Biomedical subjects

Full-Young Chang

Publications and source records attributed to Full-Young Chang.

At least 19 recordsLinked to original sources

PubMed2007

Irritable bowel syndrome in the 21st century: perspectives from Asia or South-east Asia.

Asian irritable bowel syndrome (IBS) studies not only confirm the truth of this functional disorder but also describe the current disease situation of this continent, with its variable socioeconomic backgrounds. Most Asian community IBS prevalence is within 5-10%, regardless of gender or ethnic character. As well as meeting the main Rome II criteria, Asian IBS subjects also have many minor symptoms. Thus this recommendation remains useful to diagnose Asian IBS. Also, female patients commonly express constipation-predominant (C-) symptoms. Extra-colonic symptoms are common in Asia, for example dyspepsia, insomnia and irritable urinary bladder. Asian IBS subjects do experience psychological disturbances including anxiety, depression, agoraphobia and neuroticism. Accordingly, their quality of life is poor and there is absenteeism leading to excessive physician visits. Abnormal gut motor and sensory functions have been indicated among the Asian IBS subjects. Now, there is evidence of altered colonic neuroimmune function leading to gut hypersensitivity and dysmotility. An Asia-Pacific trial also confirmed tegaserod efficacy on female C-IBS subjects. More than 90% of nurses have very limited IBS knowledge, and are unable even to explain it clearly. In conclusion, Western recommended criteria clearly diagnose Asian IBS and many factors are mutual leading to IBS. Current IBS treatments remain useful but additional reeducation for medical professionals appears to be needed.

Asia↗

PubMed2006

Dexamethasone inhibits epidermal growth factor-stimulated gastric epithelial cell proliferation.

Epidermal growth factor (EGF) is essential to heal gastric ulcers, whereas glucocorticoid delays rat gastric ulcer healing. We found that dexamethasone inhibited EGF-stimulated rat gastric epithelial cell (RGM-1) proliferation by cell count and DNA synthesis analysis of flow cytometry and attempted to elucidate the possible mechanistic pathway via Western blot analysis. EGF (10 ng/ml) treatment for 24 h significantly increased RGM-1 cell proliferation, and dexamethasone (10(-8) and 10(-6) M) markedly suppressed EGF-stimulated cell proliferation. Western blotting results demonstrated that the phosphorylated extracellular signal-regulated kinase (pERK) (pERK1/pERK2) significantly increased at 10 min after EGF treatment. This was followed by increase of cyclooxygenase (COX)-2 expression at 3 h after EGF treatment. The continued increase of COX-2 (up to 18 h) resulted in increased intracellular prostaglandin E(2) and cyclin D1 expression significantly after 8 and 12 h of EGF treatment. Dexamethasone substantially reduced EGF-stimulated COX-2 expression at 3 and 6 h and cyclin D1 expression at 8 and 12 h. Pretreatment of RGM-1 cells with dexamethasone or 2'-amino-3'-methoxyflavone (PD98059)-mitogen-activated protein kinase kinase inhibitor (5 x 10(-5) M) significantly reduced EGF-stimulated pERK1/pERK2 expression. Simultaneous treatment of RGM-1 cells with PD98059 and EGF also markedly decreased EGF-stimulated COX-2 expression at 6 h. These findings indicate that dexamethasone significantly suppresses EGF-stimulated gastric epithelial cell proliferation, and one of the pathways involved is via inhibiting activation of ERK1/ERK2, followed by inhibition of COX-2, cyclin D1 expression, and finally DNA synthesis.

Animals↗

PubMed2006

Estrogen rapidly modulates mustard oil-induced visceral hypersensitivity in conscious female rats: A role of CREB phosphorylation in spinal dorsal horn neurons.

