erythrocytes and the action of highly purified prolyl-d-l-alanine peptidyl hydrolase (pe-a) from bovine adenohypophysis on teprotide (bpp9a, sq 20881), a nonapeptide from venom of the snake bothrops jararaca--an inhibitor of peptidyl dipeptidase a (carboxycathepsin). both the purified preparation pe-e and highly purified preparation pe-a split teprotide at the bonds pro3-arg4 and pro5-gln6. the ...19852985149
alterations of the blood coagulation system after accidental human inoculation by bothrops jararaca venom.blood coagulation studies carried out on 78 patients up to 30 h after they were bitten by bothrops jararaca snakes demonstrated clotting defects in 37 patients which included afibrinogenemia, reduced levels of prothrombin, of factors v and viii, thrombocytopenia and activation of the fibrinolytic system. factor ix and x levels were within normal range for all patients. these in vitro data suggest that the disseminated intravascular clotting observed in vivo following envenomation may be triggere ...19863103794
release of creatine kinase from skeletal muscles by bothrops venoms: heparin potentiation of inhibition by antivenin.the glycosaminoglycan, heparin (50 micrograms/ml) inhibited the increase in creatine kinase (ck) released from rat extensor digitorum longus (edl) muscles exposed to bothrops jararaca venom (150 micrograms/ml). heparin (2 micrograms/ml) and polyvalent antivenin (0.5 microliter/ml) did not affect the increase in ck release induced by exposure of the muscles to 50 micrograms/ml b. jararacussu venom. simultaneous exposure of the muscles to venom plus heparin (2 micrograms/ml) plus antivenin (0.5 or ...19883228636
isolation and characterization of a thrombin-like enzyme from the venom of the snake bothrops insularis (jararaca ilhoa).a thrombin-like enzyme (i-sii-r) from the venom of the brazilian snake bothrops insularis (jararaca ilhoa) was purified to homogeneity by gel filtration on sephadex g-150 followed by precipitation of contaminating proteins with half-saturated nacl and two further gel filtrations under the same conditions. i-sii-r showed specific activities of 820 clotting units/mg protein and 530 tame units/mg protein (a 23-fold purification) and a single precipitation band against antibothropic horse antiserum ...19873433290
interaction of bothrops venoms and antivenin on the release of creatine kinase from skeletal muscle.a polyvalent antivenin (5 microliter/ml) inhibited the increase in creatine kinase (ck) release from rat extensor digitorum longus muscles exposed to the venoms of b. jararacussu (20 micrograms/ml) or b. jararaca (150 micrograms/ml). the increase in plasma ck activity induced by intramuscular injection of b. jararacussu venom (2.5 micrograms/g) into mice was reduced by pretreatment with antivenin and was abolished by preincubation of the venom with the antivenin. changes in ck release from isola ...19873455262
comparison of immunological, biochemical and biophysical properties of three hemorrhagic factors isolated from the venom of bothrops jararaca (jararaca).compared to the crude velonom of bothrops jararaca, which needs 5000 ng to produce a hemorrhagic spot of 1 cm2 on rabbit skin, the isolated hemorrhagic factors hf1, hf2 and hf3 require 100, 20 and 15 ng of protein, respectively. although these hemorrhagic factors possess different biochemical and biophysical properties, they are immunologically related proteins. the hemorrhagic, as well as the proteolytic, activities of these factors are destroyed by edta, acidic ph or heat treatments.19863810664
the anticoagulant effect of bothrops castelnaudi snake venom (castelnaud's pit viper).an inhibitory effect of bothrops castelnaudi venom was observed on the following systems: prothrombin time, activated partial thromboplastin time, thrombin time, thromboplastin generation time, activation of factor x by russell's viper venom and russell's viper venom activated factor x (factor xa). this effect did not require previous incubation and was prevented by the addition of bothrops-antivenom. the prolonged activated partial thromboplastin time was not shortened by increased phospholipid ...19853895581
haemorrhagic and permeability increasing effects of 'bothrops jararaca' and other crotalidae venoms as related to amine or kinin release. 19744153369
[on various pharmacodynamic and biologic properties of venom of serpents of the genus bothrops (b. jararaca, b. atrox, b. lanceolatus and b. carribeaus)]. 19684306531
