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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
La violeta de genciana es un colorante orgánico sintético, descrito por primera vez por Charles Lauth en 1861. Tiene propiedades antibacterianas, antifúngicas, antihelmínticas, antitripanosómicas, antiantiogénicas y antitumorales. Tiene diversos mecanismos de acción, entre los que principalmente se encuentra bloquear la actividad de las nicotinamida adenina dinucleótido fosfato oxidasas, evitando la generación de radicales superoxidativos y la posterior inflamación. En los últimos años se ha utilizado en marcadores para procedimientos en diferentes especialidades médicas, incluidos los de oftalmología. La tinta de violeta de genciana se describe por el fabricante como no tóxica, sin embargo existe evidencia clínica y experimental que sugiere que puede ser tóxica para el endotelio corneal y puede llegar a generar queratitis lamelar difusa posterior a LASIK y Femto-LASIK. Se describe el caso de una paciente de 23 años de edad, que presentó diversas patologías en la córnea después del uso de marcador quirúrgico durante procedimiento refractivo Femto-LASIK.
Gentian violet is a synthetic and organic dye. First described by Charles Lauth in 1861. It has antibacterial, antifungal, anthelmintic, antitrypanosomal, antiangiogenic, and antitumoral properties. It has various mechanisms of action, among which is mainly blocking the activity of nicotinamide adenine dinucleotide phosphate oxidases, preventing the generation of superoxidative radicals and subsequent inflammation. In recent years, it has been used as markers for procedures in different medical specialties, including ophthalmology. Gentian violet ink is described by the manufacturer as non-toxic, however, there is clinical and experimental evidence suggesting that it may be toxic to the corneal endothelium and may cause diffuse lamellar keratitis after LASIK and Femto-LASIK. The case about a 23-year-old female patient who presented various pathologies in the cornea after the use of a surgical marker during the Femto-LASIK refractive procedure is described.
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Humanos , Feminino , AdultoRESUMO
Natural Rubber Field Latex (NRFL) allergens restrict its use in some markets due to health-threatening allergic reactions. These molecules are proteins that are related to asymptomatic sensitization and hypersensitivity mediated by immunoglobulin E (IgE). Although NRFL allergens have been investigated since the 1980s, there are still gaps in knowledge regarding the development of deproteinized natural rubber (DPNR). Therefore, in this study, the deproteinization of NRFL from the lower basin of the Cauca River, Antioquia-Colombia was evaluated using eight systems. The highest removal value was 84.4% and was obtained from the treatment containing SDS (Sodium dodecyl sulfate), Urea, and Ethanol. It was also possible to determine that at high concentrations of SDS, removal percentages higher than 70% are reached. On the other hand, all deproteinizing systems decreased NRFL Zeta potentials without self-coagulation, suggesting enhanced colloidal stability in DPNR latex. On the other hand, the bibliometric analysis presented technological advances in DPRN through different parameters and bibliometric networks. The analysis presented makes an important contribution from the bibliometric approach that could be positive for the development of research on DPNR.
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Recently, bismuth oxyiodide (BiOI) is an attractive semiconductor to use in heterogeneous photocatalysis processes. Unfortunately, BiOI individually shows limited photocatalytic efficiency, instability, and a quick recombination of electron/holes. Considering the practical application of this semiconductor, some studies show that synthetic zeolites provide good support for this photocatalyst. This support material permits a better photocatalytic efficiency because it prevents the quick recombination of photogenerated pairs. However, the optimal conditions (time and temperature) to obtain composites (BiOI/ synthetic zeolite) with high photocatalytic efficiency using a coprecipitation-solvothermal growth method have not yet been reported. In this study, a response surface methodology (RSM) based on a central composite design (CCD) was applied to optimize the synthesis conditions of BiOI/mordenite composites. For this purpose, eleven BiOI/mordenite composites were synthesized using a combined coprecipitation-solvothermal method under different time and temperature conditions. The photocatalytic activities of the synthesized composites were evaluated after 20 min of photocatalytic oxidation of caffeic acid, a typical organic pollutant found in agro-industrial wastewater. Moreover, BiOI/mordenite composites with the highest and lowest photocatalytic activity were physically and chemically characterized using nitrogen adsorption isotherms, scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and diffuse reflectance spectroscopy (DRS). The optimal synthesis conditions prove to be 187 °C and 9 h. In addition, the changes applied to the experimental conditions led to surface property modifications that influenced the photocatalytic degradation efficiency of the BiOI/mordenite composite toward caffeic acid photodegradation.
