ß2-Adrenoceptor agonist formoterol attenuates NLRP3 inflammasome activation and GSDMD-mediated pyroptosis in microglia through enhancing IκBα/NF-κB inhibition, SQSTM1/p62-dependent selective autophagy and ESCRT-III-mediated plasma membrane repair.

Microglia are immune cells that play important roles in the formation of the innate immune response within the central nervous system (CNS). The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a multiple protein complex that is crucial for innate immunity, and excessive activation of the inflammasome for various reasons contributes to the pathogenesis of neurodegenerative diseases (NDs). ß2-adrenoceptor agonists have become the focus of attention in studies on NDs due to the high synthesis of ß2-adrenoceptors in the central nervous system (CNS). Promising results have been obtained from these studies targeting anti-inflammatory and neuroprotective effects. Formoterol is an effective, safe for long-term use, and FDA-approved ß2-adrenoceptor agonist with demonstrated anti-inflammatory features in the CNS. In this study, we researched the effects of formoterol on LPS/ATP-stimulated NLRP3 inflammasome activation, pyroptosis, NF-κB, autophagy, and ESCRT-III-mediated plasma membrane repair pathways in the N9 microglia cells. The results showed that formoterol, through the IκBα/NF-κB axis, significantly inhibited NLRP3 inflammasome activation, reduced the level of active caspase-1, secretion of IL-1ß and IL-18 proinflammatory cytokine levels, and the levels of pyroptosis. Additionally, we showed that formoterol activates autophagy, autophagosome formation, and ESCRT-III-mediated plasma membrane repair, which are significant pathways in the inhibition of NLRP3 inflammasome activation and pyroptosis. Our study suggests that formoterol efficaciously prevents the NLRP3 inflammasome activation and pyroptosis in microglial cells regulation through IκBα/NF-κB, autophagy, autophagosome formation, and ESCRT-III-mediated plasma membrane repair.

Analytical performance evaluation of sensitive and old generation reagent in routine practical use: estradiol experience.

Evaluation of the analytical performance of tests in medical laboratories is important. Total Error (TE) and sigma analysis have been used as a quantitative indicator of quality for many years. The aim of this study is to evaluate the analytical performance of Beckman Coulter Access Estradiol (E2) and Sensitive E2 reagents. Analytical performance of two reagents were evaluated with TE, six sigma and measurement uncertainty values. Two Beckman Coulter Unicel DxI-800 autoanalyzers (A1 and A2) included in the study. Quality control data between December 2017 and December 2019 were used. CLIA-2019 values were used for total allowable error (TEa) limits. Uncertainty values were calculated with ISO/TS 20914. The median TE of the old generation and sensitive E2 reagent were 27.46% (between 13.49 and 48.88) and 11.16% (between 7.08 and 24.81), respectively (p < .005) The process sigma results were below 3 sigma in all months with the old reagent, whereas with the new reagents it was seen to be above 3 sigma in 11 of 12 months for both autoanalyzers. Uncertainty of old reagent is higher than new reagent. Imprecisions decrease as concentration increases with both reagents. The uncertainty values of low concentration levels are greater than high concentration levels. In conclusion, in both auto analyzers, Sensitive E2 reagent was found to have better performance than old reagent in terms of TE, process sigma and measurement uncertainty. We believe that the sensitive E2 reagent still needs further improvement for patients who have low E2 levels.

Reference change value and measurement uncertainty in the evaluation of tumor markers.

