RESUMEN
The contribution of the lymphatic system to the absorption and systemic bioavailability of Micrurus fulvius venom after subcutaneous (SC) administration was assessed using a central lymph-cannulated sheep model. Micrurus fulvius venom was administered either by intravenous bolus (IV) or subcutaneous injection (SC) in 12 sheep with and without thoracic duct cannulation and drainage. Venom concentration in serum and lymph was determined by a sandwich enzyme-linked immunosorbent assay (ELISA) in samples collected over a 6-hour period and in tissues harvested at the end of the experiment. Pharmacokinetic parameters were determined by a non-compartmental analysis. In the lymphatic cannulated group, over the 6 hours after the venom was administered, 69% of administered dose was accounted for in blood (45%) and lymph (25%). Negligible levels of venom were detected in organs and urine implying that the steady state observed after SC administration is maintained by a slow absorption process. Comparison of kinetics of the thoracic duct cannulated and non-cannulated groups showed that lymphatic absorption contributed in an important way to maintenance of this steady state. These results show that the limiting process in the pharmacokinetics of Micrurus fulvius venom following SC administration is absorption, and that the lymphatic system plays a key role in this process.
Asunto(s)
Venenos Elapídicos/farmacocinética , Elapidae , Sistema Linfático/metabolismo , Oveja Doméstica/metabolismo , Animales , Área Bajo la Curva , Disponibilidad Biológica , Transporte Biológico , Venenos Elapídicos/administración & dosificación , Femenino , Semivida , Inyecciones Intravenosas , Inyecciones Subcutáneas , Masculino , Ovinos , Distribución TisularRESUMEN
THE TITLE COMPOUND [SYSTEMATIC NAME: 5-(trifluoro-meth-oxy)-1H-indole-2,3-dione], C9H4F3NO3, crystallized with two mol-ecules in the asymmetric unit. Inter-molecular N-Hâ¯O hydrogen bonds link the mol-ecules to form layers parallel to the ab plane. In addition, π-π stacking inter-actions are observed with a centroid-centroid distance of 3.721â (1)â Å. The near planarity of the two isatin ring systems is illustrated by by the maximum deviations of 0.023â (1) and 0.025â (1)â Å for the N atom in each case.
RESUMEN
In the title compound, [Re(2)(CH(3)O)(2)(CO)(6)(C(4)H(6)N(3)O)], the two Re(I) atoms are linked by a methoxo and methanolato bridge, as well as by a creatinine ligand that coordinates in a bidentate fashion. Three fac-carbonyl ligands occupy the rest of the slightly distorted octa-hedral geometry around each Re(I) atom. The bridging methanolato and methoxo ligands are bent out of the Re(2)O(2) plane by 49.2â (4) and 47.8â (3)° respectively. This is normally associated with a methanolato-bridging-type coordination rather that the more planar methoxo-type bridging. Furthermore, the creatinine bridging molecule is very slightly distorted from the Re(2)N(2)C plane, indicating that the pyrazolo N atom bonded to the Rh(I) atom is not protonated. Charge balance can thus only be attained if one assumes a positional disorder for the methanolato/methoxo H atom. All attempts to locate disordered protons around these O atoms were unsuccessful. Four hydrogen bonds, one N-Hâ¯O and three C-Hâ¯O, are observed in the structure. The mol-ecules pack in a head-to-head and tail-to-tail fashion when viewed along the c axis, in alternating columns.
RESUMEN
In the title compound, C(15)H(11)NO(2), two C-Hâ¯O hydrogen bonds are observed in the crystal structure, as well as π-π stacking with a centroid-centroid distance of 3.623â (2)â Å. The planarity of the two ring systems is illustrated by very small deviations of all the atoms from these planes [largest deviations = 0.003â (3) and 0.010â (3)â Å for the phenyl and fused-benzene rings, respectively]. The dihedral angle between these two planes is 77.65â (9)°.
RESUMEN
In the crystal of the title hydrated molecular salt, C(6)H(10)N(2) (2+)·SO(4) (2-)·H(2)O, N-Hâ¯O and O-Hâ¯O hydrogen bonds link the mol-ecules into layers parallel to the ab plane. C-Hâ¯O hydrogen bonds are observed both within these layers and between mol-ecules and ions in adjacent layers.
