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Introducción: Las toxinas botulínicas son medicamentos bioterapéuticos con grandes aplicaciones en el campo de la neurología, como la cefalea y los movimientos anormales. Debido a la importancia médica y al incremento de las indicaciones terapéuticas de la toxina botulínica, este artículo pretende hacer claridad acerca de la terminología básica con respecto a la naturaleza de este medicamento, a las diferencias estructurales con medicamentos convencionales y aspectos importantes en relación con su potencia biológica e inmunogenicidad, para así comprender las potenciales diferencias entre las toxinas disponibles y conceptuar en torno a la no intercambiabilidad o sustitución de una toxina por otra. Materiales y métodos: Revisión no sistemática, según lo recomendado en la Escala para la Verificación de los Artículos Revisiones Narrativas (Sanra). Conclusiones: Los medicamentos biológicos no son intercambiables entre sí, aunque demuestren bioequivalencia. No se pueden evaluar como medicamentos genéricos intercambiables porque son biológicos; no existen estudios comparativos cabeza a cabeza; son diferentes, debido al proceso individual de manufactura.
Introduction: Botulinum toxins are biotherapeutic drugs with great applications in the field of neurology such as headache and abnormal movements. Due to the medical importance and the increase in therapeutic indications of botulinum toxin, this article aims to clarify the basic terminology regarding the nature of this drug, the structural differences with conventional drugs and important aspects in relation to its biological potency and immunogenicity in order to understand the potential differences between the available toxins and conceptualize regarding the non-interchangeability or substitution of one toxin for another. Materials and methods: Non-systematic review as recommended in the Scale for the Verification of Narrative Review Articles (SANRA). Conclusions: Biological drugs are not interchangeable with each other, even if they demonstrate bioequi-valence. They cannot be evaluated as interchangeable generic drugs because they are biologics. There are no head-to-head comparative studies. They are different due to the individual manufacturing process.
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Toxinas Botulínicas Tipo A , Medicamentos Biossimilares , Intercambialidade de MedicamentosRESUMO
INTRODUCTION: The emergence of multiple variants of SARS-CoV-2 during the COVID-19 pandemic is of great world concern. Until now, their analysis has mainly focused on next-generation sequencing. However, this technique is expensive and requires sophisticated equipment, long processing times, and highly qualified technical personnel with experience in bioinformatics. To contribute to the analysis of variants of interest and variants of concern, increase the diagnostic capacity, and process samples to carry out genomic surveillance, we propose a quick and easy methodology to apply, based on Sanger sequencing of 3 gene fragments that code for protein spike. METHODS: Fifteen positive samples for SARS-CoV-2 with a cycle threshold below 25 were sequenced by Sanger and next-generation sequencing methodologies. The data obtained were analyzed on the Nextstrain and PANGO Lineages platforms. RESULTS: Both methodologies allowed the identification of the variants of interest reported by the WHO. Two samples were identified as Alpha, 3 Gamma, one Delta, 3 Mu, one Omicron, and 5 strains were close to the initial Wuhan-Hu-1 virus isolate. According to in silico analysis, key mutations can also be detected to identify and classify other variants not evaluated in the study. CONCLUSION: The different SARS-CoV-2 lineages of interest and concern are classified quickly, agilely, and reliably with the Sanger sequencing methodology.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Pandemias , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Combination therapy with ampicillin plus ceftriaxone (AMP+CRO) is the first-line therapy for treating severe infections due to Enterococcus faecalis. However, the pharmacokinetic/pharmacodynamic (PK/PD) index linked to the in vivo efficacy of the combination is not yet defined, hindering dose optimization in the clinic. Because classical PK/PD indices are not directly applicable to antimicrobial combinations, two novel indices were tested in the optimized murine model of infection by E. faecalis to delineate the potentiation of AMP by CRO: the time above the CRO threshold (T>threshold) and the time above the AMP instantaneous MIC (T>MICi). The potential clinical relevance was evaluated by simulating human doses of AMP and CRO. Hill's equation fitted well the exposure-response data in terms of T>threshold, with a CRO threshold of 1 mg/L. The required exposures were 46%, 49%, and 52% for stasis and 1- and 2-log10 killing, respectively. Human ceftriaxone doses of 2 g every 12 h (q12h) would reach the target in >90% of strains with thresholds ≤64 mg/L. The AMP T>MICi index also fitted well, and the required exposures were 37%, 41%, and 46% for stasis and 1- and 2-log10 killing, respectively. In humans, the addition of CRO would allow use of lower AMP doses to reach the same T>MICi and to treat strains with higher MICs. This is the first report of the PK/PD indices and required magnitudes linked to AMP+CRO against E. faecalis; these results can be used as the basis to guide the design of clinical trials to improve combined therapy against enterococci.
