Purpose: Heart to liver ratio on T1-201 per rectal scintigraphy (shunt index) is known to be useful in the assessment of portal systemic shunt. We assessed T1-201 uptake pattern and early liver/heart uptake rate of T1-201 and correlated with shunt index in patients with chronic active hepatitis (CAH) and liver cirrhosis (LC). Materials and Methods: Fifty eight patients with biopsy-proven chronic liver disease (35 with CAH, 23 with LC) underwent T1-201 per rectum scintigraphy after instillation of 18.5 MBq of T1-201 into the upper rectum. We evaluated hepatic uptake (type 1 : homogeneous, 2: inhomogeneous segmental, 3: inhomogeneous nonsegmental) and extrahepatic uptake of spleen, heart and kidney (grade 0: no uptake, 1: less than liver, 2: equal to liver, 3: greater than liver). We measured the early liver/heart uptake rate (the slope of the liver to heart uptake ratio for 10 min) and shunt index (heart to liver uptake ratio). T1-201 uptake pattern and early liver/heart uptake rate of T1-201 was correlated with the pathologic diagnosis and shunt index. Results: Hepatic uptake patterns of type 1 and 2 were dominant in CAH (CAH: 27/35, LC. 8/23), and type 3 in LC (CAH: 8/35, LC: 15/23)(p<0.005). The grades of extrahepatic uptake were higher in LC than in CAH (spleen: p<0.001, other soft tissue: p<0.005). The early liver/heart uptake rate of CAH ($0.110{\pm}0.111$) was significantly higher than that of LC ($0.014{\pm}0.090$)(p<0.001). The sensitivity and specificity of the early liver/heart uptake rate were 77.7% and 67.7% in differentiating LC from CAH. There was negative correlation between early liver/heart uptake rate and shunt index (r=-0.3347, p<0.01). Conclusion: Hepatic and extrahepatic uptake pattern and early liver/heart uptake rate on T1-201 per rectum scintigraphy are useful in the assessment of portal systemic shunt in patients with chronic liver disease.
It is well known that hepatobiliary agent are taken up by metastatic hepatocellular carcinoma(HCC) as well as primary HCC. But the reported cases of the extrahepatic metastasis of HCC diagnosed by hepatobiliary scintigraphy are for the most part hematogenous ones. The relation of the uptake pattern of hepatobiliary agent in the primary and metastatic HCC is also still remains unknown. So we undertook this study to evaluate the relation of the hepatobiliary scintigraphic patterns of primary and metastatic HCC with different metastatic routes. Nine patients with primary HCC and twelve cases of metastatic HCC including four lung metastases, one bone metastasis, one right atrial metastasis, one peritoneal wall metastasis, and five lymph node metastases were studied with $^{99m}Tc-DISIDA$ scintigraphy. The images were taken on 10, 30 minutes, 1, 2, 4-6 hours. The overall detection rates of hematogenous metastases(lung and bone) is 60%(3 of 5), direct metastasis(right atrium and peritoneal wall), 100%(2 of 2) and lymphatic metastases, 0%(0 of 5). In four of five metastatic cases demonstrated with hepatobiliary scintigraphy, biliary agent is also taken up by primary HCC lesions. And the appearing time of the radioactivity in the direct metastatic HCC lesioin is same as that of primary HCC and in the cases of hematogenous metastasis, earlier than that of primary HCC. Hepatobiliary scintigraphy is more useful in the diagnosis of the metastatic HCC than primary HCC, in the cases of hematogenous and direct metastasis.
