Abstract: This invention relates to botulinum toxin formulations that are stabilized without the use of any proteinaceous excipients. The invention also relates to methods of preparing and using such botulinum toxin formulations.

Abstract: Disclosed are proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of c-MYC protein. The disclosed PROTACs typically include a first targeting moiety that binds to c-MYC (Mc-MYC) which may be derived from a substituted heterocycle that binds to c-MYC such as a substituted pyrazole. The first targeting moiety typically is linked via a bond or a linker (L) to a second targeting moiety that binds to an E3 ubiquitin ligase (ME3). As such, the disclosed PROTACS may be described as having a formula Mc-MYC-L-ME3 or ME3-L-Mc-MYC.

Abstract: The invention provides compositions comprising commensal bacterial strains and organic acids and the uses thereof in the treatment of diseases.

Abstract: The present invention relates to a device (1) for fractional flow reserve determination. The device (1) comprises a model generator (10) configured to generate a three-dimensional model (3DM) of a portion of an imaged vascular vessel tree (VVT) surrounding a stenosed vessel segment (SVS), based on a partial segmentation of the imaged vascular vessel tree (VVT). Further, the device comprises an image processor (20) configured to calculate a blood flow (Q) through the stenosed vessel segment (SVS) based on an analysis of a time-series of X-ray images of the vascular vessel tree (VVT). Still further, the device comprises a fractional-flow-reserve determiner (30) configured to determine a fractional flow reserve (FFR) based on the three-dimensional model (3DM) and the calculated blood flow.

Abstract: The present invention relates to certain microorganisms or mixtures thereof for use in the treatment and/or prevention of inflammation in the oral cavity, preferably for the treatment and/or prevention of gingivitis and/or peridontitis. In particular, the present invention relates to microorganisms or mixtures thereof for use as probiotic agents for forming co-aggregates with microorganisms associated with gingivitis and/or peridontitis. Furthermore, the present invention provides oral pharmaceutical compositions, oral care products or products for nutrition or pleasure comprising one or more of the probiotic microorganisms as active agents as well as a method of production thereof.

Abstract: Disclosed is the hypolipidemic potential of Bacillus coagulans. More specifically the invention discloses the cholesterol lowering potential of Bacillus coagulans MTCC 5856 and therapeutic/biological indications thereof.

Abstract: A polypeptide having an amino acid sequence corresponding to a binding domain of a botulinum toxin is described. The polypeptide modulates expression of genes involved in, for example, collagen production and extra cellular matrix organization, and finds use, therefore in modulating skin quality attributes such as elasticity, firmness etc. Moreover, the polypeptide inhibits lipogenesis in specialized cells and finds use, therefore, in reducing skin oiliness, which is frequently observed in skin tissue afflicted with large pores and acne. Nucleic acids encoding the polypeptide, as well as vectors, host cells, and systems comprising the nucleic acids, are further described.

Abstract: The invention provides compositions comprising bacterial strains for treating and preventing a neurodegenerative disorder.

Abstract: Methods are disclosed herein for treating depression in the subject. A method includes the use of Botulinum toxin to cause paralysis of a facial muscle, such as the depressor anguli oris, procerus, frontalis, orbicularis oculi, or corrugator supercilii muscle to treat depression in the subject.

Abstract: The present invention provides methods for improving observed or determined efficacy by administration of agents to more severely diseased subjects, as contrasted with less severely diseased subjects. The present disclosure specifically demonstrates that, with respect to treatment of certain skin conditions, and particularly conditions associated with dysregulated and/or diseased skin cells, administration to more severely diseased subjects improves observed or determined efficacy.

Abstract: The present invention provides a method for preparing epirubicin and an intermediate adaptive to the method. The preparation method may include: reacting tert-Butyldimethylsilyl chloride with N-trifluoroacetyl adriamycin to obtain a compound of formula I N-trifluoroacetyl-14-O-tert-Butyldimethylsilyl adriamycin; oxidizing the compound of formula I to obtain a compound of formula II 4?-ketone-N-trifluoroacetyl-14-O-tert-Butyldimethylsilyl adriamycin; reducing the compound of formula II to obtain a compound of formula III N-trifluoroacetyl-14-O-tert-Butyldimethylsilyl epirubicin; and performing deprotection and hydrolysis reactions on the compound of formula III to obtain epirubicin. The method of the present invention needs low cost, fewer reaction steps, provides high yield and high product purity, and avoids serious pollution caused by a bromination reaction in a conventional method.

