1. A method of treating or preventing an axonopathy in a mammal in need thereof, the method comprising administering to the mammal an effective amount of an agent that acts by increasing NAD activity in diseased andor injured neurons andor supporting cells.
2. A method according to claim 1, wherein the agent is NAD, NADH, an intermediate of a de novo pathway for synthesizing NAD, an intermediate of an NAD salvage pathway, an intermediate of a nicotinamide riboside kinase pathway or a combination thereof.
3. A method according to claim 2, wherein the agent is NAD, nicotinamide mononucleotide, nicotinic acid mononucleotide or nicotinamide riboside.
4. A method according to claim 1, wherein the agent comprises an enzyme of a de novo pathway for synthesizing NAD, an enzyme of a NAD salvage pathway or an enzyme of a nicotinamide riboside kinase pathway; a nucleic acid encoding an enzyme of a de novo pathway for synthesizing NAD, an enzyme of a NAD salvage pathway or an enzyme of a nicotinamide riboside kinase pathway; an agent that increases expression of an enzyme of a de novo pathway for synthesizing NAD, an enzyme of a NAD salvage pathway or an enzyme of a nicotinamide riboside kinase pathway; or an agent that increases catalytic activity andor stability of an enzyme of a de novo pathway for synthesizing NAD, an enzyme of a NAD salvage pathway or an enzyme of a nicotinamide riboside kinase pathway.
5. A method according to claim 4, wherein the agent comprises a nicotinamide mononucleotide adenylyltransferase (NMNAT) or a nucleic acid encoding an NMNAT.
6. A method according to claim 5, wherein the agent comprises an enzyme having NMNAT activity and at least 50% identity with a human NMNAT1 or at least 50% identity with a human NMNAT3.
7. A method according to claim 6, wherein the agent has at least 70% identity with a human NMNAT1 or at least 70% identity with a human NMNAT3.
8. A method according to claim 5, wherein the agent is selected from the group consisting of a human NMNAT1, a human NMNAT3 and conservatively substituted variants thereof.
9. A method according to claim 5, wherein the agent comprises a nucleic acid having at least 50% identity with a nucleic acid encoding a human NMNAT1 or a nucleic acid having at least 50% identity with a nucleic acid encoding a human NMNAT3.
10. A method according to claim 9, wherein the agent comprises a nucleic acid having at least 70% identity with a nucleic acid encoding a human NMNAT1 or a nucleic acid having at least 70% identity with a nucleic acid encoding a human NMNAT3.
11. A method according to claim 10, wherein the agent comprises a nucleic acid encoding a human NMNAT1 or a human NMNAT3 or a nucleic acid variant thereof.
12. A method according to claim 1, wherein the axonopathy is hereditary or congenital or associated with neurodegenerative disease, motor neuron disease, neoplasia, endocrine disorder, metabolic disease, nutritional deficiency, an autoimmune disease, mechanical injury, chemical or drug-induced injury, thermal injury, radiation injury, nerve compression, retinal or optic nerve disorder, mitochondrial dysfunction, progressive dementia, demyelinating diseases, ischemia andor stroke, infectious disease; or inflammatory disease.
13. A method according to claim 12, wherein the axonopathy is induced by a cytotoxic anticancer agent.
14. A method according to claim 12, wherein the retinal or optic nerve disorder is glaucoma, retinal ganglion degeneration, optic neuritis andor degeneration, ischemic optic neuropathy, traumatic injury to the optic nerve, hereditary optic neuropathy, metabolic optic neuropathy, neuropathy due to a toxic agent or caused by adverse drug reactions or vitamin deficiency.
15. A method according to claim 12, wherein the neuropathy associated with mitochondrial dysfunction results from oxidative damage, from mutations in mitochondrial proteins encoded either in the mitochondrial genome or nuclear genome, from exposure to toxins, or from the process of aging.
16. A method according to claim 1, wherein the mammal is a human.
17. A method of treating or preventing an optic neuropathy in a mammal in need thereof, the method comprising administering to the mammal an effective amount of an agent that acts by increasing NAD activity in diseased andor injured neurons.
18. A method according to claim 17, wherein administering to the mammal comprises intraocular administering.
19. A method according to claim 18, wherein intraocular administering comprises intraocular administering of a sustained release delivery system.
20. A method according to claim 18, wherein intraocular administering comprises intravitrial injection, administration by eye drops or administration by trans-scleral delivery.
21. A method according to claim 17, wherein the agent is NAD, NADH, an intermediate of a de novo pathway for synthesizing NAD, an intermediate of a NAD salvage pathway, an intermediate of a nicotinamide riboside kinase pathway or a combination thereof.