Cytochrome P450 2J2 (CYP2J2) is an enzyme mainly found in human extrahepatic tissues, with predominant expression in the cardiovascular system. CYP2J2 plays important roles in the metabolism of endogenous metabolites and therapeutic drugs, such as arachidonic acid, astemizole, ebastine, and terfenadine. CYP2J2 is also overexpressed in human cancer tissues and cancer cell lines and may represent a potential target for therapy of human cancers. In this study, 10 natural products obtained from plants and microorganisms were screened as potential CYP2J2 inhibitors. Among them, thelephoric acid showed strong inhibition of astemizole O-demethylation activity ($IC_{50}=3.23{\mu}M$) in a dose-dependent manner. Evaluation of the substrate dependency of the inhibitory activity of thelephoric acid showed that it strongly inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}=5.32{\mu}M$) and terfenadine hydroxylation ($IC_{50}=3.27{\mu}M$) in a substrate nondependent manner. The present data suggest that this compound might be a potential candidate for further evaluation for anticancer activity.
The reaction of lecithin cholesterol acyltransferase(LCAT) and cholesteryl ester transfer protein (CETP) are important in cholesterol esterification and transfer for the reverse cholesterol transport(RCT) system. The purpose of this study were to assess the effects of fatty acid unsaturation on RCT system. After 12 female human subjects consumed a prescribed high saturated fat diet prior to the period, two groups of six subjects were provided with a high PUFA(corn oil) or a high SFA(butter) as major fats in a 40 en % fat diet. Butter feeding increased plasma total-(34%), esterified-(96%), HDL_3$-(23%), LDL-(20%), and VLDL plus LDL(35%) cholesterol while corn oil feeding decreased esterified-(25%), LDL(15%) cholesterol and TG(27%). There were significant differences of fats on total-(p=0.0001), esterified-(p=0.0001), total HDL-(p=0.005), $HDL_2$-(p=0.01)and LDL-(p=0.0001) cholesterol. LCAT activity did not change during the period but highly correlated to apo A-I in HDL which was increased in the corn oil group. The 2.5 fold increased CETP activity in the butter group during the period might be related to changes in plasma VLDL plus LDL cholesterol level which were increased in the butter group.
Park, Young-Ha;Kim, Choon-Yul;Kim, Sung-Hoon;Park, Seog-Hee;Park, Yong-Whee
The Korean Journal of Nuclear Medicine
/
v.21
no.1
/
pp.9-16
/
1987
It is well-known that hepatic scintigraphv have been found to be less sensitive and specific in the detection of the diffuse hepatocellular diseases than that of the space-occupying lesions. To obtain the higher diagnostic specificity and sensitivity, we, using the computer quantitation, have attempted to analyze hepatic and extrahepatic $^{99m}Tc-tin$ colloid uptake patterns in various diffuse hepatocellular diseases retrospectively. The studied groups consisted of 116 cases of normal, 67 cases of acute hepatitis, 112 cases of chronic hepatitis, 61 cases of liver cirrhosis, 47 cases of fatty liver, 12 cases of hepatoma and 9 cases of metastasis, making total 424 cases. Scintigraphic imagings were obtained in the anterior, right lateral and posterior projections using high-resolution collimation, and simultaneously these gamma data were acquisited into the computer system. Both large region of interest (ROI) using light pen and ROI computer program were placed over right lobe, left lobe of liver, spleen and cardiac blood pool. Total counts in ROI were divided by the number of pixels in the ROI, and mean count rate per pixels calculated. Mean right-lobe counts were divded by mean-left lobe counts to determine right-to-left hepatic lobe ratio and mean spleen counts were divided by mean liver counts to determine spleen to liver ratio. The results were as follows. 1) Of 424 cases, 292 were male and 132 were female. The majority of age distribution was in $30\sim49$ (54.5%). 2) Inter-observer between two independant operators and inter-method between drawing by light-pen and ROI computer program variations were not significant. 3) The uptake count values (per pixel) determined at each area in normal group were $106.53{\pm}18.35$ in right lobe, $79.00{\pm}13.82$ in left lobe, $17.52{\pm}8.31$ in spleen and $8.09{\pm}3.43$ in cardiac blood pool. 4) In liver cirrhosis, right lobe uptake was decreased but spleen and cardiac blood pool uptakes were increased (p<0.01). 5) Right-to-left hepatic lobe uptake ratio was $1.37{\pm}0.24$ in normal group and significantly low in chronic hepatitis, liver cirrhosis and fatty liver, and more or less low in acute hepatitis. 6) Spleen-to-right hepatic lobe uptake ratio was $0.17{\pm}0.09$ in normal group and high in chronic hepatitis and liver cirrhosis. 7) The computer-quantitation of hepatic and extrahepatic uptake patterns thought to be sensitive and useful method in the interpretation of liver scintigram.