Abstract: A method for treating a patient who has a neutralizing antibody to a type A1 botulinum toxin. The method includes administering 150 kDa type A neurotoxin from type A2 Clostridium botulinum (A2 NTX) to the patient. In accordance with the present invention, a problem can be solved of decrease in clinical response caused by a neutralizing antibody to a type A1 botulinum toxin produced when a patient is treated with a pharmaceutical preparation containing a type A1 botulinum toxin.

Abstract: This invention relates to a sterilization agent for livestock bedding or a composting accelerator for organic waste or livestock bedding, comprising at least one Bacillus coagulans thermophilic bacterium or a combination of the at least one Bacillus coagulans thermophilic bacterium and at least one Bacillus subtilis mesophilic bacterium, as an active ingredient, wherein the Bacillus coagulans thermophilic bacterium as a preferable bacterium is viable at a temperature of 40 to 60° C. and the Bacillus subtilis mesophilic bacterium is viable at a temperature of 30 to 50° C., and the mesophilic bacterium also has a sterilizing effect on harmful bacteria in bedding; and to a method for sterilizing livestock bedding or a method for accelerating composting of organic waste or livestock bedding by using these agents each as an active ingredient.

Abstract: This invention discloses a method for treating or preventing heart diseases by using a probiotic composition. The method for treating or preventing heart diseases comprises administering to a subject an effective amount of a probiotic composition to prevent the myocardial cells from myocardial hypertrophy, fibrosis and apoptosis, wherein the probiotic composition comprising Lactobacillus rhamnosus LCR177 (BCRC910473), Pediococcus acidilactici PA318 (BCRC910474) and Bifidobacterium adolescentis (BCRC14609).

Abstract: The present invention pertains to pharmaceutical compositions which comprise a botulinum neurotoxin from Clostridium botulinum, the neurotoxin being free of the complexing proteins naturally present in the botulinum neurotoxin complex or being chemically modified or being modified by genetic manipulation. Moreover the pharmaceutical compositions of the instant invention have good stability and are advantageously formulated free of human serum albumin.

Abstract: Sympathetic nerves run through the adventitia surrounding renal arteries and are critical in the modulation of systemic hypertension. Hyperactivity of these nerves can cause renal hypertension, a disease prevalent in 30-40% of the adult population. Hypertension can be treated with neuromodulating agents (such as angiotensin converting enzyme inhibitors, angiotensin II inhibitors, or aldosterone receptor blockers), but requires adherence to strict medication regimens and often does not reach target blood pressure threshold to reduce risk of major cardiovascular events. A minimally invasive solution is presented here to reduce the activity of the sympathetic nerves surrounding the renal artery by locally delivering neurotoxic or nerve-blocking agents into the adventitia. Extended elution of these agents may also be accomplished in order to tailor the therapy to the patient.

Abstract: An isolated, biologically active 33 kDa hemagglutinin purified from the type A Clostridium botulinum neurotoxin complex and its uses are described.

Abstract: The present invention provides compounds, compositions, medicaments and methods comprising or using carbohydrate binding molecules. More specifically, the invention provides a means of treating diseases and/or conditions caused or contributed to by pathogens, particularly microbial pathogens and methods of screening, identifying, detecting tagging and/or labelling carbohydrates.

Abstract: Methods are disclosed herein for treating depression in the subject. A method includes the use of Botulinum toxin to cause paralysis of a facial muscle, such as the depressor anguli oris, procerus, frontalis, orbicularis oculi, or corrugator supercilii muscle to treat depression in the subject.

Abstract: The present invention pertains to pharmaceutical compositions which comprise a botulinum neurotoxin from Clostridium botulinum, the neurotoxin being free of the complexing proteins naturally present in the botulinum neurotoxin complex or being chemically modified or being modified by genetic manipulation. Moreover the pharmaceutical compositions of the instant invention have good stability and are advantageously formulated free of human serum albumin.

Abstract: The present invention relates to a pharmaceutical composition for treating scars on the skin, comprising a mixture of botulinum toxin and air. The mixture of botulinum toxin and air according to the present invention, when injected in the dermis, may temporarily removed the elasticity of the dermis and flatten out the depressed part of the scar, and thus enables elaborate intradermic resection and increases the therapeutic effects of lasers for treating pulsed dye laser or of fractional lasers. Thus, scars on the skin can be effectively improved through a one-time operation without negatively affecting the daily lives of patients.

