Effects of arachidonic acid metabolites on airway sensors.

Arachidonic acid (AA) in the cell membrane produces a variety of metabolites by different enzymatic pathways. These lipid metabolites, along with other mediators, play an important role in the inflammatory processes. Many of them can bind directly to the receptors on the sensory endings and initiate electrical impulses to be transmitted to the central nervous system, causing reflex responses. These bioactive AA metabolites may also alter the lung mechanics (mechanical environment of the sensory ending), and in turn, stimulate sensory afferents. In addition, some metabolites may sensitize the sensory endings and make them more responsive to other mechanical or chemical stimulation. These metabolites may also induce other mediators and modulators to cause physiological effects. Furthermore, some of them may attract inflammatory cells to produce a localized effect. In short, AA metabolites may come from different sources and act through multiple pathways to stimulate airway sensors. This brief review is intended to illustrate the underlying mechanisms and help elucidate the inflammatory process in the airways.

Expression analysis of the NDRG2 gene in mouse embryonic and adult tissues.

N-myc downstream-regulated gene 2 (NDRG2) is believed to be involved in cell growth events. However, its exact function is still unknown. To elucidate the role of this gene, we used an anti-Ndrg2 monoclonal antibody in immunohistochemistry and immunofluorescence assays to analyze the expression pattern of Ndrg2 protein in mouse embryos at various gestational ages and in a variety of adult mouse tissues. Ndrg2 immunoreactivity was generally localized to the cytoplasm. During mouse development, Ndrg2 expression was observed in many developing tissues and organs including the heart, brain, lung, gut, liver, kidney, skeletal muscle, cartilage, chorion, epidermis, and whisker follicles. Ndrg2 expression was developmentally dynamic, being generally lower in the early stages of development and markedly increasing during later stages. Ndrg2 expression was also observed in a variety of adult mouse tissues, particularly in the heart and brain. This is the first demonstration of Ndrg2 protein expression in both embryonic and adult mouse tissues. Our results suggest that NDRG2 plays important roles in histogenesis and organogenesis.

[Multiple organ dysfunction scoring system: comparison and evaluation of correlation and accuracy of the three scoring systems in predicting the outcome of multiple organ dysfunction syndrome on highland].

OBJECTIVE: To study the characteristics of the diagnostic parameters of acute respiratory distress syndrome/multiple organ dysfunction syndrome on plateau (H-ARDS/MODS) and compare the accuracy of the three MODS scoring criteria in predicting the outcome of syndrome. METHODS: Five hundred and forty cases fulfilling the criteria of MODS were divided into four groups according to the altitude of their inhabitation area: control group (on plain, CG, n=113, altitude: <430 m), moderate high altitude group 1 (H1G, n=314, altitude: 1,517 m), moderate high altitude group 2 (H2G, n=78, altitude: 2,261 m to 2,400 m) and high altitude group (HG, n=35, altitude: 2 808 m to 3 400 m). According to the diagnostic criteria of Lushan conference and Marshall (1995) commonly used on plain, and Lanzhou criteria drafted by the authors, three data analyzing models were set up to draw the receiver operating characteristic (ROC) curves, the Yordon Index and the optimum cutoff points of the parameters were calculated and the accuracy of the three respective diagnostic criteria was evaluated in predicting the outcome of ARDS/MODS. Multiple factors affecting the outcome of MODS were analyzed using the method of stepwise forward regress model. RESULTS: Following the increase in altitude, Lanzhou criteria was clearly superior to the other two criteria in the area of ROC, the sensitivity, the specificity, and also for the optimum cutoff points of MODS. Multi-variable regression analysis showed that the impacting factor of Lanzhou criteria was the highest (P<0.05). CONCLUSION: (1)Some parameters of the current diagnostic criteria of ARDS/MODS are not suitable in moderately high or high altitude areas. It is necessary to set up the diagnostic criteria of H-ARDS/MODS. (2)Some clinical characteristics might change in areas 1,500 m altitude or higher. The pathophysiological mechanism might be attributable to peculiar biologic reactions due to hypoxia stress reaction, and it is worth further study.

