Objectives The role of nitric oxide in mediating the early phase of hypotension and cardlovascular hyporeactivity in sepsis, and the cellular sources of inducible nitric oxide synthase expression under in vivo conditions, remain unclear. The objective of this study was to elucidate the time course and cellular location of inducible nitric oxide synthase messenger RNA (mRNA) expression in rats treated with lipopolysaccharide in vivo. Design Prospective, placebo-controlled, laboratory study. Setting Experimental laboratory of a postgraduate medical research institution. Subjects Normal, anesthetized rats. Interventions Animals were treated with lipopolysaccharide (15 mg/kg ip), saline (1 mL/kg ip), or lipopolysaccharide plus dexamethasone (3 mg/kg ip, 50 mins before lipopolysaccharide administration) in vivo 4 hrs before the removal of tissues. Measurements and Main Results Total RNA and mRNA were extracted. Total RNA was used for reverse transcription polymerase chain reaction. Poly-(A) sup + mRNA was isolated for Northern blot analysis. Cryostat sections of heart and lung were prepared for in situ hybridization to elucidate the cellular location of the inducible nitric oxide synthase gene. Hearts, lungs, aortae, and pulmonary arteries from lipopolysaccharide-treated animals expressed inducible nitric oxide synthase mRNA, which was markedly inhibited by pretreatment with dexamethasone (except in aorta). The threshold time point for inducible nitric oxide synthase mRNA induction was between 20 and 40 mins after lipopolysaccharide administration. The quantity of mRNA increased progressively thereafter, reaching a plateau between 4 and 8 hrs and decreasing markedly by 24 hrs. These findings are consistent with the time course of lipopolysaccharide-induced hypotension and cardiovascular hyporeactivity in animal models of septic shock and in man. Inducible nitric oxide synthase mRNA was mainly detected in vascular and airway smooth muscle cells, cardiac myocytes, pneumocytes, and infiltrated inflammatory cells, but was also identified in airway epithelial and vascular endothelial cells. Vascular smooth muscle represented the predominant cell type expressing inducible nitric oxide synthase under these conditions. Conclusions These results provide further molecular evidence for the involvement of nitric oxide in the early phase of hypotension and cardiovascular hyporeactivity seen in septic shock. They also suggest that nitric oxide derived from vascular smooth muscle cells may contribute significantly to this hypotension and cardiovascular reactivity. (Crit Care Med 1997; 25:512-518)
Although percutaneous coronary intervention (PCI) is a highly effective modality for the management of acute coronary syndromes, it can potentiate the existing prothrombotic state around lesion areas and lead to ischaemic complications. Adjunctive pharmacologic treatment with heparin reduces the risk of ischaemic events, but the utility of heparin is limited by its unpredictable pharmacodynamic effects and its inability to modulate fibrin-bound thrombin. Additionally, a potential risk of heparin-induced thrombocytopenia is associated with heparin use. Direct thrombin inhibitors (DTIs) have emerged as potential alternatives to heparin in patients undergoing PCI. Bivalirudin is a DTI indicated for use in PCI. Results from various studies have suggested clinical benefit associated with the use of bivalirudin, driven primarily by the reduction in bleeding risks compared with the standard treatment regimens. Of concern, however, is a significant increase in acute stent thrombosis with bivalirudin monotherapy compared with heparin plus GPIIb/IIIa inhibitors following primary PCI for ST-segment elevation myocardial infarction (STEMI). Desirudin is a highly potent DTI with greater binding affinity than bivalirudin for thrombin. This report provides a comparative overview of the pharmacology and clinical utility of desirudin and bivalirudin in the setting of PCI.
Exposure to household air pollution (HAP) from solid fuel combustion affects almost half of the world population. Adverse respiratory outcomes such as respiratory infections, impaired lung growth and chronic obstructive pulmonary disease have been linked to HAP exposure. Solid fuel smoke is a heterogeneous mixture of various gases and particulates. Cell culture and animal studies with controlled exposure conditions and genetic homogeneity provide important insights into HAP mechanisms. Impaired bacterial phagocytosis in exposed human alveolar macrophages possibly mediates several HAP-related health effects. Lung pathological findings in HAP-exposed individuals demonstrate greater small airways fibrosis and less emphysema compared with cigarette smokers. Field studies using questionnaires, air pollution monitoring and/or biomarkers are needed to better establish human risks. Some, but not all, studies suggest that improving cookstove efficiency or venting emissions may be associated with reduced respiratory symptoms, lung function decline in women and severe pneumonia in children. Current studies focus on fuel switching, stove technology replacements or upgrades and air filter devices. Several governments have initiated major programmes to accelerate the upgrade from solid fuels to clean fuels, particularly liquid petroleum gas, which provides research opportunities for the respiratory health community.
No abstract is provided for this article.
Recent observations and theoretical models have indicated the presence of a thin but extended atmosphere around Pluto. Various models predict that, besides the generally accepted methane, the atmosphere may contain significant quantities of a heavier component, with nitrogen and/or carbon monoxide being the most likely candidates. I report here a search for CO emission from such an atmospheric component in the Pluto-Charon system. A simple model is also presented that predicts the CO visibility is a distended atmosphere around Pluto.
No abstract is provided for this article.
The very long-term mortality of off-pump and on-pump coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in a randomized complex coronary artery disease population is unknown. This study aims to investigate the impact of on-pump and off-pump CABG versus PCI on 10-year all-cause mortality.The SYNTAX trial randomized 1800 patients with three-vessel and/or left main coronary artery disease to PCI or CABG and assessed their survival at 10 years. In this sub-study, the hazard of mortality over 10 years was compared according to the technique of revascularization: on-pump CABG (n = 725), off-pump CABG (n = 128) and PCI (n = 903).There was substantial inter-site variation in the use of off-pump CABG despite baseline characteristics being largely homogeneous among the 3 groups. The crude rate of mortality was significantly lower following on-pump CABG versus PCI [25.6% vs 28.4%, hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.65-0.96], while it was comparable between off-pump CABG and PCI (28.5% vs 28.4%, HR 0.98, 95% CI 0.69-1.40). After adjusting for the 9 variables included in the SYNTAX score II 2020, 10-year mortality remained significantly lower with on-pump CABG than PCI (HR 0.75 against PCI, P = 0.009).In the SYNTAXES trial, 10-year mortality adjusted for major confounders was significantly lower following on-pump CABG compared to PCI. There was no evidence for unadjusted difference between off-pump CABG and PCI, although the unadjusted estimated HR had a wide CI. Site heterogeneity in the technique used in bypass surgery has had measurable effects on treatment performance.
