Abstract: Disclosed herein are methods, kits and compositions for treating, preventing, inhibiting, or reducing a seizure, status epilepticus, neuropathogenesis or a neuropathology caused by overstimulation of the NMDA receptor pathway and/or exposure to an OP compound.

Abstract: The compounds of the invention are generally described by the formula: B1Z*2B3Z*4X*5Q6F7X8X9X10X11, ??(1) B1X2X3X4X5Q6F7X8X9X10X11, or ??(2) B1Z2B3X4Z5Q6F7Z8X9X10X11 ??(3) and the salts, esters, amides, and acyl forms thereof. Each position represented by a letter indicates a single amino acid residue: B is a basic of polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large of hydrophobic amino acid or a modified form thereof. As described below, one or more of the peptide linkages between the amino acid residues may be replaced by a peptide linkage mimic. These compounds may be used as molecular building blocks to create compounds that are optimized for inhibiting the protease activity of Botulinum b and tetanus toxins.

Abstract: The compounds of the invention are generally described by the formula (1): B1Z*2B3Z*4X*5Q6F7X8X9X10X11, (2): B1X2X3X4X5Q6F7X8X9X10X11, or (3): B1X2B3X4Z5Q6F7Z8X9X10X11 and the salts, esters, amides, and acyl forms thereof. Each position represented by a letter indicates a single amino acid residue: B is a basic or polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large or hydrophobic amino acid or a modified form thereof. As described below, one or more of the peptide linkages between the amino acid residues may be replaced by a peptide linkage mimic. These compounds may be used as molecular building blocks to create compounds that are optimized for inhibiting the protease activity of Botulinum B and tetanus toxins.

Abstract: An assay for detecting, measuring, or monitoring the activity or concentration of at least two proteins that have similar or overlapping properties is disclosed. The assay comprises first determining the sensitivity coefficients of the substrates for each of the proteins in which the concentrations are to be determined. This method may be used for detecting, measuring, or monitoring the activity and concentration of AChE, BChE, or both in a test sample which test sample may be whole and unprocessed blood or tissue. Also disclosed are methods of using the assay to detect a subject's exposure to an agent which affects cholinesterase, determine the efficacy or progress of a treatment, determine the amount of protection provided against exposure to an agent which affects cholinesterase, or both, screen a subject for having a drug sensitivity or a particular disease, detect a change in red blood cell count of a subject, determine whether a candidate compound affects cholinesterase.

Abstract: An assay for detecting, measuring, or monitoring the activity or concentration of at least two proteins that have similar or overlapping properties is disclosed. The assay comprises first determining the sensitivity coefficients of the substrates for each of the proteins in which the concentrations are to be determined. This method may be used for detecting, measuring, or monitoring the activity and concentration of AChE, BChE, or both in a test sample which test sample may be whole and unprocessed blood or tissue. Also disclosed are methods of using the assay to detect a subject's exposure to an agent which affects cholinesterase, determine the efficacy or progress of a treatment, determine the amount of protection provided against exposure to an agent which affects cholinesterase, or both, screen a subject for having a drug sensitivity or a particular disease, detect a change in red blood cell count of a subject, determine whether a candidate compound affects cholinesterase.

Abstract: The compounds of the invention are generally described by the formula: X1X2B3X4B5X*6X7X8 B9X10B11X12B13X14 B15X16B17X*18X*19B20 X21X22X23Q24F25Z*26X27 X28B29X30B31B32X33X34 B35B36X37Z38Z39  (1) and the salts, esters, amides, and acyl forms thereof. Up to 15 amino acids may be truncated from the N-terminus and up to 6 amino acids may be truncated from the C-terminus. Each position represented by a letter indicates a single amino acid residue wherein B is a basic or polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large or hydrophobic amino acid or a modified form thereof. These compounds may be used to inhibit the protease activity of Botulinum B and tetanus toxins.

Abstract: A material comprising a porous support and a plurality of enzymes for the removal, decontamination or neutralization of hazardous chemicals such as OP compounds is disclosed. The material may be used on a variety of surfaces, including natural, synthetic and biological surfaces such as skin and other delicate membranes. Also disclosed is a process of making the material, kits and various methods and reactivation devices for reactivating the enzymatic activity of the material.

Abstract: An enzymatically active reusable sponge or foam, capable of regeneration with oximes, made of a polymer such as polyurethane is prepared for detoxification of hazardous compounds such as organophosphorus and organosulfur compounds. The foam or sponge contains a plurality of enzymes including enzymes selected from acetylcholinesterase, butyrylcholinesterase, triesterase, pseudocholinesterase, organophosphate hydrase, phosphotriesterase, paraoxonase and organophosphorus and organosulfur hydrolyzing enzymes. The sponge or foam may additionally contain activated carbon and an enzyme reactivation compound. A kit can be formed containing the sponge or foam and the compound for enzyme reactivation. The enzymatically active foam or sponge may be prepared using a two chamber device where enzymes and prepolymer are passed from separate chambers into a static mixing stator and are subjected to low shear mixing and extrusion to form by the sponge or foam.

