RESUMEN Introducción: La enfermedad cardiovascular es la principal causa de mortalidad y morbilidad en la insuficiencia renal crónica. Se sabe que la calcificación vascular (CV) y el grosor de la íntima-media de la carótida (CIMT, por sus siglas en inglés) están vinculados de forma muy estrecha con enfermedades cardiovasculares. La proteína específica del gen 6 de la detención de crecimiento (Gas6) es una proteína dependiente de la vitamina K y regula diversos procesos, como la proliferación, la supervivencia celular, la migración y la inflamación. La proteína Gas6 es conocida por proteger a las células endoteliales y las células musculares lisas vasculares contra la apoptosis mediante la inhibición de la activación de la caspasa-3 inducida por la proteína Bcl-2. Se ha demostrado la relación entre la Gas6 y las enfermedades cardiovasculares en muchos modelos de ratones y cultivos celulares. Sin embargo, existen informes contradictorios acerca de si los niveles de Gas6 aumentan o disminuyen en estudios de humanos con insuficiencia renal crónica y/o diabetes. En este estudio, el objetivo fue examinar los niveles plasmáticos de Gas6 y su relación con el CIMT y la puntuación de calcificación de las arterias coronarias (CACS, por sus siglas en inglés) en pacientes con enfermedad renal crónica (ERC). Material y métodos: Un total de 137 pacientes fueron incluidos en el estudio, de los cuales 32 estaban en hemodiálisis crónica, 105 en prediálisis, y 73 pacientes representaban controles sanos. Se esudiaron los niveles de Gas6 en muestras de suero mediante el método ELISA. El CIMT se midió por medio de ecografía. La CACS se midió mediante tomografía computarizada multicorte. Resultados: La edad media fue de 54,37 ± 16,61 años en el grupo de diálisis; 55,20 ± 14,80 años en el grupo de prediálisis, y 53,26 ± 9,04 años en el grupo de control. La creatinina sérica fue de 0,78 ± 0,16 mg/dl en el grupo de control; 1,96 ± 1,64 mg/dl en el de prediálisis, y 5,94 ± 1,55 mg/dl en el de diálisis. Las concentraciones de proteína en orina de 24 horas fueron significativamente más altas en el grupo de diálisis que en los de prediálisis y control. Los valores del CIMT fueron similares en los grupos de prediálisis y de diálisis. Estos valores fueron considerablemente más altos que en el grupo de control. Aunque la CACS fue más alta en el grupo de diálisis que en los otros dos, los resultados no fueron estadísticamente significativos, ya que el rango de distribución fue muy amplio. La proteína Gas6 fue de 98,84 ± 53,32 ng/ml en el grupo de control y estadísticamente más alta que en los grupos de diálisis (63,85 ± 38,92 ng/ml) y de prediálisis (54,96 ± 38,49 ng/ml) (p = 0,001). Los niveles de Gas6 fueron más bajos en los pacientes diabéticos que en los no diabéticos (53,69 ± 35,26 ng/ml; 69,26 ± 47,50 ng/ml, [p = 0,023], respectivamente). Se detectó una correlación negativa entre la proteína Gas6 y la edad, el IMC, la CACS, el CIMT y la proteinuria. En el análisis de regresión logística, la Gas6 se mantuvo estrechamente relacionada con el IMC, el CIMT y la proteinuria. Conclusión: En nuestro estudio, la correlación negativa de Gas6 con IMC, CACS, CIMT y proteinuria, y los niveles más bajos de Gas6 en pacientes diabéticos sustentan la idea de que la disminución de los niveles de Gas6 en la insuficiencia renal crónica puede jugar un papel en la calcificación vascular a través de la tolerancia alterada a la glucosa, la inflamación crónica, la disfunción endotelial y el aumento de la apoptosis. La importancia de nuestro estudio radica en que es el primero que muestra una relación entre la Gas6 y la proteinuria, la CACS y el CIMT en pacientes con insuficiencia renal crónica.

