Apple pectin affects the efficacy of epigallocatechin gallate on oral sucrose tolerance test in adult mice.

Epigallocatechin gallate (EGCg), a dietary polyphenol and a major tea catechin, is a known sucrase inhibitor. Since dietary pectin is known to modulate some of the functions of the gastrointestinal tract, we investigated whether it could specifically affect the efficacy of EGCg on an oral sucrose tolerance test in mice. Male Crj:CD-1 (ICR) mice (seven weeks old) were randomly divided into two groups and fed a 5 % apple pectin (PE) or 5 % cellulose (CE) diet (control diet) for 28 days. After the experimental diet period, all mice were fasted overnight. A volume of 0.2 mL EGCg (20 mg/mL) was orally administered to all the mice by stainless steel feeding needle via injection syringe and a sucrose tolerance test was performed. The blood glucose levels were measured in blood collected from the tail vein using the OneTouch® Ultra® blood glucose monitoring system. Blood glucose levels at 30 minutes and 60 minutes after sucrose loading in the PE group were significantly higher than initial blood glucose levels. However, blood glucose levels at 30 minutes, 60 minutes, and 120 minutes after sucrose loading in the CE group were not significantly higher than initial blood glucose levels. After laparotomy, plasma lipids were also measured. Plasma triglyceride concentrations were significantly greater in the PE group than in the CE (control) group. This demonstrates that dietary pectin can affect the efficacy of EGCg on the oral sucrose tolerance test in mice.

Selenium-based digital radiography versus high-resolution storage phosphor radiography in the detection of solitary pulmonary nodules without calcification: receiver operating characteristic curve analysis.

OBJECTIVE: The purpose of this study was to compare selenium-based digital radiography with high-resolution storage phosphor radiography for the detection of solitary pulmonary nodules without calcification. MATERIALS AND METHODS: One hundred twenty-four patients underwent selenium-based digital radiography, high-resolution storage phosphor radiography, and chest CT for evaluation of pulmonary nodules. Thirty-one patients with pulmonary nodules smaller than 3 cm in diameter and 40 patients with normal lungs were selected for receiver operating characteristic curve analysis. Five board-certified radiologists who were unaware of the CT results independently reviewed each of the hard copies of selenium-based digital radiography and storage phosphor radiography, identified pulmonary nodules, and graded their confidence for the presence of each nodule. For each radiologist, we calculated the areas under the receiver operating characteristic curve (AUC) for selenium-based digital radiography and storage phosphor radiography. RESULTS: The average performance of selenium-based digital radiography (AUC = 0.72) was higher than that of high-resolution storage phosphor radiography (AUC = 0.64), which is statistically significant (p <0.05). CONCLUSION: Our results indicate that selenium-based digital radiography is superior to high-resolution storage phosphor radiography for detecting solitary pulmonary nodules without calcification.

Hyperintense basal ganglia on T1-weighted magnetic resonance images following postoperative parenteral nutrition in a pancreatoduodenectomized patient.

The authors reported the magnetic resonance imaging (MRI) detection of manganese (Mn) deposition in the basal ganglia of a pancreatoduodenectomized patient following 30-day parenteral nutrition. A multi-trace element supplement solution including 20 micromol Mn/day was parenterally administered for 30 days postoperatively. The serum level of total bilirubin normalized on the 3rd postoperative day, while the level of alkaline phosphatase continued to exceed the higher limit of normal controls even 2 months after operation. T1-weighted MRI on the 49th postoperative day demonstrated bilateral and symmetrical hyperintense lesions in the globus pallidus. The whole-blood Mn level on the 67th postoperative day was 3.1 (normal range 0.8-2.5) microg/l. T1-weighted MRI on the 103rd postoperative day revealed improvement in the hyperintense lesions, and MRI on the 225th postoperative day revealed no abnormality. The blood Mn level normalized on the 194th postoperative day. Even short-term postoperative parenteral nutrition may result in Mn deposition in the brain, especially in patients with cholestasis following pancreatoduodenectomy.

