Multidisciplinary diagnosis and treatment of severe acute pancreatitis associated with hypertriglyceridemia in pregnancy: a case report.

Background: Hypertriglyceridemia (HTG) is an important cause of acute pancreatitis (AP) in pregnant women. Due to the variable clinical features of acute pancreatitis, it is difficult to make a differential diagnosis when abdominal pain occurs in late pregnancy. Severe HTG induced acute pancreatitis during pregnancy is rare, but may be a fatal threat to both mothers and fetuses during the peripartum period, and can increase maternal and fetal mortality. If emotional disorder combined, difficulty of treatment increased. So, multidisciplinary diagnosis combination of psychiatric treatment could improve the diagnosis rate and cure rate of acute pancreatitis during pregnancy. Case Description: We present the case of a 27-year-old Chinese woman in her first pregnancy, who was admitted to the hospital in the planned delivery period, but then developed progressive abdominal pain and whose biochemistry parameters were high enough to underwent a cesarean section as a result of AP a few hours after admission. The patient developed organ failure after a successful labor, which rapidly evolved to multi-organ failure, accompanied by depressive symptoms. Afterwards She appeared such as agitated, uneasy, and sad, and did not comply with the treatment, according to the classification of symptoms and course of disease, postpartum depression (PPD) was highly suspected. The patient benefited from multidisciplinary treatments that combined and integrated traditional Chinese medicine (TCM) with Western medicine therapies. The patient was discharged 35 days after her admission. Conclusions: This case highlights the importance of monitoring and managing excess dyslipidemia during pregnancy. A proactive strategy should be encouraged in the management of the patients with high risk of pancreatitis to improve the outcomes of patients. Our case report elucidates the possible long-term effects of HTG and reminds us of the need for long-term management of those affected.

Epigenetic changes in inflammatory genes and the protective effect of cooked rhubarb on pancreatic tissue of rats with chronic alcohol exposure.

Chronic alcohol consumption, which is observed worldwide, can damage pancreatic tissue and promote pancreatitis. Rhubarb is a widely used traditional Chinese herbal medicine for treating pancreatitis in China. However, few pharmacological studies have investigated its epigenetic regulation. In this study, we investigated whether chronic exposure to alcohol can alter inflammatory gene expression and the epigenetic regulation effect of cooked rhubarb in the pancreatic tissue of rats. First, changes in inflammatory cytokine DNA methylation (IL-10, IL-1α, TNF-α, NF-κB and TGF-ß) were detected in pancreatic tissue of Sprague-Dawley rats with varying alcohol exposure times (4, 6, 8, or 12 weeks), and then with varying doses of cooked rhubarb treatment (3, 6, or 12 g/day). DNA methylation levels, related RNA concentrations and protein expression of specific inflammatory cytokines, and histopathological score were analysed in pancreatic tissue of Sprague-Dawley rats. The results showed that chronic alcohol exposure (8 weeks) reduced the level of IL-1α DNA methylation and increased its protein expression in acinar cells (P < 0.05). In the acinar cells, the level of IL-10 DNA methylation increased, resulting in a reduction of protein expression (P < 0.05). Simultaneously, chronic alcohol exposure increased the pathological damage to the pancreas (P < 0.05). Finally, cooked rhubarb treatment (3 g/kg/day) effectively alleviated these changes in pancreatic tissue from chronic alcohol exposure (P < 0.05). These results indicate that chronic exposure to alcohol leads to changes in DNA methylation and protein expression of inflammatory genes, and cooked rhubarb may have a protective effect on the pancreatic tissue of rats.

Effect of Sheng-Jiang Powder on Gut Microbiota in High-Fat Diet-Induced NAFLD.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is an alarming global health problem that is predicted to be the major cause of cirrhosis, hepatocellular carcinoma, and liver transplantation by next decade. Gut microbiota have been revealed playing an important role in the pathogenesis of NAFLD. Sheng-Jiang Powder (SJP), an empirical Chinese medicine formula to treat NAFLD, showed great hepatoprotective properties, but the impact on gut microbiota has never been identified. Therefore, we performed this study to investigate the effect of SJP on gut microbiota in NAFLD mice. METHODS: NAFLD was induced by 12 weeks' high-fat diet (HFD) feeding. Mice were treated with SJP/normal saline daily for 6 weeks. Blood samples were obtained for serum biochemical indices and inflammatory cytokines measurement. Liver tissues were obtained for pathological evaluation and oil red O staining. The expression of lipid metabolism-related genes was quantified by RT-PCR and Western blotting. Changes in gut microbiota composition were analyzed by the 16s rDNA sequencing technique. RESULTS: HFD feeding induced significant increase in bodyweight and serum levels of TG, TC, ALT, and AST. The pathological examination revealed obvious hepatic steatosis in HFD feeding mice. Coadministration of SJP effectively protected against bodyweight increase and lipid accumulation in blood and liver. Increased expression of PPARγ mRNA was observed in HFD feeding mice, but a steady elevation of PPARγ protein level was only found in SJP-treated mice. Meanwhile, the expression of FASN was much higher in HFD feeding mice. Microbiome analysis revealed obvious changes in gut microbiota composition among diverse groups. SJP treatment modulated the relative abundance of short-chain fatty acids (SCFAs) producing bacteria, including norank-f-Erysipelotrichaceae and Roseburia. CONCLUSIONS: SJP is efficient in attenuating HFD-induced NAFLD, and it might be partly attributed to the regulation of gut microbiota.

Effect of Different-Volume Fluid Resuscitation on Organ Functions in Severe Acute Pancreatitis and Therapeutic Effect of Poria cocos.

OBJECTIVE: To explore the effect of different-volume fluid resuscitation (FR) on organ functions in severe acute pancreatitis (SAP) and to elucidate the therapeutic effect and mechanism of Poria cocos on organ injuries caused by high-volume FR. METHODS: 1. Clinical study: retrospective analysis of thirty-one patients about the effect of titrated fluid resuscitation protocol (TFR) on the occurrence of acute kidney injury (AKI) secondary to SAP. 2. Experimental study: rats (N = 30) were randomly divided into five groups: sham, model, low-volume FR (1.5 ml/kg/h), high-volume FR (10 ml/kg/h), and Poria cocos combined with high-volume FR (10 ml/kg/h + intraintestinal administration Poria cocos 5 g/kg); serum or plasma indicators and histopathologic scores were compared to explore the effect and mechanism of different fluid volumes and Poria cocos on organ function in SAP. RESULTS: The occurrence of AKI, fluid volume, and fluid velocity in TFR group was lower than that in the control group. Logistic regression analysis showed that increased Marshall scores and fluid velocity were risk factors for predicting occurrence of AKI in SAP. Low-volume FR decreased the levels of blood urea nitrogen (BUN), serum creatinine (Cr), matrix metalloproteinase (MMP), and pathologic scores of the pancreas and kidney. High-volume FR increased ascites, MMPs, and kidney pathologic scores. Poria cocos decreased the levels of BUN, Cr, MMPs, and pathologic scores of the pancreas and kidney and increased the arterial oxygen saturation. CONCLUSION: TFR-associated lower fluid volume and velocity reduced the occurrence of AKI secondary to SAP. High volume might aggravate AKI via increased MMP release leading to endothelial glycocalyx damage and vascular endothelial dysfunction. Poria cocos reduced MMP release, relieved glycocalyx damage, and alleviated the pancreas and kidney injury aggravated by high fluid volume in SAP. Therefore, endothelial glycocalyx protection might be a new strategy in the treatment of SAP.

Effect of Da-Cheng-Qi decoction for treatment of acute kidney injury in rats with severe acute pancreatitis.