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Resumen Introducción: la pancreatitis crónica (PC) es una inflamación progresiva del páncreas que puede llevar a su destrucción e insuficiencia irreversibles. Es una patología desafiante para el médico, debido a que establecer su diagnóstico puede tomar meses e incluso años, el seguimiento de pacientes suele ser problemático y el conocimiento sobre la clínica y epidemiología en Colombia es incompleto. Este estudio pretende hacer una descripción de pacientes con PC en un centro de referencia en gastroenterología de Cali, Colombia. Metodología: estudio de corte transversal de pacientes adultos con PC confirmada por criterios clínicos y radiológicos entre 2011 y 2017. Resultados: se incluyeron 36 pacientes con PC. La mayoría fueron hombres (72,2%) y la media de edad fue 56 (+ 15,1) años. El dolor abdominal crónico fue la presentación clínica más común (83,3%). Cerca de un cuarto de pacientes presentaba diabetes mellitus (22,2%). Se consideró etiología idiopática en 58,3%, alcohólica en el 11,0% y biliar en el 11,0%. La tomografía axial computarizada (TAC), resonancia magnética (RMN) y colangiopancreatografía por RMN fueron los métodos diagnósticos más usados (60,5%), con los que en su mayoría se visualizó atrofia (53,1%), dilatación de conductos (49,0%) y calcificaciones del páncreas (34,7%). Conclusión: los síntomas inespecíficos de la PC en fases iniciales y su largo curso clínico favorecen al subdiagnóstico de esta patología. Los resultados presentados pueden contribuir a la futura creación de escalas clínicas locales que orienten estudios radiológicos y genéticos tempranos, con el fin de lograr un diagnóstico oportuno y mejorar la calidad de vida de estos pacientes.
Abstract Introduction: Chronic pancreatitis (CP) is a progressive inflammation of the pancreas that can lead to irreversible damage and failure. This condition poses great challenges to physicians since its diagnosis can take months or even years. Patient follow-up is often problematic and knowledge about its clinical presentation and epidemiology in Colombia is scarce. This study aims to describe patients with CP treated at a gastroenterology reference center in Cali, Colombia. Methodology: Cross-sectional study in adult patients with CP confirmed based on clinical and radiological criteria between 2011 and 2017. Results: 36 patients with CP were included. The majority were men (72.2%), and the mean age was 56 (+15.1) years. Chronic abdominal pain was the most common clinical presentation (83.3%). About a quarter of patients had diabetes mellitus (22.2%). Etiology was idiopathic in 58.3%, alcoholic in 11.0%, and biliary in 11.0%. Computed tomography (CT), magnetic resonance imaging (MRI), and MRI cholangiopancreatography were the most commonly used diagnostic methods (60.5%), showing mostly atrophy (53.1%), duct dilation (49.0%), and pancreatic calcifications (34.7%). Conclusion: Nonspecific symptoms of CP in early stages and its long clinical course favor the underdiagnosis of this condition. The results presented may contribute to the future creation of local clinical scales that guide early radiological and genetic studies to achieve a timely diagnosis and improve the quality of life of these patients.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Dor Abdominal , Epidemiologia , Pancreatite Crônica , Pacientes , Espectroscopia de Ressonância Magnética , Tomografia , Diagnóstico , Previsões , HospitaisRESUMO
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.
