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E L Docks

Publications and source records attributed to E L Docks.

7 recordsLinked to original sources

Acute toxicity of amine-boranes and related derivatives in mice.

Three boron derivatives, i.e. trimethylamine-carbomethoxyborane, tetrakis-mu-(trimethylamine-boranecarboxylato)-bis(trimethylamine- carboxyborane)-dicopper(II), and N,N-dimethyl-n-octadecylamine borane were evaluated for acute toxicity in male mice, at 1, 2 or 5 x their therapeutic dose in rodents for pharmacological activity. Based on organ weights, clinical chemistry, hematopoietic parameters and tissue morphology, the trimethylamine-carbomethoxyborane was shown to be free of toxicity. The dicopper(II) complex and N,N-dimethyl-n-octadecylamine borane demonstrated slight toxicity with marginal disturbance in hepatic and kidney morphology. The dicopper(II) complex may cause marginal myocardial damage and the N,N-dimethyl-n-octadecylamine borane caused elevations in cholic acid. All three derivatives demonstrated reductions in hematocrit.

Animals↗

Hypolipidemic activity of some hydropolyborate salts in rodents.

A series of hydropolyborate salts were observed to possess hypolipidemic activity in rodents. Tetramethylammonium octahydrotriborate, tetramethylammonium hexahydrohexaborate, tetramethylammonium dodecahydrododecaborate and triethyl-ammonium dodecahydrododecaborate proved to be very effective in lowering serum cholesterol and triglyceride levels in CF1 mice, i.p. and Sprague Dawley rats, orally. Tissue lipids were reduced by these agents e.g. liver cholesterol, and triglyceride and small intestine mucosa cholesterol levels. [3H] Cholesterol distribution studies confirm that steroid levels are lower in most major tissues. The rat serum lipoprotein lipid content was altered by drug treatment, with cholesterol and triglyceride being reduced in the VLDL and cholesterol being reduced in the LDL. HDL cholesterol levels were elevated by drug treatment. The fecal lipids were increased with select derivatives. The enzyme activities involved in de novo synthesis of hepatic lipids were affected by the hydropolyborate salts including cytoplasmic ATP-dependent citrate lyase, acetyl CoA synthetase, acyl CoA cholesterol acyl transferase, sn-glycerol-3-phosphate acyl transferase and phosphatidylate phosphohydrolase.

Animals↗

The effects of boron hypolipidemic agents on LDL and HDL receptor binding and related enzyme activities of rat hepatocytes, aorta cells and human fibroblasts.

Two boron-containing hypolipidemic agents, N,N-dimethyl-n-octadecylamine borane and tetrakis-mu-(trimethylamine-boranecarboxylato)bis-(trimethylamine- carboxyborane)-dicopper(II) were shown to reduce significantly serum cholesterol and triglyceride levels after 14 days administration in rats. Serum low density lipoprotein (LDL) cholesterol content was reduced by both agents; however, high density lipoprotein (HDL) cholesterol was elevated by N,N-dimethyl-n-octadecylamine borane but reduced by the dicopper (II) complex. The boron agents suppressed LDL binding and internalization in hepatocytes, fibroblasts and aorta cells and elevated HDL binding and degradation in hepatocytes. Enzyme activities were modulated by the boron derivatives which would favor less cholesterol deposition in peripheral tissues and further clearance from the plaque cells.

Animals↗

Hypolipidemic activity of N,N-dimethyl-n-octadecylamine borane in rodents.

N,N-Dimethyl-n-octadecylamine borane proved to be an effective hypolipidemic agent in rodents, lowering both serum cholesterol and triglyceride levels by greater than 40% after 16 d of administration. The agent lowered serum lipid levels by inhibiting the enzymatic activity of rate-limiting enzymes of both de novo cholesterol and triglyceride pathways in the liver. The reduction led to lower levels of lipids in the liver and small intestine tissues, with a reduction of the cholesterol and triglyceride levels of the serum low density lipoprotein (LDL) fraction. Concurrently, the cholesterol level of high density lipoproteins (HDL) was significantly elevated in rats after 14 d of treatment. The drug caused an increased rate of cholesterol clearance from the body, essentially via the feces. The ability of the agent to modulate the cholesterol levels of LDL and HDL fractions suggests that the agent should be an effective agent for the treatment of hyperlipidemic states in humans.

Animals↗

Circular dichroism studies at variable temperature: urobilinoid conformation.

Measurements of the temperature dependence of the circular dichroism spectra of l-stercobilin and d-urobilin show that the conformations of these optically-active urobilinoids change with temperature between 163 and 297 degrees K. These conformational changes depend critically on the hydrogen bonding characteristics of the solvent. Thus, in methanol-glycerol (9:1), the chiral sense of the helical conformation of the dipyrrylmethene chromophore is reversed on lowering the temperature, whereas in chloroform, reversal does not occur.

Bile Pigments↗