Machine learning for atrial fibrillation risk prediction in patients with sleep apnea and coronary artery disease.

Background: Patients with sleep apnea (SA) and coronary artery disease (CAD) are at higher risk of atrial fibrillation (AF) than the general population. Our objectives were: to evaluate the role of CAD and SA in determining AF risk through cluster and survival analysis, and to develop a risk model for predicting AF. Methods: Electronic medical record (EMR) database from 22,302 individuals including 10,202 individuals with AF, CAD, and SA, and 12,100 individuals without these diseases were analyzed using K-means clustering technique; k-nearest neighbor (kNN) algorithm and survival analysis. Age, sex, and diseases developed for each individual during 9 years were used for cluster and survival analysis. Results: The risk models for AF, CAD, and SA were identified with high accuracy and sensitivity (0.98). Cluster analysis showed that CAD and high blood pressure (HBP) are the most prevalent diseases in the AF group, HBP is the most prevalent disease in CAD; and HBP and CAD are the most prevalent diseases in the SA group. Survival analysis demonstrated that individuals with HBP, CAD, and SA had a 1.5-fold increased risk of developing AF [hazard ratio (HR): 1.49, 95% CI: 1.18-1.87, p = 0.0041; HR: 1.46, 95% CI: 1.09-1.96, p = 0.01; HR: 1.54, 95% CI: 1.22-1.94, p = 0.0039, respectively] and individuals with chronic kidney disease (CKD) developed AF approximately 50% earlier than patients without these comorbidities in a period of 7 years (HR: 3.36, 95% CI: 1.46-7.73, p = 0.0023). Comorbidities that contributed to develop AF earlier in females compared to males in the group of 50-64 years were HBP (HR: 3.75 95% CI: 1.08-13, p = 0.04) CAD and SA in the group of 60-75 years were (HR: 2.4 95% CI: 1.18-4.86, p = 0.02; HR: 2.51, 95% CI: 1.14-5.52, p = 0.02, respectively). Conclusion: Machine learning based algorithms demonstrated that CAD, SA, HBP, and CKD are significant risk factors for developing AF in a Latin-American population.

Cataloging Human PRDM9 Allelic Variation Using Long-Read Sequencing Reveals PRDM9 Population Specificity and Two Distinct Groupings of Related Alleles.

The PRDM9 protein determines sites of meiotic recombination in humans by directing meiotic DNA double-strand breaks to specific loci. Targeting specificity is encoded by a long array of C2H2 zinc fingers that bind to DNA. This zinc finger array is hypervariable, and the resulting alleles each have a potentially different DNA binding preference. The assessment of PRDM9 diversity is important for understanding the complexity of human population genetics, inheritance linkage patterns, and predisposition to genetic disease. Due to the repetitive nature of the PRDM9 zinc finger array, the large-scale sequencing of human PRDM9 is challenging. We, therefore, developed a long-read sequencing strategy to infer the diploid PRDM9 zinc finger array genotype in a high-throughput manner. From an unbiased study of PRDM9 allelic diversity in 720 individuals from seven human populations, we detected 69 PRDM9 alleles. Several alleles differ in frequency among human populations, and 32 alleles had not been identified by previous studies, which were heavily biased to European populations. PRDM9 alleles are distinguished by their DNA binding site preferences and fall into two major categories related to the most common PRDM9-A and PRDM9-C alleles. We also found that it is likely that inter-conversion between allele types is rare. By mapping meiotic double-strand breaks (DSBs) in the testis, we found that small variations in PRDM9 can substantially alter the meiotic recombination landscape, demonstrating that minor PRDM9 variants may play an under-appreciated role in shaping patterns of human recombination. In summary, our data greatly expands knowledge of PRDM9 diversity in humans.

Venom diversity in the Neotropical scorpion genus Tityus: Implications for antivenom design emerging from molecular and immunochemical analyses across endemic areas of scorpionism.