Abstract: The present invention relates to pharmaceutical compositions suitable for the treatment of chronic diseases associated with the presence of abnormal or an abnormal distribution of microflora in the gastrointestinal tract of a mammalian host, which compositions comprise viable non-pathogenic or attenuated pathogenic Clostridia. The compositions further comprise one or more additional viable non-pathogenic or attenuated pathogenic microorganisms selected from the group consisting of Bacteroides, Eubacteria, Fusobacteria, Propionibacteria, Lactobacilli, anaerobic cocci, Ruminococcus, E. Coli, Gemmiger, Desulfamonas, Peptostreptococcus, and fungi. The present invention also provides pharmaceutical compositions suitable for the treatment of the same chronic diseases comprising viable non-pathogenic or attenuated pathogenic Escherichia coli, at least one strain of viable non-pathogenic or attenuated pathoenic Bacteroides and at least one strain of viable non-pathogenic or attenuated pathogenic microorganism.

Abstract: It was found that bacteria belonging to the genus Clostridium induce accumulation of regulatory T cells (Treg cells) in the colon. Moreover, the present inventors found that regulatory T cells (Treg cells) induced by from these bacteria suppressed proliferation of effector T-cells. From these findings, the present inventors found that the use of bacteria belonging to the genus Clostridium or a physiologically active substance derived therefrom made it possible to induce proliferation or accumulation of regulatory T cells (Treg cells), and further to suppress immune functions.

Abstract: The instant invention provides various formulations comprising combinations of immunostimulating oligonucleotides, polycationic carriers, sterols, saponins, quaternary amines, TLR-3 agonists, glycolipids, and MPL-A or analogs thereof in oil emulsions, use thereof in preparations of immunogenic compositions and vaccines, and use thereof in the treatment of animals.

Abstract: Provided are therapeutic compositions containing Ecobiotic™ populations for prevention, treatment and reduction of symptoms associated with a dysbiosis of a mammalian subject such as a human.

Abstract: Sympathetic nerves run through the adventitia surrounding renal arteries and are critical in the modulation of systemic hypertension. Hyperactivity of these nerves can cause renal hypertension, a disease prevalent in 30-40% of the adult population. Hypertension can be treated with neuromodulating agents (such as angiotensin converting enzyme inhibitors, angiotensin II inhibitors, or aldosterone receptor blockers), but requires adherence to strict medication regimens and often does not reach target blood pressure threshold to reduce risk of major cardiovascular events. A minimally invasive solution is presented here to reduce the activity of the sympathetic nerves surrounding the renal artery by locally delivering neurotoxic or nerve-blocking agents into the adventitia. Extended elution of these agents may also be accomplished in order to tailor the therapy to the patient.

Abstract: The present invention relates to methods and compositions for use in modulating, including inhibiting the growth and/or reducing the virulence of gram-positive bacteria. The present invention provides methods and compositions for disrupting the cell wall and/or cell membrane in gram-positive bacteria such that cell wall or cell membrane target(s) are rendered exposed or accessible and sensitive to a modulation thereof. Methods for modulation of one or more gram-positive bacterial cell wall or cell membrane targets in a gram-positive bacteria are provided comprising disrupting the cell wall such that the cell wall or cell membrane target, which is particularly a sortase, is rendered exposed or accessible and sensitive to a modifying, modulating or binding agent, which is particularly an antibody or fragment thereof, wherein the cell wall or cell membrane target is inaccessible or relatively insensitive to the modifying, modulating or binding agent in the absence of cell wall disruption.

Abstract: The present invention is directed to analgesic Clostridial neurotoxin derivatives comprising polypeptides having a long-lasting SNARE protein-selective endopeptidase activity. These derivatives selectively bind to and are internalized by non-neuronal cells secreting cytokines or sensory neurons in preference to motor neurons or autonomic neurons. The invention is also directed to nucleic acid constructs encoding such polypeptides, and methods of making such derivatives and nucleic acid constructs, and methods of treating pain, such as chronic pain, by administering such derivatives to a patient suffering from, or at risk of suffering from such pain.