inhibition of angiotensin i converting enzyme by venom peptides.the synthetic analogues of three naturally occurring peptides from the venom of bothrops jararaca have been tested as inhibitors of angiotensin converting enzyme activity in two systems. they have widely differing absolute potencies but the relative potencies are similar in the two systems. the high inhibitory potency of the nonapeptide is compatible with a non-competitive type of inhibition.19714332776
angiotensin-converting enzyme inhibitors from the venom of bothrops jararaca. isolation, elucidation of structure, and synthesis. 19714334402
inhibition of the conversion of angiotensin i to ii and potentiation of bradykinin by small peptides present in bothrops jararaca venom. 19724341481
inhibition of homogeneous angiotensin-converting enzyme of rabbit lung by synthetic venom peptides of bothrops jararaca. 19734351262
the inactivation of bradykinin in the pulmonary circulation of isolated lungs.1. the isolated lungs of guinea-pigs, rats and dogs, perfused with krebs bicarbonate solution via the pulmonary artery, inactivated 95, 98 and 99% respectively of the bradykinin infused through them.2. this inactivation process was not inhibited by 2-mercaptoethanol (1 mm) or edta (500 mum).3. the inactivation was inhibited by 2:3-dimercaptopropanol (100 mum), n-ethylmaleimide (100 mum), and several of the bradykinin potentiating peptides from bothrops jararaca, in both natural and synthetic for ...19724625922
the bradykininase activities of extracts of dog lung.1. homogenates of dog lungs freed from blood inactivate bradykinin. the bradykininase activity is present in soluble and particulate subcellular fractions.2. the fraction with the highest relative specific activity is that sedimenting between 8,700 g and 78,000 g. this fraction has been studied in more detail.3. there is evidence for two bradykinin inactivating enzymes in this fraction with apparent k(m) values of 7.5 mum and 120 mum.4. the bradykininase activity is not dependent on the concentr ...19734723801
effects of bothrops jararaca venom on fibrin formation in vitro. 19734740702
the proteolytic action of arvin on human fibrinogen.1. human fibrinogen was subjected to proteolysis by enzyme preparations (clinical arvin and irc-50 arvin) from the venom of agkistrodon rhodostoma. 2. irc-50 arvin releases three peptides from fibrinogen, and these were identified as fibrinopeptides ap, ay and a. 3. the less purified ;clinical' arvin releases, in addition to fibrinopeptides ap, ay and a, small amounts of two heptapeptides derived from fibrinopeptides ap and a, probably because it contains another enzyme as well as arvin. 4. no f ...19705529716
hemodynamic effects of bradykinin potentiated by a factor contained in the "bothrops jararaca" venom. comparative results with eledoisin. 19675616572
[antagonism of non-narcotic analgesics to the release of plasma kinins by b. jararaca venom and pancreatic kallikrein]. 19675631688
potentiation of bradykinin and eledoisin by bpf (bradykinin potentiating factor) from bothrops jararaca venom. 19655870517
potentiation of circulatory effects of bradykinin by a factor contained in the bothrops jararaca venom. 19676030787
the kininases of bothrops jararaca plasma.evidence is presented to suggest that kininase activity of bothrops jararaca plasma is due to the presence of at least three distinct enzymes: a carboxypeptidase b type enzyme, similar to that found in human plasma in that its activity is enhanced by co2+ (1 x 10(-4) m); a carboxypeptidase b type enzyme whose activity is unaffected by co2+, and an enzyme which cleaves bradykinin to liberate phe-arg as the major peptide fragment formed. the latter enzyme is responsible for the major kininase acti ...19806100945
pulmonary angiotensin-converting enzyme and its inhibition: a historical survey.angiotensin-converting enzyme, the peptidase hydrolysing angiotensin i to angiotensin ii and first discovered in plasma, has been demonstrated in lung tissue on the luminal surface of endothelial cells lining pulmonary blood vessels. because converting enzyme is the final activating step in the renin-angiotensin system its inhibition prevents the pressor and other effects of increased renin secretion. lung converting enzyme activity is inhibited specifically by a nonapeptide (bpp9a:sq 20 881) co ...19806258881