BACKGROUND: The traditional Chinese formula Da-Cheng-Qi-decoction (DCQD) has been used to treat acute pancreatitis for decades. DCQD could ameliorate the disease severity and the complications of organ injuries, including those of the liver and lungs. However, the pharmacological effects in the kidney, a target organ, are still unclear. This study aimed to investigate the herbal tissue pharmacology of DCQD for acute kidney injury (AKI) in rats with severe acute pancreatitis (SAP). METHODS: Rats were randomly divided into the sham-operation group (SG), the model group (MG) and the low-, medium- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Sodium taurocholate (3.5%) was retrogradely perfused into the biliopancreatic duct to establish the model of SAP in rats. Different doses of DCQD were administered to the treatment groups 2 h after the induction of SAP. The major components of DCQD in kidney tissues were detected by HPLC-MS/MS. Inflammatory mediators in the kidney tissues, as well as serum creatinine (Scr), blood urea nitrogen (BUN) and pathologic scores, were also evaluated. RESULTS: Ten components of DCQD were detected in the kidneys of the treatment groups, and their concentrations increased dose-dependently. Compared with the SG, the levels of inflammatory mediators, Scr, BUN and pathological scores in the MG were obviously increased (p < 0.05). The high dose of DCQD showed a maximal effect in downregulating the pro-inflammatory mediators interleukin-6 (IL)-6 and tumour necrosis factor-α (TNF-α), upregulating anti-inflammatory mediators IL-4 and IL-10 in the kidney and alleviating the pathological damages. DCQD decreased the pancreas and kidney pathological scores of rats with SAP, especially in the HDG (p < 0.05). Compared with the MG, the level of Scr in the HDG was significantly decreased (p < 0.05). CONCLUSIONS: DCQD ameliorated AKI in rats with SAP via regulating the inflammatory response, which might be closely related to the distribution of its components in the kidney.

Optimal timing for the oral administration of Da-Cheng-Qi decoction based on the pharmacokinetic and pharmacodynamic targeting of the pancreas in rats with acute pancreatitis.

AIM: To identify the optimal oral dosing time of Da-Cheng-Qi decoction (DCQD) in rats with acute pancreatitis (AP) based on the pharmacokinetic and pharmacodynamic parameters. METHODS: First, 24 male Sprague-Dawley rats were divided into a sham-operated group [NG(a)] and three model groups [4hG(a), 12hG(a) and 24hG(a)]. The NG(a) and model groups were administered DCQD (10 g/kg.BW) intragastrically at 4 h, 4 h, 12 h and 24 h, respectively, after AP models induced by 3% sodium taurocholate. Plasma samples were collected from the tails at 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, 8 h, 12 h and 24 h after a single dosing with DCQD. Plasma and pancreatic tissue concentrations of the major components of DCQD were determined by high-performance liquid chromatography tandem mass spectroscopy. The pharmacokinetic parameters and serum amylase were detected and compared. Second, rats were divided into a sham-operated group [NG(b)] and three treatment groups [4hG(b), 12hG(b) and 24hG(b)] with three corresponding control groups [MG(b)s]. Blood and pancreatic tissues were collected 24 h after a single dosing with DCQD. Serum amylase, inflammatory cytokines and pathological scores of pancreatic tissues were detected and compared. RESULTS: The concentrations of emodin, naringin, honokiol, naringenin, aloe-emodin, chrysophanol and rheochrysidin in the 12hG(a) group were higher than those in the 4hG(a) group in the pancreatic tissues (P < 0.05). The area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration values (AUC0→t) for rhein, chrysophanol, magnolol and naringin in the 12hG(a) group were larger than those in the 4hG(a) or 24hG(a) groups. The 12hG(a) group had a higher Cmax than the other two model groups. The IL-10 levels in the 12hG(b) and 24hG(b) groups were higher than in the MG(b)s (96.55 ± 7.84 vs 77.46 ± 7.42, 251.22 ± 16.15 vs 99.72 ± 4.7 respectively, P < 0.05), while in the 24hG(b) group, the IL-10 level was higher than in the other two treatment groups (251.22 ± 16.15 vs 154.41 ± 12.09/96.55 ± 7.84, P < 0.05). The IL-6 levels displayed a decrease in the 4hG(b) and 12hG(b) groups compared to the MG(b)s (89.99 ± 4.61 vs 147.91 ± 4.36, 90.82 ± 5.34 vs 171.44 ± 13.43, P < 0.05). CONCLUSION: Late-time dosing may have higher concentrations of the most major components of DCQD, with better pharmacokinetics and pharmacodynamics of anti-inflammation than early-time dosing, which showed the late time to be the optimal dosing time of DCQD for AP.

Pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction in the liver of rats with severe acute pancreatitis.

AIM: To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis. METHODS: Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloe-emodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated. RESULTS: The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-α and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG (P < 0.05). DCQD could reduce the pathological scores in the pancreas and liver of the rats with SAP, especially in the HDG. Compared to the SOG, the ALT and AST levels in serum were higher in the MG (P < 0.05), while there was no statistical difference in the MG and HDG. CONCLUSION: DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.

Formula Compatibility Identification of Dachengqi Decoction Based on the Effects of Absorbed Components in Cerulein-Injured Pancreatic AR42J Cells.

Objective. To identify the herbal formula compatibility law based on the effects of the absorbed components from DCQD on the cerulein-injured AR42J cells. Methods. AR42J cells were pretreated for 30 min with or without the different concentrations of the absorbed components from DCQD individually or in combination or DCQD and coincubated with cerulein (10 nM) for a further 24 h. Cell viability, lactate dehydrogenase (LDH) release, and the levels of apoptosis and necrosis were measured. Results. Compared to DCQD, the individual or combination components partially protected cerulein-injured AR42J cells by increasing cell viability, reducing LDH release, and promoting apoptosis. Rhein, naringin, and honokiol were the main absorbed components from DCQD in cerulein-induced pancreatitis. Moreover, rhein in combination with naringin and honokiol had synergistic effects in protecting cerulein-injured AR42J cells and was better than the individual or the pairwise combination of the three components. Conclusions. The ten effective components from DCQD may elicit similar protective effects as DCQD on cerulein-induced pancreatitis. The principle of the formula compatibility of DCQD may be identified based on the effects of its absorbed components in cerulein-injured AR42J cells.

Tissue Pharmacology of Da-Cheng-Qi Decoction in Experimental Acute Pancreatitis in Rats.

Objectives. The Chinese herbal medicine Da-Cheng-Qi Decoction (DCQD) can ameliorate the severity of acute pancreatitis (AP). However, the potential pharmacological mechanism remains unclear. This study explored the potential effective components and the pharmacokinetic characteristics of DCQD in target tissue in experimental acute pancreatitis in rats. Methods. Acute pancreatitis-like symptoms were first induced in rats and then they were given different doses of DCQD (6 g/kg, 12 g/kg, and 24 g/kg body weight) orally. Tissue drug concentration, tissue pathological score, and inflammatory mediators in pancreas, intestine, and lung tissues of rats were examined after 24 hours, respectively. Results. Major components of DCQD could be found in target tissues and their concentrations increased in conjunction with the intake dose of DCQD. The high-dose compounds showed maximal effect on altering levels of anti-inflammatory (interleukin-4 and interleukin-10) and proinflammatory markers (tumor necrosis factor α and interleukin-6) and ameliorating the pathological damage in target tissues (P < 0.05). Conclusions. DCQD could alleviate pancreatic, intestinal, and lung injury by altering levels of inflammatory cytokines in AP rats with tissue distribution of its components.

Effect of acute pancreatitis on the pharmacokinetics of Chinese herbal micron Liuhe Pill ointment in rats.

OBJECTIVE: To explore the effect of acute pancreatitis (AP) on the pharmacokinetics of herbal ointment micron Liuhe Pill, MLHP) components in anesthetized rats. METHODS: Rats were randomly divided into a AP model group (n=6) and a normal group as a control (n=6). The rat model of AP was induced by intraperitoneal injection of L-arginine in rats (15 mg/kg, twice, interval 1 h). Chinese herbal ointment MLHP was used externally on the belly after the 2nd injection for 48 h in both groups. Emodin, rhein, aloe emodin, physcion, chrysophanol from MLHP were detected and quantified in rat serum and pancreas (at 48 h) by high performance liquid chromatography-tandem mass spectrometry. RESULTS: Among the five components, only emodin, aloe emodin and physcion from MLHP were detected in all rat serum and most of the rats' pancreas. Rhein and chrysophanol were not detected in both serum and pancreas. T1/2α of emodin and physcion in MLHP were obviously shorter in the AP model group than those in the normal group (P<0.05), while there was no difference for T1/2α of aloe emodin. The peak concentration and area under curve of all three components were much higher in the AP group than those in the normal group with MLHP in external application for 48 h (P<0.05). Furthermore, the mean residence time (MRT) and maximum plasma concentration (Tmax) of emodin and aloe emodin were obviously longer in the AP model group than those in the normal control group (P<0.05). There was no significant difference for Ka of all components between the two groups. Emodin could be detected in all rats' pancreas at 48 h in both groups, while its mean pancreatic concentration was higher in the AP model group than in the normal group (0.61±0.54 ng/mL, 0.42±0.37 ng/mL, respectively,P<0.05). Aloe emodin could be detected in all rats' pancreas at 48 h in both groups and their mean pancreatic concentration were similar (0.31±0.24 ng/mL, 0.33±0.17 ng/mL, respectively,P>0.05). Physcion could be detected in pancreas of most rats in the AP model while only two rats in the normal group. CONCLUSION: AP could significantly affect the pharmacokinetics of absorbed components of Chinese herbal MLHP ointment in rats.

Metabolomic profiles illuminate the efficacy of Chinese herbal Da-Cheng-Qi decoction on acute pancreatitis in rats.

BACKGROUND AND OBJECTIVES: Chinese herbal drug Da-Cheng-Qi decoction (DCQD) has been widely used for decades to treat acute pancreatitis (AP). Previous trials are mostly designed to state the potential mechanisms of the therapeutic effects rather than to detect its whole effect on metabolism. This study aimed to investigate the efficacy of DCQD on metabolism in AP. METHODS: Twenty-two male adult Sprague-Dawley rats were randomized into three groups. AP was induced by retrograde ductal infusion of 3.5% sodium taurocholate solution in DCQD and AP group, while 0.9% saline solution was used in sham operation (SO) group. Blood samples were obtained 12 h after drug administration and a 600 MHz superconducting Nuclear Magnetic Resonance (NMR) spectrometer was used to detected plasma metabolites. Principal Components Analysis (PCA) and Partial Least Squares-Discriminant Analysis after Orthogonal Signal Correction (OSC-PLS-DA) were applied to analyze the Longitudinal Eddy-delay (LED) and Carr-Purcell-Meiboom-Gill (CPMG) spectra. RESULTS: Differences in concentrations of metabolites among the three groups were detected by OSC-PLS-DA of 1HNMR spectra (both LED and CPMG). Compared with SO group, DCQD group had higher levels of plasma glycerol, glutamic acid, low density lipoprotein (LDL), saturated fatty acid (FA) and lower levels of alanine and glutamine, while the metabolic changes were reversed in the AP group. CONCLUSIONS: Our results demonstrated that DCQD was capable of altering the changed concentrations of metabolites in rats with AP and 1HNMR-based metabolomic approach provided a new methodological cue for systematically investigating the efficacies and mechanisms of DCQD in treating AP.

Factors affecting the evacuation rate of intracerebral hemorrhage in basal ganglia treated by minimally invasive craniopuncture.

OBJECTIVE: Minimally invasive craniopuncture has been used to treat intracerebral hemorrhage (ICH) for over 20 years in China. However, one-off total evacuation of hematoma cannot be achieved through this procedure because it is not an open surgery. This study is designed to identify factors that can increase the hematoma evacuation rate (ER) of this procedure and to evaluate the influence of ER on long-term outcome. METHODS: A total of 309 patients with basal ganglia ICH treated by minimally invasive craniopuncture were analyzed retrospectively. Univariate and multivariate linear regression analyses were used to identify factors correlated with a high ER. The correlation between ER and long-term outcome was also analyzed by logistic regression and the Spearman correlation. RESULTS: A low hematoma mean CT number (ß=-0.773, p<0.001) and postoperative cerebrospinal fluid (CSF) outflow (ß=0.193, p<0.001) were found to be independent factors associated with a high ER. In patients with 30-50ml of hematoma, a high ER was correlated with a high Barthel index improvement (r=0.611, p<0.001) and a high modified Rankin scale decline (r=0.517, p<0.001). In patients with 50-80ml of hematoma, a high ER was a protective factor of case fatality (B=-2.297, p=0.005). CONCLUSIONS: The hematoma mean CT number can predict the efficiency of minimally invasive craniopuncture in patients with ICH. In patients with ventricular involvement, the tip of the puncture needle should be placed close to the tear in the ventricle rather than at the center of the hematoma to facilitate postoperative CSF outflow.

