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Genome-Wide Non-Invasive Prenatal Testing (GW-NIPT) can provide positive results not only for common autosomal aneuploidies but also for rare autosomal trisomies (RATs) and structural chromosomal abnormalities (StrCAs). Due to their rarity, there is currently insufficient information on positive predictive value PPV of RAT and StrCA-positive cases in the literature. In this study, the screening accuracy and pregnancy outcomes of cases positive for rare chromosomal abnormalities were examined based on publications in which GW-NIPT testing was performed. True positive cases were determined using two different methodologies. One was a confirmed methodology, where only cases validated by genetic testing were considered true positives with a definite diagnosis, and the other was an extended methodology, where, in addition to cases confirmed by genetic testing, intrauterine fetal death and termination of pregnancy due to an abnormality confirmed by ultrasound examination were also considered true positives, where no diagnosis had been made but the fetus was probably affected. Seventeen studies were analyzed, with a total GW-NIPT population of 740,076. Of these, 1,738 were RAT positive. Using the confirmed method, we found the highest rates of true positives in T16, followed by T22, and T2, using the extended method, the highest rate of true positives in T15, T16 and T22. This is the first meta-analysis to determine the frequency of rare chromosomal abnormalities, test-positive rates, and the PPV of each chromosomal abnormality with high precision. Our results could aid pre- and post-test genetic counselling and help patients and clinicians in their decision-making. [ABSTRACT FROM AUTHOR]

There is no literature available about the growth differentiation factor-15 (GDF-15) biomarker in combination with mitochondrial DNA (mtDNA) deletions in insulin resistance (IR), and polycystic ovary syndrome (PCOS); however, it would be useful to achieve optimal metabolic status and improve pregnancy success. In this study, the role of GDF-15 and mtDNA deletions as biomarkers in the pathogenesis of IR and PCOS was investigated. In our study, 81 female patients who were treated for IR and/or PCOS and 41 healthy controls were included. GDF-15 levels in patients showed a marked increase compared to controls. Elevated GDF-15 levels were found in 12 patients; all of them had a BMI > 25 kg/m2, which is associated with reactive hyperinsulinemia. The presence of mitochondrial dysfunction was mainly observed in the IR-only subgroup. The increase in plasma levels of GDF-15 and the prevalence of mtDNA deletions is directly proportional to body mass index. The more marked metabolic abnormalities required more intensive drug therapy with a parallel increase in plasma GDF-15 levels. Elevated levels of GDF-15 and the presence of mitochondrial DNA deletions may be a consequence of carbohydrate metabolism disorders in patients and thus a predictor of the process of accelerated aging. [ABSTRACT FROM AUTHOR]

