Abstract: Methods of treating endotoxin-mediated disorders are provided.

Abstract: Provided are methods of simulating tissue healing. The methods comprise using a mechanistic computer model of the interrelated effects of inflammation, tissue damage or dysfunction and tissue healing to predict an outcome of healing of damaged tissue in vivo, thereby predicting the outcome of healing of damaged tissue in vivo. Implementations of these methods on a computing device also are provided. Non-limiting examples of diseases and/or conditions that are amenable to simulation according to the methods described herein include: a diabetes, diabetic foot ulcers, necrotizing enterocolitis, ulcerative colitis, Crohn's disease, inflammatory bowel disease, restenosis (post-angioplasty or stent implantation), incisional wounding, excisional wounding, surgery, accidental trauma, pressure ulcer, stasis ulcer, tendon rupture, vocal fold phonotrauma, otitis media and pancreatitis.

Abstract: The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: wherein R1 and R2 are defined in the application, or a physiologically-acceptable salt thereof. The invention also provides pharmaceutical compositions comprising these compounds.

Abstract: The present invention relates to the use of a composition including of at least a mutated antithrombin having an anticoagulant activity substantially reduced with respect to the anticoagulant activity of the non mutated antithrombin, or having no anticoagulant activity, for the preparation of a drug intended for the prevention or the treatment of pathologies associated with cellular injury, such as infection, inflammation or hypoxic injury.

Abstract: Toll Like Receptor 3 (TLR3) antagonists, polynucleotides encoding TLR3 antagonists, and methods of making and using the foregoing are disclosed.

Abstract: Disclosed are antagonists of IL-17A and IL-17F. The antagonists are based on soluble IL-17RA and IL-17RC fusion proteins, including hybrid soluble receptors comprising portions of both IL-17RC and IL-17RA (“IL-17RC/IL-17RA”). Such antagonists serve to block, inhibit, reduce, antagonize or neutralize the activity of IL-17F, IL-17A, or both IL-17A and IL-17F. Also disclosed are methods of using such antagonists for treating disease, particularly inflammatory diseases mediated at least in part by IL-17A and/or IL-17F.

Abstract: The present invention refers to fusion proteins comprising a TNF superfamily (TNFSF) cytokine or a receptor binding domain thereof fused to a trimerization domain and a nucleic acid molecule encoding the fusion protein. The fusion protein is present as a trimeric complex or as an oligomer thereof and is suitable for therapeutic, diagnostic and/or research applications.

Abstract: The present invention relates to amino acid sequences that are directed against/and or that can specifically bind Interleukin-6 Receptor (IL-6R) with improved affinity and/or avidity, and/or that have an improved efficacy and/or potency, and which are capable of (partially, or preferably totally) blocking the IL-6/IL-6R interaction and/or inhibit signalization through IL-6, 1L-6R and/or the IL-6/IL-6R complex. The invention further relates to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences.

Abstract: The present invention provides a polypeptide having a biological activity of the Chemotaxis Inhibitory Protein of Staphylococcus aureus (‘CHIPS’), the polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 2, or a fragment or variant thereof having a biological activity of CHIPS, wherein the fragment or variant retains amino acid substitutions K40E, D42V, N77H, K100R, K105R, N111 K and/or G112A relative to the wildtype CHIPS protein of SEQ ID NO:1. In one embodiment, polypeptide consists of the amino acid sequence of SEQ ID NO: 2. Related aspects of the invention provide pharmaceutical compositions comprising a polypeptide of the invention, together with methods or making and using the same.

Abstract: The present invention relates to compositions and methods relating to an interleukin18-inducible cytokine termed tumor necrosis factor-alpha inducing factor (TAIF) or interleukin-32 (IL-32). In particular, the present invention provides compositions and methods for treating autoimmune diseases and cancer, in part by regulation of tumor necrosis factor-alpha expression.

Abstract: The present invention provides Parotid Secretory Protein peptides, nucleic acids encoding the peptides, and methods of using the peptides, and methods of screening GL13 mimetics.

Abstract: The present invention provides compositions and pharmaceutical formulations of IaIp derived from plasma. Also provided are methods for the manufacture of the IaIp compositions and formulations, as well as method for the treatment of diseases associated with IaIp dysfunction.

Abstract: A novel polypeptide, and an antibacterial agent, antifungal agent and/or antiseptic containing as an effective ingredient the polypeptide are disclosed. The polypeptide of this invention has an amino acid sequence shown in SEQ ID NOs:1 to 12 and 13 to 31. This antibacterial agent, antifungal agent and/or antiseptic is useful for the prevention, amelioration or treatment of diseases such as burn, decubitus, wound, skin ulcer, leg ulcer, diabetic ulcer, occlusive arterial disease and arteriosclerosis obliterans, cellulitis, acute lymphangitis, lymphadenitis, erysipelas, skin abscess, necrotizing subcutaneous infection, staphylococcal scalded skin syndrome (SSSS), folliculitis, facial furuncle, suppurative hidradenitis, carbuncle, infectious paronychia, erythrasma and severe infection (sepsis).

Abstract: The present invention relates to: TNF-? antagonists containing IGFBP5 protein, variants thereof, or fragments thereof; and the use of the TNF-? antagonists. More specifically, the present invention relates to: a polynucleotide encoding the protein, variants thereof, or fragments thereof; a vector containing the polynucleotide; a transformant containing the vector; and a method for screening a therapeutic agent for TNF-? overexpression-related diseases by checking whether the mutual reaction thereof is facilitated after treating with candidates to the cell expressing the IGFBP5 protein, variants thereof, or fragments thereof, and the TNER1.

Abstract: Methods and compositions for using the MHC class II invariant chain polypeptide, Ii (also known as CD74), as a receptor for macrophage migration inhibitory factor (MIF), are disclosed. These include methods and compositions for using this receptor, as well as agonists and antagonists of MIF which bind to this receptor, or which otherwise modulate the interaction of MIF with CD74 or the consequences of such interaction, in treatment of conditions characterized by locally or systemically altered MIF levels, particularly inflammatory conditions and cancer.

Abstract: There is provided a composition comprising an effective amount of Annexin A5 for use in treatment of an inflammatory disorder. There is provided a composition comprising an effective amount of Annexin A5 for use in improving organ function. Methods for administering such compositions for treatment of animals are also provided.

Abstract: A polypeptide comprising one or more sequences derived from CDR2 or CDR3 of a TREM-1 protein, characterised by the ability to treat, ameliorate, or lessen the symptoms of conditions including sepsis, septic shock or sepsis-like conditions and IBD.

Abstract: Methods of suppressing the activation of microglial cells in the Central Nervous System (CNS), methods of ameliorating or treating the neurological effects of cerebral ischemia or cerebral inflammation, and methods of combating specific diseases that affect the CNS by administering a compound that binds to microglial receptors and prevents or reduces microglial activation are described. ApoE receptor binding peptides that may be used in the methods of the invention are also described, as are methods of using such peptides to treat peripheral inflammatory conditions such as sepsis. Also described are methods of screening compounds for the ability to suppress or reduce microglial activation.

Abstract: A pharmaceutical composition comprising 5-ethyl-1-phenyl-2-(1H)-pyridone (5-EPP) and its use for the treatment of sepsis are disclosed.

Abstract: The present invention relates to novel compounds that are useful for inhibition and prevention of pathogen cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of pathogen cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of infectious diseases.

Abstract: The present invention relates to novel compounds that are useful for inhibition and prevention of pathogen cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of pathogen cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of infectious diseases.

Abstract: A mutein recombinant adenosine deaminase having any oxidizable cysteine residue replaced by a non-oxidizable amino acid residue is disclosed. Stabilized recombinant adenosine deaminase, polymer conjugates and methods of treatment using the same are also disclosed.

Abstract: Chimeric therapeutics are disclosed that include a modified viral core protein and a nucleic acid bound to the modified viral core protein. The nucleic acid may be substantially homologous to a specific gene target. In some embodiments, the nucleic acid bound to the modified viral core protein is substantially non-immunogenic. Also disclosed are particles and compositions that include disclosec chimeric therapeutics.

Abstract: The subject invention pertains to peptides and salts thereof that are useful as anti-inflammatory agents and to compositions containing such peptides and salts as active ingredients. Specifically exemplified herein are endomorphin-1 peptide (EM-1), analogs and salts thereof, and uses for modulation of calcitonin gene-related peptide (CGRP) production and/or substance P (SP) and for treatment of inflammation, particularly neurogenic inflammation.

Abstract: The invention features polypeptide and polynucleotide sequences based on the 134R sequence. In some embodiments, these sequences include a heterologous signal sequence, such as the myxoma virus T7 signal sequence. The invention also features methods for treating immunological disorders and neoplasms (e.g., cancer) using the polypeptides and nucleotides described herein. Finally, the invention features fusion proteins including the myxoma virus T7 signal sequence.