Abstract: This invention relates to isolated Clostridium botulinum propeptides and neurotoxins, isolated nucleic acid molecules encoding Clostridium botulinum propeptides and neurotoxins, methods of expression, treatment methods, and methods of detecting neurotoxin trafficking. The isolated Clostridium botulinum propeptides have a light chain region; a heavy chain region, where the light and heavy chain regions are linked by a disulfide bond; an intermediate region connecting the light and heavy chain regions and comprising a highly specific protease cleavage site; and an S6 peptide sequence according to SEQ ID NO:2 positioned upstream from, but not attached directly to, the N-terminus of the neurotoxin propeptide at the light chain region to enable site specific attachment of cargo.

Abstract: The present invention describes vaccines that comprise C. perfringens Type alpha toxoids, antigenic fragments thereof, inactivated antigenic fragments of C. perfringens Type alpha toxins, or any combination thereof. The present invention further describes methods of using with these vaccines to protect animals against clostridial diseases. The present invention also describes methods of making these vaccines.

Abstract: Disclosed herein are purified bacteriophage preparations that effectively lyse a plurality of C. perfringens strains. In one embodiment, a purified bacteriophage preparation includes four or more C. perfringens-specific bacteriophage, wherein each bacteriophage has lytic activity against at least five C. perfringens strains. In another embodiment, the purified bacteriophage preparation includes five or more C. perfringens-specific bacteriophage.

Abstract: A method is provided for treating a neuromuscular defect in a subject. One step of the method includes locating a target nerve. After locating the target nerve, a treatment probe is provided. The treatment probe includes an elongated body member having a proximal end portion and a distal end portion. The distal end portion includes an energy delivery mechanism for stimulating or ablating the target nerve, a monitoring mechanism, and a fluid aspiration/delivery mechanism. Next, the target nerve is verified as an appropriate target for ablation by stimulating and then monitoring the target nerve via the energy delivery mechanism and the monitoring mechanism, respectively. After verifying the target nerve, a tumescent fluid is injected into the tissue surrounding the target nerve. An electric current is then delivered to the energy delivery mechanism to substantially ablate the target nerve.

Abstract: The present invention relates to the use of at least one botulinum neurotoxin for the production of a medicament for treating or preventing pain induced by a medicament used for treating the AIDS virus.

Abstract: The invention relates to a protein construct, comprising (i) a targeting moiety that is capable of binding to a target cell, and (ii) an effector immunogenic moiety that is capable of triggering an existing, vaccine-induced or natural, immune response. The protein construct, that is preferably in the form of a heteromultimeric protein, is useful for redirecting an immune response that was pre-existing in a patient, toward an undesired target cell.

Abstract: In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. Each mutant toxin includes a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may further include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to antibodies or binding fragments thereof that binds to said immunogenic compositions. In further aspects, the invention relates to isolated nucleotide sequences that encode any of the foregoing, and methods of use of any of the foregoing compositions.

Abstract: A vaccine adjuvant composition comprising: a lipid selected from the group consisting of: dipalmitoyl phosphatidicholine (DPPC), dipalmitoyl phosphatidylglycerol (DPPG), dioleoyl phosphatidylcholine (DOPC), and cholesterol and containing a positively or negatively charged lipid with associated/entrapped protein antigen.

Abstract: A headache can be treated more effectively by co-administration of a botulinum toxin and a triptan drug to a patient and/or the effectiveness of a triptan medication can be increased. The botulinum toxin can be botulinum toxin type A and the botulinum toxin can be administered to or to the vicinity of where a patient experiences or is predisposed to experience pain or a headache.

Abstract: The invention provides processes for improving the ability of a peptide to stimulate an immune response, comprising exposing the peptide to a chemical modifying agent. It further provides compositions comprising an antigenic peptide, wherein the peptide has been treated with a chemical modifying agent to improve its ability to stimulate an immune response. It also provides methods of stimulating an immune response in a mammal, comprising administering to the mammal an effective amount of a vaccine.

Abstract: The present invention provides methods and compositions for the stimulation of immune responses. Specifically, the present invention provides methods of inducing an immune response against one or a plurality of pathogens (e.g., vaccinia virus, H5N1 influenza virus, Bacillus anthracis, C. botulinum, Y. pestis, Hepatitis B, and/or HIV, etc.) in a subject (e.g., a human subject) and compositions useful in such methods (e.g., immunogenic composition comprising nanoemulsion and one or a plurality of pathogens (e.g., inactivated by the nanoemulsion) and/or pathogen products and/or pathogen components). Compositions and methods of the present invention find use in, among other things, clinical (e.g. therapeutic and preventative medicine (e.g., vaccination)) and research applications.