Scorpions of the Neotropical genus Tityus are responsible for most severe envenomations in the Caribbean, South America, and Lower Central America (LCA). Although Tityus is taxonomically complex, contains high toxin polymorphism, and produces variable clinical manifestations, treatment is limited to antivenoms produced against species with restricted distributions. In this study, we explored the compositional and antigenic diversity of Tityus venoms to provide improved guidelines for the use of available antivenoms at a broader geographic scale. We used immunoblotting, competitive ELISA, and in vivo studies to compare reactivity against commercial antivenoms from Brazil, Venezuela, and Mexico, as well as MALDI-TOF mass spectrometry, cDNA sequencing, and phylogenetic analyses to assess venom sodium channel-active toxin (NaTx) content from medically important Tityus populations inhabiting Brazil, Colombia, Costa Rica, Ecuador, Panama, Trinidad and Tobago, and Venezuela. Additionally, we raised rabbit antibodies against Tityus venoms from LCA to test for cross-reactivity with congeneric species. The results suggest that Tityus spp. possess high venom antigenic diversity, underlying the existence of four toxinological regions in Tropical America, based on venom composition and immunochemical criteria: LCA/Colombia/Amazonia (Region I), Venezuela (Region II), southeast South America (Region III), and a fourth region encompassing species related to toxinologically divergent Tityus cerroazul. Importantly, our molecular and cross-reactivity results highlight the need for new antivenoms against species inhabiting Region I, where scorpions may produce venoms that are not significantly reactive against available antivenoms.

Perioperative and Periprocedural Management of Antithrombotic Therapy: Consensus Document of SEC, SEDAR, SEACV, SECTCV, AEC, SECPRE, SEPD, SEGO, SEHH, SETH, SEMERGEN, SEMFYC, SEMG, SEMICYUC, SEMI, SEMES, SEPAR, SENEC, SEO, SEPA, SERVEI, SECOT and AEU.

During the last few years, the number of patients receiving anticoagulant and antiplatelet therapy has increased worldwide. Since this is a chronic treatment, patients receiving it can be expected to need some kind of surgery or intervention during their lifetime that may require treatment discontinuation. The decision to withdraw antithrombotic therapy depends on the patient's thrombotic risk versus hemorrhagic risk. Assessment of both factors will show the precise management of anticoagulant and antiplatelet therapy in these scenarios. The aim of this consensus document, coordinated by the Cardiovascular Thrombosis Working Group of the Spanish Society of Cardiology, and endorsed by most of the Spanish scientific societies of clinical specialities that may play a role in the patient-health care process during the perioperative or periprocedural period, is to recommend some simple and practical guidelines with a view to homogenizing daily clinical practice.

Analysis of Meiotic Double-Strand Break Initiation in Mammals.

The repair of programmed DNA double-strand breaks (DSBs) physically tethers homologous chromosomes in meiosis to allow for accurate segregation through meiotic cell divisions. This process, known as recombination, also results in the exchange of alleles between parental chromosomes and contributes to genetic diversity. In mammals, meiotic DSBs occur predominantly in a small fraction of the genome, at sites known as hotspots. Studies of the formation and repair of meiotic DSBs in mammals are challenging, because few cells undergo meiotic DSB formation at a given time. To better understand the initiation and control of meiotic recombination in mammals, we have devised a highly sensitive method to map the sites of meiotic DSBs genome wide. Our method first isolates DNA bound to DSB repair proteins and then specifically sequences the associated single-stranded DNA. This protocol has generated the first meiotic DSB maps in several mammals and the only map of meiotic DSBs in humans.

Infarto del omento mayor: a propósito de un caso / Omental Infarction: About a Case

El infarto del omento es una enfermedad poco frecuente que se manifiesta como causa de dolor abdominal. Se requiere un diagnóstico adecuado, basado en las características por imagen, puesto que su reconocimiento orienta el manejo que en la mayoría de los casos es conservador. Sin embargo, en algunos casos puede ser necesario el manejo quirúrgico. Dentro de las modalidades de imagen utilizadas para el estudio del dolor abdominal agudo, la tomografía computarizada multidetector (TCM) es la modalidad de imagen con mayor precisión para realizar diagnóstico de infarto del omento. Se presenta el caso de un paciente con torsión e infarto del omento mayor en el lado derecho, que requirió cirugía. Se realiza una revisión de la literatura sobre el infarto del omento mayor enfatizando los hallazgos por imágenes, los diagnósticos diferenciales más frecuentes y el tratamiento de esta entidad.

Omental infarction is a rare disease that occurs as a cause of abdominal pain. It requires an adequate diagnosis based on the image characteristics, since its recognition guides the management that in the majority of the cases is conservative. However, surgical management may be necessary in some cases. Among the imaging modalities used for the study of abdominal pain, multidetector computed tomography (MCT) is the most accurate imaging modality for the diagnosis of omental infarction. We present a case of a patient with torsion and infarct of the mayor omentum in the right side that required surgery. We make a literature review of omental infarction, emphasizing in the imaging findings, the most common differential diagnosis and treatment of the pathology.