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Antibacterianos , Ceftriaxona , Humanos , Camundongos , Animais , Ceftriaxona/uso terapêutico , Antibacterianos/uso terapêutico , Enterococcus faecalis , Ampicilina/uso terapêutico , Testes de Sensibilidade Microbiana , MitomicinaRESUMO
Introduction: The emergence of multiple variants of SARS-CoV-2 during the COVID-19 pandemic is of great world concern. Until now, their analysis has mainly focused on next-generation sequencing. However, this technique is expensive and requires sophisticated equipment, long processing times, and highly qualified technical personnel with experience in bioinformatics. To contribute to the analysis of variants of interest and variants of concern, increase the diagnostic capacity, and process samples to carry out genomic surveillance, we propose a quick and easy methodology to apply, based on Sanger sequencing of 3 gene fragments that code for protein spike. Methods: Fifteen positive samples for SARS-CoV-2 with a cycle threshold below 25 were sequenced by Sanger and next-generation sequencing methodologies. The data obtained were analyzed on the Nextstrain and PANGO Lineages platforms. Results: Both methodologies allowed the identification of the variants of interest reported by the WHO. Two samples were identified as Alpha, 3 Gamma, one Delta, 3 Mu, one Omicron, and 5 strains were close to the initial Wuhan-Hu-1 virus isolate. According to in silico analysis, key mutations can also be detected to identify and classify other variants not evaluated in the study. Conclusion: The different SARS-CoV-2 lineages of interest and concern are classified quickly, agilely, and reliably with the Sanger sequencing methodology.
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INTRODUCTION: Reverse transcriptase - polymerase chain reaction (RT-PCR) is the standard technique for SARS-CoV-2 diagnosis. The World Health Organization recommends the Charité-Berlin protocol for COVID-19 diagnosis, which requires triple PCR, limiting the process capability of laboratories and delaying the results. In order to reduce these limitations, a duplex PCR is validated for the detection of the E and ribonuclease P genes. METHODS: We compared the limit of detection, sensitivity and specificity of the duplex PCR technique (E gene and Rnasa P) against the monoplex standard (E gene) in RNA samples from a SARS-CoV-2 isolate and 88 clinical specimens with previously known results. The repeatability and reproducibility of the threshold cycle values ââ(Ct) were determined in two independent laboratories of the Faculty of Medicine of the Universidad de Antioquia, using different reagents and real time instruments. RESULTS: There were no significant differences in the Ct results between both techniques (P = .84). Using the monoplex PCR of E gene as a reference, the interrater reliability analysis showed similarity between the two techniques, with a kappa coefficient of 0.89, the sensitivity and the specificity of duplex PCR were 90% and 87%, respectively. CONCLUSIONS: Duplex PCR does not affect the sensitivity and specificity reported by the Charité, Berlin protocol, being a useful tool for SARS-CoV-2 screening in clinical samples.
