1.A comparative study on the absorption kinetics parameters of rhubarb free anthraquinones between normal dogs and dogs with severe acute pancreatitis.
Yong-Mao YANG ; Ping WANG ; Yan ZHANG
Chinese Journal of Integrated Traditional and Western Medicine 2012;32(4):494-498
OBJECTIVETo study the effects of severe acute pancreatitis (SAP) on absorption kinetic parameters of rhubarb free anthraquinones.
METHODSEleven healthy Beagle dogs were randomly divided into the normal group (n = 6) and the SAP group (n = 5). The SAP animal model was prepared by surgery through portal vein blood channel building to collect blood from normal dogs and dogs with SAP. The free anthraquinones (20 mg/kg) was given by gastrogavage. The concentrations of five anthraquinones (aloe emodin, rhein, emodin, chrysophanol, and physcion) in the blood plasma of the portal vein and the femoral artery were determined using high performance liquid chromatography (HPLC). The kinetic parameters were calculated using MATLAB2007B Software. The half life (t(1/2Ka)), the absorption peak time (Tmax), the peak concentration (Cmax), the area under the curve [AUC(0-infinity)], and the mean residence time (MRT) were calculated using the statistical moment method. The transport velocity of corresponding medicines from the gastrointestinal tract to the blood (ka) was calculated.
RESULTSThere was no difference in the chemical composition absorption type of the portal vein and the femoral artery between the two groups. Aloe emodin could be detected in the portal vein of each animal at each time point, and they were in the quantitative range. Rhein could be detected in the portal vein of each animal at each time point, and they were lower than the quantitative limit at few time points. Emodin and chrysophanol could be detected in the portal vein of partial animals at each time point, and most of them were higher than the quantitative limit. Physcion could be detected only in the portal vein of less animals at few time points. Rhein could be detected in the femoral artery at most time points, but the rhein plasma concentration at most time points were lower than the quantitative limit. Lower concentration of aloe emodin, emodin, and chrysophanol could be detected in the femoral artery at only few time points. Physcion was not detected in the femoral artery. The rhein plasma concentration of the femoral artery and the chrysophanol Cmax of the portal vein at 45 min were higher in the SAP group than in the normal group with statistical difference (P<0.05). There was no statistical difference in the rest indices. The AUC of rhein in the two groups were 59.32% and 66.07% of the total free anthraquinones respectively.
CONCLUSIONSSAP could not obviously affect the absorption kinetics parameters of rhubarb free anthraquinones. The intestinal tract and the liver might possibly play important roles in metabolizing or transforming rhubarb free anthraquinones.
Animals ; Anthraquinones ; blood ; pharmacokinetics ; Dogs ; Pancreatitis ; metabolism ; Rheum ; chemistry
2.NF-kB and cytokines in pancreatic acinar cells.
Hyeyoung KIM ; Jeong Yeon SEO ; Kyung Hwan KIM
Journal of Korean Medical Science 2000;15(Suppl):S53-S54
Reactive oxygen species (ROS), generated by infiltrating neutrophils, are considered as an important regulator in the pathogenesis and deveolpment of pancreatitis. A hallmark of the inflammatory response is the induction of cytokine gene expression, which may be regulated by oxidant-sensitive transcription factor, nuclear factor-kappaB (NF-KB). Present study aims to investigate whether neutrophils primed by 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA) affect the productions of H2O2 and lipid peroxide (LPO), NF-kappaB activation and cytokine production in pancreatic acinar cells, and whether these alterations were inhibited by N-acetylcysteine (NAC) and superoxide dismutase (SOD). ROS generation in neutrophils increased by PMA, which was inhibited by NAC and SOD. The productions of H2O2, LPO and TNF-alpha were increased with the amounts of PMA-primed neutrophils added to acinar cells while the productions of H2O2, LPO and cytokines increased with time. PMA-primed neutrophils resulted in the activation of two species of NF-kappaB dimers (a p50/p65 heterodimer and a p50 homodimer). Both NAC and SOD inhibited neutrophil-induced alterations in acinar cells. In conclusion, ROS, generated by neutrophils, activates NF-kappaB, resulting in upregulation of inflammatory cytokines in acinar cells. Antioxidants such as NAC might be clinically useful antiinflammatory agents by inhibiting oxidant-mediated activation of NF-KB and decreasing cytokine production.
Acute Disease
;
Chronic Disease
;
Cytokines/immunology*
;
Human
;
NF-kappa B/metabolism*
;
Pancreas/metabolism*
;
Pancreas/immunology*
;
Pancreas/cytology
;
Pancreatitis/metabolism
;
Pancreatitis/immunology
;
Support, U.S. Gov't, Non-P.H.S.
