Thrombopoietin receptor (Mpl) expression by megakaryocytes in myeloproliferative disorders

The thrombopoietin receptor (Mpl) is involved in the pathogenesis of chronic myeloproliferative disorders (CMPD). In this study, we determined Mpl expression by bone marrow cells and megakaryocytes in CMPD by applying laser microdissection, real-time RT-PCR, and immunohistochemistry. Mpl mRNA expression was significantly increased up to 9-fold in total bone marrow cells (p < 0.001) and up to 4-fold in megakaryocytes in chronic myeloproliferative disorders (n = 73) compared to normal controls (n = 26, p = 0.01). Immunohistochemistry revealed heterogeneous Mpl expression by megakaryocytes in CMPD with a stronger accentuation in idiopathic myelofibrosis (IMF) in comparison to polycythaemia vera (PV) and essential thrombocythemia (ET). In addition to megakaryocytes, the erythropoietic lineage was prominently labelled by Mpl antiserum, with considerably stronger staining in polycythaemia vera. We conclude that, in CMPD, megakaryocytes and erythroid cells exhibit increased Mpl expression levels which may contribute to the sustained proliferation of both cell lineages in CMPD.     

The prevalence of metabolic syndrome is increased in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Purpose

Cardiovascular disease is one of the major causes of mortality in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Metabolic syndrome (MetS) is associated with increased cardiovascular risk in the normal population. However, MetS in AAV has not been adequately investigated. We aimed to determine MetS prevalence and associated factors in AAV patients.

Methods

Thirty-seven AAV patients and 42 healthy controls were enrolled. MetS was determined by International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria. The relationship between clinical features of AAV and MetS was also investigated.

Results

MetS was significantly higher in AAV patients than controls by NCEP-ATPIII (51.4% vs. 26.2%, p 0.022) and IDF (62.2% vs. 35.7%, p 0.020). When AAV patients with MetS were compared to those without, there were significant differences in age, CRP, GFR and NT-pro-BNP. Age [58 (13) vs. 50 (8) years p: 0.028], CRP [4.0 (3.6) vs. 3.2 (1.0) mg/l, p 0.021] and NT-pro-BNP [173.5 (343.7) vs. 106.0 (103.0) pg/ml, p 0.013] were significantly higher in AAV patients with MetS than those without; GFR was significantly lower [38 (46) vs. 83 (51) ml/min/1.73 m², p 0.004]. ROC curve analysis showed NT-pro-BNP?>?58.0 ng/ml predicted MetS with 87.1% sensitivity and 46.7% specificity (Area under curve: 0.71, CI 0.536–0.902, p 0.041). Multivariate analysis revealed age [OR (95% CI): 1.180 (1.010–1.370), p 0.039] and NT-pro-BNP?>?58 pg/ml [OR (95% CI): 5.5 (1.02–30.1) p 0.047] were independent predictors of MetS in AAV patients.

Conclusion

MetS is significantly higher in AAV patients than controls and is associated with age and NT-pro-BNP. Screening and treating MetS may improve prognosis in AAV patients.

     

Carbamazepine-induced sperm disorders can be associated with the altered expressions of testicular KCNJ11/miR-let-7a and spermatozoal CFTR/miR-27a

Male infertility is a global health problem, and the underlying molecular mechanisms are not clearly known. Ion channels and microRNAs (miRNAs), known to function in many vital functions in cells, have been shown to play a significant role in male infertility through changes in their expressions. The study aimed to evaluate the alterations of testicular and/or spermatozoal potassium voltage-gated channel subfamily J member 11 (KCNJ11), Cystic fibrosis transmembrane conductance regulator (CFTR), miR-let-7a and miR-27a expressions in carbamazepine-related male infertility. Here, we showed that carbamazepine reduced sperm motility, increased abnormal sperm morphology, and impaired hormonal balance as well as increased relative testis weight and decreased relative seminal vesicle weight. On the other hand, downregulated KCNJ11 and upregulated miR-let-7a expressions were determined in testis (p < .05). Also, downregulated KCNJ11 and upregulated CFTR and miR-27a expressions were found in spermatozoa (p < .05). Interestingly, altered testicular KCNJ11 and miR-let-7a expressions were correlated with decreased sperm motility and elevated sperm tail defect. Besides, spermatozoal CFTR and miR-27a expressions positively correlated with sperm tail defects. The results indicated a significant relationship between ion channel and/or miRNA expression alterations and impaired sperm parameters due to carbamazepine usage.     

