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Biomedical subjects

G J Somjen

Publications and source records attributed to G J Somjen.

6 recordsLinked to original sources
PubMed2001

Fatty acid bile acid conjugates (FABACs)--new molecules for the prevention of cholesterol crystallisation in bile.

BACKGROUND: Cholesterol gall stones are a frequent disease for which at present surgery is the usual therapy. Despite the importance of bile acids it has become evident that phospholipids are the main cholesterol solubilisers in bile. Even phospholipid components, such as fatty acids, have anticrystallising activity. AIM: To synthesise fatty acid bile acid conjugates (FABACs) and study their effects on cholesterol crystallisation in bile in vitro and in vivo. METHODS: FABACs were prepared by conjugation of cholic acid at position 3 with saturated fatty acids of variable chain length using an amide bond. Cholesterol crystallisation and its kinetics (crystal observation time, crystal mass) were studied in model bile, pooled enriched human bile, and fresh human bile using FABACs with saturated fatty acids of varying chain length (C-6 to C-22). Absorption of FABACs into blood and bile was tested in hamsters. Prevention of biliary cholesterol crystallisation in vivo was tested in hamsters and inbred mice. RESULTS: FABACs strongly inhibited cholesterol crystallisation in model as well as native bile. The FABACs with longer acyl chains (C-16 to C-22) were more effective. At a concentration of 5 mM, FABACs almost completely inhibited cholesterol crystallisation in fresh human bile for 21 days. FABACs were absorbed and found in both portal and heart blood of hamsters. Levels in bile were 2-3 times higher than in blood, indicating active secretion. Appreciable levels were found in the systemic circulation 24-48 hours after a single administration. Ingested FABACs completely prevented the formation of cholesterol crystals in the gall bladders of hamsters and mice fed a lithogenic diet. CONCLUSIONS: FABACs are potent inhibitors of cholesterol crystallisation in bile. They are absorbed and secreted into bile and prevent the earliest step of cholesterol gall stone formation in animals. These compounds may be of potential use in cholesterol gall stone disease in humans.

Animals↗
PubMed1990

Polyamines--potential nucleating factors in bile.

Lithogenicity of human bile is dependent not only on cholesterol saturation, but also on the presence of nucleating and antinucleating factors. Most of the research in this field is directed toward biliary proteins, particularly glycoproteins. In the present study we have shown that spermine, spermidine, cadaverine and putrescine have a nucleating effect in model bile as well as in native human bile. These findings are based on 183 mixing experiments using biles from 10 patients and model biles. The effect seems to be dose dependent at concentrations up to 10 mmol/l. It is not accompanied by a shift in cholesterol distribution between its vesicular and micellar carriers. It is at present uncertain whether these effects are pharmacologic or physiologic. These findings emphasize, however, the potential importance of non-protein compounds in the cholesterol nucleation process in bile.

Bile↗
PubMed1983

A non-micellar mode of cholesterol transport in human bile.

Quasi-elastic light scattering (QELS) was used to measure particle size in fresh human hepatic bile of 14 subjects. Particles with an approximate diameter of 700 A were found in all biles. The particles were almost unchanged after the bile salt concentration was reduced to 0.06 mM by dilution or dialysis against 150 mM NaCl. During dialysis bile salts were removed, while cholesterol and phospholipids remained in solution apparently in the large particles-vesicles. These experiments suggest the presence of a novel, bile salt-independent, mode of cholesterol transport in saturated human bile.

Bile↗
PubMed1976

Demonstration of 8 S-cytoplasmic oestrogen receptor in rat mullerian duct.

1. High affinity macromolecular binding of the non-steroidal synthetic oestrogen [3H]diethylstilboestrol and of [3H] oestradiol-17beta in cytosol of Müllerian duct and uterus, and in blood plasma of perinatal rats, was investigated by sucrose density gradient sedimentation. 2. While [3H] oestradiol was bound to both the characteristic 8 S uterine cytoplasmic receptor and a 4 S component of uterine cytosol and plasma of 11-day-old rats, [3H] diethylstilboestrol was bound almost exclusively by the 8 S cytoplasmic receptor. 3. The greatly reduced binding of [3H] diethylstilboestrol to the 4 S plasma plasmic receptor in the Müllerian duct (precursor of the uterus) of 20-day-old foetuses.

Animals↗
PubMedDate not supplied

Endoscope-induced colitis: description, probable cause by glutaraldehyde, and prevention.

Six cases of acute, self-limited colitis that occurred after screening flexible sigmoidoscopy were deduced to be iatrogenic, probably caused by glutaraldehyde residues in the endoscopes after disinfection in an automatic disinfecting machine. The concentration of these residues was indirectly estimated by conductivity measurements of electrolyte concentration in the rinse-water tank of the disinfecting machine during and after five cycles and also in fluid remaining on the surface of the endoscopes and in the endoscope channels. After five cycles, residues in both the rinse water and fluid in the endoscope channels contained the equivalent of 0.2% glutaraldehyde. This was the result of a combination of technical and human errors. It can be prevented by changing the rinse water after each cycle, using forced air to dry the instruments, and washing the endoscopes before use. Users of the automatic disinfecting machine should be aware of the potential accumulation of toxic levels of residues that remain in endoscopes after disinfection.

Acute Disease↗