Assuntos
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
BACKGROUND: The use of cyanobacteria and microalgae as cell factories to produce biofuels and added-value bioproducts has received great attention during the last two decades. Important investments have been made by public and private sectors to develop this field. However, it has been a challenge to develop a viable and cost-effective platform for cultivation of cyanobacteria and microalgae under outdoor conditions. Dealing with contamination caused by bacteria, weedy algae/cyanobacteria and other organisms is a major constraint to establish effective cultivation processes. RESULTS: Here, we describe the implementation in the cyanobacterium Synechococcus elongatus PCC 7942 of a phosphorus selective nutrition system to control biological contamination during cultivation. The system is based on metabolic engineering of S. elongatus to metabolize phosphite, a phosphorus source not normally metabolized by most organisms, by expressing a bacterial phosphite oxidoreductase (PtxD). Engineered S. elongatus strains expressing PtxD grow at a similar rate on media supplemented with phosphite as the non-transformed control supplemented with phosphate. We show that when grown in media containing phosphite as the sole phosphorus source in glass flasks, the engineered strain was able to grow and outcompete biological contaminants even when the system was intentionally inoculated with natural competitors isolated from an irrigation canal. The PtxD/phosphite system was successfully used for outdoor cultivation of engineered S. elongatus in 100-L cylindrical reactors and 1000-L raceway ponds, under non-axenic conditions and without the need of sterilizing containers and media. Finally, we also show that the PtxD/phosphite system can be used as selectable marker for S. elongatus PCC 7942 transgenic strains selection, eliminating the need of antibiotic resistance genes. CONCLUSIONS: Our results suggest that the PtxD/phosphite system is a stable and sufficiently robust strategy to control biological contaminants without the need of sterilization or other complex aseptic procedures. Our data show that the PtxD/phosphite system can be used as selectable marker and allows production of the cyanobacterium S. elongatus PCC 7942 in non-axenic outdoor reactors at lower cost, which in principle should be applicable to other cyanobacteria and microalgae engineered to metabolize phosphite.
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Smoking increases susceptibility to becoming infected with and developing tuberculosis. Among the components of cigarette smoke, nicotine has been identified as the main immunomodulatory molecule; however, its effect on the innate immune system is unknown. In the present study, the effect of nicotine on molecules of the innate immune system was evaluated. Lung epithelial cells and macrophages were infected with Mycobacterium tuberculosis (Mtb) and/or treated with nicotine. The results show that nicotine alone decreases the expression of the Toll-like receptors (TLR)-2, TLR-4 and NOD-2 in all three cell types, as well as the production of the SP-D surfactant protein in type II pneumocytes. Moreover, it was observed that nicotine decreases the production of interleukin (IL)-6 and C-C chemokine ligand (CCL)5 during Mtb infection in epithelial cells (EpCs), whereas in macrophages derived from human monocytes (MDMs) there is a decrease in IL-8, IL-6, tumor necrosis factor (TNF)-α, IL-10, CCL2, C-X-C chemokine ligand (CXCL)9 and CXCL10 only during infection with Mtb. Although modulation of the expression of cytokines and chemokines appears to be partially mediated by the nicotinic acetylcholine receptor α7, blocking this receptor found no effect on the expression of receptors and SP-D. In summary, it was found that nicotine modulates the expression of innate immunity molecules necessary for the defense against tuberculosis.
Assuntos
Células Epiteliais Alveolares/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Macrófagos/imunologia , Mycobacterium tuberculosis/imunologia , Nicotina/farmacologia , Tuberculose Pulmonar/imunologia , Células A549 , Células Epiteliais Alveolares/microbiologia , Células Epiteliais Alveolares/patologia , Citocinas/imunologia , Regulação da Expressão Gênica/imunologia , Humanos , Macrófagos/microbiologia , Macrófagos/patologia , Proteína Adaptadora de Sinalização NOD2/imunologia , Receptor 2 Toll-Like/imunologia , Receptor 4 Toll-Like/imunologia , Tuberculose Pulmonar/patologiaRESUMO
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.
Assuntos
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
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.