Abstract: The present invention relates to polypeptide variants of the HMGB-1 high affinity binding domain Box-A (HMGB1 Box-A) or to a biologically active fragment of HMGB1 Box-A, which are obtained through systematic mutations of single amino acids of the wild-type HMGB1 Box-A protein and which show an increased resistance to proteases and which are therefore characterized by more favorable pharmacokinetic and pharmacodynamic profiles. Moreover, the present invention concerns the use of said polypeptide molecules of HMGB1 Box-A to diagnose, prevent, alleviate and/or treat pathologies associated with extracellular HMGB1 and associated with RAGE.

Abstract: Follistatin-like protein (FSTL-1) is a secreted glycoprotein of unknown function, first isolated from mouse osteoblastic cells as a transforming growth factor-?1-inducible gene. The inventors have discovered that FSTL-1 is a proinflammatory mediator. As such, the invention provides for composition and methods of using agents that bind to FSTL-1 to modulate various types of inflammation (e.g., autoimmune diseases). Inhibitors and antagonists of FSTL-1, particularly antibodies or antibody fragments, may be used to treat conditions related to inflammation, such as arthritis. In addition, the inventors have discovered that FSTL-1 has a role in the Th17 pathway. Accordingly, the invention provides for compositions and methods of using agents which bind to FSTL-1 to modulate the generation of Th17 cells. Such agents are useful for delaying development of and treating diseases associated with undesired production of Th17 cells, such as autoimmune diseases.

Abstract: The present invention is based on a novel, alternatively spliced human isoform of MD-2 (MD-2s). In addition, the present invention relates to modified MD-2 proteins, wherein one or more tyrosine residues have been mutated to phenylalanine. In various embodiments, the invention relates to methods and kits for preventing, reducing the likelihood of developing and/or treating various conditions using MD-2s. The invention also describes methods of determining the risk of a subject to various conditions.

Abstract: A method for treating septic hypotension, including administering at least one alpha-2 agonist or other sympatholytic, and at least one vasopressor. The alpha-2 agonist may be clonidine or dexmedetomidine, and the sympaholytic may be rilmelidine, monoxidine, alpha-methyldopa and alpha-methylparatyrosine. The vasopressor may be noradrenaline, adrenaline, vasopressin, angiotensin and phenylephrine. The method can include intravenous infusion of the patient with at least one inotrope such as dobutamine and phosphodiesterase inhibitors. Suitable inotropes include amrinone and milrinone. In a preferred embodiment, the alpha-2 agonist and the vasopressor are simultaneously administered. Also disclosed is a composition for treating septic shock hypotension which includes at least one alpha-2 agonist and at least one vasopressor.

Abstract: The invention relates to complement inhibitors that inhibit both the classical and alternative complement pathways. In particular, the invention relates to complement inhibitors derived from the salivary glands of haematophagous arthropods that inhibit both the classical and alternative complement pathways. The invention also relates to the use of such complement inhibitors in the treatment and prevention of diseases.

Abstract: Methods and compositions for treating sepsis using cell membrane-permeant peptide conjugate covalent compounds having target cell specificity are provided.

Abstract: The present invention is related to the use of alpha-1-antitrypsin as an anti-necrotic agent. This invention provides a method for the treatment of tissue necrosis by administration of alpha-1-antitrypsin. This invention further provides methods for prophylactic treatment of tissue necrosis and for inhibition of tissue necrosis in culture by addition of alpha-1-antitrypsin.

Abstract: The invention relates to the use of microfluidic chemotaxis device to identify novel active compounds of the metabolome and methods to characterize their actions on cell motility. The invention also includes the active compounds of the metabolome identified by the methods and devices disclosed herein. The results from these in vitro experiments were then correlated with in vivo physiologic responses to identify the downstream effects and therapeutic value. Thus, the invention provides novel methods for treating or preventing second organ injury resulting from ischemia-reperfusion in a patient in need thereof The invention also provides methods of treating, preventing or ameliorating connective tissue degeneration in a patient in need thereof. The invention also provides methods of treating or preventing bone loss. In addition, the invention provides method for inducing bone regeneration in patients in need thereof or preventing bone loss in patients suspected to be in need thereof.

Abstract: The present invention relates generally to peptides and more specifically to antimicrobial and immunomodulatory host defense peptides.

Abstract: The present invention relates to the use of novel compounds for the manufacture of a medicament for treatment of inter alia conditions associated with critical care as well as to a method for treatment of said conditions, wherein said compounds are administered. The compounds utilised are represented by the general formula (I), as further defined in the specification.

Abstract: The present invention relates to a method for treating and screening for compounds for the treatment of sepsis. More specifically, the treatment and screening methods are based on the discovery that granzyme B containing platelets (GzmB-platelet) causes apoptosis by direct contact with cells.