The limits of stability in patients with unilateral vestibulopathy.

OBJECTIVE: To characterize the stability limits and region in patients with unilateral vestibulopathy according to the side of the lesion and determine if that imposes any bias. To analyze if the stability limits and region depend on the functional deficit as evaluated in the sensory organization test. METHODS: Forty patients with chronic dizziness and without any vertigo spell for least 6 months prior to testing. In all of them, a unilateral vestibulopathy was diagnosed clinically and at vestibular testing. A computerized dynamic posturography system was used to test for the ability of patients and controls to displace their center of pressure (COP) to the corresponding LOS. The area was calculated and compared to other data from vestibular tests. RESULTS: The area of stability among patients shows a reduction to 35-62% of the expected total. That reduction was not found to be dependent on age. CONCLUSION: There is a symmetric reduction in the limits of stability (LOS) in patients with unilateral vestibulopathy who suffer chronic instability. None of the areas measured were correlated with the composite score of the sensory organization test and, as such, must be considered as an adjunct measure to characterize the postural limitations in those patients.

Linfoma de células del manto con presentación radiológica atípica: Presentación de caso / Mantle Cell Lymphoma with Atypical Radiologic Presentation

El linfoma de células del manto hace parte del subgrupo de linfomas no Hodgkin (LNH). Este se manifiesta con adenopatías, esplenomegalia, síntomas B y compromiso cutáneo asociado a enfermedad diseminada. El compromiso esplénico se presenta como: Esplenomegalia sin lesión focal; lesiones sólidas únicas o múltiples e infiltración del bazo sin cambios morfológicos ni lesiones focales. La aparición de linfoma con lesiones quísticas es extremadamente rara, se encuentran solo unos cuantos casos en la literatura, ninguno de ellos en el bazo. Se expone el caso de una paciente de 59 años de edad, quien consultó por dolor abdominal intermitente. En los estudios diagnósticos se observó esplenomegalia con lesiones sólidas y quísticas. Se realizó esplenectomía con estudio histopatológico que confirmó compromiso por linfoma de células del manto.

Mantle cell lymphoma is a Non-Hodgkin Lymphoma (NHL). In cases of disseminated disease, lymphadenopathy, splenomegaly, B-symptoms and skin disease are present. Lymphoma affecting the spleen has several radiologic presentations, ranging from normal appearance, to splenomegaly or multiples focal solid lesions. Cystic presentation of lymphoma is rare and few cases have been reported, none of them involving the spleen. We report a case of a 59-year old female patient with cystic spleen lesions that after splenectomy were diagnosed as Mantle cell lymphoma.

Biochemical and biological characterization of Bothriechis schlegelii snake venoms from Colombia and Costa Rica.

Snakebites inflicted by the arboreal viperid snake Bothriechis schlegelii in humans are characterized by pain, edema, and ecchymosis at the site of the bite, rarely with blisters, local necrosis, or defibrination. Herein, a comparative study of Bothriechis schlegelii snake venoms from Colombia (BsCo) and Costa Rica (BsCR) was carried out in order to compare their main activities and to verify the efficacy of Bothrops antivenom produced in Brazil to neutralize them. Biochemical (SDS-PAGE and zymography) and biological parameters (edematogenic, lethal, hemorrhagic, nociceptive, and phospholipase A2 activities) induced by BsCo and BsCR snake venoms were evaluated. The presence of antibodies in Bothrops antivenom that recognize BsCo and BsCR snake venoms by enzyme-linked immunosorbent assay and Western blotting, as well as the ability of this antivenom to neutralize the toxic activities were also verified. SDS-PAGE showed differences between venoms. Distinctive caseinolytic and hyaluronidase patterns were detected by zymography. BsCo and BsCR showed similar phospholipase A2 activity. Strong cross-reactivity between BsCo and BsCR was detected using Bothrops antivenom with many components located between 150 and 35 kDa. BsCR was more edematogenic and almost fourfold more hemorrhagic than BsCo, and both venoms induced nociception. BsCR (LD50 5.60 mg/kg) was more lethal to mice than BsCo (LD50 9.24 mg/kg). Bothrops antivenom was effective in the neutralization of lethal and hemorrhagic activities of BsCo and BsCR and was partially effective in the neutralization of edematogenic and nociceptive activities. In conclusion, geographic distribution influences the composition and activities of Bothriechis schlegelii venoms. Bothrops antivenom cross-reacted with these venoms and was partially effective in neutralizing some toxic activities of BsCo and BsCR.

