Constitutive expression of platelet glycoproteins by the human leukemia cell line K562

The human leukemia cell line K562 was derived from a patient with chronic granulocytic leukemia. This cell line has subsequently been shown to possess phenotypic markers typical of erythroid and myeloid cells. Using a rabbit antiserum directed against purified platelet glycoproteins (PGPs), we have obtained evidence for the constitutive expression of PGPs on the surface of K562 cells. PGPs expressed have been tentatively identified as IIa and III based on their apparent migration in a 7% sodium dodecylsulfate polyacrylamide gel. K562 may become an important tool for the study of early events involved in megakaryocytic differentiation.     

Early and late cardiac ventricular reverse remodeling after catheter ablation for lone paroxysmal atrial fibrillation

Aim

We sought to explore ventricular function in patients with lone paroxysmal atrial fibrillation (AF) and determine the mid- and long-term impact of pulmonary vein isolation on cardiac remodeling.

Background

The relationship between tachyarrhythmia and ventricular dysfunction is still a matter of debate. Tachycardia-induced cardiomyopathy is defined as reversible myocardial dysfunction following treatment for tachyarrhythmia.

Method

We prospectively studied 31 patients (56.4 ± 10 years) presenting with paroxysmal-AF who were treated successfully by catheter ablation and 15 age-matched controls. Left and right ventricular functions were assessed by echocardiography at baseline and at 3-month and 1-year follow-up.

Results

In AF-patients, LV-function was slightly lower at baseline than controls (LV-ejection fraction was 60% versus 64%; P = 0.06). More impressive, systolic peak velocity on Doppler tissue imaging was 9 cm/s in AF patients (versus 12 cm/s; P = 0.0004). LV global longitudinal strain was also significantly different between the two groups (patients: −16% versus controls: −19%; P = 0.005). At 1-year follow-up, most functional parameters significantly improved in the AF-patients and no longer differed from the controls. Right ventricular (RV) function was also depressed in AF patients at baseline. At 1-year follow-up, tissue Doppler showed improvement in RV-S′ (+27%, P = 0.007) and RV peak systolic strain (+36%, P < 0.0001) and became comparable to controls.

Conclusion

We demonstrate that some degree of arrhythmic cardiomyopathy exists in patients presenting with lone paroxysmal-AF. Catheter ablation improved RV and LV functions. Longitudinal function is the most sensitive component of ventricular systole to monitor when looking for this cardiac reverse remodeling.     

Contr?le du rythme sinusal ou contr?le de la fréquence ventriculaire ?

Rhythm control or rate control are the 2 therapeutic strategies for atrial fibrillation (AF) management. Despite strong physiological and epidemiological data to support a rhythm control strategy, the results of the prospective studies, especially AFFIRM and RACE trials, did not demonstrate any superiority of a rhythm control versus a rate control strategy. The AF-CHF trial conducted in heart failure patients led to the same conclusions. In clinical practice, the therapeutic management is only driven by the patient symptoms. For rhythm control, antiarrhythmic drugs are still the first step before considering, in selected patients, ablative techniques. Treatment algorithms proposed in 2006 by the European society of cardiology are the references for patient management, treatment being individually optimized.     

Cigarette smoke exposure up-regulates endothelin receptor B in human pulmonary artery endothelial cells: molecular and functional consequences

BACKGROUND AND PURPOSE

Pulmonary arteries from smokers and chronic obstructive pulmonary disease patients show abnormal endothelium-dependent vascular reactivity. We studied the effect of cigarette smoke extract (CSE) on endothelin receptor B (ET_B) expression in human pulmonary artery endothelial cells (HPAECs) and its role in endothelial dysfunction.

EXPERIMENTAL APPROACH

ET_B receptor expression was measured by real time RT-PCR, Western blot and immunofluorescence. Cell contraction, intracellular Ca²⁺, F/G-actin, RhoA activity, myosin light chain phosphorylation, ET, NO, thromboxane (Tx)A₂ and reactive oxygen species (ROS) were measured by traction microscopy, fluorescence microscopy, phalloidin fluorescence, colorimetric assay, Western blot, elisa and DCFDA fluorescence respectively.

