• Biomolecules & Therapeutics
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• 제27권2호
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• pp.222-230
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• 2019

Intestinal barrier dysfunction always accompanies cirrhosis in patients with advanced liver disease and is an important contributor facilitating bacterial translocation (BT), which has been involved in the pathogenesis of cirrhosis and its complications. Several studies have demonstrated the protective effect of Vitamin D on intestinal barrier function. However, severe cholestasis leads to vitamin D depletion. This study was designed to test whether vitamin D therapy improves intestinal dysfunction in cirrhosis. Rats were subcutaneously injected with 50% sterile $CCl_4$ (a mixture of pure $CCl_4$ and olive oil, 0.3 mL/100 g) twice a week for 6 weeks. Next, $1,25(OH)_2D_3$ ($0.5{\mu}g/100g$) and the vehicle were administered simultaneously with $CCl_4$ to compare the extent of intestinal histologic damage, tight junction protein expression, intestinal barrier function, BT, intestinal proliferation, apoptosis, and enterocyte turnover. Intestinal heme oxygenase-1 (HO-1) expression and oxidative stress were also assessed. We found that vitamin D could maintain intestinal epithelial proliferation and turnover, inhibit intestinal epithelial apoptosis, alleviate structural damage, and prevent BT and intestinal barrier dysfunction. These were achieved partly through restoration of HO-1 and inhibition of oxidative stress. Taken together, our results suggest that vitamin D ameliorated intestinal epithelial turnover and improved the integrity and function of intestinal barrier in $CCl_4$-induced liver cirrhotic rats. HO-1 signaling activation was involved in these above beneficial effects.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제24권6호
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• pp.518-527
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• 2021

Purpose: The incidence of hepatic steatosis among children has been increasing; however, data distinguishing simple steatosis from a more complex disorder are lacking. Methods: This study identified the etiologies resulting in hepatic steatosis through a retrospective review of pediatric liver biopsies performed in the last 10 years. A total of 158 patients with hepatic steatosis proven by histopathological evaluation were enrolled in the study, and baseline demographic features, anthropometric measurements, physical examination findings, laboratory data, ultrasonographic findings, and liver histopathologies were noted. Results: The two most common diagnoses were inborn errors of metabolism (IEM) (52.5%) and nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) (29.7%). The three most common diseases in the IEM group were glycogen storage disorders, Wilson's disease, and mitochondrial disease. The rates of consanguineous marriage (75.6%; odds ratio [OR], 26.040) and positive family history (26.5%; OR, 8.115) were significantly higher (p=0.002, p<0.001, respectively) in the IEM group than those in the NAFLD/NASH group. Younger age (p=0.001), normal anthropometric measurements (p=0.03), increased aspartate aminotransferase levels (p<0.001), triglyceride levels (p=0.001), and cholestatic biochemical parameters with disrupted liver function tests, as well as severe liver destruction of hepatic architecture, cholestasis, fibrosis, and nodule formation, were also common in the IEM group. Conclusion: Parents with consanguinity and positive family history, together with clinical and biochemical findings, may provide a high index of suspicion for IEM to distinguish primary steatosis from the consequence of a more complex disorder.

• Journal of Genetic Medicine
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• 제18권2호
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• pp.142-146
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• 2021

Alagille syndrome (AGS) is a rare autosomal dominant inherited disorder, with major clinical manifestations of bile duct paucity, cholestasis, cardiovascular anomaly, ophthalmic abnormalities, butterfly vertebrae, and dysmorphic facial appearance. It is caused by heterozygous mutations in JAG1 or NOTCH of the Notch signaling pathway presenting with variable phenotypic penetrance and involving multiple organ systems. The following case report describes a unique case of a 16-year-old female with AGS who presented with the primary complaint of renovascular hypertension. She had a medical history of ventricular septal defect and polycystic ovary syndrome. The patient had a dysmorphic facial appearance including frontal bossing, bulbous tip of the nose, a pointed chin with prognathism, and deeply set eyes with mild hypertelorism. Stenoocclusive changes of both renal arteries, celiac artery, lower part of the abdominal aorta, and left intracranial artery, along with absence of the left internal carotid artery were found on examination. Whole exome sequencing was performed and revealed a pathologic mutation of JAG1, leading to the diagnosis of AGS. Reverse phenotyping detected butterfly vertebrae and normal structure and function of the liver and gallbladder. While the representative symptom of AGS in most scenarios is a hepatic problem, in this case, the presenting clinical features were the vascular anomalies. Clinical manifestations of AGS are diverse, and this case demonstrates that renovascular hypertension might be in some cases a presenting symptom of AGS.