Polimialgia reumática: Presentación de caso / Polymialgia Rheumatica: a Case Report

La polimialgia reumática es una enfermedad que generalmente afecta a los individuos mayores de 50 años. Desde 1963 se ha modificado su denominación y clasificación; en la actualidad, para su diagnóstico se cuentan con criterios clínicos e imagenológicos. Entre los criterios imagenológicos se considera especialmente el ultrasonido; sin embargo, la resonancia magnética permite descartar diagnósticos diferenciales y considerar en forma oportuna el diagnóstico de la polimialgia reumática. Esto se destaca en el presente artículo que describe el caso de una paciente de 56 años con antecedentes de perioniquia secundaria a pedicura y, como complicación, una espondilodiscitis. Posteriormente aparece dolor articular simétrico, matutino, en caderas y hombros; por medio de resonancia magnética se establece el diagnóstico del proceso infeccioso inicial y se descarta el compromiso infeccioso articular, lo cual se asocia a criterios clínicos y se diagnostica y trata la polimialgia reumática.

Polymyalgia rheumatica is a disease that usually affects people over 50 years old. Since 1963, its name and classification have been modified; at present, there are clinical and imaging data criteria for its diagnosis. Among the imaging criteria, ultrasound plays a pivotal role; however, magnetic resonance helps to rule out different diagnoses, as well as to clarify the diagnosis of polymyalgia rheumatica. This paper highlights this fact by presenting the case of a 56-year old female patient with a history of paronychia secondary to pedicure, and spondylodiscitis as a complication. Later, she reports symmetrical joint pain in hips and shoulders in the morning; magnetic resonance is used to establish the initial infective process, while infective joint involvement is discarded; it is associated with clinical criteria in order to establish the diagnosis and treatment of polymyalgia rheumatic.

Sarcoma de Ewing de escápula: Presentación de casoc / Ewing Sarcoma: Case Report

El sarcoma de Ewing representa el segundo tumor primario de hueso más común en niños y adolescentes (3 % de todos los tumores óseos pediátricos), solo excedido en prevalencia por el osteosarcoma. Respecto al sitio de compromiso, el sarcoma de Ewing afecta la pelvis, las extremidades y las costillas en el 86 % de los casos, seguido por la escápula (de 4 a 5 %). Este artículo presenta un caso de sarcoma de Ewing en la escápula; se describen sus características clínicas e imaginológicas, así como su tratamiento.

Ewing´s sarcoma is the second most common primary bone tumor in children and adolescents (3% of all pediatric bone tumors), its prevalence is only exceeded by osteosarcoma. Regarding the site of involvement, Ewing's sarcoma involves pelvis, limbs and the ribs in 86% of cases, followed by the scapula (4-5%). This article presents a case of Ewing's sarcoma in the scapula; clinical and imaging characteristics are described, as well as treatment.

Evaluation of anti-Bothrops asper venom activity of ethanolic extract of Brownea rosademonte leaves.

Significant inhibition of the coagulant and hemorrhagic effects of Bothrops asper venom was demonstrated by ethanolic extract prepared from the leaves of Brownea rosademonte. In vitro experiments preincubating 5.5 mg of extract kg-1 b.m. for 30 min with a minimum hemorrhagic dose of venom (273.8 ± 16.1 µg of venom kg-1 b.m.) lowered the hemorrhagic activity of the venom alone in CD-1 mice by 51.5 ± 2.6 %. Additionally, 1.7 mg extract L-1 plasma prolonged 5.1 times the plasma coagulation time. Fractionation of the extract led to the isolation of two compounds: ononitol (1) and quercetrin (2). The structure of compounds 1 and 2 was established by spectroscopic analyses, including APCI-HRMS and NMR (1H, 13C, HSQC, HMBC and COSY). A quercetrin concentration of 0.11 µmol L-1 prolonged the plasma coagulation time 2.6 times demonstrating that this compound was one of the active constituents of the Brownea rosademonte extract.

Altered neurotransmitter release, vesicle recycling and presynaptic structure in the pilocarpine model of temporal lobe epilepsy.