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COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Teste para COVID-19 , Humanos , Reação em Cadeia da Polimerase , RNA Viral/análise , DNA Polimerase Dirigida por RNA/genética , Reprodutibilidade dos Testes , Ribonuclease P/genética , SARS-CoV-2/genéticaRESUMO
INTRODUCTION: Reverse transcriptase - polymerase chain reaction (RT-PCR) is the standard technique for SARS-CoV-2 diagnosis. The World Health Organization recommends the Charité-Berlin protocol for COVID-19 diagnosis, which requires triple PCR, limiting the process capability of laboratories and delaying the results. In order to reduce these limitations, a duplex PCR is validated for the detection of the E and RNase P genes. METHODS: We compared the limit of detection, sensitivity and specificity of the duplex PCR technique (E gene and RNase P) against the monoplex standard (E gene) in RNA samples from a SARS-CoV-2 isolate and 88 clinical specimens with previously known results. The repeatability and reproducibility of the threshold cycle values (Ct) were determined in two independent laboratories of the Faculty of Medicine of the Universidad de Antioquia, using different reagents and real time instruments. RESULTS: There were no significant differences in the Ct results between both techniques (p = 0.84). Using the monoplex PCR of E gene as a reference, the interrater reliability analysis showed similarity between the two techniques, with a kappa coefficient of 0.89, the sensitivity and the specificity of duplex PCR were 90% and 87%, respectively. CONCLUSIONS: Duplex PCR does not affect the sensitivity and specificity reported by the Charité, Berlin protocol, being a useful tool for SARS-CoV-2 screening in clinical samples.
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BACKGROUND: Acute paraquat ingestion remains a leading cause of mortality in developing countries. There is currently no evidence that treatment with high-dose immunosuppressants and antioxidants improves survival in patients with paraquat poisoning, and better options are urgently needed. Here, we describe the unexpected survival and recovery of a patient with a potentially fatal paraquat poisoning. CASE PRESENTATION: After ingesting 28 mL of paraquat (20% ion w/v), confirmed by a deep blue color in the urine dithionite test (UDT), a 17-year-old Hispanic Colombian boy was treated according to the hospital protocol with cyclophosphamide, methylprednisolone, N-acetylcysteine, vitamin E and propranolol. Gastrointestinal endoscopy showed extensive ulceration and necrosis. As a novelty, enoxaparin at a single dose of 60 mg was added to his treatment. Despite the evidence of severe mucosal burns in the gastrointestinal tract and high paraquat concentrations found in the UDT, the clinical condition began to improve after 1 day of treatment, with full recovery and discharge from hospital after 21 days. CONCLUSIONS: Although the amount of paraquat ingested by the patient was large and the UDT indicated severe poisoning with a somber prognosis, unexpected survival of the patient was observed, and the addition of enoxaparin was the only change from the standard treatment.
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Heparina de Baixo Peso Molecular , Paraquat , Adolescente , Ciclofosfamida , Humanos , Imunossupressores , Masculino , MetilprednisolonaRESUMO
The combination of ampicillin (AMP) and ceftriaxone (CRO) is considered synergistic against Enterococcus faecalis based on in vitro tests and the rabbit endocarditis model, however, in vitro assays are limited by the use of fixed antibiotic concentrations and the rabbit model by poor bacterial growth, high variability, and the use of point dose-effect estimations, that may lead to inaccurate assessment of antibiotic combinations and hinder optimal translation. Here, we tested AMP+CRO against two strains of E. faecalis and one of E. faecium in an optimized mouse thigh infection model that yields high bacterial growth and allows to define the complete dose-response relationship. By fitting Hill's sigmoid model and estimating the parameters maximal effect (Emax) and effective dose 50 (ED50), the following interactions were defined: synergism (Emax increase ≥2 log10 CFU/g), antagonism (Emax reduction ≥1 log10 CFU/g) and potentiation (ED50 reduction ≥50% without changes in Emax). AMP monotherapy was effective against the three strains, yielding valid dose-response curves in terms of dose and the index fT>MIC. CRO monotherapy showed no effect. The combination AMP+CRO against E. faecalis led to potentiation (59-81% ED50 reduction) and not synergism (no changes in Emax). Against E. faecium, the combination was indifferent. The optimized mouse infection model allowed to obtain the complete dose-response curve of AMP+CRO and to define its interaction based on pharmacodynamic parameter changes. Integrating these results with the pharmacokinetics will allow to derive the PK/PD index bound to the activity of the combination, essential for proper translation to the clinic.