Abstract: Methods for treating skin disorders by local administration of a Clostridial toxin, such as a botulinum toxin, to a patient with a skin disorder.

Abstract: A novel lipoteichoic acid (LTA) was isolated from C. difficile, the structure of which is illustrated below wherein n is an integer between 1 and 20, R3 and R4 are independently selected from C 14:0, C 16:0, C 16:1, C 18:0 or C18:1 fatty acid or any combination thereof wherein one of COR3 or COR4 may be replaced by H. Further described are conjugates comprising the novel LTA and vaccines produced using the isolated LTA and the LTA conjugates. The invention also encompasses methods of conferring immunity against C. difficile comprising administering a vaccine of the invention, and methods of detecting C. difficile using the isolated LTA of the invention.

Abstract: Methods for treating a pressure sore or for preventing development of a pressure sore by local administration of a Clostridial toxin, such as a botulinum neurotoxin, to a pressure sore or to a pressure point, or to the vicinity thereof.

Abstract: There is provided a NetB epitope polypeptide comprising at least 10 contiguous amino acids from SEQ ID NO:1 and comprising a mutation in at least one position between amino acids 130 and 297 as compared with the equivalent position in SEQ ID the mutation preferably being located within a rim domain, the polypeptide being capable of binding an antibody which binds to SEQ ID NO:1 and having reduced toxicity compared with the toxicity of SEQ ID NO:1. The polypeptide is useful to vaccinate a subject against infection by Clostridium perfringens.

Abstract: An isolated polypeptide comprising a botulinum neurotoxin C1 light chain having a modified amino acid sequence relative to the sequence of a wild-type botulinum neurotoxin C1 light chain is disclosed. The modified botulinum neurotoxin C1 light chain is capable of selectively cleaving syntaxin protein, but has substantially reduced or no activity against SNAP-25 as compared to wild type botulinum neurotoxin C1 light chain, and is thus useful as a research tool and in medical treatment.

Abstract: In one aspect, the invention provides a DNA molecule. The DNA molecule includes a nucleotide sequence that encodes the receptor-binding domain of Clostridium difficile toxin A or toxin B in which at least about 10% of the in-frame codons for each amino acid residue has a higher percentage use in the human genome than the corresponding in-frame codons of C. difficile toxin A or toxin B having a known sequence. Methods for generating antibodies to Clostridium difficile toxin A or toxin B, methods for reducing the risk of a C. difficile infection, and methods for treating a C. difficile are also provided.

Abstract: The present invention provides materials and methods to facilitate the transcutaneous delivery of therapeutic agents. In some embodiments, agonists of tight junctions are used in compositions to facilitate the uptake of therapeutic agents from the skin. In a particular embodiment, the present invention provides immunogenic compositions comprising a tight junction agonist and an antigen. In a particular embodiment, the present invention provides vaccine compositions comprising a tight junction agonist and an antigen.

Abstract: The subject invention provides compositions for alleviating type 1 diabetes (T1D). In preferred embodiments, the compositions comprise an effective amount of one or more antigen presenting cells (APCs) that have been pulsed with one or more bacterial isolates and/or compounds from the isolates. The bacteria used to pulse the APCs are, preferably, those that confer upon the APCs the ability to inhibit the generation of diabetes-promoting T cells. In specific embodiments, these bacteria may be, for example, Eubacteria or Clostridia. In a preferred embodiment, the APCs are dendritic cells (DCs).

Abstract: Methods of using tetanus toxin to modulate or control neural functions or nonneural cellular activities at selected sites in animals, particularly in mammals, and more particularly in humans, are provided. Pharmaceutical formulations to modulate neural functions or non-neural cellular activities of an animal at selected sites in animals, particularly in mammals, and more particularly in humans are also provided. Uses of tetanus toxin in preparation of medicaments for methods of treating clinical disorders or symptoms of animals, particularly mammals and more particularly humans are also provided.

Abstract: Treatment and procedures for treating bodily conduits involves deactivating, killing, or otherwise treating smooth muscle tissue of the conduit.

Abstract: In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. Each mutant toxin includes a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may further include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to antibodies or binding fragments thereof that binds to said immunogenic compositions. In further aspects, the invention relates to isolated nucleotide sequences that encode any of the foregoing, and methods of use of any of the foregoing compositions.