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Biomedical subjects

R V Blanke

Publications and source records attributed to R V Blanke.

At least 37 records · Page 2Linked to original sources

Preferential binding of chlordecone to the protein and high density lipoprotein fractions of plasma from humans and other species.

The preferential distribution of the relatively nonpolar pesticide chlordecone (CD) to liver rather than to fat tissues in humans suggests that it may be transported in plasma differently from other organochlorine pesticides. The plasma binding of [14C] CD was investigated in vitro in human, rat, and pig plasma and in vivo in rat plasma. Protein and lipoprotein fractions were separated by serial ultracentrifugation. Heparin-manganese precipitation and agarose gel electrophoresis were also carried out to determine whether separation techniques altered CD binding to plasma components. In human plasma, the distribution of [14C] CD among proteins and high density, low density, and very low density lipoproteins (HDL, LDL, and VLDL) was 46, 30, 20, and 6%, respectively. The distribution of cholesterol in the same plasma fractions was 4, 20, 63, and 7%, respectively. In the pig and rat the order of binding was similar to that in humans, with protein greater than or equal to HDL greater than LDL greater than or equal to VLDL. Separation by heparin-Mn precipitation confirmed the results obtained by ultracentrifugation. The distribution of [14C] CD in rat lipoprotein was similar whether the CD was administered in vivo or incubated with plasma in vitro, with approximately 80% bound to HDL, 11% to LDL, and 9% to VLDL in either case. Agarose gel electrophoresis of plasma-bound [14C] CD indicated that albumin was the major component of the protein fraction responsible for CD binding. Preferential binding of CD by albumin and HDL may explain its unusual tissue distribution compared to other organochlorine pesticides such as aldrin and dieldrin, which bind preferentially to VLDL and LDL and distribute preferentially to fat tissues.

Animals↗

Excretion of chlordecone by the gastrointestinal tract: evidence for a nonbiliary mechanism.

Workers exposed to chlordecone (Kepone), a toxic organochlorine pesticide, excreted larger amounts of chlordecone in bile than in stool, suggesting that it may undergo enterohepatic recirculation. We found in a single subject that equal amounts of chlordecone and of its reduced metabolite, chlordecone alcohol, were excreted in bile at a rate four times as great as in stool. When biliary contents were diverted from the intestine through a T tube, fecal excretion of chlordecone alcohol was abolished, presumably due to interruption of its passage via bile to intestine. This change was not accompanied by disappearance of chlordecone from the stool. The amount of chlordecone in stool when bile was diverted was increased six- to tenfold over that when diverted bile was continuously infused into the duodenum. Analogous experiments with [14C]-chlordecone-treated rats in which bile flow was exteriorized through a plastic cannula showed that the excretion of radioactivity in feces was in the same range when bile was reinfused in the duodenum or was totally diverted. Moreover, in rats with bile diverted, cholestyramine, an anion-exchange resin which binds chlordecone in vitro, doubled the excretion of radioactivity in stool. A similar effect was observed in intact animals. We conclude that chlordecone enters the intestinal lumen from a nonbiliary source, probably the gut, and that net excretion of chlordecone from this source can be augmented by cholestyramine.

Bile↗

Treatment of chlordecone (Kepone) toxicity with cholestyramine. Results of a controlled clinical trial.

Industrial workers exposed to the organochlorine pesticide, chlordecone (Kepone), had signs of toxicity in several organs. The extent of toxicity was proportional to the levels of this chemical in the tissues. In 22 patients, chlordecone was eliminated slowly from blood (half time of 165 +/- 27 days--mean +/- S.E.M.) and fat (half time of 125 days, with a range of 97 to 177), chiefly in the stool. Output of chlordecone in bile was 10 to 20 times greater than in stool, suggesting that chlordecone is reabsorbed in the "ntestine. Cholestyramine, an anion-exchange resin that binds chlordecone, increased its fecal excretion by seven times. In a five-month trial, cholestyramine significantly accelerated elimination of chlordecone from blood, with a half life of 80 +/- 4 days (S.E.M.) (P less than 0.005) and fat (half life of 64 days, with a range of 52 to 85) (P less than 0.05). Cholestyramine offers a practical means for detoxification of persons exposed to chlordecone and possibly to other lipophilic toxins.

Adolescent↗

Acute corneal injury by mustard gas.

Described is an acute ocular injury caused by mustard gas. The clinical course was similar to what has been established by laboratory research. Some of the histopathologic events have been discussed in theory since no tissue sample from this reported case was available for examination.

Acute Disease↗

Blood organochlorine pesticide levels in Virginia residents.

This study attempts to establish 1972 baseline levels for 31 organochlorine pesticides and industrial chemicals in postmortem human whole blood in Virginia. These pesticides and industrial chemicals have been detected previously in other parts of the food chain and environment. In the present study DDT and its metabolites, DDE and TDE, were detected most frequently and at highest levels. DDT and DDE tended to appear more frequently as people grew older although TDE levels remained constant. Dieldrin and lindane showed peak levels in the middle age group. Analyzing distribution of pesticides in blood by sex showed that females had higher levels of lindane and dieldrin and males had higher levels of DDT, DDE, and TDE. Analyzing racial distribution showed blacks with higher levels of DDT, TDE, and DDE and indicated little difference from whites for lindane and dieldrin. Higher levels were found in Richmond and Norfolk than in the Fairfax and Roanoke regions.