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Ampicilina , Ceftriaxona , Endocardite Bacteriana , Enterococcus faecalis/metabolismo , Enterococcus faecium/metabolismo , Infecções por Bactérias Gram-Positivas , Ampicilina/farmacocinética , Ampicilina/farmacologia , Animais , Ceftriaxona/farmacocinética , Ceftriaxona/farmacologia , Modelos Animais de Doenças , Quimioterapia Combinada , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/metabolismo , Endocardite Bacteriana/microbiologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/metabolismo , Infecções por Bactérias Gram-Positivas/microbiologia , Camundongos , CoelhosRESUMO
Resumen En este trabajo, reportamos y describimos evidencia de una anomalía en el trago de un individuo de Artibeus lituratus, capturado en los Andes Centrales de Colombia. En junio de 2019, durante un trabajo de campo en el Departamento de Caldas, municipio de Aranzazu, quedó atrapado un individuo de A. lituratus con inusual forma de trago. Este individuo tenía un trago de forma cilíndrica y asimetría. El individuo fue recogido y depositado en el Museo de Historia Natural de la Universidad de Caldas (MHN-UCa). Se realizó una revisión de la literatura para encontrar casos similares utilizando motores de búsqueda, pero no se encontraron informes previos de la anomalía. Además, revisamos el trago de los especímenes en el MHNUCa y ninguno de ellos presentaba malformaciones similares. Concluimos que esta anomalía no se había registrado previamente en Chiroptera.
Abstract In this work, we report and describe evidence of an anomaly in the tragus of an individual of Artibeus lituratus, captured in the Central Andes of Colombia. During field work in the Department of Caldas, municipality of Aranzazu, one individual of A. lituratus with unusual tragus form was trapped. This individual had a tragus with cylindrical shape and asymmetry. The individual was collected and deposited at the Museum of Natural History of the University of Caldas (MHN-UCa). A literature review was conducted to find similar cases using searching engines, but no previous reports of the anomaly were find. Furthermore, we reviewed the tragus of vouchers at the MHN-UCa and none of these had similar malformations. We concluded that this anomaly has not previously registered in Chiroptera.
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BACKGROUND: Paraquat self-poisonings constitute a significant contributor to the global burden of suicide. Our aim was to evaluate the relationship between social and economic variables with the incidence of self-poisoning with Paraquat in the northeast of Colombia. METHODS: Records of 154 cases of self-poisoning with Paraquat and several socio-economic variables of six regions of northeast of Colombia were analyzed. RESULTS: Most of the cases were mestizos, farmworkers, between 20 and 29 years, with intentional exposure using the oral route. Multivariate analyses revealed significant associations among the incidence of self-poisoning with PQ with the ecological factors such as poverty greater than 30% (IRR 15.9 IC95% 5.56-44.72), land Gini index < 0.7 (IRR 7.11 IC95% 3.58-14.12), private health insurance < 40% (IRR 3.39 IC95% 1.30-8.82) and planted area > 10% (IRR 2.47 IC95% 1.60-3.80). CONCLUSION: There is a relationship between ecological factors and, as such, this study opens the way to further developments in the field.
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Paraquat/intoxicação , Intoxicação/epidemiologia , Suicídio/estatística & dados numéricos , Adulto , Colômbia/epidemiologia , Feminino , Humanos , Incidência , Masculino , Fatores Socioeconômicos , Adulto JovemRESUMO
Context: During a period of 6 months, 36 people reported to health authorities in the Department of Antioquia, Colombia, presenting episodes of bleeding in varying magnitude and locations in the body and alterations in coagulation tests, after having taken a falsified dietary supplement. The identification of the first four cases were to the cell-phone line at the Drug and Poison Research Information Center (CIEMTO). The successive presentation of cases with similar manifestations, taking the same product, served to suspect a possible common link.Case details: All of the patients needed hospitalization, the administration of blood products and / or vitamin K to reverse the clinical manifestations, and to stop the oral consumption of the falsified supplement. For each patient there was a full recovery of coagulation and improvement of haemorrhagic manifestations after the first week of management. The Food and Drug administration of Colombia (INVIMA), withdrew the product from the market, alerted the medical community and the general public and conducted an investigation that finally showed warfarin as a the main contaminant in the dietary supplement.Conclusion: This cases series emphasize the importance of the Poison Control Center to detect promptly potential new exposure of hazards to hundreds of products to the population, some of them fraudulent.