Effect of electroacupuncture on the inflammatory response in patients with acute pancreatitis: an exploratory study.

OBJECTIVES: To examine the effects of electroacupuncture (EA) on inflammatory responses in patients with acute pancreatitis (AP). METHODS: Eighty patients with mild or severe AP were randomly allocated to a control group or an EA group. All patients were managed conservatively. In addition, the EA group received acupuncture for 30 min per day for 7 days at bilateral points ST36, LI4, TE6, ST37 and LR3. Interleukin (IL)-6, IL-10 and C-reactive protein (CRP) levels were measured on admission and on day 7. The time to re-feeding and length of stay in hospital were also recorded. RESULTS: A total of 58 patients provided complete data. The characteristics of the patients in the EA and control groups were similar. After 7 days the serum concentrations of IL-10 were higher in the EA group than in the control group (mild AP: 6.2±1.2 vs 5.2±0.9 pg/mL, p<0.05; severe AP: 14.9±7.8 vs 7.9±6.3 pg/mL, p<0.05). For patients with severe AP, the CRP level in the EA group was lower than in the control group (p<0.05). CONCLUSIONS: EA may reduce the severity of AP by inducing anti-inflammatory effects and reducing the time to re-feeding; however, it did not reduce the length of hospital stay. TRIAL REGISTRATION NUMBER: ChiCTR-TRC-13003572.

Rhein induces a necrosis-apoptosis switch in pancreatic acinar cells.

Objectives. The Chinese herbal medicine Da-Cheng-Qi decoction can regulate a necrosis-apoptosis switch in injured pancreatic acinar cells. This study investigated the effects of rhein, a component of this medicine, on a necrosis-apoptosis switch in pancreatic rat AR42J cells. Methods. Cerulein-treated AR42J cells were used. After pretreatment with 479, 119.8, or 29.9 µ g/L rhein, cells were cocultured with rhein and cerulein (10(-8) M) for 4, 8, or 16 h. Apoptosis and necrosis were examined using annexin V and propidium iodide costaining. Mitochondria-dependent apoptosis-associated proteins were examined using enzyme-linked immunosorbent assays and western blotting. Results. Few cells died in untreated samples. The number was significantly higher in 16-h-cerulein-treated samples and treatment with 479 µ g/L rhein most effectively increased the apoptotic-to-necrotic cell ratio (P < 0.05). In cerulein-treated cells, rhein increased the concentrations of p53, cytochrome C, and caspase-3, and increased the Bax/Bcl-2 ratio in a time- and dose-dependent manner, with the maximum effect in cells treated with 479 µ g/L rhein for 16 h (P < 0.05). Conclusions. Rhein induces the necrosis-apoptosis switch in injured pancreatic acinar cells in a time- and dose-dependent manner. Mitochondria-dependent apoptosis signaling pathways might play an important role in this effect.

Electroacupuncture Ameliorates Acute Lung Injury through Promoting Gastrointestinal Motility in Rats with Acute Pancreatitis.

Objective. Gastrointestinal disfunction and acute lung injury (ALI) were common in acute pancreatitis (AP). The effect of electro-acupuncture (EA) on gastrointestinal motility and ALI in rats with AP was investigated to verify the theory of "lung and large intestine are interior exteriorly related" in traditional Chinese medicine. Methods. Male Sprague-Dawley rats were randomly divided into the normal group, model group, and EA group. AP model was established by three injections of 20% L-arginine at 1 h intervals. EA were applied to bilateral ST-25 and ST-36 for 30 minutes twice a day after modeling for 3 days. Arterial blood, pancreas, lung, and intestinal tissues were collected for detecting the inflammatory factors and histopathology. Intestinal propulsion rate (IPR) was also measured at 72 h. Results. EA treatment improved IPR and increased CCK-8 level compared with model group (P < 0.05). It lowered the serum levels of TNF- α and IL-6 and increased the level of IL-4 with no effect on IL-10. EA treatment reduced serum vasoactive intestinal peptide (VIP) and myeloperoxidase (MPO) level in the lung and the pathologic scores of pancreas, lung and intestine were decreased (P < 0.05). Conclusion. EA treatment could promote gastrointestinal motility through inhibiting VIP, and promoting CCK expression and regulate pro- and anti-inflammatory mediators to ameliorate ALI in AP.