3.Role of CaMK II in pancreatic injury in mice with severe acute pancreatitis.
Wen JIANG ; Jun WU ; Jia Rong ZENG ; Guang Xu JING ; Li Jun TANG ; Hong Yu SUN
Journal of Southern Medical University 2022;42(2):286-292
OBJECTIVE:
To investigate the expression of Ca2+/calmodulin-dependent protein kinase II (CaMK Ⅱ) in pancreatic tissues of mice with severe acute pancreatitis (SAP) and explore the protective effect of KN93, a CaMK Ⅱ inhibitor, against pancreatic injury in SAP and the possible mechanism.
METHODS:
Thirty-six healthy male C57 mice were randomly divided into sham operation group, SAP group, KN93 group and SAP + KN93 group (n=9). Serum and pancreatic tissue samples were collected 24 h after modeling. The pathological changes in the pancreatic tissues were observed using HE staining. Serum lipase and amylase activities and the levels of inflammatory factors were detected using ELISA. Western blotting was used to detect the expressions of CaMK Ⅱ, p-CaMK Ⅱ, p-NF-κB, MAPK and p-MAPK in mouse pancreas.
RESULTS:
Compared with those in sham operation group, the expressions of p-CaMK Ⅱ, p-NF-κB and p-MAPK were significantly increased in SAP group (P < 0.05). KN93 treatment obviously alleviated pathological injuries of the pancreas in SAP mice, and significantly lowered serum levels of lipase, amylase and inflammatory factors (TNF-α and IL-6) and phosphorylation levels of NF-κB, ERK and MAPK proteins (P < 0.05).
CONCLUSION
The activity of CaMK Ⅱ is significantly increased in the pancreatic tissue of SAP mice. KN93 can alleviate pancreatic injury and inflammation in SAP mice possibly through the ERK/MAPK signaling pathway.
Acute Disease
;
Animals
;
Inflammation/metabolism*
;
Male
;
Mice
;
NF-kappa B/metabolism*
;
Pancreas/pathology*
;
Pancreatitis/pathology*
4.Study progress on mechanism of severe acute pancreatitis complicated with hepatic injury.
Xi-ping ZHANG ; Lei WANG ; Jie ZHANG
Journal of Zhejiang University. Science. B 2007;8(4):228-236
Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis (SAP) in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death. Its complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes of vasoactive substances, participation of inflammatory mediators as well as OFR (oxygen free radical), endotoxin, etc. may play important roles in its progression.
Acute Disease
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Disease Progression
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Endotoxins
;
metabolism
;
Hepatic Insufficiency
;
etiology
;
physiopathology
;
Humans
;
Inflammation Mediators
;
metabolism
;
Multiple Organ Failure
;
etiology
;
Pancreatitis
;
complications
;
metabolism
;
physiopathology
;
Pancreatitis, Acute Necrotizing
;
complications
;
metabolism
;
physiopathology
;
Reactive Oxygen Species
;
metabolism
5.A case of acute pancreatitis induced by hypertriglyceridemia in gestational diabetes.
Geun Hee KIM ; Hyun Ah JUN ; Ji Eun SONG ; Keun Young LEE ; Sun Suk KIM
Korean Journal of Obstetrics and Gynecology 2010;53(6):535-539
Hypertriglyceridemia is a rare cause of pancreatitis in pregnancy. Pregnancy is related with hypertriglyceridemia especially in the 3rd trimester due to increase of estrogen. Diabetes is known as a common cause of secondary lipid metabolism disorder and is often associated with hypertriglyceridemia. Shock and sepsis related to pancreatitis in pregnancy result in a relatively high morbidity and mortality rate for both the mother and the fetus. Hypertriglyceridemic pancreatitis complicated in gestational diabetes has not previously been reported. We report a case of 26(+4) weeks gestational aged primigravida with acute pancreatitis induced by hypertriglyceridemia in gestational diabetes. We reviewed the clinical courses and treatments of acute pancreatitis in pregnancy with the literatures.
Aged
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Diabetes, Gestational
;
Estrogens
;
Female
;
Fetus
;
Humans
;
Hypertriglyceridemia
;
Lipid Metabolism Disorders
;
Mothers
;
Pancreatitis
;
Pregnancy
;
Sepsis
;
Shock
6.Ferroptosis and its emerging roles in acute pancreatitis.