Abstract: The invention relates to methods of use of synthetic peptide amides that are ligands of the kappa opioid receptor in the treatment and prevention of kappa opioid receptor-associated diseases and conditions; and particularly to uses of these agonists in the prophylaxis, inhibition and treatment of pain, inflammation and pruritis associated with a variety of diseases, disorders and conditions. Inflammatory conditions preventable or treatable by the methods of the invention include diseases and conditions associated with elevated levels of a proinflammatory cytokines, such as TNF-?, IL-?, IL-6, MMP-1 and MMP-3.

Abstract: Methods and compositions that determine the expression levels of Stat4? and Stat4? isoforms for therapeutic efficacy of anti-inflammatory treatments, assessing an individual's risk for developing inflammatory diseases including Crohn's disease, ulcerative colitis, rheumatoid arthritis, and multiple sclerosis are disclosed.

Abstract: Provided are methods to enhance healing of wounds and tissue, especially during or pursuant to psychological and/or physical stress and to protect tissue from deleterious effects associated with oxidative, psychological and/or physical stress, including but not limited to extreme exertion, ischemia, infarct, and damage associated with reperfusion of ischemic or transplanted tissues.

Abstract: The present invention generally provides processes for purification of Inter-alpha inhibitor proteins (I?Ip) and compositions thereof from blood.

Abstract: The invention relates to active fragments of the IL-18 binding protein, to pharmaceutical compositions comprising such active fragments, and to medical uses thereof.

Abstract: An antioxidant compound is disclosed.

Abstract: The present invention is directed to compounds according to formula, (R2R3)-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-R1, and pharmaceutically-acceptable salts thereof that act as ligands for one or more of the melanocortin receptors, to methods of using such compounds to treat mammals and to pharmaceutical compositions comprising said compounds.

Abstract: Provided herein are methods, oligonucleotides and peptide nucleic acids, compositions and kits for predicting a subject's response to treatment with activated protein C or protein C-like compound or susceptibility to major organ dysfunction or susceptibility to an inflammatory condition. The method generally comprises determining a genotype of said subject at one or more of polymorphic sites in the subject's protein C gene selected from one or more of the following: rs20069915 and one or more polymorphism sites in linkage disequilibrium thereto, selected from one or more of the following: rs2069910; rs2069916; rs2069924; rs2069931; rs1799808; rs2069920; and rs6714364 and may further involve comparing the determined genotype with known genotypes for the polymorphism that correspond with an improved response to treatment with activated protein C or protein C-like compound or correspond to susceptibility to major organ dysfunction or susceptibility to an inflammatory condition.

Abstract: The invention provides methods of treating a mammal afflicted with an inflammatory disease, such as peritonitis, peritoneal adhesions or endometriosis, comprising the administration, intraperitoneal or otherwise, of a therapeutically effective amount of a SPARC polypeptide or a SPARC polypeptide-encoding isolated polynucleotide and a pharmacologic carrier.

Abstract: Subject of the present invention are assays and in vitro methods for the in vitro diagnosis, prognosis and risk stratification of a patient having a primary, non-infectious disease, whereby the level of Procalcitonin (PCT) in a sample of a body fluid of the patient is indicative for the risk of the patient to contract a further disease or medical condition.

Abstract: Disclosed herein are methods and compositions related to GHS-R antagonists.

Abstract: Peptides that selectively bind to antigens exposed in vascular disease or dysfunction have been identified by biopanning a phage library. The ligands are useful when attached to a substrate to be in contact with endothelial surfaces, especially those where drug delivery is utilized, such as following angioplasty, with release from a drug delivery reservoir in a medical device such as a stent, or by administration intravenously in the form of nano or microparticles, although the peptides may also be used with other medical devices or substrates, for targeting or to increase adhesion to endothelial surfaces. The nanoparticle technology can be used to treat injured vasculature, a clinical problem of primary importance. The targeted nanoparticles are also useful in the treatment of other diseases and disorders such as oncologic and regenerative diseases and indications where neoangiogenesis is commonly observed.

Abstract: The invention describes compositions of peptide analogs exemplified by peptides derived from vasopressin, terlipressin, and GLP1 and others 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, wherein A is a hydrophobic moiety or a metal binding moiety, 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. A may be linked to Cm by a linker group. The peptide analogs are complexed with polymeric carrier to provide enhanced half-life.

Abstract: The present invention relates to a method of protecting cells against damage caused at least in part by apoptosis, comprising administering to subjects a therapeutic dose of leumorphin having cytoprotective activity, and a pharmaceutical composition comprising an effective amount of leumorphin having a cytoprotective activity.