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author:("caki, herding")
1.  Activation of the Ubiquitin Proteasome Pathway in a Mouse Model of Inflammatory Myopathy 
Arthritis and rheumatism  2013;65(12):3248-3258.
Objective
Myositis is characterized by severe muscle weakness. We and others have previously shown that endoplasmic reticulum (ER) stress plays a role in the pathogenesis of myositis. The present study was undertaken to identify perturbed pathways and assess their contribution to muscle disease in a mouse myositis model.
Methods
Stable isotope labeling with amino acids in cell culture (SILAC) was used to identify alterations in the skeletal muscle proteome of myositic mice in vivo. Differentially altered protein levels identified in the initial comparisons were validated using a liquid chromatography tandem mass spectrometry spike-in strategy and further confirmed by immunoblotting. In addition, we evaluated the effect of a proteasome inhibitor, bortezomib, on the disease phenotype, using well-standardized functional, histologic, and biochemical assessments.
Results
With the SILAC technique we identified significant alterations in levels of proteins belonging to the ER stress response, ubiquitin proteasome pathway (UPP), oxidative phosphorylation, glycolysis, cytoskeleton, and muscle contractile apparatus categories. We validated the myositis-related changes in the UPP and demonstrated a significant increase in the ubiquitination of muscle proteins as well as a specific increase in ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL-1) in myositis, but not in muscle affected by other dystrophies or normal muscle. Inhibition of the UPP with bortezomib significantly improved muscle function and also significantly reduced tumor necrosis factor α expression in the skeletal muscle of mice with myositis.
Conclusion
Our findings indicate that ER stress activates downstream UPPs and contributes to muscle degeneration and that UCHL-1 is a potential biomarker for disease progression. UPP inhibition offers a potential therapeutic strategy for myositis.
doi:10.1002/art.38180
PMCID: PMC4080828  PMID: 24022788
2.  Hb H Interference on Measurement Of HbA1c With Ion-Exchange HPLC 
Acta Informatica Medica  2013;21(3):216-218.
In this article, an interference caused by hemoglobin H (Hb H), during the measurement of hemoglobin A1c (HbA1c) with ion exchange high pressure liquid chromatography (HPLC) method, was presented in blood sample of a 20-year-old male patient. HbA1c measurement was performed with Agilent 1200 HPLC system using a commercial Recipe HbA1c ion-exchange column. Hemoglobin electrophoresis was performed with Interlab G26 agarose electrophoresis automated compact system. HbA1c level was 18.2% and HbA0 level was 81.5% with ion-exchange HPLC method. Patient’s fasting serum glucose was assessed before HbA1c measurement and the result was 165 mg/dL (9.16 mmol/L). On the other hand, the result of HbA0 was 87.9%, Hb H was 10.8% and Hb A2 was 1.3% with electrophoresis. Whole blood test values were within reference ranges except MCV. MCV value was 79.6 fL. It is important to keep in mind that HbA1c level might be considered falsely high with ion-exchange HPLC method because of Hb H containing sample.
doi:10.5455/aim.2013.21.216-218
PMCID: PMC3804497  PMID: 24167397
Hemoglobin H; Hemoglobin A1c; High Pressure Liquid Chromatography.
3.  Simultaneous Determination of Cyclosporine A, Tacrolimus, Sirolimus, and Everolimus in Whole-Blood Samples by LC-MS/MS 
The Scientific World Journal  2012;2012:571201.