Hongyao LI ; Yujie LIN ; Ling ZHANG ; Jing ZHAO ; Peiwu LI
Chinese Medical Journal 2022;135(17):2026-2034
Acute pancreatitis (AP) is a common and potentially life-threatening pancreatic inflammatory disease. Although it is usually self-limiting, up to 20% of patients will develop into severe AP. It may lead to systemic inflammatory response syndrome and multiple organ dysfunction, affecting the lungs, kidneys, liver, heart, etc. Surviving patients usually have sequelae of varying degrees, such as chronic hyperglycemia after AP (CHAP), pancreatic exocrine insufficiency, and chronic pancreatitis. Lacking specific target treatments is the main reason for high mortality and morbidity, which means that more research on the pathogenesis of AP is needed. Ferroptosis is a newly discovered regulated cell death (RCD), originally described in cancer cells, involving the accumulation of iron and the depletion of plasma membrane polyunsaturated fatty acids, and a caspase-independent RCD. It is closely related to neurological diseases, myocardial infarction, ischemia/reperfusion injury, cancer, etc. Research in the past years has also found the effects of ferroptosis in AP, pancreatic cancer, and AP complications, such as acute lung injury and acute kidney injury. This article reviews the research progress of ferroptosis and its association with the pathophysiological mechanisms of AP, trying to provide new insight into the pathogenesis and treatment of AP, facilitating the development of better-targeted drugs.
Humans
;
Pancreatitis/pathology*
;
Acute Disease
;
Ferroptosis
;
Pancreas/pathology*
;
Acute Lung Injury/metabolism*
7.Analysis of human pancreatic juice in tests of pancreatic function.
Journal of Korean Medical Science 2000;15(Suppl):S21-S23
8.Involvement of Oxidative Stress in Sodium Taurocholate-Induced Acute Necrotizing Pancreatitis in Rats.
Kyung Chul JEON ; Hyung Geun LEE ; Jong Kwon PARK ; Jung Taik KIM ; Jin Woo RYU ; Dong Kook PARK ; Min CHUNG ; Mie Rha YANG
Journal of the Korean Surgical Society 1998;55(2):151-159
Oxidative radicals are regarded as a major factor in the pathogenesis of both acute and chronic pancreatitis. Because oxygen radicals react most readily with polyunsaturated fatty acids, resulting in peroxidation of lipids, several studies have been performed to determine the development of lipid peroxidation in pancreatitis. The purpose of this study was to evaluate the effects of free radicals and decision of the experimental model in acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced in 18 rats by retrograde injection into the bilopancreatic duct of 2%, 3%, and 5% sodium taurocholate. After a 12-hour observation time, the pancreas / the body weight, the serum amylase and the malondialdehyde content in tissue, as well as the reduced glutathione were measured in resected tissue samples. In addition, to determine the pathologic damage grade, tissue samples were examined by light microscopy. According to the amount of sodium taurocholate injected, the serum amylase and tissue malondialdehyde concentration were significantly increased. The reduced glutathione was significantly decreased, suggesting glutathione depletion due to oxidative stress. During the 12 hours after injection the pancreatic lesions were immediate and were characterized by interstitial edema, atrophy and extensive necrotic changes of the acinar cells, and hemorrhage. The pathologic damage grade increased according to the amount of sodium taurocholate injected. This study created an experimental model for studying the pathogenesis of acute necrotizing pancreatitis by using bile acid. In acute necrotizing pancreatitis, the increased levels of lipid peroxidation products in tissues and the change in glutathione metabolism suggest ongoing peroxidation of lipids due to an enhanced generation of oxygen radicals. Therefore, antioxidant treatment can reduce tissue damage, biochemical alterations, and extrapancreatic complications, thus improving the final outcome.
Acinar Cells
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Amylases
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Animals
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Atrophy
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Bile
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Body Weight
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Edema
;
Fatty Acids, Unsaturated
;
Free Radicals
;
Glutathione
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Hemorrhage
;
Lipid Peroxidation
;
Malondialdehyde
;
Metabolism
;
Microscopy
;
Models, Theoretical
;
Oxidative Stress*
;
Pancreas
;
Pancreatitis
;
Pancreatitis, Acute Necrotizing*
;
Pancreatitis, Chronic
;
Rats*
;
Reactive Oxygen Species
;
Sodium*
;
Taurocholic Acid
9.The expression of X-linked inhibitor of apoptosis protein and cell apoptosis in caerulein-stimulated rat pancreatic acinus AR42J cell lines.