This study investigated the effect of sex hormones on mustard oil (MO)-induced visceral hypersensitivity in female rats and analyzed possible involved signaling pathways. Female rats, either intact or ovariectomized (OVX), were prepared for abdominal muscle electromyography in response to colorectal distension after intracolonic instillation of MO. The effect of MO intracolonic sensitization was evaluated in intact rats, OVX rats, and OVX rats pretreated with a single injection of 17beta-estradiol (E), progesterone (P), E+P, or vehicle. cAMP-responsive element-binding protein (CREB) and phosphorylated CREB (pCREB) were detected in the superficial dorsal horn of L6 and S1 in MO or mineral oil-treated OVX rats with/without colorectal distension and estrogen replacement. The distal colorectum was removed for histological evaluation of inflammatory severity in MO-treated intact or OVX rats. The MO-treated rats had significantly higher visceromotor reflex than controls (enhanced visceral hypersensitivity), whereas OVX eliminated this hypersensitivity. After a single injection of E or E+P, the rats rapidly restored MO-induced visceral hypersensitivity within 2 h. Estrogen also rapidly induced a dose-dependent increase in pCREB expression in the superficial dorsal horn neurons in MO-treated, but not mineral oil-treated, OVX rats. The present study suggests that estrogen can rapidly modulate visceral hypersensitivity induced by MO intracolonic instillation in conscious female rats, which may involve spinal activation of the cAMP response element-mediated gene induction pathway.

Animals↗

PubMed2006

Rat small intestinal transit is independent of glucose consumption in the strenuous exercise.

The present study was to determine the effect of strenuous exercise on glucose utilization, lactate accumulation and small intestinal transit (SIT). In strenuous exercises, rats would be put on the runway of a moving treadmill for a one-hour compulsive running. Rats first performed running treadmill for 45 min. After orogastric feeding of radiochromium marker, they resumed running for additional 15 min until sacrifice to measure SIT. Saline and various doses of glucose and lactate were infused through previously placed jugular vein during the whole procedure. Blood was finally obtained to measure plasma glucose and lactate levels. Saline infusion had no effect on running rat SIT during strenuous exercise, but plasma glucose level was significantly lowered (P < 0.01). Infusion of various doses of glucose did not alter SIT during strenuous exercise; however, the initially lowered plasma glucose was restored even to a hyperglycemic state. Meanwhile, strenuous running markedly increased plasma lactate level, irrespectively of saline or glucose infusion (P < 0.01). Lactate infusion did not change rat SIT obtained on the quiet runways. In conclusion, rat SIT remained unchanged in the strenuous exercise although obvious hypoglycemia and higher plasma lactate level did exist. Glucose utilization and lactate accumulation after the strenuous exercise may not directly mediate small intestinal motility.

Animals↗

PubMed2006

Effects of gabexate mesilate on serum inflammatory cytokines in rats with acute necrotizing pancreatitis.

Gabexate mesilate is a synthetic protease inhibitor. The effectiveness of gabexate mesilate in patients with acute pancreatitis is controversial. Proinflammatory cytokines are associated with systemic inflammatory response syndrome (SIRS) in acute pancreatitis. A compensatory anti-inflammatory response occurs in parallel with SIRS. We investigated the effects of gabexate mesilate on acute necrotizing pancreatitis in rats, emphasizing the changes in serum levels of proinflammatory and anti-inflammatory cytokines. Acute necrotizing pancreatitis was induced by retrograde infusion of sodium taurodeoxycholate into the pancreatobiliary duct in rats. The rats were divided into three groups. Group I was given gabexate mesilate 2 mg/kg/h i.v. continuously 1 h before the induction of acute pancreatitis. Group II was given gabexate mesilate the same dose immediately after the induction of acute pancreatitis. Group III was given normal saline as the controls. Serum levels of amylase, lipase, tumor necrosis factor alpha, interleukin-6, and interleukin-10, pancreatic histopathology and hemodynamics were examined at 5h after the induction of acute pancreatitis. Gabexate mesilate significantly reduced serum levels of amylase, lipase, tumor necrosis factor alpha and interleukin-6 at 5 h. Serum levels of interleukin-10 significantly increased in Group I, as compared with Groups II and III. The severity of pancreatic histopathology, the reduction of mean arterial pressure, the volume of ascites and pancreatic wet weight/body weight ratios were also significantly improved by the administration of gabexate mesilate. The beneficial effects of gabexate mesilate on acute pancreatitis may be, in part, due to the modulation of inflammatory cytokine responses.

Amylases↗

PubMed2006

A randomized trial of endoscopic treatment of acute gastric variceal hemorrhage: N-butyl-2-cyanoacrylate injection versus band ligation.

