Abstract: The present invention relates to microbial multidrug resistance and, in particular, to compounds that microbial drug transporters of the ABC protein superfamily. The invention also relates to methods for selecting or designing compounds for the ability to inhibit drug transporter proteins and to methods of inhibiting drug transporter proteins. The invention concerns the new use of opioid receptor antagonists in the treatment of multidrug resistant microbial infections.

Abstract: The present invention is directed to the administration of aminoglycosides. In particular, the present invention is directed to compositions and methods for the pulmonary administration of aminoglycosides. According to a preferred embodiment, compositions and methods are provided for the localized treatment of respiratory infections.

Abstract: The present invention provides compositions and methods for extending the release times and lowering the toxicity of pharmacologically active compounds. The compounds comprise a salt of the pharmacologically active compound with a lipophilic counterion and a pharmaceutically acceptable water soluble solvent combined together to form an injectable composition. The lipophilic counterion may be a saturated or unsaturated C8-C22 fatty acid, and preferably may be a saturated or unsaturated C10-C18 fatty acid. When injected into a mammal, at least a portion of the composition precipitates and releases the active compound over time. Thus, the composition forms a slowly releasing drug depot of the active compound in the mammal. Therefore, the present invention enables one to provide a controlled dose administration of the active compound for a periods of up to 15 days or even longer.

Abstract: Methods are provided for increasing and altering the timing of antibiotic production in Streptomyces species, particularly S. coelicolor and S. lividans, by functionally deleting the S. coelicolor scbA and scbR genes, respectively, or their homologues. Also provided are strains having such mutations, and methods of producing antibiotics using such strains. Also provided are methods for identifying strains in which functional deletion of the scbA and/or scbR genes or their homologues leads to the above effects.

Abstract: Certain extracts of plants from the genera Leptospernum and Melaleuca can be used in the treatment of both mastitis and metritis to effectively reduce the amount of antibiotic employed, which extracts contain terpene.

Abstract: Compositions that include nucleic acid and cationic aminoglycosides and methods for their use are provided. The subject compositions are characterized by having nucleic acid complexed with a cationic aminoglycoside, where the nucleic acid is condensed. In certain embodiments, the cationic aminoglycoside is a cationic aminoglycoside antibiotic. The composition may further include one or more of: functional groups such as targeting moieties, nuclear localization or targeting peptides, endosomolytic peptides and/or one or more lipids and/or polymers, where the lipids may be provided in a manner to encapsulate the nucleic acid. The present invention also provides methods of using and preparing the nucleic acid-aminoglycoside compositions.

Abstract: The invention relates to a method for the antibiotic coating of bodies with interconnecting microcavities as well as bodies coated this way and their usage.

Abstract: Provided are reagents and methods useful for the synthesis of guanidinylated compounds. Also provided are methods for assaying molecules, including guanidinylated molecules that modulate viral infection and replication.

Abstract: The present invention relates to novel method of reducing microbial infections, especially bacterial infections, of animals, especially of aquatic animals such as fish maintained in tanks or aquaria. The present invention provides bathing and dipping methods for reducing a microbial infection of an animal with an antibiotic solution of enhanced antimicrobial activity comprising at least one chelating agent and at least one antibiotic effective against the microbial infection. The present invention also provides a method for reducing a microbial infection of an animal comprising bathing or dipping an animal having a microbial infection in an antimicrobial solution comprising the chelating agent EDTA, and at least one antibiotic, and optionally a pH buffering agent. The immersion of the aquatic animal in the antimicrobial solution containing the EDTA, antibiotic and pH buffering agent may be repeated until the microbial burden of the animal is eliminated.