characterization of two hemorrhagic factors isolated from the venom of bothrops neuwiedi (jararaca pintada).two hemorrhagic factors were isolated from the venom of bothrops neuwiedi (jararaca pintada) by ammonium sulfate precipitation followed by chromatography on deae-sephadex a-50 and deae-cellulose de-32, gel filtration on sephadex g-100 and polyacrylamide-gel electrophoresis. these factors were named neuwiedi hemorrhagic factors nhfa and nhfb. they are acidic proteins of pi 4.2-4.3 and consist of single polypeptide chains of molecular weights 46,000 and 58,000, respectively, as determined by sodiu ...19846427978
the inactivating effect of bothrops jararaca and waglerophis merremii snake plasma on the coagulant activity of various snake venoms.plasmas of the poisonous snake bothrops jararaca and of the non-poisonous snake waglerophis merremii were not clotted by various snake venoms. these plasmas also inactivated venom clotting activity on human plasma. this effect was absent in snake serum and in heated snake plasma. the active fraction was isolated by gel chromatography from b. jararaca plasma and corresponded to the fibrinogen-containing fractions. it is suggested that the inactivation by snake plasma of the venom coagulant activi ...19836857708
the haemorrhagic exudate and its possible relationship to neurogenic inflammation.the morphological effects of an aqueous solution of nistatin, of clostridium septicum and tityus serrulatus toxins, of bothrops jararaca and agkistrodon piscivorus venoms on the vessels of the tendinous portion of the diaphragm were investigated in guinea-pigs. it was demonstrated that all these substances, when injected intrapleurally induced not only an increase in the permeability of venules but also haemorrhages originating at this segment of the microcirculation. red cells were shown to esc ...19807400880
suppression of the antivenom antibody response by serum therapy.1. the antivenom antibody response of mice injected with bothrops jararaca venom and receiving specific serum therapy was studied under different experimental conditions. balb/c mice (18-22 g) injected with venom (1.75 mg/kg) presented the clinical symptoms observed in patients bitten by b. jararaca and a high and long-lasting antivenom antibody response. 2. injection of 0.1 ml of horse antiserum to venom 15 min after venom administration abolished the symptoms induced by the venom and induced a ...19947513588
ineffectiveness of the inhibition of the main haemorrhagic metalloproteinase from bothrops jararaca venom by its only plasma inhibitor, alpha 2-macroglobulin.observations that a haemorrhagic metalloproteinase (jararhagin) from bothrops jararaca venom had less effect on platelets suspended in plasma than in washed platelet suspensions, suggested that plasma contains naturally occurring inhibitor(s) of this enzyme. by using radiolabelled jararhagin and crossed immunoelectrophoresis, we have demonstrated the binding of this enzyme to alpha 2-macroglobulin in plasma. sds-page analysis of this binding revealed the presence of radioactivity in four bands w ...19947520756
fibronectin and 130-kda molecule complex mimics snake venom botrocetin-like structure potentially modulating association between von willebrand factor and vascular vessel wall.we established seven hybridomas secreting monoclonal antibodies (moabs) against the venom from bothrops jararaca. six of them were demonstrated to specifically recognize botrocetin, a venom protein which binds with von willebrand factor (vwf) and induces platelet agglutination. two of them, bct4-3 and bct115-2 moabs, could significantly inhibit botrocetin binding with plasma vwf. bct4-3 could react slightly with a monolayer of human endothelial cells (ecs), and bct4-3 binding to ecs was drastica ...19957608121
molecular cloning and expression of catrocollastatin, a snake-venom protein from crotalus atrox (western diamondback rattlesnake) which inhibits platelet adhesion to collagen.a 50 kda protein that inhibits platelet adhesion to collagen has been isolated from snake venom of crotalus atrox (western diamondback rattlesnake) and has been named 'catrocollastatin'. the cdna cloning of catrocollastatin has been accomplished. a full-length cdna of 2310 bp with an open reading frame between nucleotides 51 and 1880 was obtained. the deduced amino acid sequence consists of 609 amino acids. the cdna-predicted amino acid sequence is highly similar to that of haemorrhagic metallop ...19957733877
