A novel mutation of sgk-1 gene in central serous chorioretinopathy

AIM

To investigate the association of serum glucocorticoid kinase gene-1 (SGK-1) DNA variants with chronic central serous chorioretinopathy (CSC).

METHODS

We enrolled 32 eyes of 32 patients who were diagnosed with chronic CSC and composed 32 normal eyes as a control group. Peripheral blood was used for DNA extraction and polymerase chain reaction (PCR) amplification. SGK1 gene was sequenced by using BigDye^® Terminator v3.1 cycle sequencing KIT (Applied Biosystems, Foster City, CA, USA). The SGK1 gene and its variants were investigated in CSC patient group and control group.

RESULTS

We identified a new polymorphism M32V in two person in the patient group (Minor allele frequency (MAF)=0.009) on the region of 1-60 amino acids. The rs1057293 was located in the encoder region of the SGK 1 gene but not associated with CSC (P=0.68). An intrinsic rs1743966 is also not associated (P=0.28).

CONCLUSIONS

The new polymorphism M32V is located on the region of 1-60 amino acids which is necessary for localization to the mitochondria in CSC patient. This mutation is probably important for the energy metabolism and plays an important role in the cellular response to hyperosmotic stress and other stress stimuli. Both rs1057293 and rs1743966 are not associated with CSC.     

Effects of primary selective laser trabeculoplasty on anterior segment parameters

AIM:To investigate the effects of selective laser trabeculoplasty (SLT) on the main numerical parameters of anterior segment with Pentacam rotating Scheimpflug camera in patients with ocular hypertension (OHT) and primary open angle glaucoma (POAG).METHODS: Pentacam measurements of 45 eyes of 25 (15 females and 10 males) patients (12 with OHT, 13 with POAG) before and after SLT were obtained. Measurements were taken before and 1 and 3mo after SLT. Pentacam parameters were compared between OHT and POAG patients, and age groups (60y and older, and younger than 60y).RESULTS: The mean age of the patients was 57.8±13.9 (range 20-77y). Twelve patients (48%) were younger than 60y, while 13 patients (52%) were 60y and older. Measurements of pre-SLT and post-SLT 1mo were significantly different for the parameters of central corneal thickness (CCT) and anterior chamber volume (ACV) (P<0.05). These parameters returned back to pre-SLT values at post-SLT 3mo. Decrease of ACV at post-SLT 1mo was significantly higher in younger than 60y group than 60y and older group. There was no statistically significant difference in Pentacam parameters between OHT and POAG patients at pre- and post-treatment measurements (P>0.05).CONCLUSION:SLT leads to significant increase in CCT and decrease in ACV at the 1^st month of the procedure. Effects of SLT on these anterior segment parameters, especially for CCT that interferes IOP measurement, should be considered to ensure accurate clinical interpretation.     

Formation of functional nanobiocatalysts with a novel and encouraging immobilization approach and their versatile bioanalytical applications

The discovery of functional organic–inorganic hybrid nanoflowers (FNFs) consisting of proteins/enzymes as the organic components and Cu(ii) ion as the inorganic component has made an enormous impact on enzyme immobilization studies. The FNFs synthesized by an encouraging and novel approach not only showed high stabilities but also much enhanced catalytic activities as compared to free and conventionally immobilized enzymes. A recent development demonstrated that FNF formation has moved beyond the initial discovery in which enzymes and Cu²⁺ ions used as the organic and inorganic parts, respectively, are replaced with new organic (chitosan, amino acid and plant extracts) and inorganic (Cu²⁺ and Fe²⁺) materials. The new organic materials incorporated into FNFs act as Fenton-like agents and then show peroxidase-like activity owing to the metal ions and the porous structure of FNFs in the presence of hydrogen peroxide (H₂O₂). All FNFs have been widely utilized in many different scientific and industrial fields due to their greatly enhanced activities and stabilities. This review focuses primarily on the preparation, characterization, and bioanalytical applications of FNFs and explains the mechanisms of their formation and enhanced activities and stabilities.

The discovery of functional organic–inorganic hybrid nanoflowers (FNFs) consisting of proteins/enzymes as the organic components and Cu(ii) ion as the inorganic component has made an enormous impact on enzyme immobilization studies.     