Abstract: This invention provides reagents and methods for specifically delivering antibiotic, antimicrobial and antiviral compounds, drugs and agents to phagocytic mammalian cells. The invention also relates to specific delivery to and uptake of such compounds by phagocytic cells. The invention specifically relates to reagents and methods for facilitating the entry of antibiotic, antimicrobial and antiviral compounds, drugs and agents into phagocytic cells. The invention specifically provides compositions of matter and pharmaceutical embodiments of such compositions comprising such antibiotic, antimicrobial or antiviral compounds, drugs and agents conjugated to, impregnated with or coated onto particulate carriers generally termed microparticles. In particular embodiments, the antibiotic, antimicrobial and antiviral compounds, drugs and agents are covalently linked to a microparticle via a specifically-degradable linker molecule which is the target of a microorganism-specific protein having enzymatic activity.

Abstract: Compositions and methods are provided for prophylactic or therapeutic treatment of a mammal for hearing impairments involving neuronal damage, loss, or degeneration, preferably of spinal ganglion neurons, by administration of a therapeutically effective amount of a trkB or trkC agonist, particularly a neurotrophin, more preferably NT-4/5. Also provided are improved compositions and methods for treatments requiring administration of a pharmaceutical having an ototoxic side-effect, wherein the improvement includes administering a therapeutically effective amount of a trkB or trkC agonist to treat the ototoxicity.

Abstract: Disclose herein is a novel recombinant mutant protein of human Group IIA phospholipase A2 (PLA2) which has enhanced antibacterial activity when compared to the wild-type human Group IIA PLA2, pharmaceutical formulations comprising the protein and methods of use thereof. Additionally, the formulations may comprise other bioactive compounds, such as, e.g., conventional antibiotics, that act additively or synergistically with Group IIA PLA2 in order to promote bacterial killing.

Abstract: A composition including a purified antibody conjugated with at least one antibiotic, the antibody having an antigen-binding portion that binds at least one antigen derived from Staphylococcus or Streptococcus.

Abstract: Compositions and methods are provided for prophylactic or therapeutic treatment of balance impairments involving neuronal damage, loss, or degeneration, preferably of vestibular ganglion neurons, in an animal by administration of an effective amount of a trkB or trkC agonist, particularly a neurotrophin, more preferably NT-4/5

Abstract: The invention provides a method of potentiating the activity of antibacterial agents that act on bacterial cell walls, comprising the step of administering to a subject an antibacterial agent and an aminoglycoside to attain a peak concentration of at least 4 mg/l of aminoglycoside and thereafter maintaining the aminoglycoside at a concentration of up to 4 mg/l for at least 1 hour. Compositions comprising an antibacterial agent and an aminoglycoside for efficacious treatment of bacterial infection are also provided.

Abstract: This invention relates to a method of treating an inherited disease due to a point mutation producing a stop codon by administering an effective dose of an aminoglycoside antibiotic or a derivative thereof. Mdx mouse, which is an animal model for Duchenne muscular dystrophy, has been successfully treated with intramuscularly administered 1 and 5 mg gentamicin, which had for effect to suppress the premature stop mutation by inserting an amino acid at the stop codon. Dystrophin positive muscle fibers not different in number from those of normal mouse were detected at the dose of 5 mg gentamicin.

Abstract: According to the present invention there is provided a method for the treatment or prophylaxis of acidic gut syndrome resulting from the accumulation of acid and production of endotoxin in the gastrointestinal tract of a human or an animal, said accumulation resulting from the fermentation of carbohydrate in the gastrointestinal tract of said human or animal, wherein said method comprises administering to said human or animal an effective amount of an active agent capable of preventing or controlling acid and endotoxin accumulation in the gastrointestinal tract.

Abstract: Aminoglycoside antibiotics are used to treat genetic ophthalmic diseases caused by premature “stop” mutations.

Abstract: According to the invention, a novel ophthalmic medicament is made available, which contains in aqueous solution or suspension at least one carbohydrate, at least one amino acid, at least one electrolyte, a chondroitin sulfate and optionally further customary excipients.

Abstract: The present invention is directed to a method for the treatment of severe chronic bronchitis, i.e., bronchiectasis, using a concentrated aminoglycoside antibiotic formulation delivering the antibiotic to the lung endobronchial space, including alveoli, in an aerosol or dry powder having a mass medium diameter predominately between 1 to 5 microns.