The use of measurement uncertainty among clinical laboratories becomes widespread. Measurement uncertainty can be reported with the result, as well as be used in certain reference change value (RCV) calculation equations. RCV is especially recommended for use in tests with a low individuality index. In our study, we calculated the measurement uncertainty of AFP, CA 125, CA 15-3, CA 19-9, CEA tumor markers with the ISO TS 20914:2019. We compared results with limits. Two Beckman Coulter DXI-800 (Minnesota, USA) autoanalysers' results were used. We calculated the RCV values using the classical Fraser method, logarithmic Lund Method, and Clinical Laboratory Standards Institute (CLSI) method as Minimal Difference (MD). We found the same permissible measurement uncertainty limit as 15.97% for all five tumor markers. The highest RCV value was found as 90% upstream for AFP test with Lund logarithmic approach, the lowest RCV value was found as 12% for CEA with MD, all other RCV results were between these two values. We do not recommend the use of MD, as values for Biological variation are not used in the MD approach. We also recommend using the logarithmic approach, although it gives higher results. There are also clinical studies on the significance of tumor markers in a follow-up that show different results. These differences may be because the studies are conducted with different systems. Therefore, each laboratory needs to calculate its own RCV values. We also recommend informing the clinicians about the tests with high measurement uncertainty.

Tr-KIT/c-KIT ratio in renal cell carcinoma.

Truncated KIT (tr-KIT) is an alternative variant of c-KIT protein. Previous studies have clearly documented that c-KIT was associated with various oncogenic processes in RCC. However, the biological significance of tr-KIT in RCC development and progression remains unclear. So, it was aimed to investigate the possible association between RCC and tr-KIT which is thought to activate some oncogenic pathways. In this study, Kidney Cancer cDNA Array containing a total of 48 cDNA samples from the normal kidney tissues of 9 healthy subjects and kidney tumor tissues of 10 stage-1, 5 stage-2, 13 stage-3 and 11 stage-4 RCC patients was used for gene expression analysis. Real-Time PCR method was used to measure tr-KIT/c-KIT expression ratios. tr-KIT/c-KIT expression ratio was compared between tumor and normal samples, and statistically correlated with the clinical parameters of RCC patients. tr-KIT/c-KIT expression ratio was approximately 4-times higher in tumor samples than control ones (p = 0.001). Also, tr-KIT/c-KIT expression ratio was approximately two, three and six times higher in Fuhrman nuclear grades 2, 3 and 4 than normal, respectively (p = 0.009). Moreover, clear cell and papillary RCC has a significantly higher level of tr-KIT/c-KIT expression ratio than chromophobe RCC (p = 0.016). In the current study, it was stated for the first time that tr-KIT/c-KIT expression ratio was up-regulated in RCC tissues, and high tr-KIT/c-KIT expression ratio was correlated with more aggressive clinical features and poor patient prognosis. Our results suggest that increased tr-KIT/c-KIT expression ratio might be useful as a prognostic marker for RCC patients.

Blood levels of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha and cognitive functions in patients with obsessive compulsive disorder.

BACKGROUND: Cognitive dysfunction and immune system disorders are two actual issues for the patients with Obsessive Compulsive Disorder (OCD). The cognitive dysfunctions have been considered to substantial part of clinical phenomenon of OCD but exploration of various etiopathogenesis of cognitive dysfunction is needed. Immune dysfuncion has been implicated to be important part of pathopysiology of OCD and different lines of evidence suggests immune abnormalities in OCD. But whether these immune changes are traits of disease or secondary to clinical burden of the disease such as cognitive dysfunctions has not been determined. Data regarding relation between the cognitive dysfunctions and immune system disorders in OCD is unsatisfied. In this study we aimed to investigate the relation of blood levels of interleukin 1-beta (IL-1ß), interleukin-6 (IL-6) and Tumor Necrosis Factor-α (TNF-α) with various neurocognitive functions in patients with OCD in comparison with its autogenous/reactive subtypes and healthy controls. Further exploration of the effects of various clinical variables on cognitive functioning in patients with OCD and additional investigation of whether the cognitive dysfunction associated with this disorder differs from or overlap with that in other anxiety disorders are needed. METHODS: Forty-two patient with OCD and 45 age, sex and educational level matched healthy control were enrolled in the study. The diagnosis of OCD was made with Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Yale- Brown Obsessive-Compulsive Scale, Beck Anxiety and Depression Inventory Scales were administered. Neuropsychological test battery including Wisconsin Card Sorting Test (WCST), Trail Making Test A and B (TMT-A, TMT-B) were used for evaluation of the patients and healthy control. The plasma of interleukin-1beta (IL-1ß), interleukin-6 (IL-6), Tumor Necrosis Factor-Alpha (TNF-α) of both groups were measured with ELISA kits. RESULTS: Blood levels of IL-1ß, IL-6 and TNF-α were significantly higher in patients with OCD than the healthy control. There was significant difference in IL-1ß, IL-6 but not in TNF-α between autogenous/reactive subtypes and healthy controls. TNF-α is positively correlated with TMT-A, TMT-B and Stroop Test Part 5, negatively correlated with immediate memory, verbal learning, interference effect, immediate recall, delayed recall and recognition in RAVLT. IL-1ß was positively correlated with TMT-A score. IL-6 was positively correlated with scores of TMT-A, TMT-B. IL-6 was negatively correlated with immediate memory, verbal learning, interference effect, immediate recall and delayed recall in RAVLT, positively correlated with number of perseverative error and negatively correlated with the number of categories completed in WCST. CONCLUSION: This is the first study that investigates the relation of IL- 1ß, IL-6 and TNF-α levels with cognitive functions in OCD. There may be a contribution to pathogenesis of OCD and subtypes then new choices for treatment might be developed. Moreover, uncovering the effect of cytokine blood levels on cognitive function of OCD, new data concerning etiopathogenesis and further treatment choices can be gained.