RESUMEN
The title compound, [Re(4)(µ(3)-OH)(4)(CO)(12)]·4C(5)H(5)N, crystallizes with one tetranuclear rhenium(I) cubane-like molecule and four pyridine mol-ecules in the asymmetric unit. The coordination environment of each Re(I) atom is distorted octahedral. Four intra-molecular O-Hâ¯N and four inter-molecular C-Hâ¯O hydrogen-bond inter-actions are observed. Relatively strong hydrogen bonds are found between the hydrogen-bond donor (µ(3)-OH) and acceptor (basic N atom of pyridine), with Nâ¯O distances between 2.586â (10) and 2.628â (10)â Å. Inter-cube distances of 9.873â (2) and 12.376â (3)â Å are observed.
RESUMEN
We studied some biochemical, toxic and immunological characteristics of the venoms of Bothrops atrox, Bothrops brazili and Lachesis muta, Viperidae responsible for most of the bites of venomous snakes in French Guiana. Chromatographic (HPLC) and electrophoretical profiles (SDS-PAGE), lethal, hemorrhagic, defibrinogenating, coagulant, thrombin like, proteolytic, fibrino(geno)lytic and phospholipase activities were studied. In addition, the neutralization of some toxic activities conferred by four antivenins was compared. The chromatographic and electrophoretic profiles were different for the three venoms, showing differences between Bothrops and L. muta venoms. In general, bothropic venoms showed the highest toxic and enzymatic activities, while the venom of L. muta showed the lowest lethal, hemorrhagic and coagulant activities. The enzymes of bothropic venoms responsible for gelatinolytic activity were around 50-90 kDa. All the venoms were able to hydrolyze a and beta chains of the fibrinogen, showing different patterns of degradation. Although all the antivenoms tested were effective to various degrees in neutralizing the venom of B. brazili and B. atrox, neutralization of L. muta venom was significantly better achieved using the antivenom including this venom in its immunogenic mixture. For the neutralization of L. muta venom, homologous or polyvalent antivenoms that include the "bushmaster" venom in their immunogenic mixture should be preferred.
Asunto(s)
Antivenenos/uso terapéutico , Venenos de Serpiente/clasificación , Venenos de Serpiente/toxicidad , Animales , Mordeduras y Picaduras/tratamiento farmacológico , Mordeduras y Picaduras/epidemiología , Venenos de Crotálidos/toxicidad , Guyana Francesa/epidemiología , Humanos , Pruebas de Neutralización , Venenos de Víboras/toxicidadRESUMEN
A range of fac-[Mn(CO)3(L,L'-Bid)(H2O)](n) (L,L'-Bid = neutral or monoanionic bidentate ligands with varied L,L' donor atoms, N,N' and N,O, 1,10-phenanthroline, 2,2'-bipyridine, 2-picolinate, 2,4-quinolinate; n = 0, +1) has been synthesized and the methanol substitution has been investigated for the first time. The complexes were characterized by UV/vis, IR and NMR spectroscopy and X-ray crystallographic studies of the compounds fac-[Mn(CO)3(Bipy)(H2O)][CF3SO3] () and fac-[Mn(CO)3(Phen)(H2O)][CF3SO3] () are reported. A two order-of-magnitude of activation for the methanol substitution is induced as manifested by the second order rate constants with (N,N'-Bid) < (N,O-Bid). Forward and reverse rate and stability constants from slow and stopped-flow UV/vis measurements (k1, M(-1) s(-1); k-1, s(-1); K1, M(-1)) for pyridine as entering nucleophile are as follows: fac-[Mn(CO)3(Phen)(CH3OH)](+) (2.39 ± 5) × 10(-3), (1.5 ± 0.3) × 10(-5), 159 ± 32; fac-[Mn(CO)3(2,4-QuinH)(CH3OH)] (4.5 ± 0.2), (4 ± 1) × 10(-2), 113 ± 29. Activation parameters (ΔH, kJ mol(-1); ΔS, J K(-1) mol(-1)) from Eyring plots for entering nucleophiles as indicated are as follows: fac-[Mn(CO)3(Phen)(CH3OH)](+) (bromide ions) 66.7 ± 0.6, -27 ± 2; (pyridine) 80 ± 3, -25 ± 11; fac-[Mn(CO)3(Pico)(CH3OH)] (bromide ions) 68 ± 2, -24 ± 5. A dissociative interchange mechanism is proposed.