[Criteria suitable for diagnosis of acute respiratory distress syndrome/multiple organ dysfunction syndrome at moderately high altitude area].

OBJECTIVE: To compare the diagnostic parameters of acute respiratory distress syndrome/multiple organ dysfunction syndrome (ARDS/MODS) at high altitude (H-ARDS/MODS) with that on plain, and to establish a more practical diagnostic criterion of H-ARDS/MODS. METHODS: Five hundred and five cases fulfilled the criteria for the diagnosis of ARDS/MODS were divided into three groups according to the altitude of their habitation: control group including inhabitants (<430 m) on plain (CG, n=113), moderate high altitude group 1 inhabitants at the altitude of 1,517 m (H1G, n=314), moderate high altitude group 2 inhabitants at the altitude of 2,261 m to 2,400 m (H2G, n=78). The ARDS/MODS scores of the three groups were made according to the diagnostic criteria of Lushan conference, Marshall(1995) and Lanzhou criteria drafted by the authors respectively to set up three data analyzing models, followed by plotting of receiver operating characteristic curves (ROC curve) and calculation of the Yordon Index and the optimum cutoff points of the parameters,in order to study the accuracy of the three diagnostic criteria in predicting the outcome of the patients suffering from ARDS/MODS. RESULTS: In CG group, the differences were not significant in area of ROC, the maximal Yordon Index, the optimum cutoff points and the sensitivity and the specificity for three criteria; but the differences were significant for the three criteria in H1G group. Further investigation in comparing the ROC values of lung, brain, heart and kidney, the Lanzhou criteria were more advantageous in the high altitude than the other criteria. CONCLUSION: (1)The current diagnostic criteria of ARDS/MODS are not suitable for the diagnosis of these syndromes in moderately high or high altitude areas. It is necessary to revise the diagnostic criteria of H-ARDS/MODS. (2)One thousand five hundred and seventeen meters in altitude might be considered to be an important borderline, above with the diagnostic criteria of ARDS/MODS for patients inhabiting on plain could not be suitably applied to those living above this level.

NDRG2 expression and mutation in human liver and pancreatic cancers.

AIM: To investigate the expression of NDRG2 and mutation of the entire coding region of NDRG2 in human liver and pancreatic cancers, and to further discuss the possible causes of NDRG2 distinct expression patterns. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze the expression of NDRG2 mRNA in 37 fresh cancer specimens (including 8 cases of pancreatic cancer and 29 cases of liver cancer) and adjacent normal tissues collected from clinical operation. In addition, mutation analysis of the whole coding region of NDRG2 in these cancers was examined by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). RESULTS: Compared with adjacent normal tissues, the expression levels of NDRG2 mRNA in corresponding cancer tissues reduced significantly (pancreatic cancer: 0.680+/-0.112 vs 2.089+/-0.214, P<0.01) (liver cancer: 0.894+/-0.098 vs 1.345+/-0.177, P<0.05). Using PCR-SSCP, the mutation of the whole coding region of NDRG2 was not found in those cancer tissues where the expression of NDRG2 mRNA reduced markedly. CONCLUSION: NDRG2 gene might express differently between normal tissues and cancer tissues, and might play an important role in the development of pancreatic cancer and liver cancer. Low expression of NDRG2 might be unrelated to the mutation of coding region of NDRG2.

[Vasorelaxing effect of idoxifene on human internal mammary arteries].