university discoveries and intellectual property rights: from bothrops jararaca bradykinin potentiating peptides to angiotensin converting enzyme inhibitors.the academic basic research which led to the discovery of bradykinin potentiating peptides, the drug prototype for the new class of angiotensin converting enzyme inhibitors for the treatment of hypertension, is described. this case study is used to illustrate the situation of the academic scientist and his intellectual property rights for discoveries made at the university.19947749362
properties of fibrinogen cleaved by jararhagin, a metalloproteinase from the venom of bothrops jararaca.haemorrhagic metalloproteinases from bothrops jararaca and other venoms degrade vessel-wall and plasma proteins involved in platelet plug and fibrin clot formation. these enzymes also cause proteolytic digestion of fibrinogen which has been suggested to cause defective platelet function. fibrinogen degradation by jararhagin, a metalloproteinase from b. jararaca, and the effect of jararhagin fibrinogenolysis on both platelet aggregation and fibrin clot formation were investigated. jararhagin was ...19947831660
cdna cloning and deduced amino acid sequence of prothrombin activator (ecarin) from kenyan echis carinatus venom.the complete amino acid sequence of ecarin is deduced from the nucleotide sequence of a cdna clone isolated by screening a venomous gland cdna library of kenyan echis carinatus. the cdna sequence with 2379 base pairs encodes an open reading frame of 616 amino acids with a remarkable sequence homology to the putative precursor protein of trigramin from trimeresurus gramineus venom (61% identity) and a large hemorrhagin, jararhagin, from the pit viper bothrops jararaca venom (62% identity). thus, ...19957849037
edematogenic responses induced by bothrops jararaca venom in rats: role of lymphocytes.the intraplantar injection of bothrops jararaca venom (bjv) caused an edematogenic response in the rat which was of rapid onset, and reached a peak in about 60 min. the response was markedly attenuated in animals rendered leucopenic by the administration of amethopterin. this inhibition was partially reverted when leucopenic rats were given i.v. suspensions of lymphocytes. suspensions of neutrophils were ineffective. if the animals were submitted to an experimental obstruction of the thoracic du ...19947886700
microbiological studies of abscesses complicating bothrops snakebite in humans: a prospective study.forty patients with abscesses at the site of bothrops bite were evaluated. ten brought the snake responsible for the bite, bothrops jararaca in all cases. on admission a sample was collected from each case for aerobic and anaerobic culture, and no abscesses drained spontaneously. none of the patients had received antibacterial therapy at this time. the bacteria most frequently isolated were morganella morganii (23 patients), providencia rettgeri (7) enterobacter sp. (4), escherichia coli (3), gr ...19947940580
hyperalgesia induced by bothrops jararaca venom in rats: role of eicosanoids and platelet activating factor (paf).in this study we investigated the ability of bothrops jararaca venom (bjv) to induce hyperalgesia and the modulation of this effect by lipid mediators. it was found that intraplantar injection of bjv (1 to 25 micrograms) caused a dose and time-related hyperalgesia. the peak of the hyperalgesic response was 1 hr after injection of the venom and persisted for 24 hr with the higher dose. the bjv-induced hyperalgesia was markedly attenuated by dexamethasone. dexamethasone blocks the generation of bi ...19948052996
inhibition of the myotoxic and hemorrhagic activities of crotalid venoms by eclipta prostrata (asteraceae) extracts and constituents.the antimyotoxic and antihemorrhagic effects of eclipta prostrata (ep) and three of its constituents (wedelolactone, we; stigmaterol, st; and sitosterol, si) were investigated. the myotoxicity of crotalid venoms (bothrops jararaca, bothrops jararacussu and lachesis muta), purified myotoxins (bothropstoxin, bthtx; bothropasin; and crotoxin), and polylysine was quantified in vitro by the release rate of creatine kinase (ck) from rat or mouse extensor digitorum muscles, and in vivo by the plasma ck ...19948079371
purification and characterization of low molecular weight fibrinolytic/hemorrhagic enzymes from snake (bothrops jararaca) venom.two low molecular weight fibrinolytic/hemorrhagic enzymes, jararafibrase iii and jararafibrase iv, were purified from bothrops jararaca venom using a fast protein liquid chromatography system. the purified jararafibrase iii and jararafibrase iv were single chain proteins with molecular weights of 20,400 +/- 500 and 21,200 +/- 400, respectively, by sds-page. the isoelectric points of jararafibrase iii and jararafibrase iv were 9.4 and 6.9, respectively. the activity of the enzyme was inhibited by ...19938087204