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Context: The clinical consequences of excess vitamin B12 induced by multiple oral doses of cyanocobalamin are not well-known.Case details: A young woman was treated with multiple daily doses of 1 mg of cyanocobalamin for severe pernicious anemia. After a total dose of 12 mg, she developed acne, palpitations, anxiety, akathisia, facial ruddiness, headache, and insomnia. She improved two weeks after stopping the drug. There were no sequelae nor complications.Discussion: Although these symptoms of cobalamin toxicity were unexpected and unusual, the case reminds us that the administration of any drug is not entirely safe.
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Acne Vulgar/induzido quimicamente , Anemia Perniciosa/tratamento farmacológico , Vitamina B 12/toxicidade , Acne Vulgar/diagnóstico , Adulto , Anemia Perniciosa/sangue , Ansiedade/induzido quimicamente , Ansiedade/diagnóstico , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Intramusculares , Resultado do Tratamento , Vitamina B 12/administração & dosagem , Vitamina B 12/sangue , Vitamina B 12/uso terapêuticoRESUMO
During the last decades, enterococci have emerged as important etiological agents in bacteremia, osteomyelitis, endocarditis and soft tissue infections. Antimicrobial combinations have been the most used therapeutic strategies for these infections, aiming for a bactericidal synergistic effect. However, besides in vitro and in vivo models, the clinical usefulness of such combinations is controversial, especially in non-endocardic systemic infections. For example, although beta-lactam and aminoglycoside combinations or double beta-lactam treatment have achieved high cure rates in endocarditis, the optimal treatment has not yet been clarified or if these combinations are useful in other infections. The aim of this review was to analyze and summarize the results from several experimental models of antienterococcal combined therapy and from clinical trials available in PubMed/Medline, to better assess the evidence that supports the use of these combinations. In conclusion, the available information is scarce, and more and better in vivo models and clinical studies are required to confirm the potential synergistic activity of antienterococcal combinations.
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Antibacterianos/farmacologia , Enterococcus/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Ensaios Clínicos como Assunto , Sinergismo Farmacológico , Quimioterapia Combinada , Endocardite/induzido quimicamente , Humanos , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
Mujer quien inició tratamiento de rescate de segunda línea para Helicobacter pylori con levofloxacina un gramo cada 12 horas, amoxicilina 500 mg cada 8 horas y lansoprazol 40 mg cada 24 horas. Al quinto día de tratamiento manifestó mialgias generalizadas seguido por artralgias y limitación del movimiento en rodillas y codos. Al séptimo día, sin mejora, la paciente suspende la medicación y presenta resolución completa de los síntomas una semana después. No hubo secuelas, ni complicaciones, ni re-exposición al medicamento. El caso fue clasificado como probable, con un puntaje de siete en la escala de Naranjo. Este caso nos recuerda que la administración de fluoroquinolonas puede asociarse con artralgias y artropatía reversible aguda, y debería ser la primera sospecha diagnóstica en pacientes sin comorbilidad.
Woman who initiated second-line rescue therapy for Helicobacter pylori with levofloxacin one gram every 12 hours, amoxicillin 500 mg every 8 hours and lansoprazole 40 mg every 24 hours. On the fifth day of treatment, she manifested generalized myalgia followed by bilateral knee and elbow arthralgia with limitation of movements. On the seventh day, without improvement, the patient discontinues the medication and achieve complete resolution of the symptoms one week later. There were no sequelae, no complications, no re-exposure to the drug. The case was classified as probable attaining a score of seven under the Naranjo's scale. This case reminds us that administration of fluoroquinolones may be associated with arthralgia and acute reversible arthropathy and should be the first diagnostic suspicion in patients without comorbidity.
