RESUMO
Monoclonal antibodies or fusion proteins, defined as biological drugs, have modified the natural history of numerous immune-mediated disorders, allowing the development of therapies aimed at blocking the pathophysiological pathways of the disease, providing greater efficacy and safety than conventional treatment strategies. Virtually all therapeutic proteins elicit an immune response, producing anti-drug antibodies (ADAs) against hypervariable regions of immunoglobulins. Immunogenicity against biological drugs can alter their pharmacokinetic and pharmacodynamic properties, thereby reducing the efficacy of these drugs. In more severe cases, ADAs can neutralize the therapeutic effects of the drug or cause serious adverse effects, mainly hypersensitivity reactions. The prevalence of ADAs varies widely depending on the type of test used, occurrence of false-negative results, and non-specific binding to the drug, making it difficult to accurately assess their clinical impact. Concomitant use of immunosuppressors efficiently reduces the immunogenicity in a dose-dependent manner, either by decreasing the frequency of detectable ADAs or by delaying their appearance, thereby enhancing the effectiveness of biological therapies. Among the new therapeutic strategies for the management of psoriasis, biological agents have gained increasing importance in recent years as they interrupt key inflammation pathways involved in the physiopathology of the disease. Reports regarding ADA in new biologics are still scarce, but the most recent evidence tends to show little impact on the clinical response to the drug, even with prolonged treatment. It is therefore essential to standardize laboratory tests to determine the presence and titles of ADAs to establish their administration and management guidelines that allow the determination of the real clinical impact of these drugs.
Assuntos
Humanos , Psoríase/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Anticorpos MonoclonaisRESUMO
En la actualidad, las infecciones de piel y partes blandas forman parte de un alto porcentaje de las consultas en salud. Estas van desde infecciones leves, donde el manejo se realiza con tratamiento tópico, hasta aquellas con severo compromiso sistémico, requiriendo terapia antibiótica sistémica e incluso el desbridaje quirúrgico. En general, son producto de un desbalance entre los mecanismos de defensa de la barrera cutánea y los factores de virulencia y patogenicidad de los microorganismos que la afectan. Se pueden clasificar según distintos criterios, como por ejemplo, profundidad, gravedad, microorganismos involucrados y si estas son purulentas o no. El reconocer estas entidades clínicas es de suma importancia para llevar a cabo un adecuado tratamiento en los pacientes que presentan estas afecciones, ya que los diagnósticos erróneos llevan a las múltiples consultas con el consiguiente aumento de costos asociados en atención en salud.
Currently, skin and soft tissue infections are part of a high percentage of health consultations. These range from mild infections, where management is performed with topical treatment, to those with severe systemic compromise requiring systemic antibiotic therapy and even surgical debridement. In general, they are the product of an imbalance between the defense mechanisms of the skin barrier and the virulence and pathogenicity factors of the microorganisms that affect it, which can vary from bacterial, viral, fungal and parasites agents. Skin and soft tissue infections can be classified according to different criteria, such as depth, severity, microorganisms involved and whether they are purulent or not. Recognizing these clinical entities is of utmost importance to carry out adequate treatment in patients with these conditions, since erroneous diagnoses lead to multiple consultations with the consequent increase in costs associated with health care
Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Dermatopatias Infecciosas/diagnóstico , Dermatopatias Infecciosas/microbiologia , Dermatopatias Infecciosas/tratamento farmacológico , Dermatopatias Infecciosas/classificação , Fatores de Risco , Antibacterianos/uso terapêuticoRESUMO
American populations are one of the most interesting examples of recently admixed groups, where ancestral components from three major continental human groups (Africans, Eurasians and Native Americans) have admixed within the last 15 generations. Recently, several genetic surveys focusing on thousands of individuals shed light on the geography, chronology and relevance of these events. However, even though gene flow could drive adaptive evolution, it is unclear whether and how natural selection acted on the resulting genetic variation in the Americas. In this study, we analysed the patterns of local ancestry of genomic fragments in genome-wide data for ~ 6000 admixed individuals from 10 American countries. In doing so, we identified regions characterized by a divergent ancestry profile (DAP), in which a significant over or under ancestral representation is evident. Our results highlighted a series of genomic regions with DAPs associated with immune system response and relevant medical traits, with the longest DAP region encompassing the human leukocyte antigen locus. Furthermore, we found that DAP regions are enriched in genes linked to cancer-related traits and autoimmune diseases. Then, analysing the biological impact of these regions, we showed that natural selection could have acted preferentially towards variants located in coding and non-coding transcripts and characterized by a high deleteriousness score. Taken together, our analyses suggest that shared patterns of post admixture adaptation occurred at a continental scale in the Americas, affecting more often functional and impactful genomic variants.