purification and characterization of bothrombin, a fibrinogen-clotting serine protease from the venom of bothrops jararaca.a fibrinogen-clotting enzyme (bothrombin) was purified from the venom of bothrops jararaca. bothrombin showed m(r) values of 33,000 under nonreducing and 35,000 under reducing conditions on sds polyacrylamide gel electrophoresis and specific fibrinogen-clotting activity equivalent to 814-904 nih alpha-thrombin units/mg. diisopropyl fluorophosphate totally abolished its activity, but hirudin, a specific alpha-thrombin inhibitor, had negligible effect on bothrombin activity. unlike alpha-thrombin, ...19948110787
peptide t, a novel bradykinin potentiator isolated from tityus serrulatus scorpion venom.a bradykinin-potentiating peptide was isolated and characterized from venom of the scorpion tityus serrulatus by chromatographic techniques followed by biological assays. the complete amino acid sequence (13 residues) of peptide is presented. the peptide potentiated the contractile activity of bradykinin on the isolated guinea-pig ileum, and inhibited the hydrolysis of bradykinin by angiotensin-converting enzyme from b. jararaca plasma and the conversion of angiotensin i to angiotensin ii by kin ...19938212046
purification, physicochemical characterization and n-terminal-amino acid sequence of a phospholipase a2 from bothrops jararaca venom.snake venoms usually contain multiple molecular forms of phospholipase a2 enzymes (phosphatide acyl hydrolase, e.c. 3.1.1.4; pla2). phospholipases a2 induce a wide range of pharmacological effects which may depend or not on the hydrolysis of phospholipids. in this study, a pla2 from bothrops jararaca venom was purified to homogeneity by gel filtration on a sephacryl s-200 column, followed by fplc reverse-phase chromatography on a pep-rpc hr 5/5 column (yield 1.63% of venom protein). the pla2 act ...19938257916
c-type galactoside-binding lectin from bothrops jararaca venom: comparison of its structure and function with those of botrocetin.a ca(2+)-dependent type (c-type) galactoside-binding lectin was purified from venom of the snake bothrops jararaca by thiodigalactoside-sepharose affinity column chromatography. b. jararaca lectin is a disulfide-linked homodimer composed of 14-kda subunits. the n-terminal 55-residue amino acid sequence was determined and appeared to belong to the animal c-type lectin family. this 55-residue sequence showed 37% identity with botrocetin, an exogenous von willebrand factor modulator purified from t ...19948311467
randomized comparative trial of three antivenoms in the treatment of envenoming by lance-headed vipers (bothrops jararaca) in são paulo, brazil.in são paulo city, brazil, 121 patients with moderately severe envenoming by bothrops snakes (principally b. jararaca) were randomized for treatment with brazilian polyspecific bothrops antivenoms: instituto butantan (39 patients), instituto vital brazil (41), fundação ezequiel dias (funed) (41). the initial dose was four ampoules (40 ml) in 89 patients with less severe envenoming and eight ampoules (80 ml) in 32 patients with more severe envenoming. a second dose of four ampoules was required i ...19938327649
different clotting mechanisms of bothrops jararaca snake venom on human and rabbit plasmas.bothrops jararaca venom is approximately 3.5 times more effective at coagulating rabbit plasma than human plasma. to investigate this difference b. jararaca venom was treated with several enzymatic inhibitors and the minimum coagulant dose was determined both on plasma anticoagulated with sodium citrate or a mixture of sodium citrate and heparin, and on fibrinogen (both human and rabbit). on human plasma, the thrombin-like component of the venom accounted for c. 60% of the coagulant activity, su ...19938342171
bothrojaracin, a new thrombin inhibitor isolated from bothrops jararaca venom: characterization and mechanism of thrombin inhibition.a new thrombin inhibitor, bothrojaracin, has been identified and purified to homogeneity from the venom of bothrops jararaca, the most common venomous snake of south america. bothrojaracin has an isoelectric point of 4.2 and a molecular mass of 27 kda and is made of two distinct polypeptide chains of 15 and 13 kda, linked by disulfide bridges. purified bothrojaracin is devoid of phospholipase a2, amidolytic, or fibrino (geno)lytic activity. bothrojaracin forms a noncovalent complex with alpha-th ...19938399228
