Abstract: Fructose-1,6-diphosphate (FDP) has been shown, in double-blinded controlled clinical trials on patients with sickle cell anemia, to substantially reduce the pain suffered by such patients during the recurrent ischemic crises that are caused by red blood cell sickling. Tests on patients who have been hospitalized for such crises demonstrated that when they received an intravenous injection of FDP, they reported substantially lower pain levels during their hospital stays than control groups that received identical treatment without any FDP. Apparently, FDP has never previously been used or even tested in human clinical trials, to treat sickle cell anemia. In addition, FDP has never previously been reported to have any analgesic (pain-reducing) activity.

Abstract: Newly-created fluorenone drugs can be used to prevent, treat, or otherwise reduce damage to a brain or spinal cord following a medical crisis. These new drugs are markedly improved analogs of previously-known fluorenone compounds that were never commercialized or developed into medically useful treatments. The new analogs have the following structure: where X is a lower alkyl, substituted alkyl, or cycloalkyl group, R is selected from certain types of ether, ester, or amide groups, and Y1 and Y2 are halogen, hydrogen, or methyl. These new compounds can penetrate a blood-brain barrier and potently inhibit the unwanted release of excitotoxic neurotransmitters by astrocyte cells following an injury or insult to the brain or spinal cord. As an illustration, some of these new analogs were more than 30 times more potent than the previously known best compound in reducing aspartate release by stressed astrocytes.

Abstract: Fructose-1,6-diphosphate (FDP) is used to treat patients who are undergoing coronary artery bypass grafting (CABG) surgery. Before cardiopulmonary bypass begins, a liquid that contains FDP is intravenously infused in the patient, preferably for about 10 to 30 minutes, to allow the FDP to enter the heart and lung tissue while the heart is still beating. FDP can also be added to cardioplegia solution; in addition, FDP can be injected after bypass is terminated, but if post-bypass injection is used, steps should be taken to avoid excess lactic acid accumulation, which appears to increase the risk of atrial fibrillation. To prevent or control lactic acidosis, a buffering or alkalizing agent, such as sodium bicarbonate, or an agent which reduces lactic acid formation, such as dichloroacetate, can be used.

Abstract: Fructose-1,6-diphosphate (FDP) has been shown, in double-blinded controlled clinical trials on patients with sickle cell anemia, to substantially reduce the pain suffered by such patients during the recurrent ischemic crises that are caused by red blood cell sickling. Tests on patients who have been hospitalized for such crises demonstrated that when they received an intravenous injection of FDP, they reported substantially lower pain levels during their hospital stays than control groups that received identical treatment without any FDP. Apparently, FDP has never previously been used or even tested in human clinical trials, to treat sickle cell anemia. In addition, FDP has never previously been reported to have any analgesic (pain-reducing) activity.

Abstract: Neuroprotective drugs are disclosed with at least 3 branches extending outwardly from a center atom or group, each branch having a guanidino group at its terminus. All branches preferably should be identical, and distributed around the center atom or group in a radial manner. Three branches can be bonded to a nitrogen atom, or four branches can be coupled to a carbon atom; other center groups include stable aromatic, cycloalkyl, heterocyclic, or bicyclic structures. Starting reagents are disclosed with a center atom or group, and with reactive groups (such as primary amines or hydroxyl groups) at the ends of short "spacer chains" bonded to the center atom or group. Reagents derived from arginine (an amino acid having a terminal guanidino group) can be bonded to these center components, using protective groups on the arginyl reagents to ensure desired final products with accessible guanidino groups at the ends of spacer chains.

Abstract: A method is disclosed for using fructose-1,6-diphosphate (FDP) to reduce and prevent two very serious problems caused by surgery that requires cardiopulmonary bypass. Before bypass begins, a liquid that contains FDP is intravenously injected into the patient, preferably over a period such as about 10 to 30 minutes, to allow the FDP to permeate in significant quantity into the heart and lungs while the heart is still beating. FDP can be added to the cardioplegia solution that is pumped through the heart to stop the heartbeat, and/or during bypass. This treatment was found to reduce two very important and serious problems that have unavoidably plagued CPB surgery in the past, which are: (1) elevated levels of pulmonary vascular resistance (PVR), which includes pulmonary hypertension; and (2) high occurrence rates for atrial fibrillation. Prior to this discovery, there has never been any satisfactory treatment which could reduce the severity and occurrence rates for these two major problems.

