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Sutar P, Pethe A, Kumar P, Tripathi D, Maity D. Hydrogel Innovations in Biosensing: A New Frontier for Pancreatitis Diagnostics. Bioengineering (Basel) 2025; 12:254. [PMID: 40150718 PMCID: PMC11939681 DOI: 10.3390/bioengineering12030254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 02/24/2025] [Accepted: 02/27/2025] [Indexed: 03/29/2025] Open
Abstract
Pancreatitis is a prominent and severe type of inflammatory disorder that has grabbed a lot of scientific and clinical interest to prevent its onset. It should be detected early to avoid the development of serious complications, which occur due to long-term damage to the pancreas. The accurate measurement of biomarkers that are released from the pancreas during inflammation is essential for the detection and early treatment of patients with severe acute and chronic pancreatitis, but this is sub-optimally performed in clinically relevant practices, mainly due to the complexity of the procedure and the cost of the treatment. Clinically available tests for the early detection of pancreatitis are often time-consuming. The early detection of pancreatitis also relates to disorders of the exocrine pancreas, such as cystic fibrosis in the hereditary form and cystic fibrosis-like syndrome in the acquired form of pancreatitis, which are genetic disorders with symptoms that can be correlated with the overexpression of specific markers such as creatinine in biological fluids like urine. In this review, we studied how to develop a minimally invasive system using hydrogel-based biosensors, which are highly absorbent and biocompatible polymers that can respond to specific stimuli such as enzymes, pH, temperature, or the presence of biomarkers. These biosensors are helpful for real-time health monitoring and medical diagnostics since they translate biological reactions into quantifiable data. This paper also sheds light on the possible use of Ayurvedic formulations along with hydrogels as a treatment strategy. These analytical devices can be used to enhance the early detection of severe pancreatitis in real time.
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Affiliation(s)
- Prerna Sutar
- School of Health Sciences and Technology, UPES, Bidholi Campus, Dehradun 248007, Uttarakhand, India
| | - Atharv Pethe
- School of Health Sciences and Technology, UPES, Bidholi Campus, Dehradun 248007, Uttarakhand, India
| | - Piyush Kumar
- School of Health Sciences and Technology, UPES, Bidholi Campus, Dehradun 248007, Uttarakhand, India
| | - Divya Tripathi
- School of Health Sciences and Technology, UPES, Bidholi Campus, Dehradun 248007, Uttarakhand, India
| | - Dipak Maity
- Integrated Nanosystems Development Institute, Indiana University Indianapolis, Indianapolis, IN 46202, USA
- Department of Chemistry and Chemical Biology, Indiana University Indianapolis, Indianapolis, IN 46202, USA
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The endothelin system as target for therapeutic interventions in cardiovascular and renal disease. Clin Chim Acta 2020; 506:92-106. [DOI: 10.1016/j.cca.2020.03.008] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 03/05/2020] [Accepted: 03/05/2020] [Indexed: 12/12/2022]
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Gupta S, Prajapati A, Gulati M, Gautam SK, Kumar S, Dalal V, Talmon GA, Rachagani S, Jain M. Irreversible and sustained upregulation of endothelin axis during oncogene-associated pancreatic inflammation and cancer. Neoplasia 2020; 22:98-110. [PMID: 31923844 PMCID: PMC6951489 DOI: 10.1016/j.neo.2019.11.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 11/13/2019] [Accepted: 11/14/2019] [Indexed: 12/13/2022]
Abstract
Endothelin-1 (ET-1) and its two receptors, endothelin receptor A (ETAR) and endothelin receptor B (ETBR) exhibit deregulated overexprerssion in pancreatic ductal adenocarcinoma (PDAC) and pancreatitis. We examined the expression pattern of endothelin (ET) axis components in the murine models of chronic and acute inflammation in the presence or absence of oncogenic K-ras. While the expression of endothelin converting enzyme-1 (ECE-1), ET-1, ETAR and ETBR in the normal pancreas is restricted predominantly to the islet cells, progressive increase of ET receptors in ductal cells and stromal compartment is observed in the KC model (Pdx-1 Cre; K-rasG12D) of PDAC. In the murine pancreas harboring K-rasG12D mutation (KC mice), following acute inflammation induced by cerulein, increased ETAR and ETBR expression is observed in the amylase and CK19 double positive cells that represent cells undergoing pancreatic acinar to ductal metaplasia (ADM). As compared to the wild type (WT) mice, cerulein treatment in KC mice resulted in significantly higher levels of ECE-1, ET-1, ETAR and ETBR, transcripts in the pancreas. Similarly, in response to cigarette smoke-induced chronic inflammation, the expression of ET axis components is significantly upregulated in the pancreas of KC mice as compared to the WT mice. In addition to the expression in the precursor pancreatic intraepithelial neoplasm (PanIN lesions) in cigarette smoke-exposure model and metaplastic ducts in cerulein-treatment model, ETAR and ETBR expression is also observed in infiltrating F4/80 positive macrophages and α-SMA positive fibroblasts and high co-localization was seen in the presence of oncogenic K-ras. In conclusion, both chronic and acute pancreatic inflammation in the presence of oncogenic K-ras contribute to sustained upregulation of ET axis components in the ductal and stromal cells suggesting a potential role of ET axis in the initiation and progression of PDAC.
