Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0152025 (polyneuropathy)
 7,862 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some organophosphorous esters cause a polyneuropathy which becomes clinically evident 2 weeks after a single dose. The pathogenesis involves modifications of a target protein, neuropathy target esterase, in the axons and a selective inhibition of retrograde axonal transport. It was suggested that copper metabolism might also be involved because of increased levels of plasma copper and ceruloplasmin in animals developing this polyneuropathy. Our results do not confirm this observation; treatment of hens with highly neuropathic single doses of two organophosphates (dihexyl-2,2-dichlorovinyl phosphate and mono-o-cresyl diphenyl phosphate) does not affect total and plasma free copper when measured several times during the development of polyneuropathy. We concluded that copper homeostasis is not affected and that copper changes are unlikely to be involved in the pathogenesis of this polyneuropathy.
 ...
PMID:Blood copper in organophosphate-induced delayed polyneuropathy. 283 31

Thioctic (alpha-lipoic) acid (TA) is a drug used for the treatment of diabetic polyneuropathy in Germany. It has been proposed that TA acts as an antioxidant and interferes with the pathogenesis of diabetic polyneuropathy. We suggest that one component of its antioxidant activity requiring study is the direct transition metal-chelating activity of the drug. We found that TA had a profound dose-dependent inhibitory effect upon Cu(2+)-catalysed ascorbic acid oxidation (monitored by O2 uptake and spectrophotometrically at 265 nm) and also increased the partition of Cu2+ into n-octanol from an aqueous solution suggesting that TA forms a lipophilic complex with Cu2+. TA also inhibited Cu(2+)-catalysed liposomal peroxidation. Furthermore, TA inhibited intracellular H2O2 production in erythrocytes challenged with ascorbate, a process thought to be mediated by loosely chelated Cu2+ within the erythrocyte. These data, taken together, suggest that prior intracellular reduction of TA to dihydrolipoic acid is not an obligatory mechanism for an antioxidant effect of the drug, which may also operate via Cu(2+)-chelation. The R-enantiomer and racemic mixture of the drug (alpha-TA) generally seemed more effective than the S-enantiomer in these assays of metal chelation.
 ...
PMID:Thioctic (lipoic) acid: a therapeutic metal-chelating antioxidant? 760 37

Eighty-six workers exposed to zinc phosphide (Zn3P2) pesticide were studied for evidence of neuropsychiatric manifestations. They were evaluated clinically, by electroencephalography (EEG), and, in some cases, by electromyography (EMG). All were males (mean age, 35.8 years; mean duration of exposure to zinc phosphide, 11.3 years). Most presented with one (or more) neuropsychiatric symptom(s), including fear of poisoning, anxiety, impotence, and easy fatigue. About half showed evidence of neuropsychiatric signs, including hyperreflexia, polyneuropathy, lumber radiculopathy, and cervical myelopathy, as well as anxious mood, impaired attention, and psychomotor stimulation. EEG recordings showed abnormal findings in 17.4% of the subjects. The mean age in that group was 39.1 years; mean duration of exposure to Zn3P2 was 15.1 years. EMG studies showed evidence of partial denervation of the anterior tibial group of muscles and flexor digiti minimi in 2 of the 30 workers (6.7%) who underwent EMG examination. Serum levels of zinc (Zn) and cadmium (Ca) were significantly higher in exposed workers than in controls (P < 0.005). Serum copper (Cu), iron (Fe), phosphorus (P), and magnesium (Mg) were significantly lower in exposed workers than in controls. Electrophoretic pattern of globulin showed that gammaglobulin fraction was significantly increased (P < 0.005); alpha2 and beta-globulin were decreased (P < 0.005) in exposed workers. Lipoprotein pattern showed that the total lipids, B-lipoprotein, and B/alpha ratio were significantly increased (P < 0.005) in exposed workers; the alpha1 lipoprotein was decreased. Triglycerides and cholesterol were significantly increased (P < 0.001), and phospholipids and phospholipid/cholesterol ratio were significantly decreased (P < 0.005) in exposed workers compared to controls. The study findings indicated that exposure to Zn3P2 not only caused mild acute and subacute liver cell damage, but also affected renal function and perhaps B-cells of the pancreas. A total of 68.6% of the exposed workers had chest symptoms; only 24.4% presented with chest or cardiac signs. Ventilatory functions were abnormal in 70% of the exposed workers; abnormal ECG findings were present in 12.8%.
 ...
PMID:Neuropsychiatric syndromes and occupational exposure to zinc phosphide in Egypt. 931 48

Acquired copper deficiency constitutes an under-recognised cause of myelopathy. Aim of the study was to describe the clinical and imaging features at admission and after copper supplementation of a patient with acquired copper deficiency myeloneuropathy. A 73-year-old woman presented with anaemia and signs of posterior column dysfunction. Somatosensory evoked potentials showed impaired central pathway conduction. Serum copper and caeruloplasmin levels were low. Nerve conduction assessment revealed axonal polyneuropathy. Spinal magnetic resonance imaging (MRI) showed posterior column hyperintensity. Diffusion tensor imaging disclosed decreased fractional anisotropy (FA) corresponding to the hyperintensity. Copper supplementation normalised the haematological picture, whereas vibratory sensitivity was only slightly improved. Control MRI revealed a slight hyperintensity at C1-C2 level; FA values normalised. In conclusion, in acquired copper-deficiency-associated myelopathy, correction of blood and MRI alterations precedes that of neurological manifestations, which may remain suboptimal.
 ...
PMID:Myeloneuropathy due to copper deficiency: clinical and MRI findings after copper supplementation. 1976 78

