Provided is a long-acting method for preventing or treating glucose metabolism disorders that includes administering a beta-lactam compound or a pharmaceutically acceptable salt thereof to a subject in need thereof. The method for preventing or treating glucose metabolism disorders has a long-acting effect that lasts more than two days even after medication has been stopped.

Provided is a long-acting method for preventing or treating glucose metabolism disorders that includes administering a beta-lactam compound or a pharmaceutically acceptable salt thereof to a subject in need thereof. The method for preventing or treating glucose metabolism disorders has a long-acting effect that lasts more than two days even after medication has been stopped.

Provided herein are methods and compositions for treating cancer or a tumor in a subject by administering to the subject a first agent that disrupts the interaction between PD-L2/RGMb and a second agent that disrupts the interaction between PD-1/PD-L1. The subject may have dysbiosis and/or be nonresponsive to immune checkpoint therapy.

Bromine induced lactamization of vinyl acetohydroxamates facilitated syntheses of monocyclic β-lactams suitable for incorporation of a thiomethyl and extended functionality at the C(4) position. Elaboration of the resulting substituted N-hydroxy-2-azetidinones allowed incorporation of functionalized α-amino substituents appropriate for enhancement of antibiotic activity. Evaluation of antibacterial activity against a panel of Gram-positive and Gram-negative bacteria revealed structure-activity-relationships (SAR) and identification of potent new monobactam antibiotics. The corresponding bis-catechol conjugate, 42, has excellent activity against Gram-negative bacteria including carbapenemase and carbacephalosporinase producing strains of Acinetobacter baumannii which have been listed by the WHO as being of critical concern worldwide.

Bromine induced lactamization of vinyl acetohydroxamates facilitated syntheses of monocyclic β-lactams suitable for incorporation of a thiomethyl and extended functionality at the C(4) position. Elaboration of the resulting substituted N-hydroxy-2-azetidinones allowed incorporation of functionalized α-amino substituents appropriate for enhancement of antibiotic activity. Evaluation of antibacterial activity against a panel of Gram-positive and Gram-negative bacteria revealed structure-activity-relationships (SAR) and identification of potent new monobactam antibiotics. The corresponding bis-catechol conjugate, 42, has excellent activity against Gram-negative bacteria including carbapenemase and carbacephalosporinase producing strains of Acinetobacter baumannii which have been listed by the WHO as being of critical concern worldwide.

Low permeability across the outer membrane is a major reason why most antibiotics are ineffective against Gram-negative bacteria. Agents that permeabilize the outer membrane are typically toxic at their effective concentrations. Here, we report the development of a broad-spectrum homodimeric tobramycin adjuvant that is non-toxic and more potent than the gold standard permeabilizing agent, polymyxin B nonapeptide. In pilot studies, the adjuvant confers potent bactericidal activity on novobiocin against Gram-negative bacteria, including carbapenem-resistant and colistin-resistant strains bearing plasmid-borne mcr-1 genes. Resistance development to the combination was significantly reduced, relative to novobiocin alone, and there was no induction of cross-resistance to other antibiotics, including the gyrase-acting fluoroquinolones. Tobramycin homodimer may allow the use of lower doses of novobiocin, overcoming its twin-problem of efficacy and toxicity.

Low permeability across the outer membrane is a major reason why most antibiotics are ineffective against Gram-negative bacteria. Agents that permeabilize the outer membrane are typically toxic at their effective concentrations. Here, we report the development of a broad-spectrum homodimeric tobramycin adjuvant that is non-toxic and more potent than the gold standard permeabilizing agent, polymyxin B nonapeptide. In pilot studies, the adjuvant confers potent bactericidal activity on novobiocin against Gram-negative bacteria, including carbapenem-resistant and colistin-resistant strains bearing plasmid-borne mcr-1 genes. Resistance development to the combination was significantly reduced, relative to novobiocin alone, and there was no induction of cross-resistance to other antibiotics, including the gyrase-acting fluoroquinolones. Tobramycin homodimer may allow the use of lower doses of novobiocin, overcoming its twin-problem of efficacy and toxicity.

The present invention relates to a pharmaceutical composition for the treatment of sepsis or systemic inflammatory response syndrome (SIRS) comprising mitochondria as effective ingredient. When activated macrophages and monocytes are treated with mitochondria which are effective ingredient of the pharmaceutical composition of the present invention, expression of IL-1β, TNF-α and IL-6 which are pro-inflammatory cytokines can be restored to normal levels. Furthermore, when the pharmaceutical composition of the present invention is administered to a subject suffering from sepsis, the survival rate of the subject can be remarkably increased. Therefore, the pharmaceutical composition according to the present invention can be useful for the treatment of sepsis.

The present invention relates to a pharmaceutical composition for the treatment of sepsis or systemic inflammatory response syndrome (SIRS) comprising mitochondria as effective ingredient. When activated macrophages and monocytes are treated with mitochondria which are effective ingredient of the pharmaceutical composition of the present invention, expression of IL-1β, TNF-α and IL-6 which are pro-inflammatory cytokines can be restored to normal levels. Furthermore, when the pharmaceutical composition of the present invention is administered to a subject suffering from sepsis, the survival rate of the subject can be remarkably increased. Therefore, the pharmaceutical composition according to the present invention can be useful for the treatment of sepsis.

An object of the present invention is to provide a pharmaceutical composition and a kit which exhibit strong antibacterial activity against Gram-negative bacteria and/or drug-resistant Gram-negative bacteria.

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A pharmaceutical composition and a kit containing a compound represented by General Formula [1] (the meaning of each reference numeral is as described above in the present specification) or a salt thereof and one or more compounds selected from a β-lactamase inhibitory compound and an antibacterial compound have strong antibacterial activity against Gram-negative bacteria such as Pseudomonas aeruginosa and/or drug-resistant Gram-negative bacteria including multidrug-resistant Pseudomonas aeruginosa, and are useful for treating infections caused by these bacteria.