Deficiency effects cyanide

Much of the toxicological interest in cyanide relating to mammals has focused on its rapid lethal action. However, its most widely distributed toxicologic problems are due to its toxicity from dietary, industrial, and environmental factors (Way 1981, 1984 Gee 1987 Marrs and Ballantyne 1987 Eisler 1991). Chronic exposure to cyanide is correlated with specific human diseases Nigerian nutritional neuropathy, Leber s optical atrophy, retrobulbar neuritis, pernicious anemia, tobacco amblyopia, cretinism, and ataxic tropical neuropathy (Towill etal. 1978 Way 1981 Sprine etal. 1982 Beminger et al. 1989 Ukhun and Dibie 1989). The effects of chronic cyanide intoxication are confounded by various nutritional factors, such as dietary deficiencies of sulfur-containing amino acids, proteins, and water-soluble vitamins (Way 1981). 

Oral exposure to cyanide usually results from accidental, homicidal, or suicidal ingestion of cyanide salts. Sodium cyanide and potassium cyanide are the most frequently studied cyanide compounds. Copper cyanide, potassium silver cyanide, silver cyanide, and calcium cyanide are other compounds that humans could encounter through oral or dermal exposure. Cassava roots and certain fruit pits contain compounds that can be broken down to form cyanide. Cassava roots form the staple diet of some populations in Africa, Central and South America, and Asia. However, it must be noted that cassava roots are notoriously deficient in protein and other nutrients and contain many other compounds, in addition to cyanide, that could be responsible for some of the observed toxic effects. Thiocyanate is a metabolite of cyanide that is formed in the body after exposure to cyanide compounds. When possible, all oral exposures are expressed as mg CN/kg/day. 

The nervous system is the most sensitive target for cyanide toxicity, partly because of its high metabolic demands. High doses of cyanide can result in death via central nervous system effects, which can cause respiratory arrest. In humans, chronic low-level cyanide exposure through cassava consumption (and possibly through tobacco smoke inhalation) has been associated with tropical neuropathy, tobacco amblyopia, and Leber s hereditary optic atrophy. It has been suggested that defects in the metabolic conversion of cyanide to thiocyanate, as well as nutritional deficiencies of protein and vitamin B12 and other vitamins and minerals may play a role in the development of these disorders (Wilson 1965). 

A number of dietary deficiencies may increase the risk of deleterious cyanide effects. Iodine deficiency is involved in the etiology of such thyroid disorders as goiter and cretinism. These disorders may be exacerbated by excess exposure to cyanide (Delange and Ermans 1971 Ermans et al. 1972). Protein deficiencies and vitamin B12, riboflavin and other vitamins and elemental deficiencies may subject people... 

A simple tandem Michael addition of cyanide ion with alkylation on Jt-deficient alkenes has been effected on diethyl l -methylpropylidenecyanoacetates and benzyl-idenemalonates using benzyltriethylammonium chloride to yield 2-alkyl-2,3-dicyanopropanoates and the analogous 2-ethoxycarbony derivatives [44]. 

The antibody-dependent lysis of tumor cells by PMNs exhibited some of the characteristics of damage mediated by products of the burst in the presence of tumor cells there was increased consumption of O2, increased formation of O and activation of the hexose monosphosphate shunt However, although a reduction in the concentration of O2 in the medium inhibited lysis neither catalase nor superoxide dismutase inhibited. The lack of effect on these enzymes was attributed to their inability to interpose themselves between the plasma membranes of the PMN and its target. Similar conclusions were reached by Clark, and Klebanoff whose data incriminated the products of the burst by the reduced killing of tumor cells by PMNs from patients with chronic granulomatous disease. Myeloperoxidase, however, appeared not to he required since neither azide or cyanide inhibited and killing by PMNs from patients with inherited deficiency of myeloperoxidase was normal. 

Another problem associated with saturation analysis is that abnormally low results may be obtained unless cyanide is present when the vitamin is freed from its binder. It appears that forms other than cyanocobalamin are difficult to separate completely from the binding protein. Early studies that failed to recognize this not infrequently found that results from patients with pernicious anemia gave negative values (R9). A recent study by Brown et al. (B6) examined the effect of varying the concentration of cyanide used in the test. They found that an excess of cyanide resulted in a significant increase in apparent vitamin B12 levels in sera from patients who were deficient in the vitamin, but it had little effect on sera from normal patients. They found the mean of 12 vitamin B12-deficient sera to be 49 ng/liter when 3 mg/liter of cyanide was used in the extraction mixture, 104 ng/liter in the presence of 30 mg/liter of cyanide, and 196 ng/liter when 300 mg/liter of cyanide was used. The authors emphasized that cyanide was necessary to convert all of the several forms of vitamin B12 present in serum to cyanocobalamin but warned that the concentration should not be greater than 5 mg/liter. 

The only pharmacological use of vitamin B12, other than for the treatment of deficiency or for rare children with vitamin dependency diseases affecting the binding of the coenzyme to methylmalonyl CoA mutase (Section 10.8.2), is as an antidote for cyanide poisoning. Supplements of vitamin B12 are available for strict vegetarians who might be at risk of deficiency. There is no evidence of any adverse effects of high intakes of vitamin B12. 

Why did cyanide not kill Rasputin immediately It has been suggested that he had a deficiency in his stomach acid, a condition known as achlorhydric gastritis, which might have decreased the production of hydrogen cyanide from the potassium cyanide. There is no evidence for this, however, and it has been disputed the potassium cyanide should still have killed him. The cyanide had been taken with food and wine, which would have delayed the absorption and therefore slowed down the lethal effects. 

Scheme 1 shows the desired Heck reaction of alkoxy-DSB 1 with 2. The formation of 3 is accompanied by two destructive pathways the reductive debromination of 1 to 4 as a side reaction and the protodesilylation to 5 as a subsequent reaction. Particularly the latter limits the reaction conditions in terms of time and temperature. The phosphine is a decisive factor in this system consisting of three reactions a fine-tuning of the reaction conditions is possible via electronic and steric effects of the substituents in the phosphine electron-rich trialkylphosphines 6 and 7 strongly favor the reduction. Fast coupling reactions were observed with tris-o-tolylphosphine 8, the chelating diphosphine dppe 9 being even more efficient in terms of turnover, yield, and suppression of side reactions. Compared with Heck reactions of polycyclic or electron-deficient arenes with 2 [21, 22], the yield of 3 is only moderate. The reactivity of bromo-distyrylbenzenes 1 and 12 -14 in the coupling reaction is controlled by the substituents on the opposite side of the n-system (Fig. 1, Table 2) a compensation for the electron-donating alkoxy groups by a cyanide (13) or exchange of donors with electronically neutral alkyl side chains strongly improves the yields.

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