Prediction of first-trimester preeclampsia: Relevance of the oxidative stress marker MDA in a combination model with PP-13, PAPP-A and beta-HCG.

OBJECTIVE: Early diagnosis of preeclampsia (PE) is very important and various parameters, individually or in combined models, are reported useful for prediction of PE. The objective of this study is to investigate the predictive value of pregnancy-associated plasma protein-A (PAPP-A), placental protein-13 (PP-13), human Chorionic Gonadotropin (B-HCG), and oxidative stress marker malondialdehyde (MDA), individually and in combination. MATERIALS AND METHODS: Maternal sera of 38 cases with PE and 122 controls were collected for first trimester screening and tested for PAPP-A and B-HCG by chemiluminescence, for PP-13 by using ELISA, and for MDA by high-performance liquid chromatography. Combined models of parameters were constituted as "MDA + PP-13", "PP-13 + PAPP-A + B-HCG" and "MDA + PP-13 + PAPP-A + B-HCG". The diagnostic performances of serum markers of preeclampsia were examined by nonparametric receiver-operator characteristics (ROC) analysis. RESULTS: PP-13 levels were significantly lower (p < 0.001) and MDA levels were significantly higher (p < 0.001) in PE. The area under the ROC curve (AUC) for MDA and PP-13 were greater than those for PAPP-A and B-HCG (p < 0.001). The AUCs of the combined models were significantly larger than those of individual parameters. The combined model "MDA + PP-13 + PAPP-A + B-HCG" exhibited the best predictive outcome with an AUC of 0.91 [95% CI 0.86-0.95], 97% [95% CI 86.2-99.9] sensitivity and 75% [95% CI 66.5-82.6] specificity, and was significantly different from that of "PAPP-A + PP-13 + B-HCG" model, but similar to that of "MDA + PP-13" model. CONCLUSION: Combined models consisting of various parameters of different origin, may provide better predictive outcomes, and oxidative markers should be considered in combination with other placental biomarkers in prediction of PE.

The protective effect of L-arginine, tadalafil, and their combination in rat testes after ischemia and reperfusion injury.

INTRODUCTION: Nitric oxide (NO) plays an important role in the ischemia and reperfusion process. In this study, we aimed to examine the effect of L-arginine, tadalafil, and their combination for prevention of the ischemia reperfusion injury after testis torsion in rats. METHODS: A total of 40 adult, male Sprague-Dawley rats were allocated into five groups. Three hours of left testicular torsion was performed in each group, excluding the control group. While the ischemia reperfusion (I/R) group had no treatment, I/R + Arg group received L-arginine, I/R + Td group received tadalafil and I/R + Arg + Td group received tadalafil and L-arginine 30 minutes before the detorsion. Then the left testis was untwisted for four hours of reperfusion. After bilateral orchiectomy, lipid peroxidation (LPx) and glutathione (GSH) activities were examined in testicular tissue. Spermatogenesis was evaluated with Johnsen's score. RESULTS: LPx levels of the I/R group were found to be significantly higher than for groups that received drugs for both testes (p<0.001). GSH levels of the combination group were higher than I/R group in ipsilateral testis (p<0.01) and it was significantly higher than other groups for contralateral testis (p<0.001 for I/R group, p<0.01 for I/R + Arg, p<0.05 for I/R + Td). Mean Johnsen's score of the I/R group was found to be significantly lower than treatment groups in ipsilateral testis (p<0.001 for I/R + Arg + Td group, p<0.01 for other treatment goups) and contralateral testis (p<0.001). The mean Johnsen score of the combination group was significantly higher than that of other treatment groups in ipsilateral testis (p<0.05) and it was significantly higher than in the I/R + Td group in the contralateral testis (p<0.05). CONCLUSIONS: L-arginine, tadalafil, and combination of these two molecules showed protective effect against ischemia/reperfusion injury for both testes after unilateral testis torsion.

Correlation between arterial stiffness and inflammatory markers in autosomal dominant polycystic kidney disease patients with preserved renal function.

AIM: To evaluate the association between arterial stiffness and inflammatory markers including C-reactive protein (CRP), pentraxin 3 (PTX3) and neutrophil-to-lymphocyte ratio (NLR) in autosomal dominant polycystic kidney disease (ADPKD) patients with preserved renal function. METHODS: A total of 52 ADPKD patients [mean (SD) age 38.2 (12.8) years, 69.2 % were females] with preserved renal function and 25 healthy volunteers [mean (SD) age 35.5 (6.5) years, 48.0 % were females] were included. Data on patient characteristics, blood biochemistry, inflammatory markers [PTX3 (pg/mL), CRP (mg/dL) and NLR] and arterial stiffness [large artery elasticity index (LAEI) (mL/mmHg × 10) and small artery elasticity index (SAEI) (mL/mmHg × 100)] were recorded in patient and control groups. Correlation between inflammatory markers and arterial stiffness parameters was analysed in patients. RESULTS: Overall, 42.3 % of ADPKD patients were hypertensive and 44.4 % were receiving renin-angiotensin-aldosterone system (RAAS) blockade therapy. Median levels for PTX3 [442.0 (20.0-4140.0) pg/mL vs. 220.5 (14.7-393.0) pg/mL, p < 0.001] and SAEI [4.90 (1.60-11.80) mL/mmHg × 100 vs. 6.45 (2.80-15.70) mL/mmHg × 10, p = 0.013] were significantly higher in ADPKD patients than in controls. PTX3 and CRP were not correlated with arterial elasticity, while NLR was significantly correlated with LAEI negatively (Rho = -0.278, p = 0.042). CONCLUSION: In conclusion, our findings revealed increased PTX3 levels and reduced SAEI in patients as compared with controls, while no correlation between inflammatory markers studied and the small artery elasticity.

Arterial dysfunction in early autosomal dominant polycystic kidney disease independent of fibroblast growth factor 23.

INTRODUCTION: Recent studies report reduced vascular compliance and elevated levels of fibroblast growth factor 23 (FGF23) in patients with autosomal dominant polycystic kidney disease (ADPKD) and preserved kidney function. In the present study, we investigated the relationship between vascular compliance and FGF23 in patients in early phases of ADPKD. MATERIALS AND METHODS: We studied 54 ADPKD patients with preserved kidney function and 24 healthy individuals. All participants underwent noninvasive pulse wave analysis in order to determine large arterial elasticity index (LAEI) and small arterial elasticity index (SAEI) using a modified Windkessel model. Levels of FGF23 in addition to several cardiovascular risk factors were evaluated. Linear regression analyses were performed to determine independent correlates of LAEI, SAEI, and FGF23. RESULTS: In the ADPKD group, 33 patients were hypertensive and the remaining patients were normotensive. Serum FGF23 levels of both ADPKD groups were significantly higher than that in the controls. Both hypertensive and normotensive ADPKD patients had lower LAEI and SAEI levels compared to the controls. There was no significant correlation between vascular compliance parameters and FGF23 levels. Having ADPKD was independently associated with increased FGF23 levels and decreased SAEI. CONCLUSIONS: Fibroblast growth factor 23 was found substantially elevated and arterial compliance was found significantly decreased in early ADPKD patients regardless of hypertension. However, there was no significant correlation between FGF23 levels and arterial function parameters. Additional studies are required to determine possible mechanisms of these disturbances and cardiovascular effects of FGF23 in ADPKD patients.