Cofactor metals and antioxidant enzymes in cisplatin-treated rats: effect of antioxidant intervention

We explored the association between the activities of antioxidant enzymes and their metallic cofactors in rats treated with cisplatin. The antioxidant effects of aminoguanidine, and a combination of vitamins E and C were investigated. Plasma platin was significantly lower than liver and kidney. Cisplatin treatment caused significant increase in plasma Se-glutathione peroxidase activity. Activities of Se-glutathione peroxidase, glutathione S-transferase, catalase and Cu,Zn-superoxide dismutase have been found to be significantly decreased in liver and kidney compared to controls. Zn levels in these organs were diminished upon cisplatin treatment, while levels of Cu were unaffected. Interestingly, levels of iron, the cofactor of catalase, were found to be significantly increased in liver and kidney. Intervention with aminoguanidine or vitamins was generally prevented cisplatin-caused changes in the activity of enzymes and in the tissue levels of cofactor metals. These observations suggest that relation between activities of enzymes and levels of cofactor metals is multifactorial.     

Plasma soluble adhesion molecules; intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin levels in patients with isolated coronary artery ectasia

Plasma soluble adhesion molecules, intercellular adhesion molecule-1 (ICAM)-1, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin leves of patients with isolated coronary artery ectasia (CAE), patients with obstructive coronary artery disease without CAE and subjects with angiographically normal coronary arteries were evaluated. Patients with isolated CAE were detected to have significantly higher levels of plasma soluble ICAM-1, VCAM-1 and E-selectin in comparison with patients with obstructive coronary artery disease without CAE (ICAM, 673 +/- 153 versus 381 +/- 106, respectively, P < 0.001; VCAM-1, 2366 +/- 925 versus 1136 +/- 208, respectively, P < 0.001; E-selectin, 74 +/- 21 versus 61 +/- 18, respectively, P = 0.01) and subjects with normal coronary arteries (ICAM-1, 673 +/- 153 versus 303 +/- 131, respectively, P < 0.001; VCAM-1, 2366 +/- 925 versus 729 +/- 231, respectively, P < 0.001; E-selectin, 74 +/- 21 versus 49 +/- 9, respectively, P < 0.001), suggesting the presence of a more severe and extensive chronic inflammation in the coronary circulation in patients with isolated CAE. BACKGROUND: The common coexistence of coronary artery ectasia (CAE) with coronary artery disease (CAD) suggests that it may be a variant of CAD. However, it is not clear why some patients with obstructive CAD develop CAE whereas most do not. Inflammation has been reported to be a major contributing factor to both obstructive and aneurysmatic vascular disorders and therefore, in the present study, the plasma soluble adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin levels in isolated CAE were investigated. METHODS: The study population consisted of three groups: the first consisted of 32 patients with isolated CAE without stenotic lesion; the second of 32 patients with obstructive CAD without CAE; and the third group of 30 control subjects with normal coronary arteries. Coronary diameters were measured as the maximum diameter of the ectasic segment by use of a computerized quantitative coronary angiography analysis system. According to the angiographic definition used in the Coronary Artery Surgery Study, a vessel is considered to be ectasic when its diameter is > or =1.5 times that of the adjacent normal segment in segmental ectasia. Plasma soluble ICAM-1, VCAM-1 and E-selectin levels were measured in all patients and control subjects using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Patients with isolated CAE were found to have significantly higher levels of plasma soluble ICAM-1, VCAM-1, and E-selectin in comparison with patients with obstructive CAD without CAE (ICAM, 673 +/- 153 versus 381 +/- 106, respectively; P < 0.001; VCAM-1, 2366 +/- 925 versus 1136 +/- 208, respectively; P < 0.001; E-selectin, 74 +/- 21 versus 61+/-18, respectively; P = 0.01) and control subjects with normal coronary arteries (ICAM-1, 673 +/- 153 versus 303 +/- 131, respectively;, P < 0.001; VCAM-1, 2366 +/- 925 versus 729 +/- 231, respectively; P < 0.001; E-selectin, 74 +/- 21 versus 49 +/- 9, respectively; P < 0.001). In addition, we detected statistically significant positive correlation between the total length of ectasic segments and the levels of plasma soluble ICAM-1 (r = 0.625; P < 0.001), VCAM-1 (r = 0.548; P = 0.001) and E-selectin (r = 0.390; P = 0.027). Multivariate logistic regression analysis revealed a significant independent relation between isolated CAE and ICAM-1 [odds ratio (OR) = 1.023; 95% confidence interval (CI) = 1.0048-1.0414; P = 0.0129] and VCAM-1 (OR = 1.0057; 95% CI = 1.0007-1.0106; P = 0.0240). CONCLUSIONS: We have shown that patients with isolated CAE have raised levels of plasma soluble ICAM-1, VCAM-1 and E-selectin in comparison with patients with obstructive CAD without CAE and control subjects with normal coronary arteries, suggesting the presence of a more severe and extensive chronic inflammation in the coronary circulation in these patients.     