In searching for persistent seizure-induced alterations in brain function that might be causally related to epilepsy, presynaptic transmitter release has relatively been neglected. To measure directly the long-term effects of pilocarpine-induced status epilepticus on vesicular release and recycling in hippocampal mossy fibre presynaptic boutons, we used (i) two-photon imaging of FM1-43 vesicular release in rat hippocampal slices; and (ii) transgenic mice expressing the genetically encoded pH-sensitive fluorescent reporter synaptopHluorin preferentially at glutamatergic synapses. In this study we found that, 1-2 months after pilocarpine-induced status epilepticus, there were significant increases in mossy fibre bouton size, faster rates of action potential-driven vesicular release and endocytosis. We also analysed the ultrastructure of rat mossy fibre boutons using transmission electron microscopy. Pilocarpine-induced status epilepticus led to a significant increase in the number of release sites, active zone length, postsynaptic density area and number of vesicles in the readily releasable and recycling pools, all correlated with increased release probability. Our data show that presynaptic release machinery is persistently altered in structure and function by status epilepticus, which could contribute to the development of the chronic epileptic state and may represent a potential new target for antiepileptic therapies.

[Tityus asthenes scorpion stings: epidemiological, clinical and toxicological aspects]. / Picaduras por escorpión Tityus asthenes en Mutatá, Colombia: aspectos epidemiológicos, clínicos y toxinológicos.

INTRODUCTION: Scorpion stings are a public health problem in many countries. However, in Colombia, very few epidemiological, clinical or toxicological studies have been undertaken. OBJECTIVE: Ecological and epidemiological aspects were related to the prevalence of scorpion stings by Tityus asthenes. The clinical features of envenomization were described in patients and in an experimental animal model. MATERIALS AND METHODS: The study was conducted in four localities of Mutatá and Urabá Counties in the province of Antioquia, Colombia. The sample consisted of 1,593 (929 urban, 664 rural) of the 5,305 exposed people, inhabitating 324 households (188 urban (58%); 136 rural (42%) of 1,448 houses total in the study area. An interview survey was performed in every selected family for a more realistic estimate of sting prevalence. Additionally, a prospective study was directed toward patients presenting scorpion stings at care at the local hospital over an 18-month period. RESULTS: The probability was 12.9 times greater of finding T. asthenes inside or around houses in places near to forest and high agrarian plantations (odds ratio = 13). Eighty scorpion stings were reported in the retrospective study (4.1% prevalence [95% CI 3.3-4.8%] ), but only 14 of the patients (17.5%) sought care in the local hospital (an 82.5% underreportage). Seventy percent of the stings occurred in rural places; 50% occurred in the locality of Caucheras, with an attack rate of 10.6%. The overall household infestation rate was 269% (95% CI 22.9-30.8%) and an area dispersion ratio of 100%. Signs of systemic envenomization occurred mainly in children (67%). The 50% lethal dose of T. asthenes venom was 121.6 µg for 18-20 g Swiss Webster rats (95% CI 103.7-139.6). Immunodetection of T. asthenes and Centruroides gracilis/C.margantatus venoms in the experimental animals was possible when were tested by Western blot against Alacramyn (Instituto Bioclón, México) and Soro antiaracnídico (Instituto Butantan, Brasil) antivenoms. Scorpion interspecific differences were noted. CONCLUSIONS: The prevalence of stings by T. asthenes were common and their presence was associated with tropical rainforests. Envenomization at low density can be neutralized efficiently by anti-scorpion antivenoms produced in México and Brazil but with differing specificities for the venom of each scorpion species.

Picaduras por escorpión Tityus asthenes en Mutatá, Colombia: aspectos epidemiológicos, clínicos y toxinológicos / Tityus asthenes scorpion stings: epidemiological, clinical and toxicological aspects