• 한국간담췌외과학회지
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• 제27권4호
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• pp.388-393
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• 2023

Backgrounds/Aims: Acute cholecystitis is a rare condition in pregnant women, potentially affecting the maternal and fetal prognosis. Our aim was to report the main clinical and paraclinical features of acute cholecystitis during pregnancy and therapeutic modalities. Methods: We conducted a case series analysis recording pregnant patients with acute cholecystitis admitted to our surgery department over a period of 11 years. We collected clinical data, paraclinical features, and management modalities related to cholecystitis. Results: There were 47 patients. Twenty-eight percent was in the first trimester of pregnancy, 40% in the second, and 32% in the third trimester. Abdominal pain was located in the right hypochondrium in 75% of cases. Fever was noted in 21% of cases. C-reactive protein was elevated in 39% of patients. Cholestasis markers were high in four patients. Abdominal ultrasound showed a distended gallbladder in 39 patients, with thickened wall in 34 patients, and gallbladder lithiasis in all cases. No patient had a dilated main bile duct. All patients received intravenous antibiotic therapy. Tocolysis was indicated in 32 patients. Laparoscopic cholecystectomy was performed in 32 cases (68%), and open cholecystectomy in 15 cases (32%). Postoperative course was uneventful in 42 patients, and complicated in 5 patients. Rate of complications was statistically higher after open cholecystectomy (p = 0.003). Morbidity rate was higher in the third trimester (p = 0.003). Conclusions: Delay in the diagnosis of acute cholecystitis during pregnancy can lead to serious complications. Management is based on antibiotic therapy and cholecystectomy. Laparoscopic cholecystectomy appears to be less morbid than open cholecystectomy.

• Clinical Endoscopy
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• 제56권5호
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• pp.633-649
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• 2023

Background/Aims: Mechanical properties (MPs) and axial and radial force (AF and RF) may influence the efficacy and complications of self-expandable metallic stent (SEMS) placement. We measured the MPs of various SEMSs and examined their influence on the SEMS clinical ability. Methods: We evaluated the MPs of 29 types of 10-mm SEMSs. RF was measured using a conventional measurement device. AF was measured using the conventional and new methods, and the correlation between the methods was evaluated. Results: A high correlation in AFs was observed, as measured by the new and conventional manual methods. AF and RF scatterplots divided the SEMSs into three subgroups according to structure: hook-and-cross-type (low AF and RF), cross-type (high AF and low RF), and laser-cut-type (intermediate AF and high RF). The hook-and-cross-type had the largest axial force zero border (>20°), followed by the laser-cut and cross types. Conclusions: MPs were related to stent structure. Hook-and-cross-type SEMSs had a low AF and high axial force zero border and were considered safest because they caused minimal stress on the biliary wall. However, the increase in RF must be overcome.

• 대한유전성대사질환학회지
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• 제17권2호
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• pp.69-76
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• 2017

Citrin 결핍증은 요소회로 이상 질환 중 하나로, 7q21.3에 위치한 SLC25A13 유전자에 돌연변이로 발생하는 상염색체 열성 유전질환이다. 세 가지 표현형 중에 신생아 간내 담즙 정체형, 제 2형 시트룰린혈증은 잘 알려졌지만, 성장부진과 이상지질혈증형은 최근에 밝혀지고 있는 표현형으로 아직 우리나라에 보고된 적이 없다. 성장부진과 이상지질혈증형에서는 경미할 수는 있으나 식욕감소, 피곤함, 성장부진, 저혈당, 시트룰린 상승, 이상지질혈증, 젖산염/피루브산염 상승과 같은 이상이 관찰될 수 있다. 또한 저혈당으로 내원하였을 때 일반적인 검사로는 원인 규명이 어려울 수 있다. 저자들은 생후 30개월에 반복적인 저혈당으로 내원하여 소변 유기산 분석, 호르몬 검사와 같은 대사 이상 검사에서 명확한 특정 진단명이 의심되지 않아, 생후 31개월에 targeted exome sequencing을 통해 복합이형접합 SLC25A13 유전자 돌연변이[c.852_855del (p.Met285Profs*2), c.1177+1G>A]를 발견하여 성장부진과 이상지질혈증으로 발현한 citrin 결핍증을 우리나라에서 최초로 진단하여 보고하는 바이다.