A Comparison of the Effects of Grayanotoxin-Containing Honey (Mad Honey), Normal Honey, and Propolis on Fracture Healing.

OBJECTIVES: Delayed healing and non-union of fractures have a significant effect upon patient morbidity. Studies have therefore largely concentrated on accelerating fracture healing. This study was intended to compare the effect of "mad honey" and propolis on fracture healing using radiological and histopathological analysis. SUBJECTS AND METHODS: Femur fracture was surgically performed on 48 rats, followed by fixation. Animals were then divided into 8 groups: 2 control groups (15- and 30-day) and 6 treatment groups (15- and 30-day normal honey, 15- and 30-day "mad honey," and 15- and 30-day propolis). Rats were sacrificed at the end of these periods, and radiological and histological examinations were performed. RESULTS: Radiological healing in the propolis group after 15-day therapy was statistically better than in the control (p = 0.004) and normal honey (p = 0.006) groups. After 30-day therapy, healing in the propolis group (p = 0.005) and grayanotoxin-containing "mad honey" group (p = 0.007) were significantly better than in the control group. Histologically, there was a statistically significant difference between the 15-day propolis group and the other groups (control, honey, mad honey: p = 0.003, p = 0.003, and p = 0.002, respectively). We also found a statistically significant difference when the 30-day propolis group (p = 0.005) and "mad honey" group (p = 0.007) were compared to the control group. CONCLUSIONS: This study shows that grayanotoxin-containing "mad honey" and propolis can accelerate fracture healing.

The prognostic significance of serum TGF-ß1 levels in patients with Crimean-Congo hemorrhagic fever.

Crimean-Congo Hemorrhagic Fever (CCHF) may exhibit a mild clinical course or a severe profile like mortal bleeding. The pathogenesis of the illness and reason of bleeding are unclear. However, endothelial injury is a key factor in the pathogenesis of the illness. Transforming growth factor beta (TGF-ß) is one of the materials involved in repairing injured endothelium. This is a significant polypeptide released in pretty much all cells and important for the regulation of cellular events, epithelium formation, inflammation, blood coagulation, and collagen synthesis. This study aimed to determine the prognostic significance of serum TGF-ß1 levels in CCHF patients. We examined 120 patients hospitalized with CCHF diagnosis and their serum TGF-ß1 was investigated, retrospectively. Patients were put into two groups according to the existence of hemorrhage. Forty-four (36.7%) patients had hemorrhage. TGF-ß1 levels in patients with bleeding were 5.2 ± 1.8, and 7.1 ± 2.2 for non-bleeding (P < 0.0001). When ROC analysis was performed in patients with CCHF alone in order to identify patients with bleeding, at a TGF-ß1 cut-off point of 4.9, AUC was 0.762 (0.675-0.835), sensitivity 59.1%, specificity 85.5%, PPV 70.3%, and NPV 78.3%. We summarize that TGF-ß1 level and endothelial dysfunction can be related. A decreased TGF-ß1 level is a likely prognostic and diagnostic factor for bleeding in CCHF patients. Therefore, this marker should be considered in the treatment strategy for these patients. J. Med. Virol. 89:413-416, 2017. © 2016 Wiley Periodicals, Inc.

