Hirotsune Igimi

Studies on the Metabolism of d-Limonene (p-Mentha-1,8-diene): I. The Absorption, Distribution and Excretion of d-Limonene in Rats

Abstract1. The absorption, distribution and excretion of d-limonene were investigated in rats using the 14C-labelled compound.2. The highest concentration of radioactivity in blood was obtained 2 h after oral administration of [14C]d-limonene and most occurred in the serum fraction. Radioactivity in the tissues reached maximum 1 or 2 h after administration. Radioactivity in liver, kidney and blood was higher than in other tissues, but was negligible 48 h after administration. An autoradiographic study confirmed these findings of tissue distribution.3. About 60% of administered radioactivity was recovered from urine, 5% from faeces and 2% from expired CO2 within 48 h. In bile duct cannulated rats, about 25% of the dose was excreted in bile within 24 h.

The use ofd-limonene preparation as a dissolving agent of gallstones

The dissolving mixture is administered through a choledochal drain to treat postoperatively retained cholesterol gallstones. It is preparted 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.

Ursodeoxycholate-a common bile acid in gallbladder bile of Japanese subjects

Abstract Bile acid composition was investigated in normal gallbladder-bile collected from the Japanese patients suffering from the diseases other than hepatobiliary tracts. In addition to cholate, chenodeoxycholate, deoxycholate and lithocholate, ursodeoxycholate was detected as a predominant bile acid in all cases tested and its quantity was higher than that of lithocholate in most cases. A simplified method has been developed for the quantitative determination of bile acids. They were derived to their methyl ester-trimethylsilyl ethers and determined by gas-liquid chromatography on a column of 3% poly-phenyldiethanol amine succinate-80-100 mesh Chromosorb WHP. Average recoveries of added amounts of standard bile acids were found to range from 97 to 100%.

Effects of β-lactam antibiotics on intestinal microflora and bile acid metabolism in rats

Wistar male rats were treated for six days with broad spectrum β-lactam antibiotics, latamoxef, and cefotaxime. On the seventh day, the number of fecal anaerobic microbes decreased, total fecal bile acids decreased, and bile acid pools increased. Secondary bile acids such as β-hyocholic, hyodeoxycholic, lithocholic, and deoxycholic acids decreased in the feces while the primary bile acids, cholic, β-muricholic, and chenodeoxycholic acids, became predominant. Coprostanol, a microbial metabolite of cholesterol, also disappeared from the feces during the treatment. The cecum enlarged to almost twice the size of that in control rats, whereas the liver weight was not significantly changed. After treatment was stopped, the number of fecal microbes returned to the initial counts within a week, but restoration of bile acid and cholesterol metabolism required at least three weeks.

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 postchole-cystectomy syndromes. A solventd-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 anin 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.

Management Considerations for Purported Spontaneous Regression of Hepatocellular Carcinoma: A Case Report

Spontaneous regression of hepatocellular carcinoma (HCC) is an extraordinary phenomenon that occurs rarely. While more than 80 cases have been described, most have been established via radiological findings or examination of biopsy tissues rather than via pathological examination of a resected specimen. The present report describes a purported case of spontaneous regression of HCC as indicated by radiological examination. Subsequent immunostaining of surgically resected specimens revealed viable cancer cells, though only necrotic tissues were seen on hematoxylin and eosin staining. These data indicate that viable cancer cells may still be present even if imaging findings suggest spontaneous regression of HCC. Therefore, these patients should receive aggressive treatment similar to that used for patients with established HCC.

A comparative study usefulness of magnetic resonance imaging in the diagnosis of acute cholecystitis

The utility of magnetic resonance imaging (MRI) in the diagnosis of acute cholecystitis was evaluated in 72 consecutive individuals (5 healthy, 13 with chronic cholecystitis andsilent gallbladder stones, 43 without biliary or diffuse liver disease, and 11 with acute cholecystitis and gallbladder stones) with a 0.5-T superconducting unit. On the T1-weighted (500/20) and less T1-weighted axial spin-echo images (620/25), the liver/gallbladder signal intensity ratio (mean±SD) was 2.5±0.51 (n=5) and 1.8±0.29 (n=8) in acute cholecystitis; 0.9±0.42 (n=6) and 1.0±0.29 (n=9) in chronic cholecystitis; and 0.9±0.14 (n=5) and 0.8±0.19 (n=43) in normal gallbladder, respectively. Our results indicate that the liver/gallbladder signal intensity ratio on the T1-weighted image may be a simple and reliable indicator for the diagnosis of acute cholecystitis; we suggest further investigation to confirm these results.