Abstract: A material comprising a porous support and a plurality of enzymes for the removal, decontamination or neutralization of hazardous chemicals such as OP compounds is disclosed. The material may be used on a variety of surfaces, including natural, synthetic and biological surfaces such as skin and other delicate membranes. Also disclosed is a process of making the material, kits and various methods and reactivation devices for reactivating the enzymatic activity of the material.

Abstract: The compounds of the invention are generally described by the formula: B1Z*2B3Z*4X*5Q6F7X8X9X10X11  (1), B1X2X3X4X5Q6F7X8X9X10X11  (2), or B1X2B3X4Z5Q6F7Z*8X9X10X11  (3) and the salts, esters, amides, and acyl forms thereof. Each position represented by a letter indicates a single amino acid residue: B is a basic or polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large or hydrophobic amino acid or a modified form thereof. As described below, one or more of the peptide linkages between the amino acid residues may be replaced by a peptide linkage mimic. These compounds may be used as molecular building blocks to create compounds that are optimized for inhibiting the protease activity of Botulinum B and tetanus toxins.

Abstract: A reusable sponge or foam made of a polymer such as polyurethane is prepared containing a plurality of different enzymes or a cross-linked complex of the plurality of enzymes for detoxification of a diverse array of hazardous chemicals such as organophosphorus and/or organosulfur compounds. The plurality of enzymes include enzymes selected from acetylcholinesterase, butyrylcholinesterase, triesterase, pseudocholinesterase, choline oxidase, peroxidase, organophosphate hydrolase, phosphotriesterase, paraoxonase and laccase. A preferred mixture of enzymes contains organophosphate hydrolase and acetylcholinesterase or butyrylcholinesterase. The sponge or foam may additionally contain carbon, an enzyme reactivation compound and/or an indicator for measuring capacity for detoxification. The indicator can be fluorescent, chemiluminescent or visible chromogen or an electrode, and be encapsulated in a liposome or crushable packet.

Abstract: An assay for detecting, measuring, or monitoring the activity or concentration of at least two proteins that have similar or overlapping properties is disclosed. The assay comprises first determining the sensitivity coefficients of the substrates for each of the proteins in which the concentrations are to be determined. This method may be used for detecting, measuring, or monitoring the activity and concentration of AChE, BChE, or both in a test sample which test sample may be whole and unprocessed blood or tissue. Also disclosed are methods of using the assay to detect a subject's exposure to an agent which affects cholinesterase, determine the efficacy or progress of a treatment, determine the amount of protection provided against exposure to an agent which affects cholinesterase, or both, screen a subject for having a drug sensitivity or a particular disease, detect a change in red blood cell count of a subject, determine whether a candidate compound affects cholinesterase.

Abstract: Methods, compositions and materials useful in the detection of organophosphorous and organosulfur compounds are disclosed. In particular, biosensors wherein a porous or a non-porous support having an enzyme immobilized upon or within are disclosed. The biosensors exhibit enzymatic stability at extreme temperatures and/or denaturing conditions, and similar kinetic characteristics of the soluble form of the enzymes utilized. The enzyme does not leach from the porous or non-porous support and the material retains enzymatic activity after prolonged storage. Differential biosensors are also disclosed.

Abstract: Novel carbaphens are provided of the formula ##STR1## wherein R is OH, OCON(CH.sub.3).sub.2 or OCONHCH.sub.3, and R' is H, OH or sub.2 OCON(CH.sub.3).sub.2, stereoisomers thereof, pharmaceutically-acceptable salts thereof or mixtures thereof.Compositions comprise the carbaphens with pharmaceutically acceptable carriers, and they may further comprise other drugs as well.Methods of treating patients either prophylactically or therapeutically which suffer from organophosphate poisoning, coronary insufficiency, cerebral vasospasms, spastic cholitis and cholecystitis comprise the administration of the carbaphens of the invention.

Abstract: Novel carbaphens are provided of the formula ##STR1## wherein R is OH, OCON(CH.sub.3).sub.2 or OCONHCH.sub.3, and R' is H, OH or .sub.2 OCON(CH.sub.3).sub.2, stereoisomers thereof, pharmaceutically-acceptable salts thereof or mixtures thereof.Compositions comprise the carbaphens with pharmaceutically acceptable carriers, and they may further comprise other drugs as well.Methods of treating patients either prophylactically or therapeutically which suffer from organophosphate poisoning, coronary insufficiency, cerebral vasospasms, spastic cholitis and cholecystitis comprise the administration of the carbaphens of the invention.