Jingjing JIANG ; Zongguang ZHOU ; Ling WANG ; Lihui CHEN ; Yuan LI ; Hui YAN ; Bin ZHOU ; Yong LIU ; Keling CHEN
Journal of Biomedical Engineering 2011;28(2):332-351
To study the expression of X-linked inhibitor of apoptosis protein (XIAP) and cell apoptosis in vitro model of acute pancreatitis (AP), we carried out experiments to stimulate AR42J cell line with caerulein (10(-8) mol/L) for 12 hours, then collected cells at various time points (0 h, 4 h, 8 h, 12 h, and 24 h, respectively). We then observed the morphologic changes of AR42J cells with the stimulation of caerulein with electronic microscope. The gene expression of XIAP, caspase-3 and caspase-9 was detected using real-time fluorescence quantitative polymerase chain reaction (FQ-PCR), and the protein expression of XIAP was assessed by western blot. The activation of nuclear factor-kappa B (NF-kappaB) was measured by flow cytometry (FCM). With the stimulation of caerulein, the expression of XIAP and the NF-kappaB activation could first decrease and then increase, but the change of caspase-3 and caspase-9 expressions were opposite. XIAP may inhibit the cell apoptosis in rat pancreatic acinus AR42J cell lines at first with the stimulation of caerulein, then NF-kappaB can upgrade the expression of XIAP and increase the cell apoptosis.
Acinar Cells
;
cytology
;
metabolism
;
Animals
;
Apoptosis
;
physiology
;
Cell Line
;
Ceruletide
;
pharmacology
;
NF-kappa B
;
metabolism
;
Pancreas
;
cytology
;
metabolism
;
Pancreatitis
;
metabolism
;
Rats
;
X-Linked Inhibitor of Apoptosis Protein
;
genetics
;
metabolism
10.Predictive value of PASS score combined with NLR and CRP for infected pancreatic necrosis in patients with severe acute pancreatitis.
Qianqian HE ; Mengwei CUI ; Huihui LI ; Haifeng WANG ; Jiye LI ; Yaodong SONG ; Qiaofang WANG ; Sanyang CHEN ; Changju ZHU
Chinese Critical Care Medicine 2023;35(11):1207-1211
OBJECTIVE:
To investigate the predictive value of pancreatitis activity scoring system (PASS) combined with Neutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP) for infected pancreatic necrosis (IPN) in patients with severe acute pancreatitis (SAP).
METHODS:
Clinical data of SAP patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected, including basic information, vital signs at admission, first laboratory indexes within 48 hours of admission. The PASS scores at admission and 24, 48 and 72 hours after admission were calculated. According to the diagnostic criteria of IPN, the patients were divided into the non-IPN group and the IPN group, and the independent risk factors of SAP complicating IPN were determined by using univariate analysis and multifactorial Logistic regression. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of NLR, CRP, and PASS score, alone and in combination for IPN in patients with SAP.
RESULTS:
A total of 149 SAP patients were enrolled, including 102 in the non-IPN group and 47 in the IPN group. The differences in PASS score at each time point, NLR, CRP, procalcitonin (PCT), blood urea nitrogen, blood chloride, and days of hospitalization between the two groups were statistically significant. Multifactorial Logistic regression analysis showed that 72 hours admission PASS score [odds ratio (OR) = 1.034, 95% confidence interval (95%CI) was 1.005-1.065, P = 0.022], NLR (OR = 1.284, 95%CI was 1.139-1.447, P = 0.000), and CRP (OR = 1.015, 95%CI was 1.006-1.023, P = 0.001) were independent risk factors for IPN in patients with SAP. ROC curve analysis showed that the area under the ROC curve (AUC) of the PASS score at 72 hours of admission, NLR, and CRP alone in predicting IPN in SAP patients were 0.828, 0.771, and 0.701, respectively. The AUC of NLR combined with CRP, PASS combined with NLR, and PASS combined with CRP were 0.818, 0.895, and 0.874, respectively. The combination of PASS score at 72 hours after admission, NLR, and CRP had a better predictive ability for IPN in patients with SAP (AUC = 0.922, 95%CI was 0.877-0.967), and the sensitivity was 72.3% when the cut-off value was 0.539.
CONCLUSIONS
The predictive value of the PASS score at 72 hours after admission, NLR and CRP in combination for IPN in SAP patients is better than that of the combination of each two and individual detection and has better test efficacy.
Humans
;
Pancreatitis, Acute Necrotizing/diagnosis*
;
C-Reactive Protein/metabolism*
;
Acute Disease
;
Neutrophils/metabolism*
;
Retrospective Studies
;
ROC Curve
;
Lymphocytes
;
Prognosis