Shear stress activation of nitric oxide synthase and increased NO levels in human red blood cells

Since the discovery of nitric oxide (NO) as a vasoactive molecule, red blood cells (RBC) have been considered to participate in NO-mediated control of the circulation. The classical role attributed to RBC was scavenging of NO, thereby impacting the local bioavailability of this important regulator of vascular tone^1^. RBC have been shown to be a source of NO, primarily via its transport bound to haemoglobin^2, 3^. Under specific conditions, haemoglobin plays an active role in converting NO derivatives (e.g., nitrite) to NO^4, 5^, with this NO originating from RBC being an effective modulator of vascular smooth muscle tone^6^. Interestingly, RBC contain a NO synthase (NOS) protein^7^, can actively synthesize NO using L-arginine as a substrate^8^, and can export NO under appropriate conditions^8, 9^. It has been previously hypothesized that RBC NOS may be activated by shear forces acting on the cell^10^, and we have recently shown that RBC NOS phosphorylation can be enhanced by subjecting RBC in suspension to shearing forces^9^: NO concentration in the suspending medium was increased subsequent to flow of RBC suspensions through five [mu]m pores^11^. We have now directly demonstrated increased RBC NOS activity and intracellular NO levels in immobilized RBC exposed to well-defined fluid shear stress. Immunostaining for serine 1177 phosphorylation and the NO-sensitive fluorescent probe diaminofluorescein were employed. Our results suggest that RBC deformation in constricted vessels may increase NO levels and favor vasodilation, thereby providing an important role for RBC in regulating the circulation

Маркеры воспаления при атеросклеротических изменениях сосудистой стенки у пациентов с ишемической болезнью сердца

ишемическая болезнь сердцаатеросклерозцитокин

Two Cases of BCG Osteomyelitis Diagnosed Through Polymerase Chain Reaction/Electrospray Ionization-Mass Spectrometry Technology.

Barts Charity [grant MGU0294]Wellcome Trust [grant 108065/Z/15/Z to A. J. P.]

Effect of Antihypertensive Therapy with Alpha Methyldopa on Levels of Angiogenic Factors in Pregnancies with Hypertensive Disorders

Antihypertensive drugs are believed to lower blood pressure in pre-eclampsia by direct or central vasodilatory mechanisms. However, they could also act by decreasing production of anti-angiogenic proteins involved in the pathophysiology of hypertension and proteinuria in pre-eclampsia (PE). The aim of our study was to evaluate the impact of antihypertensive therapy with alpha methyldopa on maternal circulating levels and placental production of soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in hypertensive disorders of pregnancy

Immune Modulating Peptides for the Treatment and Suppression of Multiple Sclerosis

Multiple sclerosis (MS) is a neurodegenerative disease in which the immune system recognizes proteins of the myelin sheath as antigenic, thus initiating an inflammatory reaction in the central nervous system. This leads to demyelination of the axons, breakdown of the blood-brain barrier, and lesion formation. Current therapies for the treatment of MS are generally non-specific and weaken the global immune system, thus making the individual susceptible to opportunistic infections. Antigenic peptides and their derivatives are becoming more prevalent for investigation as therapeutic agents for MS because they possess immune-specific characteristics. In addition, other peptides that target vital components of the inflammatory immune response have also been developed. Therefore, the objectives of this review are to (a) summarize the immunological basis for the development of MS, (b) discuss specific and non-specific peptides tested in EAE and in humans, and (c) briefly address some problems and potential solutions with these novel therapies

Controversy and consensus on the management of elevated sperm DNA fragmentation in male infertility: a global survey, current guidelines, and expert recommendations

PURPOSE: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. MATERIALS AND METHODS: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. RESULTS: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4-6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. CONCLUSIONS: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians