Abstract: A method of managing non-infective nasal symptoms may include combining a steroid with a diluent, and acetylcysteine, azelastine, or theophylline. The combined ingredients may be mixed to formulate a topical composition for intranasal irrigation or nebulization. The steroid may include fluticasone, budesonide, or methylprednisolone.

Abstract: ?-Hairpin peptidomimetics of the general formula cyclo(-Tyr1-His2-Xaa3-Cys4-Ser5-Xaa6-DPro7-Xaa8-Arg9-Tyr10-Cys11-Tyr12-Xaa13-Xaa14-Xaa15-Pro16-), disulfide bond between Cys4 and Cys11, and pharmaceutically acceptable salts thereof, with Xaa3, Xaa6, Xaa8 Xaa13, Xaa14 and Xaa15 being amino acid residues of certain types which are defined in the description and the claims, have favorable pharmacological properties and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immunosuppression; or during apheresis collections of peripheral blood stem cells and/or as agents to induce mobilization of stem cells to regulate tissue repair. These peptidomimetics can be manufactured by a process which is based on a mixed solid-and solution phase synthetic strategy.

Abstract: A pharmaceutical composition using natural gonadotropin-releasing hormone (GnRH), and/or some of its mimetic peptides, indistinctly bound by its amino or carboxyl extremes to a carrier molecule; in one case by its carboxyl extreme and in the other case by the amino terminal extreme, thus eliciting a faster and more potent immunological response against the endogenous GnRH hormone. This finally leads to the ablation of the GnRH and consequently of the rest of the involved hormones in the stream GnRH/LH-FSH/Testosterone-(estrogens). An advantage of this formulation consists on facilitating the exposition to the immune system of a greater number of epitopes of the GnRH or its mimetics, minimizing thus the steric hindrance produced by the carriers.

Abstract: A method for recognizing and evaluating the presence and function of GnRH receptors on tumor cells including those originating in the brain and/or nervous system and/or the meninges and/or reactive neuroglia cells and/or primitive neuroectodermal tumor cells and/or on Kaposi sarcoma is provided. Furthermore, a method for reducing degenerate GnRH-positive tumor cells and/or for decreasing cellular replication of the above GnRH-positive tumor cells comprising administering to a cell or to a subject a replication decreasing amount of a GnRH agonist and/or GnRH antagonist and/or an erythropoietin agonist, and/or a thrombopoietin agonist, and/or a endothelin antagonist and/or a gonadotropin inhibiting hormone agonist is also provided. Furthermore, a diagnostic kit for detecting GnRH receptors on tumor cells according to the present methods is disclosed.

Abstract: Fusion protein for immunocastration (Sequences la and Ib) that comprises the primary amino acid sequence of the gonadotrophin-liberating protein fused to a theoretical sequence: Sequence la NH2-QHWSYGLRPGGPPFSGGGGPPFSA-COOH (SEQ ID NO: 1) Sequence Ib NH2-GPPFSGGGGPPFSAQHWSYGLRPG-COOH (SEQ ID NO: 2); DNA sequences coding for said fusion protein; vaccine comprising said fusion protein; use of the fusion protein for mammal immunocastration; process for producing the vaccine; process for preparing the fusion protein that comprises fusing the amino acid sequence of the gonadotrophin-liberating hormone (GnRH-I) to a theoretical glycosilable sequence having immunogenic activity that does not include pathogen or “carrier” protein sequences in its structure.

Abstract: Adrenocortical disease (ACD) in ferrets develops as a result of the effect of increased concentration of Luteinizing Hormone (LH) on adrenal LH receptors. This increase in LH often results from the neutering of male or female ferrets. Neutered ferrets have no negative feedback of the ovarian or testicular hormone and as a result LH is elevated 3 to 10 times normal. Elevated LH may be prevented and/or treated by injection of GnRH vaccine. Administration of GnRH produces antibodies to endogenous GnRH. The GnRH-anti-GnRH immune-complex is ineffective in stimulating the release of LH and FSH in the anterior pituitary resulting drop in concentration of LH in the systemic circulation. This reduction in LH significantly reduces the occurrence or clinical symptoms of ACD therein. Moreover, treatment of ferrets with the GnRH provides long term relief from ACD for a period of a year or more.

Abstract: LHRH analogs and LHRH antagonists for use in the treatment or prophylaxis of hormone-dependent cancers, in particular prostate cancer, prostate carcinoma and/or advanced prostate carcinoma, by administering an initial dose of an LHRH analog over a first period sufficient to effect hormonal castration, then administering a maintenance dose of an LHRH antagonist over a second period, the dose being insufficient to achieve and/or maintain hormonal castration.