Assuntos
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
The effect of protein enriched Opuntia cladodes supplementation upon changes of serum total protein, urea, cholesterol, glucose as related to estrus induction (EI%), estrus latency (EL, h), and ovulation rate (OR, units) in adult anestrous goats exposed to the male effect was evaluated. In late April, anestrus goats (n = 45, 25° N) homogeneous regarding live weight (LE; 43.8 ± 1.6 kg) and body condition score (BCS; 2.3 ± 0.1 units) were randomly assigned to: (1). Protein-enriched Opuntia (PEO; n = 15; 29.8% CP, 2.2 Mcal ME kg-1), (2). Non-enriched Opuntia (NEO; n = 15; 6.4% CP, 2.1 Mcal ME kg-1), and (3). Control (CON; n = 15). NEO and PEO goats were individually supplemented with cladodes (160 g d-1; 0900-1000 h), thereafter all groups grazed in a marginal rangeland (1000-1800 h). Neither LW (p > 0.05) nor BCS (p > 0.05) differed among groups, yet an increased (p < 0.05) EI % (100, 57, 42 ± 0.16%), EL h (62, 60, 32 ± 4.2 h), and OR (1.33, 0.71, 0.43 ± 0.23 units) occurred in PEO and NEO vs. CONT, respectively. However, neither blood metabolites differed among groups nor a treatment x time interaction occurred. Peri-breeding protein enriched Opuntia cladodes supplementation of anestrous goats exposed to active males increased (p < 0.01) reproductive outcomes during the non-breeding season.
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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.
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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.
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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
A key biomarker in the study of differentiated thyroid cancer is thyroglobulin. Measurements of the levels of this protein in the blood are determined using laboratory instruments that cannot detect very small concentrations below a threshold, generating left-censored measurements. In the presence of censoring, ordinary least-squares regression models generate biased parameter estimates; therefore, it is necessary to resort to more complex models that consider the censored observations and the behavior of the distribution of the response variable, such as censored and mixed regression models. These techniques were used to model the relationship between thyroglobulin levels in individuals with differentiated thyroid cancer before and after treatment with radioactive iodine (I-131). Log-normal, log-skew-normal, log-power-normal, and log-generalized-gamma probability distributions were used to model the behavior of errors in the adjusted models. Log-generalized-gamma distribution yielded the best results according to the established model selection criteria.
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Modelos Estatísticos , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/radioterapia , Adulto , Biomarcadores Tumorais/sangue , Feminino , Humanos , Radioisótopos do Iodo , Funções Verossimilhança , Masculino , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
La estenosis aórtica severa sintomática secundaria a calcificación degenerativa constituye un reto terapéutico si el paciente no es tributario de tratamiento quirúrgico de reemplazo valvular. La colocación de un implante valvular aórtico transcatéter (TAVI) es una alternativa terapéutica para estos casos. Se presenta el caso de un varón de 78 años con antecedentes de hipertensión arterial, enfermedad renal crónica (estadio IIIa), tabaquismo pesado, portador de marcapaso definitivo, enfermedad arterial periférica y policitemia vera. A la evaluación, el paciente cursaba con una disnea de clase III (escala NYHA) desde hace un año. El ecocardiograma transtorácico mostró calcificación severa de velos aórticos, una fracción de eyección ventricular izquierda de 44,7% y un área valvular de 0,58 cm2 (0,31 cm2/m2); la angiografía mostró enfermedad arterial coronaria moderada y la angiotomografía una calcificación severa de la aorta torácica ('aorta en porcelana'). Por considerarlo de alto riesgo, se realizó colocación de TAVI por vía transapical (válvula bioprotésica Braile Biomédica N° 30), con controles ecocardiográficos satisfactorios. El caso que presentamos constituye el primero realizado en el norte del país