Progression of gastric variceal hemorrhage (GVH) is poorer than esophageal variceal bleeding. However, data on its optimal treatment are limited. We designed a prospective study to compare the efficacy of endoscopic band ligation (GVL) and endoscopic N-butyl-2-cyanoacrylate injection (GVO). Liver patients with cirrhosis with or without concomitant hepatocellular carcinoma (HCC) and patients presenting with acute GVH were randomized into two treatment groups. Forty-eight patients received GVL, and another 49 patients received GVO. Both treatments were equally successful in controlling active bleeding (14/15 vs. 14/15, P = 1.000). More of the patients who underwent GVL had GV rebleeding (GVL vs. GVO, 21/48 vs. 11/49; P = .044). The 2-year and 3-year cumulative rate of GV rebleeding were 63.1% and 72.3% for GVL, and 26.8% for both periods with GVO; P = .0143, log-rank test. The rebleeding risk of GVL was sustained throughout the entire follow-up period. Multivariate Cox regression indicated that concomitance with HCC (relative hazard: 2.453, 95% CI: 1.036-5.806, P = .041) and the treatment method (GVL vs. GVO, relative hazard: 2.660, 95% CI: 1.167-6.061, P = .020) were independent factors predictive of GV rebleeding. There was no difference in survival between the two groups. Severe complications attributable to these two treatments were rare. In conclusion, the efficacy of GVL to control active GVH appears not different to GVO, but GVO is associated with a lower GV rebleeding rate.

Acute Disease↗

PubMed2006

Proposal of a modified Child-Turcotte-Pugh scoring system and comparison with the model for end-stage liver disease for outcome prediction in patients with cirrhosis.

The model for end-stage liver disease (MELD) has a better predictive accuracy for survival than the Child-Turcotte-Pugh (CTP) system and has been the primary reference for organ allocation in liver transplantation. The CTP system, with a score range of 5-15, has a ceiling effect that may compromise its predictive power. In this study, we proposed a refined CTP scoring method and investigated its predictive ability. An additional point was given to patients with serum albumin < 2.3 g/dL, bilirubin > 8 mg/dL or prothrombin time prolongation > 11 seconds. The modified CTP system, containing class D, was compared to the MELD and original CTP system in 436 patients. There was a significant correlation between the MELD and modified CTP score (rho = 0.59, P< 0.001). Using mortality as the endpoint, the area under receiver operating characteristic curve for modified CTP system was 0.895 compared with 0.872 for MELD (P = 0.450) and 0.809 for original CTP system (P < 0.001) at 3 months; the area was 0.890, 0.837 and 0.756, respectively (P = 0.051 and < 0.001, respectively) at 6 months. The risk ratio per unit increase for the modified CTP score was 2.7 and 3.08 at 3 and 6 months respectively (P < 0.001). In conclusion, the modified CTP system can be proposed as an alternative prognostic model for cirrhotic patients. By extending the score range according to the influence of the laboratory-derived variables, the modified CTP system has a better performance than the original system and is as efficient as the MELD for outcome prediction.

Adult↗

PubMed2006

Analysis of humoral immunity of hepatitis D virus DNA vaccine generated in mice by using different dosage, gene gun immunization, and in vivo electroporation.

BACKGROUND: Hepatitis D virus (HDV) DNA vaccine can produce Th1 and cytotoxic T-cell immune responses but only a low anti-HDV antibody titer is generated with a large hepatitis D antigen (L-HDAg) construct. In contrast, DNA vaccine expressing small hepatitis D antigen (S-HDAg) can generate a high titer of anti-HDV antibodies. Whether the low humoral immunity of L-HDAg DNA vaccine is due to inadequate dosage or can be ameliorated by other modes of immunization needs further evaluation. METHODS: Plasmid (p25L) encoding L-HDAg and plasmid (pS/p25L) coexpressing hepatitis B surface antigen (HBsAg) and L-HDAg were used in this study. We compared the humoral response generated in mice using different plasmid DNA dosages and modes of immunization, including gene gun and in vivo electroporation (EP). RESULTS: Intramuscular injection with a high dose of plasmid DNA (10 mg/kg) produced strong antibodies to HBsAg earlier than the usual dose did, but did not augment the anti-HDV response. Gene gun DNA immunization could not provide a better humoral immune response to HDV. EP DNA immunization had a higher anti-HDV seroconversion rate of 80%, but the anti-HDV antibody responses were generally weak (titer < or = 400:1). CONCLUSION: The low humoral immunogenicity of DNA vaccine with L-HDAg cannot be ameliorated by different dosage, gene gun immunization, or in vivo EP intramuscular injection. DNA vaccine with a L-HDAg construct may not be a candidate HDV vaccine to generate anti-HDV humoral immunity.

