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Biomedical subjects

H Igimi

Publications and source records attributed to H Igimi.

At least 37 records · Page 2Linked to original sources
PubMed1993

[A healthy carrier of verotoxin-producing Escherichia coli, who was detected by periodic feces examinations].

Verotoxin-producing Escherichia coli (VTEC) was rapidly detected by the PCR method in one of the 9 feces samples. They were collected from the people who had been cooking meals for patients on a periodic feces examination on November 25, 1992. It was confirmed by PCR that the isolate had both VT1 and VT2vh toxic genes and showed cytotoxicity on Verocells. In this case, the isolate was highly susceptible to common antibiotic agents, it was removed by the administration of tosfulaxacin. Some isolates which had the same properties as those of the strain described in "VITEK GNI card" and the antimicrobial susceptibility and VT toxin types, were detected in 2 of the 3 members of her family, they were healthy carriers and did not have any subjective symptoms such as diarrhea or abdominal pain. In order to detect Verotoxic genes, the sample of feces preincubated for 3 h in trypticase broth was subjected to PCR. We recommend that this method is much more useful because of rapid detection and identification of VTEC compared with the classical culture method.

Adult↗
PubMed1993

Ursodeoxycholic acid in the Ursidae: biliary bile acids of bears, pandas, and related carnivores.

The biliary bile acid composition of gallbladder bile obtained from six species of bears (Ursidae), the Giant panda, the Red panda, and 11 related carnivores were determined by reversed phase liquid chromatography and gas chromatography-mass spectrometry. Bile acids were conjugated solely with taurine (in N-acyl linkage) in all species. Ursodeoxycholic acid (3 alpha, 7 beta-dihydroxy-5 beta-cholan-24-oic acid) was present in all Ursidae, averaging 1-39% of biliary bile acids depending on the species; it was not detected or present as a trace constituent (< 0.5%) in all other species, including the Giant panda. Ursodeoxycholic acid was present in 73 of 75 American Black bears, and its proportion averaged 34% (range 0-62%). Ursodeoxycholic acid averaged 17% of biliary bile acids in the Polar bear (n = 4) and 18% in the Brown bear (n = 6). Lower proportions (1-8%) were present in the Sun bear (n = 2), Ceylon Sloth bear (n = 1), and the Spectacled bear (n = 1). Bile of all species contained taurine-conjugated chenodeoxycholic acid and cholic acid. In some related carnivores, deoxycholic acid, the 7-dehydroxylation product of cholic acid, was also present. To determine whether the 7 beta hydroxy group of ursodeoxycholic acid was formed by hepatic or bacterial enzymes, bile acids were determined in hepatic bile obtained from bears with chronic biliary fistulae. Fistula bile samples contained ursodeoxycholic acid, chenodeoxycholic acid, and a trace amount of cholic acid, all as taurine conjugates, indicating that ursodeoxycholic acid is a primary bile acid formed in the liver in Ursidae.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Direct gallstone dissolution therapy with GS-100].

We have developed GS-100, a new direct dissolving drug with strong dissolution property for cholesterol stone by supplementing d-limonene, a dissolvent used since 1974, with 30% medium-chain monoglyceride (MCM). The new drug was applied in 23 patients with gallbladder stones and three with bile duct stone. The presumptive analysis of the composition of the stones was drawn from the CT recordings. As non-invasive therapies, methyl tert-butyl ether (MTBE) dissolution and extracorporeal shock wave lithotripsy (ESWL), which are commonly used in Europe and America, have been reported as being favourable; however, GS-100 is superior in respect to safety and applicative dimension, suggesting of the possibility of using GS-100 as an important drug in the non-invasive therapy for gallstone in the near future.

Adult↗
PubMed1992

A useful cholesterol solvent for medical dissolution of gallstones.