Prognostic impact of platelet distribution width in patients with Crimean-Congo hemorrhagic fever.

Platelet distribution width (PDW) is a readily available blood test involving calculations performed by automated blood analyzers. Crimean-Congo hemorrhagic fever (CCHF) may exhibit a severe profile with fatal hemorrhaging or else present with a mild clinical process. The purpose of our study was to investigate the importance of PDW in CCHF patients and its clinical prognostic value. This study was conducted with patients with CCHF. Patients were divided into two groups on the basis of presence or absence of bleeding. Demographic characteristics, clinical findings, PDW, and other laboratory tests were recorded onto forms. A total of 423 patients were included. Hemorrhaging was observed in 27.9% during hospitalization. PDW on the first day of hospitalization was 17.2 ± 0.9% in the hemorrhagic patients and 17.1 ± 0.6% in the cases without hemorrhage (P = 0.290). On the third day of hospitalization, PDW was 17.6 ± 0.8% in the hemorrhagic patients and 17.0 ± 0.7% in the cases without hemorrhage (P < 0.001). At a third-day PDW level cut-off point of 17.1%, AUROC was 0.677, sensitivity 65.5%, specificity 54.6%, PPV 35.5%, and NPV 80.6%. A one-unit raise in third day PDW stepped up the probability of bleeding in patients with CCHF 3.45-fold at logistic regression analysis. This study shows that PDW is a parameter that may be used to determine disease severity. This parameter may be at least as useful as platelet count in helping clinicians identify severe cases. Early identification of cases with a severe course will make it possible to provide early planning of modalities such as intensive care support. J. Med. Virol. 88:1862-1866, 2016. © 2016 Wiley Periodicals, Inc.

Systemic oxidant/antioxidant balance in human abdominal aortic aneurysm.

The aim of this study was to evaluate the oxidant-antioxidant balance in patients with abdominal aortic aneurysms (AAA). Forty-two consecutive patients with AAA and 46 control subjects were included. Total oxidant status (TOS) and total antioxidant status (TAS) levels were measured and the oxidative stress index (OSI) value determined. Serum TOS and OSI values in patients with AAA were higher than those in the controls (p < 0.001, p < 0.001, respectively). There was a positive correlation between abdominal aortic diameters, serum TOS levels (r = 0.592, p < 0.001) and OSI values (r = 0.598, p < 0.001). A cut-off value of 17.68 µmol H2O2equivalent/L for TOS was associated with 86% sensitivity and 83% specificity and a cut-off value of 1.77 for OSI was associated with 86% sensitivity and 81% specificity for predicting AAA. Systemic oxidative imbalance develops in patients with AAA, particularly as a result of an increase in TOS.

Can signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) be used as an indicator of endothelial dysfunction in acromegaly patients?

