Abstract: A method for enhancing the expression of aquaporin proteins by contacting aquaporin producing cells with interferon-&agr; is described. The method enables treatment of patients afflicted with disease states characterized by xerosis.

Abstract: The present invention provides novel cationic amphiphiles containing novel N-hydroxyalkyl group and therapeutic formulations containing the said amphiphiles that are capable of facilitating transport of biologically active molecules into cells.

Abstract: Plasminogen activator acts as an anti-inflammatory agent by inhibiting generation of superoxide anion by a mechanism that is not related to L-arginine, is not dependent on thrombolytic activity, and is not a function of oxygen free radical scavenging. Moreover, in in vivo models of inflammation, treatment with plasminogen activator reduces edema without inhibiting neutrophil infiltration in in vivo models of inflammation.

Abstract: Substituted condensation products of N-benzyl-3-indenylacetamides with heterocyclic aldehydes and other such inhibitors are useful for the treatment of cystic fibrosis.

Abstract: The invention is based on the finding that the secretin receptor is expressed in tissues present in the distal lung of humans. In patient with CF, levels of the receptor are elevated compared to normal tissue. Treatment of tissue by secretin stimulates the movement of negative ions in the tissue. The invention provides methods of treatment of cystic fibrosis or COPD in a patient by administering to said patient an effective amount of an agent which triggers anion efflux in respiratory tissue via the activation of a secretin receptor.

Abstract: Compounds of Formula I: wherein: X1, and X2 are each independently either O− or S−; X3 and X4 are each independently either —H or —OH, with the proviso that X3 and X4 are not simultaneously —H; R1 is selected from the group consisting of O, imido, methylene and dihalomethylene; R2 is selected from the group consisting of H, halo, alkyl, substituted alkyl, alkoxyl, nitro and azido; R3 is selected from the group consisting of H, alkyl, acyl, aryl, and arylalkyl; and R4 is selected from the group consisting of —OR′, —SR′, —NR′, and —NR′R″, wherein R′ and R″ are independently selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, alkoxyl, and aryloxyl, with the proviso that R′ is absent when R4 is double bonded from an oxygen or sulfur atom to the carbon at the 4-position of the pyrimidine ring, are used in methods of hydrating lung mucus secr

Abstract: Improved porous particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the porous particles are made of a biodegradable material and have a mass density less than 0.4 g/cm3/. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear &agr;-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, porous particles having a relatively large mean diameter, for example greater than 5 &mgr;m, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung.

Abstract: There are provided according to the invention novel compounds of formula (I) wherein R1, R2, and R3 are as described in the specification, processes for preparing them, formulations containing them and their use in therapy for the treatment of inflammatory diseases.

Abstract: A method of increasing glutathione levels in mammalian cells comprising administering an oral bolus of encapsulated pharmaceutically stabilized glutathione in a rapidly dissolving formulation to a mammal on an empty stomach. Pharmaceutical formulations including glutathione are also disclosed.

Abstract: The present invention provides novel cationic amphiphiles containing novel N-hydroxyalkyl group and therapeutic formulations containing the said amphiphiles that are capable of facilitating transport of biologically active molecules into cells.

Abstract: This invention provides the methodology and agents for treating any disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention of proteins. Thus, the methods and agents of the present invention provide for the release of normally retained proteins from the endoplasmic reticulum. The present invention is particuarly useful for treating any disease or clinical condition which is at least partly the result of endoplasmic reticulum-associated retention or degradation of mis-assembled or mis-folded proteins.

Abstract: Compositions and methods for therapy of cystic fibrosis and other conditions are provided. The compositions comprise one or more compounds such as flavones and/or isoflavones capable of stimulating chloride transport in epithelial tissues. Therapeutic methods involve the administration (e.g., orally or via inhalation) of such compositions to a patient afflicted with cystic fibrosis and/or another condition responsive to stimulation of chloride transport.

Abstract: Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride (Cl−) channel regulated by phosphorylation and intracellular nucleotides. CFTR is the major Cl− transport pathway in airway epithelial cells. The abnormal transepithelial Cl− transport and subsequent defective fluid transport caused by CF is a result of the genetic mutations of the gene coding for the CFTR protein. The present invention is directed to the novel use of ionophores as artificial Cl− transport pathways into CF epithelia to treat the defective Cl− and fluid transport lonophores and in particular, small molecule ionophores, represent a potential novel means of treating CF. The invention also includes using an ionophore to generate chloride secretion on intact monolayers of airway epithelia cells and other epithelia cells by administering an ionophore to a mammal.

