[Efficacy and side effect of continuous intra-arterial infusion of high-dose 5-FU for liver metastases of colorectal cancer].

Fifteen patients with liver metastases of colorectal cancer were entered in our study, and 5-FU was given continuously by hepatic intra-arterial route at 1 g/day over 6 days. No leukopenia (< 3,000/mm3), anemia (< 10 g/dl), or thrombocytopenia (< 75,000/mm3) occurred, and no elevation of serum AST (> 150 IU/l) or serum T-Bil (> 2 mg/ml) appeared. One patient (4.2%) had nausea with vomiting 1-5 per day, and another (4.2%) had mucositis requiring treatment. In patients with multiple liver metastases, survival of the continuous infusion group [total dose of 5-FU > or = 12 g] (n = 5) seems to be longer than those of the hepatectomy only group (n = 3) or the control group (n = 7). We suggest that this continuous intra-arterial infusion of high-dose 5-FU is a useful chemotherapy with few side effects or complications.

[A case report: successful resection of advanced intrahepatic cholangiocarcinoma responding to preoperative hepatic artery infusion of 5-FU].

A patient with advanced intrahepatic cholangiocarcinoma had a tumor embolus in the right main branch of the portal vein and lymph node metastases. Hepatic arterial infusion (HAI) therapy with 5-FU (1 g/day) was given as a continuous infusion for 6 days. The treatment was repeated after a one-week interval. As a result the tumor diameter decreased by half, and the tumor embolus contracted. Cytoreductive surgery was then performed. The patient has been disease-free for over 9 months postoperatively with adjuvant HAI with 5-FU. We consider preoperative HAI with 5-FU (two courses of 1 g/day x 6 days) is both safe and effective.

Dietary effect of conjugated linoleic acid on lipid levels in white adipose tissue of Sprague-Dawley rats.

We examined the effect of dietary conjugated linoleic acid (CLA) on lipid parameters in the liver, white adipose tissue (WAT) and brown adipose tissue (BAT) of Sprague-Dawley rats and found that it reduced the levels of triglycerides and non-esterified fatty acid in the liver and WAT without significant change in the BAT lipid levels. These results suggest that CLA has an obesity-preventing action.

SEM and EDS analysis of calcospherites in human teeth.

The present study was designed to characterize the morphology and composition of calcospherites in the coronal and root predentin of human permanent teeth by scanning electron microscopy (SEM) and scanning electron microscopy energy dispersive spectroscopy (SEM-EDS). Human incisors, premolars, and molars were used. The calcospherites in the coronal predentin were globular and 10-20 microm in diameter. The calcospherites in the root predentin were smaller and their shape was different. Polygonal calcospherites and stellate calcospherites were observed in the intermediate region of the root predentin. Calcospherites were rarely present in the apical region of the root predentin. Calcified matrix fibers were observed in the apical region of the root predentin. The Ca/P molar ratio in crown calcospherites (1.63 +/- 0.27) differed significantly from that in root calcospherites (1.46 +/- 0.28). Sulfur was detected from the cervical region to the root region, but not in the horn region. Odontoblast activity and the local environment of the predentin are thought to determine the shape, size, and composition of calcospherites.

[Evaluation of prophylactic hepatic arterial infusion chemotherapy after hepatectomy for metastases from colorectal cancer].

The significance of continuous hepatic arterial infusion (HAI) chemotherapy of 5-FU to prevent recurrence in the remnant liver following curative hepatectomy for colorectal metastases was analyzed in the prospective randomized study. Patients of HAI chemotherapy group received 6 weeks of 5-FU 500 mg/day. The one- and two-year overall survival rates of nine patients with HAI therapy were 87.5% and 87.5%, respectively, while the rates of ten cases without the regional chemotherapy were 100% and 66.7%, respectively, indicating no obvious difference. On the other hand, the disease-free survival rates of HAI Group were higher than those of control group. The disease-free survival rates of the former were 75.0% at one-year and 75.0% at two-year, and the rates of the latter were 47.6% and 47.6%, respectively. No serious complications such as severe liver dysfunction, sclerotic cholangitis or hepatic necrosis were observed. Although the follow-up period was not enough long to accurately evaluate the efficacy, local prophylactic chemotherapy by continuous infusion of 5-FU could be a promising method as an adjuvant chemotherapy after hepatic resection for colorectal metastases.

[A case of advanced gastric cancer successfully treated with resection after FEP (5-FU, epirubicin, CDDP) combined chemotherapy].