Pharmacokinetic and pharmacodynamic comparison of chinese herbal ointment liu-he-dan and micron liu-he-dan ointment in rats with acute pancreatitis.

Aim. To compare the pharmacokinetics and pharmacodynamics of herbal ointment Liu-He-Dan (LHD) and micron LHD (MLHD) in rats with acute pancreatitis (AP). Methods. Twenty rats were allocated into normal, AP, LHD, and MLHD groups. LHD or MLHD was applied on rats' abdomens. Plasma levels of emodin, rhein, aloe emodin, physcion, and chrysophanol were determined by high performance liquid chromatography-mass spectrometry-mass spectrometry (HPLC-MS-MS) at different time points, and the pharmacokinetic parameters were calculated. Serum amylase, TNF- α , IL-6, and IL-10 levels, and the pancreatic pathological scores were determined at 48 h after LHD or MLHD treatment. Results. T 1/2 α and area under the curve (AUC) of emodin in the MLHD group were lower than those in the LHD group, while T 1/2 α and AUC of aloe emodin in the MLHD group were higher than those in the LHD group (P < 0.05). T 1/2 α and T max of physcion in the MLHD group were significantly shorter than those in the LHD group (P < 0.05). Compared with the AP group, the amylase, malondialdehyde (MDA), TNF- α , and IL-6 levels decreased significantly after three days of treatment in LHD and MLHD groups, while the levels of superoxide dismutase (SOD), TNF- α , and the pancreatic pathological score, were similar. The pharmacodynamic parameters between the LHD and MLHD groups were similar. Conclusion. MLHD had better pharmacokinetics than, and similar pharmacodynamics to, LHD in the management of rats with AP, which indicated that MLHD might be substituted for LHD in the treatment of AP and thus reduce the amount of medicinal herbs used.

Effect of acute pancreatitis on the pharmacokinetics of Chinese herbal ointment Liu-He-Dan in anaesthetized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal preparation of Liu-He-Dan ointment has been adapted for acute pancreatitis in external application for many years in West China. AIM OF THE STUDY: To investigate the effect of acute pancreatitis on the pharmacokinetics of Liu-He-Dan ointment in rats while it was used externally on belly. MATERIALS AND METHODS: Twelve male Sprague-Dawley rats were randomly divided into acute pancreatitis model group (n=6) and normal group as a control (n=6). Chinese herbal Liu-He-Dan ointment was used externally on belly. Emodin, rhein, aloe emodin, physcion and chrysophanol in plasma and pancreas (at 48 h) were detected and quantified by liquid chromatography-tandem mass spectrometry. Amylase in plasma were determined with iodide process. RESULTS: Among the five components, only emodin, aloe emodin and physcion from Liu-He-Dan were detected in plasma and pancreas. The absorption of each component was tended to decrease in acute pancreatitis group after topically management with Liu-He-Dan ointment on rats' abdomen. The T(max), C(max) and area under curve (AUC) of each component were distinctly lower in AP group than those in normal group (p<0.05). However, the T(1/2α) and mean retention time (MRT) of emodin lasted longer in acute pancreatitis group than those in normal group (p<0.05). There was no statistical difference in the MRT of aloe emodin and physcion between the two groups. Emodin could be detected in all rats' pancreas at 48 h in both groups, while its mean pancreatic concentration was higher in acute pancreatitis model group than in normal group (0.91 ± 0.68, 0.41 ± 0.36, respectively). Physcion could be detected in pancreas of most acute pancreatitis models, but not in normal rats. Aloe emodin was found in all pancreas from acute pancreatitis models while only one in normal group. The level of amylase in Liu-He-Dan group was obviously lower than that in the AP model group (p=0.0055). CONCLUSION: We concluded that acute pancreatitis may significantly affect the pharmacokinetics of Liu-He-Dan while external applied on belly, which indicated the dosage modification in AP. However, acute pancreatitis seems to promote the distribution of the detected components into pancreas. The ointment could help relieve the disease of pancreatitis.

