The purpose of the study was to compare exhaled nitric oxide (NO) determined by three techniques. Ninety-one subjects performed a slow vital capacity maneuver: (1) through the mouth directly into a ...NO chemiluminescence analyzer (peak oral NO), (2) through the mouth into a collection bag (mean oral NO), and (3) through the nose into a collection bag (mean nasal NO). Peak oral NO was higher in patients with asthma (n = 18, 174.2 +/- 27.0 ppb), but lower in smokers (n = 36, 39.6 +/- 4.8 ppb) compared with nonsmoking control subjects (n = 23, 105.5 +/- 8.4 ppb, p < 0.05 both comparisons). Mean oral NO levels were significantly lower than peak oral NO levels (p < 0.05), but still higher in patients with asthma in comparison with nonsmoking healthy control subjects and asymptomatic smokers (27.2 +/- 3.5 versus 14.5 +/- 1.1 and 7.3 +/- 0.7 ppb, respectively, p < 0.05). In contrast, there was no significant difference in mean nasal NO levels between the three groups. Peak oral NO and mean oral NO levels correlated (r = 0.772, p < 0.0001). Determination of exhaled oral NO levels is qualitatively independent of the technique used, but nasal exhalation may affect NO determination in conditions associated with airway inflammation.
Selenoprotein P (Se‐P) is a selenium‐rich plasma protein important in selenium (Se) homeostasis. It has two domains with respect to Se. Its N‐terminal domain (amino acid residues 1–238) contains one ...selenocysteine (Sec) and has been postulated to have enzymatic activity. Its C‐terminal domain (amino acid residues 239–361) contains 9 Sec and has been postulated to function in delivery of Se to tissues. Deletion of Se‐P (Se‐P KO) disrupts Se homeostasis, leading to decreased whole‐body Se and dysfunction of several tissues. We have produced a mouse expressing a truncated form of Se‐P (Se‐P(t)). The expressed protein contains the N‐terminal domain but not the C‐terminal domain. Mass spec analysis of purified Se‐P(t) shows that the protein terminates after the serine‐238 that precedes the second Sec. Thus, Se‐P(t) is the N‐terminal domain of Se‐P. Se‐P(t) mice fed a Se‐deficient diet did not have the shortened stride displayed by Se‐P KO mice, but, when fed a low‐Se diet, they displayed episodes of hyperactivity and died in a manner similar to Se‐P KO mice. Se supplementation prevented the hyperactive episodes and death. Tissue Se levels in Se‐P(t) mice were similar to those in Se‐P KO mice. Male Se‐P(t) mice were infertile and had abnormal spermatozoa that appeared similar to those in Se‐P KO mice. These results are consistent with the C‐terminal domain of Se‐P being important in Se transport and homeostasis.
Supported by NIH ES02497.
Tumor necrosis factor-alpha (TNF-alpha) is released in inflammatory lung conditions, raising airway nitric oxide (NO) concentrations through the cytokine-mediated induction of nitric oxide synthase ...(NOS). Cardiopulmonary bypass (CPB) creates an inflammatory state, characterized by the release of TNF-alpha, that may result in lung injury following CPB. This study measured plasma levels of TNF-alpha and interleukin-6 (IL-6) as well as airway NO concentrations during CPB, and the effect of methylprednisolone (MPSS) on the levels of these inflammatory products. Twenty adult males scheduled for coronary artery bypass grafting (CABG) were anesthetized and randomized to a group given MPSS at 1 gm intravenously 5 min before CPB (Group S) or a group not given MPSS (Group N). Plasma levels of TNF-alpha and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) and the airway NO concentration by chemiluminescence. TNF-alpha was significantly (p < 0.05) increased at 30 min after the termination of CPB, while IL-6 was significantly (p < 0.05) increased at 50 min into CPB and 30 min after the end of CPB in Group N as compared with controls in the same group and with Group S at the same time intervals. A group of 10 patients undergoing repair of infrarenal aortic aneurysms, which served as a control group for plasma levels of TNF-alpha, showed no significant changes in TNF-alpha concentrations at any time during aneurysm repair. Airway NO increased significantly (p < 0.01) in Group N as compared with Group S at 5, 20, 35, and 50 min of CPB.