PURPOSE: Acromegaly is closely related to increased oxidative stress and endothelial dysfunction (ED). This study aimed to evaluate, for the first time in the literature, signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) and endothelial nitric oxide synthase e(NOS) levels in the setting of acromegaly. METHOD: A total of 56 acromegaly patients and a control group composed of 30 healthy volunteers were included in this study. In the postoperative follow-up, patients were grouped as active or in-remission according to their GH and IGF-1 levels in oral glucose stimulation test (OGST). After detailed physical examination of acromegaly patients and the control subjects, 8-hour fasting blood samples were collected to evaluate biochemical parameters including lipid profile, anterior pituitary hormones, and SCUBE-1 and e(NOS) levels. RESULTS: Inactive and active acromegaly was noted in 78.6% and 21.4% of patients, respectively. The median (min-max) SCUBE-1 levels were significantly higher in the inactive acromegaly and active acromegaly groups than in the control group (1.6(0.4-2.4) and 1.8(1.1-2.5) vs. 0.4(0.2-1.0) ng/mL, respectively, p < 0.001 for each). The median (min-max) e(NOS) levels were significantly higher in the inactive acromegaly and active acromegaly groups than in the control group (132.7 (26.8-602.9) and 137.3 (69.7-488.7) vs. 83.9 (16.4-218.7) pg/mL, p = 0.018 and p = 0.048, respectively). We have also detected positive correlations of e(NOS) with leukocyte (r = 0.307, p = 0.021) and neutrophil counts (r = 0.309, p = 0.021). CONCLUSION: Our study revealed for the first time in literature that SCUBE-1 levels, being a novel marker for ED, were significantly higher in acromegaly patients than in control subjects. When supported with clinical studies, SCUBE-1can be used as an early indicator of endothelial damage in acromegaly patients.

Functional and biochemical improvement following total knee arthroplasty in early postoperative period.

OBJECTIVE: There are very few studies about total knee arthroplasty biomechanical and biochemical effects in the early postoperative period. The aim of this study was to investigate the effect of total knee arthroplasty on pain intensity, knee joint valgus angle, malalignment, functional status, knee joint position sense, and cytokine levels. METHODS: A total of 29 patients (female/male: 24/5) who underwent total knee arthroplasty were included in the late-stage knee osteoarthritis group, and 22 patients (female/male: 13/9) with grade 4 osteoarthritis were included in the early-stage knee osteoarthritis group. The visual analog scale and the Western Ontario and McMaster Universities Osteoarthritis Index were used to evaluate the pain intensity and functional status. Alignment and knee position sense measurements were also calculated. Systemic venous blood samples were taken to evaluate the interleukin-6, tumor necrosis factor-alpha, and interleukin-1 beta cytokine levels. RESULTS: In the study group, there were positive improvements in pain intensity, functional status, valgus angle, malalignment, amount of joint position sense deviation at 70° knee flexion angle parameters, and interleukin-6 of patients at the postoperative 6th week compared to the preoperative period (p<0.05). The patients in the study group had similar or better results in pain intensity, functional status, valgus angle, malalignment, amount of joint position sense deviation at 35°, 55°, and 70° knee flexion angles parameters, and in interleukin-6, compared to the control group at postoperative 6th week. CONCLUSION: Total knee arthroplasty provides improvements in pain, function, valgus angle, joint position sense, and interleukin-6 in the early postoperative period.

The relationship between diabetic retinopathy and serum levels of ischemia-modified albumin and malondialdehyde.

PURPOSE: To establish the correlation between ischemia-modified albumin (IMA) and malondialdehyde (MDA) and the development of diabetic retinopathy (DRP) in patients with diabetes mellitus. METHODS: Seventy Type 2 diabetic patients, 35 with DRP, and 36 healthy controls were enrolled in this study. Serum IMA and MDA levels were compared statistically. Receiver operating characteristic curve analysis was also performed to calculate the value of IMA and MDA in distinguishing DRP. RESULTS: Mean serum IMA levels were 0.658 ± 0.128 absorbance units in the non-DRP group, compared with 0.767 ± 0.074 absorbance units in the DRP group and 0.619 ± 0.044 absorbance units in the control group. Mean serum MDA levels were 0.325 ± 0.172 nmol/mL, 0.244 ± 0.152 nmol/mL, and 0.178 ± 0.131 nmol/mL, respectively. The differences in IMA and MDA levels were statistically significant for all groups (P < 0.05 for all). The areas under the receiver operating characteristic curves for the determination of DRP in diabetic patients were 0.789 (95% confidence interval, 0.682-0.896) for IMA and 0.3 (95% confidence interval, 0.175-0.426) for MDA. CONCLUSION: Both serum IMA and serum MDA levels were higher in the diabetic patients compared with the control group. In particular, the high sensitivity of IMA toward DRP showed that it reflected retinal vascular complication better than MDA. Ischemia-modified albumin may be a useful marker in monitoring the risk of DRP development.