Dissolution of cholesterol gallstones by direct instillation of an agent into the biliary tract has been considered an alternate to surgical procedures. We developed an excellent direct solubilizer by combining d-limonene and medium-chain monoglyceride. This mixture enhances the advantages of each individual solvent and minimizes the disadvantages. In vitro experiments were done to determine the viscosities and the cholesterol dissolving rates of various combinations, and in vivo experiments were conducted to study their irritation effects on tissues. The optimal combination was a 3:2 mixture of d-limonene and medium-chain monoglyceride. It could quickly dissolve cholesterol gallstones with minimal or no observable side effect.

Animals↗
PubMed1992

Gallbladder mucosal function: studies in absorption and secretion in humans and in dog gallbladder epithelium.

The gallbladder is conventionally regarded as an absorptive organ such that dilute hepatic bile is both stored and concentrated. We studied 35 patients who had recovered from a percutaneous transhepatic gallbladder drainage performed for acute cholecystitis. After an overnight fast, gallbladder bile was dark brown in color and had a wide scatter in the lipid composition. Two hours after a meal, the gallbladder bile was opalescent white in color and had the composition of an extracellular fluid. This phenomenon was uniformly observed in all 35 patients and was also consistently reproducible when five patients were repeatedly studied. We used normal dog gallbladder epithelial cell monolayers grown in culture and examined sodium flux. Control gallbladder cells absorbed sodium. When secretin (0.5-2.5 x 10(-7) M) was added, there was a prompt reversal of sodium flux, resulting in net secretion. We conclude that secretion is a physiological function of the gallbladder mucosa. After feeding, the neural and humoral factors divert stored and newly secreted bile into the duodenum and induce active de novo secretion thus producing a gallbladder bile that is opalescent white with no lipids. Our results also have important implications on the origin of the pathological "white bile," the pathogenesis and treatment of gallbladder sludge, as well as the kinetic analysis of compounds undergoing enterohepatic recirculation.

Absorption↗
PubMed1992

Studies on the antibiotic transfer into the bile of canines with different bile duct pressures.

There have been many studies on the transport of antibiotics into the bile; however, these studies have not taken the bile duct pressure into consideration. The bile duct pressure of the patient with acute obstructive cholangitis is high, and after drainage of the bile, the pressure is not always decreased to the normal range. We studied the effects of the bile duct pressure on the antibiotic (flomoxef sodium) transfer into the bile using beagles after creating the model of acute obstructive cholangitis. Our results showed that sufficient bile flow after drainage is important for the antibiotic transport, and, moreover, the bile acid concentration which may be related to the bilirubin concentration is also highly considerable.

Animals↗
PubMed1991

Medical dissolution of gallstones. Clinical experience of d-limonene as a simple, safe, and effective solvent.

Retained gallstones in the bile ducts account for 60-70% of all the cases of postcholecystectomy syndromes. A solvent d-limonene preparation was injected directly to the biliary system of 200 patients to dissolve or disintegrate the retained gallstones. The outcomes were: retained stones completely disappeared in 96 cases (48%); partial dissolution in 29 (14.5%); chelating agent was also used with partial dissolution in 16 (8%); ineffective in 59 (24.5%). To make this method more effective, several guidelines should be observed including an in vitro trial dissolution test. Cautious observation for possible side effects and frequent hepatic and pancreatic function tests during the treatment with this preparation also should be performed.

Bile Duct Diseases↗
PubMed1991

Differential effects of ursodeoxycholic acid and ursocholic acid on the formation of biliary cholesterol crystals in mice.