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Humanos , Feminino , Helicobacter pylori , Artralgia , Levofloxacino , Fluoroquinolonas , Mialgia , Gastrite , Antibacterianos , Antibacterianos/efeitos adversosRESUMO
BACKGROUND: Isoniazid (INH) is a first-line antituberculosis (TB) agent with a pharmacokinetic profile characterized by high interindividual variation; however, population pharmacokinetic studies in patients with TB are scarce. The aim was to develop a population model for INH in Colombian patients with TB suitable for predicting drug exposure and assessing the probability of target attainment of pharmacodynamic goals. METHODS: Ten hospitalized adult patients with TB undergoing INH treatment were recruited. After an 8-hour fasting, subjects took 300 mg of INH, and 10 samples were taken from 0 to 12 hours. INH was quantified by high-performance liquid chromatography-UV, and data were analyzed with the Pmetrics R package software. A Monte Carlo simulation with the model parameters was run to determine the probability of target attainment for optimal efficacy. RESULTS: The best model included 2 compartments, first-order absorption (Ka), delayed absorption (Tlag), and linear clearance (CL). Median Tlag was 0.25 hours, 5.54 hour for Ka, (Equation is included in full-text article.)for CL, (Equation is included in full-text article.)for the volume of the central compartment (Vc), 1.04 L/h for intercompartmental clearance (Q), and 788 L for the volume of the peripheral compartment (Vp). CL and Vc were allometrically scaled on basis of the normalized body weight. CONCLUSIONS: The Monte Carlo simulation indicated that 300 mg of INH per day is appropriate for Mycobacterium tuberculosis strains with minimal inhibitory concentration (MIC) up to 0.03 mg/L (target: area under the concentration-time curve/MIC >597); however, to cover strains with MIC up to 0.125 mg/L (80% of clinical isolates), a dose of 900 mg per day would be required.
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Antituberculosos/farmacocinética , Isoniazida/farmacocinética , Tuberculose/sangue , Tuberculose/tratamento farmacológico , Adulto , Antituberculosos/sangue , Colômbia/epidemiologia , Simulação por Computador , Feminino , Humanos , Isoniazida/sangue , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Método de Monte Carlo , Tuberculose/epidemiologiaRESUMO
Resumen Durante las últimas décadas, especies del género Enterococcus han emergido como importantes agentes etiológicos de bacteriemia, osteomielitis, endocarditis e infecciones de tejidos blandos. La combinación de antibacterianos ha sido la estrategia terapéutica más utilizada para dichas infecciones, buscando un potencial efecto sinérgico bactericida. Sin embargo, aparte de los modelos in vitro e in vivo, la utilidad clínica del tratamiento combinado genera controversia, especialmente en infecciones sistémicas no endocárdicas. Aunque las combinaciones entre β-lactámicos y aminoglucósidos o el tratamiento dual con β-lactámicos, han mejorado las tasas de curación de la endocarditis, aún no se ha esclarecido cuál es su tratamiento óptimo o si estas combinaciones también son útiles en otro tipo de infecciones graves sistémicas. El propósito de esta revisión es analizar y resumir los resultados obtenidos de diferentes modelos experimentales de combinaciones anti-enterocócicas y de los estudios clínicos disponibles en PubMed/Medline, a fin de evaluar mejor la evidencia que soporta la utilización de estas combinaciones. En conclusión, la información disponible es escasa, e indica la necesidad de mejores modelos in vivo y estudios clínicos que permitan comprobar la potencial actividad sinérgica de las combinaciones anti-enterocóciccas.
During the last decades, enterococci have emerged as important etiological agents in bacteremia, osteomyelitis, endocarditis and soft tissue infections. Antimicrobial combinations have been the most used therapeutic strategies for these infections, aiming for a bactericidal synergistic effect. However, besides in vitro and in vivo models, the clinical usefulness of such combinations is controversial, especially in non-endocardic systemic infections. For example, although beta-lactam and aminoglycoside combinations or double beta-lactam treatment have achieved high cure rates in endocarditis, the optimal treatment has not yet been clarified or if these combinations are useful in other infections. The aim of this review was to analyze and summarize the results from several experimental models of antienterococcal combined therapy and from clinical trials available in PubMed/Medline, to better assess the evidence that supports the use of these combinations. In conclusion, the available information is scarce, and more and better in vivo models and clinical studies are required to confirm the potential synergistic activity of antienterococcal combinations.