Asunto(s)
Manganeso/química , Donantes de Óxido Nítrico/química , Compuestos Organometálicos/química , Cristalografía por Rayos X , Ligandos , Manganeso/metabolismo , Donantes de Óxido Nítrico/metabolismo , Compuestos Organometálicos/metabolismoRESUMEN
The immunochemical cross-reactivity and neutralizing capacity of four crotalinae antivenoms consisting in equine F(ab')2 fragments and available in Argentina (bothropic Bivalent, against Bothrops alternatus and B. neuwiedii venoms; bothropic Tetravalent, against B. alternatus, B. neuwiedii; B. jararaca and B. jararacussu venoms; bothropic crotalic Trivalent, against B. alternatus, B. neuwiedii and Crotalus (C.) durissus terrificus venoms and anticrotalic against C. d. terrificus venom) were studied against B. alternatus, B. ammodytoides; B. jararaca; B. jararacussu, B. moojeni; B. neuwiedii and C. d. terrificus venoms. SDS-PAGE analysis of the Bothrops venoms showed protein bands of high (>40 kDa) medium (20-40 kDa) and low (<15 kDa) molecular weights, while that of C. d. terrificus exhibited a large amount of material with molecular weight of 15.0 kDa or lower. Immunoblotting showed a high cross-reactivity of all the major protein bands with all the antivenoms (even heterologous) tested. All the antivenoms were effective in neutralizing the lethal activity of the venoms tested, and in some cases (B. jararaca and B. jararacussu) heterologous antivenoms exhibited similar neutralizing capacity than the homologous ones. In spite of the differences in biochemical composition and pharmacology, Bothropic antivenoms displayed a significant neutralizing capacity on lethal activity of C. d. terrificus venom. In addition, all the antivenoms (including the anticrotalic) were highly effective in neutralizing the hemorragic, necrotizing, procoagulant, and proteolytic activities. The antivenoms tested produced different degrees of inhibition of phospholipase A2 activity, which exhibited a certain specificity but was also related to the enzyme content in the venom.
Asunto(s)
Antivenenos/uso terapéutico , Bothrops , Venenos de Crotálidos/inmunología , Crotalus , Mordeduras de Serpientes/terapia , Animales , Antivenenos/inmunología , Argentina , Coagulación Sanguínea/inmunología , Reacciones Cruzadas , Gelatina/metabolismo , Humanos , Ratones , Pruebas de NeutralizaciónRESUMEN
The hemorrhagic activity of Bothrops (B.) alternatus, B. ammodytoides, B. jararaca, B. jararacussu, B. moojeni and B. neuwiedii venoms from specimens captured in Argentina was assayed after i.d. injection to mice. The hemorrhagic haloes produced by each venom had different color intensities, although no significant differences were observed by measurement of the average diameters or the weight of the excised hemorrhagic haloes. Conversely, important differences were found by measuring the amount of hemoglobin extracted from excised hemorrhagic haloes of similar size produced by different venoms. The relationship between the amount of hemoglobin extracted and the weight of the excised hemorrhagic haloes was linear, with a slope (hemoglobin released per gram of hemorrhagic halo) characteristic for each venom, and proportional to the potency. On this basis, the activity of B. alternatus, B. ammodytoides and B. jararaca is similar, about 1.5 times higher than that of B. jararacussu and B. moojeni venoms and threefold higher than that of B. neuwiedii venom. Thus, measurement of the of hemoglobin released provides additional information in comparative studies, and may be used to assess the antihemorrhagic potency of antivenoms.
