Permissive effect of nitric oxide in arachidonic acid induced dilation in isolated rat arterioles

OBJECTIVE: Prostaglandins and nitric oxide play an important role in the regulation of arteriolar tone. L-Arginine analogues inhibit nitric oxide formation, but may also inhibit arachidonic-acid induced dilation. Nitric oxide was found to stimulate cyclooxygenase activity in cultured endothelial cells. Therefore, we hypothesized that the non-specific inhibition of prostaglandin-related dilation by L-arginine analogues is a consequence of the absence of nitric oxide. METHODS: To test this hypothesis, arteriolar segments from rat cremaster muscle were studied in a pressure myograph at 75 mmHg. Segments developed spontaneous tone, the diameter reduced from 179 +/- 3 to 98 +/- 3 microns (n = 41). In this condition, responses to exogenous arachidonic acid (1 microM) were recorded and compared with responses after addition of L-NNA, and addition of either SNAP, nitroprusside or 8-Br-cGMP in the presence of L-NNA. RESULTS: Inhibition of basal nitric oxide production with L-NNA (0.1 mM) reduced arachidonic acid-induced dilation (from 52 +/- 9 to 31 +/- 6 microns). In the presence of L-NNA, responses to arachidonic acid were augmented when exogenous nitric oxide was also present (SNAP, 31 +/- 6 microns vs. 75 +/- 5 microns; nitroprusside, 31 +/- 8 microns vs. 42 +/- 7 microns). Responses were not augmented with the second messenger of nitric oxide-mediated dilation 8-Br-cGMP (37 +/- 9 microns vs. 32 +/- 9 microns). CONCLUSIONS: These results indicate that nitric oxide directly increases arachidonic acid-induced dilation. Thus, the non-specific effect of L-arginine analogues can be explained by a permissive effect of nitric oxide on endothelial arachidonic acid metabolism.     

Rendez-vous with metric semantics

A comparative semantic study is made of an element of the family of concurrent object-oriented programming languages. Particular attention is paid to two notions: (i) dynamically evolving process structures, including a mechanism to name and refer to processes and a means to create new processes, and (ii) rendez-vous between processes involving the sending and answering of messages and the induced execution of method calls. The methodology of metric semantics is applied in the design of operational and denotational semantics, as well as in the proof of their equivalence. Both semantics employ domains which are determined as fixed points of a contracting functor in the category of complete metric spaces. Moreover, fruitful use is made of the technique of defining semantic meaning functions as fixed points of contracting higher-order mappings. Finally. syntactic and semantic continuations play a pervasive role.     

Free volume changes in mechanically milled PS and PC studied by positron annihilation lifetime spectroscopy (PALS)

The effect of mechanical milling on free volume was studied by means of positron annihilation lifetime spectroscopy (PALS) in polystyrene (PS) as a typical brittle polymer and in polycarbonate (PC) as a tough representative. Long‐time milling increases the free volume, while a decrease is observed for short milling times. The changes are mostly irreversible in PS. The irreversible fraction is much smaller for PC. Gel permeation chromatography (GPC) measurements show a decrease of the molecular weight, which is much more pronounced in PS. The milling‐induced irreversible changes in free volume are attributed to chain‐end defects resulting from chain scission. In PC, other deformation‐induced defects that anneal upon heat treatment above the glass transition temperature dominate. Polym. Eng. Sci. 44:1351–1359, 2004. © 2004 Society of Plastics Engineers.     

Effect of purified Trichoderma reesei cellulases on formation of cotton powder from cotton fabric

The mode of action of monocomponent purified Trichoderma reesei cellobiohydrolases (CBHI and CBHII) and endoglucanases (EGI and EGII) on cotton fabrics was studied by analyzing the weight loss of the fabric, the reducing sugars, the soluble oligosaccharides and the molecular weight of the cotton powder formed. The impact of mechanical action on these factors was also evaluated. EGI and EGII released the highest amounts of reducing sugars and soluble oligosaccharides in both treatments with or without additional mechanical action. After cellulase treatment without additional mechanical action, all of the cellulases were found to have reduced the molecular weight of cotton poplin powder. When mechanical action was combined with enzyme treatments, only EGII reduced the molecular weight. The weight loss of EG‐treated fabrics was clearly higher than the weight loss of CBH‐treated fabrics with both low and high mechanical action levels. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1917–1922, 2003     

Methotrexate osteopathy in long-term, low-dose methotrexate treatment for psoriasis and rheumatoid arthritis

OBJECTIVES: Herein we describe an additional case of myelolipoma of the adrenal gland, an uncommon tumor of the adrenal cortex, that had been incidentally discovered during abdominal US evaluation of the biliary tree. The clinical features, diagnosis and treatment of the condition are discussed. METHODS: Surgical treatment of the biliary tree and myelolipoma was performed through a Chevron transversal incision during the same surgical session. RESULTS: Surgery achieved good results and the postoperative course was unremarkable. CONCLUSIONS: Myelolipoma is a benign nonfunctioning tumor of the adrenal cortex comprised of adipose and hematopoietic tissue. It is usually asymptomatic and incidentally discovered during diagnostic evaluation for other pathologies. The diagnosis is made by US, CT and MRI. There is no agreement on whether surgical treatment is warranted.     