Animals↗

PubMed2006

Acute hepatitis induced by Chinese hepatoprotective herb, xiao-chai-hu-tang.

Xiao-chai-hu-tang (syo-saiko-to in Japanese) is a herbal remedy that has been widely used in China for treatment of respiratory, hepatobiliary, and gastrointestinal diseases, particularly among patients with chronic liver disease. However, its safety has recently been challenged. We, herein, report a Chinese patient with acute hepatitis induced by this herb. A 52-year-old woman presented with weakness, fatigue, and tea-colored urine after continual consumption of the decoction of xiao-chai-hu-tang for 1.5 months. Laboratory studies disclosed acute hepatitis even though all of the viral hepatitis markers were negative. Liver biopsy also revealed a picture of acute hepatocellular hepatitis. The symptoms improved after discontinuing the drug, and liver biochemical tests normalized 2 months later. The case report reminds us of the probable adverse drug reaction of herbs, even in some that are claimed to have hepatoprotective effects.

Acute Disease↗

PubMed2006

Nonalcoholic fatty liver disease manifesting esophageal variceal bleeding.

Nonalcoholic fatty liver disease (NAFLD) is a fatty liver disease occurring in patients without alcohol consumption. It includes a broad spectrum of liver disease, from fatty infiltration, inflammation and fibrosis, to cirrhosis, usually having obesity, hyperlipidemia, and diabetes mellitus as its etiology. NAFLD-related cirrhosis has rarely been reported in Taiwan. We herein report a 41-year-old male patient with nonalcoholic fatty liver cirrhosis (NAFLC), with the first clinical manifestation being bleeding esophageal varices (EV). The patient was obese with diabetes mellitus, but without hyperlipidemia or any history of drinking alcohol. The laboratory tests, abdominal sonography, and computed tomography revealed a typical case of liver cirrhosis. The pan-endoscopy disclosed EV with red-color sign. EV ligation was performed successfully to stop the bleeding. When the patient was in a stabilized clinical condition, a liver biopsy showed a typical histologic finding of NAFLD. Most of the cases of NAFLC reported in the literature have silent signs and symptoms. Sudden onset of the EV as the first clinical manifestation, as in this case, is rare. This case reminds us that NAFLD may indeed induce severe liver impairment, such as liver cirrhosis. Liver biochemical tests and abdominal sonography should be considered in patients with overt obesity and diabetes.

Adult↗

PubMed2006

Lanreotide on collateral response to endothelin-1 and vasopressin in cirrhotic rats.

BACKGROUND: Portosystemic collaterals in cirrhosis are often complicated with hemorrhage. Endothelin-1 (ET-1) and arginine vasopressin (AVP) have been shown to directly constrict collaterals of portal hypertensive rats. Furthermore, octreotide, a long-acting somatostatin analog, enhances ET-1-related collateral vasoconstriction if administered in the perfusate before ET-1 incubation. However, long-term effects of somatostatin analogs on collateral response to ET-1 and AVP remain unclarified. This study investigated the effects of lanreotide (a longer-acting somatostatin analog when compared with octreotide) on the portosystemic collateral vascular reactiveness to ET-1 and AVP in cirrhotic rats. METHODS: Liver cirrhosis was induced in Sprague-Dawley rats by common bile duct ligation (BDL). On the 33rd day after BDL, rats received 1 intramuscular injection with lanreotide (10 mg/kg) or distilled water. On the 43rd day after BDL, systemic, and portal hemodynamics were evaluated. By an in situ perfusion model, ET-1 (10(-10) - 10(-7) mol/L) and AVP (10(-10) - 3 x 10(-7) mol/L) were applied to assess the collateral responses. RESULTS: Heart rate, mean arterial pressure, and portal pressure were not modified by lanreotide. Lanreotide pretreatment enhanced collateral vascular response to ET-1 and reached statistical significance at 10(-7) mol/L without inducing changes to AVP. CONCLUSION: Lanreotide augmented the collateral vascular responsiveness to ET-1 but not to AVP in cirrhotic rats.