Abstract: The invention relates to fusion constructs, methods of using fusion constructs and methods of treating undesirable or aberrant cell proliferation or hyperproliferative disorders, such as tumors, cancers, neoplasia and malignancies.

Abstract: The invention features targeted cytotoxic compounds and methods relating to their therapeutic use for the treatment of neoplasia and other conditions.

Abstract: Disclosed are compounds, compositions and methods for systemic and local delivery of biologically active molecules.

Abstract: The present invention provides methods and kits for assessing the state of oocyte maturation in a female mammal based on the level of PAPP-A found in the female's bodily fluid sample.

Abstract: An artificial decapeptide for inducing vitellogenesis in fish, being an analogue of gonadotropin-releasing hormone of chicken is set forth in SEQ ID NO: 2. The artificial decapeptide can be further developed and manufactured into a preparation, which is capable of inducing vitellogenesis in fish. With the implantation of the preparation into body cavity or body wall of bony fish, the induction of vitellogenesis and ovum maturation in bony fish can be successfully achieved.

Abstract: Lytic peptides, including fusion peptides of lytic peptides conjugated with luteinizing hormone-releasing hormone or modified versions thereof to target luteinizing hormone-releasing hormone receptors, are disclosed. The lytic peptides show anti-proliferative activity against human prostate cancer cell lines, but are nontoxic to normal primary human prostate epithelial cells or to bone marrow stromal cells in co-culture. The lytic peptides have specificity for and anti-proliferative activity against prostate cancer tumor cells, and low toxicity for normal prostate cells, making the peptides useful in therapies for prostate cancer.

Abstract: Lytic peptides, including fusion peptides of lytic peptides conjugated with luteinizing hormone-releasing hormone or modified versions thereof to target luteinizing hormone-releasing hormone receptors, are disclosed. The lytic peptides show anti-proliferative activity against human prostate cancer cell lines, but are nontoxic to normal primary human prostate epithelial cells or to bone marrow stromal cells in co-culture. The lytic peptides have specificity for and anti-proliferative activity against prostate cancer tumor cells, and low toxicity for normal prostate cells, making the peptides useful in therapies for prostate cancer.

Abstract: Antagonistic peptides of GnRH having improved water solubility are disclosed. These peptides are capable of suppressing serum testosterone levels in vivo to chemical castration levels of ?0.5 ng/ml. Stable, filter sterilizable, non-gelling solutions containing the GnRH antagonists at least at levels typically used in sustained release formulations also are disclosed, as is a method of increasing the solubility of GnRH antagonist in a polymer containing dispersed phase, which method comprises addition of an acid to the dispersed phase.

Abstract: The peptides Ac-D-2Nal-D-4ClPhe-D-3Pal-OH and Boc-D-2Nal-D-4ClPhe-D-3Pal-OH are intermediates useful in the synthesis of LHRH analogs by coupling with suitable heptapeptides, in particular with the heptapeptides P1-Ser(P2)-MMeTry(P3)-D-Lys(Nic)-Leu-Lys(iPr,P4)-Pro-D-AlaNH2 and P1-Ser(P2)-NMeTry(P3)-D-Asn-Leu-Lys(iPr,P4)-Pro-D-AlaNH2.

Abstract: The invention is directed to analogs of LHRH-II and, more generally, to analogs of the LHRH family in which modifications have been made that confer enhanced binding affinity for LHRH receptors and/or improved metabolic stability. The invention is further directed to methods of targeted therapy and targeted imaging in patients with sex-hormone-related cancers or other LHRH-mediated diseases.

Abstract: The present invention relates generally to the field of synthetic vaccines, components thereof and methods for producing same. More particularly, the present invention provides a component of synthetic vaccines and its use in a modular approach to vaccine production.

Abstract: The invention describes compositions of peptide analogs that are active in blood or cleavable in blood to release an active peptide. The peptide analogs have a general formula: A-(Cm)x-Peptide (SEQ ID NO: 76), wherein A is hydrophobic moiety or a metal binding moiety, e.g., a chemical group or moiety containing 1) an alkyl group having 6 to 36 carbon units, 2) a nitrilotriacetic acid group, 3) an imidodiacetic acid group, or 4) a moiety of formula (ZyHisw)p (SEQ ID NO: 50), wherein Z is any amino acid residue other than histidine, His is histidine, y is an integer from 0-6; w is an integer from 1-6; and p is an integer from 1-6; wherein if A has alkyl group with 6 to 36 carbon units x is greater than 0; and Cm is a cleavable moiety consisting of glycine or alanine or lysine or arginine or N-Arginine or N-lysine, wherein x is an integer between 0-6 and N may be any amino acid or none. The peptide analogs are complexed with polymeric carrier to provide enhanced half-life.

Abstract: The present invention provides a method of preparing an intermediate for LHRH antagonists, which requires fewer steps than conventional methods and provides the intermediate in high yield and high purity.

Abstract: The present invention provides conjugates of disorazoles and their derivatives with cell-binding molecules, such as peptides, proteins, hormones, blood proteins and antibodies. The present invention further provides novel disorazole derivatives and processes of manufacturing such conjugates and disorazole derivatives. These compounds can be used as medicaments for the treatment of physiological and/or pathophysiological conditions in mammals, in particular for the treatment of various tumors.

Abstract: Specially designed non-mammalian GnRH analogs resistant to degradation by the tumor tissue enzymes, post-proline peptidases as well as endopeptidases, are disclosed. The GnRH analogs are further defined as analogs of chicken II GnRH, salmon GnRH, or herring GnRH, but can include any non-mammalian GnRH analog with similar amino acid structure. These non-mammalian analogs incorporate D-arginine, D-leucine, D-tBu-Serine or D-Trp or other similar amino acids at position 6 and ethylamide or aza-Gly-amide or similar amides at position 10. These analogs demonstrate preferential binding to tumor cell GnRH receptors that is greater relative to the binding of the mammalian analogs to the tumor cell GnRH receptor. These non-mammalian GnRH analogs may be used in pharmaceutical preparations, and it specifically in various treatments as an anti-tumor, anti-proliferation, anti-metastatic and/or an apoptotic agent.

Abstract: Disclosed are compounds, compositions and methods for systemic and local delivery of biologically active molecules.

Abstract: The invention provides for a cell permeable peptide conjugated to an insulin compound for improved cell penetration of the insulin moiety. The composition may be delivered by intravenous, intramuscular, subcutaneous, intranasal, oral inhalation, intrarectal, intravaginal or intraperitoneal means for the treatment, including prophylaxis of Type I, Type II diabetes, prediabetes and/or metabolic syndrome.

Abstract: The invention relates to the field of pharmaceutical formulations of follicle-stimulating hormone (FSH), luteinising hormone (LH), and mixtures of FSH and luteinising hormone (LH), and to methods of producing such formulations. The invention provides a liquid or freeze-dried formulation of FSH, or LH, or FSH and LH comprising a surfactant selected from Pluronic® F77, Pluronic F87, Pluronic F88 and Pluronic F68.

Abstract: The invention relates to the field of pharmaceutical formulations of a mixture of follicle stimulating hormone (FSH) and luteinising hormone (LH), and to methods of producing such formulations.

Abstract: It is intended to provide a model animal faithfully reproducing the pathogenic conditions of spinal and bulbar muscular atrophy, a method of screening a remedy for polyglutamine disease using the same, and a remedy for spinal and bulbar muscular atrophy. Namely, a nonhuman animal having the following characteristics (1) to (5) in its conditions or pathological findings: (1) showing progressive myoatrophy; (2) showing lowering in muscular power; (3) in immunostaining with the use of an anti-polyglutamine antibody, showing nuclear diffuse staining and nuclear inclusions; (4) in immunostaining with the use of an anti-androgen receptor antibody, showing nuclear diffuse staining and nuclear inclusions; and (5) showing a neurogenic change. A remedy for polyglutamine disease is screened by administering a test substance to this nonhuman animal and examining changes in its conditions or pathological findings.

Abstract: Herein disclosed is a method of rescuing gonadotropin-releasing hormone receptor (GnRHR) mutants with IN3 or a mimetic thereof. IN3 significantly rescues 11 missense mutations as assessed by radioligand binding and by IP production. Such rescue occurred despite widely disparate loci along the receptor. In addition, many altered GnRH receptors (terminally truncated, internal deletions, or lacking the ability to form bridges to form tertiary structure) were rescued with IN3.

Abstract: The present invention concerns the use of an agonist of an hypothalamic hormone for the preparation of a pharmaceutical agent to support the luteal phase during infertility treatment of female mammals and more specifically of woman. According to this invention, the pharmaceutical agent is suitable to be used for supporting the luteal phase after a spontaneous ovulation or after stimulation of follicular growth, trigger of final follicular maturation and ovulation with one or several additional agents.

Abstract: A novel lyophilizate and method of preparation as well as the use of the lyophilizate to treat female infertility and for gonad protection. Cetrorelix is dissolved in acetic acid 30% v/v, the solution is transferred to water and freeze dried.

Abstract: The present invention provides a method of preparing an intermediate for LHRH antagonists, which requires fewer steps than conventional methods and provides the intermediate in high yield and high purity.