Objectives. Cyclosporine A (CyA), tacrolimus (TRL), sirolimus (SIR), and everolimus (RAD) are immunosuppressive drugs frequently used in organ transplantation. Our aim was to confirm a robust sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of CyA, TRL, SIR, and RAD in whole-blood samples. Materials and Methods. We used an integrated online solid-phase extraction-LC-MS/MS system and atmospheric pressure ionization tandem mass spectrometry (API-MS/MS) in the multiple reaction monitoring (MRM) detection mode. CyA, TRL, SIR, and RAD were simultaneously analyzed in whole blood treated with precipitation reagent taken from transplant patients. Results. System performance parameters were suitable for using this method as a high-throughput technique in clinical practice. The high concentration of one analyte in the sample did not affect the concentration of other analytes. Total analytical time was 2.5 min, and retention times of all analytes were shorter than 2 minutes. Conclusion. This LC-MS/MS method can be preferable for therapeutic drug monitoring of these immunosuppressive drugs (CyA, TRL, SRL, and RAD) in whole blood. Sample preparation was too short and simple in this method, and it permits robust, rapid, sensitive, selective, and simultaneous determination of these drugs.
doi:10.1100/2012/571201
PMCID: PMC3354445  PMID: 22629148
4.  Serum Uric Acid Level and Endothelial Dysfunction in Patients with Nondiabetic Chronic Kidney Disease 
American Journal of Nephrology  2011;33(4):298-304.
Background
An elevated serum uric acid level is strongly associated with endothelial dysfunction and inflammation, both of which are common in chronic kidney disease (CKD). We hypothesized that endothelial dysfunction in subjects with CKD would correlate with uric acid levels.
Materials and Methods
We evaluated the association between serum uric acid level and ultrasonographic flow-mediated dilatation (FMD) in 263 of 486 patients with recently diagnosed CKD (stage 3–5) (48% male, age 52 ± 12 years). To minimize confounding, 233 patients were excluded because they were diabetic, had established cardiovascular complications or were taking drugs (renin-angiotensin system blockers, statins) interfering with vascular function.
Results
Serum uric acid level was significantly increased in all stages of CKD and strongly correlated with estimated glomerular filtration rate (eGFR-MDRD); FMD was inversely associated with serum uric acid (r = −0.49, p < 0.001). The association of serum uric acid with FMD remained after adjustment for age, gender, smoking, LDL cholesterol, eGFR, high-sensitivity C-reactive protein, systolic blood pressure, proteinuria, and homeostatic model assessment index (β = −0.27, p < 0.001).
Conclusion
Increased serum uric acid is an independent predictor of endothelial dysfunction in subjects with CKD.
doi:10.1159/000324847
PMCID: PMC3064939  PMID: 21389694
Chronic kidney disease; Uric acid; Endothelial dysfunction
5.  The relation between intraocular pressure change and plasma natriuretic peptide under simulated hypobaric conditions 
Indian Journal of Ophthalmology  2010;58(3):195-198.
Purpose:
To ascertain whether the changes in intraocular pressure (IOP) that occur during hypobaric hypoxic exposure are related to plasma N-terminal pro-brain natriuretic peptide (BNP) levels.
Materials and Methods:
The study group comprised 26 healthy participants (all male, mean age 23.1 years). IOP was measured at local ground level, (792 m above sea level), then while in a chamber providing hypobaric hypoxic conditions (the subjects were exposed to a pressure equivalent to 9144 m for 1-3 min), and again after exit from the chamber. In each condition, the mean of three consecutive measurements of IOP was calculated for each eye. For BNP measurements, blood samples were drawn before the participants entered the chamber and just after they left the chamber.
Results:
IOP during hypobaric hypoxic exposure (18.00 ± 3.70 mmHg) was significantly greater than that before (15.66 ± 2.10 mmHg, P < 0.001) or after (16.10 ± 2.63 mmHg, P = 0.001) the exposure. IOP levels before and after the exposure were not significantly different (P = 0.136). Plasma BNP levels measured before and after exposure to hypobaric hypoxic conditions were not significantly different (P = 0.462).
Conclusion:
Plasma BNP levels did not change after short-term hypobaric hypoxic exposure, while the IOP increased. This increase may have been caused by some other systemic factors. As the hypobaric hypoxic conditions were reversed, IOP decreased to normal levels.
doi:10.4103/0301-4738.62642
PMCID: PMC2886248  PMID: 20413920
Brain natriuretic peptide; high-altitude; hypobaric chamber; hypoxia; intraocular pressure

Results 1-5 (5)