Vitamin D and Pancreatitis: A Narrative Review of Current Evidence.

Emerging research indicates that vitamin D metabolic disorder plays a major role in both acute pancreatitis (AP) and chronic pancreatitis (CP). This has been demonstrated by studies showing that vitamin D deficiency is associated with pancreatitis and its anti-inflammatory and anti-fibrotic effects by binding with the vitamin D receptor (VDR). However, the role of vitamin D assessment and its management in pancreatitis remains poorly understood. In this narrative review, we discuss the recent advances in our understanding of the molecular mechanisms involved in vitamin D/VDR signaling in pancreatic cells; the evidence from observational studies and clinical trials that demonstrate the connection among vitamin D, pancreatitis and pancreatitis-related complications; and the route of administration of vitamin D supplementation in clinical practice. Although further research is still required to establish the protective role of vitamin D and its application in disease, evaluation of vitamin D levels and its supplementation should be important strategies for pancreatitis management according to currently available evidence.

Chai-Qin-Cheng-Qi Decoction and Carbachol Improve Intestinal Motility by Regulating Protein Kinase C-Mediated Ca2+ Release in Colonic Smooth Muscle Cells in Rats with Acute Necrotising Pancreatitis.

Chai-Qin-Cheng-Qi decoction (CQCQD) improves intestinal motility in acute pancreatitis (AP), but the mechanism(s) require elucidation. We investigated the effects of CQCQD and carbachol, a prokinetic agent, on colonic smooth muscle cells (SMCs) in L-arginine-induced necrotising AP model in rats. In treatment groups, intragastric CQCQD (20 g/kg, 2 hourly × 3 doses) or intraperitoneal carbachol (60 µg/kg) was given 24 hours after induction of AP. Both CQCQD and carbachol decreased the severity of pancreatic and colonic histopathology (all P < 0.05). Both CQCQD and carbachol reduced serum intestinal fatty acid binding protein, vasoactive intestinal peptide, and substance P and increased motility levels. CQCQD upregulated SMC phospholipase C-beta 1 (PLC-ß1) mRNA and PLC protein (both P < 0.05), while both treatments upregulated protein kinase C-alpha (PKC-α) mRNA and PKC protein and downregulated adenylate cyclase (AC) mRNA and protein compared with no treatment (all P < 0.05). Neither treatment significantly altered L-arginine-induced PKC-ß1 and PKC-ε mRNA reduction. Both treatments significantly increased fluorescence intensity of SMC intracellular calcium concentration [Ca2+]i (3563.5 and 3046.9 versus 1086.9, both P < 0.01). These data suggest CQCQD and carbachol improve intestinal motility in AP by increasing [Ca2+]i in colonic SMCs via upregulating PLC, PKC and downregulating AC.

Effect of Chaiqin Chengqi Decoction on cholecystokinin receptor 1-mediated signal transduction of pancreatic acinar cells in acute necrotizing pancreatitis rats.

OBJECTIVE: To investigate the effect of Chaiqin Chengqi Decoction (,CQCQD) on cholecystokinin receptor 1 (CCKR1)-mediated signal transduction of pancreatic acinar cell in rats with acute necrotic pancreatitis (ANP). METHODS: Twenty-seven Sprague-Dawley rats were randomized into three groups: the control group, the ANP group, and the CQCQD group (9 in each group). ANP rats were induced by two intraperitoneal injections of 8% L-arginine (pH=7.0, 4.4 g/kg) over a 2-h period. Rats were treated with 1.5 mL/100 g body weight of CQCQD (CQCQD group) or physiological saline (control and ANP groups) at 2 h interval. And 6 h after induction, pancreatic tissues were collected for histopathological examination. Pancreatic acinar cells were isolated for determination of CCKR1 mRNA and protein expression, phospholipase C (PLC) and inositol-1,4,5-triphosphate (IP3), and determination of fluorescence intensity (FI) as a measure of intracellular calcium ion concentration [Ca(2+)]i. RESULTS: The pancreatic histopathological score (6.2 ± 1.1) and the levels of PLC (1,187.2 ± 228.2 µg/mL) and IP3 (872.2 ± 88.4 µg/mL) of acinar cells in the ANP group were higher than those in the control (2.8 ± 0.4, 682.5 ± 121.8 µg/mL, 518.4 ± 115.8 µg/mL) and the CQCQD (3.8 ± 0.8, 905.3 ± 78.5 µg/mL, 611.0 ± 42.5 µg/mL) groups (P<0.05). [Ca(2+)]i FI for the ANP group (34.8±27.0) was higher than that in the control (5.1 ± 2.2) and CQCQD (12.6 ± 2.5) groups (P<0.05). The expression of pancreatic acinar cell CCKR1 mRNA in the ANP group was up-regulated (expression ratio=1.761; P=0.024) compared with the control group. The expression of pancreatic acinar cell CCKR1 mRNA in the CQCQD group was down-regulated (expression ratio=0.311; P=0.035) compared with the ANP group. The ratio of gray values of the CCKR1 and ß-actin in the ANP group (1.43 ± 0.17) was higher than those in the control (0.70 ± 0.15) and CQCQD (0.79 ± 0.11) groups (P<0.05). CONCLUSIONS: Pancreatic acinar cell calcium overload of ANP induced by L-arginine was related to the up-regulated expressions of pancreatic acinar cell CCKR1 mRNA and protein. CQCQD can down-regulate expressions of pancreatic acinar cell CCKR1 mRNA and protein to reduce the PLC and IP3 of pancreatic acinar cells, relieving the calcium overload and reducing the pathological changes in rats with ANP.