We reported an experience with an advanced gastric cancer patient with direct invasion into liver and metastases to liver, who had responded extremely well to an FEP combined chemotherapy. He had curatively undergone total gastrectomy with partial hepatectomy and enlarged lymph node dissection. The patient received three courses of 5-FU (750 mg/m2/day, for four days, continuous infusion), epirubicin (30 mg/m2, on day 1, i.v.), CDDP (17.5 mg/m2/day, on days 1, 2, 3, 4 i.v.) every 3 weeks in our hospital. No remarkable side effect was encountered. Partial response in the primary and invasive lesions was observed by X-P, endoscopy and CTscan. Accordingly, we could perform curative resection of the stomach with lymph nodes and parts of liver. The effect (partial response) of neoadjuvant chemotherapy was confirmed by histological examinations. FEP combined chemotherapy appears useful as a neoadjuvant approach to advanced gastric cancer.

[Evaluation of prophylactic intra-hepatic-arterial infusion chemotherapy after resection of hepatic metastases from colorectal primaries].

To prevent recurrence in the residual liver after surgical treatment for colorectal metastases, the efficacy of intermittent or continuous intra-hepatic-arterial chemotherapy was analyzed. The three- and five-year survival rate of patients with intermittent infusion of ADM or MMC (n = 11) was 36.4% and 36.4%, respectively, while the survival rate of the patients without the regional chemotherapy (n = 32) was 41.9% and 23.3%, respectively, indicating no statistical significance. On the other hand, one patient out of 8 with continuous infusion of 5-FU and 2 patients out of 6 without local chemotherapy developed recurrent disease during the median follow-up time of 12 months. No serious complication such as sclerotic cholangitis or hepatic necrosis was observed. Although the follow-up was not long enough to accurately evaluate the efficacy, local chemotherapy with continuous infusion of 5-FU could be a promising method as an adjuvant chemotherapy after hepatic resection for colorectal metastases.

Scanning electron microscopy-energy dispersive spectroscopy and X-ray diffraction analyses of human salivary stones.

Ten salivary stones in the human submandibular gland were investigated by scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and X-ray diffraction analyses. The stones usually showed a lamellar pattern. SEM observations revealed cubical, plate-like, granular, small and large granules, polyhedral or globular structures in these stones. By X-ray powder diffraction analysis, the main constituents of salivary stones were found to be apatite and whitlockite. SEM-EDS analyses showed that Ca and P were the major elements, frequently accompanied by Mg and S, and less frequently by Na, Al, Si, Cl, K, Fe, Cu and Zn. Ca/P molar ratios ranged from 1.00 to 2.00 with the average of 1.53, showing two maxima of about 1.50 and 1.60. The Ca/P molar ratio of about 1.50 corresponded to the value of whitlockite. The Ca/P molar ratio of 1.60 corresponded approximately to the value of apatite.

Metabolism of drugs in the eye. Menadione-dependent reduction of tertiary amine N-oxide by preparations from bovine ocular tissues.

As described previously, the microsomes and cytosol from bovine ciliary body exhibited a significant reductase activity toward tertiary amine N-oxide such as imipramine N-oxide when supplemented with menadione. In the present study, the menadione-dependent N-oxide reduction was further examined with preparations of bovine ocular tissues. The reduction of imipramine N-oxide occurred much more significantly when the microsomes and cytosols from bovine ciliary body were supplemented with both menadione and NAD(P)H, compared with menadione alone. The cytosolic menadione-dependent reduction, but not the microsomal one, was markedly inhibited by dicumarol, suggesting the involvement of DT-diaphorase in the reaction. Localization of the menadione-dependent N-oxide reductase activity in bovine ocular tissues indicated that the highest activity resided in the ciliary body, followed by retinal pigment epithelium-choroid, iris, retina and cornea. When the cytosol from bovine ciliary body was fractionated with ammonium sulfate, the distribution of the menadione-dependent N-oxide reductase activity in the resultant fractions was parallel, but roughly, to that of DT-diaphorase activity, supporting the assumption that the flavoenzyme was involved in the cytosolic menadione-dependent N-oxide reduction. We proposed a new mechanism for the metabolic reduction of tertiary amine N-oxide in the eye: Menadione is reduced to the corresponding diol by quinone-reducing enzymes and then tertiary amine N-oxide is reduced by the diol to the corresponding amine nonenzymatically.

Morphology and chemical composition of dental calculi mainly composed of whitlockite.

