Ruthenium Olefin Metathesis Catalysts Bearing a Macrocyclic N-Heterocyclic Carbene Ligand: Improved Stability and Activity.

Formation of sterically hindered C-C double bonds via catalytic olefin metathesis is considered a very challenging task for Ru catalysts. This limitation led to the development of specialised catalysts bearing sterically reduced N-heterocyclic carbene (NHC) ligands that are very active in such transformations, yet significantly less stable as compared to general purpose catalysts. To decrease the small-size NHC catalysts susceptibility to decomposition, a new NHC ligand was designed, in which two sterically reduced aryl arms were tied together by a C-8 alkyl chain.

Total synthesis of ezetimibe, a cholesterol absorption inhibitor.

Ezetimibe (1), a strong β-lactamic cholesterol absorption inhibitor, was synthesized from (R)-6-(4-fluorophenyl)-5,6-dihydro-2H-pyran-2-one 7. Independent pathways were analyzed in order to select the optimal one, which involved 1,3-dipolar cycloaddition with C-(4-benzyloxyphenyl)-N-(4-fluorophenyl)-nitrone (8), intramolecular nucleophilic displacement at the benzylic position of the lactone, cleavage of the N-O bond, elimination of a water molecule, hydrogenation of the double bond, rearrangement of the six-membered lactone ring into a β-lactam moiety, and final deprotection of the phenolic hydroxyl group. Highly stereoselective Sc(OTf)3-catalyzed 1,3-dipolar cycloaddition was the most crucial step of the synthesis.

Computerised controllers for safety critical medical applications.

A novel design for a computer control system to be employed in safety critical applications, as found in medical environments, is presented. It features a low complexity, fault detecting hardware architecturally supporting a strictly cyclic operating mode, as known from programmable logic controllers, and a specification level, graphical programming technique based on the interconnection of application oriented standard software function modules. By design, there is no semantic gap between the programming and machine execution levels.

Responses to calcium and binding of 3H-nimodipine in the atrioventricular node, atria, and ventricles of mature and old male Fischer 344 rats.

To determine whether aging alters cardiac calcium dose responses or dihydropyridine receptor density or affinity, we performed (a) calcium (Ca2+) dose-response studies (3-5 mM) in Langendorff perfused hearts from 12 mature (4-7 month) and 12 old (23-27 month) Fischer 344 rats, and (b) quantitative autoradiography experiments with 3H-nimodipine (50-3,000 pM) in 20-microns tissue sections containing the compact AV node from hearts of eight mature and eight old F344 rats. Baseline AA interval, AV conduction time, AV Wenckebach block cycle length, and QRS duration were prolonged in isolated hearts from old compared with mature rats. In contrast, neither left ventricular developed pressure nor peak dP/dt was altered by age.

Influence of autonomic blockade and aging on AV conduction and responses to verapamil in the beagle.

Background: Age-related differences in responses to verapamil have been noted in both intact humans and isolated denervated perfused rat hearts. The study was designed to determine the effects of aging on intracardiac conduction and pharmacodynamic responses to verapamil, and also to determine the potential role of autonomic responses in previously reported age-related differences in responses to verapamil.

Methods: After stability of measures was demonstrated in senescent animals, nine young (aged 3-4 years: 12.

Inflammatory responses to Pneumocystis carinii in mice selectively depleted of helper T lymphocytes.

Pneumocystis carinii is the most important pulmonary pathogen in patients with the acquired immunodeficiency syndrome, but host defenses against P. carinii are not well characterized. We recently reported an experimental model of P.

Altered release of eicosanoids by rat alveolar macrophages during granulomatous pulmonary inflammation.

Release of arachidonic acid metabolites (eicosanoids) by alveolar macrophages may be important in regulating pulmonary inflammatory reactions. The purpose of this study was to characterize eicosanoids released by rat alveolar macrophages during the evolution of experimentally induced pulmonary inflammation. Immunization with subcutaneous bacillus Calmette-Guerin (BCG) followed 2 wk later by intravenous BCG challenge resulted in mild granulomatous pulmonary inflammation for up to 30 days.

Interferon-gamma increases alveolar macrophage Ia antigen expression despite oral administration of dexamethasone to rats.

Corticosteroids have multiple effects on immune and inflammatory responses and decrease host resistance to a broad range of microorganisms. Resident tissue macrophages have been proposed as a target for the immunosuppressive effects of corticosteroids and are important in host defense against infections. During infection-induced immune responses, macrophages are activated after exposure to interferon-gamma (IFN-gamma), and class II major histocompatibility (Ia) antigens on their surface are increased.

Cellular influx and activation increase macrophage cytotoxicity and interleukin-1 elaboration during pulmonary inflammation in rats.

This study was undertaken to investigate the effects of pulmonary inflammation induced by bacillus Calmette-Guérin (BCG) on the density distribution of lavaged alveolar macrophages. We sought to determine macrophage cytotoxicity and interleukin-1 elaboration in density-defined subpopulations of macrophages during tissue inflammation. At all time points after intravenously administered BCG, lavaged alveolar macrophages contained increased percentages of higher density cells.

Acquisition of peroxidase activity by rat alveolar macrophages during pulmonary inflammation.

The authors investigated the ability of rat alveolar macrophages to acquire peroxidase activity in the course of pulmonary inflammation. Granulomatous pulmonary inflammation was induced in bacille Calmette-Guérin (BCG)-immunized rats by intravenous injection of BCG in mineral oil. In contrast to normal alveolar macrophages, which are peroxidase-negative, alveolar macrophages lavaged from the BCG-treated rats showed significant peroxidase activity in large cytoplasmic inclusions compatible with internalized exogenous material.

Endogenous peroxidase activity as a marker of macrophage renewal during BCG-induced inflammation in the rat lung.

To determine whether the cytochemical localization of peroxidase activity could be used as a marker of monocyte influx into the lung during an inflammatory response, the authors studied the peroxidase phenotypes of lavaged alveolar macrophages from rats with bacille Calmette-Guérin (BCG)-induced pulmonary inflammation. Rats were immunized subcutaneously and 2 weeks later intravenously with BCG. During the early phase of pulmonary inflammation, an increase was observed in the numbers of alveolar macrophages with no peroxidase activity in the endoplasmic reticulum.

Visualization of protein kinases in lymphocytes stimulated to proliferate with concanavalin A or inhibited with a phorbol ester.

Stimulation of lymphocytes with a mitogenic lectin such as concanavalin A (ConA) results in differentiation and cell division. Among the changes which occur after stimulation are increases in phosphorylation of proteins and in protein kinase activity. We used a high-resolution, nondenaturing gel system to separate and visualize protein kinases in situ.

The effect of removal of adherent cells in lectin and allogeneic cell stimulation of bovine lymphocytes.

Macrophages have been shown to play an important role in lymphocyte activation in many species but not unequivocally for bovine. In this study we have shown that when sufficient care is taken to remove macrophages by adherence or by anti-macrophage serum and complement, bovine lymphocytes respond poorly to lectins or to allogenic cells in mixed lymphocyte culture. Addition of macrophages to approximately the same level as found in the unseparated cells restores the proliferative responses.