Ischemia-modified albumin levels in carbon monoxide poisoning.

OBJECTIVES: Ischemia-modified albumin (IMA) is an emerging diagnostic biomarker for many ischemic conditions. This study was conducted to investigate whether there is a change in IMA levels in carbon monoxide (CO) poisoning and, if so, the clinical relevance of IMA levels. METHODS: This cohort study, performed between November 2008 and April 2009, compared the serum IMA levels of 33 CO-poisoned patients taken at the time of presentation at the emergency department and after 3 hours of treatment and 49 healthy controls. In addition, IMA and carboxyhemoglobin levels were analyzed according to CO poisoning patients' poisoning severity scores. RESULTS: Carbon monoxide patients' IMA levels were higher than those of the control group both at time of admission and at the third hour of the treatment, P < .0001. A significant fall was determined in carboxyhemoglobin (CO-Hb) levels at the end of the third hour of treatment, P < .0001. However, there was no significant difference between the IMA levels measured at admission and at the end of the third hour of treatment (P > .05). There was no significant correlation between IMA and CO-Hb levels in CO-poisoned patients. Also, there was no difference in blood IMA levels in classification according to patients' poisoning severity score and CO-Hb levels. CONCLUSION: Results from this pioneering study established a high level of IMA in CO-poisoned patients, suggesting that IMA may also be sensitive to hypoxia. Considering the preliminary nature of this study, the clinical utility of IMA levels in CO poisoning should be further investigated with more comprehensive studies.

Effects of different lipid emulsions on serum adipokines, inflammatory markers and mortality in critically ill patients with sepsis: A prospective observational cohort study.

BACKGROUND & AIMS: Intravenous lipid emulsions in parenteral nutrition may cause different metabolic responses and immune effects in critically ill patients with sepsis. The aim of this study is to investigate the effects of different lipid emulsions on changes in concentrations of adipokine and cytokine and their relationship with mortality in patients. METHODS: Patients enrolled in this prospective, single-center, observational cohort study, were estimated to require more than ten days of parenteral nutrition. They were treated with soybean oil-based or olive oil-based parenteral lipid emulsions. Adipokine and cytokine concentrations of septic patients were determined at enrollment and ten days after, in accordance with the diagnostic criteria of SEPSIS-3. The concentrations levels were measured in an enzyme-linked immunosorbent assay. Mortality was analyzed using the Kaplan-Meier method and Cox regressions. RESULTS: Over a 25-month period, 145 patients were assessed for eligibility and consequently, 40 patients were analyzed. On admission, both groups had comparable physiological scores, comorbidities, malnutrition risk, anthropometric measurements, metabolic/hematologic biomarkers and concentrations of adipokines and cytokines (p > .05). Serum leptin, resistin, and cytokines (IL-6, IL-10, IL-1ß and TNF-α) decreased significantly in the entire cohort over ten days following sepsis (p < .05). Serum resistin decreased in both olive oil-based and soybean oil-based lipid emulsions groups. Serum adiponectin only decreased in soybean oil-based lipid emulsions group (p < .05). There was association between survival and percentage changes in adiponectin, resistin and visfatin concentrations (log rank test: p < .05). CONCLUSION: Adipokine and cytokine responses are affected by medical nutritional therapy in the sepsis process and adipokines may represent functional prognostic biomarkers in critically ill patients with sepsis.

Differences in ischemia-modified albumin levels between end stage renal disease patients and the normal population.