Asunto(s)
Bothrops , Venenos de Crotálidos/toxicidad , Hemorragia/inducido químicamente , Animales , Venenos de Crotálidos/administración & dosificación , Relación Dosis-Respuesta a Droga , Hemoglobinas/metabolismo , Hemorragia/sangre , Inyecciones Intradérmicas , Ratones , Peroxidasas/sangreRESUMEN
A study on the venom yield of snakes from Argentina over a three year period was carried out on adult specimens of Bothrops alternatus (n = 74); Bothrops neuwiedii (n = 127); Bothrops ammodytoides (n = 30); Bothrops moojeni (n = 14); Bothrops jararaca (n = 14); B. jararacussu (n = 6); Crotalus durissus terrificus (n = 120) and Micrurus spp. (n = 6) as well as with 12 specimens of newborn C. d. terrificus kept in captivity. While for each species there was a positive correlation between venom yield and number of snakes milked, the correlation with the snake's body weights after individual milkings was even better, suggesting that the size of the snakes is more important in determining the venom yield than the number of snakes milked or the specimen's sex. Individual milkings indicated that, in addition to the snake size, when the amount of venom is normalized per 100 g body weight there is a species specific difference in venom yield. It follows the order B. jararacussu > B. moojeni approximately = B. jararaca approximately = B. alternatus > B. neuwiedii> Micrurus spp approximately = B. ammodytoides> C. d. terrificus. Although the venom yield per 100 g body weight of newborn C. d. terrificus specimens is 2-fold higher than that of adults, no correlation was observed between venom yield and body weight.
Asunto(s)
Venenos de Serpiente/análisis , Serpientes/fisiología , Factores de Edad , Animales , Animales Recién Nacidos , Argentina , Peso Corporal , Bothrops/fisiología , Venenos de Crotálidos/análisis , Crotalus/fisiología , Elapidae/fisiología , Femenino , Masculino , Factores SexualesRESUMEN
Bothrops ammodytoides, the smallest representative of this genus, is found only in Argentina. Venom was extracted from thirty adult specimens (35-70 cm in length, 90-300 g in weight) captured in the Province of Buenos Aires and kept in captivity. Venom yield was 3-30 mg. SDS-PAGE showed strong bands at 14.0; 23-25; 45; 54 and 63 kDa and weak bands at 17.0; 30.0; 40.0 and 85.0 kDa. Toxic activities were: LD50 (intravenous, mice) 0.5+/-0.2 microg/g; minimal procoagulant dose on human plasma (MPD-P) 35+/-2 mg/l; and minimal defibrinogenating dose (MDD, mice) 6-12 microg. Hemorrhagic and/or necrotic activities appear to play a major role in lethality; minimal hemorrhagic dose (MHD, mice) is 10+/-2 microg/g and minimal necrotizing dose (MND, mice) is 38+/-5 microg. The LD50, MPD-P and MND are among the lowest in venoms from Bothrops species found in Argentina. B. ammodytoides venom exhibited high proteolytic and phospholipase A2 activities. Most of the B. ammodytoides venom components cross-react with Bivalent Bothropic antivenom (Instituto Nacional de Producción de Biológicos ANLIS Dr. G. Malbrin, against B. alternatus and B. neuwiedii venoms). One ml of antivenom neutralizes 1.2 mg of B. ammodytoides venom.