22. A method according to claim 21, wherein the agent is NAD, nicotinamide mononucleotide, nicotinic acid mononucleotide or nicotinamide riboside.
23. A method according to claim 17, wherein the agent comprises an enzyme of a de novo pathway for synthesizing NAD, an enzyme of a NAD salvage pathway or an enzyme of a nicotinamide riboside kinase pathway; a nucleic acid encoding an enzyme of a de novo pathway for synthesizing NAD, an enzyme of a NAD salvage pathway or an enzyme of a nicotinamide riboside kinase pathway; an agent that increases expression of an enzyme of a de novo pathway for synthesizing NAD, an enzyme of a NAD salvage pathway or an enzyme of a nicotinamide riboside kinase pathway; or an agent that increases catalytic activity andor stability of an enzyme of a de novo pathway for synthesizing NAD, an enzyme of a NAD salvage pathway or an enzyme of a nicotinamide riboside kinase pathway.
24. A method according to claim 23, wherein the agent comprises a nicotinamide mononucleotide adenylyltransferase (NMNAT) or a nucleic acid encoding an NMNAT.
25. A method according to claim 23, wherein the agent comprises a nucleic acid having at least 50% identity with a nucleic acid encoding a human NMNAT1 or a nucleic acid having at least 50% identity with a nucleic acid encoding a human NMNAT3.
26. A method according to claim 25, wherein the agent comprises a nucleic acid having at least 70% identity with a nucleic acid encoding a human NMNAT1 or a nucleic acid having at least 70% identity with a nucleic acid encoding a human NMNAT3.
27. A method according to claim 26, wherein the agent comprises a nucleic acid encoding a human NMNAT1 or a human NMNAT3 or a nucleic acid variant thereof.
28. A method according to claim 17, wherein the mammal is a human.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method of making a lithographic image by
providing an imaging material comprising a support and a heat- or light-sensitive coating;
image-wise exposure of the coating to heat or light, thereby obtaining a latent image in said coating, the latent image consisting of a set of exposed areas in the coating and a set of non-exposed areas in the coating;
development of the latent image by supplying a processing liquid to the coating and evacuating, by means of a suction device, the processing liquid together with
(i) substances removed from the exposed areas without removing such substances from the non-exposed areas or
(ii) substances removed from the non-exposed areas without removing such substances from the exposed areas.
2. A method according claim 1 wherein the suction device is a porous material that is capable of absorbing the processing liquid.
3. A method according claim 1 wherein the development step is carried out by means of an apparatus comprising
an elongated housing (25) having at an end thereof an edge (29) which surrounds an opening (39);
a jet or spray nozzle (24), which is disposed in the housing and spaced from the opening (39), for jetting or spraying the processing liquid on the imaging material;
a supply channel (30) connected to the jet or spray nozzle (24) for supplying the processing liquid to the jet or spray nozzle;
a suction chamber (32) surrounding the jet or spray nozzle;
an evacuation channel (31) connected to the suction chamber (32) for maintaining a sub-pressure in the suction chamber (32) in order to remove the processing liquid from the imaging material.
4. A method according to claim 1 wherein the development step is carried out by means of an apparatus comprising
an elongated housing (1) having at an end thereof an edge (2) which surrounds an opening (3);
a jet or spray nozzle (4), which is disposed in the housing and spaced from the opening (3), for jetting or spraying the processing liquid on the imaging material through a portion (5) of the opening (3), said portion (5) having a perimeter (6);
a supply channel (10) connected to the jet or spray nozzle (4) for supplying the processing liquid to the jet or spray nozzle (4);
rubbing means (8) for mechanically treating the layer(s), which are rotatably mounted and which extend from within the housing (1) towards the opening (3) and are disposed along said perimeter (6); said rubbing means (8) and said housing (1) defining a suction chamber (9);
an evacuation channel (11) connected to the suction chamber (9) for maintaining a sub-pressure in the suction chamber (9) in order to remove the processing liquid drawn from between the rubbing means (8).
5. A method according to any preceding claims wherein the coating is not substantially ablated during the image-wise exposure.
6. A method according to any preceding claims wherein the processing liquid is an aqueous alkaline liquid.
7. A method according to any preceding claims further comprising a rinsing step in which water or an aqueous liquid is supplied to the image.
8. A method according to any of the preceding claims wherein the steps of exposure and development are carried out while the lithographic printing plate precursor is mounted in a plate-setter or a printing press.
9. A method according to any of the preceding claims wherein the support has a hydrophilic surface or is provided with a hydrophilic layer and wherein the coating is hydrophobic or is rendered hydrophobic by the exposure.