Neutrophil-endothelial adhesion is the initiating event in neutrophil migration to areas of infection or injury. The binding of neutrophils to endothelium depends upon adhesive glycoproteins, of ...which the CD11/CD18 glycoproteins are the most important. Because of known upregulation of one of these adhesive glycoproteins (CD11b) during cardiopulmonary bypass (CPB) in humans, we evaluated CD11a, CD11b, and CD11c surface expression before, during, and after CPB in humans, with or without pre-CPB administration of a glucocorticoid (methylprednisolone). Fourteen patients were randomized into two groupsGroup S received methylprednisolone (1 g intravenously) 5 min prior to CPB; Group N received no steroid. CD11b was significantly upregulated (P < 0.01) during, and 24 h after, CPB in Group N when compared with controls and Group S at similar time intervals, while in Group S no significant changes were found. Since interleukin-1, tumor necrosis factor, and endotoxin are known to upregulate neutrophil CD11b surface expression and are released during CPB in humans, while steroids are known to suppress the release of these cytokines, the authors conclude that the blunting effect by steroids on CD11b surface expression upregulation during and after CPB in humans is attributed to suppressed cytokine release.
Proinflammatory cytokines, including tumor necrosis factor (TNF) α and the interieukins, are important in the metabolic response to injury or infection. Although the importance of cytokine release ...during cardiopulmonary bypass (CPB) is not fully appreciated, increasing num bers of publications present evidence that cytokine release during CPB is detrimental. In addition, endoge nous inhibitors of cytokine function, including TNF-sol uble receptor and interleukin 1 receptor antagonist, are released in response to elevated proinflammatory cyto kine levels during and after CPB. The involvement of these endogenous inhibitors in the pathophysiology of proinflammatory cytokine-induced solid organ injury after CPB remains to be defined.
Cell expression of inducible nitric oxide synthase (iNOS) is increased by cytokines, which results in high endogenous concentrations of nitric oxide (NO) and has been implicated in organ injury, ...including myocardial reperfusion injury. Serine protease inhibitors reduce cytokine-induced iNOS expression. The protease inhibitors aprotinin and tranexamic acid, which are used to reduce blood loss after cardiac surgery, were evaluated in vitro on cytokine-induced iNOS expression and the resulting NO production to demonstrate the relative antiinflammatory effects of each drug. A murine bronchial epithelial cell line (LA-4) was stimulated with cytomix (tumor necrosis factor alpha, interleukin 1beta, and gamma-interferon) with or without aprotinin, tranexamic acid, or N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK; a protease inhibitor). The resultant iNOS expression was measured by using Northern blot analysis and cell supernatant nitrite concentrations (in aqueous media, NO is oxidized primarily to nitrite, NO2-) by chemiluminescence. Nitrite concentrations in the supernatant were significantly increased by cytomix, not affected by any concentration of tranexamic acid, but significantly (P < 0.05) reduced by aprotinin and TLCK. Consistent with the nitrite reduction, aprotinin significantly (P < 0.05) reduced cytokine-induced iNOS expression, while tranexamic acid had no effect. Aprotinin but not tranexamic acid reduces endogenous cytokine-induced NO production by inhibiting iNOS expression. Since increased endogenous NO concentrations secondary to iNOS activation have been implicated in organ injury, aprotinin may have clinical benefits when compared with tranexamic acid.
Treatment of heat stroke with dantrolene Lydiatt, J S; Hill, G E
JAMA : the journal of the American Medical Association,
07/1981, Letnik:
246, Številka:
1
Journal Article
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