snakebite-induced acute renal failure: an experimental model.acute renal failure (arf) has been frequently reported after bites from the viperidae snake family. the lack of a reproducible animal model has hampered the study of renal damage mechanisms. intravenous injection of rats with 0.4 mg/kg of bothrops jararaca venom produced functional and morphologic changes similar to those observed in human snakebite-induced arf. there was an acute and significant decrease in the glomerular filtration rate, diuresis, and renal plasma flow. serum fibrinogen levels ...19938427392
primary structure of two-chain botrocetin, a von willebrand factor modulator purified from the venom of bothrops jararaca.the complete amino acid sequence and location of the disulfide bonds of two-chain botrocetin, which promotes platelet agglutination in the presence of von willebrand factor, from venom of the snake bothrops jararaca are presented. sequences of the alpha and beta subunits were determined by analysis of peptides generated by digestion of the s-pyridylethylated protein with achromobacter protease i or alpha-chymotrypsin and by chemical cleavage with cyanogen bromide or 2-(2'-nitrophenylsulfenyl)-3- ...19938430107
hematological changes induced by bothrops jararaca venom in dogs.the mechanism of consumption coagulopathy observed in cases of human envenomation by bothrops jararaca is well established. however, this mechanism may vary according to the animal species studied. in order to study both the clinical and laboratory aspects of bothropic envenomation in dogs, a sublethal defibrinating dose of venom (100 micrograms/kg) was given intravenously. a coagulopathy similar to that observed in humans - including fibrinogen depletion, consumption of factors ii, x, v and ant ...19958520523
isolation and characterization of jararaca gpib-bp, a snake venom antagonist specific to platelet glycoprotein ib.a platelet glycoprotein ib-binding protein (gpib-bp) was isolated from the snake venom of bothrops jararaca. jararaca gpib-bp showed a single band with m(r) of 30,000, and two distinct bands with m(r) of 17,000/13,000 under non-reducing and reducing conditions, respectively, on sds-polyacrylamide gel electrophoresis. jararaca gpib-bp itself induced neither platelet aggregation nor serotonin release from platelets, but specifically bound to gpib (40,629 +/- 2,521 molecules per normal platelet, wi ...19958585016
complete amino acid sequence and identification of the platelet glycoprotein ib-binding site of jararaca gpib-bp, a snake venom protein isolated from bothrops jararaca.jararaca gpib-bp, a snake venom protein composed of alpha and beta subunits purified from bothrops jararaca, binds to platelet glycoprotein (gp)ib and functions as a receptor blocker for von willebrand factor binding to gpib (fujimura, y., ikeda, y., miura, s., yoshida, e., shima, h., nishida, s., suzuki, m., titani, k., taniuchi, y., and kawasaki, t. (1995) thromb. haemostasis 74, 743-750). we present here the entire 142- and 123-residue amino acid sequence of the respective alpha and beta subu ...19968631868
determination of the neutralizing potency of horse antivenom against bothropic and crotalic venoms by indirect enzyme immunoassay.the use of elisa to determine antisnake venom potency of horse immune sera should provide benefits of costs and reproducibility compared to in vivo assays. in the present investigation we evaluated the correlation between elisa antibody levels and in vivo neutralization assays. for the indirect elisa method, 0.016 micrograms/well of bothrops jararaca or crotalus durissus terrificus venom were used to coat the plates and 100 microliters/well of each sample of antibothropic or anticrotalic venom s ...19958634680
pharmacological profile of rat pleurisy induced by bothrops jararaca venom.bothrops jararaca venom (30 micrograms/site) triggered a marked inflammatory reaction in the pleural cavity that was long-lasting and reproducible. in the first 1 h after pleurisy induction, a significant decrease of total and differential cell count was observed in comparison with control values, despite the gradual enhancement of fluid leakage. a significant increase of cell migration was observed after 3 h of pleurisy induction, due to mononuclear and neutrophil cells that peaked 8 h later an ...19968722506