A case of hypothalamic hamartoma associated with arachnoid cyst.

A 14-year-old girl presented with seizures. Radiological examinations revealed an arachnoid cyst in left middle fossa and a cystic mass in the interpeduncular cistern. The cyst was opened and the wall of the cyst and a mass were biopsied. The histological findings were characteristic of an arachnoid cyst and hamartoma, respectively. A hypothalamic hamartoma associated with an arachnoid cyst is comparatively rare; however, such a case may help clarify the genesis of this malformation.

Manganese deposition in the brain following parenteral manganese administration in association with radical operation for esophageal cancer: report of a case.

We report herein the case of a patient in whom manganese (Mn) deposition in the basal ganglia was detected by magnetic resonance imaging (MRI) subsequent to thoracic esophagectomy, performed following perioperative parenteral nutrition. A multi-trace-element supplement solution which included 20 micromol of Mn per day had been parenterally administered for 7 days preoperatively and 21 days postoperatively. The serum level of total bilirubin reached a maximum value of 5.1 mg/dl postoperatively. The T1-weighted MRI on the 32nd postoperative day demonstrated bilateral and symmetrical hyperintense lesions in the globus pallidus and the whole-blood Mn level on the 34th postoperative day was 4.9 microg/l, the normal range being 0.8-2.5 microg/l. This hyperintensity on T1-weighted MRI was gradually improved following normalization of the blood Mn level. This case report serves to demonstrate that even short-term perioperative parenteral nutrition may result in Mn deposition in the brain following radical surgery for esophageal cancer, especially in patients with hyperbilirubinemia.

Effectiveness of kampo medicine (sai-boku-to) in treatment of patients with glossodynia.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of a Kampo medicine (Sai-boku-to) for treatment of patients with glossodynia. STUDY DESIGN: Sai-boku-to or an antianxiety drug (diazepam) with vitamin B complex was administered orally for 3 months to each of 200 patients with glossodynia. Clinical examination evaluated the following subjective symptoms: pain, burning sensation, and discomfort. Effectiveness was evaluated as follows: "markedly effective," all 3 symptoms disappeared; "effective," pain improved; "ineffective," no improvement in pain. RESULTS: The effective rates were 70% after 1 month, 85% after 2 months, and 92% after 3 months of administration of Sai-boku-to (the Kampo group) and 74% after 1 month, 71% after 2 months, and 69% after 3 months of administration of the antianxiety drug with vitamin B complex (the control group). No significant side effect was noted in the Kampo group, but sleepiness was recorded in 33 cases in the control group. CONCLUSIONS: The results indicate that Sai-boku-to may be a clinically useful medicine for the long-term treatment of patients with glossodynia.

Effects of the endothelin receptor antagonist TAK-044 on hepatocyte element alterations in the ischemic-reperfused liver in Beagle dogs.

BACKGROUND/AIMS: This study was designed to investigate elemental alterations of subcellular organelles (cytoplasm, nucleus, mitochondria) after ischemia of the liver, and the effects of the pre-ischemic administration of an endothelin ETA/ETB receptor antagonist (TAK-044) on subcellular elements. METHODS: We determined serial changes in subcellular elements by X-ray microanalysis using liver biopsy specimens, and we compared the liver functions of a control and a TAK-044-treated group of Beagle dogs, before and after 70% partial ischemia (60 min). TAK-044 was given intravenously at a dose of 3 mg/kg before ischemia. RESULTS: In the control, the Ca concentration in the cytoplasm showed a slight increase after ischemia and a marked increase immediately after reperfusion. It returned to approximately pre-ischemic levels at 6 h after reperfusion. In contrast, in the TAK-044 group, the increase was significantly suppressed. The changes in Na and Cl, which increased in parallel with Ca, were also suppressed in the TAK-044 group. The alterations in K were opposite to those Ca. These changes were also suppressed to a significant degree in the TAK-044 group. Elemental alterations in the nucleus and mitochondria were similar to those in the cytoplasm in both the control and TAK-044 groups. The changes in the liver functions and the electron microscopic findings supported the differences in serial changes in subcellular elements between the two groups. CONCLUSIONS: TAK-044 exhibited a hepatoprotective effect on ischemia-reperfusion injury from the aspect of subcellular elemental dynamics and liver functional and morphologic changes.

