Disfunción tiroidea inducida por amiodarona en pacientes portadores de arritmias / Thyroid dysfunction induced by Amiodarone in patient with arrhythmias

Evaluar la presencia de disfunción tiroidea en pacientes con arritmias cardíacas tratados con Amiodarona (AMD) Métodos: se realizó el estudio en 24 pacientes que presentaron arritmias supraventriculares o ventriculares tratados con AMD, atendidos en el Servicio de Medicina Interna de la Ciudad Hospitalaria "Dr. Enrique Tejera" durante el período julio 2015 ­ abril 2016. Se les determinaron T3L, T4L y TSH a manera de tamizaje previo a la administración de AMD y fueron citados y divididos en 3 grupos de 3, 6 y 12 meses de tratmiento de AMD con determinación del perfil tiroideo en la consulta. Resultados: El hipotiroidismo inducido por AMD (HIA) se presentó en 20,83% (n=5), siendo más frecuente en aquellos pacientes asculinos que tenían 3 meses de tratamiento y que recibían una dosis de 1400 mg/semanal. La tirotoxicosis inducida por AMD (TIA) se presentó en 8,33% (n=2) ambos masculinos con dosis de 1400 mg/semanal. No se encontró asociación entre HIA y TIA con el tiempo, dosis, grupo etario ni género (P>0,05). T3L, T4L y TSH registraron el mayor y menor promedio a los 12 y 3 meses (P < 0,05); 12 y 6 meses; 3 y 12 meses respectivamente. Conclusión: La frecuencia de HIA fue de 20,83 % y TIA de 8,33 %. No hubo asociación estadísticamente significativa entre la HIA o TIA con la duración de consumo, dosis, grupo etario ni género. La TSH presentó el mayor promedio a los 3 meses, la T3L y T4L a los 12 meses (AU)

to evaluate the presence of thyroid dysfunction in patients with cardiac arrhythmia who were treated with Amiodarone (AMD). Methods: the study was done in 24 patients who were treated for supraventricular or ventricular arrhythmia at the Department of Internal Medicine of Hospital "Dr. Enrique Tejera" in Valencia, Venezuela from July 2015 to April 2016. FT3, FT4 and TSH were measured to the administration of AMD. The patients were divided in 3 groups according to time of use of the drug as follows: 3, 6 and 12 months, and their thyroid function was measured at each of these periods. Results: 20.83 % (n=5) presented Amiodarone induced hypothyroidism (AIH), which was more frequent in males at 3 months of treatment and who received 1400 mg weekly. Amiodarone induced thyrotoxicosis (AIT) was found in 8.33% (n=2) also in male patients using 1400mg weekly. There was no association between AIH or AIT and duration, dose of AMD, age or gender. (p>0.05) FT3, FT4 and TSH registered their higher and lower averages on 12 and 3 months (P < 0,05); 12 and 6 months; 3 and 12 months respectively. Conclusion: AIH's frequency was 20.83 % and 8.33% for AIT. There was no statistically significant association between AIH or AIT and duration, dose of AMD, age or gender TSH average measure was higher at 3 months and the FT3 and FT4 at 12 months(AU)

UVA photoinduced yeast protein modifications by methylene blue and naproxen.

UVA photosensitization by methylene blue (MB) or by naproxen (NAP) towards cell proteins in yeast Saccharomyces cerevisiae was investigated in order to compare this system with two simpler models, such as free Trp in solution and as a component of bovine and human serum albumin. The process was studied by monitoring protein tryptophan (Trp) residue integrity. The sensitized photodegradation of proteins resulted in different degrees of Trp damage with different Trp (photo)-products. Indeed, many of these Trp derivatives are diagnostic for the photosensitization mechanism and some of them were obtained from cells by UVA photosensitization for the first time in this work. The analysis of quantum yields of photoproduct distribution allowed us to weigh up the type I/II contribution on a UVA photosensitization mechanism. The UVA mediated generation of these Trp derivatives is consistent with the occurrence of singlet oxygen formation (almost dominant in MB), and photoionization (significant in NAP) within the protein matrix. The results obtained in the case of this more complex system (cell) are in agreement with the two simpler models recently studied in our lab. The quantum yields of Trp photoinduced degradation, as well as of its photoproducts formation, decrease with increasing the complexity of the investigated target.

