BackgroundPravastatin, a known inducer of endothelial nitric-oxide synthase (eNOS) was demonstrated in human placenta, however the exact mechanism of it’s action is not fully understood. Since placental NO (nitric oxide) synthesis is of primary importance in the regulation of placental blood flow, we aimed to clarify the effects of pravastatin on healthy (n = 6) and preeclamptic (n = 6) placentas (Caucasian participants).MethodsThe eNOS activity of human placental microsomes was determined by the conversion rate of C14 L-arginine into C14 L-citrulline with or without pravastatin and Geldanamycin. Phosphorylation of eNOS (Ser1177) was investigated by Western blot. Microsomal arginine uptake was measured by a rapid filtration method.ResultsPravastatin significantly increased total eNOS activity in healthy (28%, p<0.05) and preeclamptic placentas (32%, p<0.05) using 1 mM Ca2+ promoting the dissociation of a eNOS from it’s inhibitor caveolin. Pravastatin and Geldanamycin (Hsp90 inhibitor) cotreatment increased microsomal eNOS activity. Pravastatin treatment had no significant effects on Ser1177 phosphorylation of eNOS in either healthy or preeclamptic placentas. Pravastatin induced arginine uptake of placental microsomes in both healthy (38%, p < 0.05) and preeclamptic pregnancies (34%, p < 0.05).ConclusionsThis study provides a novel mechanism of pravastatin action on placental NO metabolism. Pravastatin induces the placental microsomal arginine uptake leading to the rapid activation of eNOS independently of Ser1177 phosphorylation. These new findings may contribute to better understanding of preeclampsia and may also have a clinical relevance.

Background Both peroxisome activator proteins (PPARs) and fetuin-A play a role in lipid and glucose metabolism. Aims We investigated whether PPARα intron 7 G2468/C and PPARγ2 Pro12Ala and PPARγ exon 6 C161T polymorphisms are associated with serum fetuin-A concentrations. Patients and Methods The PPARα intron 7 G/C polymorphism was studied in cohort 1 (79 reference individuals, 165 postinfarction patients). The two PPARγ polymorphisms were investigated in cohort 2 (162 reference individuals, 165 postinfarction patients). Fetuin-A levels and PPAR polymorphisms were determined by radial immunodiffusion and polymerase chain reaction-restriction fragment length polymorphism techniques. Results The C allele variant of PPARα intron 7 G2467C was associated with higher fetuin-A levels (p = 0.018). Postinfarction status (p = 0.001), PPARα intron 7 GG/GC/CC genotypes (p = 0.032), and the C allele (p = 0.021) were the strongest determinants of fetuin-A concentration in a multiple regression model. Higher fetuin-A levels were associated with the Pro variant of PPARγ2 (p = 0.047). Postinfarction status (p = 0.041) and BMI (p < 0.001) but not PPARγ2 Pro were the strongest determinants of fetuin-A concentrations. PPARγ exon 6 C161T genotypes were not associated with fetuin-A levels. Conclusions Fetuin-A was determined mainly by the PPARα intron 7C allele and postinfarction status in cohort 1 and the BMI and postinfarction in cohort 2. The PPARα intron 7C and PPARγ2 Pro variants are associated with fetuin-A levels.

e111 and the presence of polyhydramnios, gestational age at diagnosis, lung-to-head ratio (LHR) and observed/expected LHR (O/E LHR) values, gestational age at birth and birth weight. Intrathoracic liver herniation was a statistically significant parameter adversely affecting survival (37.2% in survivors, 68.8% in non-survivors, p = 0.031) and logistic regression confirmed this relationship. The presence of pneumothorax and severe pulmonary hypertension were significantly associated with mortality (82% non-survivors versus 15% in survivors, p = 0.0001).Conclusion: Intrathoracic liver herniation seems to be a reliable parameter in the prediction of survival and neonatal respiratory morbidity in fetuses with isolated left-sided CDH. In contrast, we found no significant correlation between perinatal outcome and LHR, O/E LHR values, birth weight and gestational age. This study was supported by the OPPK CZ.2.16/3.1.00/25015 project (Operational Program Prague, an EU funding mechanism). (D. Supák).Based on our previous studies and observations concerning the effects of acylated ghrelin and resistin on weight gain and insulin resistance, our current aim is to examine the association of these proteins with pregnancy-induced obesity and insulin resistance in a cross-sectional study carried out in patients with GDM, healthy pregnant women and non-pregnant controls of the same age. The diagnosis of GDM was done as specified by the WHO classification protocol using the 75 g oral glucose tolerance test (OGTT). The patients enrolled in our study according to the degree of dysfunction in their carbohydrate metabolism. Serum ghrelin and adiponectin levels were established using RIA kits, while serum resistin, soluble (s) TNF-receptor-1 and leptin levels were measured and published using the ELISA technique. The fasting serum levels of biologically active (acylated) ghrelin showed to be significantly lower in patients with GDM in comparison to those of non-pregnant healthy controls and healthy pregnant women in the 1st trimester. GDM values were significantly lower than those of healthy expectants in the 3rd trimester, as compared to the non-pregnant control group, the GDM patients, and the healthy pregnant women in the 1st and 3rd trimesters. Acylated ghrelin levels showed a negative correlation (p < 0.05) with body mass index (BMI), resistin, TNF-␣, sTNFR-2, leptin, C-peptide concentrations, C-peptide/blood glucose ratio and daily insulin dose required to maintain euglycemia, and in the GDM group, showed a positive correlation with adiponectin levels. Fasting serum resistin concentrations were significantly elevated in patients with GDM and in healthy pregnant women in the 3rd trimester in comparison to the non-pregnant control group. In the GDM group, serum resistin correlated positively with serum TNF-␣, sTNFR-1 and -2 and Cpeptide concentrations, C-peptide/blood glucose ratio and daily insulin dose. While analyzing antropometric data in the fetus, we found a negative correlation between fasting serum levels of biologically ac...