Hepatoprotective effect of a nonselective endothelin receptor antagonist (TAK-044) in the transplanted liver.

This study was designed to investigate whether or not a novel nonselective endothelin A/B (ETA/ETB) receptor antagonist (TAK-044) provides hepatoprotection during porcine liver transplantation. The grafts were stored in chilled Euro-Collins solution and recirculated following reflush with lactated Ringer's with (TAK group) or without (control group) TAK-044 (10 mg/kg). Intracellular (cytoplasma, mitochondria, and nucleus) calcium (Ca) concentrations were measured in the hepatic biopsy materials obtained serially at varying time point from donor laparotomy to recipient closure using an electron probe X-ray microanalyzer. Liver function tests also were determined. The cold and warm ischemia times of the grafts were comparable between the two groups. The peak endothelin-1 T-1) concentration after recirculation was significantly higher in the TAK group than in the control group (129 +/- 30 pg/ml vs 26 +/- 6.5 pg/ml). However, release of liver enzymes, increases in total bile acid, and deterioration of indocyanine green retention rate were significantly suppressed in the TAK group. In the control group, the intracellular Ca concentrations, especially in the mitochondrial fraction, were elevated markedly following recirculation of the hepatic arterial flow. In the TAK group, this effect was suppressed. Thus, the supplementary use of the nonselective ETA/ETB receptor antagonist TAK-044 via a rinse route may alleviate an early postreperfusion microcirculatory disturbance of the liver grafts without adverse effects by the increased ET-1 on the systemic circulation.

EUK-134, a synthetic superoxide dismutase and catalase mimetic, protects rat kidneys from ischemia-reperfusion-induced damage.

The effect of a new synthetic superoxide dismutase and catalase mimetic was investigated on renal ischemia-reperfusion syndrome in rats. Synthetic salen-manganese complexes have characteristics that might facilitate their potential usefulness as therapeutic agents: (1) unlike proteinaceous antioxidant enzymes, synthetic complexes, due to their low molecular weight, have a better stability and bioavailability; (2) they have a catalytic activity enhancing their efficiency over noncatalytic reactive oxygen metabolite scavengers; and finally, (3) exhibiting combined superoxide dismutase and catalase activity, they destroy both superoxide anions and hydrogen peroxides, thereby enhancing their protective effect on ischemically injured tissues. One such compound, EUK-134, was tested in uninephrectomized rats that underwent a left renal artery clamping. After a 75-min left renal artery clamping, a single intravenous injection of EUK-134 at 0.2 mg/kg, just before unclamping, provided significantly better renal function recovery during the week after the ischemic insult compared with recovery of untreated animals. Two hours after several periods of renal ischemia (30, 45, 60, and 75 min of left renal artery clamping), EUK-134 given at a similar dose significantly improved the glomerular filtration rate after an acute ischemia of 30 and 45 min, as assessed by EDTA 51Cr. Overall, these results show that synthetic superoxide dismutase-catalase mimetics such as EUK-134 can protect ischemically injured rat kidneys from ischemia-reperfusion syndrome when administered just before reperfusion.

Hepatocellular carcinoma: efficacy of transcatheter oily chemoembolization in relation to macroscopic and microscopic patterns of tumor growth among 100 patients with partial hepatectomy.

PURPOSE: To evaluate the efficacy of transcatheter oily chemoembolization (TOCE) for hepatocellular carcinoma (HCC) on the basis of microscopic and macroscopic findings postembolization. METHODS: HCCs ranging in size from 0.5 to 13 cm (mean 3.6 cm) were obtained from partial hepatectomies of 100 consecutive patients who had undergone TOCE between 20 and 246 days (mean 59.5 days) prior to surgery. The efficacy of TOCE was assessed on the basis of the necrotic to live cell ratio of the tumors. The microscopic pattern of tumor growth was grouped into expanding type (complete capsule formation) and replacing type (incomplete or no capsule). There were five types of macroscopic groupings: single nodule, single nodule with extranodular growth (SNE), contiguous and noncontiguous multinodular, and massive growth type. RESULTS: Among 79 cases with the expanding type, 29 (37%) had 100% HCC necrosis, but none with 100% necrosis were in the replacing type. By macroscopic grouping, the efficacy of TOCE decreased from the single nodule type (50% of patients had 100% necrosis) to the SNE type (21%), and the other types (9%). CONCLUSION: TOCE appears to be most efficacious for HCC with the expanding growth pattern and HCC forming single nodules. Poor results are to be expected in HCC of replacing growth type and multinodular or massive growth types.

[Doses of epirubicin used in oily chemoembolization of hepatocellular carcinoma].

Epirubicin (EPIR), an anticancer agent, has recently been used with increasing frequency in transcatheter oily chemoembolization (TOCE) of hepatocellular carcinoma. We conducted a dose-finding study of EPIR with regard to its safety. One hundred thirty-four patients were divided into five groups according to the EPIR doses (mg/m2), Group A (< 30 mg/m2), Group B (> or = 30 - < 40 mg/m2), Group C (> or = 40 - < 50 mg/m2), Group D (> or = 50 - < 60 mg/m2), and Group E (> or = 60 mg/m2). The number of leukocytes decreased at 2 weeks but recovered at 4 weeks with no significant differences among the groups. However, there were significantly fewer leukocytes in Group E than in Groups A to D. There were no significant differences among the groups in either the number of erythrocytes or platelets. The number of platelets tended to remain at increased levels even at 4 weeks. Liver function as represented by GOT, GPT, LDH, and total bilirubin was not aggravated, but tended to improve. GOT and LDH in Groups D and E, in particular, improved significantly at 4 weeks, probably because of the antitumor effect of TOCE. These results suggest that EPIR can be administered up to 50 mg/m2 for TOCE.

Five-year survival after transcatheter chemoembolization for hepatocellular carcinoma.

The 5-year cumulative survival rate of 443 patients who underwent transcatheter chemoembolization (TCE) for non-resectable hepatocellular carcinoma (HCC) before December 1986 was 8.0%, and 29 patients survived for 5 years or more. Of these 29 patients, 25 were men and 4 were women; their mean age was 63.9 years. Macroscopic classification showed lesions of the single nodular type in 16 cases, the multiple nodular type in 10 cases, and the massive type in 3 cases; 12 of the single nodular lesions measured 5 cm or less in size. The TNM classification showed lesions of stage I in 3 cases, stage II in 14 cases, stage III in 6 cases, and stage IV in 6 cases. Lesions classified as Child A were found in 23 patients, and they were thus much more common than Child B lesions (2 patients) and Child C lesions (1 patient). The response was analyzed in relation to the use of iodized oil (Lipiodol). It was used in 215 of the patients, and the 5-year cumulative survival rate of those patients was 12.9% (23 of them survived for 5 years or more). Lipiodol was not used in 228 patients, and they showed a 5-year cumulative survival rate of 3.4%, with 6 patients surviving for 5 years or more. The 6 patients with stage III disease and the 6 with stage IV disease received Lipiodol. TCE with Lipiodol thus contributed greatly in prolonging the survival of patients with HCC complicated by intrahepatic metastases or intraportal tumor thrombi.

Detection of viable tumor cells in hepatocellular carcinoma following transcatheter arterial chemoembolization with iodized oil. Pathologic correlation with dynamic turbo-FLASH MR imaging with Gd-DTPA.