Dissolution of human gallstone

A new water-soluble preparation of terpene derivative, natural limonene with polyoxyethylene hydrogenated castor oil was introduced. This preparation made it possible to dissolve completely 1.412 to 3.250 gm human gallstones, such as pure cholesterol stone, cholesterol pigment-calcium stone in extraordinary short time, about 2 hoursin vitro. And remarkable dissolving effects were shown on 1.925 to 2.801 gm human cholesterol stone placed into the pig gallbladder after only two times of instillation of this preparationin vivo. Histological examination after this instillation was within normal limits on various organ of pig, such as the gallbladder, common bile duct, duodenum, small and large intestines, liver, kidneys, suprarenal glands and sternal-marrow. LD50 value of this new solvent was higher than 5g/kg, therefore it was revealed as non-toxic preparation. These results indicate that this new preparation can be applied clinically with safety especially to cholesterol stone. Moreover dissolving effect was shown even on bile pigment-calcium stone and fatty acid-calcium stone, however the dissolving velocity was not so high as that of cholesterol stone. When this new preparation will be used clinically, the conventional surgical procedures on residual gallstone can be improved.

胸水中抗酸菌DNAの検出におけるnested polymerase chain reactionの有用性の検討

A protocol based on the polymerase chain reaction (PCR) is the most sensitive method for detecting mycobacteria in clinical samples. However, few studies have assessed the usefulness of this method in the diagnosis of tuberculous effusion. We developed a highly sensitive and specific nested PCR method, that amplifies the bovine tuberculous MPB70 gene and the mycobacterial 16S rRNA gene for use in detecting Mycobacterium tuberculosis (M. tuberculosis) and mycobacteria, respectively, in clinical samples. We determined the sensitivity of this method for detecting mycobacteria in samples containing known amounts of mycobacterial DNA and in DNA extracted from pleural effusions obtained from 10 patients with pulmonary tuberculosis in whom standard microbiological techniques had detected mycobacteria in sputum but not in pleural effusion. The nested PCR method for the bovine tuberculous MPB70 gene and the mycobacterial 16S RNA gene was able to detect M. tuberculosis and mycobacterial genomes only if there were at least 2 copies per sample. Positive results for M. tuberculosis and the mycobacterial genomes were obtained by nested PCR in 2 of 10 and in 3 of 10 samples of pleural fluid, respectively but no mycobacteria were detected in malignant effusions obtained from 9 patients with lung cancer. The nested PCR method represents a rapid means for detecting mycobacteria in some pleural effusions previously found to be negative by culture. We speculate that the reaction of the host against mycobacteria is more important than the mycobacteria themselves in the pathogenesis of pleural effusion in which mycobacteria are not detected.

MR imaging of traumatic hepatic laceration: evaluation and course of healing after surgery.

Six patients with hepatic laceration underwent magnetic resonance imaging (MRI) at 0.5T. Acute hepatic laceration was slightly hypointense on T1-weighted spin-echo (SE) image, and hyperintense on T2- and proton-weighted SE images. Subacute laceration was heterogeneously intense on T1-weighted image and hyperintense on T2- and proton-weighted images. Consistent changes in signal intensity of postoperative hepatic laceration were observed. On Tl-weighted image, the signal intensity at first increased and then decreased from periphery to the center. On the T2- and proton-weighted images, the laceration was uniformly hyperintense relative to the liver prior to the appearance and growth of a hypointense ring at its periphery. The appearance of the above changes in signal intensity was also observed in postoperative recurrent hemorrhage. The postoperative biloma had none of the above changes in signal intensity. Our cases show that MRI is effective in the evaluation of hepatic laceration and in the assessment of the course of healing after operation.