Introducción. El escorpionismo afecta a países tropicales como Colombia.Objetivo. Determinar los indicadores ecológicos y epidemiológicos de las picaduras por Tityus asthenes en cuatro localidades de Mutatá, Colombia, y las características clínicas del envenenamiento y toxinológicas del veneno. Materiales y métodos. Es un estudio prospectivo/retrospectivo descriptivo y experimental; se visitaron aleatoriamente 324 de las 1.448 viviendas del municipio: 188 urbanas (58,0%) y 136 rurales (42,0%), con 1.593 habitantes. En 18 meses se estudiaron prospectivamente los pacientes picados por T. asthenes que ingresaron al hospital local y, retrospectivamente en encuestas domiciliarias, se determinó el subregistro. Se recolectaron escorpiones vivos y se realizaron experimentos con el veneno. Resultados. Hubo 12,9 más probabilidades de hallar ejemplares de T. asthenes en el área rural (OR=6,5; IC95% 3,9-10,8), en el intradomicilio y peridomicilio cercano a bosques y plantaciones agrarias altas (OR=13,0; IC95% 7,5-23,0). Se reportaron 80 picaduras ocurridas en los dos últimos años (prevalencia de 4,1%; IC95% 4,8-3,3); sólo 14 personas (17,5%) consultaron al hospital (subregistro de 82,5%). La prevalencia ponderada de infestación por escorpiones en las viviendas encuestadas fue de 26,9% (112 casas) (IC95% 30,8-22,9). El 50% de los accidentes ocurrió en la localidad de Caucheras: 10,6% de proporción de ataque. El envenenamiento sistémico fue más frecuente en niños (67%). La dosis letal 50 del veneno en ratones de 18 a 20 g, fue 121,6 μg (IC95% 103,7-139,6). Hubo reactividad inmunológica por Western blot de los antivenenos del Instituto Bioclón, México (Alacramyn®) y del Instituto Butantan, Brasil (Soro antiaracnídico®)...

Introduction. Scorpion stings are a public health problem in many countries. However, in Colombia, very few epidemiological, clinical or toxicological studies have been undertaken. Objective. Ecological and epidemiological aspects were related to the prevalence of scorpion stings by Tityus asthenes. The clinical features of envenomization were described in patients and in an experimental animal model. Materials and methods. The study was conducted in four localities of Mutatá and Urabá Counties in the province of Antioquia, Colombia. The sample consisted of 1,593 (929 urban, 664 rural) of the 5,305 exposed people, inhabitating 324 households (188 urban (58%); 136 rural (42%) of 1,448 houses total in the study area. An interview survey was performed in every selected family for a more realistic estimate of sting prevalence. Additionally, a prospective study was directed toward patients presenting scorpion stings at care at the local hospital over an 18-month period. Results. The probability was 12.9 times greater of finding T. asthenes inside or around houses in places near to forest and high agrarian plantations (odds ratio=13). Eighty scorpion stings were reported in the retrospective study (4.1% prevalence [95% CI 3.3-4.8%] ), but only 14 of the patients (17.5%) sought care in the local hospital (an 82.5% underreportage). Seventy percent of the stings occurred in rural places; 50% occurred in the locality of Caucheras, with an attack rate of 10.6%. The overall household infestation rate was 269% (95% CI 22.9-30.8%) and an area dispersion ratio of 100%. Signs of systemic envenomization occurred mainly in children (67%). The 50% lethal dose of T. asthenes venom was 121.6 μg for 18-20 g Swiss Webster rats (95% CI 103.7-139.6). Immunodetection of T. asthenes and Centruroides gracilis/C.margantatus venoms in the experimental animals was possible when were tested by Western blot against Alacramyn® (Instituto Bioclón, México) and Soro antiaracnídico®...

Human heterophilic antibodies against equine immunoglobulins: assessment of their role in the early adverse reactions to antivenom administration.

The presence of human heterophilic antibodies against horse immunoglobulins (HHA-HI) was determined by ELISA in sera from healthy volunteers and from patients who received equine antivenom for therapy of snake bite envenoming. These patients were selected from two independent clinical studies: one in Colombia in which patients received antivenom constituted by whole IgG (n=25); and the other in Brazil where an antivenom constituted by F(ab')(2) fragments was administered (n=31). Results show that healthy volunteers have antibodies, mainly of the IgG class, able to react with whole equine IgG. Additionally, patients have IgG antibodies that react both with whole equine IgG and F(ab')(2) fragments. In both clinical studies, no significant differences were observed in the HHA-HI titres between the patients who presented early adverse (anaphylactoid) reactions and those who did not develop them. In addition, no variation in titre was observed in samples collected before and after antivenom administration. These results do not support the hypothesis that the incidence of early adverse reactions to antivenom administration correlates with the titre of HHA-HI in the serum of patients. Nevertheless, participation of these antibodies as part of a multifactorial pathogenic mechanism associated with these reactions cannot be ruled out.

Efficacy and safety of two whole IgG polyvalent antivenoms, refined by caprylic acid fractionation with or without beta-propiolactone, in the treatment of Bothrops asper bites in Colombia.