The purpose of this study was to investigate the vasorelaxing effect and mechanism of idoxifene (a new estrogen receptor modulator) on human internal mammary artery (HIMA). HIMA segments were harvested from men during coronary artery bypass grafting surgery. Patients with diabetes mellitus, hypercholesterolemia, hypertension, or smoking habit were excluded. The vasorelaxing effect of idoxifene on artery rings from HIMA with and without endothelium was measured by means of perfusion in vitro. Cumulative dose-response to idoxifene in the range of 0.01-10 micromol/L was observed in the presence and absence of NO synthase inhibitor L-NAME. It was also studied whether the vasodilation effect of idoxifene on HIMA was blocked by methylene blue (MB), an inhibitor of guanylate cyclase (GC). The results obtained from idoxifene were compared with those from 17beta-estradiol (E(2)). It was found that idoxifene caused a concentration-dependent relaxation on HIMA. The dose range was from 0.03 micromol/L (minimal vasodilatory concentration) to 3 mmol/L (maximal vasodilatory concentration). It was also found that the vasorelaxation effect of idoxifene on HIMA was dependent on endothelium. E(2) (0.1-100 micromol/L) also resulted in an endothelium-dependent vasorelaxation, but the vessels were 15-fold less sensitive to E(2) than to idoxifene in their vasorelaxation responses. The EC(50) for E(2) was 4.65+/-0.34 micromol/L, compared with 0.32+/-0.02 micromol/L for idoxifene. The mean maximal vasodilatory value of E(2) was 88.3+/-5.7%, compared with 88.6+/-7.2% for idoxifene. Pretreatment with L-NAME (100micromol/L) abolished idoxifene-induced vasodilation virtually by blocking nitric oxide production. The vasorelaxing effect of idoxifene disappeared in the presence of MB (10 micromol/L). These findings demonstrate that idoxifene results in an endothelium-dependent vasorelaxation of HIMA, like estrogen. The effect of idoxifene is more potent than that of traditional estrogen, and is possibly mediated by NO-GC-cGMP pathway.

[Study of diagnostic criteria of acute respiratory distress syndrome and multiple organ dysfunction syndrome at high altitude: revised draft of the diagnostic criteria of high acute respiratory distress syndrome drawn in Lanzhou conference].

OBJECTIVE: To compare the difference of the diagnostic parameters of acute respiratory distress syndrome/multiple organ dysfunction syndrome (ARDS/MODS) at high altitude (H-ARDS/MODS) with that on plains and reevaluate the practicality and feasibility of the diagnostic criteria of H-ARDS (Lanzhou conference, 1999). METHODS: Three hundred and sixty cases with relatively complete data were divided into three groups according to their originating altitude: control group on plains (CG, n=93), high altitude group 1 at the altitude of 1,517 m (H1G, n=223), high altitude group 2 at the altitude of 2,261-2,400 m (H2G, n=44). The ARDS/MODS scorings of the three groups were carried out according to the diagnostic criteria of Lushan Conference, Marshall (1995) and Lanzhou criteria drafted by the authors and the receiver operating characteristic curves (ROC curve) were made to predict the outcome of MODS. RESULTS: In CG group, the area of ROC, the susceptibility and specificity were 0.823, 0.833, 0.731, respectively according to Lushan criteria, which were better than those (0.815, 0.767, 0.763) according to Marshall criteria. Then in group H2G, the area of ROC, the susceptibility and specificity according to Lushan criteria were lower than those according to Marshall criteria: 0.855, 0.583, 0.969 vs 0.914, 1.000, 0.657. The optimum cutoff points of partial pressure of oxygen in artery (PaO(2))/fractional concentration of inspired oxygen (FiO(2)) were 198.32 mmHg, 131.50 mmHg and 97.58 mmHg in group CG, H1G and H2G. CONCLUSION: (1) There are significant differences between the diagnostic criteria of ARDS at high altitude and that on plains. The altitude of 1 517 m would be an important border line in diagnosing H-ARDS. (2) The drafted diagnostic criteria of ARDS at high altitude are feasible and practical in this region, but the range of the parameters is still wide, which need to be properly amended. (3) The changing tendency of the parameters of MODS at high altitude is different from that on plains, but the amount of sample needs to be accumulated further and the Lanzhou criteria needs to be perfected.