Structure-function relationship of the inhibition of the 3,5,3'-triiodothyronine binding to the alpha1- and beta1-thyroid hormone receptor by amiodarone analogs

Desethylamiodarone (DEA), the major metabolite of the potent antiarrhythmic drug amiodarone (A), acts as a competitive inhibitor of T3, binding to the alpha1-thyroid hormone receptor (alpha1-T3R), but as a noncompetitive inhibitor with respect to the beta1-T3R. To gain insight into the structure- function relationship of the interaction between A metabolites and T3Rs, we investigated the effects of several A analogs on T3 binding to the alpha1-T3R and beta1-T3R in vitro. The analogs tested were: 1) compounds obtained by deethylation of A, DEA, and desdiethylamiodarone (DDEA); 2) compounds obtained by deiodination of A, monoiodoamiodarone and desdiiodoamiodarone (DDIA); and 3) benzofuran derivatives with various iodination grades, 2-butyl-3-(4-hydroxy-3,5-diiodo-benzoyl)benzofuran (L3373, two iodine atoms), L6424 (L3373 with one iodine atom), and L3372 (L3373, no iodine atoms). IC50, values of inhibition of T3 binding to alpha1-T3R and beta1-T3R, respectively, were as follows (mean +/- SD, expressed x 10(-5) M): DEA, 4.7 +/- 0.9 and 2.7 +/- 1.4 (P < 0.001); DDEA, 3.7 +/- 0.9 and 1.9 +/- 0.3 (P < 0.001); monoiodoamiodarone, more than 20 and more than 20; DDIA, 16.2 +/- 5.6 and 9.1 +/- 2.1 (P < 0.01); L3373, 3.8 +/- 1.0 and 3.6 +/- 0.5 (P = NS); L6424, 11.3 +/- 5.7 and 10 +/- 2.0 (P = NS); and L3372, no inhibition. Scatchard analyses in the presence of DDEA, DDIA, and L3373 demonstrated a dose-dependent decrease in Ka, but no change in the maximum binding capacity (MBC) of T3 binding to alpha1-T3R. Langmuir plots clearly indicated competitive inhibition of T3 binding to alpha1-T3R by DDEA, DDIA, and L3373. In contrast, these three analogs acted differently with respect to the beta1-T3R. DDEA and DDIA decreased both Ka and MBC in Scatchard plots using beta1-T3R, demonstrating noncompetitive inhibition. L3373 decreased dose-dependently Ka, but not MBC, values of T3 binding to the beta1-T3R and clearly acted as a competitive inhibitor. Ki plots indicated that DDEA, DDIA, and L3373 do not interfere significantly with occupied T3Rs. KI (inhibition constant for the unoccupied receptor) plots demonstrated increasing inhibition of the T3 binding to unoccupied receptors with increasing analog concentrations. In summary, 1) removal of one or two ethyl groups of A results in compounds with strong but almost equal potency of inhibiting T3R binding, whereas removal of one or two iodine atoms of A has a lower potency in this respect. The strong inhibitory potency of the benzofuran derivative L3373 (equalling that of the deethylated compounds) is lost upon deiodination. 2) All tested A analogs acted as competitive inhibitors to the alpha1-T3R. The behavior to the beta1-T3R was different; deethylation or deiodination of A resulted in noncompetitive inhibition, whereas L3373 was a competitive inhibitor. The potency of deethylated and deiodinated compounds (but not of the benzofuran derivatives) for inhibiting T3 binding was twice as high for the beta1-T3R as for the alpha1-T3R. 3) All tested A analogs preferentially interfere with T3 binding to unoccupied receptors. The implications of these findings for the structure-activity relationship are the following: 1) the size of the diethyl-substituted nitrogen group and of the two bulky iodine atoms in the A molecule hamper the binding of A at the T3 binding site of T3Rs; and 2) differences in the hormone-binding domain of alpha1- and beta1-T3Rs are likely to account for the competitive or noncompetitive nature of inhibition of T3 binding by A analogs.     

Do science-technology interactions pay off when developing technology?

We investigate the relationship between the science intensity of technology domains and country's performance within these domains. The number of references in patents to scientific articles is considered as an approximation of the science intensity of a technology domain whereas a country's technological performance is measured in terms of its technological productivity (i.e. number of patents per capita). We use USPTO patent-data for eight European countries in ten technological domains. A variance analysis (ANOVA) is applied. Country as an independent variable does not explain a significant portion of the observed variance in science intensity (p=0.25). Technology domain, however, explains a significant portion of the observed variance (p<0.001). Moreover, in science intensive fields we find a positive relation between the science linkage intensity of these fields and the technological productivity of the respective countries involved. These findings seem to suggest the relevancy of designing innovation policies, aimed at fostering interaction between knowledge generating actors and technology producers, in a field specific manner. This revised version was published online in August 2006 with corrections to the Cover Date.