Abstract: The present invention is directed to analogs of aminoglycoside compounds of the class having a glycosylated 2-deoxystreptamine (2-DOS) ring as well as their preparation and use as prophylactic or therapeutics against microbial infection. Compounds of the invention comprises at least one aryl, heteroaryl, substituted aryl or substituted heteroaryl group in place of a glycosyl group attached to the 2-deoxystreptamine ring.

Abstract: A method of screening for and treating subjects with a therapeutically effective amount of a compound that is effective in reducing cellular damage related to an ischemic condition, such as stroke or glaucoma. Test compounds are selected and therapeutically effective amount determined based on the relative efficacy of test compounds in preventing cell death in primary cultures of excitable cells, such as retinal ganglion cells, in vitro.

Abstract: The invention provides a method of potentiating the activity of antibacterial agents that act on bacterial cell walls, comprising the step of administering to a subject an antibacterial agent and an aminoglycoside to attain a peak concentration of at least 4 mg/l of aminoglycoside and thereafter maintaining the aminoglycoside at a concentration of up to 4 mg/l for at least 1 hour. Compositions comprising an antibacterial agent and an aminoglycoside for efficacious treatement of bacterial infection are also provided.

Abstract: Topically administrable aqueous solution compositions containing tobramycin and xanthan gum are disclosed. The solution compositions contain a buffering agent and a pH-adjusting agent in an amount sufficient to achieve a pH above 7.8 in order to minimize or avoid compatibility problems between tobramycin and xanthan gum.

Abstract: According to the present invention there is provided a method for the treatment or prophylaxis of acidic gut syndrome resulting from the accumulation of acid and production of endotoxin in the gastrointestinal tract of a human or an animal, said accumulation resulting from the fermentation of carbohydrate in the gastrointestinal tract of said human or animal, wherein said method comprises administering to said human or animal an effective amount of an active agent capable of preventing or controlling acid and endotoxin accumulation in the gastrointestinal tract.

Abstract: This invention relates to the use of gallium-containing compounds, to inhibit intracellular pathogens including pathogens that are members of the genus Mycobacteria, Legionella, Histoplasma, and Leishmania and to organisms causing chronic pulmonary infection such P. aeruginosa.

Abstract: The invention described here concerns the unique utility of fatty acids and their derivatives to eradicate existing fungal and bacterial infections in plants. Also, described herein are combination treatments whereby fatty acids are used to enhance or augment the activity of fungicides, bactericides, and biological control agents.

Abstract: A method and composition are provided for treating intracellular pathogens that reside in phagosomes. The compositions include antibiotics which are conjugated with transferrin or other ligands to form conjugates that target membrane-bound pathogens. The conjugates are selectively taken up by infected phagosomes. Conjugates are provided which utilize transferrin as the targeting ligand for treating mycobacterium which reside in membrane-bound phagosomes.

Abstract: This invention relates to a selective medium for the culture and isolation of Gram.sup.- bacteria comprising at least one antibiotic specifically active against Gram.sup.+ bacteria and at least one bacteriocin.

Abstract: Cysteine protease inhibitors are provided.

Abstract: Lysostaphin is an effective antibiotic in the treatment of staphylococcal infection. Large doses of lysostaphin or lysostaphin analogues are effective in short course, or even one dose administrations, in treating and eradicating staphylococcal infections, including those resistant to conventional antibiotics.

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: The present invention relates generally to a method for, and pharmaceutical compositions useful in, the prophylaxis and/or treatment of cardiac dysfunction in a mammal by the administration of an effective amount of an agent capable of blocking or inhibiting the effect or release of inositol(1,4,5)trisphosphate in cardiac tissue.

