Graphite Oxide and Aromatic Amines: Size Matters

Experimental and theoretical studies are performed in order to illuminate, for first time, the intercalation mechanism of polycyclic aromatic molecules into graphite oxide. Two representative molecules of this family, aniline and naphthalene amine are investigated. After intercalation, aniline molecules prefer to covalently connect to the graphene oxide matrix via chemical grafting, while napthalene amine molecules bind with the graphene oxide surface through π–π interactions. The presence of intercalated aromatic molecules between the graphene oxide layers is demonstrated by X‐ray diffraction, while the type of interaction between graphene oxide and polycyclic organic molecules is elucidated by X‐ray photoelectron spectroscopy. Combined quantum mechanical and molecular mechanical calculations describe the intercalation mechanism and the aniline grafting, rationalizing the experimental data. The present work opens new perspectives for the interaction of various aromatic molecules with graphite oxide and the so‐called “intercalation chemistry”.     

Relationship between haemodynamics and morphology in pulmonary hypertension. A quantitative intravascular ultrasound study

BACKGROUND: Intravascular ultrasound imaging of the pulmonary arteries has been demonstrated to be a reliable method of quantifying vessel diameter, luminal area and pulsatility. Simultaneous measurement of flow velocity and its response to vasodilators allows the relationship between morphology and functional compromise to be studied, especially endothelial dysfunction. METHODS: In 51 patients (mean age = 49.8 +/- 12.6 years, 17 female) we performed right heart catheterization and simultaneous intravascular ultrasound of pulmonary artery branches. The patients were divided in two groups: group 1 with normal pulmonary artery pressure and pulmonary vascular resistance, and group 2 with pulmonary hypertension (peak pulmonary artery pressure > 30 mmHg and/or mean pulmonary artery pressure > 20 mmHg). Vessel wall and lumen were studied using a 2.9 F intravascular ultrasound catheter with a 30 MHz phased array transducer. Measurement of blood flow velocity was accomplished by a Doppler flow wire (0.018 inch). The maximal flow change during acetylcholine infusion (adjusted to 10(-6); 10(-5), and 10(-4) M concentration in the blood vessel) was measured. RESULTS: There were no significant differences between groups 1 and 2 with respect to age (48.5 +/- 14.3 years vs 50.3 +/- 12.3 years; P = ns), gender (4 female/8 male vs 13 female/26 male; P = ns), luminal area of the vessel segment in which the intravascular ultrasound measurements were obtained (11.8 +/- 6.1 mm2 vs 16.7 +/- 14.3 mm2; P = ns), internal diameter (3.9 +/- 1.2 mm vs 4.2 +/- 1.7 mm; P = ns), and external diameter (6.1 +/- 1.3 mm vs 6.9 +/- 2.1 mm; P = ns). Cross-sectional images of the pulmonary artery wall demonstrated a single ring with high echodensity with a thin inner layer regarded as intima in group 1. In contrast, the majority of patients (n = 35/39) in group 2 demonstrated a thickening of the intimal layer and/or a disturbance of layering of the echogenic arterial wall. The relative wall thickness was higher in group 2 than in group 1 (22.5 +/- 10.4% vs 15.3 +/- 6.5%; P < 0.05). There were no significant correlations between pulmonary artery pressure and wall thickness pulmonary artery pressure and area change in the cardiac cycle, acetylcholine-dependent increase in pulmonary flow and morphological changes in the vessel wall. CONCLUSION: We conclude that intravascular ultrasound is capable of detecting morphological changes in the pulmonary vessel wall in pulmonary hypertension and that vessel wall hypertrophy of small pulmonary segment arteries, as detected by intravascular ultrasound, is not predictive of functional vasodilatory response of resistance vessels of the same vessel area.     

Time and cost securing in complex large-scale projects

Meeting time and cost objectives in complex projects involves specific problems and risks. An attempt is made to analyse the components of total cost increase of a project caused by time delay. An outline is given as to how these considerations can be used to estimate cost increases in investors' decision situations as well as to ascertain fair contractual penalties and claims for compensation and for the evaluation of justified project acceleration costs.     

Immunostimulatory DNA: sequence-dependent production of potentially harmful or useful cytokines

Certain bacterial immunostimulatory (i.s.) DNA sequences containing unmethylated CpG motifs stimulate antigen-presenting cells (APC) to express a full complement of costimulatory molecules and to produce cytokines including interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha. While IL-12 is key to their T helper cell (Th)1-promoting adjuvant activity, secretion of toxic levels of TNF-alpha is harmful in that it promotes toxic shock. Given the beneficial as well as harmful consequences of i.s. DNA, we investigated the possibility of identifying DNA sequences, i.e. CpG oligodeoxynucleotides (ODN) which differentially activate IL-12 versus TNF-alpha cytokine production in APC. Here, we describe an i.s. DNA sequence with these characteristics. While its potential to induce IL-12 is preserved, its ability to trigger TNF-alpha release is strongly curtailed both in vitro and in vivo. I.s. DNA could be segregated into lethal and non-lethal in a mouse toxic shock model. The non-toxic i.s. DNA was useful as an adjuvant, thus allowing cytotoxic T cell responses to the soluble protein ovalbumin and conferring a resistant Th 1 phenotype to BALB/c mice lethally infected with Leishmania major. This i.s. CpG motif may thus be prototypic for a useful immunostimulating DNA sequence that lacks harmful side effects.     

Role of nitric oxide in the regulation of the hepatic microcirculation in vivo

BACKGROUND/AIMS: Nitric oxide (NO) is an important mediator in the regulation of vascular tone. However, no data exist on the physiological role of NO in the regulation of the hepatic microcirculation. This study was designed to evaluate the role of NO in the hepatic microcirculation in vivo under physiological conditions. METHODS: The hepatic microcirculation was investigated in anesthetized rats by intravital fluorescence microscopy after injection of fluorescein-isothiocyanate-labeled erythrocytes. Following assessment of baseline sinusoidal perfusion, animals were randomly treated with L-NMMA (n=6), L-arginine (n=6), nitroprusside sodium (NPS, n=5) or a comparable volume of NaCl (n=4). Drugs were given through a portal vein catheter at three doses (Dx), each followed by intravital microscopy. L-NMMA was given: 5 mg/kg (D1), 25 mg/kg (D2), 50 mg/kg (D3); L-arginine 30 mg/kg (D1), 150 mg/kg (D2), 300 mg/kg (D3); and NPS continuously 80 microg x kg(-1) x h(-1). RESULTS: L-NMMA induced a significant increase of mean arterial blood pressure (MAP) (114 vs. 129 mm Hg; p<0.05). In contrast, MAP of NPS-treated animals decreased (107 vs. 91 mm Hg; p<0.01) whereas MAP of animals receiving L-arginine did not significantly differ. Sinusoidal blood flow revealed dose-dependent changes: L-NMMA significantly decreased perfusion of sinusoids (D1: 65%, D2: 57%, D3: 50% of baseline, p<0.05). Injection of L-arginine increased the sinusoidal flow even with the lowest dose (D1: 137%, D2: 133%, D3: 123%, p<0.05). Continuous infusion of NPS had little effect on sinusoidal blood flow at the first and second times of microscopy but sinusoidal blood flow was significantly increased at the third time (D1: 103%, D2: 106%, D3: 122%). CONCLUSIONS: Inhibition of NOS results in a dose-dependent disturbance of the hepatic microcirculation despite significantly increased MAP, whereas L-arginine increases the sinusoidal blood flow. The results indicate an important role for NO in the regulatory mechanisms of hepatic sinusoidal perfusion under physiological conditions.