Certain steroidal compounds have an antioxidant effect in humans. Our aim was to test whether the synthetic steroid tibolone and its metabolites are also able to display such a property. For this, granulocytes from healthy men and women were incubated for two hours with different concentrations (10−7, 10−8, 10−9 M) of either estradiol, tibolone, 3α-hydroxytibolone, 3β-hydroxytibolone, Δ4-tibolone, 3α-sulfated-tibolone, 3α-17β-disulfated-tibolone, 3β-sulfated-tibolone or 3β-17β-disulfated-tibolone. Superoxide anion generation of neutrophils was measured by photometry. Results of different steroids were given as percentages of their controls. A more simple superoxide generating system, the xanthine-xanthine oxidase reaction was also tested. We found that granulocyte superoxide production did not differ from the control using 10−9 M of steroids. Using 10−8 M concentration: estradiol (80.9 ± 2.5%); 3β-sulfated-tibolone (83.3 ± 4.7%); 3β-17β-disulfated-tibolone (81.0 ± 4.2%) caused a significant decrease in superoxide production, compared to the control. In addition at 10−7 M, 3β-hydroxytibolone and 3α-sulfated-tibolone also showed antioxidant effects. In the xanthine-xanthine oxidase system estradiol (67.4 ± 1.0%), 3α-sulfated-tibolone (85.8 ± 5.3%), 3α-17β-disulfated-tibolone (71.9 ± 2.5%), 3β-sulfated-tibolone (73.9 ± 5.0%), and 3β-17β-disulfated-tibolone (65.8 ± 3.4%) caused a significant decrease in superoxide production. Conclusively, although tibolone itself did not show significant antioxidant capacity, most of its active metabolites have antioxidant effects. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by hyperandrogenism and insulin resistance, both of which have been connected to atherosclerosis. Indeed, an increased risk of clinical manifestations of arterial vascular diseases has been described in PCOS. On the other hand endothelial dysfunction can be detected early on, before atherosclerosis develops. Thus we assumed that vascular dysfunction is also related directly to the hormonal imbalance rather than to its metabolic consequences. To detect early functional changes, we applied a novel rodent model of PCOS: rats were either sham operated or hyperandrogenism was achieved by implanting subcutaneous pellets of dihydrotestosterone (DHT). After ten weeks, myograph measurements were performed on isolated aortic rings. Previously we described an increased contractility to norepinephrine (NE). Here we found a reduced immediate relaxation to estradiol treatment in pre-contracted aortic rings from hyperandrogenic rats. Although the administration of vitamin D3 along with DHT reduced responsiveness to NE, it did not restore relaxation to estradiol. Poly-(ADP-ribose) polymerase (PARP) activity was assessed by poly-ADP-ribose immunostaining. Increased PAR staining in ovaries and circulating leukocytes from DHT rats showed enhanced DNA damage, which was reduced by concomitant vitamin D3 treatment. Surprisingly, PAR staining was reduced in both the endothelium and vascular smooth muscle cells of the aorta rings from hyperandrogenic rats. Thus in the early phase of PCOS, vascular tone is already shifted towards vasoconstriction, characterized by reduced vasorelaxation and vascular dysfunction is concomitant with altered PARP activity. Based on our findings, PARP inhibitors might have a future perspective in restoring metabolic disorders in PCOS. [ABSTRACT FROM AUTHOR]

The aim of this study was to clarify the effects of dihydrotestosterone (DHT)-induced polycystic ovary syndrome (PCOS) on pharmacological reactivity of a resistance vessel in a rat model and the possible modulatory role of 1,25-(OH)2-cholecalciferol (vitamin D3). The PCOS model was induced in adolescent female Wistar rats by a 10-week DHT treatment. Norepinephrine induced contractility and acetylcholine relaxation were tested in arterioles by pressure arteriography in control as well as DHT- and DHT plus vitamin D3-treated (DHT+D3) animals. Decreased vasoconstriction and dilatation were detected after DHT treatment. Concomitant vitamin D3 treatment increased the contractile response and resulted in more relaxed vessels. Endothelial dilation tested with acetylcholine was lower after DHT treatment, this effect was not depend on vitamin D3 supplementation. In conclusion, hyperandrogenic state resulted in reduced endothelium- and smooth muscle-dependent vasorelaxation and constriction with a complete loss of nitric oxide (NO)-dependent relaxation compared with controls. These alterations caused by chronic DHT treatment were partially reversed by concomitant vitamin D3 administration. [ABSTRACT FROM AUTHOR]

Steroid hormones influence the antioxidant processes of cells. However, the molecular mechanism of this effect is not fully clear. Our aim was to examine how steroid hormones affect the expression of certain genes that play a role in antioxidant processes. Blood was taken from ten healthy volunteers. Neutrophil granulocytes were separated and treated either with 17-β-estradiol, progesterone, testosterone, or cortisol. Whole RNA was isolated and reverse transcription was carried out in treated and control groups. Relative quantification was performed with SYBR Green assay and gene-specific oligonucleotides. We found that the expression of Mn-superoxide dismutase was significantly increased by 17-β-estradiol and testosterone, myeloperoxidase expression was significantly elevated by cortisol and progesterone, and the expression of NADPH oxidase was significantly decreased by progesterone. We conclude that the antioxidant effect of steroid hormones is in part carried out through transcriptional regulation of certain enzymes. Subsequent studies are required in order to examine the non-genomic, membrane receptor mediated effect of steroids on antioxidant processes. [ABSTRACT FROM AUTHOR]