Abstract: The invention described herein provides for methods of screening for compounds that can be used to prevent or inhibit the growth of microbial eukaryotes, particularly plant or animal pathogens. The screening methods of the invention involve the step of screening compounds for the ability to inhibit Group I intron I splicing. In addition, to directly screening for compounds that inhibit Group I intron splicing, the screening methods of the invention include screening for compounds that bind to prokaryotic 16S ribosomal RNA because of the correlation, described herein, between group I intron inhibition and binding to prokaryotic 16S ribosomal RNA. The range of possible compounds for screening by the screening methods of the invention is preferably limited to 2-deoxystreptamine derivatives.Another aspect of the invention is to provide methods of treating or preventing infections with eukaryotic microbes by administering an effective amount of a compound that inhibits group I intron splicing.

Abstract: Methods for screening for compounds which potentiate the activity of antibacterial agents against bacteria resistant to the antibacterial agent alone, pharmaceutical compositions including such potentiators, and methods of treating bacterial infections using a combination of a potentiator and a potentiated antibacterial agent, which are useful for overcoming the resistance of a bacterial strain for an antibacterial agent.

Abstract: The subject invention encompasses methods for prevention and treatment of a human or lower animal subject having a urogenital disorder caused or mediated by one or more parasitic protozoa comprising administering to the subject bismuth and one or more antimicrobials. The subject invention also encompasses compositions comprising bismuth and one or more antimicrobials for the prevention and treatment of a human or lower animal subject having a urogenital disorder caused or mediated by one or more parasitic protozoa.

Abstract: The invention involves pharmaceutical compositions for topical application comprising:(a) a safe and effective amount of a pharmaceutical active; and(b) from about 0.05% to about 5% of a non-ionic polyacrylamide having a molecular wight of from about 1,000,000 to about 30,000,000.

Abstract: A method is disclosed for reducing excitotoxic damage to neurons, which can occur as a result of stroke, cardiac arrest, or other events or conditions. This method involves administering an aminoglycoside that suppresses the flow of calcium ions into neurons through N-type calcium channels. To be effective for such use, an aminoglycoside must suppress N-channel activity at a potency greater than streptomycin. Aminoglycosides which meet this criterion (which includes neomycin and Gentamicin) can suppress the depolarizing activation of neurons, which in turn controls the release of glutamate, a neurotransmitter that becomes an endogenous toxin under excitotoxic conditions. Numerous aminoglycosides were tested in in vitro screening tests using brain cell membrane fragments to evaluate N-channel blocking potency.

Abstract: The invention relates to a liposomal formulation containing a therapeutic agent. The formulation of the invention when administered to animals, allows a substantial increase in antibacterial activity of the agent, through an enhanced penetration of the agent inside the bacterial cell. More specifically, the invention relates to a liposomal formulation containing at least one therapeutic agent such as an antibiotic and to a method of treatment of bacterial infections through the administration of such a formulation.

Abstract: Methods of treating optic neuritis comprising administering a protective agent which inhibits glutamate-mediated retinal cell damage to a mammal at risk of developing optic neuritis.

Abstract: The present invention relates to novel amino glycoside salts of sucrose-octa-O-sulfonic acid of formula I:([sucrose-octa-O-sulfonic acid.sup.8- ]-[R-(NH.sub.3.sup.+).sub.x ].sub.y -M.sub.z.sup.n+) (I)(x.multidot.y)+(z.multidot.n)=8x.multidot.y.epsilon.N.vertline.[4.ltoreq.x.multidot.y.ltoreq.8], wherein N is the set of natural numbers,x.epsilon.Z.vertline.[4.ltoreq.x.ltoreq.6], wherein Z is the set of integersz.epsilon.N.vertline.[0.ltoreq.z.ltoreq.4],n.epsilon.Z.vertline.[1.ltoreq.n.ltoreq.3],wherein R is a sugar moiety of an amino glycoside and M is a metal ion or an ammonium ion, said compounds being useful for treating ulcerations of the stomach and duodenum.

