Biomedical subjects
Publications and source records attributed to H Igimi.
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We examined by titration the electrochemical properties, apparent pK (pK'a), precipitation pH, and undissociated bile acid solubilities of chenodeoxycholic acid and its 7 beta epimer, ursodeoxycholic acid and their glycine conjugates as functions of a number of physical-chemical variables. Despite comparable pK'a values, ursodeoxycholic acid and its glycine conjugate precipitated from H2O(37 degrees C) at pH values of 8.0-8.1 and 6.5-7.4 whereas chenodeoxycholic acid and its glycine conjugate precipitated at pH values of 7.0-7.1 and 4.,-5.0, respectively. These differences were related to the low solubility of undissociated ursodeoxycholic acid in water (53 microM) and in ursodeoxycholic micelles (saturation ratio of anion:acid, 90-400:1) compared with the higher solubility of chenodeoxycholic acid in water and in chenodeoxycholate micelles (250 microM and 5-25:1, respectively). In model bile systems including those composed of conjugated ursodeoxycholate-chenodeoxycholate mixtures, ursodeoxycholic acid was less soluble than chenodeoxycholic acid and induced the mixtures to gel between pH 7.0 and 4.5-6.5. These results suggest that in vivo 1) the solubility and absorption of oral ursodeo;ycholic acid from the duodenum-jejunum may be limited, 2) ursodeoxycholic acid will precipitate in the colon at pH values less than 8.0 but chenodeoxycholic acid is soluble at pH values greater than 6.9 and hence is capable of eliciting a secretory diarrhea, 3) the precipitation pH of glycoursodeoxycholic acid, the predominant bile acid in bile during therapy with ursodeoxycholic acid, falls within the physiological range, thus it is poss;ble that this bile acid may short-circuit the entero-hepatic circulation and even precipitate from bile or gut luminal contents as crystals.
The mechanism for concentrating function of gallbladder was studied in vitro, turning and attention to changes in the gallbladder bile composition, especially a marked increase of Na+ and a marked decrease of Cl- in the concentrating process of hepatic bile to gallbladder one. The following results were obtained by the present investigations: 1) bile acids present in bile regulate the rate of Na+ and Cl- transport: 2) the epithelial membrane of the gallbladder can be regarded as being a simple semi-permeable membrane.
To investigate the mechanism of concentration of bile, the normal canine gallbladders were cannulated through the cystic duct into the gallbladder neck with polyethylene tube, and hypotonic, isotonic and hypertonic salines as well as hepatic and gallbladder biles were placed in the gallbladder. Low molecular electrolytes such as Na+ and Cl- were transported across the epithelial membrane against water flux. The hepatic bile was decreased markedly in volume and each level of electrolytes including bile acids approached that in the gallbladder bile. The different results were obtained by concentration of the hepatic bile in the gallbladder with chemically induced cholecystitis.
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The dissolving mixture is administered through a choledochal drain to treat postoperatively retained cholesterol gallstones. It is prepared by mixing 97.0 parts of d-limonene with 2.1 parts of polysorbate 80 and 0.9 part of sorbitan monooleate, a mixture of which may easily reach the surface of the gallstones which are wetted by bile. The d-limonene preparation was found to be safe both in laboratory experiments and clinical trials. Before applying the preparation, the usual choledochal drain must be replaced with a recently developed catheter made from epichlorohydrine rubber, which is chemically resistant to the preparation. Three cases of retained gallstones are described where the preparation was successfully used. In the fourth case treatment with the preparation was tried in lieu of surgery but was not successful due to other complications. However, some dissolution of retained stones was observed. There were no postoperative complaints in the long-term follow-up of some cases for more than 2 yr after treatment with the preparation. This procedure promises to be of value because retained cholesterol stones may be dissolved without the necessity of further surgery.
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