This paper presents a review of the effect of arsenic (As) and its inorganic compounds on the nervous system. In humans, inhalation exposure mostly occurs in occupational conditions. In the occupational environment, the most extensive exposure to this element is observed in the copper industry. Chronic As poisoning is manifested by skin and mucous membrane lesions, impairment of the nervous system in the form of disorders of psychic functions and polyneuropathies, retrobulbar neuritis, disorders of peripheral circulation and the risk for Raynaud's syndrome. Arsenic-induced polyneuropathy is usually a very serious and chronic disease. A complete recovery is observed in only 15-20% of patients. As-induced encephalopathy is an irreversible process.
 ...
PMID:[Nervous system disorders induced by occupational exposure to arsenic and its inorganic compounds: a literature review]. 2018

Wilson's Disease (WD) is an autosomal recessive disorder of copper metabolism resulting in a pathological accumulation of this metal, initially in the liver and later in other organs, mainly brain. Treatment with copper chelating agents and zinc salts results in a depletion of copper deposits and prevents or reverses the clinical manifestations. Copper deficiency may cause haematological and neurological changes, the latter principally being polyneuropathy and myelopathy. We report a patient with WD who developed a myelopathy associated with a deficiency of copper following prolonged treatment with D-penicillamine and zinc salts.
 ...
PMID:Myelopathy secondary to copper deficiency as a complication of treatment of Wilson's disease. 2260 46

Neurologic complications of bariatric surgery have become increasingly recognized with the rising numbers of procedures and the increasing prevalence of obesity in the US. Deficits are most commonly seen with thiamine, vitamin B(12), folate, vitamin D, vitamin E, and copper deficiencies. The neurological findings observed with these nutritional deficiencies are variable and include encephalopathy, optic neuropathy, myelopathy, polyradiculoneuropathy, and polyneuropathy. We review the neurological complications of bariatric surgery and emphasize that these findings may vary based on the specific type of bariatric surgery and time elapsed from the procedure.
 ...
PMID:The Neurological Complications of Nutritional Deficiency following Bariatric Surgery. 2297 Mar 51

We report a case of double domino liver transplantation in a 32-year-old woman who was diagnosed with familial amyloid polyneuropathy (FAP) and liver dysfunction. A two-stage surgical plan was designed, and one domino graft was implanted during each stage. During the first stage, an auxiliary domino liver transplantation was conducted using a domino graft from a 4-year-old female child with Wilson's disease. After removing the right lobe of the FAP patient's liver, the graft was rotated 90 degrees counterclockwise and placed along the right side of the inferior vena cava (IVC). The orifices of the left, middle, and right hepatic veins were reconstructed using an iliac vein patch and then anastomosed to the right side of the IVC. Thirty days later, a second domino liver graft was implanted. The second domino graft was from a 3-year-old female child with an ornithine carbamyl enzyme defect, and it replaced the residual native liver (left lobe). To balance the function and blood flow between the two grafts, a percutaneous transcatheter selective portal vein embolization was performed, and "the left portal vein" of the first graft was blocked 9 mo after the second transplantation. The liver function indices, blood ammonia, and 24-h urinary copper levels were normal at the end of a 3-year follow-up. These two domino donor grafts from donors with different metabolic disorders restored normal liver function. Our experience demonstrated a new approach for resolving metabolic disorders with domino grafts and utilizing explanted livers from children.
 ...
PMID:First case of cross-auxiliary double domino donor liver transplantation. 2920 35

Recessive mutations in the mitochondrial copper-binding protein SCO2, cytochrome c oxidase (COX) assembly protein, have been reported in several cases with fatal infantile cardioencephalomyopathy with COX deficiency. Significantly expanding the known phenotypic spectrum, we identified compound heterozygous variants in SCO2 in two unrelated patients with axonal polyneuropathy, also known as Charcot-Marie-Tooth disease type 4. Different from previously described cases, our patients developed predominantly motor neuropathy, they survived infancy, and they have not yet developed the cardiomyopathy that causes death in early infancy in reported patients. Both of our patients harbour missense mutations near the conserved copper-binding motif (CXXXC), including the common pathogenic variant E140K and a novel change D135G. In addition, each patient carries a second mutation located at the same loop region, resulting in compound heterozygote changes E140K/P169T and D135G/R171Q. Patient fibroblasts showed reduced levels of SCO2, decreased copper levels and COX deficiency. Given that another Charcot-Marie-Tooth disease gene, ATP7A, is a known copper transporter, our findings further underline the relevance of copper metabolism in Charcot-Marie-Tooth disease.
 ...
PMID:SCO2 mutations cause early-onset axonal Charcot-Marie-Tooth disease associated with cellular copper deficiency. 3008 72