The role of neuronal NO synthase in the respiratory effects of TNF-α

It was shown that an increase level of proinflammatory cytokines has a modulating effect on the reflex control of respiration. The aim of this study was to investigate the involvement of neuronal nitric oxide synthase (nNOS) in the mechanisms of the influence of an increased level of Tumor necrosis factor – α (TNF-α) on the hypoxic ventilatory response. To achieve this goal, experiments were carried out on urethane anesthetized rats with intravenous administration of TNF-α before and after pretreatment with 7-nitroindazole specific nNOS inhibitor. The hypoxic ventilation response was assessed by rebreathing with a hypoxic gas mixture before and after administration of TNF-α. We found that TNF-α decreased the ventilatory response to hypoxia. Pretreatment with nNOS inhibitor reduced respiratory effects of TNF-α. Key words: cytokines, TNF-α, hypoxia, chemoreflex, respiration, ventilation, neuronal nitric oxide synthase.

Предикторы неблагоприятного исхода программ экстракорпорального оплодотворения

Identification of factors determining both adverse and favorable outcome of IVF will increase the effectiveness of this method and optimize infertility treatment. Objective. The aim of the research is to determine the relationship between hormonal and cytokine status indicators with an adverse outcome of the IVF procedure in women with tubal-peritoneal infertility. Patients and methods. The study involved 120 women with tubal-peritoneal infertility who underwent a “short” protocol of stimulation of superovulation in the IVF program. Depending on the result, women were divided into two groups: group 1 – with clinically confirmed pregnancy (n = 40), group 2 – non-pregnant women (n = 80). The content of IL-1α, IL-1β, IL-1Ra and hormones in serum were determined by ELISA. Genotyping of polymorphic markers rs1800587 (C/T) of the IL-1α gene, rs16944 (С511Т) of the IL-1β gene and rs2234663 (2/4) of the IL-1Ra gene was performed. Results. Markers of adverse IVF outcome that had prognostic significance were: C/C genotype of the IL-1α gene (OR = 2 [0.9–4.6], p = 0.043113), serum IL-1α concentration <11.4 pg/mL (OR = 3, 2 [1.1-9.1], p = 0.025347), endometrial thickness on the 2nd day of the menstrual cycle was >5 mm (OR = 3.2 [1.1–9.1], p = 0.025347), the concentration of prolactin on the 3rd day of the menstrual cycle was >363.8 mU/mL (OR = 6.3 [1.8–22.2], p = 0.001745), genotype T/T of the IL-1β gene (OR = 15.8 [5.1–48.9], p < 0.001), the concentration of progesterone was <16 nmol/L (OR = 22.2 [2.3–170], p = 0.000057). Key words: cytokines, IVF, IL-1α, IL-1β, IL-1Rа, rs1800587, rs16944, rs2234663

Strong relationships between inflammation, atherosclerosis and end stage renal disease

End-stage renal disease (ESRD) is characterized by an exceptional mortality rate, much of which is the result of cardiovascular disease (CVD). Although traditional risk factors are common in ESRD patients, they may not be sufficient alone to account for the high prevalence of CVD in this condition. Recent evidence demonstrates that chronic inflammation is a common feature in ESRD patients and it may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. The causes of inflammation in ESRD are multifactorial and, while it may reflect underlying CVD, an acute-phase reaction may also be a direct cause of vascular injury by several pathogenetic mechanisms. There is strong evidence that inflammatory markers are closely linked to ESRD. There seems to be a strong evidence of inflammatory markers, inflammation and atherosclerosis in ESRD patients and it is likely that proinflammatory cytokines and the genetic polymorphism in these cytokines may be important players in this scenario. Key Words: Cytokines; ESRD; Inflammation; Polymorphisms; CVD DOI: 10.3126/ajms.v2i1.3731 Asian Journal of Medical Sciences 2 (2011) 46-48

The Cytokines and Heart Failure - A Review

Heart Failure (HF) develops in several stages - the first stage is some disorder that places a hemodynamic burden on the myocardium or causes myocardial injury. The second stage is that of cardiac compensation, which involves neurohormonal activation to preserve cardiac output and tissue perfusion. And the final stage is the progression of HF, which is complex and is the result of the harmful effects of the compensatory mechanisms of the second stage; an immune-system activation manifested by increases in inflammatory cytokines, including tissue necrosis factor–alpha (TNF-á), soluble receptors of TNF-á (sTNFR1 and 2), interleukin (IL)-1, IL-6 and IL-10, and C-reactive protein (CRP). It has recently been recognized that elevated circulating levels of various proinflammatory cytokines (TNF- á, IL-1, IL-6) leading to free radical overproduction, as well as to cardiac myocyte and endothelial cell apoptosis, play a significant role in the pathophysiology of CHF. The extracellular domains of proinflammatory cytokine receptors (sTNFR1, sTNFR2 and sIL- 6R) are also elevated in CHF and provide more complete information on cytokine activation in this syndrome. This article reviews the contribution of inflammatory cytokines in the disease progression in patients with heart failure, their diagnostic as well as prognostic values and possibly therapeutic interventions on these biologic active molecules. Key words: Cytokines; cytokine receptors; Heart failure. DOI: http://dx.doi.org/10.3329/cardio.v3i2.9190 Cardiovasc. J. 2011; 3(2): 200-212