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Humanos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Enterococcus/efeitos dos fármacos , Antibacterianos/farmacologia , Reprodutibilidade dos Testes , Ensaios Clínicos como Assunto , Resultado do Tratamento , Sinergismo Farmacológico , Quimioterapia Combinada , Endocardite/induzido quimicamenteRESUMO
RESUMEN Objetivo Caracterizar los casos de envenenamiento por animales marinos y dulceacuícolas atendidos por el CCT de la Universidad de Antioquia, Colombia, entre 2016 y 2018. Metodología Estudio observacional, retrospectivo, realizado a partir de la base de datos del CCT, que contiene las características demográficas y clínicas reportadas durante el manejo médico de cada emergencia toxicológica asesorada. El periodo analizado fue desde el 1 de enero del 2016 al 31 de diciembre de 2018. Los casos identificados como envenenamiento por animales acuáticos tuvieron seguimiento telefónico para saber si hubo complicaciones o secuelas. Resultados En el periodo se reportaron doce casos, once de ellos ocasionados por rayas dulceacuícolas. Siete de los afectados fueron hombres. La mediana de edad fue 30 años (rango: 8 a 44). En Antioquia y Caquetá se registraron 58% de los accidentes reportados. Aunque el uso empírico de antibióticos se dio en la mayoría de los casos, solo en cuatro de ellos se documentaron complicaciones infecciosas de piel y tejidos blandos, por lo cual requirieron tratamiento intrahospitalario. Conclusión El envenenamiento por animales de agua dulce y salada se presenta en Colombia. Aunque fueron pocos los casos en 3 años, el bajo registro nacional puede ser importante, pues amerita mayor preparación del personal médico y más investigación en este tema.(AU)
ABSTRACT Objective To characterize the cases of poisoning by marine and freshwater animals treated by the PCC of the University of Antioquia, Colombia, between 2016 and 2018. Methodology An observational, retrospective study using the PCC database that contains the demographic and clinical characteristics reported during the medical management during a toxicological emergency. Period analyzed was from January 1st, 2016 to December 31st, 2018. The cases identified as poisoning by aquatic animals had telephone follow-up to understand if there were complications or sequelae. Results Twelve cases were reported in the period, eleven of them caused by the freshwater stingray. Seven of those affected were men. The median age was 30 years (range: 8 to 44). Antioquia and Caquetá reported 58% of the accidents recorded. Although the empirical use of antibiotics was done in the majority of cases, only four of them documented infectious skin and soft tissue complications that required intrahospital treatment. Conclusion Poisoning by freshwater and saltwater animals occurs in Colombia. Although there were few cases in 3 years, the low national registry may be relevant, meriting greater preparation of medical personnel, and more research in this area.(AU)
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Humanos , Intoxicação , Acidentes , Animais Peçonhentos , Fauna Aquática/efeitos adversos , Estudos Retrospectivos , ColômbiaRESUMO
Intoxications caused by organophosphorus compounds (OPs) are associated with the reversible, and sometimes irreversible interaction with acetylcholinesterase (AChE). OPs are commonly used as pesticides mainly in developing countries, where the associated poisoning is a major health problem related to suicidal attempts, careless manipulation, and chemical warfare. The current antidotes are oxime-based drugs that can regenerate the AChE catalytic activity. Nevertheless, challenges associated with lack of efficiency and difficulties for crossing blood-brain barrier have motivated the design of novel alternatives. We used a validated molecular docking approach for the virtual screening of 579,890 synthetic ligands and 478 drugs against a human AChE in its apo conformation, and a murine AChE conjugated with the OP tabun. After filtering, 7 hits were selected as potential competitors due to the formation of key interactions within the active site gorge of the AChE structure, and potential reactivators based on interactions with amino acids of the catalytic triad in the presence of organophosphorus compounds. The selected candidates will be further evaluated through inâ vitro and inâ vivo assays.
