The effect of L-thyroxine replacement therapy on ischemia-modified albümin and malondialdehyde levels in patients with overt and subclinical hypothyroidism.

BACKGROUND AND OBJECTIVES: The main objective of this study was to evaluate the levels of ischemia-modified albumin (IMA) and malondialdehyde (MDA) in patients with subclinical (SHypo) and overt hypothyroidism (OHypo), and to assess the effects of levothyroxine (LT4) therapy on the oxidative stress (OS) parameters. We also investigated the relationships among serum thyroid hormones, lipid parameters, and IMA and MDA in these patients. DESIGN AND METHODS: Thirty untreated patients with OHypo, 25 untreated patients with Shypo, and 30 age- and sex-matched healthy controls were prospectively included in the study. Biochemical and hormonal parameters including IMA and MDA were evaluated in all patients just before and one month after the maintenance of euthyroidism. RESULTS: Compared with the control subjects, the levels of MDA and triglycerides (TG) significantly increased in patients with SHypo (p < 0.001 and p < 0.05, respectively), whereas high density lipoprotein cholesterol (HDL-C) levels significantly decreased (p = 0.01). Patients with OHypo showed significantly high MDA, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and TG levels (p = 0.001, p < 0.01, p = 0.01, and p < 0.01, respectively), and significantly low HDL-C levels compared with the controls (p < 0.05). MDA levels and lipid profile were not significantly different in the patients with OHypo when compared with the patients with SHypo. Serum IMA levels did not significantly change in patients with OHypo and SHypo compared with the controls. In the pre-treatment period, MDA levels were inversely correlated with HDL-C levels in patients with OHypo (r: -0.471, p = 0.009). Plasma MDA and LDL-C levels significantly decreased and HDL-C levels significantly increased in the groups of OHypo and SHypo after LT4 treatment. Serum IMA levels did not significantly change with the therapy in all patient groups. CONCLUSIONS: Increased MDA levels in both patient groups represent increased lipid peroxidation which might play an important role in the pathogenesis of the atherosclerosis seen in these patients. Increased OS in patients with SHypo and OHypo could be improved by LT4 treatment. Also, MDA can be used as a reliable marker of OS and oxidative damage, while IMA is considered to be inappropriate.

Ischemia-modified albümin and malondialdehyde levels in patients with overt and subclinical hyperthyroidism: effects of treatment on oxidative stress.

The main purpose of this study was to evaluate the levels of ischemia-modified albumin (IMA) and malondialdehyde (MDA) in patients with OHyper and SHyper, to assess the effects of antithyroid drug (ATD) therapy on the oxidative stress (OS) parameters. Forty-five untreated patients with overt hyperthyroidism (OHyper), 20 untreated patients with subclinical hyperthyroidism (SHyper) and 30 age-and sex-matched healthy controls were prospectively included in the study. Biochemical and hormonal parameters were evaluated in all patients before and after treatment. Compared with the control subjects, the levels of MDA, glucose and TG were significantly increased in patients with SHyper (p<0.05), whereas LDL-C levels were significantly decreased (p<0.01). Patients with OHyper showed significantly elevated MDA and glucose levels (p<0.001) and significantly decreased LDL-C and HDL-C levels compared with the controls (p<0.01). In patients with Graves' disease, serum TSH levels were inversely correlated with plasma MDA levels (r: -0.42, p<0.05). Plasma MDA levels significantly decreased and levels of TC, LDL-C and HDL-C significantly increased in the groups of OHyper and SHyper after treatment. Serum IMA levels did not significantly change at baseline and with the therapy in all subjects. In conclusion, increased MDA levels in both patient groups represent increased lipid peroxidation which might play an important role in the pathogenesis of the atherosclerosis in these patients. Increased oxidative stress in patients with SHyper and OHyper could be improved by ATD therapy. Also, MDA can be used as a reliable marker of OS and oxidative damage, while IMA is considered to be inappropriate.

Diagnostic value of plasma signal peptide-Cub-Egf domain-containing protein-1 (SCUBE-1) in an experimental model of acute ischemic stroke.