The preventive effect of 3 alpha, 7 beta, 12 alpha-trihydroxy-5 beta-cholanoic acid (ursocholic acid) and ursodeoxycholic acid on the formation of biliary cholesterol crystals was studied in mice. Cholesterol crystals developed with 80% incidence after feeding for five weeks a lithogenic diet containing 0.5% cholesterol and 0.25% sodium cholate. When 0.25% ursocholic acid or ursodeoxycholic acid was added to the lithogenic diet, the incidence as well as the grade (severity) of the gallstones were reduced. Plasma and liver cholesterol levels were decreased by ursodeoxycholic acid but not by ursocholic acid. Gallbladder cholesterol and phospholipid levels were decreased by both bile acids. The biliary bile acid level was decreased by ursocholic acid but not by ursodeoxycholic acid. After feeding ursocholic acid, its level in the bile was about 25% and the levels of cholic acid and beta-muricholic acid decreased. Fecal sterol excretion was not changed by ursocholic acid, but was increased by ursodeoxycholic acid. After feeding ursocholic acid, fecal excretion of deoxycholic acid, cholic acid, and ursocholic acid increased. No differences were found between mice, with or without gallstones, in plasma and liver cholesterol levels, biliary phospholipid and bile acid levels, fecal sterol and bile acid levels, and biliary and fecal bile acid composition. The results suggest that the lower incidence of crystal formation after treatment with ursocholic acid is probably by a different mechanism than with ursodeoxycholic acid. In the mouse model, ursodeoxycholic acid exerts its effect at least partially, by decreasing cholesterol absorption. Ursocholic acid is well absorbed and excreted into bile and transformed into deoxycholic acid by the intestinal microflora in mice.

Animals↗
PubMed1985

Biliary excretion of latamoxef and N-methyltetrazolethiol in humans and rats.

The biliary excretions of latamoxef and N-methyltetrazolethiol (NMTT) were studied in patients with T-tubes inserted in their common bile ducts, and in bile fistulated male rats. The highest concentrations of latamoxef and NMTT in 6 patients with cholelithiasis were obtained 1-2 h after intravenous injection of a single 1-g dose, and the mean peak values were 66.2 and 0.85 microgram/ml, respectively. The values in patients with gallbladder carcinoma or pancreas head carcinoma were much lower than those with cholelithiasis. The biliary excretions of latamoxef and NMTT in rats were much higher and faster than in humans, with the highest levels being obtained within 30 min after injection. About 20% of the injected dose was recovered as latamoxef and 4% as decomposed materials in 2.5 h after injection. Latamoxef was not decomposed in human or rat bile when kept at -20 degrees C for 4 weeks if the pH was adjusted to 6; some decomposition occurred (10-20%) if the pH was not adjusted.

Animals↗
PubMed1984

Dissolution of human cholesterol gallstones in stimulated chenodeoxycholate-rich and ursodeoxycholate-rich biles. An in vitro study of dissolution rates and mechanisms.

We have compared the kinetics and physical-chemical mechanisms of human cholesterol gallstone dissolution in simulated normal, chenodeoxycholate-rich, and ursodeoxycholate-rich " biles ." Owing to reduced micellar cholesterol solubilizing capacities, dissolution rates in ursodeoxycholate-rich biles were initially slower than in normal or chenodeoxycholate-rich biles . At later time points, dissolution rates in ursodeoxycholate-rich bile became accelerated; this was shown to be associated with the development of a lamellar liquid-crystalline phase that took place first on the stones' surfaces and was then followed by dispersion of liquid-crystalline vesicles into the micellar solution. As subsequent dissolution occurred in a two-phase system of micelles and liquid-crystalline vesicles, the quantity of cholesterol solubilized exceeded micellar saturation. In normal and chenodeoxycholate-rich biles , no phase changes were observed either on the surfaces of the stones or in the micellar solution, and the quantity of cholesterol solubilized was limited by micellar saturation. These results was limited by micellar saturation. These results are consistent with phase equilibria diagrams of the simulated bile systems and suggest that the predominant physical-chemical mechanism of in vivo gallstone dissolution with ursodeoxycholic acid is via liquid crystalline dispersion of cholesterol. In contrast, micellar dissolution of cholesterol is the only mechanism possible with chenodeoxycholic acid.