Antioxidant,anticholinesterase and tyrosinase inhibition activities,and fatty acids of Crocus mathewii – A forgotten endemic angiosperm of Turkey

Context We report the first ever chemical/biochemical study on Crocus mathewii Kerndorff (Iridaceae) – a Turkish endemic angiosperm. This plant has never been explored for its phytochemistry and bioactivities.

Objective This study explores C. mathewii corm and aerial parts for the chemical and biological properties of hexane, ethyl acetate, methanol and water fractions of the extracts.

Material and methods Plant material (20 g) was extracted by methanol (250?mL?×?5, 3 days each) and fractioned into hexane, ethyl acetate, methanol and water. All fractions were subjected to β-carotene–linoleic acid, DPPH^·, ABTS^·+, CUPRAC, metal chelating and tyrosinase inhibition activities. Hexane fractions were submitted to GC–MS analysis.

Results Ethyl acetate fractions showed excellent IC₅₀ values in DPPH^· (aerial 36.21?±?0.76 and corm 33.87?±?0.02?mg/L) and ABTS^·+ (aerial 33.01?±?0.79 and bulb 27.87?±?0.33?mg/L); higher than the IC₅₀ of the standard α-tocopherol (DPPH 116.25?±?1.97; ABTS 52.64?±?0.37?mg/L), higher than BHA in DPPH (57.31?±?0.25?mg/L), but slightly lower in ABTS (19.86?±?2.73?mg/L). Methanol extract of aerial parts also showed higher activity than α-tocopherol in DPPH (85.56?±?11.51?mg/L) but slightly less (72.90?±?3.66?mg/L) than both the standards in ABTS. Linoleic (aerial 53.9%, corm 43.9%) and palmitic (aerial 22.2%, corm 18%) were found as the major fatty acids.

Discussion and conclusion Some fractions of C. mathewii showed higher antioxidant activities than the standards. There is a need to explore more about this plant.     

Efficacy of vaginal misoprostol before hysteroscopy for cervical priming in patients who have undergone cesarean section and no vaginal deliveries

We wanted to investigate the effect of misoprostol administered vaginally before operative hysteroscopy on cervical dilation, complications, and failure rates in patients who have undergone cesarean section and who have never delivered vaginally. Sixty patients who had undergone cesarean section, who had never delivered vaginally before, and were about to undergo hysteroscopy for various intrauterine lesions were included in this randomized controlled study. Thirty-two patients in the study group were given misoprostol 400 microg, and 28 patients in the control group were given placebo (hexetidine pill) vaginally twice, 6 and 12 hours before the procedure. Primary endpoints were cervical width detected with Hegar dilators and complication and failure rates. Mean cervical width was greater in patients in the study group (6.5 +/- 0.8) than it was in patients in the control group (3.0 +/- 0.6), (p = .0001). Complication and failure rates were lower in patients in the study group (p = .01). Administration of vaginal misoprostol before hysteroscopy proved to be effective in cervical ripening and in reducing complication and failure rates.     

Cumulative exposure to high estradiol levels during the follicular phase of IVF cycles negatively affects implantation

Purpose: To investigate the effect of the cumulative exposure to estradiol (E₂) during the follicular phase on IVF outcome. Methods: Patients were stimulated with recombinant FSH after GnRH agonist suppression and had a day 3-embryo transfer. Estrogen exposure was determined as the area under the curve (AUC) for serum E₂ levels measured from the first day of stimulation through the day after hCG administration. Results: E₂ AUC thresholds for 10th and 90th percentiles were 4704 pg/ml and 16338 pg/ml, respectively. The pregnancy and implantation rates were highest in the 10th–90th percentile group, and were statistically higher in this group than in the >90th percentile group (54.6% vs. 33.3% and 24.8% and 12.9%, respectively, for pregnancy and implantation rates, P < 0.05). Recovered mature oocytes, fertilization, and number and mean score of transferred embryos were similar. Conclusions: High cumulative E₂ exposure during the follicular phase of IVF cycles has detrimental effects on implantation.