glycogen and Thiamine-Deficiency

The pharmacological and toxicological properties of furazolidone have been briefly reviewed. Among the most important pharmacological actions of furazolidone is the inhibition of mono- and diamine oxidase activities, which seem to depend, at least in some species, on the presence of the gut flora. The drug also seems to interfere with the utilization of thiamin, which is probably instrumental in the production of anorexia and loss of body weight of the treated animals. Furazolidone is known to induce a condition of cardiomyopathy in turkeys, which could be used as a model to study alpha 1-antitrypsin deficiency in man. The drug is most toxic to ruminants. The toxic signs observed were of nervous nature. Experiments are in progress in this laboratory to try to explain the mechanism(s) by which this toxicity is brought about. It is uncertain whether the use of furazolidone at the recommended therapeutic dose would result in drug residues in tissues of treated animals. This is a matter of public health importance as the drug has been shown to possess a carcinogenic activity. It is important that a simple and reliable method of identification and estimation of furazolidone residues be devised. More work is needed to elucidate the mode of action and biochemical effects caused by the drug in both the host and the infective organisms.

Topics: Adrenal Glands; Alcoholism; Animals; Anorexia; Brain; Cardiomyopathies; Cattle; Chick Embryo; Chickens; Chromatography, High Pressure Liquid; Ducks; Female; Furazolidone; Glycogen; Guinea Pigs; Humans; In Vitro Techniques; Liver; Mice; Monoamine Oxidase Inhibitors; Poultry Diseases; Pregnancy; Rabbits; Rats; Thiamine Deficiency; Turkeys

The causality of vascular and parenchymal damage to the central nervous system (CNS) was examined in rats with thiamine deficiency. Male Sprague-Dawley rats were divided into two groups; one was given a thiamine-deficient diet (TDD) and injected intraperitoneally with 10 micrograms/100 g bodyweight pyrithiamine (PT) in order to analyze morphometrically the topographical and sequential relationship between vascular and parenchymal changes and vasodilatation, and the other was given a TDD and 50 micrograms/100 g bodyweight PT in order to determine hemorrhagic sites using serial sections. Histological examination showed that spongiotic change occurred selectively in the inferior colliculus (100%) from day 19, and thereafter in the thalamus (95%), mammillary body (50%) and nuclei olivaris and vestibularis of the pons (25%), with or without hemorrhage. Simultaneously, glycogen accumulation was also observed in these regions at a frequency similar to that of hemorrhage. Ultrastructurally, however, hydropic swelling of astrocytic and neuronal processes without glycogen accumulation was observed as early as day 9 in the inferior colliculus, at which time an increase of glial fibrillary acidic protein-positive processes was also recognized. The superior colliculus was completely spared. From day 22 vasodilatation of the inferior colliculus occurred, concomitantly with bodyweight loss and neurological symptoms. Twenty-two examined hemorrhages, which occurred in the thalamus and inferior colliculus, were distributed along the arterioles or capillaries on the arterial side. In conclusion, the morphological CNS changes caused by thiamine deficiency with administration of low-dose PT in rats begin as hydropic swelling of neuronal and astrocytic processes, followed by hemorrhage and, thereafter, by vasodilation. The predilection for hemorrhage on the arterial side without parenchymal changes suggests that petechial hemorrhage is not simply secondary to parenchymal changes, but is due to hemodynamic change resulting from thiamine deficiency-induced vascular dysfunction.

Topics: Animals; Antimetabolites; Ataxia; Body Weight; Brain; Cerebral Hemorrhage; Glial Fibrillary Acidic Protein; Glycogen; Hypothermia; Immunohistochemistry; Inferior Colliculi; Male; Mammillary Bodies; Pyrithiamine; Rats; Rats, Sprague-Dawley; Seizures; Thalamus; Thiamine Deficiency; Vasodilation; Wernicke Encephalopathy

Topics: Adenosine Triphosphate; Animals; Diet; Energy Metabolism; Female; Glucose; Glycogen; Lactates; Lactic Acid; Mice; Phosphocreatine; Pyridinium Compounds; Pyrithiamine; Spinal Cord; Tectum Mesencephali; Thiamine Deficiency; Vestibular Nuclei; Vestibular Nucleus, Lateral

Topics: Animals; Cerebellar Diseases; Female; Glycogen; Male; Microscopy, Electron; Microscopy, Phase-Contrast; Nerve Fibers, Myelinated; Rats; Thiamine Deficiency

Topics: Animals; Carbon Dioxide; Carbon Isotopes; Female; Glycogen; Glyoxylates; Keto Acids; Liver; Male; Oxidation-Reduction; Protein Deficiency; Pyruvates; Rats; Thiamine Deficiency