Abstract: A process for efficiently preparing bis-tetrameric hemoglobin in which the tetramers are specifically linked at predetermined sites on the ?-sub-units and in which the tetramers themselves are effectively bonded to prevent dissociation into dimeric ??-hemoglobin sub-units therefrom is provided. The process uses as cross-linking reagent a hexafunctional aromatic acyl phosphate containing amide groups, The concept is to use a cross-linking reagent which has an excess of site-specific hemoglobin reacting groups, namely six acyl phosphate groups, so that at least four of them will react site specifically to form the bis-tetrameric product of particular therapeutic interest.

Abstract: Hemoglobin is site-specifically crosslinked into its tetrameric form by reaction with a trifunctional reagent which combines electrostatic effects, steric effects and the presence of functional groups so that two of the functional groups react with specific sites on the hemoglobin whilst the third site is left free for reaction with endogenous nucleophilic compounds. A specific example of such a crosslinking reagent is trimesoyl tris(3,5-dibromosalicylate), TTDS, which effects specific crosslinking between the amino groups of lysine-82 on each respective .beta. sub-unit. While the crosslinking reagent TTDS has three available carboxyl groups for the crosslinking reaction, only two so react, leaving one free carboxyl for reaction with exogenous nucleophiles, e.g. to render the hemoglobin product useful as a carrier for nucleophilic compounds through the body's circulatory system.

Abstract: Oxidation of C--H bonds in organic chemical compounds to C--OH bonds is accomplished by utilizing, as a monooxygenase, a heme protein such as methemoglobin or metmyoglobin in the presence of sulfate ion, in an aqueous medium.

Abstract: A modified hemoglobin comprising hemoglobin which is cross-linked with a cross-linking reagent. The cross-linking reagent is selected such that the .beta.-chains are cross-linked within the 2,3-diphosphoglycerate binding site and the linkage distance between the .beta.-chains is between about 5 to 9 angstroms. A method of preparing the modified hemoglobin and its use as a blood substitute or a plasma expander are also described.

Abstract: Sleep disorders in mammals, such as insomnia and narcolepsy, are treated by administering an effective amount of ethyl 4-acetoxybutanoate, or a closely related homolog thereof. The compounds may also be administered to mammals to cause muscle relaxation and as animal anaesthetics. Moreover the compounds appear to inhibit the release of dopamine in the brain, and are hence useful also in treatment of conditions which are associated with abnormalities of dopamine release and dopamine sensitivities, such as Parkinson's disease, schizophrenia and tardive dyskenesia.

Abstract: Sleep disorders in mammals, such as insomnia and narcolepsy, are treated by administering an effective amount of ethyl 4-acetoxybutanoate, or a closely related homolog thereof.