INTRODUCTION: Conventional biomarkers suffer from the drawback of being elevated in chronic renal failure even in the absence of myocardial ischemia. Ischemia-modified albumin (IMA) is a new biomarker proposed for the diagnosis of myocardial ischemia. This study was performed with the primary aim of determining IMA levels in patients with end stage renal disease (ESRD). The secondary aim of the study was to determine the impact of hemodialysis (HD), HD speed, and hemoglobin (Hb) levels on IMA levels. METHODS: The study was conducted with 108 ESRD patients entering HD and 30 healthy volunteers. The serum IMA levels of ESRD patients were compared with the post-HD levels and also with healthy individuals. The interaction between Hb levels and HD treatment and the IMA levels were tested by using the Generalized Linear Model for repeated measurements. RESULTS: The IMA levels of ESRD patients, both pre- and post-HD, were significantly higher than those of the control group. The baseline IMA levels of "low" and "high Hb groups" were not significantly different. Hb level modifies the effect of HD treatment on IMA concentration in ESRD patients. Furthermore, post-HD levels of IMA were increased at a lower dialysis speed. CONCLUSIONS: Both pre- and post-dialysis IMA levels are higher in ESRD patients entering HD than in healthy individuals. Anemia is an effect-modifier for the effect of HD treatment on IMA levels in ESRD patients.

HMGB-1, TLR4, IL-1R1, TNF-α, and IL-1ß: novel epilepsy markers?

The purpose of this study was to compare HMGB-1, TLR4, IL-1ß, IL-1R1, and TNF-α levels in patients with mild and severe epilepsy with those in a healthy control group. Children aged 4-17 years, diagnosed with epilepsy for at least three years and with no progressive neurological disease, metabolic disease or infection, were selected for the study. The severe epilepsy group consisted of 28 children with at least one episode a week despite receiving three or more antiepileptic drugs. The mild epilepsy group consisted of 29 children with no seizures in the previous year, receiving only one antiepileptic drug, while 27 healthy children were selected as the control group. HMGB-1, TLR4, IL-1R1, TNF-α and IL-1ß levels were investigated in these three groups. The MRI findings and clinical characteristics of the patients in the epilepsy group were also compared with these markers. HMGB-1, TLR4, TNF-α, and IL-1ß levels in the severe epilepsy group were higher than in the control group and the mild epilepsy group (p<0.05), and were higher in the mild epilepsy group than in the control group (p<0.05). IL-1R1 was also higher in the severe epilepsy group than in the control group (p<0.05). In this first report to identity a possible correlation between HMGB-1, TLR4, IL-1ß, IL-1R1, and TNF-α levels and severity of epilepsy, our data demonstrates that the serum level of these cytokines is higher in cases of drug-refractory epilepsy.

Ischemia-modified albumin in the diagnosis of pulmonary embolism: an experimental study.

STUDY OBJECTIVE: We designed this experimental study to determine the value of ischemia-modified albumin in the diagnosis of pulmonary embolism. METHODS: Twenty-four mature female New Zealand rabbits were divided into 4 groups, each consisting of 6 animals. These were classified into group 1 ,the control group; group 2, the deep venous thrombosis group; group 3, the deep venous thrombosis with pulmonary embolism group; and group 4, the pulmonary embolism-alone group. Deep venous thrombosis was produced by ligation of the iliac vein. To establish pulmonary embolism, 2 clots were administered from the iliac vein. Blood samples were taken from all the groups at hours 0, 1, 3, and 6 for ischemia-modified albumin measurement. RESULTS: Pulmonary embolism was established in all the rabbits in groups 3 and 4, and this was confirmed by tomographic and histologic findings. Measurement of mean ischemia-modified albumin levels for all rabbits at hours 0, 1, 3, and 6 revealed that mean ischemia-modified albumin levels in groups 3 and 4 were statistically significantly higher than those in groups 1 and 2. There was no difference between the mean ischemia-modified albumin levels in groups 1 and 2 nor between groups 3 and 4. The alteration in ischemia-modified albumin levels over time was statistically significant. CONCLUSIONS: The results of our experimental study demonstrate that ischemia-modified albumin levels may be useful in the diagnosis of pulmonary embolism.

Thiol/Disulphide Homeostasis, Ischemia Modified Albumin, and Ferroxidase as Oxidative Stress Markers in Women with Obesity with Insulin Resistance.