Bile↗
PubMed1983

Liquid crystal formation in ursodeoxycholate-rich human gallbladder bile.

We studied liquid crystal formation in bile samples obtained from the patients with radiolucent gallstones who had been administered either ursodeoxycholic acid (UDCA) at a dose of 600 mg/day or chenodeoxycholic acid (CDCA) at 400 mg/day for one week preoperatively. The UDCA/total bile acids ratio was found to range from 50 to 60% and the CDCA/total bile acids ratio ranged from 70 to 80%. Cholesterol molar percent was 5 in UDCA-rich bile and 6 in CDCA-rich bile. Phospholipid molar percentage was about the same in both groups. Liquid crystal formation was confirmed only in the UDCA-rich bile samples but not in the CDCA-rich bile samples. This result suggests that cholesterol in the UDCA-rich bile samples is not solubilized by the bile salt and phospholipid mixed micelles but also consumed to form liquid crystals.

Bile↗
PubMed1983

Bilayer membrane formation in the chenodeoxycholate, phosphatidylcholine and cholesterol solution.

The physicochemical process whereby bilayer membranes are formed in the chenodeoxycholate, phosphatidylcholine and cholesterol solution is described. Observations were made by electron microscopy using both the negative stain method and the freeze fracture method after excess amounts of cholesterol monohydrate crystals were incubated at varying ratios in sodium taurochenodeoxycholate and phosphatidylcholine solutions. A hypothesis of the transformational processes from bilayer disk to multilamellar liposome in the artificial bile is presented.

Chemical Phenomena↗
PubMed1983

The developmental process from micelle to liquid crystal in the ursodeoxycholate, phosphatidylcholine and cholesterol solution.

The developmental process from micelle to liquid crystal via the bilayer membrane is described based on electron microscopic observations using the freeze fracture method in solutions containing ursodeoxycholate, phosphatidylcholine and cholesterol. Comparisons of sodium tauroursodeoxycholate and sodium taurochenodeoxycholate solutions were performed and this developmental process was confirmed only in the sodium tauroursodeoxycholate, phosphatidylcholine and cholesterol solution under physiological conditions.

Chemical Phenomena↗
PubMed1983

[A new direct solubilizer for bilirubinate calcium stones].

Hepatobiliary surgeons must have faced difficulty in treating patients with intrahepatic gallstones. In spite of considerable progress in operative methods or mechanical techniques, it is very difficult to remove intrahepatic gallstones completely. Under such circumstances, the development of a solubilizer that can dissolve intrahepatic bilirubinate calcium stones by means of injecting it through a postoperative catheter or PTCD catheter has been awaited. Up to now, a chelating agent, so-called hexametaphosphate (HMP) has been used for removing the calcium from calcium bilirubinate. But this chelating agent, in itself, cannot dissolve the bilirubin. The authors found a direct solubilizer for bilirubin, dimethyl sulfoxide (DMSO) which is a well known bi-polar non protonic solvent and used as an accelerator for bilirubin determination. After the purification of DMSO to 99.98%, toxicity was examined by oral administration, intravenous administration and infusion into biliary tract. But no remarkable toxicity or side effects were detected on biochemical and pathological examinations. Clinical application of 90% DMSO together with 5% HMP was performed and a satisfactory effect was obtained as a direct solubilizer for bilirubinate calcium stones.

Aged↗
PubMed1983

Cholesterol gallstone dissolution in bile. Dissolution kinetics of crystalline cholesterol monohydrate by conjugated chenodeoxycholate-lecithin and conjugated ursodeoxycholate-lecithin mixtures: dissimilar phase equilibria and dissolution mechanisms.