Animals↗

PubMed2006

Methimazole alleviates hepatic encephalopathy in bile-duct ligated cirrhotic rats.

BACKGROUND: Acute or chronic liver damage may lead to hepatic encephalopathy. Previous studies have indicated the hemodynamic and hormonal mimicry between portal hypertension and hyperthyroidism. Furthermore, medically or surgically induced hypothyroidism has been found to be beneficial in ameliorating hyperdynamic circulation in the portal hypertensive state and in alleviating acute or chronic liver injury in rats. However, the effect of chronic thyroid hormone inhibition on chronic hepatic encephalopathy in cirrhosis remains unknown. METHODS: Liver cirrhosis was induced by bile-duct ligation (BDL) in male Sprague-Dawley rats. Three weeks after BDL, rats were randomized to receive either tap water (control) or 0.04% methimazole in drinking water for 3 weeks. At the end of 6 weeks after BDL, severity of encephalopathy was assessed by the Opto-Varimex animal activity meter and hemodynamic parameters were measured. Blood samples were collected for determination of thyroid stimulating hormone, ammonia and liver biochemistry. RESULTS: The heart rate of the methimazole-treated group was significantly lower than that of the control group (p = 0.015), whereas there were no differences in the mean arterial pressure and portal pressure. The total amount of movements were significantly increased in the methimazole group (p = 0.029). Plasma levels of ammonia, aspartate aminotransferase and alkaline phosphatase were significantly lower (p = 0.01) and thyroid stimulating hormone significantly higher (p = 0.035) in the methimazole group. CONCLUSION: Chronic methimazole treatment alleviates hepatic encephalopathy and liver damage in rats with BDL-induced hepatic cirrhosis.

Alanine Transaminase↗

PubMed2006

Psychosocial distress is associated with abnormal gastric myoelectrical activity in patients with functional dyspepsia.

OBJECTIVE: Functional dyspepsia (FD) is a heterogeneous and loosely defined clinical syndrome that is characterized by persistent or recurrent abdominal pain or discomfort centered in the upper abdomen without any identifiable structural or biochemical basis. Gastric myoelectrical activity in functional dyspepsia patients with gastric reddish streaks as a subgroup has not previously been investigated and the potential role of psychosocial distress in the genesis of gastric dysrhythmia in patients with FD is unclear. MATERIAL AND METHODS: Electrogastrography was performed in 45 patients with FD and 35 healthy controls for 30 min in the fasting state and 30 min postprandially. Psychological distress and the number and severity of stressful life events were measured using self-rating questionnaires. RESULTS: FD patients had a higher percentage of pre- and postprandial dysrhythmia, lower dominant frequency, and a higher instability coefficient as compared to healthy controls. In FD patients, severity of stressful life events was positively correlated with the percentage of tachygastria in the fasting state (r=0.43, p=0.005) and marginally positively correlated with the percentage of postprandial tachygastria (r=0.253, p=0.098) and instability coefficient of the dominant frequency (r=0.256, p=0.093). Total number of stressful life events was marginally positively correlated with fasting tachygastria (r=0.25, p=0.098) and instability coefficient of the postprandial dominant frequency (r=0.287, p=0.056). Interpersonal sensitivity was found to be negatively correlated with fasting dominant frequency in FD patients (r= - 0.311, p<0.05). CONCLUSIONS: FD patients with gastric reddish streaks have abnormal fasting and postprandial gastric myoelectrical activity. Perceived severity of stressful life events and interpersonal sensitivity are associated with disturbance of gastric myoelectrical activity.

Adult↗

PubMed2006

Chronic cyclooxygenase blockade enhances the vasopressin responsiveness in collaterals of portal hypertensive rats.