Thrombin activatable fibrinolysis inhibitor activity, thrombin-antithrombin complex and D-dimer levels in preterm neonates with early respiratory distress syndrome

Intraalveolar fibrin deposition found in neonates with respiratory distress syndrome (RDS) is explained by the activation of the coagulation system and inefficient fibrinolysis. However, thrombin activatable fibrinolysis inhibitor activity (TAFIa), an inhibitor of fibrinolysis, and the ratio of D-dimer to thrombin-antithrombin complex (D-dimer/TAT), an index of fibrinolytic activity, have not been reported previously in neonatal RDS. Aim of this study is to evaluate the influence of plasma TAFIa levels on the fibrinolytic state in neonatal RDS. The RDS group (Group 1) consisted of 29 neonates, and 18 neonates served as the control group (Group 2). Plasma TAFIa levels and D-dimer/TAT ratios were evaluated in all neonates in the first 6 hr of life. Neonates in the RDS group were further divided into two subgroups; Group 1a consisted of 12 neonates with evidence of mild asphyxia (Apgar score at 5 min <7 and cord pH <7.26), and Group 1b consisted of 17 nonasphyxiated neonates. No significant difference was found in TAFIa levels and D-dimer/TAT ratios between Groups 1 and 2 [214% (56.2-361%) and 124.3 (4.4-3,921) in Group 1 and 201% (60.3-381%) and 147 (5.9-1,426) in Group 2]. There were negative correlations between cord pH and TAFIa levels in both groups. Increased TAFIa levels and decreased D-dimer/TAT ratios and platelet counts were detected in mildly asphyxiated neonates when compared with nonasphyxiated ones. TAFIa is not responsible for the hypofibrinolytic state reported in RDS. However, asphyxia influences TAFIa levels and increased TAFIa levels depress fibrinolysis.     

Issues in cross‐cultural validity: Example from the adaptation,reliability, and validity testing of a Turkish version of the Stanford Health Assessment Questionnaire

Objective

Guidelines have been established for cross‐cultural adaptation of outcome measures. However, invariance across cultures must also be demonstrated through analysis of Differential Item Functioning (DIF). This is tested in the context of a Turkish adaptation of the Health Assessment Questionnaire (HAQ).

Methods

Internal construct validity of the adapted HAQ is assessed by Rasch analysis; reliability, by internal consistency and the intraclass correlation coefficient; external construct validity, by association with impairments and American College of Rheumatology functional stages. Cross‐cultural validity is tested through DIF by comparison with data from the UK version of the HAQ.

Results

The adapted version of the HAQ demonstrated good internal construct validity through fit of the data to the Rasch model (mean item fit 0.205; SD 0.998). Reliability was excellent (α = 0.97) and external construct validity was confirmed by expected associations. DIF for culture was found in only 1 item.

Conclusions

Cross‐cultural validity was found to be sufficient for use in international studies between the UK and Turkey. Future adaptation of instruments should include analysis of DIF at the field testing stage in the adaptation process.

     

The spectrum of diseases causing fever of unknown origin in Turkey: a multicenter study.

OBJECTIVE: The purpose of this trial was to determine the spectrum of diseases with fever of unknown origin (FUO) in Turkey. METHODS: A prospective multicenter study of 154 patients with FUO in twelve Turkish tertiary-care hospitals was conducted. RESULTS: The mean age of the patients was 42+/-17 years (range 17-75). Fifty-three (34.4%) had infectious diseases (ID), 47 (30.5%) had non-infectious inflammatory diseases (NIID), 22 (14.3%) had malignant diseases (MD), and eight (5.2%) had miscellaneous diseases (Mi). In 24 (15.6%) of the cases, the reason for high fever could not be determined despite intensive efforts. The most common ID etiologies were tuberculosis (13.6%) and cytomegalovirus (CMV) infection (3.2%). Adult Still's disease was the most common NIID (13.6%) and hematological malignancy was the most common MD (7.8%). In patients with NIID, the mean duration of reaching a definite diagnosis (37+/-23 days) was significantly longer compared to the patients with ID (25+/-12 days) (p=0.007). In patients with MD, the mean duration of fever (51+/-35 days) was longer compared to patients with ID (37+/-38 days) (p=0.052). CONCLUSIONS: Although infection remains the most common cause of FUO, with the highest percentage for tuberculosis, non-infectious etiologies seem to have increased when compared with previous studies.