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.     

Extraarticular manifestations in Turkish patients with rheumatoid arthritis: impact of EAMs on the health-related quality of life in terms of disease activity, functional status, severity of pain, and social and emotional functioning

The aim of our study was to investigate extraarticular manifestations (EAMs) in Turkish patients with rheumatoid arthritis (RA) and also assess the impact of EAMs on various health-related quality of life (HRQoL) domains, including physical, social, emotional, mental functioning, and bodily pain. A total of 150 patients were included in the study. EAMs were identified clinically. Pulmonary involvement was confirmed by using pulmonary function tests (PFT) and high-resolution computed tomography (HRCT), atlantoaxial subluxation by cervical spine X-rays. Peripheral neuropathy, rheumatoid nodules, and Sicca symptoms were picked up on clinical examination. Peripheral neuropathy was also confirmed by electroneurophysiologic studies. Patients were evaluated by Rheumatoid Arthritis Quality of Life (RAQoL), and Short form-36 (SF36). The quadrivariate Disease Activity Score- 28 (DAS28) was used for measuring disease activity. Functional status was evaluated by using the Stanford Health Assessment Questionnaire (HAQ). The severity of pain was documented by using 10-cm Visual Analog Scale-Pain (VAS-pain). EAMs were observed in 50 patients (33.3%). These were pulmonary involvement (28.7%), rheumatoid nodules (14.7%), Sicca Syndrome (8%), peripheral neuropathy (2.7%), and atlantoaxial subluxation (0.7%), respectively. It was not recorded any statistically significant difference in HAQ, DAS28, VAS-pain, and RAQoL scores between the patient groups with and without EAMs. Patients with EAMs scored significantly lower in physical functioning, role-physical, and role-emotional subgroups of SF36 (P?<?0.01). Presence of EAMs is not directly associated with disease activity and functional status, but influences negatively HRQoL including physical and emotional functioning.     

Cardiac Autonomic Function and Global Left Ventricular Performance in Autoimmune Eauthyroid Chronic Thyroiditis: Is Treatment Necessary at the Euthyroid Stage?

Objective: Autoimmune chronic thyroiditis (ACT) is characterized by lymphocyte infiltration in the thyroid gland and the presence of antithyroid antibodies in serum. Medical treatment does not affect antibody levels and treatment decision is not definite yet for the euthyroid patients. We aimed to evaluate cardiac autonomic function and global left ventricular performance in autoimmune euthyroid chronic thyroiditis and determine the need for medical treatment. Method: We studied 30 ACT patients and 25 healthy control subjects. Cardiac autonomic function is evaluated by heart rate recovery (HRR). Global left ventricular performance is evaluated by two‐dimensional echocardiography and pulsed‐wave tissue Doppler echocardiography. Results: There was no difference between patients and controls with respect to clinical and biochemical parameters except hemoglobin (13.67 ± 1.25 g/dL, 14.51 ± 1.35 g/dL, p:0.047) and low density lipoprotein (120.71 ± 24.91 mg/dL, 100.55 ± 14.73 mg/dL, p: 0.003). Tei index was significantly higher in ACT group (0.521 ± 0.074, 0.434 ± 0.034, P < 0.0001). E′/A′ was found to be significantly lower (1.234 ± 0.42, 1.750 ± 0.291, P < 0.0001) and E/E′ was found to be higher than the controls (8.482 ± 0.449, 6.039 ± 0.209, P < 0.0001). HRR was significantly lower than the controls (20 ± 4 BPM, 30 ± 8 BPM, P < 0.0001). Conclusion: Although left ventricular performance is found to be normal by conventional echocardiographic methods, it is found to be impaired when Tei index and tissue Doppler parameters are used. Cardiac autonomic function is also impaired in ACT patients. As a result of these cardiac changes, medical treatment may be considered earlier, even at the euthyroid stage. (Echocardiography 2011;28:15‐21)