OBJECTIVE: Collateral vascular responsiveness to vasoconstrictors may be crucial in the management of acute variceal bleeding. In an in situ perfusion model, arginine vasopressin (AVP) has been shown to cause a direct vasoconstrictive effect on portal-systemic collaterals and this effect is enhanced by preincubation of indomethacin (INDO). The purpose of this study was to investigate the effects of chronic INDO administration on the portal-systemic collateral responsiveness to AVP and the degree of portal-systemic shunting in portal hypertensive rats. MATERIAL AND METHODS: Rats with partial portal vein ligation randomly received daily subcutaneous injections with INDO (5 mg/kg) or distilled water (control group) 2 days prior to until 7 days after ligation. Systemic and portal hemodynamics was evaluated on the 8th day. Using an in situ collateral perfusion model, AVP (10(-10)-10(-7) M) at a constant flow rate (20 ml/min) was applied. In another series, Krebs solution with different flow rates (5-30 ml/min) was used to obtain flow-pressure curves: the slopes represent collateral vascular resistances--the higher resistances indicate fewer collaterals. RESULTS: Mean arterial pressure and portal pressure were not significantly different between the INDO-treated group and the control group (p>0.05). In the first series of experiments, INDO treatment increased the collateral perfusion pressure to AVP at 10(-8) M, 3x10(-8) M, and 10(-7) M (p<0.05). In the second series, INDO did not change collateral vascular resistance, which suggests that the degree of shunting was not altered. CONCLUSIONS: Chronic INDO treatment improves the collateral vascular responsiveness to AVP without ameliorating portal-systemic shunting in portal hypertensive rats.

Animals↗

PubMed2006

Fever and infectious complications after percutaneous acetic acid injection therapy for hepatocellular carcinoma: incidence and risk factor analysis.

BACKGROUND: Ultrasound-guided percutaneous acetic acid injection (PAI) therapy is effective for hepatocellular carcinoma (HCC). Posttreatment fever (>37.5 degrees C) may occur owing to acetic acid-induced tumor necrosis, but its incidence and clinical significance are not clear. METHODS: A total of 402 treatment sessions in 127 consecutive patients undergoing PAI for HCC were prospectively studied. The incidence and risk factors associated with post-PAI fever were analyzed. RESULTS: There were 37 (9.2%) episodes of fever occurring in 29 HCC patients after PAI. Patients who developed fever more often had large-sized (3.5+/-1.3 cm vs. 2.7+/-1.2 cm, P=0.0002) tumor and a higher injection volume (2.6+/-0.1 mL vs. 2.2+/-0.1 mL, P=0.001) of acetic acid compared with those without fever. Multivariate logistic regression analysis showed that tumor size >3 cm was the only significant predictor associated with occurrence of posttreatment fever (odds ratio: 4.4, 95% confidence interval: 2.2-8.9, P<0.001). Three patients, all of whom had HCC diameter >3 cm, had 4 episodes of bacteremia after treatment; one of them developed liver abscess that required percutaneous drainage. CONCLUSIONS: Fever after PAI is not an uncommon event. Patients with tumor size >3 cm have a higher risk of posttreatment fever. Bacteremia and significant infectious complication could occur in a minority of patients. Prophylactic antibiotics before treatment may be necessary for high-risk patients.

Abscess↗

PubMed2006

Interaction of carbohydrate metabolism and rat liquid gastric emptying in sustained running.

BACKGROUND: Moderate to severe running usually leads to gastrointestinal dysmotility and critical energy exhaustion. It is unknown whether the carbohydrate metabolism of runners can influence gastric emptying (GE). Using a running rat model, the present study explored the impact of exercise/carbohydrate metabolism on liquid GE. METHODS: Rats were put on the runways of a moving treadmill for 1 h. Trained rats underwent daily running 5 days a week for 4 weeks. Untrained rats were those put on a quiet treadmill to serve as sham exercise. On the motility study day, trained and untrained rats ran for 45 min. After orogastric feeding of radiochromium marker, they resumed running for an additional 15 min and were then killed in order to measure GE. Another group of trained and untrained rats received lactate infusion for 1 h in the quiet condition to measure their GE. The third group of rats received glucose infusion during running to measure GE. RESULTS: Running of untrained (P < 0.05) and trained (P < 0.01) rats enhanced GE compared to sham exercise. Running for the untrained rats rather than the trained counterparts had diminished plasma glucose level (P < 0.05). Running also elevated plasma lactate levels for both untrained (P < 0.001) and trained rats (P < 0.01). Lactate infusion delayed GE in untrained (P < 0.01) and trained rats (P < 0.05). Glucose infusion of untrained rats during running was not only to correct hypoglycemia (P < 0.01) but also to restore their enhanced GE (P < 0.01). CONCLUSIONS: Running-induced hypoglycemia, rather than lactate accumulation, is one of the essential factors leading to enhanced liquid GE in untrained rats.