The clinical significance of hepatic resection for gastric metastases is controversial, even though hepatic resection has been widely accepted as a modality for colorectal metastases. Very few patients with gastric hepatic metastases are good candidates for hepatic resection because of multiple bilateral metastases, extrahepatic disease, or advanced cancer progression, such as peritoneal dissemination or extensive lymph node metastases. Therefore, several authors have reported the clinical significance of hepatic resection for gastric metastases in a small number of patients. Considering the present results with previous reports. The number and distribution of tumors in hepatic metastases from gastric cancer was considered based on the present and previous reports. Several authors have reported significantly better survival in patients with metachronous metastasis than in those with synchronous disease. However, metachronous hepatic resection necessitates the dissection of adhesions between the pancreas, liver, and residual stomach to prepare for Pringle's maneuver. Patients with unilobar liver metastasis, and/or metastatic tumors <4 cm in diameter may be good candidates for hepatic resection. Synchronous metastasis is not a contraindication for hepatic resection. Most of the long-term survivors underwent anatomic hepatic resection with a sufficient resection margin. After hepatic resection, the most frequent site of recurrence was the remaining liver, which was associated with a high frequency of mortality within 2 years. A reasonable strategy for improvement in survival would be to prevent recurrence by means of adjuvant chemotherapy and careful follow-up studies.
Purpose: Proliferation of bile duct-like structures and fibrosis is a hepatic cellular reaction observed in most forms of human liver disease and in a variety of experimental conditions associated with liver injury. The aim of this study was to investigate the activation of Ito cells and bile duct proliferation in the rat after common bile duct ligation (CBDL). Methods: Hepatic morphological abnormalities were examined in rats whose bile ducts had been irreversibly ligated for 15, 21, 24 and 28 days. The liver was examined by immunohistochemical staining for ${\alpha}$-smooth muscle actin, the known marker of activated Ito cells, and light and electron microscopes. Results: After CBDL, the bile canalicular proliferation and interstitial fibrosis were gradually increased in the periportal areas extended to hepatic sinusoids. Ito cells positive for ${\alpha}$-smooth muscle actin were frequently observed in the periductular space and in perisinusoidal space of Disse. Ito cells and myofibroblasts were gradually increased in the interstitial fibrosis until the 28th day after CBDL. Ito cells and myofibroblasts had microfilaments with dense body at the periphery of the cell. Conclusions: Our results suggest that Ito cells may be fibroblastic or myogenic. It has also been postulated that during the development of hepatic fibrosis, Ito cells become myofibroblasts or fibroblast like cells.
Unique cartilage matrix-associated protein (UCMA) is an extrahepatic vitamin K-dependent protein rich in γ-carboxylated (Gla) residues. UCMA has been recognized for its ability to promote osteoblast differentiation and enhance bone formation; however, its impact on osteoblasts under hyperglycemic stress remains unknown. In this paper, we investigated the effect of UCMA on MC3T3-E1 osteoblastic cells under hyperglycemic conditions. After exposure to high glucose, the MC3T3-E1 cells were treated with recombinant UCMA proteins. CellROX and MitoSOX staining showed that the production of reactive oxygen species (ROS), which initially increased under high-glucose conditions in MC3T3-E1 cells, decreased after UCMA treatment. Additionally, quantitative polymerase chain reaction revealed increased expression of antioxidant genes, nuclear factor erythroid 2-related factor 2 and superoxide dismutase 1, in the MC3T3-E1 cells exposed to both high glucose and UCMA. UCMA treatment downregulated the expression of heme oxygenase-1, which reduced its translocation from the cytosol to the nucleus. Moreover, the expression of dynamin-related protein 1, a mitochondrial fission marker, was upregulated, and AKT signaling was inhibited after UCMA treatment. Overall, UCMA appears to mitigate ROS production, increase antioxidant gene expression, impact mitochondrial dynamics, and modulate AKT signaling in osteoblasts exposed to high-glucose conditions. This study advances our understanding of the cellular mechanism of UCMA and suggests its potential use as a novel therapeutic agent for bone complications related to metabolic disorders.