Assuntos
Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Ligantes , Sítios de Ligação/efeitos dos fármacos , Biocatálise/efeitos dos fármacos , Bases de Dados de Produtos Farmacêuticos , Humanos , Estrutura Molecular , Compostos Organofosforados/antagonistas & inibidores , Compostos Organofosforados/farmacologia , Oximas/química , Oximas/farmacologia , Relação Estrutura-AtividadeRESUMO
BACKGROUND: We demonstrated therapeutic nonequivalence of "bioequivalent" generics for meropenem, but there is no data with generics of other carbapenems. METHODS: One generic product of imipenem-cilastatin was compared with the innovator in terms of in vitro susceptibility testing, pharmaceutical equivalence, pharmacokinetic (PK) and pharmacodynamic (PD) equivalence in the neutropenic mouse thigh, lung and brain infection models. Both pharmaceutical forms were then subjected to analytical chemistry assays (LC/MS). RESULTS AND CONCLUSION: The generic product had 30% lower concentration of cilastatin compared with the innovator of imipenem-cilastatin. Regarding the active pharmaceutical ingredient (imipenem), we found no differences in MIC, MBC, concentration or potency or AUC, confirming equivalence in terms of in vitro activity. However, the generic failed therapeutic equivalence in all three animal models. Its Emax against S. aureus in the thigh model was consistently lower, killing from 0.1 to 7.3 million less microorganisms per gram in 24 hours than the innovator (P = 0.003). Against K. pneumoniae in the lung model, the generic exhibited a conspicuous Eagle effect fitting a Gaussian equation instead of the expected sigmoid curve of the Hill model. In the brain infection model with P. aeruginosa, the generic failed when bacterial growth was >4 log10 CFU/g in 24 hours, but not if it was less than 2.5 log10 CFU/g. These large differences in the PD profile cannot be explained by the lower concentration of cilastatin, and rather suggested a failure attributable to the imipenem constituent of the generic product. Analytical chemistry assays confirmed that, besides having 30% less cilastatin, the generic imipenem was more acidic, less stable, and exhibited four different degradation masses that were absent in the innovator.
Assuntos
Bactérias/efeitos dos fármacos , Infecções Bacterianas/sangue , Combinação Imipenem e Cilastatina/farmacocinética , Medicamentos Genéricos/farmacocinética , Imipenem/química , Animais , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Cilastatina/química , Cilastatina/farmacocinética , Cilastatina/farmacologia , Combinação Imipenem e Cilastatina/química , Combinação Imipenem e Cilastatina/farmacologia , Modelos Animais de Doenças , Estabilidade de Medicamentos , Medicamentos Genéricos/química , Medicamentos Genéricos/farmacologia , Humanos , Imipenem/farmacocinética , Imipenem/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Equivalência TerapêuticaRESUMO
BACKGROUND: Paraquat (PQ) poisoning is a public health problem in many regions of Colombia. This study aimed to estimate the burden of PQ poisoning in the Department of Antioquia, Colombia. METHODS: Disability-adjusted life year (DALYs) were calculated as the sum of years of life lost (YLL) and years of life lived with disability (YLD) due to paraquat poisoning in Antioquia; a bootstrapped method with 1000 iterations was used to estimate each statistical parameter using the package DALY calculator in R. For this instance, the annual incidence of paraquat poisoning was obtained from the reported surveillance data according to regional Government. RESULTS: From 2010 to 2016, 3299 DALYs were estimated in the department of Antioquia for PQ intoxication, with a rate of 53.4 DALYs per 100,000 inhabitants. The majority of the DALYs (2852 DALYs) were generated for men ranging from 15 to 44 years old. CONCLUSION: The rate of DALYs reported here is higher than that reported by all chemical poisonings. Better strategies to regulate and restrict the market of this dangerous products are required in Colombia.