ABSTRACT Introduction: Cardiovascular disease is the main cause of mortality and morbidity in chronic renal failure. It s known that vascular calcification (VC) and carotid intima media thickness (CIMT) are strongly associated with cardiovascular diseases. Growth arrest specific protein 6 (Gas6) is a vitamin K-dependent protein and regulates various processes such as proliferation, cell survival, migration and inflammation. Gas6 is known to protect endothelial cells and vascular smooth muscle cells against apoptosis by inhibiting Bcl-2 induced Caspase 3 activation. The relationship between Gas6 and cardiovascular diseases has been demonstrated in many mouse models and cell cultures. However, there are conflicting reports whether Gas6 levels are increasing or decreasing in human studies of diabetic and/or chronic renal failure. In present study the aim was to examine plasma Gas6 levels and its relation with CIMT and coronary artery calcification score (CACS) in chronic kidney disease (CKD) patients. Methods: Total of 137 patients of which 32 chronic hemodialysis and 105 predialysis patients as well as 73 healthy controls were enrolled in the study. Human Gas6 levels in serum samples were studied by ELISA method. CIMT was measured by ultrasonography. CACS was measured by multislice computed tomography. Results: The mean age was 54.37±16.61 years in dialysis group, 55.20±14.80 years in predialysis group and 53.26±9.04 years in control group. Serum creatinine was 0.78±0.16 mg/dl in the control group and 1.96±1.64 mg/dl in the predialysis and 5.94±1.55 mg/dl in the dialysis group. 24 hours urine protein levels were significally higher in the dialysis group than the predialysis and the control group. CIMT values were similar in predialysis and dialysis groups. These values were significantly higher than control group. Although CACS was higher in dialysis group than predialysis and control group, the results were not statistically significant since the distribution range was very wide. Gas6 was 98.84±53.32 ng/mL in the control group and statistically higher than dialysis (63.85±38.92 ng/mL) and predialysis groups (54.96±38.49 ng/mL) (p=0.001). Gas6 levels were lower in diabetic patients than non-diabetics (53.69±35.26 ng/mL, 69.26±47.50 ng/mL, p=0.023, respectively). Negative correlation was detected between Gas6 and age, BMI, CACS, carotid IMT and proteinuria. In the logistic regression analysis, Gas6 remained significantly associated with BMI, CIMT and proteinuria. Conclusion: In our study, a negative correlation of Gas6 with BMI, CACS, CIMT and proteinuria and lower Gas6 levels in diabetic patients support that decreased Gas6 levels in chronic renal failure may have a role in vascular calcification through altered glucose tolerance, chronic inflammation, endothelial dysfunction and increased apoptosis. Our study has an importance because it is the first study showing a relation between Gas6 and proteinuria, CACS and carotid IMT in patients with chronic renal failure.

Resumo Introdução: A etiologia exata da paralisia de Bell ainda permanece obscura. Os únicos achados confirmados são a inflamação e o edema do nervo facial (NF) que levam ao aprisionamento no canal facial. Objetivo: Identificar se há alguma relação entre o grau de paralisia de Bell e o diâmetro do canal facial e também estudar qualquer possível predisposição anatômica do canal facial para a paralisia de Bell incluindo as partes que ainda não foram estudadas. Método: Os prontuários médicos e exames de tomografia computadorizada de 34 pacientes com paralisia de Bell foram avaliados neste estudo clínico retrospectivo. Os diâmetros de ambos os canais faciais (acometidos e não acometidos) de cada paciente foram medidos no segmento labiríntico, gânglio geniculado, segmento timpânico, segundo joelho, segmento mastoideo e forame estilomastoideo. As escalas de House-Brackmann (HB) de cada paciente na apresentação inicial e três meses após o tratamento foram avaliadas a partir de seus prontuários. O teste t de amostras pareadas e o teste dos postos sinalizados de Wilcoxon foram usados para comparação de largura entre o lado acometido e o lado não acometido. O teste de postos sinalizados de Wilcoxon também foi usado para avaliação da relação entre o diâmetro do canal facial e o grau de paralisia de Bell. Diferenças significativas foram estabelecidas em um nível de p = 0,05 (IBM SPSS Statistics for Windows, versão 21.0; Armonk, NY, IBM Corp). Resultados: Foram incluídos 34 pacientes - 16 mulheres, 18 homens; idade média ± desvio padrão (DP), 40,3 ± 21,3 com paralisia de Bell. De acordo com o sistema de classificação do nervo facial de HB, oito pacientes eram de grau V, seis de grau IV, 11 de grau III, oito de grau II e um de grau I. A largura média no segmento labiríntico do canal facial no osso temporal acometido foi significativamente menor do que o equivalente no osso temporal não acometido (p = 0,00). Não houve diferença significativa entre os ossos temporais acometidos e não acometidos no gânglio geniculado (p = 0,87), segmento timpânico (p = 0,66), segundo joelho (p = 0,62), segmento mastoide (p = 0,67) e forame estilomastoideo (p = 0,16). Não houve relação entre o grau de HB e o diâmetro do canal facial no nível do segmento labiríntico (p = 0,41), segmento timpânico (p = 0,12), segmento mastoideo (p = 0,14), gânglio geniculado (p = 0,13) e forame estilomastoideo (p = 0,44), mas houve uma relação significativa no nível do segundo joelho (p = 0,02). Conclusão: O diâmetro do segmento labiríntico do canal facial foi um fator de risco anatômico para a paralisia de Bell. Também houve relação significativa entre o grau de HB e o diâmetro do CF no nível do segundo joelho. Estudos futuros (RM-TC combinadas ou modelagem 3D) são necessários para promover essa possível relevância especialmente no segundo joelho. Assim, no futuro, pode ser possível descomprimir segmentos específicos em pacientes com alto grau de PB.

