Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030552 (paresis)
 5,831 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In rats the application of 10 mg/kg 6-amino-nicotinamide (6-AN) leads to an accumulation of 6-phosphogluconate, by inhibition of 6-phosphogluconate dehydrogenase in the pentose phosphate pathway, in the cells of the spinal cord. The accumulation reaches its maximum after 18-24 h. It seems that there exists a relationship between the accumulation of 6-phosphogluconate and the lesion of the neuroglia, which is found in electron microscopic studies. Symptoms of a spastic paresis only develop later when the spinal interneurones are destroyed as a consequence of the lesion of the neuroglia. The accumulation of 6-phosphogluconate almost exceeds the 400 fold of the norm. No considerable differences are found between the effects of a dose of 35 mg 6-AN/kg and one of 10 mg 6-AN/kg. Free gluconate is identified enzymically in the cells of the spinal cords of the rats treated with 6-AN. The compound is very probably formed by dephosphorylation and diffuses into the blood. 6-Phosphogluconate is an inhibitor of the phosphoglucose isomerase. Its accumulation shifts the equilibrium towards glucose 6-phosphate. The lactate concentration decreases as compared with the untreated controls. Muscular action potentials are recorded extracellularly with a concentric needle electrode from the musculus gastrocnemius of rats treated with 6-AN. First activations of the electromyograms are found 48 h after the application of 10 mg 6-AN/kg. The electrical activities increase during the time in which a progressive destruction of the interneurones occurs. The electromyogram displays a permanent state of excitation with high amplitudes and an increased frequency. The continuity and intensity of the increased activity recorded by the electromyograph is the most important pathological finding. p-Chlorophenyl-GABA and, still more so, chlorpromazine cause temporary reduction of the excitation processes and an electromyogram nearly at rest. Under the same conditions, haloperidol is only slightly effective. The symptoms developed by the chemical destruction of the interneurones of the spinal cord, with rigidity and spasticity of the hind limbs, are suitable for testing antispastic drugs.
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PMID:Spastic paresis after 6-aminonicotinamide: metabolic disorders in the spinal cord and electromyographically recorded changes in the hind limbs of rats. 13 91

Daily doses of 6-aminonicotinamide (3-5 mg/kg) given by ip injection produced ataxia of the hind limbs progressing to an ascending paresis/paralysis, anorexia, diarrhoea and death in male and female New Zealand White and Dutch Belted rabbits. At autopsy, caecal and gastric distention were seen and the apex of the gall bladder had necrotic foci. Light microscopic lesions included atrophy and necrosis of the white lobe of Harder's gland and atrophy of seminiferous tubules with cellular necrosis, vacuolation and the presence of multinucleated giant cells. Cytoplasmic vacuolation was observed in epithelial cells from many tissues, usually in the basal portion of the cells. Vacuolation of the epithelium of the sacculus rotundus and vermiform appendix was found within the same time frame as histiocytic hyperplasia in these organs. Spongiosis and gliosis were seen in certain parts of the central nervous system. Ultrastructural alterations in the gall bladder epithelium consisted of distention of intercellular space, mild distention of perinuclear space and coalescing, intracytoplasmic, membrane-bound vacuoles, a few of which contained membranous debris. Some alterations of 6-aminonicotinamide toxicosis were prevented by simultaneous administration of nicotinamide with 6-aminonicotinamide.
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PMID:Pathology of 6-aminonicotinamide toxicosis in the rabbit. 293 36

Activity of transport ATPases was studied in erythrocyte membranes and synaptosomal fraction of cervical department of spinal cord obtained from rats in dynamics of botulinic C intoxication Na+, K+-ATPase was inhibited by the competitive type in the synaptosomal brain fraction at the preclinical period of intoxication and by the noncompetitive type at the step of skeletal muscle paresis. In erythrocyte membranes activity of Na+, K+-ATPase was inhibited by the mixed type at the preclinical period of intoxication and the enzymatic activity was inhibited by the noncompetitive type at the step of skeletal muscle paresis. The Na+, K+-ATPase from biological membranes was reactivated by unithiol and nicotinamide in dynamics of intoxication. The toxin was shown to activate Mg2+-ATPase in brain synaptosomal fraction.
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PMID:[Effect of botulinum toxin on the activity of transport ATPases in biological membranes]. 298 43

6-Aminonicotinamide, an antimetabolite of nicotinamide, given by intraperitoneal injection produced diarrhea, ascending paresis/paralysis, death, and bilateral ocular alterations in both sexes of New Zealand white and Dutch belted rabbits. Ocular vascular lesions consisted of iridal congestion with iridal hemorrhage and associated acute iritis and aqueous flare in some rabbits. Cytoplasmic swelling, vacuolation, and loss of staining affinity that represented hydropic change were present in both layers of ciliary epithelium and the inner layer of iridal epithelium. Cells in the outer layer of the iridal processes and the ciliary ridge, were most severely affected. Vacuoles were also present in the retinal pigment epithelium and scattered throughout the outer plexiform layer of the retina with a few in the inner and outer nuclear layers. Ocular alterations were prevented by simultaneous administration of nicotinamide and their development appeared related to nicotinamide deficiency. No ocular alterations were caused by nicotinamide administration alone.
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PMID:Ocular lesions of 6-aminonicotinamide toxicosis in rabbits. 315 43

To further explore the role of dietary nicotinamide in both brain development and diseases, particularly those of ageing. Articles cover neurodegenerative disease and cancer. Also discussed are the effects of nicotinamide, contained in meat and supplements and derived from symbionts, on the major transitions of disease and fertility from ancient times up to the present day. A key role for the tryptophan - NAD 'de novo' and immune tolerance pathway are discussed at length in the context of fertility and longevity and the transitions from immune paresis to Treg-mediated immune tolerance and then finally to intolerance and their associated diseases. Abstract: Nicotinamide in human evolution increased cognitive power in a positive feedback loop originally involving hunting. As the precursor to metabolic master molecule NAD it is, as vitamin B3, vital for health. Paradoxically, a lower dose on a diverse plant then cereal-based diet fuelled population booms from the Mesolithic onwards, by upping immune tolerance of the foetus. Increased tolerance of risky symbionts, whether in the gut or TB, that excrete nicotinamide co-evolved as buffers for when diet was inadequate. High biological fertility, despite disease trade-offs, avoided the extinction of Homo sapiens and heralded the dawn of a conscious, creative, and pro-fertility culture. Nicotinamide equity now would stabilise populations and prevent NAD-based diseases of poverty and affluence.
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PMID:Nicotinamide's Ups and Downs: Consequences for Fertility, Development, Longevity and Diseases of Poverty and Affluence. 3032 78