L-arginine administration ameliorates serum and pulmonary cytokine response after gut ischemia-reperfusion in immature rats

AIM: Small intestinal ischemia-reperfusion (IR) has been demonstrated to result in both local mucosal injury and systemic injuries. The exact role of nitric oxide (NO) in intestinal IR is unclear. We propose that NO and some other cytokines change in the reperfusion period and these changes are associated with lung injury. The aim of this study was to determine the effect of supplementing NO substrate, L-arginine (L-arg), on serum and pulmonary cytokine production during small intestinal IR in immature rats.METHODS: Immature rats underwent 60 min. of superior mesenteric artery occlusion followed by 90 min of reperfusion. L-arg (250 mg/kg) was given intravenously to the experimental group (IR+L-arg) which received L-arg after 45 min of intestinal ischemia. Serum and lung endothelin-1 (ET-1), NO, malondialdehyde (MDA), and tumor necrosis factor α (TNFα) were measured. Sham operation (SHAM) and intestinal IR (IR) groups were performed as control. The lavage fluid of the lung was collected by bronchoalveolar lavage (BAL) and white blood cells and polymorphonuclear cells (PMNs) were immediately counted to identify lung damage.RESULTS: When L-arg was given during small intestinal IR, serum NO concentration increased significantly in IR+L-arg group (162.17±42.93 μmol/L) when compared with IR group (87.57±23.17 μmol/L, t= 3.190, P = 0.008＜0.01). Serum MDA reduced significantly in IR+L-arg group (8.93±1.50 nmol/L) when compared with SHAM(23.78±7.81 nmol/L, t = 3.243, P = 0.007＜0.01) and IR (25.54±9.32 nmol/L, t = 3.421, P = 0.006＜0.01).ET-1 level in lung tissues was significantly lower in IR+L-arg group (13.81±7.84 pg/mL) than that in SHAM(35.52±10.82 pg/mL, t = 2.571, P= 0.03＜0.05) and IR(50.83±22.05 pg/mL, t = 3.025, P = 0.009＜0.01) groups.MDA contents in lung tissues were significantly lower in IR+L-arg group (10.73±1.99 nmol/L) than in SHAM(16.62±2.28 nmol/L, t = 3.280, P = 0.007＜0.01) and IR(21.90±4.82 nmol/L, t= 3.322, P= 0.007＜0.01)groups.Serum and lung TNFα concentrations were not significantly different in three groups. NO contents in lung homogenates and white blood cell counts in BAL had no significant difference in three groups; but the percentage of PMNs in BAL was 13.50±8.92, 33.20±16.59, and 22.50±6.09 in SHAM, IR, and IR+L-arg groups, respectively.CONCLUSION: Small intestinal IR induced increases of pulmonary neutrophil infiltration in immature rats.Neutrophil infiltration in lung tissues was reduced by L-arg administration but remained higher than in SHAM group.L-arg administration during intestinal IR enhances serum NO production, reduces serum MDA and lung ET-1 and MDA levels, resulting in the improvement of systemic endothelial function. L-arg supplementation before reperfusion may act as a useful clinical adjunct in the management of intestinal IR, thus preventing the development of adult respiratory distress syndrome, even multiple organ dysfunction syndrome (MODS).

DNA fragmentation in apoptosis and homeostasis

Apoptosis is a highly regulated physiological process critical in development and tissue homeostasis. Abnormal apoptosis can lead to disease conditions including neurodegeneration, autoimmunity and cancer. DNA fragmentation is an integral part of apoptosis and has long been suspected to be of critical importance in cleaning up potentially antigenic DNA and genetic material capable of inducing neoplasmic transformation in neighboring cells. Direct evidence for this function of DNA fragmentation however, is still lacking. The identification of a heterodimeric DNA fragmentation factor 45 and 40 (DFF45 and DFF40, also called ICAD for Inhibitor of Caspase Activated DNase and CAD for Caspase Activated DNase respectively) as well

Trafficking of α1B-adrenergic receptor mediated by inverse agonist in living cells

AIM The project is aimed at understanding the action of inverse agonist at single molecule level and capturing the real time picture of molecular behavior of α1B-adrenergic receptor (AR) mediated by inverse agonist in living cells by single molecule detection (SMD). METHODS The location and distribution of α1B-AR was detected by laser confocal and whole cell ^3H-prazosin binding assay. Dynamic imaging of BODIPY-FL-labeled prazosin (Praz), specific antagonist of (1-AR, was observed in α1B-AR stably expressed human embryonic kidney 293 (HEK293) living cells. The detection of real-time dynamic behaviors of AR was achieved by using fluorescence-labeled AR and its ligand combined with SMD techniques. RESULTS α1B-AR was predominantly distributed on the cell surface and 8.2% of the total receptors were located in cytosol.

ON THE CHARACTERIZATION OF METALLIC SUPERLATTICE STRUCTURES BY X—RAY DIFFRACTION

To solve the problem on the microstructural characterization of metallic superlattices,taking the NiFe/Cu superlattices as example,we show that the sturctures of metallic superlattices can be characterized exactly by combining low-angle X-ray diffraction with high-angle X-ray diffraction.First,we determine exactly the total film thickness by a straightforward and precise method based on a modified Bragg law from the subsidiary maxima around the low-angle X-ray diffraction peak.Then.by combining with the simulation of high-angle X-ray diffraction.we obtain the sturctural parameters such as the superlattice period,the sublayer and buffer thickness,This characterization procedure is also applicable to other types of metallic superlattices.