[The influnence of dachengqi tang on acute lung injury and intra abdominal hypertension in rats with acute pancreatitis].

OBJECTIVE: To test the hypothesis "lung and large intestine are interior exteriorly related" through investgating into the effect of Dacheng qi tang (DCQT) on intra abdominal hypertension (IAH) and acute lung injury (ALI) in rats with acute pancreatitis. METHODS: Male SD rats were randomly divided into three groups with ten rats for each group: rats with sham-operations (SO); rats with acute necrosis pancreatitis (ANP); rats with ANP plus DCQT treatment. ANP was induced by retrograde infusion of 5% taurocholic acid into pancreatic duct. Two hours after operations, 10 mL/kg of normal saline was orally adminstered to the rats in both SO and ANP groups, whereas 10 mL/kg DCQT was adminstered to the rats in the treatment group. Aterial blood, pancreas and lung tissues were collected for biomarkers and histopathology 24 hours after operations. Intra-abdominal pressure and intestinal propulsion rate were also measured. RESULTS; DCQT treatment reduced intra-abdominal pressure and improved intestinal propulsion rate compared with those treated with saline (P < 0.05). The ANP rats treated with DCQT had lower wet to dry weight ratio, and milder myeloperoxidase activity and histopathology changes in pancreas and lung than those treated with saline (P < 0.05). Higher pressure of oxygen (PO2) was found in the rats treated with DCQT, while no difference in PCO2 was found between the DCQT and ANP groups (P > 0.05). Only two rats in the ANP group died. CONCLUSION: DCQT can effectively relieve IAH and cure ALI at the same time in rats with acute pancreatitis. The result provides evidence to support the hypothesis "lung and large intestine are interior exteriorly related".

The cryoprotective effects of ascorbic acid supplementation on bovine semen quality.

To investigate the effects of ascorbic acid supplementation on standard semen quality parameters and antioxidant activities after thawing of bovine frozen semen, antioxidant ascorbic acid was added at concentrations of 2.5, 4.5, 6.5 and 8.5 mg/ml to bovine semen cryoprotective medium. The results showed that the sperm motility and motion characteristics were improved in the presence of ascorbic acid in extender, as compared to the control. The motility and straight linear velocity (VSL), linearity index (LIN), average path velocity (VAP), wobble coefficient (WOB), lateral head displacement (ALH) values and the percentage of "grade A" sperm in the extender supplemented with 4.5 mg/ml ascorbic acid were significantly higher than that of other treatment groups (P<0.05). The acrosome integrity and membrane integrity were significantly improved (P<0.05) by supplementing with 4.5 mg/ml ascorbic acid in the extender compared with a control. The extender supplemented with ascorbic acid did not lead to any improvement in superoxide dismutase (SOD) levels. The catalase (CAT) activity was higher in the extender supplemented with ascorbic acid at 4.5 mg/ml, when compared with other groups (P<0.05) and the extender supplemented with ascorbic acid significantly decreased glutathione peroxidase (GSH-Px) activity, whereas reduced glutathione (GSH) activities were significantly enhanced, compared with the control (P<0.05). Increasing the doses level of ascorbic acid decreased GSH-Px and GSH activity, the supplementation of 8.5 mg/ml ascorbic acid produced the lowest level of GSH-Px and GSH activity among groups (P<0.05). The extender supplemented with ascorbic acid could reduce the oxidative stress provoked by freezing-thawing and improve bovine semen quality. The particular properties of ascorbic acid are poorly related to its effectiveness in membrane cryopreservation. Further studies are required to determine lipid peroxidation and antioxidant capacities of ascorbic acid in cryopreserved bovine semen.