Park, Kyoung Soo;Shin, Myung Seok;Chang, Mea Young
Clinical and Experimental Pediatrics
/
v.49
no.8
/
pp.851-856
/
2006
Purpose : The purpose of this study is to find out the diagnostic significance of serum bile acid on total parenteral nutrition induced cholestasis in premature infants. Methods : Infants without cholestasis were classified into postnatal days and each change of serum bile acid was measured and analyzed. Also, the serum direct bilirubin, serum bile acid, ${\gamma}$-glutamic acid transferase, and alkaline phosphatase of premature infants with total parenteral nutrition induced cholestasis were measured for comparison and analysis of their correlation. Results : Changes of serum bile acid analysis after birth showed no significant difference between boys and girls, between premature infants and term infants without cholestasis. Serum bile acid levels are constant after two weeks after birth in neonates without cholestasis. In premature infants with total parenteral nutrition induced cholestasis, the increase of serum direct bilirubin over 2 mg/dL was $34.9{\pm}18.3$ days after birth, and the increase of serum bile acid was $28.1{\pm}18.3$ days. Its increase was about 1 week faster than serum direct bilirubin, however, there was no statistical significance(P=0.114). Comparing analysis of serum bile acid, ${\gamma}$-glutamic acid transferase, and alkaline phosphatase, serum bile acid showed the highest correlation to serum direct bilirubin(r=0.487, P=0.000). Conclusion : Serum bile acid is an important parameter of total parenteral nutrition induced cholestasis in premature infants and will be useful for early diagnosis and treatment.
Keum Ki Chang;Park Hee Chul;Seong Jinsil;Chang Sei Kyoung;Han Kwang Hyub;Chon Chae Yoon;Moon Young Myoung;Kim Gwi Eon;Suh Chang Ok
Radiation Oncology Journal
/
v.20
no.2
/
pp.123-129
/
2002
Purpose : The purpose of this study 띤as to determine the potential role of three-dimensional conformal radiotherapy (3D-CRT) in the treatment of primary unresectable hepatocellular carcinoma. The preliminary results on the efficacy and the toxicity of 3D-CRT are reported. Materials and Methods : Seventeen patients were enrolled in this study, which was conducted prospectively from January 1995 to June 1997. The exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child-Pugh classification C, tumors occupying more than two thirds of the entire liver, and a performance status of more than 3 on the ECOG scale. Two patients were treated with radiotherapy only while the remaining 15 were treated with combined transcatheter arterial chemoembolization. Radiotherapy was given to the field including the tumor plus a 1.5 cm margin using a 3D-CRT technique. The radiation dose ranged from $36\~60\;Gy$ (median; 59.4 Gy). Tumor response was based on a radiological examination such as the CT scan, MR imaging, and hepatic artery angiography at $4\~8$ weeks following the completion of treatment. The acute and subacute toxicities were monitored. Results : An objective response was observed in 11 out of 17 patients, giving a response rate of $64.7\%$. The actuarial survival rate at 2 years was $21.2\%$ from the start of radiotherapy (median survival; 19 months). Six patients developed a distant metastasis consisting of a lung metastasis in 5 patients and bone metastasis in one. The complications related to 30-CRT were gastro-duodenitis $(\geq\;grade\;2)$ in 2 patients. There were no treatment related deaths and radiation induced hepatitis. Conclusion : The preliminary results show that 3D-CRT is a reliable and effective treatment modality for primary unresectable hepatocellular carcinoma compared to other conventional modalities. Further studies to evaluate the definitive role of the 3D-CRT technique in the treatment of primary unresectable hepatocellular carcinoma are needed.
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