Abstract: The present invention provides a novel dithiocarbamamte disulfide dimer useful in various therapeutic treatments, either alone or in combination with other active agents. In one method, the disulfide derivative of a dithiocarbamate is coadministered with an agent that inactivates (or inhibits the production of) species that induce the expression of nitric oxide synthase to reduce the production of such species, while, at the same time reducing nitric oxide levels in the subject. In another embodiment, free iron ion levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate(s) to scavenge free iron ions, for example, in subjects undergoing anthracycline chemotherapy. In another embodiment, cyanide levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate so as to bind cyanide in the subject. In a further aspect, the present invention relates to compositions and formulations useful in such therapeutic methods.

Abstract: Diazoimidazole compounds for activating Cl-secretion are disclosed that can be used for treating cystic fibrosis.

Abstract: Gastrointestinal mucus from patients suffering from cystic fibrosis has been found to contain large amounts of chondroitin sulfate polymer. This finding indicates that the enzyme chondroitinase is useful for preventing gastrointestinal mucus from accumulating in cystic fibrosis patients, and subjects suffering from other diseases or conditions characterized by excess mucus secretion.

Abstract: This invention relates to acylated enol derivatives of &agr;-ketoesters and &agr;-ketoamides. The compounds of this invention are either prodrugs of known elastase inhibitors or are elastase inhibitors in their own right and are useful in the treatment of various inflammatory diseases, including cystic fibrosis and emphysema.

Abstract: A method for the administration of glutathione orally comprising the administration of a bolus of glutathione which is pharmaceutically stabilized and encapsulated. The glutathione is administered on an empty stomach. The preferred stabilizer is ascorbic acid.

Abstract: Compounds of Formula I: ##STR1## wherein: X.sub.1, and X.sub.2 are each independently either O.sup.- or S.sup.- ;X.sub.3 and X.sub.4 are each independently either --H or --OH, with the proviso that X.sub.3 and X.sub.4 are not simultaneously --H;R.sub.1 is selected from the group consisting of O, imido, methylene and dihalomethylene;R.sub.2 is selected from the group consisting of H, halo, alkyl, substituted alkyl, alkoxyl, nitro and azido;R.sub.3 is selected from the group consisting of H, alkyl, acyl, aryl, and arylalkyl; andR.sub.4 is selected from the group consisting of --OR', --SR', --NR', and --NR'R", wherein R' and R" are independently selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, alkoxyl, and aryloxyl, with the proviso that R' is absent when R.sub.

Abstract: The present invention provides a novel dithiocarbamate disulfide dimer useful in various therapeutic treatments, either alone or in combination with other active agents. In one method, the disulfide derivative of a dithiocarbamate is coadministered with an agent that inactivates (or inhibits the production of) species that induce the expression of nitric oxide synthase to reduce the production of such species, while, at the same time reducing nitric oxide levels in the subject. In another embodiment, free iron ion levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate(s) to scavenge free iron ions, for example, in subjects undergoing anthracycline chemotherapy. In another embodiment, cyanide levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate so as to bind cyanide in the subject. In a further aspect, the present invention relates to compositions and formulations useful in such therapeutic methods.

Abstract: Autoinducer molecules, e.g., N-(3-oxododecanoyl)homoserine lactone, for Pseudomonas aeruginosa are described. The molecules regulate gene expression in the bacterium. Therapeutic compositions and therapeutic methods involving analogs and/or inhibitors of the autoinducer molecules also are described. The molecules are useful for treating or preventing infection by Pseudomonas aeruginosa.

Abstract: A method and medicant for the inhibition of activation of the nuclear transcription NF-.kappa.B comprising administering an effective amount of a compound of the formula: ##STR1## where R=ethylene, R'=C.sub.4 to C.sub.14 straight chain or branched alkyl, x is greater than 1, and y=8 to 18 is provided. The medicant is preferably administered by aerosolization into the mammalian respiratory system. The medicant may also be applied to the mammalian skin. Preferably the medicant includes a physiologically acceptable carrier which may be selected from buffered saline, isotonic saline, normal saline, petroleum-based ointments and U.S.P. cold cream. There is further provided a method wherein the medicant includes an anti-inflammatory steroid. In addition a method and medicant for treating cutaneous inflammatory disorders, inhibiting the secretion of the pro-inflammatory cytokines TNF, IL-1, IL-6, IL-8 and the growth factor GM-CSF is provided.