Asunto(s)
Bothrops/fisiología , Venenos de Crotálidos/enzimología , Venenos de Crotálidos/toxicidad , Animales , Antivenenos/farmacología , Coagulación Sanguínea/efectos de los fármacos , Western Blotting , Cromatografía en Gel , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Eritrocitos/efectos de los fármacos , Hemólisis/efectos de los fármacos , Hemorragia/inducido químicamente , Hemorragia/patología , Inmunoquímica , Dosificación Letal Mediana , Ratones , Músculo Esquelético/patología , Mordeduras de Serpientes/patologíaRESUMEN
A series of structures of trans-dichlorobis(triphenylarsine)platinum(II), recrystallized from four different solvents, have been characterized by X-ray crystallography and were shown to crystallize as different solvates (same metal complex, different crystallization solvents). Their geometric differences induced by packing and solvent molecules were analysed with half-normal probability plots and root-mean-square deviations. The recrystallization solvents used in the investigation were 1,1,1-trichloroethane, dichloromethane, 1,2-dichloroethane and benzene, and the following crystallization modes were obtained. From 1,1,1-trichloroethane the metal complex crystallizes without solvent as trans-[PtCl2(AsPh3)2] in P2(1)/n with Z = 2, a = 9.271 (2), b = 19.726 (4), c = 9.830 (2) A, beta = 111.83 (3)degrees, V = 1668.8 (6) A3, R = 0.0262, and from dichloromethane with two solvent molecules as trans-[PtC12(AsPh3)2].2CH2C12 in Pbca with Z= 4, a = 20.582 (4), b = 8.146 (2), c = 23.491 (5) A, V = 3938.5 (14) A3 and R = 0.0316. From dichloroethane it crystallizes with one solvent molecule as trans-[PtC12(AsPh3)2].C2H4C12 in P1 with Z = 1, a = 9.390 (2), b= 9.548 (2), c = 11.931 (2) A, alpha = 109.70 (3), beta = 108.26 (3), gamma = 98.77 (3) , V= 915.6 (3) A3, R = 0.0390, and from benzene with half a solvent molecule as trans- [PtC12(AsPh3)2].0.5C6H6 in P2(1)/n with Z = 4, a = 11.778 (2), b = 18.712 (4), c = 16.647 (3) A, beta = 104.78 (3) , V= 3547.3 (12) A3 and R = 0.0303. In all four compounds platinum(II) coordinates to triphenylarsine and chloride in a pseudo-square-planar trans configuration. The Pt-As distances are in the range 2.4104 (4)-2.3923 (4) A and the Pt-C distances are in the range 2.309 (2)-2.2839 (9) A. The solvents have a large influence on the packing, resulting in different space groups or different occupancies in the same space group. Half-normal probability plots show that the largest geometric differences, within the metal complex, are in the bond and torsion angles around the As-C bonds. Very similar torsion angles were observed around the Pt-As bond for all the structures, except for one AsPh3 ligand in the benzene solvate, which differs by about 10 from the others. The metal-donor bond distance varies by as much as 0.019 and 0.025 A (95% confidence interval) for Pt-As and Pt-C1, respectively. The variations are essentially caused by intermolecular interactions. Packing efficiency is expressed as the volume filled by each metal complex in the unit cell and is calculated by subtracting the sum of the solvent molecule volumes from the total volume of the unit cell and then dividing by Z. The efficiency is largest in the dichloroethane solvate and smallest in the non-solvated compound, with a difference of approximately 22 A3 per metal complex.
RESUMEN
A common complication in patients with breast or prostate cancer is bone metastases causing pain. New radionuclide therapy methods have recently been proposed for palliation, including 186Re-hydroxyethylidene diphosphonate (186Re-HEDP). This paper reports on the local development of 186Re-HEDP and the biodistribution studied in animals for eventual use in patients. Adult dose was computed assuming a 70 kg standard man. The 186Re was labelled to HEDP using standard techniques. The biodistribution in five Chacma baboons (Papio ursinus) was studied. Doses ranging from 39.4 to 44.9 MBq kg(-1) (mean 43.6 +/- 2.8 MBq kg[-1]) were administered, corresponding to an adult human dose of 2960 MBq (80 mCi). Whole-body images of the animals were obtained with a dual-headed scintillation camera on an hourly basis for 6 h post-injection and then daily for 3 days. The bone, soft tissue, kidneys and urinary bladder were considered source organs and data from these organs were used in a compartmental model to obtain the mean residence times of the radionuclide in the different source organs. Radiation dose estimates for 186Re-HEDP were subsequently obtained with the MIRDOSE 3 program. The estimated absorbed radiation doses to some of the organs (expressed in mGy MBq[-l]) were as follows: bone surface 1.69; kidneys 0.09; liver 0.04; ovaries 0.04; red marrow 0.75; total body 0.12; urinary bladder wall 0.43. 186Re-HEDP yielded an effective dose of 0.17 mSv MBq(-1). The radiation dose delivered to the bone marrow in this study did not cause any detrimental effect to the baboons, indicating that locally produced 186Re-HEDP is suitable for clinical use.