• 대한수의학회지
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• 제32권3호
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• pp.347-356
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• 1992

In oriental medicine, Artemisia Iwayomogi(Compositae) has been used clinically for jaundice, hepatitis, liver cirrhosis etc. The purposes of present study were to examine pharmacological effects of Artemisia lwayomogi water extract(AIWE) on weights of body, liver, kidney, spleen and adrenal, and on biochemical parameters (activities of AST, ALT and LDH, contents of cholesterol and triacylglycerol, and levels of hepatic lipid peroxide) against hepatic injury by carbon tetrachloride($CCl_4$) in rats. The results were as follow; 1. Body weights were reduced by $CCl_4$. In AIWE pretreatment groups, reduction of body weights was inhibited at 48 hours. Increased liver weights by $CCl_4$ were reduced in proportion to numbers of treatment of AIWE in AIWE pre- and posttreatment groups. Increased kidney weights by $CCl_4$ were reduced in AIWE pretreatment groups at 72 hours. Increased weights of spleen and adrenal by $CCl_4$ were not affected by AIWE treament. 2. Increased AST activities by $CCl_4$ were significantly (p<0.05) decreased in AIWE posttreatment groups at 48 and 72 hours. Increased ALT activities by $CCl_4$ were significantly(p<0.05) decreased in AIWE posttreatment groups at 48 hours. Increased LDH activities by $CCl_4$ were very significantly (p<0.01, p<0.001) decreased in AIWE posttreatment groups at 48 and 72 hours, respectively. 3. Increased cholesterol contents by $CCl_4$ were significantly (p<0.05) decreased in AIWE posttreatment groups at 24 and 48 hours. Decreased triacylglycerol contents by $CCl_4$ were significantly (p<0.05) increased in AIWE posttreatment at 48 and 72 hours. 4. Increased hepatic lipid peroxide levels by $CCl_4$ were significantly (p<0.05, p<0.01) decreased in AIWE posttreatment groups at 48 and 72 hours, respectively. In conclusion, AIWE did not affect normal liver function and had property of antioxidant, due to reduced lipid peroxidation by $CCl_4$. AIWE seems to have hepatoprotective effects rather than direct preventive effects to $CCl_4$-induced necrotic degeneration of liver cell, cholestasis and damages in metabolism of lipid.

• Clinical and Experimental Pediatrics
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• 제53권6호
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• pp.694-700
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• 2010

Purpose: To assess the validity of individual and combined prognostic effects of severe bronchopulmonary dysplasia (BPD), brain injury, retinopathy of prematurity (ROP), and parenteral nutrition associated cholestasis(PNAC). Methods: We retrospectively analyzed the medical records of 80 extremely low birthweight (ELBW) infants admitted to the neonatal intensive care unit (NICU) of the Severance Children's Hospital, and who survived to a postmenstrual age of 36 weeks. We analyzed the relationship between 4 neonatal morbidities (severe BPD, severe brain injury, severe ROP, and severe PNAC) and poor outcome. Poor outcome indicated death after a postmenstrual age of 36 weeks or survival with neurosensory impairment (cerebral palsy, delayed development, hearing loss, or blindness) between 18 and 24 months of corrected age. Results: Each neonatal morbidity correlated with poor outcome on univariate analysis. Multiple logistic regression analysis revealed that the odds ratios (OR) were 4.9 (95% confidence interval [CI], 1.0-22.6; $P$=0.044) for severe BPD, 13.2 (3.0-57.3; $P$<.001) for severe brain injury, 5.3 (1.6-18.1; $P$=0.007) for severe ROP, and 3.4 (0.5-22.7; $P$=0.215) for severe PNAC. Severe BPD, brain injury, and ROP were significantly correlated with poor outcome, but not severe PNAC. By increasing the morbidity count, the rate of poor outcome was significantly increased (OR 5.2; 95% CI, 2.2-11.9; $P$<.001). In infants free of the above-mentioned morbidities, the rate of poor outcome was 9%, while the corresponding rates in infants with 1, 2, and more than 3 neonatal morbidities were 46%, 69%, and 100%, respectively. Conclusion: In ELBW infants 3 common neonatal mornidifies, severe BPD, brain injury and ROP, strongly predicts the risk of poor outcome.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제2권1호
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• pp.59-64
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• 1999