Abstract: Compounds of Formula I: ##STR1## wherein: X.sub.1, and X.sub.2 are each independently either O.sup.- or S.sup.- ;X.sub.3 and X.sub.4 are each independently either --H or --OH, with the proviso that X.sub.3 and X.sub.4 are not simultaneously --H;R.sub.1 is selected from the group consisting of O, imido, methylene and dihalomethylene;R.sub.2 is selected from the group consisting of H, halo, alkyl, substituted alkyl, alkoxyl, nitro and azido;R.sub.3 is selected from the group consisting of H, alkyl, acyl, aryl, and arylalkyl; andR.sub.4 is selected from the group consisting of --OR', --SR', --NR', and --NR'R", wherein R' and R" are independently selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, alkoxyl, and aryloxyl, with the proviso that R' is absent when R.sub.

Abstract: This invention relates generally to medical treatment methods. Specifically, the invention relates to methodology for the correction of defective chloride transport by activation of chloride channels of the lung and other epithelia using genetic or chemical modification. These methods relate to the treatment of epithelia with compounds which cause activation of the channel as measured by increased probability (Po) of opening of the channel at physiologically relevant holding potentials. These methods also relate to the treatment of epithelia with gene therapy to introduce chloride channels genes with site mutations which cause activation of the channel as measured by increased probability (Po) of opening of the channel at physiologically relevant holding potentials. These treatments will reduce life-threatening complications frequently found in diseases such as cystic fibrosis. These methods of activation of chloride channels also comprise treatment of chloride channels with amidation reactions.

Abstract: The present invention relates, in general, to a adenovirus mediated transfer of genes to the lung. In particular, the present invention relates to a method of recombinant, replication-deficient adenovirus mediated transfer of desired genes to the lung whereby desired proteins of interest are produced for local and/or systemic use.

Abstract: This invention relates to methods for using gallium-containing compounds to inhibit the growth of pathogenic P. aeruginosa in a mammal infected with the pathogen.

Abstract: Methods and compositions for treating CF by mobilizing mutant forms of CFTR, which retain at least some functional activity, to the plasma membrane where they can mediate chloride ion transport are disclosed.

Abstract: A method of treating a mammalian patient suffering from or prone to a condition characterized by late phase allergic reactions, airway hyperresponsiveness or inflammatory reactions, e.g., asthma, allergic rhinitis, allergic dermatitis, allergic conjunctivitis, inflammatory bowel disease or rheumatoid arthritis, comprising the administration to the patient of an oral, parenteral, intrabronchial, topical, intranasal or intraocular pharmaceutical composition containing in each dose about 0.005 to about 1.0 mg per kilogram of patient body weight of ultra-low molecular weight heparins (ULMWH) or other sulfated polysaccharides having average molecular weights of about 1,000-3,000 daltons. Suitable inhalant and other pharmaceutical compositions for use in the novel treatment method are also disclosed.

Abstract: The cystic fibrosis gene and its gene product are described for mutant forms. The genetic and protein information is used in developing DNA diagnosis, protein diagnosis, carrier and patient screening, cloning of the gene and manufacture of the protein, and development of cystic fibrosis affected animals.

Abstract: Plasmid-lipid particles which are useful for transfection of cells in vitro or in vivo are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. The particles are typically 65-85 nm, fully encapsulate the plasmid and are serum-stable.

Abstract: The present invention provides compositions that are cell permeable antagonists of inositol polyphosphates. In addition, the invention provides methods for enhancing chloride ion secretion from a cell by contacting the cells with cell permeable antagonists of inositol polyphosphates. The invention also provides methods for enhancing chloride ion secretion in an individual by administering cell permeable antagonists of inositol polyphosphates to the individual. The invention additionally provides methods for alleviating a sign or symptom associated with cystic fibrosis in an individual by administering a cell permeable antagonist of inositol polyphosphates to the individual. The invention also provides compositions that are cell permeable agonists of inositol polyphosphates. In addition, the invention provides methods for decreasing chloride ion secretion from a cell by contacting the cell with cell permeable agonists of inositol polyphosphates.

