Moderate aerobic exercise improves haematological indices without altering cardio-metabolic enzyme activities in sedentary healthy young adults.

Background: Regular aerobic exercise regulates cardiorespiratory functions by its effect on specific enzyme activities. This study investigated the immediate effects of moderate aerobic exercise on haematological parameters and cardio-metabolic enzymes activity in healthy young male and female adults.

Methods: Forty young healthy sedentary subjects, twenty males (25 ± 5.

Chronic reduction of store operated Ca entry is viable therapeutically but is associated with cardiovascular complications.

Loss of function mutations in store-operated Ca entry (SOCE) are associated with severe paediatric disorders in humans, including combined immunodeficiency, anaemia, thrombocytopenia, anhidrosis and muscle hypotonia. Given its central role in immune cell activation, SOCE has been a therapeutic target for autoimmune and inflammatory diseases. Treatment for such chronic diseases would require prolonged SOCE inhibition.

Downregulation of by 20-hydroxyecdysone: plasma progesterone and its vasodilatory properties.

Aim: To investigate the effect of 20-hydroxyecdysone on steroidogenic pathway genes and plasma progesterone, and its potential impact on vascular functions.

Methods: Chimeric mice with humanized liver were treated with 20-hydroxyecdysone for 3 days, and hepatic steroidogenic pathway genes and plasma progesterone were measured by transcriptomics and GC-MS/MS, respectively. Direct effects on muscle and mesenteric arterioles were assessed by myography.

Depot- and diabetes-specific differences in norepinephrine-mediated adipose tissue angiogenesis, vascular tone, collagen deposition and morphology in obesity.

Aims: Norepinephrine (NE) is a known regulator of adipose tissue (AT) metabolism, angiogenesis, vasoconstriction and fibrosis. This may be through autocrine/paracrine effects on local resistance vessel function and morphology. The aims of this study were to investigate, in human subcutaneous and omental adipose tissue (SAT and OAT): NE synthesis, angiogenesis, NE-mediated arteriolar vasoconstriction, the induction of collagen gene expression and its deposition in non-diabetic versus diabetic obese subjects.

Oxidant-induced disruption of vascular K channel function: implications for diabetic vasculopathy.

Diabetes in humans a chronic metabolic disorder characterised by hyperglycaemia, it is associated with an increased risk of cardiovascular disease, disruptions to metabolism and vascular functions. It is also linked to oxidative stress and its complications. Its role in vascular dysfunctions is generally reported without detailed impact on the molecular mechanisms.

Untargeted Metabolomics Identifies a Novel Panel of Markers for Autologous Blood Transfusion.

Untargeted metabolomics was used to analyze serum and urine samples for biomarkers of autologous blood transfusion (ABT). Red blood cell concentrates from donated blood were stored for 35−36 days prior to reinfusion into the donors. Participants were sampled at different time points post-donation and up to 7 days post-transfusion.

Horseradish-peroxidase-conjugated anti-erythropoietin antibodies for direct recombinant human erythropoietin detection: Proof of concept.

Antidoping testing for recombinant human erythropoietin (EPO) is routinely performed by gel electrophoresis followed by western blot analysis with primary and secondary antibodies. The two antibody steps add more than 24 h to the testing time of a purified sample. The aim of this study was to test the concept of using directly horseradish-peroxidase (HRP)-conjugated anti-EPO primary antibody, without the need for a secondary antibody, to reduce the analysis time and eliminate non-specific cross-reactivity with secondary antibodies.

Altered cyclooxygenase-1 and enhanced thromboxane receptor activities underlie attenuated endothelial dilatory capacity of omental arteries in obesity.

Aims: Obesity is a risk factor for endothelial dysfunction, the severity of which is likely to vary depending on extent and impact of adiposity on the vasculature. This study investigates the roles of cyclooxygenase isoforms and thromboxane receptor activities in the differential endothelial dilatory capacities of arteries derived from omental and subcutaneous adipose tissues in obesity.

Main Methods: Small arteries were isolated from omental and subcutaneous adipose tissues obtained from consented morbidly obese patients (n = 65, BMI 45 ± 6 kg m [Mean ± SD]) undergoing bariatric surgery.

Studies on vascular response to full superantigens and superantigen derived peptides: Possible production of novel superantigen variants with less vasodilation effect for tolerable cancer immunotherapy.

Superantigens (SAgs) are a class of antigens that cause non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release and causing symptoms similar to sepsis, e.g. hypotension and subsequent hyporeactivity.

Ex vivo relaxations of pulmonary arteries induced by prostacyclin mimetics are highly dependent of the precontractile agents.

Prostacyclin (PGI2) mimetics (iloprost, treprostinil) are potent vasodilators (primarily via IP-receptor activation) and major therapeutic interventions for pulmonary hypertension (PH). Increased plasma levels of endothelin (ET-1), thromboxane (TxA2) and catecholamines have been demonstrated from patients with PH. In this study, we aimed to compare relaxant effects of iloprost and treprostinil on human (HPA) and rat pulmonary arteries precontracted with either ET-1, thromboxane (U46619) or an α-adrenergic receptor agonist (Norepinephrine, NE or phenylephrine, PE).