Animals↗

PubMed2006

Lack of detrimental or therapeutic effects of cyclooxygenase inhibition in bile duct-ligated rats with hepatic encephalopathy.

BACKGROUND: The pathogenetic mechanisms of hepatic encephalopathy (HE) are not fully understood. Cerebral blood flow regulated by cyclooxygenase (COX) may be involved in the development of HE. There are no comprehensive data concerning the effects of COX inhibition on HE in chronic liver disease. METHODS: Male Sprague-Dawley rats weighing 240-270 g at the time of surgery were selected for experiments. Secondary biliary cirrhosis was induced by bile duct ligation (BDL). Those rats were then divided into two groups to receive i.p. injection of indomethacin (5 mg/kg per day) or distilled water for 7 days from day 36 to day 42 after BDL. The control group consisted of rats receiving a sham operation. Severity of encephalopathy was assessed by counts of motor activity. Plasma levels of tumor necrosis factor (TNF)-alpha and 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), and liver biochemistry tests were determined after treatment. RESULTS: The motor activity in both groups of BDL rats were significantly lower than that of the control group (P < 0.001). As compared with the BDL rats treated with distilled water, BDL rats treated with indomethacin had significant lower levels of 6-keto-PGF(1alpha), but the motor activity, TNF-alpha levels and serum biochemistry tests were not significantly different between both BDL groups. CONCLUSIONS: Chronic indomethacin administration did not have significantly detrimental or therapeutic effects on the severity of encephalopathy in BDL rats.

6-Ketoprostaglandin F1 alpha↗

PubMed2006

Hemorheology in patients with liver cirrhosis: special emphasis on its relation to severity of esophageal variceal bleeding.

BACKGROUND: Patients with decreased blood viscosity are supposed to have a higher risk of bleeding and increased severity of bleeding (severity of bleeding proportional to transmural pressure x area of variceal tear/blood viscosity). However, the hemorheological factors have never been assessed in patients with esophageal variceal bleeding. Therefore, the purpose of the present study was to examine the hemorheological factors in liver cirrhotic patients with special emphasis on the outcome of variceal bleeding. METHODS: Forty-two liver cirrhosis patients with variceal bleeding and another 44 matched patients without bleeding were enrolled. The hemorheological and hemostatic factors of their peripheral blood were examined. The clinical course was under careful surveillance. RESULTS: Patients with poor hepatic reserve (Child B + C vs A) had lower whole blood viscosity (4.34 +/- 0.56 mPa.s vs 5.06 +/- 1.35 mPa.s, P < 0.05), lower hematocrit levels (32.86 +/- 5.97% vs 36.62 +/- 5.44%, P < 0.05), lower platelet counts (79.7 +/- 47.6 x 10(3)/mL vs 108.0 +/- 71.2 x 10(3)/mL, P < 0.05) and prolonged prothrombin time (2.88 +/- 2.33 s vs 1.27 +/- 1.37 s, P < 0.05). Patients with bleeding (vs non-bleeding group) had lower hematocrit levels (31.44 +/- 5.75% vs 36.57 +/- 5.19%, P < 0.01) and lower fibrinogen levels (226.7 +/- 92.7 mg/dL vs 286.4 +/- 111.8 mg/dL, P < 0.05). Patients with bleeding with shock had worse liver cirrhosis (Child A/B/C = 0/5/4 vs 11/18/4, P < 0.05), lower whole blood viscosity (4.01 +/- 0.17 mPa.s vs 4.57 +/- 0.76 mPa.s, P < 0.05), reduced erythrocyte aggregability (2.94 +/- 0.41 vs 3.54 +/- 0.61, P < 0.001), and lower platelet counts (56.22 +/- 17.05 x 10(3)/mL vs 88.87 +/- 38.12 x 10(3)/mL, P < 0.001). The Child-Pugh grade and erythrocyte aggregability were two independent factors associated with bleeding shock. CONCLUSIONS: Whole blood viscosity, hematocrit levels and platelet counts were lower in patients with advanced liver cirrhosis. Advanced liver cirrhosis and reduced erythrocyte aggregability were independent factors for hypovolemic shock in cirrhotic patients with esophageal variceal bleeding. However, the causal relationship between hemorheology and bleeding needs to be clarified in further studies.

Aged↗