Abstract Introduction: The exact etiology of Bell's palsy still remains obscure. The only authenticated finding is inflammation and edema of the facial nerve leading to entrapment inside the facial canal. Objective: To identify if there is any relationship between the grade of Bell's palsy and diameter of the facial canal, and also to study any possible anatomic predisposition of facial canal for Bell's palsy including parts which have not been studied before. Methods: Medical records and temporal computed tomography scans of 34 patients with Bell's palsy were utilized in this retrospective clinical study. Diameters of both facial canals (affected and unaffected) of each patient were measured at labyrinthine segment, geniculate ganglion, tympanic segment, second genu, mastoid segment and stylomastoid foramen. The House-Brackmann (HB) scale of each patient at presentation and 3 months after the treatment was evaluated from their medical records. The paired samples t-test and Wilcoxon signed-rank test were used for comparison of width between the affected side and unaffected side. The Wilcoxon signed-rank test was also used for evaluation of relationship between the diameter of facial canal and the grade of the Bell's palsy. Significant differences were established at a level of p = 0.05 (IBM SPSS Statistics for Windows, Version 21.0.; Armonk, NY, IBM Corp). Results: Thirty-four patients - 16 females, 18 males; mean age ± Standard Deviation, 40.3 ± 21.3 - with Bell's palsy were included in the study. According to the HB facial nerve grading system; 8 patients were grade V, 6 were grade IV, 11 were grade III, 8 were grade II and 1 patient was grade I. The mean width at the labyrinthine segment of the facial canal in the affected temporal bone was significantly smaller than the equivalent in the unaffected temporal bone (p = 0.00). There was no significant difference between the affected and unaffected temporal bones at the geniculate ganglion (p = 0.87), tympanic segment (p = 0.66), second genu (p = 0.62), mastoid segment (p = 0.67) and stylomastoid foramen (p = 0.16). We did not find any relationship between the HB grade and the facial canal diameter at the level of labyrinthine segment (p = 0.41), tympanic segment (p = 0.12), mastoid segment (p = 0.14), geniculate ganglion (p = 0.13) and stylomastoid foramen (p = 0.44), while we found significant relationship at the level of second genu (p = 0.02). Conclusion: We found the diameter of labyrinthine segment of facial canal as an anatomic risk factor for Bell's palsy. We also found significant relationship between the HB grade and FC diameter at the level of second genu. Future studies (MRI-CT combined or 3D modeling) are needed to promote this possible relevance especially at second genu. Thus, in the future it may be possible to selectively decompress particular segments in high grade BP patients.

OBJECTIVE: The aim of this prospective study was to compare the resistive index (RI) values, which is a parameter of testicular parenchymal perfusion, in testicular microlithiasis (TM) cases and normal cases. MATERIALS AND METHODS: 2179 volunteers, all healthy men (17-42 years of age) from the Annual Army Reserve Officer Training Corps training camp were included in the study. A screening scrotal ultrasound was performed and all men diagnosed with TM underwent a scrotal Doppler ultrasonography scan (US). US examinations were performed for subjects with TM and without TM as a control group and RI was determined. RESULTS: 53 men with TM were identified in the 2179 US. Spectral Doppler examination was applied to 50 randomly selected cases (100 testicles) without TM and 92 testicles with TM, 39 cases (78 testicles) with bilateral and 14 cases with unilateral involvement. However, 48 normal testicles (17 bilateral and 14 unilateral) and 47 testicles with TM (15 bilateral and 17 unilateral, 10 of which were cases with bilateral TM) where flow from the centripetal artery could be obtained and analyzed were included in the statistical analysis for resistive indices. There was no significant difference regarding the RI and spectral examinations between subjects with and without TM. An interesting finding was the twinkling artifact observed in three cases. CONCLUSION: Microliths did not alter the RI values and thus had no influence on testicular perfusion on Doppler US examination.