Using compressed discs and microcrystals of cholesterol monohydrate, we evaluated the mechanisms and kinetics of dissolution in conjugated bile salt-lecithin solutions. In stirred conjugated ursodeoxycholate-lecithin and cheno-deoxycholate-lecithin solutions, dissolution of 10,000-psi discs was micellar and linear with time for 10 hours. The dissolution rate constants (k) decreased in proportion to the lecithin content and dissolution rates and k values were appreciably smaller in conjugated ursodeoxycholate-lecithin solutions. After dissolution for 5 to 10 days the discs incubated with ursodeoxycholate-lecithin systems became progressively transformed into macroscopic liquid crystals. Unstirred dissolution of 3,000-psi discs in "simulated" human bile containing physiological lecithin concentrations gave apparent k values that decreased in the following order: ursodeoxycholate-rich >/= chenodeoxycholate-rich > normal. In most cases the discs incubated with ursodeoxycholate-rich bile became covered with a microscopic liquid-crystalline layer. With 20-25 moles % lecithin, these layers eventually dispersed into the bulk solution as microscopic vesicles. During dissolution of microcrystalline cholesterol in conjugated ursodeoxycholate-lecithin systems, a bulk liquid-crystalline phase formed rapidly (within 12 hours) and the final cholesterol solubilities were greater than those in conjugated chenodeoxycholate-lecithin micellar systems. Prolonged incubation of cholesterol microcrystals with pure lecithin or lecithin plus bile salt liposomes did not reproduce these effects. Condensed ternary phase diagrams of conjugated ursodeoxycholate-lecithin-cholesterol systems established that cholesterol-rich liquid crystals constituted an equilibrium precipitate phase that coexisted with cholesterol monohydrate crystals and saturated micelles under physiological conditions. Similar phase dissolution-relationships were observed at physiological lecithin-bile salt ratios for a number of other hydrophilic bile salts (e.g., conjugated ursocholate, hyocholate, and hyodeoxycholate). In contrast, liquid crystals were not observed in conjugated chenodeoxycholate-lecithin-cholesterol systems except at high (nonphysiological) lecithin contents. Based on these and other results we present a molecular hypothesis for cholesterol monohydrate dissolution by any bile salt-lecithin system and postulate that enrichment of bile with highly hydrophilic bile salts will induce crystalline cholesterol dissolution by a combination of micellar and liquid crystalline mechanisms. Since bile salt polarity can be measured and on this basis the ternary phase diagram deduced, we believe that the molecular mechanisms of cholesterol monohydrate dissolution as well as the in vivo cholelitholytic potential of uncommon bile salts can be predicted.-Salvioli, G., H. Igimi, and M. C. Carey. Cholesterol gallstone dissolution in bile. Dissolution kinetics of crystalline cholesterol monohydrate by conjugated chenodeoxycholate-lecithin and conjugated ursodeoxycholate-lecithin mixtures: dissimilar phase equilibria and dissolution mechanisms.

Bile↗
PubMed1982

The "mirroring" of gallstones: description of a novel silvering method to determine the surface area of an irregular object. In vitro demonstration that multiple gallstones from the same gallbladder dissolve in unsaturated "bile" at the same rate.

We describe a novel "silvering" method to determine the surface area of nonspherical objects and have applied this method to human cholesterol gallstones. A standard curve is first constructed, using data obtained from the dissolution rates of silver-coated plastic spheres of known dimensions in unstirred thiosulfate-ferricyanide solutions. Silver dissolution rates of silver-coated gallstones are then correlated with the standard curve so that the equivalent spherical surface area of the gallstones may be estimated. The technique has been applied to cholesterol dissolution rates of gallstones from the same patient and from different patients in unstirred bile salt (sodium chenodeoxycholate) solutions. The results demonstrate that cholesterol dissolution rates per unit surface area are identical for small stones as well as large ones, are identical for all stones from the same gallbladder, but are somewhat dissimilar for those originating from different gallbladders. The experimental results are in agreement with a priori theoretical predictions of mass transfer from spherical objects, and correlate satisfactorily with experimental dissolution rates of pure cholesterol monohydrate disks in unstirred bile salt solutions.

Bile Acids and Salts↗