A syringe (1) comprises a barrel (2), a stopper (3) and a plunger (4). The barrel (2) has a hollow interior, an orifice (21) and an opening (22) opposite to the orifice (21). The stopper (3) is arranged in the hollow interior of the barrel (2) thereby defining a sealed chamber (5) in the interior of the barrel (2). The stopper (3) is displaceable in the interior of the barrel (2) thereby varying a volume of the chamber (5). The plunger (4) extends through the opening (22) of the barrel (2) into the hollow interior of the barrel (2). The plunger (4) has a distal end (41) outside of the barrel (2) and a proximal end (42) inside the hollow interior of the barrel (2). The stopper (3) has a distal face (31) directed towards the plunger (4), a proximal face (32) directed towards the chamber (5) and an internal cavity (33) opening at the distal face (31). The syringe (1) is equipped with a sealing structure sealing the cavity (33) of the stopper (3) such that the cavity (33) of the stopper (3) is microbiologically sealed.

The invention relates to a derivative of a GLP-1 analogue of a general Formula I, which derivative comprises a side chain attached to a Lys residue at position 34, 35, 36, 37, or 38 of the GLP-1 analogue, which side chain comprises a Branched linker, a 1.sup.st and a 2.sup.nd Protractor selected from C18 diacid, C20 diacid, and sulfonic acid C16, and at least one Linker element-1 incorporating ethylene glycol units. Linker element-1 may be incorporated in an optional Pre-linker, and/or in a 1.sup.st or 2.sup.nd Post-linker. The invention also relates to novel GLP-1 analogues, novel side chain intermediate products and their manufacture and use to prepare derivatives of biologically active peptides and proteins, as well as pharmaceutical compositions and medical uses of the analogues and derivatives. The derivatives have very long half-lives while maintaining a satisfactory potency, which makes them potentially suitable for once-monthly administration.

The present invention provides compounds, compositions thereof, and methods of using the same.

Cranial placodes are embryonic structures essential for sensory and endocrine organ development. The efficient derivation of cranial placodes from human pluripotent stem cells is disclosed where the timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Further fate specification at the pre-placode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers and anterior pituitary hormone-producing cells that upon transplantation produce hormones including, but not limited to, human growth hormone and adrenocortiocotropic hormone in vivo. Alternatively, anterior pituitary hormone-producing cells are generated in cell culture systems in vitro.

The present disclosure provides an ophthalmic composition comprising 4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate or its pharmaceutically acceptable salts; about 0.01% weight/volume to about 1.0% weight/volume of a buffer; and about 0.01% weight/volume to about 10% weight/volume of a tonicity agent.

Provided are methods and compositions for maintaining the viability of photoreceptor cells following retinal detachment. The viability of photoreceptor cells can be preserved by administering an apoptosis inhibitor to a mammal having an eye with retinal detachment. The apoptosis inhibitor maintains the viability of the photoreceptor cells until such time that the retina becomes reattached to the underlying retinal pigment epithelium and choroid. The treatment minimizes the loss of vision, which otherwise may occur as a result of retinal detachment.

The present invention provides compositions and methods for modulating one or more phenotypes of a macrophage-related cell, e.g., a macrophage. The invention further provides methods of treating disease by modulating macrophage phenotype. Representative phenotypes include pro-inflammatory, anti-inflammatory, immunogenic, tolerogenic, tissue-destructive, tissue restorative, cytotoxic, migratory, bone-resorbing, pro-angiogenic, anti-angiogenic, suppressor, antigen presentation, or phagocytic. Representative diseases include atherosclerosis, arthritis, and multiple sclerosis.

The invention relates generally to methods and compositions for treating conditions associated with angiogenesis, and, more specifically, the invention relates to methods and compositions for treating conditions associated with angiogenesis using vascular adhesion protein-1 (VAP-1) inhibitors. The invention also relates to methods and compositions for treating conditions associated with lymphangiogenesis using VAP-1 inhibitors.

This invention provides, but is not limited to, novel oleanolic acid derivatives having the formula:

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wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds, methods and intermediates useful for making the compounds, and methods of using the compounds and compositions.

The present invention provides novel compounds useful as proteasome inhibitors. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.