ABSTRACT
We aim to study the SCN5A gene in a cohort of Brugada syndrome (BS) patients and evaluate the genotype-phenotype correlation. BS is caused by mutations in up to 10 different genes, SCN5A being the most frequently involved. Large genomic rearrangements in SCN5A have been associated with conduction disease, but its prevalence in BS is unknown. Seventy-six non-related patients with BS were studied. Clinical characteristics and family risk profile were recorded. Direct sequencing and multiplex ligation-dependent probe amplification (MLPA) of the SCN5A gene for identification of mutations and larger rearrangements were performed, respectively. Eight patients (10.5%) had point mutations (R27H, E901K, G1743R (detected in three families), V728I, N1443S and E1152X). Patients with mutations had a trend toward a higher proportion of spontaneous type I Brugada electrocardiogram (ECG) (87.5% vs 52.9%, p = 0.06) and had evidence of familial disease (62.5%, vs 23.5%, p = 0.03). The symptoms and risk profile of the carriers were not different from wild-type probands. There were non-significant differences in the prevalence of type I ECG, syncope and history of arrhythmia in carriers of selected polymorphisms. None of the patients had any deletion/duplication in the SCN5A gene. In conclusion, 10.5% of our patients had mutations in the SCN5A gene. Patients with mutations seemed to have more spontaneous type I ECG, but no differences in syncope or arrhythmic events compared with patients without mutations. Larger studies are needed to evaluate the role of polymorphisms in the SCN5A in the expression of the phenotype and prognosis. Large rearrangements were not identified in the SCN5A gene using the MLPA technique.
Subject(s)
Brugada Syndrome/genetics , Genetic Predisposition to Disease/genetics , Mutation , NAV1.5 Voltage-Gated Sodium Channel/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Brugada Syndrome/pathology , Child , Child, Preschool , Cohort Studies , DNA Mutational Analysis , Female , Gene Frequency , Genotype , Humans , Infant , Logistic Models , Male , Middle Aged , Multiplex Polymerase Chain Reaction , Phenotype , Young AdultABSTRACT
Las abejas melíferas son afectadas por gran cantidad de enfermedades infecciosas principalmente producidas por bacterias, hongos, virus y parásitos eucariotas. Dentro de las ocasionadas por procariotas, la loque americana es una enfermedad extremadamente grave que afecta a larvas y pupas de abejas; su agente causal es la bacteria esporulada Paenibacillus larvae. La administración de antibióticos es la principal alternativa para el control de esta enfermedad en colmenares con altos niveles de infección. El objetivo del presente trabajo fue determinar, mediante un método biológico, la unión de los antibióticos tilosina, tilmicosina y oxitetraciclina a las proteínas presentes en abejas adultas, larvas menores de 72 horas, larvas mayores de 72 horas, jalea de obreras, miel y polen, con la finalidad de diseñar un modelo de ruta cinética de los antibióticos. Los límites de sensibilidad de la técnica de valoración de estos antibióticos fueron 0,05 μg/ml para tilosina y tilmicosina, y 0,01 μg/ml para oxitetraciclina. Los coeficientes de correlación fueron superiores a 0,90 y los coeficientes de variación intra e inter-ensayo inferiores al 5%. Tanto tilosina como oxitetraciclina presentaron un porcentaje de unión a proteínas de un 15% en promedio en tejidos y subproductos de la colmena, lo cual resultó inferior a lo observado con tilmicosina (29% en promedio). En conclusión, por sus características químicas, su actividad antimicrobiana y su baja tasa de unión a las abejas, larvas y subproductos de la colmena, la tilosina presenta propiedades farmacocinéticas que podrían representar una ventaja terapéutica para el tratamiento de la loque americana en colmenas.
American Foulbrood (AFB) caused by the spore-forming bacterium Paenibacillus larvae is the most serious disease of bacterial origin affecting larvae and pupae of honeybees. Antibiotics are used in many countries for the control of AFB in high incidence areas, but their misuse may lead to antibiotic resistance of bacterial strains and honey contamination. The objective of the present work was to determine, through a biological method, the protein binding of tylosin, tilmicosin and oxytetracycline to worker jelly; honey; pollen; adult bees and larvae in order to propose their kinetic routes. The sensitivity limit of the technique used was 0.05 μg/ml for tylosin and tilmicosin and 0.01 μg/ml for oxytetracycline, respectively. The method had intra and inter-assay correlation coefficients over 0.90, respectively and a coefficient variation of intra-and inter-assay for all antibiotics and processed samples under 5%. Tylosin and oxytetracycline presented lower percentages of protein binding in tissues and hive products (average 15%) in relation to those observed for tilmicosin (29%). In conclusion, tylosin is useful for AFB control in honey bee colonies due to its chemical characteristics, antimicrobial activity and levels of protein binding in bees, larvae, and beehive products.
Subject(s)
Animals , Anti-Bacterial Agents/metabolism , Bees/metabolism , Insect Proteins/metabolism , Oxytetracycline/metabolism , Tylosin/analogs & derivatives , Tylosin/metabolism , Anti-Bacterial Agents/pharmacokinetics , Bees/growth & development , Fatty Acids/analysis , Fatty Acids/metabolism , Honey/analysis , Larva/metabolism , Oxytetracycline/pharmacokinetics , Protein Binding , Pollen/chemistry , Pollen/metabolism , Tylosin/pharmacokineticsABSTRACT
American Foulbrood (AFB) caused by the spore-forming bacterium Paenibacillus larvae is the most serious disease of bacterial origin affecting larvae and pupae of honeybees. Antibiotics are used in many countries for the control of AFB in high incidence areas, but their misuse may lead to antibiotic resistance of bacterial strains and honey contamination. The objective of the present work was to determine, through a biological method, the protein binding of tylosin, tilmicosin and oxytetracycline to worker jelly; honey; pollen; adult bees and larvae in order to propose their kinetic routes. The sensitivity limit of the technique used was 0.05 µg/ml for tylosin and tilmicosin and 0.01 µg/ml for oxytetracycline, respectively. The method had intra and inter-assay correlation coefficients over 0.90, respectively and a coefficient variation of intra-and inter-assay for all antibiotics and processed samples under 5%. Tylosin and oxytetracycline presented lower percentages of protein binding in tissues and hive products (average 15%) in relation to those observed for tilmicosin (29%). In conclusion, tylosin is useful for AFB control in honey bee colonies due to its chemical characteristics, antimicrobial activity and levels of protein binding in bees, larvae, and beehive products.