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Affiliation(s)
- Suprit Gupta
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Avi Prajapati
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Mansi Gulati
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Shailendra K Gautam
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Sushil Kumar
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Vipin Dalal
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Geoffrey A Talmon
- Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Satyanarayana Rachagani
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Maneesh Jain
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
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Wang W, Bo Q, Du J, Yu X, Zhu K, Cui J, Zhao H, Wang Y, Shi B, Zhu Y. Endogenous H 2S sensitizes PAR4-induced bladder pain. Am J Physiol Renal Physiol 2018; 314:F1077-F1086. [PMID: 29357418 DOI: 10.1152/ajprenal.00526.2017] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Bladder pain is a prominent symptom of interstitial cystitis/painful bladder syndrome. Hydrogen sulfide (H2S) generated by cystathionine β-synthase (CBS) or cystathionine γ-lyase (CSE) facilitates bladder hypersensitivity. We assessed involvement of the H2S pathway in protease-activated receptor 4 (PAR4)-induced bladder pain. A bladder pain model was induced by intravesical instillation of PAR4-activating peptide in mice. The role of H2S in this model was evaluated by intraperitoneal preadministration of d,l-propargylglycine (PAG), aminooxyacetic acid (AOAA), or S-adenosylmethionine or the preintravesical administration of NaHS. SV-HUC-1 cells were treated in similar manners. Assessments of CBS, CSE, and macrophage migration inhibitory factor (MIF) expression, bladder voiding function, bladder inflammation, H2S production, and referred bladder pain were performed. The CSE and CBS pathways existed in both mouse bladders and SV-HUC-1 cells. H2S signaling was upregulated in PAR4-induced bladder pain models, and H2S-generating enzyme activity was upregulated in human bladders, mouse bladders, and SV-HUC-1 cells. Pretreatment with AOAA or NaHS inhibited or promoted PAR4-induced mechanical hyperalgesia, respectively; however, PAG only partially inhibited PAR4-induced bladder pain. Treatment with PAG or AOAA decreased H2S production in both mouse bladders and SV-HUC-1 cells. Pretreatment with AOAA increased MIF protein levels in bladder tissues and cells, whereas pretreatment with NaHS lowered MIF protein levels. Bladder pain triggered by the H2S pathway was not accompanied by inflammation or altered micturition behavior. Thus endogenous H2S generated by CBS or CSE caused referred hyperalgesia mediated through MIF in mice with PAR4-induced bladder pain, without causing bladder injury or altering micturition behavior.
