Methods of treating infections caused by free-living amoeba are disclosed. The methods generally include systemic administration of an effective amount of miltefosine, such as an oral or intravenous formulation, and optionally local administration of an effective amount of miltefosine, such as a topical formulation of miltefosine. The methods may further include administration of one or more secondary agents. Exemplary secondary agents include steroids, polyhexamethylene biguanide (PHMB), chlorhexidine, propamidine isethionate, dibromopropamidine isethionate, neomycin, paromomycin, polymyxin B, clotrimazole, ketoconazole, miconazole, and itraconazole. The methods may be used to treat patients with infections caused by a free-living amoeba such as Naegleria fowleri, Balamuthia mandrillaris, Sappinia diploidea, and Acanthamoeba species. Exemplary infections include Acanthamoeba keratitis, granulomatous amoebic encephalitis, cutaneous acanthamoebiasis, primary amoebic meningoencephalitis, Sappinia amoebic encephalitis, or a disseminated disease associated with a free-living amoeba.

The present invention relates to nucleic acids of the general formula (I): (N.sub.uG.sub.lX.sub.mG.sub.nN.sub.v).sub.a and derivatives thereof as an immunostimulating agent/adjuvant and to compositions containing same, optionally comprising an additional adjuvant. The present invention furthermore relates to a pharmaceutical composition or to a vaccine, each containing nucleic acids of formula (I) above and/or derivatives thereof as an immunostimulating agent, and optionally at least one additional pharmaceutically active component, e.g. an antigenic agent. The present invention relates likewise to the use of the pharmaceutical composition or of the vaccine for the treatment of cancer diseases, infectious diseases, allergies and autoimmune diseases etc. Likewise, the present invention includes the use of nucleic acids of the general formula (I): (N.sub.uG.sub.lX.sub.mG.sub.nN.sub.v).sub.a and/or derivatives thereof for the preparation of a pharmaceutical composition for the treatment of such diseases.

There is disclosed herein a composition for treating extracellular parasitic infections, the composition comprising one or more of the following combinations: at least one quinolone or fluoroquinolone together with at least one tetracycline, iodoquinol, an azole or imidazole; or at least two agents selected from the group consisting of iodoquinol, thiazolidones, tetracycline, nitroimidazoles, cotrimoxazole and diloxanide furoate.

There is also disclosed herein a method for treating extracellular parasitic infections in a vertebrate in need of said treatment, wherein said treatment comprises administering to said vertebrate a therapeutically effective amount of (i) a composition comprising a quinolone or fluoroquinolone together with a pharmaceutically acceptable carrier or (ii) a composition of the invention or (iii) a combination of at least one quinolone or fluoroquinolone optionally together with at least one tetracycline, is iodoquinol, an azole or imidazole; or (iv) a combination of at least two agents selected from the group consisting of iodoquinol, thiazolidones, tetracycline, nitroimidazoles, cotrimoxazole and diloxanide furoate.

The present disclosure provides isolated monoclonal antibodies, particularly human monoclonal antibodies that specifically bind to PD-L1 with high affinity. Nucleic acid molecules encoding the antibodies of this disclosure, expression vectors, host cells and methods for expressing the antibodies of this disclosure are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The disclosure also provides methods for detecting PD-L1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-L1 antibodies.

To provide novel pesticides, especially insecticides or acaricides. A condensed heterocyclic compound represented by the formula (1) or its salt, or N-oxide thereof: ##STR00001##
wherein Q is a structure represented by Q1, Q2 or the like, D substituted with S(O).sub.nR.sup.1 is a structure represented by D1 or D2, A.sup.1 is N(A.sup.1 a) or the like, A.sup.1 a is C.sub.1-C.sub.6 alkyl or the like, A.sup.4 is a nitrogen atom or C(R.sup.4), A.sup.5 is a nitrogen atom or C(R.sup.5), R.sup.1 is C.sub.1-C.sub.6 alkyl or the like, each of R.sup.2, R.sup.5 and R.sup.6 is independently a hydrogen atom or C.sub.1-C.sub.6 alkyl, each of R.sup.3, R.sup.4, Y1, Y2, Y3 and Y4 is independently a halogen atom, halo (C.sub.1-C.sub.6) alkyl or the like, and n is an integer of 0, 1 or 2.

The present invention relates generally to novel depsipeptides, to methods for the preparation of these novel depsipeptides, to pharmaceutical compositions comprising the novel depsipeptides; and to methods of using the novel depsipeptides to treat or inhibit various disorders.

A substituted alkenylbenzene compound of formula (4):

##STR00001##

wherein X.sup.1 is selected from the group consisting of a halogen atom, SF.sub.5, C.sub.1-C.sub.6haloalkyl, hydroxy C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.8halocycloalkyl, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.3haloalkoxy C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl and C.sub.1-C.sub.6haloalkylsulfonyl; X.sup.3 is selected from the group consisting of a hydrogen atom, halogen atom, cyano, nitro, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy and C.sub.1-C.sub.6alkylthio; X.sup.4 is selected from the group consisting of a hydrogen atom, halogen atom, cyano, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy and C.sub.1-C.sub.4haloalkoxy; R.sup.3 is C(R.sup.3a)(R.sup.3b)R.sup.3c, where R.sup.3a and R.sup.3b independently of each other are a halogen atom, or R.sup.3a and R.sup.3b together form 3- to 6-membered ring together with the carbon atom bonding them by forming a C.sub.2-C.sub.5haloalkylene chain, and R.sup.3c is selected from the group consisting of a hydrogen atom, halogen atom, C.sub.1-C.sub.5alkyl, C.sub.1-C.sub.5haloalkyl, C.sub.1-C.sub.4haloalkoxy and C.sub.1-C.sub.4haloalkylthio, with a proviso that in case where X.sup.1 is a fluorine atom, chlorine atom or trifluoromethyl, and both X.sup.2 and X.sup.3 are a hydrogen atom, in case where both X.sup.1 and X.sup.2 are fluorine atom and X.sup.3 is a hydrogen atom, and in case where both X.sup.1 and X.sup.2 are trifluoromethyl and X.sup.3 is a hydrogen atom, R.sup.3c is a hydrogen atom, chlorine atom, bromine atom, iodine atom, C.sub.1-C.sub.5alkyl, C.sub.1-C.sub.5haloalkyl, C.sub.1-C.sub.4haloalkoxy or C.sub.1-C.sub.4haloalkylthio.

This invention relates to compounds useful for treating fungal infections, more specifically topical treatment of onychomycosis and/or cutaneous fungal infections. This invention is directed to compounds that are active against fungi and have properties that allow the compound, when placed in contact with a patient, to reach the particular part of the skin, nail, hair, claw or hoof infected by the fungus. In particular the present compounds have physiochemical properties that facilitate penetration of the nail plate.

The invention provides compounds of Formula (I), and their use in methods for treating or preventing a protozoan infection in a subject using a compound of Formula (I). The invention also provides the use of a compound of Formula (I) in the manufacture of a medicament for the treatment of a protozoan infection in a subject. The invention further provides a medical device when used in a method of treating or preventing a protozoan infection in a subject and to a medical device comprising the composition of the invention.

Composition for treatment of mucus on fish gills for a therapeutic or a prophylactic treatment of an amoebic gill disease in fish, where the composition comprises an extruded fish feed supplemented with arginine; said fish feed comprising protein, binder, fat, vitamins and minerals; and a total arginine content of the fish feed is at least 3.0% (wt/wt) of a total feed weight.