목 적: 저자들은 백서에서 수술적으로 담도 결찰전과 결찰 4주 후에 지용성 비타민(vitamin A와 D)의 혈중 농도 변화 및 담도 결찰 후 담즙산을 투여했을 때 장관내 지용성 비타민의 흡수 변화에 대하여 알아보고자 하였다. 대상 및 방법: 생후 4주된 Sprague-Dawley rats을 대상으로 하여 수술적으로 담도를 결찰하였다. 담도 결찰 전과 결찰 4주후의 혈중 ALT, total bilirubin, vitamin A, vitamin D의 농도를 측정하였다. 백서들은 담도 결찰 후 4주간 사육하였으며, 사육기간 중 비타민만을 투요한 군, 담즙산을 투여한 군 및 UDCA를 투여한 3군으로 나누었다. 결 과: 1) 수술전 혈중 농도(평균): ALT 74.2 IU, total bilirubin 0.26 mg/dL; vitamin D 13.01 ng/mL vitamin A $0.87\;{\mu}g/mL$, total bile acids $25.16\;{\mu}mol/L$. 2) 수술 4주후 농도(평균): ALT 100.7 IU, total bilirubin 2.58 mg/dL; vitamin D 7.89 ng/mL vitamin A $1.37\;{\mu}g/mL$, total bile acids $278.22\;{\mu}mol/L$. 3) 수술후 각 군간의 혈중 vitamin A와 vitamin D의 농도 차이는 없었다. 결 론: 담도 결찰 후 vitmain A 혈중 농도는 상승 하였으며, vitamin D 농도는 감소하였다. 경구로 담즙산을 투였을 때 혈중 지용성 vitamin 농도는 투여하지 않은 경우와 차이가 없었다.

• 대한임상검사과학회지
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• 제36권2호
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• pp.163-172
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• 2004

Mast cells (MCs) have been implicated in the pathogenesis of tissue fibrosis. However, the role of MC in the development of liver fibrosis has not been fully elucidated. Stem cell factor (SCF) is known to recruit MCs to the liver following injury as it induces mast cell proliferation, survival and differentiation from resident tissue precursors. This study examines the interaction between activated hepatic stellate cells (HSCs) and MCs in rat fibrotic liver, and SCF production by HSCs during culture in vitro. Rats were studied 4, 7, 14 and 21 days after bile duct ligation (BDL). Fibrogenesis was assessed by a measurement of collagen stained with sirius red F3B. Activated HSCs and MCs were identified by ${\alpha}$-smooth muscle actin (${\alpha}-SMA$) immunohistochemical and alcian blue staining and measured by a computerized image analysis system. SCF production was determined in rat HSC cultures using Western blotting. Mild fibrotic changes were noted in BDL rat livers as early as 4 days after induction of cholestasis. Significant expansion and organization of fibrous tissue has occurred in day 14 BDL rats which progressed to bridging fibrosis by day 21. In BDL rats, both a large number of activated HSCs and MCs were detected in portal tracts and fibrous septa. Both area of activated HSCs infiltration and density of MCs were significantly higher in all BDL group compared with Shams. In BDL rats, both areas of activated HSCs infiltration and density of MCs were no significant difference between day 4 and 7 and were significantly higher in day 14. However, the areas of activated HSCs infiltration were significantly lesser in day 21 and the densities of MCs were significantly higher in day 21 compared with day14 BDL. In BDL rats, both areas of activated HSCs infiltration and density of MCs were highly correlated with areas of fibrosis. Western blotting showed that SCF protein was consistently produced in activated HSCs by culture on plastic and freshly isolated HSCs expressed relatively little 30kD SCF compared to late primary culture activated HSCs (day 14) and passaged HSCs. These results suggest that HSCs activated in vitro produce SCF, and may play an important role in recruiting mast cells to the liver during injury and fibrosis.