The effect of Chaiqin Chengqi Decoction () on modulating serum matrix metalloproteinase 9 in patients with severe acute pancreatitis.

OBJECTIVE: To investigate the effect of Chaiqin Chengqi Decoction (, CQCQD) on regulating serum matrix metalloproteinase 9 (MMP-9) in patients with severe acute pancreatitis (SAP). METHODS: Thirty-five SAP patients hospitalized in West China Hospital from September 1, 2008 to February 28, 2009 were randomly assigned to two groups using a computer-derived random number sequence in a ratio of 1:1, treatment group (18 patients) and the placebo control group (17 patients). The patients in the treatment group were administered with CQCQD by gastric perfusion (50 mL/2 h) and retention enema (200 mL/6 h) for 7 days. The two groups had similar baseline information. The clinical indicators, including the initial Balthazar's computed tomography (CT) score, acute physiology and chronic health evaluation II (APACHE II) scores on 1st, 3rd, 5th and 7th day, incidences and durations of complications and the serum C-reactive protein (CRP), levels of MMP-9 on the 1st, 3rd, 5th and 7th day, were recorded and compared between the two groups. RESULTS: The serum MMP-9, CRP and the APACHE II scores on the 3rd, 5th and 7th day in the treatment group were lower than those in the control group (P<0.05). The serum MMP-9 was positively correlated with the APACHE II score on the 1st day (r=0.430, P=0.01). The durations of acute respiratory distress syndrome (5.4±2.4 vs. 2.9±1.3), acute hepatitis (4.6±0.8 vs. 1.9±0.6) and acute heart failure (3.9±1.6 vs. 1.3±0.6, <0.05) in the control group were longer than those in the treatment group. CONCLUSION: CQCQD could decrease the serum MMP-9 to relieve the severity of clinical symptoms and prevent the development of multiple organ dysfunction syndrome in patients with SAP.

[Health economic evaluation of clinical pathway of traditional Chinese medicine in the treatment of mild acute pancreatitis].

OBJECTIVE: To evaluate the health economic value clinical pathway (CP) of traditional Chinese medicine in the treatment of mild acute pancreatitis (MAP). METHODS: Ninty one patients with MAP were enrolled prospectively in TCM clinical pathway group from June 2012 to February 2013, while the data of 80 MAP patients who were treated without TCM clinical pathway from June 2011 to May 2012, were analyzed retrospectively as control group. The health economic evaluation data used for the two groups comparison included: average length of stay, hospitalization expenses (total hospitalization expenses, total treatment cost, TCM treatment cost, herbal fees, medicine fees, and nursing care cost), as well as the usage of antibiotics/somatostatin, the release time of abdominal pain, the time of re-feeding, and patient satisfaction. RESULTS: There were no significant statistical differences in demographics, etiology, Ranson and Balthazar CT scores between the two groups (P > 0.05). Compared with non-CP group, the usage of antibiotics and somatostatin, the release time of abdominal pain, the time of re-feeding and patient satisfaction were all improved significantly in CP group (P < 0.05). The average length of stay in CP group was shorter than that of non-CP group (P < 0.05). Total hospitalization expenses [yen (11,089.89 +/- 4,318.29) vs. yen (8,960.34 +/- 4,328.91)], medicine fees [yen (6,563.80 +/- 2,743.87) vs. yen (3,988.28 +/- 2,128.10)] and nursing care cost [yen (110.51 +/- 37.24) vs. yen (93.32 +/- 35.20)] were all reduced in CP group, while TCM treatment cost [yen (609.59 +/- 624.42) vs. (968.29 +/- 769.68)] and herbal fees [yen (162.72 +/- 135.13) vs. yen (303.49 +/- 149.90)] were increased (P < 0.05). There was no significant statistical difference in total treatment cost between the two groups (P > 0.05). CONCLUSION: TCM clinical pathway of MAP can not only ensure the therapeutic effects, but also shorten the average length of stay, reduce medical cost and increase patient satisfaction.