Asunto(s)
Neoplasias Óseas/radioterapia , Neoplasias Óseas/secundario , Ácido Etidrónico , Compuestos Organometálicos/farmacocinética , Adulto , Animales , Huesos/metabolismo , Neoplasias de la Mama/radioterapia , Femenino , Humanos , Riñón/metabolismo , Masculino , Tasa de Depuración Metabólica , Cuidados Paliativos , Papio , Neoplasias de la Próstata/radioterapia , Radiofármacos/farmacocinética , Radiofármacos/uso terapéutico , Renio/farmacocinética , Renio/uso terapéutico , Distribución Tisular , Vejiga Urinaria/metabolismoRESUMEN
From September 1997 to June 2000 148 scorpions (118 findings) from the province and city of Buenos Aires were sent to the INPB and the CeNDIE. The species involved were Tityus trivittatus (32/33 found in the city) and Bothriurus bonariensis (81/85 found in the province around the city). The population spontaneous report of both species increased from January 1999 to May 2000. The climatic, spatial and social variables that could be involved in these phenomena were analyzed. The influence of the media was essential for the 'peak' generation. However, the amount of findings or accident by scorpions, as well as the area of the city colonized by T. trivittatus, have shown a progressive increase during the last decades.
Asunto(s)
Registros Médicos , Escorpiones , Accidentes , Animales , Animales Ponzoñosos , Argentina , Medios de Comunicación , Humanos , Lluvia , Estaciones del Año , Temperatura , UrbanizaciónRESUMEN
Human poisoning by Lepidoptera (butterflies, caterpillars and moths) has been known to physicians since old times. In the last few years, several factors have been causative of a great number of contacts between different stages of these insects and humans, occasionally with epidemic features. Species of medical interest in Argentina are those related to Megalopygidae, Saturniidae, Hemileucidae, Arctiidae, Notodentidae and Eucliedae families. Among all the species involved, it is important to describe the pathology produced by contact with Lonomia obliqua caterpillar (Saturniidae). The caterpillar Lonomia has several enzymes with procoagulant and fibrinolytic activities, acting on various components of the hemostatic system inducing hemorrhage that can lead to death. In the South of Brazil during the last years caterpillars of this butterfly caused a great number of cases of erucism including some deaths. In the past two years, there have been some cases of poisoning by Lonomia obliqua in Misiones, in the North East of Argentina on the border with Southern Brazil. This presents a potential risk, taking into account the poor knowledge regarding this insect and its venom in Argentina. This brief actualization gives some biochemical, clinical and epidemiologic tools towards understanding human Lepidopterism, an uncommon medical problem in this country.
Asunto(s)
Venenos de Artrópodos/envenenamiento , Lepidópteros , Animales , Hemorragia/etiología , Humanos , Larva , Mariposas Nocturnas , Periartritis/etiología , Síndrome , Urticaria/etiologíaRESUMEN
A male patient from Peru presented a nodule localized in the left costal region. All other clinical and laboratory data were normal. Upon biopsy, an helminth parasite emerged from the subcutaneous tissue, which presented a marked eosinophil infiltrate. The helminth was classified as a plerocercoid larva of Spirometra; the species was not determined. Since Spirometra are not common in Argentina, it is presumed that the patient was infested during his two year sojourn in the peruvian forest. Some epidemiological aspects are discussed. As far as we know, this is the first case of subcutaneous sparganosis and the second of sparganosis reported in Argentina.