OBJECTIVES: This study was intended to examine possible diagnostic value of plasma Signal Peptide-Cub-Egf domain-containing protein-1 (SCUBE1) levels in an experimental model of acute ischemic stroke. METHODS: Twenty-four female Sprague Dawley rats were divided into four groups. Blood and brain tissue specimens were collected immediately following artery ligation (control; Group 1), 1h after ligation (Group 2), 2 h after ligation (Group 3) and 6h after ligation (Group 4). SCUBE1 levels were investigated in the serum specimens. The brain samples were examined histopathologically. Correlation analysis was performed between the values. RESULTS: Median SCUBE1 values were 1.75 ng/ml in the control group, 3.80 ng/ml, 3.71 ng/ml and 4.19 ng/ml in the groups 2, 3 and 4, respectively (n=6 for each, P=0.004, for each group compared to control values). Histopathological analysis revealed median atrophic neuron percentages of 16% (in group 1), 42%, 55% and 76% in group 2, 3 and 4 respectively (n=6 for each, P=0.004, for each group compared to control group). A higly significant correlation was determined between SCUBE-1 levels and percentage of atrophic neurons (r=0.744 P=0.000). CONCLUSIONS: In this experimental model of acute ischemic stroke plasma SCUBE1 levels rose from the 1st hour of induced stroke and remained high up to 6th hour tested. Results of this experimental study has a potential to become the basis for a clinical study to confirm whether SCUBE1 can be used as a biomarker in the early diagnosis of acute ischemic stroke patients.

Pentraxin-3: A novel biomarker for discriminating parapneumonic from other exudative effusions.

BACKGROUND AND OBJECTIVE: Pentraxin-3 (PTX-3) is a relatively new marker of inflammation that has not been previously tested in pleural effusions. We aimed to assess whether PTX-3 is an accurate biomarker of parapneumonic effusions (PPE) and whether it discriminates complicated (CPPE)from non-complicated PPE. METHODS: The concentrations of pleural fluid PTX-3 were measured by a commercial enzyme-linked immunosorbent assay in a prospective cohort of 84 patients with pleural effusions, including 24 PPE, 40 malignant, and 20 miscellaneous exudative effusions. The area under the curve quantified the overall diagnostic accuracy of the test. A multivariate logistic regression analysis selected pleural fluid biochemistries predictive of PPE. RESULTS: Median pleural fluid PTX-3 levels were higher in PPE than in both malignant effusions and other exudates (32.4 ng/mL vs 6.7 ng/mL, and 8.5 ng/mL, respectively, P < 0.001). PTX-3 > 12 ng/mL yielded 88% sensitivity, 73% specificity, likelihood ratio positive 3.3 and likelihood ratio negative 0.17 for diagnosing PPE, with an area under the curve of 0.855 (95% CI: 0.769-0.941). In the multivariate analysis, pleural PTX-3 levels remained associated with increased diagnostic odds for PPE (odds ratio 17.7, 95% confidence interval: 3.7-85.1, P < 0.001). There was a non-significant trend towards higher pleural PTX-3 levels in CPPE as compared with non-complicated. CONCLUSIONS: High concentrations of PTX-3 in pleural effusions are very sensitive to differentiate PPE from non-PPE. However, they do not seem to differentiate uncomplicated-complicated from CPPE differentiation.

Arg-Phe-amide-related peptides influence gonadotropin-releasing hormone neurons.

The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis. These peptides may modulate the effects of kisspeptins because they are presently recognized as the most potent activators of the hypothalamus-pituitary-gonadal axis. However, their effects on gonadotropin-releasing hormone neurons have not been investigated. In the current study, the GT1-7 cell line-expressing gonadotropin-releasing hormone was used as a model to explore the effects of Arg-Pheamide-related peptides on kisspeptin activation. Intracellular calcium concentration was quantified using the calcium-sensitive dye, fura-2 acetoxymethyl ester. Gonadotropin-releasing hormone released into the medium was detected via enzyme-linked immunosorbent assay. Results showed that 100 nmol/L kisspeptin-10 significantly increased gonadotropin-releasing hormone levels (at 120 minutes of exposure) and intracellular calcium concentrations. Co-treatment of kisspeptin with 1 µmol/L gonadotropin-inhibitory hormone or 1 µmol/L Arg-Phe-amide-related peptide-1 significantly attenuated levels of kisspeptin-induced gonadotropin-releasing hormone but did not affect kisspeptin-induced elevations of intracellular calcium concentration. Overall, the results suggest that gonadotropin-inhibitory hormone and Arg-Phe-amide-related peptide-1 may have inhibitory effects on kisspeptin-activated gonadotropin-releasing hormone neurons independent of the calcium signaling pathway.

A comparison of the effects of N-acetylcysteine and ethyl pyruvate on experimental testicular ischemia-reperfusion injury.