The morphology and chemical composition of two subgingival calculus samples, which were composed of magnesium-whitlockite with a Mg/Ca molar ratio of approximately 0.1 as shown by X-ray powder diffraction, were analyzed semiquantitatively using energy-dispersive spectroscopy (EDS) combined with scanning electron microscopy (SEM). The Ca/P molar ratio values for 33 EDS-analyzed materials ranged from 1.24 to 2.03 with an average of 1.49, and the (Mg+Ca)/P molar ratio values ranged from 1.43 to 2.28 with an average of 1.63. The average Mg/Ca molar ratio was 0.10, a value very close to that obtained by X-ray diffraction analysis. The EDS-analyzed materials were grouped morphologically into three types; Type A materials were typical rhombohedral crystals, Type B were crystals of ill-defined form or small crystallite aggregations and Type C materials had a small granular structure or were amorphous. The values of (Mg+Ca)/P molar ratio for Type A ranged from 1.57 to 2.28 and averaged 1.81, those for Type B ranged from 1.43 to 1.56 and averaged 1.48, and those for Type C ranged from 1.46 to 2.06 and averaged 1.62. Type A crystals had higher molar ratios while Type B crystallites had values similar to that of whitlockite. Type C materials covered the ranges of both Type A and Type B. These results show that the materials resembling whitlockite morphologically did not have the (Mg+Ca)/P ratio of whitlockite and vice versa. This suggests that whitlockite crystals may substitute some ions for PO4 as well as Mg for Ca to a larger extent than thought previously, and that care is needed in the identification of these materials.

[Energy dispersive X-ray analysis of human deciduous teeth dentin].

Human deciduous molars were ground and polished in order to be examined by an analytical electron microscopy. An energy dispersive X-ray analysis system attached with a scanning electron microscope was used to analyze the teeth dentin both qualitatively and quantitatively. Calcium and phosphorus and also magnesium could be detected in the intertubular dentin of their teeth. The calcium content of the interglobular dentin was lower than those of the other part of dentin. The magnesium content was almost 4% (atomic %). The magnesium content in the dentin was higher than those in the enamel and cementum of the same specimen. It was suggested that some magnesium was contained in the dentin crystal structure.

Metabolism of drugs in the eye. Drug-reducing activity of preparations from bovine ciliary body.

Drug-metabolizing activities, especially the reductase activities towards N-oxide, hydroxamic acid, sulfoxide and nitro compounds were comparatively examined with bovine ciliary body. As described previously, the cytosol from the ocular tissue exhibits the nicotinamide N-oxide reductase activity when supplemented with 2-hydroxypyrimidine, an electron donor of aldehyde oxidase. When the cytosol was fractionated with ammonium sulfate, followed by assays of aldehyde oxidase and nicotinamide N-oxide reductase activities in each fraction, the distribution of aldehyde oxidase activity in the resultant ammonium sulfate fractions was nearly parallel to that of nicotinamide N-oxide reductase activity. Furthermore, reductase activities towards drugs such as sulfoxide, hydroxamic acid and nitro compounds were observed with the cytosol in the presence of 2-hydroxypyrimidine or N1-methylnicotinamide. In general, these reductase activities of the fraction were markedly inhibited by menadione, an inhibitor of aldehyde oxidase. These results suggest that aldehyde oxidase present in ciliary body plays an important role in the reduction of a variety of xenobiotics in mammalian eyes. However, in the case of imipramine N-oxide, its reduction in the ocular tissue appears to be more readily catalyzed by a menadione-linked enzyme different from aldehyde oxidase.

Nicotinamide N-oxide reductase activity in bovine and rabbit eyes.

The nicotinamide N-oxide reductase activity of a variety of ocular tissues was investigated. The 9,000g supernatant of ciliary body, retinal pigment epithelium-choroid, iris, retina and cornea, but not lens, exhibited reductase activity under anaerobic conditions when supplemented with 2-hydroxypyrimidine, an electron donor of aldehyde oxidase. Among these tissues, the highest activity was observed with ciliary body. When the 9,000g supernatant of ciliary body was fractionated, the 2-hydroxypyrimidine-linked reductase activity was mainly associated with the cytosolic fraction and was markedly inhibited by menadione, an inhibitor of aldehyde oxidase. Similarly, in the presence of 2-hydroxypyrimidine, the cytosolic fraction of rabbit ciliary body exhibited nicotinamide N-oxide reductase activity which was susceptible to inhibition by menadione. These facts strongly suggest that aldehyde oxidase present in mammalian eyes is involved in the reduction of nicotinamide N-oxide to nicotinamide.

Phlebolithiasis associated with intramuscular hemangioma. X-ray diffractometric, X-ray microanalytical and scanning electron microscopic investigations.

Phlebolithiasis associated with intramuscular hemangioma is relatively rare. Combined crystallographic, microanalytical and morphological studies have not been done before. We investigated a case of phlebolithiasis by scanning electron microscopy, X-ray microdiffractometry and energy-dispersive X-ray microanalysis. The calculus revealed a lamellar structure with irregular distribution of radipaque and radiolucent portions. The radiopaque portions contained apatite which could be demonstrated in prismlike as well as globular granular structures. In contrast to other authors, brushite was not detected by us. The radiolucent protions adjacent to the stone surface contained sulfur and showed undefined diffraction peaks supposing the presence of organic crystals. The possible milieu factors govering calculus formation are discussed.