Encephalopathy

The alimentary symptoms may be overshadowed by neuromuscular dysfunction, accompanied by signs of motor weakness that may progress to paralysis of the exterior muscles or the wrist (wrist drop), and less often, of the ankles (foot drop). Encephalopathy, the most serious result of lead poisoning, frequendy occurs in children as a result of pica, ie, ingestion of inorganic lead compounds in paint chips this rarely occurs in adults. Nephropathy has also been associated with chronic lead poisoning (147). The toxic effects of lead may be most pronounced on the developing fetus. Consequendy, women must be particulady cautious of lead exposure (148). The U.S. Center for Disease Control recommends a blood level of less than 10 p.m per 100 mL for children. 

Acute benzene poisoning results in CNS depression and is characterized by an initial euphoria followed by staggered gait, stupor, coma, and convulsions. Exposure to approximately 4000 ppm benzene results in complete loss of consciousness. Insomnia, agitation, headache, nausea, and drowsiness may persist for weeks after exposure (126). Continued inhalation of benzene to the point of euphoria has caused irreversible encephalopathy with tremulousness, emotional lability, and diffuse cerebral atrophy (125). In deaths arising from acute exposure, respiratory tract infection, hypo- and hyperplasia of sternal bone marrow, congested kidneys, and cerebral edema have been found at autopsy. 

Tripotassium dicitratobismuthate [57644-54-9] (bismuth subcitrate), De-Nol is a buffered aqueous suspension of a poorly defined, water-insoluble bismuth compound. It is said to very effective for the treatment of gastric and duodenal ulcers (180,184). There have not yet been any reports of bismuth encephalopathy following the use of this dmg. 

Bihmbin oxidase [80619-01 -8] derived from Mjrothecium verrucaria was modified with polyethyleneglycol when this conjugate was injected intravenously to jaundiced rats, the plasma bihmbin dropped to normal levels. This approach might have potential in the treatment of hyperbihmbinemia, fulminant hepatitis, and neonatal bihmbin encephalopathy (177). 

Chemistry and molecular biology of transmissible spongiform encephalopathies 97AG(E)1674. 

Beri-beri or clinically manifest thiamin deficiency exists in several subforms infantile beri-beri and adult beri-beri. Infantile beri-beri occurs in exclusively breastfed infants of thiamin-deficient mothers. Adults can develop different forms of the disease, depending on their constitution, environmental conditions, the relative contribution of other nutrients to the diet as well as the duration and severity of deficiency. First of all, there is a so called dry or atrophic (paralytic or nervous) form, including peripheral degenerative polyneuropathy, muscle weakness and paralysis. Second, a wet or exudative (cardiac) form exists. In this form, typical symptoms are lung and peripheral oedema as well as ascites. Finally, there is a cerebral form, that can occur as Wernicke encephalopathy or Korsakoff psychosis. Tli is latter form mostly affects chronic alcoholics with severe thiamin deficiency. 

Reye syndrome is a rare disorder in children, characterized by a combination of severe liver disorder and encephalopathy (central nervous system (CNS) disturbances) that can follow an acute viral illness and which has a relatively high mortality. It has been found to be... 

Hypoxic-ischemic encephalopathy in asphyxiated full-term infants... 

Thiamin has a very low toxicity (oral LD5o of thiaminchloride hydrochloride in mice 3-15 g/kg body weight). The vitamin is used therapeutically to cure polyneuropathy, beri-beii (clinically manifest thiamin deficiency), and Wernicke-Korsakoff Syndrome ( Wernicke encephalopathy and Korsakoff psychosis). In mild polyneuropathy, 10-20 mg/d water-soluble or 5-10 mg/d lipid-soluble thiamin are given orally. In more severe cases, 20-50 mg/d water-soluble or 10-20 mg/d lipid-soluble thiamin are administered orally. Patients suffering from beri-beri or from early stages of Wernicke-Korsakoff Syndrome receive 50-100 mg of thiamin two times a day for several days subcutaneously or intravenously until symptoms are alleviated. Afterwards, the vitamin is administered orally for several weeks. 

Appendices This section is most likely to contain additional data associated with biological-based products. It should contain information as regards the facilities and equipment used for the manufacture of biotech products. Assessment of the risk of contamination from adventitious agents such as transmissible spongiform encephalopathy agents (TSEs), bacteria, mycoplasma, fungi or viruses should also be provided. Additional information on novel excipients that have not been used before should also be included in this section. 

D. Specific measures concerning prevention of transmission of animal Spongiform Encephalopathies (TSEs) (if applicable)... 

This complex consists of four subunits, all of which are encoded on nuclear DNA, synthesized on cytosolic ribosomes, and transported into mitochondria. The succinate dehydrogenase (SDH) component of the complex oxidizes succinate to fumarate with transfer of electrons via its prosthetic group, FAD, to ubiquinone. It is unique in that it participates both in the respiratory chain and in the tricarboxylic acid (TC A) cycle. Defects of complex II are rare and only about 10 cases have been reported to date. Clinical syndromes include myopathy, but the major presenting features are often encephalopathy, with seizures and psychomotor retardation. Succinate oxidation is severely impaired (Figure 11). 

Succinylcholine-induced rhabdomyolysis Hypoxic encephalopathy Intrathecal administration of constant agents Defective temperature-monitoring devices Stimulation during light anesthesia... 

Behar KL, Rothman DL, Petersen KF, et al Preliminary evidence of low cortical GABA levels in localized 1FF-MR spectra of alcohol-dependent and hepatic encephalopathy patients. Am J Psychiatry 136 952-954, 1999... 

Knox JW, Nelson JR Permanent encephalopathy from toluene inhalation. N Engl J Med 275 1494-1496, 1966... 

Feldman RG, White RF, Eriater II (1993) Trimethyltin encephalopathy. Archives of Neurology, 50(12) 1320-1324. 

The transmissible spongiform encephalopathies, or prion diseases, are fatal neurodegenerative diseases characterized by spongiform changes, astrocytic gliomas, and neuronal loss resulting from the deposition of insoluble protein aggregates in neural cells. They include Creutzfeldt-Jakob disease in humans, scrapie in... 

Prions—protein particles that lack nucleic acid— cause fatal transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, scrapie, and bovine spongiform encephalopathy. Prion diseases involve an altered secondary-tertiary strucmre of a namrally occurring protein, PrPc. When PrPc interacts with its pathologic isoform PrPSc, its conformation is transformed from a predominantly a-helical strucmre to the P-sheet strucmre characteristic of PrPSc. 

The condition known as fatal infantile mitochondrial myopathy and renal dysfunction involves severe diminution or absence of most oxidoreductases of the respiratory chain. MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke) is an inherited condition due to NADHiubiquinone oxidoreductase (complex I) or cytochrome oxidase deficiency. It is caused by a muta-... 

Thiamin deficiency can result in three distinct syndromes a chronic peripheral neuritis, beriberi, which may or may not be associated with heart ilure and edema acute pernicious (fulminating) beriberi (shoshin beriberi), in which heart failure and metabolic abnormalities predominate, without peripheral neuritis and Wernicke s encephalopathy with KorsakofPs psychosis, which is associated especially with alcohol and dmg abuse. The central role of thiamin diphosphate in... 

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