OBJECTIVE: To compare the effects of N-acetylcysteine (NAC) and ethyl pyruvate (EP) on experimental testicular ischemia-reperfusion (I/R) injury. DESIGN: Randomized, controlled, experimental study. SETTING: University hospital. ANIMAL(S): Twenty-four mature male Wistar rats. INTERVENTION(S): Rats were divided into four groups: control group, torsion-detorsion (T/D) group, EP group, and NAC group. In the pretreatment of the NAC and EP groups, 20 mg/kg NAC and 50 mg/kg EP were given intraperitoneally (IP) 30 minutes before detorsion. MAIN OUTCOME MEASURE(S): Serum ischemia-modified albumin (IMA), tissue and serum malondialdehyde, and myeloperoxidase activity levels and histopathological damage scores were then compared. RESULT(S): Ethyl pyruvate and N-acetylcysteine exhibited a protective effect against I/R injury. Of the biochemical parameters evaluated as a result of testicular I/R, only IMA levels were significantly elevated. There was a strong and significant correlation between serum IMA levels and histopathological injury scores, and the increase in serum IMA level exhibited a strong parallel with the increase in histopathological injury. In the EP group, although the histopathological injury score was similar to that of the control group, serum IMA levels were significantly elevated. CONCLUSION(S): Both NAC and EP, the effects of which on I/R injury are evaluated in the present study, reduce such injury in testicular torsion-detorsion. Comparing their effects on IMA levels, NAC may be regarded as a relatively more effective treatment than EP.

Is there any way to protect from tacrolimus-induced renal and pancreas injury?

BACKGROUND: The aim of this study was to explore effects of erythropoietin and pentoxifylline in tacrolimus-induced pancreatic beta cell and renal injury in rats. METHODS: Rats in group I were given saline; rats in group II were injected with tacrolimus; rats in group III were received erythropoietin (Epo) and tacrolimus; while rats in group IV were injected pentoxifylline (Ptx) plus tacrolimus for nine d. On 10th day, blood and tissue samples were taken for biochemical and pathological evaluations. RESULTS: Tacrolimus-injected animals exhibited significant elevation in blood urea nitrogen (BUN), and serum BUN levels were improved in rats pretreated with Ptx. Significantly more apoptotic nuclei were observed in kidneys of tacrolimus group. In rats subjected to tacrolimus and pretreated with Epo, there was significant decrease in apoptotic nuclei staining than those in tacrolimus group. Blood trough levels of tacrolimus were significantly higher in erythropoietin-pretreated group, although same amount of tacrolimus was injected with other groups. CONCLUSION: Results of our study demonstrated significant antiapoptotic effects of erythropoietin on renal tubules, increasing effect of erythropoietin on tacrolimus blood levels, and insignificant antioxidant effects of both erythropoietin and pentoxifylline on renal and pancreas tissues. Study with clinically greater tacrolimus levels may be useful to confirm these findings.

The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in Crimean-Congo hemorrhagic fever.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease caused by a tick-borne virus from the Bunyaviridae family. It has recently been reported that soluble urokinase-type plasminogen activator receptor (suPAR), secreted from endothelial cells and the mononuclear phagocyte system, one of the main targets of the CCHF virus, is a potential biomarker for several bacterial and viral infection diseases. OBJECTIVES: This study was intended to determine the diagnostic and prognostic significance of suPAR levels in CCHF. STUDY DESIGN: This retrospective study was conducted between June 2006 and August 2009 using plasma from patients monitored with a diagnosis of CCHF and from healthy blood donors. Levels of plasma suPAR were determined using an enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturer's instructions. RESULTS: One hundred CCHF patients were enrolled in the study. The control group was made up of 53 healthy blood donors. suPAR values of 6.2 ± 4.2 were determined in the CCHF patients and of 2.3 ± 0.6 in the control group (p<0.0001). A suPAR level optimum diagnostic cut-off point of 3.06 ng/mL was determined, with an area underneath the ROC (AUROC) curve of 0.94 (95% CI: 0.89-0.97), sensitivity of 87% (95% CI: 79-93%), specificity of 92% (95% CI: 82-98%), PPV of 95% and NPV of 79%. Five of the patients died. suPAR was 18.4 ± 9.1 in the patients that died and 5.6 ± 2.6 in the survivors (p=0.034). In terms of mortality, suPAR level had an optimum diagnostic cut-off point of 10.6 ng/mL, AUROC of 0.97 (95% CI: 0.94-0.99), sensitivity of 100% (95% CI: 48-100%), specificity of 96% (95% CI: 90-99%), PPV of 50% and NPV of 100%. CONCLUSIONS: Plasma suPAR level, a new biomarker, is a test that can be used in the differential diagnosis and monitoring of CCHF in patients admitted to hospital with suspected infection. The test is at the same time important in being a possible predictor of mortality.