To evaluate the effect of transcatheter arterial chemoembolization (TACE) with iodized oil for hepatocellular carcinoma (HCC), dynamic turbo-fast low angle shot (turbo-FLASH) (TR/TE/flip angle/TI, 8.5/4.6/10/200) MR imaging with gadopentetate dimeglumine was performed in 10 patients with HCC after TACE with iodized oil and before partial hepatectomy. Immediately after 0.05 mmol/kg b.w. of gadopentetate dimeglumine was administered intravenously, 10 images were obtained in the first 20 s (early phase). Then, one image every 30 s from 1 to 3 min (late phase), and images at 5 min and 7 min (delayed phase) were obtained serially. In the early phase, HCC showed no enhancement in 5 patients, partial hyperintense enhancement in 4, and total hyperintense enhancement in one. Viable regions of the tumor, evaluated at histopathology, showed hyperintense enhancement relative to the surrounding liver parenchyma in the early phase, while necrotic regions showed no enhancement. Both viable and necrotic regions showed lower signal intensities than the surrounding liver parenchyma in both late and delayed phases. By using dynamic turbo-FLASH MR imaging, we were able to accurately evaluate the effect of TACE with iodized oil for HCC in 8 of the 10 patients. In 2 patients, in whom small viable cells were seen in the HCC, viable regions could not be detected with our technique. It is concluded that turbo-FLASH dynamic MR imaging was useful for evaluating the effect of TACE for HCC.

[Transcatheter chemoembolization of hepatocellular carcinoma (TAE)--its application and limitations].

Transcatheter Chemoembolization of Hepatocellular Carcinoma (TCE) shows an excellent anti-cancer effect and improves prognosis thanks to the recent improvement of embolic materials and technique of catheterization. Thus, TCE is considered the therapy of choice for hepatocellular carcinoma (HCC). The anticancer drug adriamycin, mixed with Lipiodol injected via hepatic artery, accumulates in HCC and shows a good anti-cancer effect, TCE with Lipiodol also improves the prognosis. As segmental TCE is possible with the recent microcatheter technique, the application of TCE has become widespread, and an excellent anti-cancer effect almost equal to that of resection has been reported. But in order to decrease the complications and achieve the best effect, strict control before and after treatment and a TCE method suited to the patient are necessary. Sometimes because of poor liver function or the development of HCC (portal thrombus etc), TCE is impossible or its use is limited; and some HCC is hard to control with TCE, and other adjuvant therapy is necessary.

Response to transcatheter oily chemoembolization in hepatocellular carcinoma 3 cm or less: a study in 50 patients who underwent surgery.

The response of 50 patients who underwent hepatectomy for hepatocellular carcinoma measuring 3 cm or less (at the time of surgery) to transcatheter oily chemoembolization was evaluated. The response was assessed in 5 categories, A: complete necrosis (100%), B: necrosis of at least 95%, C: at least 80%, but less than 95%, D: at least 50% but less than 80%, and E: less than 50% of the tumor cells. Response A was observed in 19 patients (38%), B in 7 (14%), C in 9 (18%), D in 7 (14%), and E in 8 (16%). These results were classified with respect to the histological degree of tumor differentiation, the WHO histological classification, the microscopic patterns of tumor growth, and macroscopic classification. The response was evaluated in relation to the histological grade of tumor differentiation and the WHO histological classification in all categories of response except response A, and there was no significant difference between the categories. The response was obviously better with the expansive type than with the replacing type. Single nodular type lesions were more responsive than the single nodular type lesions with extranodular growth and the contiguous multinodular type. Pretreatment estimation of the microscopic patterns of tumor growth and macroscopic classification appears to be valuable in predicting prognosis.

Treatment of hepatocellular carcinoma by chemoembolization: evaluation with 3DFT MR imaging.