Abstract: Disclosed is a method for the inhibition of binding of a ligand to an RNA, the inhibition being mediated by a small organic molecule which binds to the RNA, thereby inhibiting ligand binding. A preferred class of small organic molecules are the 2-deoxystreptamine (2-DOS) aminoglycosides. Disclosed herein are members of the 2-DOS class that are useful for the inhibition of binding of Rev to an RNA containing an RRE. In an HIV infected cell, a consequence of the inhibition of the ability of Rev to bind to the RRE in HIV encoded transcripts is inhibition of HIV replication.

Abstract: Compounds having the formula (I): ##STR1## in which any two of K, L and M are nitrogen and the other is CE; X and Y are independently hydrogen, halogen, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, C.sub.2-4 alkynyloxy, phenyl, benzyloxy, cyano, isocyano, isothiocyanato, nitro, NR.sup.1 R.sup.2, NR.sup.1 OR.sup.2,N.sub.3, NHCOR.sup.1, NR.sup.1 CO.sub.2 R.sup.2, NHCONR.sup.1 R.sup.2, N.dbd.CHNR.sup.1 R.sup.2, NHSO.sub.2 R.sup.1, OR.sup.1, OCOR.sup.1, OSO.sub.2 R.sup.1, SR.sup.1, SOR.sup.1, SO.sub.2 R.sup.1, SO.sub.2 OR.sup.1, SO.sub.2 NR.sup.1 R.sup.2, COR.sup.1, CR.sup.1 .dbd.NOR.sup.2, CHR.sup.1 CO.sub.2 R.sup.2, CO.sub.2 R.sup.1, CONR.sup.1 R.sup.2, CSNR.sup.1 R.sup.2, CH.sub.3 O.sub.2 C.C:CH.OCH.sub.

Abstract: Aminoglycosides, analogs and derivatives thereof, in the form of phosphate salts are described as well as the process for making and utilizing same. Aminoglycoside phosphate liposomes and nonguanadino aminoglycoside phosphate liposomes, their preparation and use, are particularly described.

Abstract: Potentiating agents which enhance the efficacy of antineoplastic agents are disclosed. The potentiating agents disclosed are piperazinyl benzyl compounds such as 1-[.alpha.-(4-Chlorophenyl)-3-methoxybenzyl]-4-allylpiperazine dihydrochloride.

Abstract: Potentiating agents which enhance the efficacy of antineoplastic agents are disclosed. The potentiating agents disclosed are acrivastine esters and the pharmaceutically acceptable salts thereof.

Abstract: A method of killing microorganisms which form a biofilm on a tissue or implant surfaces in a patient, and which are refractory to a biocide at a dose which is effective to kill the microorganism in planktonic form. The effect of the biocide is potentiated, to an effective killing level, by applying an electric field across the surface containing the biofilm.

Abstract: Methods, for the treatment of humans and lower animal subjects having a gastrointestinal disorder, comprising administering bismuth and administering an antimicrobial. From about 50 to about 5000 milligrams of bismuth are administered, per day, for from 3 to 56 days. A safe and effective amount of antimicrobial is administered for from 1 to 21 days. Preferred processes also include a step for performing a diagnostic test on the subject for detection of a campylobacter-like organism infection of the subject. The invention also provides compositions containing a safe and effective amount of bismuth and a safe and effective amount of antimicrobial.

Abstract: The invention relates to a stabile, aqueous suspoemulsion containing as active ingredient 0.2-5 weight % of primycin, 5-25 weight % of propylene glycol, 0.5-5 weight % of non-ionic surface active agent, if desired 15 weight % of auxiliary agent and distilled water in an amount necessary to 100 weight %, as well as to a process for the preparation thereof.

Abstract: Potentiating agents which enhance the efficacy of antineoplastic agents are disclosed. The potentiating agents disclosed are 2-(aminoethylamino) pyridines such as (E)-3-(6-(N-(2-Dimethylaminoethyl)-4-methoxybenzylamino)-2-pyridyl)acrylic acid.