Abstract: Compositions and methods for therapy of cystic fibrosis and other conditions are provided. The compositions comprise one or more flavones and/or isoflavones capable of stimulating chloride transport in epithelial tissues. Therapeutic methods involve the administration (e.g., orally or via inhalation) of such compositions to a patient afflicted with cystic fibrosis and/or another condition responsive to stimulation of chloride transport.

Abstract: This invention provides a method of selectively decreasing pulmonary vascular resistance in a subject by administering endobronchially a drug chosen from among cAMP analogs, cGMP analogs, phosphodiesterase inhibitors, nitric oxide precursors, nitric oxide donors, and nitric oxide analogs.

Abstract: Pharmaceutical compositions comprising an inorganic pyrophosphate (PPi) in a form that renders the PPi accessible to ABC proteins when administered to a subject in vivo, as well as use of the compositions for treating subjects having a disease or disorder associated with inappropriate or inadequate ABC protein activity (e.g., cystic fibrosis, multi drug resistance, Zellweger's Syndrome) is disclosed.

Abstract: Methods for treating respiratory disease, including cystic fibrosis, emphysema, bronchitis, and sinusitis are presented. Methods comprise administering to a patient an effective amount of DNA in a manner so as not to be effect gene transfer and expression.

Abstract: This invention relates to acylated enol derivatives of .alpha.-ketoesters and .alpha.-ketoamides. The compounds of this invention are either prodrugs of known elastase inhibitors or are elastase inhibitors in their own right and are useful in the treatment of various inflammatory diseases, including cystic fibrosis and emphysema.

Abstract: A method of treating cystic fibrosis by generating cystic fibrosis transmembrane conductance regulator (CFTR) function in cells containing mutant CFTR and the therapeutic composition for treatment are described. The method of treatment comprising administering an effective amount of genistein, or genistein analogues and derivatives, to a person afflicted with cystic fibrosis.

Abstract: A pharmaceutical formulation comprises, in an amount effective to hydrate lung mucous secretions, a compound of Formula (I): ##STR1## wherein n is from 1 to 6;X is --OH or --SH;A and B are each independently selected from the group consisting of: ##STR2## wherein R is H or Br; or a pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier. A method of hydrating mucous secretions in the lungs of a subject in need of such treatment, comprising administering to the lungs of the subject a compound of Formula I as given above, is also disclosed.

Abstract: This disclosure is of a surfactant mixed with an aerosollizing agent, and deposited by such agent, as a treatment for airway obstruction. It has been extensively tested, and has proved successful. It has been hypothesized that the addition of a hypersmolor drug will help to minimize mucus in the airways.

Abstract: The present invention relates to therapeutic methods for treating diseases characterized by an accumulation of high molecular weight DNA in mucous, thereby contributing to the viscosity of the mucous. Such diseases include cystic fibrosis and chronic bronchitis. Treatment includes administration of weak organic acids to promote acidification of cells and consequently apoptosis-induced DNA fragmentation. The invention also relates to therapeutic apparatus for administering the acid compositions.

Abstract: The present invention relates to a method to protect an animal from a disease involving inflammation by treating that animal with an effective amount of IL-12. The present invention also relates to a method for prescribing treatment for a respiratory disease involving an inflammatory response and a method for monitoring the success of a treatment for a respiratory disease involving an inflammatory response in an animal. Also included in the present invention is a formulation comprising IL-12 and a compound capable of enhancing the effectiveness of the IL-12 at protecting an animal from a disease involving inflammation.

Abstract: The present invention relates to a method to protect an animal from a disease involving inflammation by treating that animal with an effective amount of IL-12. The present invention also relates to a method for prescribing treatment for a respiratory disease involving an inflammatory response and a method for monitoring the success of a treatment for a respiratory disease involving an inflammatory response in an animal. Also included in the present invention is a formulation comprising IL-12 and a compound capable of enhancing the effectiveness of the IL-12 at protecting an animal from a disease involving inflammation.

