Role of serum amitriptyline concentration and CYP2C19 polymorphism in predicting the response to low-dose amitriptyline in irritable bowel syndrome.

BACKGROUND: Low-dose amitriptyline (AMT) is an effective treatment for diarrhea-dominant irritable bowel syndrome (IBS-D). Its efficacy depends upon its serum concentration and the patient's CYP2C19 genotype. AIMS: To identify the association between serum AMT and nortriptyline (NT) concentration and CYP2C19 polymorphism and the clinical response in IBS-D patients. METHODS: Ninety IBS-D patients were treated of AMT for 6 weeks. Efficacy was evaluated by the results of the Adequate Relief question each week and an IBS severity scoring system (IBS-SSS) at 0, 3, and 6 weeks. CYP2C19 genotyping was performed by direct sequencing. AMT and NT steady-state serum concentrations were detected by high-performance liquid chromatography. RESULTS: The CYP2C19 polymorphism exhibited a significant influence on the NT serum concentration but did not predict the clinical efficacy of AMT for treating IBS-D. The NT steady-state and dose-corrected serum concentrations were significantly correlated with an improvement in the IBS-SSS score after 6 weeks, whereas the AMT serum concentration was not correlated with clinical improvement. The cut-off NT steady-state serum concentration of 2.91 ng/ml may help distinguish responders from non-responders. CONCLUSIONS: NT serum concentration but not CYP2C19 polymorphism may be correlated with the clinical efficacy of AMT for treating IBS-D, and such a response may occur at the upper NT threshold of 2.91 ng/ml.

Incidence and clinical features of hyperlipidemic acute pancreatitis from Guangdong, China: a retrospective multicenter study.

OBJECTIVE: This study aimed to investigate the clinical features and incidence trends of hyperlipidemic acute pancreatitis (HLAP) of multicenter studies in Guangdong, China, for 15 years. METHODS: The medical records of 1582 patients with acute pancreatitis who were admitted to 4 general hospitals of Guangdong from January 1990 to December 2005 were reviewed. The inpatient medical and radiologic records were reviewed to determine clinical features, severity, complications, mortality, and recurrence rate. RESULTS: A total of 7.8% (123/1582) patients met the HLAP criteria. Incidence of HLAP was approximately 2.6 times increased during 15 years (3.4% in 1990-1994, 5.9% in 1995-1999, and 8.9% in 2000-2005, respectively) and ranged from 3.3% to 15.5% in 4 hospitals across Guangdong. A history of diabetes was present in 31.7% and alcohol use in 18.7%. The mean (SD) triglyceride levels were 13.6 (7.2) mmol/L. Amylase was elevated higher than normal in 81.2% but only 2 times normal in 17.1% and 3 times normal in 37.6%. The frequency of severe acute pancreatitis, organ dysfunction, rate of recurrence, and mortality of HLAP was significantly higher than biliary-induced pancreatitis. CONCLUSIONS: The incidence of HLAP had significantly increased during the past 15 years with a clear geographic variation and remarkable severity and recurrent trend.

Surveillance of intra-abdominal pressure and intestinal barrier function in a rat model of acute necrotizing pancreatitis and its potential early therapeutic window.

OBJECTIVES: To monitor intra-abdominal pressure (IAP) and intestinal barrier function in a rat model of acute necrotizing pancreatitis (ANP) to elucidate a potential relevant therapeutic window. METHODS: Sprague-Dawley rats were randomly divided into experimental or control groups. The ANP group (n = 40) was injected with 4.5% sodium taurocholate into the pancreatic duct to induce ANP. The controls received only abdominal opening surgery (sham-operated, SO; n = 40) or no treatment or surgery (baseline; 0 h, n = 20). The SO and ANP groups were then randomly subdivided into 3, 6, 12 and 24 h groups (n = 10 each). IAP was measured at each time point and the rats were sacrificed to measure the weight of accumulated ascites fluid and the amylase, endogenous creatinine (Cr), total bilirubin (TB), tumor necrosis factor- alpha (TNF-alpha), diamine oxidase (DAO), and D-lactate. Mortality and the development of pathological changes in the pancreas and intestines were also monitored. RESULTS: IAP showed a continuous upward trend in the ANP group, with values 2 to 3 times higher than those in the SO group at the corresponding time points and the rising rate was peaking at 6 h. The levels of plasma amylase, TNF-alpha, Cr, TB, DAO, and D-lactate also gradually increased in the ANP group over time and were significantly higher than in the SO group at 3, 6, 12 and 24 h (all P<0.05). Moreover, the rising rate of TNF-alpha, DAO, and D-lactate also peaked at 6 h. CONCLUSIONS: The ANP-induced changes in IAP, inflammatory factors and intestinal barrier that we observed in the rat model were especially obvious at 6 h post-induction, suggesting an early therapeutic window for the treatment of ANP in humans.

Effect of amitriptyline on gastrointestinal function and brain-gut peptides: a double-blind trial.

AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period cross-over trial. Twenty-eight healthy volunteers were randomised and administered 1-wk treatments of AMT (12.5 mg tid) or placebo. Before and during the final two days of treatment, gastric emptying, proximal gastric accommodation and visceral sensitivity were measured by drinking-ultrasonography test; the orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were measured by enzyme-linked immunosorbent assay kits. RESULTS: AMT slowed the OCTT (109.2 ± 29.68 min vs 96.61 ± 23.9 min, P = 0.004) but did not affect liquid gastric emptying and had no effect on proximal gastric accommodation. AMT resulted in decreases in the visual analogue scale (VAS) for difficulty in drinking 600 and 800 mL of water (3.57 ± 0.94 vs 2.98 ± 0.85, 5.57 ± 0.82 vs 4.57 ± 0.98, P < 0.01 for both), although it had no significant effect on the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly increased the plasma ghrelin level (442.87 ± 176.79 pg/mL vs 526.87 ± 158.44 pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 ± 131.46 pg/mL vs 965.64 ± 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level. CONCLUSION: Low-dose AMT could slow OCTT, make the stomach less sensitive and increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low-dose AMT for functional gastrointestinal disorders.

Infliximab enhances the therapeutic effectiveness of octreotide on acute necrotizing pancreatitis in rat model.

OBJECTIVES: To investigate the synergistic activity of infliximab to the therapeutic effectiveness of octreotide in a rat model of acute necrotizing pancreatitis (ANP). METHODS: Forty Sprague-Dawley rats were randomly divided into sham-operated group (SO), ANP group (ANP), octreotide group (OG), infliximab group (IG), and combination group (CG) (n = 8 in each group). The ANP model was induced by biliopancreatic duct injection with 4.5% of sodium taurocholate solution. Rats of the OG, IG, and CG were given a tail vein injection of octreotide (10 µg/kg), infliximab (8 mg/kg), and infliximab (8 mg/kg), respectively, combined with octreotide (10 µg/kg) at 6 hours after modeling. All rats in each group were killed at 24 hours after modeling. Serum biochemical indicator and partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) of rats were determined. Pathological severity score of organs were evaluated. RESULTS: The serum biochemical indicator and organs' pathology score of OG , IG, and CG were obviously lower than those in the ANP group, and those in the CG were the lowest (P < 0.05). The PaO2/FiO2 levels in the OG, IG, and CG were significantly higher than that in the ANP group (P < 0.05). CONCLUSION: Infliximab could significantly lower the serum biochemical indicator, improve organs' function, and enhance the therapeutic effectiveness of octreotide on ANP.

Investigation of the incidence of pancreatic cancer-related depression and its relationship with the quality of life of patients.

AIM: To investigate the incidence of pancreatic cancer-related depression and the relationship between symptoms of depression and the quality of life (QoL) of patients. METHODS: 262 inpatients with cancer of the digestive system (pancreatic cancer, liver cancer, esophageal cancer, gastric cancer, and colorectal cancer) from four Guangzhou hospitals were enrolled into the study between June 2007 and June 2009. The Hamilton Rating Scale for Depression-24 questionnaire was used to assess the degree of depression. QoL of all patients was evaluated by EORTC QLQ-C30. Additionally, EORTC QLQ-PAN-26 was used for patients with pancreatic cancer. RESULTS: The incidence of depression among pancreatic cancer patients was significantly higher than among other digestive cancers. More pancreatic cancer patients suffered severe depression than those with liver cancer and gastric cancer. Compared with other groups with depression, QoL of pancreatic cancer patients in each functioning scale was significantly worse, while the symptoms of fatigue and pain were significantly severe. QoL of pancreatic cancer patients with depression in role, emotional, and social functioning were sharply poorer than those without depression. The symptoms of fatigue, pain and appetite loss in cancer patients with depression were significantly more frequent than those without depression. CONCLUSION: Compared with other cancers of the digestive system, depressive symptoms are common psychological disturbances in pancreatic cancer patients. Moreover, depression significantly lowers QoL in pancreatic cancer patients.

[Relationship between symptoms of pancreatic cancer-related depression and quality of life of patients].

OBJECTIVE: To investigate the relationship between symptoms of pancreatic cancer-related depression and quality of life of patients. METHODS: Fifty inpatients with pancreatic cancer from 3 Guangzhou hospitals between June 2007 and October 2008 were enrolled. Hamilton rating scale for depression-24 (HAMD-24) questionnaire was used to assess the degree of depression. Quality of Life (QoL) was evaluated by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30 (EORTC QLQ-C30) and QLQ-PAN-26 respectively. RESULTS: Thirty-nine (78.0%) of these patients reported depression and 12 patients (30.8%) had severe depression. The incidence of depression in pancreatic cancer patients with chemotherapy was 92.3% (24/26), which was significantly higher than that of patients with surgical therapy (62.5%, 15/24) (P = 0. 011). The QoL of pancreatic cancer patients with depression in role functioning, emotional functioning and social functioning was significantly worse than that of patients without depression. The symptoms of fatigue, pain and appetite loss in pancreatic cancer patients with depression were significantly more than those without depression (P < 0.05). CONCLUSIONS: Depressive symptoms are common psychological disturbance in pancreatic cancer patients. Moreover, depression significantly lowers quality of life for pancreatic cancer patients.