BACKGROUND: The purpose of the study was to determine oxidative stress-related plasma thiol/disulphide, ischemia-modified albumin (IMA) levels and ferroxidase activity among women with obesity in insulin-resistant and non-insulin-resistant groups in comparison with an overweight group. METHODS: We compared plasma thiol/disulphide, IMA levels, and ferroxidase activity between the study groups. We analyzed plasma thiol/disulphide homeostasis with a newly developed automated measurement method; IMA with Albumin Cobalt Binding Test and ferroxidase (ceruloplasmin) levels with an automated, colourimetric method. RESULTS: There were no significant differences between insulin-resistant and non-insulin-resistant women with obesity in terms of plasma native thiol, total thiol, disulphide, disulphide/native thiol ratio, disulphide/total thiol or native thiol/total thiol values. Ferroxidase activity was higher in insulin-resistant than in non-insulin-resistant women with obesity and higher in the total women with obesity group than in the overweight subjects (p<0.001, and p=0.014, respectively). IMA was lower in the insulin-resistant group than in the non-insulin-resistant group and overweight groups (p=0.011, and p=0.042, respectively). CONCLUSIONS: The significantly greater increase in ferroxidase activity in insulin-resistant subjects with obesity may reflect its role as a positive acute phase protein. These findings may be related to the pathogenesis of the disease. Changes in oxidative status occur in women with obesity, and partially in overweight subjects. The ferroxidase activity of ceruloplasmin plays a crucial role in iron homeostasis and lowers oxidative stress by reducing the detrimental effects of iron.

Ischemia-modified albumin in the diagnosis of acute mesenteric ischemia: a preliminary study.

Ischemia-modified albumin (IMA) is a sensitive marker of myocardial ischemia, skeletal muscle ischemia, pulmonary embolism, and stroke. However, there are no studies showing whether IMA increases in mesenteric ischemia. The aim of this study was to determine whether IMA was elevated in acute mesenteric ischemia. This case-controlled study was performed in an emergency department of a university hospital. The measurement of IMA levels in patient plasma yielded means of 0.264 +/- 0.057 absorbance units (ABSU) in the thromboembolic occlusion of the superior mesenteric artery (SMA) group and 0.163 +/- 0.025 ABSU in the control group. When plasma IMA levels in the thromboembolic occlusion SMA group were compared with those in the control group, statistically significant increases in IMA were observed in the occlusion group (P = .003). Findings indicating that IMA may have a place in the diagnosis of acute mesenteric embolism were obtained in this preliminary study. Further prospective studies are needed to see if IMA is clinically useful in the early detection of thromboembolic occlusion of the SMA.

Ischemia-modified albumin levels in cerebrovascular accidents.

BACKGROUND: Previous studies have demonstrated that ischemia-modified albumin (IMA) is a useful marker for the diagnosis of ischemic events. It was also recently demonstrated that IMA levels increase in the acute phase of cerebrovascular diseases. Yet the data regarding IMA levels in various types of cerebrovascular events are insufficient. The aim of this study was to evaluate IMA levels in various types of cerebrovascular events such as ischemic stroke, subarachnoid hemorrhage (SAH), and intracranial hemorrhage. METHODS: This case-controlled study consisted of 106 consecutive patients, 43 with brain infarction (BI), 11 with brain hemorrhage (ICH), 52 with SAH, and a 43-member control group. We investigated whether there was a statistical correlation between these 3 groups and the control group. The relations among the 3 groups were also examined. Comparisons among groups were done with analysis of variance. RESULTS: Mean serum IMA levels were 0.280 +/- 0.045 absorbance units (ABSU) for BI patients, 0.259 +/- 0.053 ABSU for ICH patients, 0.243 +/- 0.061 ABSU for SAH patients, and 0.172 +/- 0.045 ABSU for the control group.There was a statistically significant difference between the mean IMA levels of BI, ICH, and SAH patients and the mean control patient IMA levels (P b .0001). CONCLUSIONS: Ischemia-modified albumin levels are high in cerebrovascular diseases. Ischemia-modified albumin measurement can also be used to distinguish SAH from BI during the acute phase of cerebrovascular event in the emergency department.