Patients facing severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infections with comorbidities, especially patients whose immune system is weakened have higher chances to face severe outcomes. One of the main reasons behind the suppression of the immune system is iatrogenic, in patients who have autoimmune diseases and/or had an organ transplant. Although there are studies that are examining immunocompromised and/or transplanted patients with COVID-19 infection, furthermore there is a limited number of studies available which are dealing with COVID-19 in pregnant women; however, it is unique and is worth reporting when these factors are coexisting. In this study, we present the case of a 33-year-old Caucasian pregnant woman, who had a kidney transplant in 2009 and contracted the SARS-CoV-2 virus on the 26th gestational week, in 2021. After her infection, superimposed preeclampsia was diagnosed and due to the worsening flowmetric parameters, she gave birth to a premature male newborn with cesarean section. Our kidney transplant patient’s case highlights how COVID-19 disease can lead to preeclampsia and artificial termination of gestation.

Absztrakt: Bevezetés: A terhességek 3–8%-ában megjelenő praeeclampsia kezelése még jelenleg sincs megoldva. Praeeclampsiában elégtelen a NO szintézise, ami hozzájárulhat az emelkedett vérnyomáshoz, proteinuriához, a placenta kóros vascularisatiójához is. Praeeclampsiás placentában a csökkent NO-szintézisnek az is oka lehet, hogy a NO-szintáz affinitása csökken a tetrahidrobiopterinhez (BH4), ezzel BH4-rezisztencia alakul ki. Az utóbbi években állatmodellekben és humánvizsgálatokban is megfigyelték, hogy a pravasztatin védhet a praeeclampsia kialakulása ellen. A pravasztatin egyik ismert pleiotrop hatása az, hogy emeli a NO-szintáz aktivitását. Célkitűzés: A pravasztatin hatásának leírása a BH4-rezisztens NO-szintáz aktivitására praeeclampsiás placentában. Módszer: A NO-szintáz aktivitását placentamikroszómában mértük C14-arginin szubsztráttal egészséges (n = 9) és praeeclampsiás (n = 9) minta felhasználásával. A NO-szintáz aktivitását 0,02 µM, fiziológiás 0,2 µM és farmakológiás 50 µM BH4 mellett mértük. Eredmények: 9 praeeclampsiás mintából egy volt BH4-rezisztens; a fiziológiás BH4-koncentráció nem növelte szignifikánsan a NO-szintáz aktivitását, míg az egészséges placenta-mikroszómák aktivitását átlagosan 60%-kal (p<0,01), a BH4-szenzitív praeeclampsiás minták NO-szintáz-aktivitását 67%-kal (p<0,01) növelte. 10 µM pravasztatin 32–38%-kal növelte a NO-szintáz aktivitását mindegyik BH4-koncentrációnál az egészséges, a BH4-szenzitív és a BH4-rezisztens praeeclampsiás mintákban is. Következtetés: 10 µM pravasztatin a BH4-rezisztens placenta NO-szintáz-aktivitását hasonló mértékben növelte, mint a placenta fiziológás BH4-koncentrációja (0,06–0,20 µM) a BH4-érzékeny NO-szintáz aktivitását. Vizsgálatunkkal tehát kimutattuk, hogy a pravasztatin a BH4-rezisztens praeeclampsiás placenta NO-szintáz-aktivitását fiziológiás szintre emeli. Orv Hetil. 2020; 161(10): 389–395.