Photoinduced protein modifications by methylene blue and naproxen.

HPLC and emission spectroscopy were used to investigate UVA photosensitization of methylene blue (MB) or naproxen (NAP) towards bovine serum albumin (BSA). In addition, time resolved singlet oxygen measurements were carried out. The most stable drug : protein adducts stoichiometry of MB-BSA (1 : 1) and NAP-BSA (9 : 1) were verified by means of binding constant determination. UVA photosensitization of MB or NAP on BSA was studied by monitoring tryptophan (Trp) residue integrity. The sensitized photodegradation of the BSA resulted in different degrees of Trp damage. Thus, protein damage was determined by quantitative measurements of the different Trp (photo)-products. Indeed, many of these Trp derivatives are diagnostic for the photosensitization mechanism and some of them, for the first time in this work, were obtained by UVA photosensitization in proteins. The analysis of quantum yields of the photoproduct distribution allowed to weigh up the type I/II contribution to the UVA photosensitization mechanism. As expected, additional experiments in deuterated solvent resulted in an increase of the photodegradation quantum yields for those species where a singlet oxygen mechanism was involved. The UVA mediated generation of these Trp derivatives is consistent with the occurrence of singlet oxygen formation (almost dominant in MB), and photoionization (significant in NAP) within the protein matrix. Additional experiments at lower NAP concentration, as well as with human serum albumin (which differs for Trp content and, partially, localization), support further the molecular mechanism of photosensitization proposed. The results obtained in the case of this more complex system are in agreement with the free Trp model, even if, in almost all cases, the Trp photoproduct formation quantum yields are lower, due to the higher number of sensitization targets in the proteins.

Photosensitization reactions of fluoroquinolones and their biological consequences.

This review focuses on damage photosensitized by the fluoroquinolone (FQ) antibacterial drugs. Different models are employed to study biosubstrate photodamage mediated by FQs (organisms, cells, isolated biomolecules and super molecules). Being that the effect of environment (polarity of the medium, ions, pH, binding with bio-molecules, etc.) is crucial in FQ photochemistry, photobiological reactions can be consequently dramatically influenced. Thus, the photosensitization processes induced by FQs are here discussed taking into account that such extensive and cross-targeted pathological implications request an excursus covering photosensitization in systems of increasing molecular complexity. In vivo and in vitro evidences for photoallergy, phototoxicity, photomutagenesis and photocarcinogenesis mediated by FQs are discussed.

Role of aromatic amino acid tryptophan UVA-photoproducts in the determination of drug photosensitization mechanism: a comparison between methylene blue and naproxen.

The aromatic amino acid tryptophan is the most susceptible protein residue involved in various photosensitized adverse effects. Of these processes, the tryptophan photosensitization induced by methylene blue has been well studied. A predominant type II photosensitizing activity, mediated by singlet oxygen, has been already demonstrated on various models. The purpose of this study is to compare this photosensitization system with that induced by naproxen, belonging to the class of non-steroidal anti-inflammatory drugs. For this compound, a type I (radical) and type II (singlet oxygen) cooperative mechanism of photoinduced damage was previously proposed. This study represents an example of testing drugs on the simple experimental model of amino acid residues in proteins. Particular emphasis is dedicated to modifications caused by the formation of drug photomediated toxic species, such as reactive oxygen species (ROS). This is achieved following the kinetics of photodegradation of the sensitizers and of the amino acid, as well as the formation of their photoproducts and by evaluation of quantum yields of the various processes. Tryptophan photoproducts represent biomarkers of oxidative damage indicative for protein photooxidation and for the molecular mechanism of photosensitization; some of these have been identified for the first time as UVA photosensitization products. The pattern of Trp photoproducts formed by the two compounds differs and is specific for each type of sensitization process. These observations support extending the investigation to systems of increasing molecular complexity, that is Trp in isolated proteins and in cells and represent an effort to provide a simplified rationale of the complex picture coming out from literature data and our experimental results.