Assuntos
Humanos , Genômica , PopulaçãoRESUMO
Background: Postoperative nausea and vomiting (PONV) prophylaxis with dexamethasone may produce significant hyperglycemia in the postoperative period. Aim: To evaluate if this effect is of greater severity in type 2 diabetics compared with non-diabetic patients. Material and Methods: Forty non-diabetic and thirty type 2 diabetic patients undergoing laparoscopic cholecystectomy were studied in a prospective and double-blind fashion manner. Patients were randomly distributed into 4 groups: Group I, non-diabetics control (n = 20), Group II, non-diabetics dexamethasone (n = 20), Group III, type 2 diabetics control (n = 15), and Group I V, type 2 diabetics dexamethasone (n = 15). Immediately after induction, patients in groups I and III received isotonic saline and patients in the dexamethasone groups received 8 mg iv of the steroid. Capillary blood glucose concentrations were measured at baseline and every 2 hours during the first 12 hours since the start of surgery. A linear mixed effect model, adjusted for baseline capillary glucose concentration, age and duration of surgery was used to analyze the data. Results: No effect of the presence of diabetes mellitus was observed in the evolution of glucose concentrations. There was a difference in capillary glucose concentrations between patients who received dexamethasone and placebo that started 2 hours post-intervention, reaching a mean maximum difference of 34 mg/dl (adjusted model, p < 0.001) at 10 hours post-intervention. Conclusions: In this study, Type 2 diabetic patients did not show a higher susceptibility than non-diabetics to develop postoperative hyperglycemia after the use of prophylactic dexamethasone for PONV.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antieméticos/efeitos adversos , Glicemia/efeitos dos fármacos , Dexametasona/efeitos adversos , /metabolismo , Hiperglicemia/induzido quimicamente , Náusea e Vômito Pós-Operatórios/prevenção & controle , Glicemia/metabolismo , Colecistectomia Laparoscópica/efeitos adversos , /cirurgia , Métodos Epidemiológicos , Hiperglicemia/diagnósticoRESUMO
En los últimos años el despertar transoperatorio es uno de los principales temores de los enfermos que van a ser intervenidos quirúrgicamente y se relaciona a consecuencias como el síndrome de estrés postraumático y a las implicaciones legales resultantes. Diversos reportes que han enfatizado la elevada incidencia del despertar transoperatorio y sus efectos adversos se han diseñado diferentes técnicas para su detección temprana y monitorización; entre los cuales el más importante es el índice biespectral (BIS). El objetivo principal del presente trabajo es el de comparar el consumo de agentes anestésicos durante la anestesia general, monitorizando parámetros hemodinámicos vs. valores BIS. Se realizó un estudio prospectivo, longitudinal observacional y comparativo en la unidad de quirófano y salas de recuperación del Instituto Gastroenterologico Boliviano-Japonés desde junio-agosto 2008 ingresan a este estudio 40 pacientes, de ambos sexos, ASA l-ll, edad entre 20-60 años, programados para cirugía abdominal. Se aplico una ficha de recolección de datos aleatoriamente divididos en 2 grupos de estudio: Grupo I se dosifico los agentes anestésicos a la monitorización del grado de hipnosis mediante el BIS. Grupo II se dosifico los agentes anestésicos a la monitorización de signos clínicos y cambios hemodinámicos. Según los resultados obtenidos se puede observar menor dosificación de drogas durante la anestesia general, en el Grupo monitorizado con BIS con relación al Grupo que se monitorizó con cambios hemodinámicos, lo que significa mayor dosis de anestésicos en los monitorizados con cambios hemodinámicos.
In recent years, intraoperative awakening is one of the main fears of patients who will undergo surgery and is related to consequences such as posttraumatic stress syndrome and the resulting legal implications. Several reports have emphasized the high incidence of intraoperative awakening and adverse effects are designed techniques for early detection and monitoring, among which the most important is the bispectral Índex (BIS).The main objective of this study is to compare the use of anesthetics during general anesthesia, hemodynamic monitoring vs. BIS valúes. We performed a prospective, longitudinal observational and comparative unit of operating and recovery rooms Gastroenterological Bolivian-Japanese Institute from June to August 2008 entered this study 40 patients of both sexes.ASA l-ll, aged between 20 - 60 years, scheduled for abdominal surgery. It applied a data collection sheet randomly divided into 2 study groups: Group I was dosed anesthetic agents to monitor the degree of hypnosis through the BIS. Group II was dosed anesthetic agents to the monitoring of dinical and hemodynamic changes. According to the results you can see lower dosage of drugs during general anesthesia in the BIS monitored group compared with the group that was monitored with hemodynamic changes, which means higher doses of anesthetics on the hemodynamic changes monitored.
RESUMO
El concepto de anestesia describe un fenómeno en el cual los pacientes, mediante unos fármacos, se hacen insensibles frente a un estímulo quirúrgico. La acción de los anestésicos se efectuán sobre el sistema nervioso central, produciéndo inconsciencia y a mayores concentraciones inhibiendo el movimiento frente a un estímulo quirúrugico. La acción de los anestésicos sobre el sistema nervioso central tiene como objetivo producir el estado de inconsciencia y la inhibición de la respuesta somática frente a un estímulo doloroso. De esta manera se introduce el concepto de la CAM (concentración alveolar media) de un anestésico inhala torio como aquella concentración alveolar mínima que inhibe el movimiento en el 50% de los pacientes 1 y la CAM como la concentración que proviene la respuesta frente a un estímulo verbal. A su vez se define el término CAM como aquella concentración de anestésico que inhibe una respuesta automática frente a la incisión quirúrgica 4.