Vascular calcification and growth arrest specific protein 6 levels in chronic renal failure / Calcificación vascular y detención de crecimiento de proteína específica 6 niveles en insuficiencia renal crónica

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 group 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 the 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 the dialysis (63.85±38.92 ng/mL) and the 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

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 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 diabética. 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 considerablemnete 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

Role of Adipokines and Hormones of Obesity in Childhood Asthma

PURPOSE: The aim of this study was to evaluate serum levels of leptin, ghrelin, and adiponectin in obese and non-obese children with asthma and in healthy non-asthmatic children, and analyze their relationships with clinical outcomes. METHODS: This study enrolled 40 obese and 51 non-obese children with asthma and 20 healthy children. Body mass index and serum leptin, ghrelin, and adiponectin levels were determined in all children. Asthma symptom scores and lung function test results were recorded for subjects with asthma. RESULTS: Serum leptin levels (11.8+/-7.9, 5.3+/-6.8, and 2.1+/-2.4 ng/mL in the obese asthmatic, non-obese asthmatic, and control groups, respectively) and adiponectin levels (12,586.2+/-3,724.1; 18,089.3+/-6,452.3; and 20,297.5+/-3,680.7 ng/mL, respectively) differed significantly among the groups (P<0.001 for all). Mean ghrelin levels were 196.1+/-96.8 and 311.9+/-352.8 pg/mL in the obese and non-obese asthmatic groups, respectively, and 348.8+/-146.4 pg/mL in the control group (P=0.001). The asthma symptom score was significantly higher in the obese children with asthma than in the non-obese children with asthma (P<0.001). Leptin and adiponectin levels were correlated with the asthma symptom score in non-obese children with asthma (r=0.34 and r=-0.62, respectively). CONCLUSIONS: Obesity leads to more severe asthma symptoms in children. Moreover, leptin, adiponectin, and ghrelin may play important roles in the inflammatory pathogenesis of asthma and obesity co-morbidity.

The relationship between symptoms and patient characteristics among psoriasis patients.

Background: Pruritus is a common symptom of many dermatological and systemic diseases. It is a common complaint among patients with psoriasis of the chronic plaque type. Patients with pruritus suffer from more severe psoriasis although some authors did not find a significant relationship between pruritus intensity and psoriasis severity. Aims: In this study, we aimed to investigate the relationship between clinical features and symptoms among psoriasis patients. And also we aimed to evaluate whether the severity of disease, depression and quality of life scores could effect these symptoms or not. Methods: Eighty seven patients with psoriasis were enrolled in this study. Epidemiological data of patients were noted. Clinical symptoms, such as pruritus, pain, burning, exudation, bleeding, weakness, etc. were interrogated. The answers to these questions were classified as 'never', 'rare', 'sometimes', 'often' and 'all the time'. Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), Hamilton Anxiety-Depression Scale (HAD) were calculated for each patient. PASI and DLQI scores were classified as ≥ and <10. Results: We found that the most frequent symptom was pruritus (96.6%). Other frequent symptoms were burning (56.3%), exudation (56.3%) and bleeding (49.4%). Hurting, sensitiveness and bothering were more frequent in women. Percentages of hurting, pain, exudation and weakness symptoms had been increasing with age. Frequency of weakness was significantly high in PASI ≥ 10 patients. Conclusion: Pruritus is a very common symptom in psoriasis. Burning, exudation and bleeding are also common symptoms seen in psoriasis. New scoring systems including symptoms of psoriasis patients may be developed for evaluating the severity of the disease.

Comparison of the efficacy of combination and monotherapy with caspofungin and liposomal amphotericin B against invasive candidiasis

To investigate if combination therapy with liposomal amphotericin B LAmB, and caspofungin CAS is superior to monotherapies in an experimental model with azole-resistant Candida albicans. This study was carried out between October 2006 and August 2007 in Celal Bayar University, Manisa, Turkey. A total of 144 mice were included in the study, and divided into 4 groups as: control n=36, CAS treatment group n=36, LAmB treatment group n=36, and combination therapy group n=36. Treatment efficacy was assessed by determining survival, as well as, the decrease in tissue fungal densities. The fungal densities in tissues were significantly reduced, and the survival rates were prolonged with either CAS only, or LAmB only, or with combination therapy compared to those of controls p<0.05. There was no significant difference between monotherapy groups. Decrease in tissue fungal densities were significant in CAS and LAmB 1mg/kg combination group, compared to CAS 1mg/kg and LAmB 1mg/kg groups p=0.004 for CAS, p=0.009 for LAmB. Survival rates were similar in both treatment groups. The combination treatment was superior with 1mg/kg of doses of LAmB and CAS in terms of reducing the tissue fungal burden. Although with combination therapy the survival rates prolonged in all subgroups, no significant difference between the combination and monotherapies could be shown. Additional studies with a large number of cases are warranted to investigate the superiority of combination therapy

Drug-resistant pulmonary tuberculosis in western Turkey: prevalence, clinical characteristics and treatment outcome

Although high antituberculosis [anti-TB] drug resistance rates have been reported in Turkey, the clinical characteristics and implications for the outcome of anti-TB treatment have not been fully investigated. We determined the prevalence of anti-TB drug resistance and examined demographic data, clinical characteristics and treatment outcome in relation to patterns of resistance. From the TB case registry of a university hospital and the two largest dispensaries in Manisa city, we identified all pulmonary TB cases with a culture-proven definitive diagnosis and antimicrobial susceptibility results for a 7-year period. We collected and analyzed demographic and clinical data and information on treatment outcome for those cases in relationship to anti-TB drug resistance. Of 355 M. tuberculosis strains, 71.5% were susceptible to streptomycin, isoniazid, rifampicin and ethambutol. Any drug resistance and multi-drug resistance [MDR] rates were 21.1% and 7.3% and were higher in males [53% and 9%, respectively] than in females [22% and 1%, respectively]. Drug resistance was significantly higher in old cases [acquired drug resistance] vs new cases [primary drug resistance], and was associated with treatment failure [P<0.001]. The prevalence of MDR was significantly higher in the old cases [22.4%] than in the new cases [4.4%] [P<0.001]. Symptoms, radiographic findings, associated diseases, and sputum smear positivity were unrelated to the development of resistance. The prevalence of any drug resistance and MDR was significantly higher in those with treatment failure than in patients with treatment success. High resistance rates, particularly for acquired MDR, indicate a need for improvement in the TB control programme in our region