Effect of Chaiqinchengqi decoction on serum amyloid A in severe acute pancreatitis patients.

OBJECTIVE: To investigate the effect of Chaiqinchengqi decoction (CQCQD) on serum amyloid A (SAA) in severe acute pancreatitis (SAP) patients. METHODS: Thirty-five participants enrolled and were randomly assigned into either a treatment condition (n = 17, treated with CQCQD) or a control condition (n = 18, treated with placebo) 24 hours following the onset of the disease. No statistical difference was observed in either group at baseline. Upon admission, the Acute Physiology and Chronic Health Evaluation score II (APACHE II), SAA, serum C-reactive protein (CRP) and interleukin-6 (IL-6) were measured, as well as on the first, 3rd and 7th day and were compared between the two groups. Organ complications, infection, operation rate, mortality and hospital stay were also compared. RESULTS: The duration of acute respiratory distress syndrome, acute hepatitis, acute renal failure, gastrointestinal failure and blood coagulation dysfunction were shorter in the treatment group than in those in the control group (P < 0.05). The secondary infection rates and the hospital fees in the treatment group were lower than those in the control group (P < 0.05) as well as length of hospital stay (P < 0.01). After 3 days of hospitalization, the APACHEII, score SAA levels, serum CRP and IL-6 in the treatment group was lower than those in the control group (P < 0.05). SAA was positively correlated with serum CRP (R = 0.346, P = 0.042), Ranson score (R = 0.442, P = 0.008) and serum IL-6 (R = 0.359, P = 0.034). The area under the receiver operating characteristic curve of admission SAA predict pancreatic necrosis (PN) was 0.815 (95% CI: 0.625-0.954; P = 0.006). The best cut-off value of admission SAA was 7.85 mg/L with the sensitivity 84.6% and specificity 68.2%. CONCLUSIONS: The CQCQD can reduce the duration of organ damage through lowering the SAA in SAP patients and the SAA can early predict the PN and severity of SAP patients.

[Influence of integrated traditional Chinese and Western medicine therapy on serum resistin levels in patients with severe acute pancreatitis: a randomized controlled trial].

BACKGROUND: Resistin level is high in patients with severe acute pancreatitis (SAP), and resistin is expected to be a new marker for evaluating the severity of acute pancreatitis. OBJECTIVE: To explore the influence of integrated traditional Chinese and Western medicine therapy on serum resistin levels in SAP patients. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Twenty-eight SAP patients meeting inclusion criteria from Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University were included, and the patients were randomly divided into treatment group and placebo group. There were 13 patients in the treatment group and 15 patients in the placebo group. Patients in the treatment group were given traditional Chinese herbal medicine in addition to the conventional treatment. Patients in the placebo group were given placebo in addition to the conventional treatment. MAIN OUTCOME MEASURES: The serum resistin levels on admission, and days 1, 3, 5, and 7 after the admission were detected. RESULTS: The serum resistin levels on admission in all the patients were higher than normal level, and there was no significant difference between the two groups (P>0.05). On days 1, 3, 5, and 7 after admission, the resistin levels in the treatment group were (3.29 + or - 1.66) microg/L, (3.71 + or - 1.05) microg/L, (3.08 + or - 1.47) microg/L and (3.62 + or - 1.67) microg/L, and in the control group (5.16 + or - 1.93) microg/L, (5.07 + or - 1.53) microg/L, (4.88 + or - 1.47) microg/L and (5.12 + or - 1.48) microg/L, respectively. The resistin levels were lower in the treatment group than in the control group (P<0.05). CONCLUSION: Serum resistin level in SAP patients can be decreased by integrated traditional Chinese medicine and Western medicine therapy.