Abstract:
Soluble alkyl [5-[amino(phenyl)methyl]-2H-benzimidazol-2-yl]carbamates, their enantiomorphic forms, and acid addition salts thereof are well absorbed and possess curative anthelmintic activity, especially against filarial worms, when administered orally or parenterally. Pharmaceutical compositions containing the compounds and methods of employing the compounds in methods of treating helminth infections in mammals are also disclosed, together with methods of synthesis.
Abstract:
L'invention concerne des complexes moléculaires utilisés pour cibler un gène codant une protéine secrétoire sur une cellule spécifique in vivo et obtenir une secrétion de la protéine par la cellule ciblée. Un gène exprimable codant une protéine secrétoire voulue est transformé en complexe pour obtenir un conjugué d'un agent de liaison spécifique de cellule et d'un agent de liaison de gène. L'agent de liaison spécifique de cellule présente une spécificité pour une structure de surface cellulaire induisant l'intégration de ligands par endocytose. On peut citer à titre d'exemple l'asialoglycoprotéine récepteur d'hépatocytes. L'agent de liaison de gène est un composé tel qu'un polycation transformant en complexe stable le gène dans des conditions extra-cellulaires, et libérant ledit gène dans des conditions intra-cellulaires de manière qu'il peut fonctionner à l'intérieur d'une cellule. Le complexe moléculaire est stable et soluble dans des liquides phisiologiques et il peut être utilisé en thérapie des gènes afin de transfecter sélectivement des cellules in vivo pour permettre la production et la sécrétion d'une protéine secrétoire voulue.
Abstract:
An ultrasound system and method for performing relatively non-invasive cardiac ablation on a patient. The system of the present invention includes a plurality of ultrasound transducers forming a phased array that is to be located externally of the patient. The array produces a focused beam of sufficient energy to ablate a predetermined cardiac tissue volume. The system is capable of refocusing the beam so that acoustical aberrations encountered by the beam, as it is transmitted through inhomogenous body tissues between the array and the treatment volume, are taken into account and will not impede operation of the system. To refocus the beam, the system includes a sensor which senses the phase distribution caused by the aberrations allowing a controller to calculate a compensating driving phase distribution and accordingly drive the array. The system also allows for real time correction of the beam's position enabling the beam to follow a moving myocardial target volume.
Abstract:
Molecular complexes for targeting a gene encoding a secretory protein to a specific cell in vivo and obtaining secretion of the protein by the targeted cell are disclosed. An expressible gene encoding a desired secretory protein is complexed to a conjugate of a cell-specific binding agent and a gene-binding agent. The cell-specific binding agent is specific for a cellular surface structure which mediates internalization of ligands by endocytosis. An example is the asialoglycoprotein receptor of hepatocytes. The gene-binding agent is a compound such as a polycation which stably complexes the gene under extracellular conditions and releases the gene under intracellular conditions so that it can function within a cell. The molecular complex is stable and soluble in physiological fluids and can be used in gene therapy to selectively transfect cells in vivo to provide for production and secretion of a desired secretory protein.
Abstract:
Biodegradable controlled release nanoparticles as sustained release bioactive agent delivery vehicles include surface modifying agents to target binding of the nanoparticles to tissues or cells of living systems, to enhance nanoparticle sustained release properties, and to protect nanoparticle-incorporated bioactive agents. Unique methods of making small (10 nm to 15 nm, and preferably 20 nm to 35 nm) nanoparticles having a narrow size distribution which can be surface-modified after the nanoparticles are formed is described. Techniques for modifying the surface include a lyophilization technique to produce a physically adsorbed coating and epoxy-derivatization to functionalize the surface of the nanoparticles to covalently bind molecules of interest. The manoparticles may also comprise hydroxy-terminated or epoxide-terminated and/or activated multiblock copolymers, having hydrophobic segments which may be polycaprolactone and hydrophilic segments. The nanoparticles are useful for local intravascular administration of smooth muscle inhibitors and antithrombogenic agents as part of interventional cardiac or vascular catheterization such as a balloon angioplasty procedure; direct application to tissues and/or cells for gene therapy, such as the delivery of osteotropic genes or gene segments into bone progenitor cells; or oral administration in an enteric capsule for delivery of protein/peptide based vaccines.