The influence of membranous glomerulonephritis (MGN) on maternal and fetal outcome is controversial, as is the effect of pregnancy on the course of preexisting nephrotic syndrome. We report a case of successful management of a pregnancy with preexisting severe nephrotic syndrome due to biopsy-proven primary MGN. Our patient became pregnant in a non-compliance period, discontinued the nephrological follow-up program and her kidney disease decompensated. From the 22nd gestational week the patient was treated with intermittent pulses of methylprednisolone (250 mg i.v.) and a maintenance dose of 32–64 mg/day orally, along with azathioprine 100 mg/day. She also received antihypertensive, diuretic, and anticoagulant therapy, and supplementation with fresh frozen plasma and albumin. In the 33rd gestational week a cesarean section was performed due to deteriorating creatinine clearance, low serum total protein levels, increasing edema and progression of intrauterine growth retardation of the fetus. Three months after delivery, the patient’s renal disease went into complete remission. To our knowledge, this is the first report of using azathioprine during pregnancy with severe nephrotic syndrome due to primary MGN. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background . The prevalence of cardiovascular disorders is higher among men than in age-matched women. This is probably related, in part, to gender-dependent differences in coronary function including thromboxane-A 2 (TXA 2 ) sensitivity. This question has been examined only on major, epicardial coronaries. The intramural small arteries directly responsible for supplying the myocardial arterioles with blood have been hardly accessible for investigation, owing to difficulties in their preparation. Vasoconstrictor TXA 2 excess generated by platelets and the vascular wall may play an important role in coronary ischemic events. In the present study we tested the vasoconstrictor reactivity of intramural coronary arteries to TXA 2 . Methods . Secondary, intramural branches of the left anterior descendent coronary artery of Sprague–Dawley rats (diameter: 200 µm) were placed into a vessel chamber. TXA 2 vasoconstrictor reactivity was measured on the basis of pressure–diameter curves in normal Krebs–Ringer solution and after addition of TXA 2 receptor agonist. Results . Vasoconstrictor response induced by TXA 2 agonist was twice as strong in males compared with females for the whole pressure range ( p < 0.001). Conclusions . A gender-dependent difference was demonstrated in TXA 2 -induced contraction of intramural coronary artery segments. In some pathologic situations the enhanced TXA 2 release from platelets and injured vascular wall may cause greater vasoconstriction of intramural coronary arteries in males than in females. [ABSTRACT FROM AUTHOR]

Abstract: Introduction. : The leiomyomatous type of uterine sarcoma with osteoclast-type giant cell component is a rare variant of uterine tumors with poor prognosis. The histological diagnosis of these rare tumors can be problematic and only five such tumors have been published previously. Case Report. : A 54-year-old woman presented with fever and weight loss for 7 months and laboratory findings suggestive of inflammation. After extensive clinical investigation, a uterine tumor was found, which was considered to be an incidental finding and was thought to be unlikely to explain the symptoms. After hysterectomy, the patient had a surprising and quick recovery with the complete relief of systemic symptoms and normalization of laboratory changes. The tumor was a dedifferentiated leiomyosarcoma with osteoclast-like giant cells and contained extensive necrosis. The patient continues to do well and is tumor-free 1 year after the operation. Discussion. : To our knowledge, this is the first report of a patient being alive and disease-free 12 months after surgery with a dedifferentiated uterine leiomyosarcoma with osteoclast-like giant cells. [Copyright &y& Elsevier]