Abstract: Lamprey GnRH-III polypeptides for the four species of fish lamprey are disclosed. Also disclosed is a procedure for producing such polypeptides by recombinant techniques. Also disclosed are methods for utilizing such polypeptides for sterilizing fish.

Abstract: The peptides Ac-D-2Nal-D-4ClPhe-D-3Pal-OH and Boc-D-2Nal-D-4ClPhe-D-3Pal-OH are intermediates useful in the synthesis of LHRH analogs by coupling with suitable heptapeptides, in particular with the heptapeptides P1-Ser(P2)-MMeTry(P3)-D-Lys(Nic)-Leu-Lys(iPr,P4)-Pro-D-AlaNH2 and P1-Ser(P2)-NMeTry(P3)-D-Asn-Leu-Lys(iPr,P4)-Pro-D-AlaNH2.

Abstract: A novel peptide found as gonadotropin-releasing hormone (GnRH) in octopuses, a member of mollusks. The structure and the activities of the peptide have been unraveled. The peptide finds use as a reagent used in the studies of correlations between the structure and the activities of GnRH and the information processing mechanisms of the nervous systems in higher animals. It can also serve as a base compound in the development of pesticides and drugs. The peptide has the GnRH activity and has the following amino acid sequence (I): <Glu-Zaa-Zaa-His-Zaa-Ser-Zaa-Zaa-Zaa-Zaa-Pro-Gly-NH2 (SEQ ID NO: 7) ??(I) wherein <Glu represents pyroglutamic acid and Zaa represents any amino acid. Specifically, the peptide has the following amino acid sequence (1): <Glu-Asn-Tyr-His-Phe-Ser-Asn-Gly-Trp-His-Pro-Gly-NH2 (SEQ ID NO: 1) ??(1) wherein <Glu represents pyroglutamic acid.

Abstract: The present invention relates to methods of inducing ovulation in a female host comprising the administration of a non-polypeptide cyclic adenosine monophosphate (cAMP) level modulator to the female host. In another aspect, the invention provides for specific administration of the phosphodiesterase inhibitor prior to the luteal phase of the host's ovulatory cycle. Preferred non-polypeptide cAMP level modulators include phosphodiesterase inhibitors, particularly inhibitors of phosphodiesterase 4 isoforms.

Abstract: The invention provides a new use for LH, and analogues having LH-activity for aiding folliculogenesis in controlled ovarian hyperstimulation (COH), in which the LH or an analogue thereof is administered during a priming period lasting from day 1 to about day 4 of the stimulatory phase in COH.

Abstract: Claimed are a series of somatostatin agonists and uses thereof, according to formula (I), A1-cyclo[Cys-A2-D-Trp-A3-A4-Cys]-A5-Y1, ??(I) wherein A1, A2, A3, A4, A5 and Y1 are as defined in specification provided that the amine nitrogen of at least one peptide bond is substituted with a methyl group or pharmaceutically acceptable salts thereof.

Abstract: The present invention relates to a method for improving homogeneity and/or secretion of a recombinant protein of interest expressed in mammalian cells by replacing the endogenous signal peptide sequence of the DNA encoding the protein of interest with that of human hGH. Specifically, the present invention relates to a method wherein the protein of interest is a subunit of the follicle stimulating hormone (FSH). The invention also relates to DNA expression vectors containing the sequence encoding such proteins of interest fused to the signal peptide sequence of the hGH and to cells harbouring such vectors.

Abstract: A sustained-release drug composition consisting essentially of microparticles of hyaluronic acid having a high molecular weight or an inorganic salt thereof and a protein or peptide drug encased in said microparticles, wherein the average size of said microparticles ranges from 0.1 to 40 ?m.

Abstract: PEG-LHRH analog conjugates, where a PEG moiety is covalently bound to a serine residue of a LHRH analog, and methods for producing these conjugates are provided in the present invention. Also provided are a pharmaceutical composition and a method for treating pathologies in which LHRH analog administration is beneficial.

Abstract: The invention relates to medicaments for initiating ovulation comprising LH in an administrable form which ensures an increase in LH plasma levels for a period of some 40 to 60 hours.

Abstract: Methods for treating FSH related conditions, such as prostatic intraepithelial neoplasia, pedophilia, infertility, or vaginal bleeding, with GnRH antagonists are disclosed. The methods of the invention generally feature administering to a subject a GnRH antagonist suitable for in vivo administration and able to reduce both plasma FSH and LH levels in a subject, in an amount or in a formulation effective to reduce plasma FSH levels in the subject to a symptom alleviating level. In vitro fertilization and male contraceptive methods are also provided.