OBJECTIVE: We evaluated the usefulness of an MR imaging technique that used dynamic three-dimensional Fourier transformation (3DFT) fast imaging with steady-state precession (FISP) with gadopentetate dimeglumine for detecting viable regions of hepatocellular carcinoma following transcatheter arterial chemoembolization with iodized oil (Lipiodol). Images obtained with the 3DFT FISP technique were directly correlated with hepatectomy specimens. SUBJECTS AND METHODS: Dynamic 3DFT FISP MR imaging was performed after transcatheter arterial chemoembolization and before partial hepatectomy in 10 patients with 10 tumors of hepatocellular carcinoma. Imaging parameters were 20/8/30 degrees (TR/TE/flip angle) with a slab thickness of 21-75 mm and seven or 15 partitions. 3DFT FISP images were obtained at the slice level where a tumor had been detected on T1- and/or T2-weighted spin-echo MR images before, just after (early phase), and 1 and 2 min after (late phase) IV administration of gadopentetate dimeglumine (0.1 mmol/kg). We directly compared the dynamic MR images of the 10 patients with the gross and microscopic findings. RESULTS: On early-phase images, tumors of hepatocellular carcinoma showed no enhancement in three patients and partial intense enhancement in seven. Viable regions of the tumor showed intense enhancement relative to the surrounding liver parenchyma in the early phase, whereas necrotic regions showed no enhancement in either the early or the late phase. Both viable and necrotic regions had lower signal intensities than did the surrounding liver parenchyma in the late phase. By using dynamic 3DFT MR imaging, we were able to accurately assess the effect of transcatheter arterial chemoembolization with iodized oil in nine of the 10 patients. However, in one patient in whom microscopically viable cells were seen in the capsule of the carcinoma, viable regions could not be detected with our technique. CONCLUSION: Dynamic 3DFT MR imaging was useful in differentiating viable regions of hepatocellular carcinoma from necrotic regions following transcatheter arterial chemoembolization with iodized oil.

[An experimental study of a new embolic material--Lipiodol suspension of water-absorbent particle].

A water-absorbent particle (a polymer of polyacrylic acid soda) was investigated as a new embolic material. The size of a single particle is 200 microns (N-100) or 10 microns (NP-1010). A particle absorbs 100 times its own weight of physiologic NaCl solution within a few seconds. The particles have no acute or chronic toxicity or immunogenicity. This material suspended by Lipiodol was evaluated in an in vitro study using an AVM model composed of a plastic syringe and polyurethane sponge. The AVM model was perfused by physiological NaCl solution at a pressure of 150 mmHg. The swollen polymer worked as an adequate embolic material in the AVM model, using a minimum quantity. The embolic effect depended upon the quantity and concentration of the suspension. Restoration of flow was not observed within a period of ten minutes. The embolized part was clearly visualized due to the retention of Lipiodol. This material is a promising agent for arterial embolization.

[Stage III, IV hepatocellular carcinoma patients surviving more than five years after transcatheter chemoembolization].

Twelve of the patients with advanced (Stage III or IV) hepatocellular carcinoma who received transcatheter chemoembolization survived for more than 5 years. These survivors consisted of 6 Stage III cases and 6 Stage IV cases. Of the 6 Stage III cases, 5 had multiple tumors (larger than 2 cm) in one lobe of the liver, and 1 had tumor invasion into the second portal branch before treatment. Of the 6 Stage IV cases, 4 had had multiple tumors in both lobes, and 2 had had tumor invasion into the main portal branches. Before treatment, 9 of the 12 survivors had been rated as Child's class A. Lipiodol was used in all 12 cases. The results of the present study suggest the usefulness of Lipiodol in treating advanced hepatocellular carcinoma.

Cloning and expression of a cDNA encoding an endothelin receptor.

Endothelins are a newly described peptide family consisting of three peptides (ET-1, ET-2 and ET-3) which are the most potent vasoconstrictive peptides known. They are crucial in the regulation of vascular smooth muscle tone. The diverse functions of endothelins are thought to be mediated by interaction with many different receptors coupled to the inositol phosphate/calcium ion messenger pathway. However, because of the structural resemblance of the three peptides, the presence and nature of multiple endothelin receptors remain to be elucidated. We report here the cloning of a complementary DNA encoding a bovine endothelin receptor, which has a transmembrane topology similar to that of other G protein-coupled receptors and shows specific binding, with the highest selectivity to ET-1 in animal cells transfected with the cloned cDNA. This receptor messenger RNA is widely distributed in the central nervous system and peripheral tissues, particularly in the heart and lung. Our results support the view that there are other receptor subtypes.