Adolescent↗

Marihuana.

Explore the source record for details and available documents.

Cannabis↗

Chlordecone alcohol formation in the Mongolian gerbil (Meriones unguiculatus): a model for human metabolism of chlordecone (kepone).

In seeking a practical animal model of chlordecone metabolism in humans, we found that among rats, hamsters, guinea pigs, or gerbils treated with a single injection of chlordecone, only in gerbils was this organo-chlorine pesticide converted to chlordecone alcohol, a reduced metabolite found in the stool of chlordecone poisoned humans. Analogous to these patients, chlordecone treated gerbils eliminated chlordecone alcohol exclusively in stool with none being detected in urine. Moreover, the gerbils excreted chlordecone alcohol in bile in an amount more than twice that of chlordecone and in the form of a glucuronide conjugate. The ratio of chlordecone to chlordecone alcohol in gerbil stool was 10 times higher than the ratio in human stool. This suggests that the newly recognized nonbiliary mechanism(s) for entry of chlordecone into the intestinal lumen (Boylan et al., Clin. Pharm. Ther. 25:579-585, 1979) may be extremely active in the gerbil. Biliary excretion of chlordecone alcohol in gerbils progressively increased following chlordecone treatment while biliary excretion of chlordecone remained unchanged. Incubation of the cytosolic fraction of gerbil liver homogenate in the presence of NADPH and chlordecone produced chlordecone alcohol, whereas rat liver cytosol was inactive. This observation indicates that bioreduction of chlordecone is catalyzed in gerbil liver by a species-specific reductase. Rats given [3H]-chlordecone alcohol excreted twice as much (80%) of the compound in stool after three days as compared to gerbils (40%), while the latter species accumulated three times more chlordecone alcohol in the liver than did the former. An unexpected finding was that the livers of these [3H]-chlordecone alcohol treated animals also contained chlordecone in amounts eight times (rat) and 14 times (gerbil) higher than the respective amounts of chlordecone alcohol. From this result, the existence of a separate enzyme(s) catalyzing dehydrogenation of chlordecone alcohol to chlordecone may be inferred.

Animals↗

Estimation of the body burden of arsenic in a child fatally poisoned by arsenite weedkiller.

A three-year-old child died after ingestion of a mouthful of an estimated 44% sodium arsenite solution. Litigation was initiated based on the quality of emergency treatment at a rural hospital. An issue raised in litigation was whether the child could have survived if he had received an additional dose of BAL (dimercaprol). BAL had been sent for from a neighboring city and arrived approximately 2.0 h after admission. The first 50-mg dose of BAL could have combined with a maximum of 30 mg arsenic; a second dose could have brought the total of chelated arsenic to 60 mg. To determine the total body burden of arsenic in the child, multiple tissues were analyzed. The total body burden was estimated at 113 mg, with 100 mg of this total attributable to the ingested solution. The actual body burden after two doses of BAL therefore would have been at least 40 mg, a fatal level.

Arsenic↗

Rapid, simultaneous quantification of morphine, codeine, and hydromorphone by GC/MS.

Morphine, codeine, and hydromorphone were extracted from blood or serum using a one step extraction. The extract was derivatized and the trifluoroacetyl opiates were quantified by GC/MS selected ion monitoring (SIM) using nalorphine as the internal standard. Calibration curves were linear and sensitivity as low as .02 mg/L for morphine and codeine, and .08 mg/L for hydromorphone, was achieved. Urine or tissue homogenates could be processed similarly after acid hydrolysis.

Autoanalysis↗

The Schotten-Baumann reaction as an aid to the analysis of polar compounds: application to the determination of tris(hydroxymethyl)aminomethane (THAM).

The separation of polar, low molecular weight, water-soluble compounds from specimens prior to quantitation has long been a problem in analytical toxicology. Others have successfully used in situ derivatization, prior to extraction, to resolve this problem (1,3). An application of the Schotten-Baumann reaction leading to a simple extraction of tris(hydroxymethyl)aminomethane (THAM) followed by HPLC is presented. This may be a generic approach to the analysis of other polyhydroxy, water-soluble compounds.

Benzoates↗

The effects of storage conditions on the stability of carbon monoxide in postmortem blood.

The stability of carbon monoxide (CO) in blood was studied under various conditions of storage using both spectrophotometric and gas chromatographic-flame ionization detector (GC-FID) methods of analysis. Changes (losses) in percent carbon monoxide saturation occurred under some conditions but not under others. Various mechanisms for CO losses are considered and one (passive diffusion of CO gas) best explains these observations. Losses of up to 60% of the original saturation occurred when blood was kept in uncapped containers at room temperature for 2 1/2 weeks or at 4 degrees C for 3 weeks. However, no changes occurred when blood was kept in tightly sealed containers for at least 4 months at either temperature.

Blood Preservation↗