Abstract: When fructose-1,6-diphosphate (FDP) is used as an inotropic drug in patients who have undergone surgery involving cardiopulmonary bypass, it can increase the pumping strength of a struggling heart, without increasing the heartbeat rate. As such, FDP can reduce the dosages of (and in some some cases eliminate the need for) other inotropic drugs such as dobutamine, epinephrin, or amrinone lactate, which have undesired and potentially dangerous side effects, mainly involving increasing the heartbeat rate, which imposes substantial additional stresses on hearts that are struggling to regain strength after cardiopulmonary bypass surgery.

Abstract: A method and device are disclosed which enable on-site pre-diagnostic emergency treatment of people suffering from life-threatening injuries (such as victims of auto accidents, shootings, stabbings, and near-drownings), or from a collapse or loss of consciousness that might be due to a heart attack, stroke, cardiac arrest, internal hemorrhage, or various other causes that cannot be diagnosed until after a physician or ambulance has arrived on the scene. This on-site pre-diagnostic emergency treatment involves intravenous injection of fructose-1,6-diphosphate (FDP, a naturally-occurring chemical which functions as an intermediate in glycolysis) into the patient. Such injections can be administered by police, firemen, military personnel, lifeguards, nursing home attendants, ambulance attendants, or anyone else who has been trained to administer intravenous injections. The FDP should be injected into the patient as soon as possible, without delaying until the patient can be diagnosed and treated by a doctor.

Abstract: A method is disclosed for preparing a partially lyophilized (freeze-dried) powder or solidified cake containing fructose-1,6-diphosphate (FDP), a naturally-occurring intermediate in glycolysis. Preferably, about 10% to 25% residual water (by weight) is left in the powder or cake. This high moisture content does not degrade or limit FDP's stability or shelf life, and it provides for faster, less expensive processing. The methods disclosed herein also allow direct lyophilization inside a vial or other sealed container that will hold the lyophilized FDP, to avoid any need for milling, handling, or other treatment under conditions that might endanger its sterility. Lyophilized FDP can be used to create emergency injection kits which also contain aqueous solutions for mixing, and syringes and needles for injection. These kits can be carried in ambulances, police cars, firetrucks, etc.

Abstract: A method is disclosed for reducing excitotoxic damage to neurons, which can occur as a result of stroke, cardiac arrest, or other events or conditions. This method involves administering an aminoglycoside that suppresses the flow of calcium ions into neurons through N-type calcium channels. To be effective for such use, an aminoglycoside must suppress N-channel activity at a potency greater than streptomycin. Aminoglycosides which meet this criterion (which includes neomycin and Gentamicin) can suppress the depolarizing activation of neurons, which in turn controls the release of glutamate, a neurotransmitter that becomes an endogenous toxin under excitotoxic conditions. Numerous aminoglycosides were tested in in vitro screening tests using brain cell membrane fragments to evaluate N-channel blocking potency.

Abstract: AICA riboside and prodrugs of AICA riboside are provided which lower blood glucose for the treatment of various pathologic conditions, including hypoglycemia, insulin deficiency, insulin resistance diabetes and Syndrome X. Prodrugs of AICA riboside provide AICA riboside in an orally bioavailable form. The use of adenosine kinase inhibition and ZMP enhancement for lowering blood glucose are also described.

Abstract: This invention discloses a rapid-diffusion injectable formulation, comprising disulfiram or a suitable salt or analog of disulfiram. Unlike slow-release injectable formulations designed to ensure that chronic alcoholics have significant quantities of disulfiram in their blood at all time, the rapid-diffusion injectable formulation disclosed herein is designed to reduce the hypoxic or ischemic damage caused by crisis events such as stroke, heart attack, cardiac arrest, or asphyxiation. A rapid-diffusion injectable formulation can contain disulfiram mixed with water, an organic compound having a plurality of hydroxyl groups (such as pharmaceutically acceptable glycols or polysaccharides; propylene glycol, dextrans, and cyclodextrins are often used for such purposes), and a buffer.

Abstract: A method is disclosed for reducing cardiovascular damage caused by hypoxic or ischemic events such as heart attack and cardiac arrest. This method involves the administration of disulfiram, or a suitable salt or analog of disulfiram, to a mammal in need of such treatment. Disulfiram can inhibit enzymes such as xanthine oxidase which would otherwise generate oxygenated free radicals, which are highly reactive chemical compounds that non-specifically attack and damage essential molecules and cells. It can also chelate copper and iron, thereby suppressing lipid peroxidation and protecting cell membranes from destruction. It also generates metabolites such as tryptophol which reduce the rate of metabolic activity in neurons and affected tissue, which can be useful during cytotoxic events. This invention also discloses injectable formulations that rapidly release disulfiram into the circulating blood.

Abstract: A test method for identifying for and evaluating anti-seizure activity of candidate compounds is provided which shows superior sensitivity for adenosinergic activity and which is believed to be predictive of other adenosine releasing activities for the candidate compounds.