Abstract: The present invention relates to the use of at least one polyene macrolide for the preparation of pharmaceutical compositions for the treatment of diseases that are associated with an impaired energy turnover. Particularly, the present inventions allows to specifically stimulate the energy conversion in human cell, i.e. to stimulate the cell metabolism, and thus to treat or prevent a series of diseases.

Abstract: The present invention provides compositions that are cell permeable antagonists of inositol polyphosphates. In addition, the invention provides methods for enhancing chloride ion secretion from a cell by contacting the cells with cell permeable antagonists of inositol polyphosphates. The invention also provides methods for enhancing chloride ion secretion in an individual by administering cell permeable antagonists of inositol polyphosphates to the individual. The invention additionally provides methods for alleviating a sign or symptom associated with cystic fibrosis in an individual by administering a cell permeable antagonist of inositol polyphosphates to the individual. The invention also provides compositions that are cell permeable agonists of inositol polyphosphates. In addition, the invention provides methods for decreasing chloride ion secretion from a cell by contacting the cell with cell permeable agonists of inositol polyphosphates.

Abstract: Methods of hydrating lung mucous secretions in the lungs of a subject are disclosed. The methods involve administering benzamil or phenamil to the lungs of the subject in an amount effective to hydrate lung mucous secretions. The administering step is preferably carried out by inhalation administration. The method is useful in the treatment of diseases such as cystic fibrosis and chronic bronchitis.

Abstract: Methods and compositions for the treatment of the symptoms of a patient who has a pulmonary condition associated with an inhibition of surfactant secretion by type II alveolar cells are described. The method of treatment involves causing a patient to inhale an amount of a pH-raising buffer effective to raise the pH of the aqueous fluid in the microenvironment of the type II alveolar cell lumenal surface, thereby inducing an increase in the rate of surfactant secretion by type II alveolar cells.

Abstract: A method and medicant for the inhibition of activation of the nuclear transcription NF-.kappa.B comprising administering an effective amount of a compound of the formula: ##STR1## where R=ethylene, R'=C.sub.4 to C.sub.14 straight chain or branched alkyl, x is greater than 1, and y=8 to 18 is provided. The medicant is preferably administered by aerosolization into the mammalian respiratory system. The medicant may also be applied to the mammalian skin. Preferably the medicant includes a physiologically acceptable carrier which may be selected from buffered saline, isotonic saline, normal saline, petroleum-based ointments and U.S.P. cold cream. There is further provided a method wherein said medicant includes an anti-inflammatory steroid. In addition a method and medicant for treating cutaneous inflammatory disorders, inhibiting the secretion of the pro-inflammatory cytokines TNF, IL-1, IL-6, IL-8 and the growth factor GM-CSF is provided.

Abstract: A method and medicament for the inhibition of oxidants comprising administering a treatment effective amount of alkylaryl polyether alcohol polymers to a chemical or biologic system in need thereof. Also, a method and medicament for mucociliary clearance, inhibition of cytokine production, and inhibition of interleukin-8 production in cystic fibrosis patients. The method involves administering a treatment effective amount of alkylaryl polyether alcohol polymers to a chemical or biologic system in need thereof. The medicament is preferably administered by aerosolization into the mammalian respiratory system. The medicament may also be applied to the mammalian skin. Preferably, the medicament includes a physiologically acceptable carrier which may be selected from the group consisting of physiologically buffered saline, isotonic saline, normal saline, petrolatum based ointments and U.S.P. cold cream.

Abstract: Peptides derived from mutant CFTR protein which inhibit intracellular degradation and/or retention of mutant CFTR proteins are disclosed. A method of inhibiting intracellular degradation and/or retention of mutant CFTR protein by administering peptides having an amino acid sequence corresponding to mutant CFTR amino acid sequences is also disclosed. Further, a method of preventing cellular retention and degradation of an otherwise membrane bound protein by competitively inhibiting intracellular degradation (proteolysis) and retention which would otherwise retain or degrade synthesized mutant proteins prior to arrival of the protein at the cell surface is disclosed.

Abstract: Methods for treating cystic fibrosis are described. The methods involve the administration of a protein enhancing agent, differentiating agent and/or carboxy-compound to a subject afflicted with cystic fibrosis such that mutant cystic fibrosis transmembrane regulator protein present within cystic fibrosis-associated cells becomes functional. Other aspects described include therapeutic compositions and packaged drugs.