Asunto(s)
Enfermedades Cutáneas Parasitarias/patología , Esparganosis/parasitología , Plerocercoide/anatomía & histología , Adulto , Animales , Argentina/epidemiología , Humanos , Masculino , Enfermedades Cutáneas Parasitarias/diagnóstico , Enfermedades Cutáneas Parasitarias/epidemiología , Esparganosis/diagnóstico , Esparganosis/epidemiología , Plerocercoide/fisiologíaRESUMEN
In the production of current therapeutic antisera used in Argentina for Bothrops snakebite, the Bothrops moojeni venom is not used as immunogen, since this snake is not considered a serious public health problem. Accidents caused by this species have not been reported in this country even though Bothrops moojeni is not unfrequent in some regions of Misiones. Despite the high degree of immunological cross reactivity found among the Crotalinae venoms and, in this particular case, among the venoms from the Bothrops Genus, there exists a significant intraspecific variation in venom composition, particularly in specimens arising from different geographic regions. In this study, the antivenoms prepared at the Instituto Nacional de Producción de Biológicos A.N.L.I.S. Dr. Carlos G. Malbrán have been tested for their immunochemical cross reactivity and neutralizing ability of enzymatic and toxic activities of venom from Argentinian specimens of Bothrops moojeni from Misiones. Immunological cross-reactivity was tested by double-immunoprecipitation, immunoelectrophoresis, Western-blot and ELISA. Neutralizing ability of antivenoms against proteolytic, indirect hemolytic activity, procoagulant activity, he-morrhagic activity and necrotizing activity. The Lethal Dose 50 was 1.5 mg/kg body weight; this value is located in the range to those obtained with the venom from Brazilian specimens. It was observed that all the antivenoms exhibited a strong immunochemical cross reactivity and that they were able to neutralize in different degree both, enzymatic and toxic activities of B. moojeni venom. From these results, it can be assumed that the antivenom tested could be employed successfully in cases of B. moojeni snakebites.
Asunto(s)
Antivenenos/farmacología , Bothrops , Venenos de Crotálidos , Pruebas de Neutralización , Animales , Dosificación Letal Mediana , RatonesRESUMEN
We have studied the immunochemical cross-reactivity and cross-neutralization of the lethal potency, hemorrhagic, necrotizing, procoagulant and (indirect) hemolytic activities of Bothrops jararacussu venom by the standard antivenoms produced in Argentina. These antivenoms are horse immunoglobulin F (ab')2 fragments from animals immunized with 1) Crotalus durissus terrificus venom (Monovalent Anticrotalic antivenom); 2) Bothrops alternatus and B. neuwiedii venoms (Bivalent Botropic antivenom); 3) B. alternatus, B. neuwiedii, B. jararaca and B. jararacussu venoms (Tetravalent Bothropic, or "Misiones" antivenom) and 4) B. alternatus, B. neuwiedii and C. d. terrificus venoms (Trivalent Botropic-Crotalic antivenom). In preincubation experiments, all the heterologous antivenoms neutralized the toxic and biological activities of B. jararacussu venom with a potency at least as high as the Tetravalent Botropic (i.e. the only homologous) antivenom, in which B. jararacussu venom was included as immunogen. These results suggest the possibility of using heterologous antibothropic antivenoms for the treatment of snake bites by B. jararacussu.
Asunto(s)
Antivenenos/uso terapéutico , Bothrops , Venenos de Crotálidos/inmunología , Mordeduras de Serpientes/terapia , Animales , Reacciones Cruzadas , Venenos de Crotálidos/administración & dosificación , Pruebas de Neutralización , RatasRESUMEN
CONTEXT: Therapy for snakebites relies on the application of antivenoms, which may be produced with different immunogenic mixtures of venom and possess different pharmaceutical characteristics. For these reasons, immunological cross-reactivity and heterologous neutralization were analyzed relative to the protein content of three antivenoms used in the Americas. METHODS: The antivenoms studied were composed of equine F(ab')2 fragments from animals immunized with Crotalinae venoms. The antivenoms were tested against venoms of seven pit viper species from Argentina, seven from Mexico, one from Costa Rica, and one from Colombia. RESULTS: Immunoblotting showed high cross-reactivity of all major protein bands with all the antivenoms tested. ELISA results also showed high cross-reactivity among the different venoms and antivenoms, and a high heterologous neutralization was observed. The results can be interpreted in different ways depending on whether the reactivity is considered in terms of the volume of antivenom used or by the amount of protein contained in this volume of antivenom. The antivenoms with high immunochemical reactivity and neutralizing capacity were those with higher protein content per vial; but when doses were adjusted by protein content, antivenoms of apparently lower neutralizing capacity and immunochemical reactivity showed at least similar potency and reactivity although volumetrically at higher doses. CONCLUSION: Protein content relative to neutralization potency of different products must be taken into account when antivenoms are compared, in addition to the volume required for therapeutic effect. These results show the importance of obtaining high-affinity and high-avidity antibodies to achieve good neutralization using low protein concentration and low-volume antivenoms.