Severe symptomatic aortic stenosis secondary to degenerative calcification may be a real therapeutic challenge if the patient does not undergo an aortic valve replacement. Transapical transcatheter aortic valve replacement is a valid therapeutic option for these cases. We present the case of a 78-year old male with the following past and current medical history: high blood pressure, chronic kidney disease (stage IIIa), heavy tobacco smoking, use of a permanent pacemaker, peripheral arterial disease, and polycythemia vera. When assessed, the patient had had class III heart failure (NYHA classification) for one year. Transthoracic ultrasonography showed severe calcification of the aortic cusps, a 44.7% left ventricular ejection fraction, and a 0.58 cm2 (0.31 cm2/m2) valve surface area. Angiography showed moderate coronary heart disease, and angiotomography showed severe calcification of the aortic valve ('porcelain aorta'). Since this patient was considered at high-risk, a transapical transcatheter aortic valve replacement was performed (Braille Biomedical N° 30 bioprosthetic valve), and the ultrasonography controls showed satisfactory results. This case is the first procedure of its kind performed in Northern Peru
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RESUMEN Introducción: Las mordeduras de serpiente continúan siendo un problema de salud pública, especialmente en países tropicales como Colombia. Objetivo: Caracterizar los casos de accidente ofídico atendidos en un nuevo centro de asesoría toxicológica de Medellín, Colombia. Metodología: Se realizó un estudio descriptivo, retrospectivo, revisando la base de datos donde se registra la información relacionada con la asesoría brindada por dicho centro desde el 1 de enero hasta el 31 de diciembre de 2016. Resultados: Se registraron 117 casos de accidente ofídico, de los cuales 93 (79%) eran hombres y 24 (21%) mujeres, con una mediana de edad de 32 años (rango: 2 a 82 años). El seguimiento de los casos pudo lograse en 55 de los 117 accidentes (47%), y se describieron complicaciones en 18 de los 55 (33%) pacientes. La complicación descrita con mayor frecuencia fue brote maculopapular pruriginoso asociado con la administración del suero, sin que se identificaran diferencias entre las distintas marcas de suero antiofídico utilizado. Se documentó la muerte de un paciente (0,85%). El género Bothrops produjo la mayoría de los accidentes. Discusión: Los datos obtenidos coinciden con la bibliografía publicada.
ABSTRACT Introduction: Snakebites continue to be a public health problem, especially in tropical countries like Colombia. Objetive: To characterize the snakebite cases attended by a new poison center in Medellin, Colombia. Methodology: A descriptive, retrospective study was carried out, reviewing the information of the Center's database from January 1st to December 31st, 2016. Results: There were 117 cases of ophidian accidents, affecting 93 men (79%) and 24 women (21%), with a median age of 32 years (range: 2 to 82 years). The follow-up of the cases could be done in 55 of the 117 accidents (47%), and complications were described in 18 of those 55 (33%) patients. The most commonly reported complication was a pruritic maculopapular rash that was associated to serum administration, without differences between the several brands of anti-ophidian serum used. The death of one patient (0.85%) was documented. The genus Bothrops caused most of the accidents. Discussion: Our results agree with previously published data.
Assuntos
Humanos , Mordeduras de Serpentes , Doença do Soro , Toxicologia , Colômbia , Animais PeçonhentosRESUMO
Estimado editor, Hemos leído el informe “El debate de la regulación de medicamentos biotecnológicos: Colombia en el contexto internacional” (1). El artículo inicia describiendo la regulación de precios de medicamentos basada en referencias nacionales e internacionales como una estrategia de “alivio fiscal parcial al sistema de salud colombiano”, y resalta que solo mediante la competencia esta estrategia sería completa y duradera. La figura 1 ilustra, sin lugar a dudas, el impacto positivo en la reducción de precios (-23%). En el resto del artículo se busca justificar la llamada “ruta abreviada de la comparabilidad colombiana” (RACC), que elimina la obligatoriedad de estudios preclínicos y clínicos, y se concluye que se “evidencia que dicha posición no es aislada y está basada en tendencias regulatorias globales”. Lamentamos estar en desacuerdo. La información contenida en el mismo estudio y otras referencias nos llevan a una conclusión diferente. No es lo mismo eximir que reducir. Aunque los autores usan el término exención en forma permanente, por ejemplo, “en la ruta abreviada colombiana no se permite exenciones para los estudios analíticos, las posibles exenciones se refieren exclusivamente a los estudios clínicos o preclínicos”; en la conclusión modifican el término y sostienen que la RACC solo implica “reducción de pruebas clínicas”, lo cual seguiría la tendencia mundial...