The efficacy and safety of two whole IgG polyvalent antivenoms (A and B) were compared in a randomised, blinded clinical trial in 67 patients systemically envenomed by Bothrops asper in Colombia. Both antivenoms were fractionated by caprylic acid precipitation and had similar neutralising potencies, protein concentrations and aggregate contents. Antivenom B was additionally treated with beta-propiolactone to lower its anticomplementary activity. Analysing all treatment regimens together, there were no significant differences between the two antivenoms (A=34 patients; B=33 patients) in the time taken to reverse venom-induced bleeding and coagulopathy, to restore physiological fibrinogen concentrations and to clear serum venom antigenaemia. Blood coagulability was restored within 6-24 h in 97% of patients, all of whom had normal coagulation and plasma fibrinogen levels 48 h after the start of antivenom treatment. Two patients (3.0%) had recurrent coagulopathy and eight patients suffered recurrence of antigenaemia within 72 h of treatment. None of the dosage regimens of either antivenom used guaranteed resolution of venom-induced coagulopathy within 6 h, nor did they prevent recurrences. A further dose of antivenom at 6 h also did not guarantee resolution of coagulopathy within 12-24 h in all patients. The incidence of early adverse reactions (all mild) was similar for both antivenoms (15% and 24%; P>0.05).

Proteomic analysis of the venom and characterization of toxins specific for Na+ - and K+ -channels from the Colombian scorpion Tityus pachyurus.

The Colombian scorpion Tityus pachyurus is toxic to humans and is capable of producing fatal accidents, but nothing is known about its venom components. This communication reports the separation of at least 57 fractions from the venom by high performance liquid chromatography. From these, at least 104 distinct molecular weight compounds were identified by mass spectrometry analysis. The complete amino acid sequences of three peptides were determined and the partial sequences of three others were also identified. Electrophysiological experiments conducted with ion-channels expressed heterologously on Sf9 cells showed the presence of a potent Shaker B K(+)-channel blocker. This peptide (trivial name Tpa1) contains 23 amino acid residues closely packed by three disulfide bridges with a molecular mass of 2,457 atomic mass units. It is the third member of the sub-family 13, for which the systematic name is proposed to be alpha-KTx13.3. The mice assay showed clearly the presence of toxic peptides to mammals. One of them named Tpa2, containing 65 amino acid residues with molecular mass of 7,522.5 atomic mass units, is stabilized by four disulfide bridges. It was shown to modify the Na(+)-currents of F-11 and TE671 cells in culture, similar to the beta scorpion toxins. These results demonstrate the presence of toxic peptides in the venom of T. pachyurus and confirm that accidents with this species of scorpion should be considered an important human hazard in Colombia.

[Toxicological and immunological aspects of scorpion venom (Tytius pachyurus): neutralizing capacity of antivenoms produced in Latin America]. / Aspectos toxinológicos e inmunoquímicos del veneno del escorpión Tityus pachyurus Pocock de Colombia: capacidad neutralizante de antivenenos producidos en Latinoamérica.

The toxicity and immunochemical properties of Tityus pachyurus Pocock scorpion venom was characterized, as well as the neutralization capacity against it by three anti-scorpion antivenoms (Alacramyn, Instituto Bioclón, México; Suero antiescorpiónico, Instituto Butantán, Sao Paulo, Brasil; and Suero antiescorpiónico, Centro de Biotecnología, Universidad Central de Venezuela, Caracas, Venezuela). The venom yield, obtained by manual milking, 680+/-20 microg venom, a 50% lethal dose in mice was 4.8 microg/kg (90 microg for an 18-20 g mouse). The most common symptoms of venom poisoning in mice were sialorrhea, respiratory distress, profuse sweating, ataxia, behavior alterations (restlessness, somnolence) and hyperglycemia at 3 and 24 hours after subcutaneous venom injection (0.5 LD50). The neutralizing capacity of Bioclón (México City) and Butantán (Sao Paulo) antivenoms (for a 50% effective dose) was 330 and 292 microg venom/ml antivenom, respectively. The Biotecnología (Caracas) antivenom did not neutralize the lethal effect of venom. By electrophoresis (SDS-PAGE) was demonstrated that the venom contains proteins from less than 14 kd to 97 kd. The Western blots indicated immunological reactivity of the three antivenoms with most of venom components, including proteins of low molecular mass (<14 kd). The results allow to conclude that T. pachyurus venom is neutralized efficiently by anti-scorpion antivenoms produced in México and Brasil.