[epidemiology of accidents due to bites of poisonous snakes: a study of cases attended in 1988].the attendance given to patients by ta specialized hospital, in s. paulo, brazil, during 1988 is studied. the study is based on the medical records of 322 patients and on questionnaires filled out by author during interviews with 209 patients or their companions. the 322 snake-bites occurred mainly between october and april, in the diurnal period, mainly in the afternoon. most of patients were adult males, mainly between 10 and 20 years of age. the parts of the body most frequently affected were ...19958731278
angiotensin-converting enzyme and enkephalinase in human breast cyst fluid.palpable breast cysts with an apocrine epithelial lining (type 1) are reported to be associated with a higher risk of developing breast cancer. the composition of breast cyst fluid (bcf) might include those factors involved in this increased risk. in this study peptidase activities that were active against the substrate [125i]metenkephalin-arg-phe were detected in bcf. the products were identified by reversed phase high-performance liquid chromatography (hplc) as [125i]tyr-gly-gly and [125i]met- ...19968795586
purification and characterization of bitiscetin, a novel von willebrand factor modulator protein from bitis arietans snake venom.we have screened 20 snake venoms and purified a novel snake venom protein, named bitiscetin, from bitis arietans venom that specifically binds to human von willebrand factor (vwf) and induces platelet agglutination. bitiscetin showed a heterodimeric structure composed of disulfide-linked alpha (16kda) and beta (13kda) subunits on sds-page and showed a basic nature with pi value of 9.1, in contrast to botrocetin (pi 4.6), a vwf modulator isolated from another snake (bothrops jararaca) venom. biti ...19968806626
isolation and identification of angiotensin-like peptides from the plasma of the snake bothrops jararaca.two distinct hypertensive peptides were purified and characterized from bothrops jararaca (bj) plasma incubated at ph 4, 37 degrees c, 24 hr. these peptides were active on rat and bj blood pressure, on rat isolated uterus, on guinea pig isolated ileum and on bj isolated duodenum. at the releasing conditions no further activities were found for kininases, angiotensinases or angiotensin converting enzymes. the peptides were purified by ethanol/ether extraction, sephadex g-25 gel filtration, semipr ...19968829801
amino acid sequence of a lectin-like protein from lachesis muta stenophyrs venom.the primary structure of the lectin-like protein from lachesis muta stenophyrs venom was deduced from analysis of the n-terminus and the sequence of peptides obtained after digestion with trypsin, arg-c enzyme, staphylococcus aureus v8 protease and endoproteinase asp-n. peptides generated by cleavage of the lectin with cyanogen bromide and o-iodosobenzoic acid were also sequenced. comparison of the complete 135 amino acid residues sequence with those of the lectin from the venom of crotalus atro ...19968843577
enhancement of plasma fibrinolysis in vitro by jararhagin, the main haemorrhagic metalloproteinase in bothrops jararaca venom.jararhagin, a haemorrhagic metalloproteinase from bothrops jararaca venom, plays an important role in systemic as well as local haemorrhage. in this study, the effect of jararhagin on the fibrinolytic system was investigated. the fibrinolytic activity of various kinds of animal plasmas was measured by the fibrin plate method. no activity was detected in plasma alone. however, after mixing plasma with jararhagin, strong fibrinolytic activity was recorded in guinea-pig, horse, dog, rabbit and huma ...19958866618
inhibition of angiotensin converting enzyme and potentiation of bradykinin by retro-inverso analogues of short peptides and sequences related to angiotensin i and bradykinin.there is pharmacological evidence indicating that, in addition to the inhibition of angiotensin converting enzyme (ace; ec 3.4.15.1), the potentiation of bradykinin (bk) responses may also involve the bk receptor or some binding site in the structures involved in the contractile response to this peptide. dipeptides such as val-trp and some of its analogues as well as tripeptide homologues, including total and partial retro-inverso peptides, were synthesized and assayed for their ability to inhib ...19968866827
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