KEY RESULTS

Cigarette smoke extract dose-dependently increased ET_B receptor expression in HPAECs after 24 h incubation. CSE-induced ET_B expression was attenuated by bosentan, the ET_B receptor antagonist BQ788, the Rho kinase antagonist Y27632 and the antioxidant N-acetylcysteine. A monoclonal antibody to ET-1 prevented CSE-induced ET_B receptor overexpression. Twenty-four hour exposure to ET-1 dose-dependently increased ET_B receptor expression, mimicking the effect of CSE. CSE-induced ET_B receptor overexpression caused greater cell contraction; increased intracellular Ca²⁺; increased F/G-actin and RhoA activity; increased myosin light chain phosphorylation; augmented TxA₂ and ROS production; and decreased NO after acute ET-1 (10 nM). These effects were attenuated by bosentan, BQ788, Y27632 and N-acetylcysteine.

CONCLUSIONS AND IMPLICATION

Cigarette smoke extract induced ET_B receptor overexpression by a feed forward mechanism mediated partly by ET release, promoting HPAEC dysfunction and attenuated by ET_B receptor blockade, Rho kinase and ROS inhibition. These results provide support for the use of bosentan in CS-related endothelial dysfunction.     

Induction of apoptosis by the ginsenoside Rh2 by internalization of lipid rafts and caveolae and inactivation of Akt

Background and purpose:

Lipid rafts and caveolae are membrane microdomains with important roles in cell survival signalling involving the Akt pathway. Cholesterol is important for the structure and function of these microdomains. The ginsenoside Rh2 exhibits anti-tumour activity. Because Rh2 is structurally similar to cholesterol, we investigated the possibility that Rh2 exerted its anti-tumour effect by modulating rafts and caveolae.

Experimental approach:

A431 cells (human epidermoid carcinoma cell line) were treated with Rh2 and the effects on cell apoptosis, raft localization and Akt activation measured. We also examined the effects of over-expression of Akt and active-Akt on Rh2-induced cell death.

Key results:

Rh2 induced apoptosis concentration- and time-dependently. Rh2 reduced the levels of rafts and caveolae in the plasma membrane and increased their internalization. Furthermore, Akt activity was decreased and consequently, Akt-dependent phosphorylation of Bad, a pro-survival protein, was decreased whereas the pro-apoptotic proteins, Bim and Bax, were increased upon Rh2 treatment. Unlike microdomain internalization induce by cholesterol depletion, Rh2-mediated internalization of rafts and caveolae was not reversed by cholesterol addition. Also, cholesterol addition did not restore Akt activation or rescue cells from Rh2-induced cell death. Rh2-induced cell death was attenuated in MDA-MB-231 cells over-expressing either wild-type or dominant-active Akt.

Conclusions and implications:

Rh2 induced internalization of rafts and caveolae, leading to Akt inactivation, and ultimately apoptosis. Because elevated levels of membrane rafts and caveolae, and Akt activation have been correlated with cancer development, internalization of these microdomains by Rh2 could potentially be used as an anti-cancer therapy.     

To test or not to test: A cross-sectional survey of the psychosocial determinants of self-testing for cholesterol,glucose, and HIV

Background  

Although self-tests are increasingly available and widely used, it is not clear whether their use is beneficial to the users, and little is known concerning the determinants of self-test use. The aim of this study was to identify the determinants of self-test use for cholesterol, glucose, and HIV, and to examine whether these are similar across these tests. Self-testing was defined as using in-vitro tests on body materials, initiated by consumers with the aim of diagnosing a particular disorder, condition, or risk factor for disease.     

Type 1 diabetes mellitus associated or not with primary hypothyroidism and women’s fertility

Abstract

The aim of this study is to evaluate the prevalence of infertility and other reproductive parameters in women with type 1 diabetes mellitus (DM1) with and without primary hypothyroidism (PH). This is a cross-sectional study conducted at Division of Endocrinology. We evaluated 110 female, aged over 18 years, 79 had DM1 and 31 had DM1 plus PH. They were interviewed to obtain data on their gynecological and obstetric history; medical charts were reviewed to determine the characteristics of the diseases and to assess clinical/laboratory data. Infertility was defined as 12 months of unprotected sexual intercourse without conception. We used the chi-square and Mann–Whitney’s tests, and logistic regression analysis. The prevalence of infertility in the total sample was 24.5%, no differences were found between groups regarding obstetric outcomes and gynecologic variables. Factors associated with infertility were microvascular complication (OR: 11.36; 95% CI: 2.488–52.632; p?=?.029), polycystic ovary syndrome (OR: 9.80; 95% CI: 2.247–43.478; p?=?.016), PH (OR: 3.38; 95% CI: 1.078–10.638; p?=?.047), and older age at onset of DM1 (OR: 1.12; 95% CI: 1.029–1.215; p?=?.019). The presence of PH in women with DM1 was a predictive factor for infertility. Women with DM1 showed poorer reproductive outcomes compared to the general population.