Abstract: The present invention relates to methods of inducing ovulation in a female host comprising the administration of a non-polypeptide cyclic adenosine monophosphate (cAMP) level modulator to the female host. In another aspect, the invention provides for specific administration of the phosphodiesterase inhibitor prior to the luteal phase of the host's ovulatory cycle. Preferred non-polypeptide cAMP level modulators include phosphodiesterase inhibitors, particularly inhibitors of phosphodiesterase 4 isoforms.

Abstract: The present invention relates to two novel Gonadotropin releasing hormones muGnRH I and muGnRH II of amino acid SEQ ID 1 as QHWSAWRLPG, and SEQ ID 2 QHWSWGILPG respectively, useful for induced breeding in fish both in combination and alone, by activating production of Gonadotropin, and a method of isolating the same from Indian Murrel brain, and further, a method of inducing breeding in fishes using the said novel gonadotropin releasing hormones.

Abstract: A sustained-release preparation which comprises a physiologically active peptide of general formula wherein X represents an acyl group; R1, R2 and R4 each represents an aromatic cyclic group; R3 represents a D-amino acid residue or a group of the formula wherein R3? is a heterocyclic group; R5 represents a group of the formula —(CH2)n—R5? wherein n is 2 or 3, and R5? is an amino group which may optionally be substituted, an aromatic cyclic group or an O-glycosyl group; R6 represents a group of the formula —(CH2)n—R6? wherein n is 2 or 3, and R6? is an amino group which may optionally be substituted; R7 represents a D-amino acid residue or an azaglycyl residue; and Q represents hydrogen or a lower alkyl group, or a salt thereof and a biodegradable polymer having a terminal carboxyl group. The sustained-release preparation shows a constant release of the peptide over a long time and is substantially free from an initial burst.

Abstract: The present invention relates to two novel Gonadotropin releasing hormones muGnRH I and muGnRH II of amino acid SEQ ID 1 as QHWSAWRLPG, and SEQ ID 2 QHWSWGILPG respectively, useful for induced breeding in fish both in combination and alone, by activating production of Gonadotropin, and a method of isolating the same from Indian Murrel brain, and further, a method of inducing breeding in fishes using the said novel gonadotropin releasing hormones.

Abstract: The present invention relates particularly to neoplastic cells targeted chimeric toxins comprising of cell targeting moieties and cell killing moieties for recognizing and for destroying the neoplastic cells, wherein the cell targeting moieties consist of gonadotropin releasing hormone homologues and the cell killing moieties consist of Pseudomonas Exotoxin A. The present invention further relates to pharmaceutical compositions containing as an active ingredient these neoplastic cells targeted chimeric toxins and to a method for the production of these chimeric toxins. The said invention also relates to a method for cancer therapy, treating malignant carcinoma cells and benign hyperplasia including uterine lyomyoma cells, extra uterian endometrial island cells, benign hyperplasia of prostate and breast and pituitary tumor adenoma cells, by the use of the above-mentioned chimeric toxins.

Abstract: Certain toxic compounds (T) such as, for example, compounds based upon diphtheria toxin, ricin toxin, pseudomonas exotoxin, ?-amanitin, pokeweed antiviral protein (PAP), ribosome inhibiting proteins, especially the ribosome inhibiting proteins of barley, wheat, corn, rye, gelonin and abrin, as well as certain cytotoxic chemicals such as, for example, melphalan and daunomycin can be conjugated to certain analogs of gonadotropin-releasing hormone to form a class of compounds which, when injected into an animal, destroy the gonadotrophs of the animal's anterior pituitary gland. Hence such compounds may be used to sterilize such animals and/or to treat certain sex hormone related diseases.

Abstract: PEG-LHRH analog conjugates, where a PEG moiety is covalently bound to a serine residue of a LHRH analog either directly or via a bifunctional linker molecule, such as an amino acid, and methods for producing these conjugates are provided in the present invention. Also provided are a pharmaceutical composition and a method for treating pathologies in which LHRH analog administration is beneficial.

Abstract: The invention relates to a modified tandem LHRH-peptide vaccine preparation in which the amino acid glycine at position (6) of one or both LHRH decapeptides that constitute the tandem unit is substituted by a dextrorotatory amino acid that contains a side chain to which a carrier compound can be coupled. In addition, the tandem LHRH-peptide can be brought into a tandem-dimer form which is also suitable for producing a vaccine that is effective against LHRH (luteinizing hormone releasing hormone), also referred to as GaRH (gonadotropin-releasing hormone), for immunological castration to inhibit or affect reproductive functions or to affect behaviour in vertebrates in general and in domesticated animals and man in particular.