Attenuated vascular responsiveness to K+ channel openers in diabetes mellitus: the differential role of reactive oxygen species.

The current study examined the responsiveness of blood vessels from diabetic rats to K+ channel openers and explored whether ROS might be involved in any changes. Responses were measured in aortic rings isolated from four weeks streptozotocin (65 mg/kg)-induced diabetic rats. Relaxation to levcromakalim (ATP-sensitive potassium channel KATP opener, 10(-9)-10(-5) mol/l) and (+/-)-naringenin (large conductance calcium-activated channel BKCa opener, 10(-8)-10(-3) mol/l) were recorded in phenylephrine (1 µmol/l) pre-contracted segments in the absence and presence of superoxide dismutase (SOD, 100 µmol/l) and apocynin (an antioxidant and inhibitor of NADPH oxidase, 100 µmol/l).

Inhibition of vascular adenosine triphosphate-sensitive potassium channels by sympathetic tone during sepsis.

Objective: Excessive opening of the adenosine triphosphate-sensitive potassium channel in vascular smooth muscle is implicated in the vasodilation and vascular hyporeactivity underlying septic shock. Therapeutic channel inhibition using sulfonylurea agents has proved disappointing, although agents acting on its pore appear more promising. We thus investigated the hemodynamic effects of adenosine triphosphate-sensitive potassium channel pore inhibition in awake, fluid-resuscitated septic rats, and the extent to which these responses are modulated by the high sympathetic tone present in sepsis.

BK large conductance Ca²+-activated K+ channel-deficient mice are not resistant to hypotension and display reduced survival benefit following polymicrobial sepsis.

Nitric oxide-mediated activation of large conductance calcium-activated potassium (BK) channels is considered an important underlying mechanism of sepsis-induced hypotension. Indeed, the nonselective K-channel inhibitor, tetraethylammonium chloride (TEA), has been proposed as a potential treatment to raise blood pressure in septic shock by virtue of its ability to inhibit BK channels. As experimental evidence has so far relied on pharmacological inhibition, we examined the effects of channel deletion using BKα subunit knockout (α, Slo) mice in two mouse models of polymicrobial sepsis, namely, intraperitoneal fecal slurry and cecal ligation and puncture.

Role of prostanoid IP and EP receptors in mediating vasorelaxant responses to PGI2 analogues in rat tail artery: Evidence for Gi/o modulation via EP3 receptors.

Prostanoid IP receptors coupled to Gs are thought to be the primary target for prostacyclin (PGI(2)) analogues. However, these agents also activate prostanoid EP(1-4) receptor subtypes to varying degrees, which are positively (EP(2/4)) or negatively (EP(3)) coupled to adenylate cyclase through Gs or Gi, respectively. We investigated the role of these receptors in modulating relaxation to PGI(2) analogues cicaprost, iloprost and treprostinil in pre-contracted segments of rat tail artery.

Differential effects of vasopressin and norepinephrine on vascular reactivity in a long-term rodent model of sepsis.

Objective: There is escalating interest in the therapeutic use of vasopressin in septic shock. However, little attention has focused on mechanisms underlying its pressor hypersensitivity, which contrasts with the vascular hyporesponsiveness to catecholamines. We investigated whether a long-term rodent model of sepsis would produce changes in endogenous levels and pressor reactivity to exogenous norepinephrine and vasopressin comparable with those seen in septic patients.

Evidence that inward rectifier K+ channels mediate relaxation by the PGI2 receptor agonist cicaprost via a cyclic AMP-independent mechanism.

Objective: We investigated the role of the inward rectifier potassium (KIR) channel and the cyclic AMP-dependent pathway in mediating vasorelaxation induced by the prostacyclin analogue cicaprost.

Methods: Small vessel myography was used to assess responses to cicaprost in segments of rat tail artery contracted with phenylephrine. Microelectrode recordings were made from helical strips to assess effects on membrane potential.

S-nitroso-albumin carries a thiol-labile pool of nitric oxide, which causes venodilation in the rat.

It is now established that S-nitroso-albumin (SNO-albumin) circulates at low nanomolar concentrations under physiological conditions, but concentrations may increase to micromolar levels during disease states (e.g., cirrhosis or endotoxemia).

Nitration of endogenous para-hydroxyphenylacetic acid and the metabolism of nitrotyrosine.

Reactive nitrogen species, such as peroxynitrite, can nitrate tyrosine in proteins to form nitrotyrosine. Nitrotyrosine is metabolized to 3-nitro-4-hydroxyphenylacetic acid (NHPA), which is excreted in the urine. This has led to the notion that measurement of urinary NHPA may provide a time-integrated index of nitrotyrosine formation in vivo.