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Affiliation(s)
- Wenfu Wang
- Department of Urology, Qilu Hospital of Shandong University , Jinan , China
| | - Qiyu Bo
- Department of First Operation Room, Qilu Hospital of Shandong University , Jinan , China
| | - Jian Du
- Department of Urology, Qilu Hospital of Shandong University , Jinan , China
| | - Xin Yu
- Department of Physiology, Shandong University School of Physiology , Jinan , China
| | - Kejia Zhu
- Department of Urology, Qilu Hospital of Shandong University , Jinan , China
| | - Jianfeng Cui
- Department of Urology, Qilu Hospital of Shandong University , Jinan , China
| | - Hongda Zhao
- Department of Urology, Qilu Hospital of Shandong University , Jinan , China
| | - Yong Wang
- Department of Urology, Qilu Hospital of Shandong University , Jinan , China
| | - Benkang Shi
- Department of Urology, Qilu Hospital of Shandong University , Jinan , China
| | - Yaofeng Zhu
- Department of Urology, Qilu Hospital of Shandong University , Jinan , China
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Oz HS. Multiorgan chronic inflammatory hepatobiliary pancreatic murine model deficient in tumor necrosis factor receptors 1 and 2. World J Gastroenterol 2016; 22:4988-4998. [PMID: 27275091 PMCID: PMC4886374 DOI: 10.3748/wjg.v22.i21.4988] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2016] [Accepted: 04/07/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To provoke persistent/chronic multiorgan inflammatory response and to contribute to stones formation followed by fibrosis in hepatobiliary and pancreatic tissues.
METHODS: Tumor necrosis factor receptors 1 and 2 (TNFR1/R2) deficient mice reared in-house were given dibutyltin dichloride (DBTC) twice within 10 d by oral gavage delivery. Sham control animals received vehicle treatment and naïve animals remained untreated throughout the study. Animals were monitored daily for symptoms of pain and discomfort. The abdominal and hindpaw hypersensitivity were assessed with von Frey microfilaments. Exploratory behaviors were recorded at the baseline, after initiation of treatment, and before study termination. Histopathological changes were examined postmortem in tissues. Collagen accumulation and fibrosis were confirmed with Sirius Red staining.
RESULTS: Animals lost weight after oral administration of DBTC and developed persistent inflammatory abdominal and hindpaw hypersensitivity compared to sham-treated controls (P < 0.0001). These pain related secondary mechanical hypersensitivity responses increased more than 2-fold in DBTC-treated animals. The drastically diminished rearing and grooming rates persisted after DBTC administration throughout the study. Gross as well as micropathology at one month confirmed that animals treated with DBTC developed chronic hepatobiliary injuries evidenced with activation of stellate cells, multifocal necrosis, fatty degeneration of hepatocytes, periportal infiltration of inflammatory cells, and prominent biliary ductal dilation. The severity of hepatitis was scored 3.7 ± 0.2 (severe) in DBTC-treated animals vs score 0 (normal) in sham-treated animals. Fibrotic thickening was extensive around portal ducts, in hepatic parenchyma as well as in lobular pancreatic structures and confirmed with Sirius Red histopathology. In addition, pancreatic microarchitecture was presented with distortion of islets, and parenchyma, infiltration of inflammatory cells, degeneration, vacuolization, and necrosis of acinar cells and distention of pancreatic ducts. Extent of pancreatic damage and pancreatitis were scored 3.6 ± 0.4 (severe) for DBTC-treated in contrast to score 0 (normal) in sham-treated animals. The gall bladder became expanded with ductal distention, and occasional bile stones were detected along with microscopic hepatic lesions. DBTC-treated animals developed splenic hypertrophy with increased weight and length (P < 0.01) along with thymic atrophy (P < 0.001). Finally, colitic lesions and colitis were prominent in DBTC-treated animals and scored 3.4 ± 0.3 (moderately severe) vs 0 (normal) for the sham-treated animals.
CONCLUSION: This is the first report of chronic inflammatory multiorgan hepatobiliary pancreatitis, along with fibrosis and calculi formation induced reliably utilizing oral DBTC administration in TNFR1/R2 deficient mice.
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MESH Headings
- Abdominal Pain/chemically induced
- Abdominal Pain/genetics
- Abdominal Pain/metabolism
- Animals
- Behavior, Animal
- Bile Ducts/metabolism
- Bile Ducts/pathology
- Chemical and Drug Induced Liver Injury/etiology
- Chemical and Drug Induced Liver Injury/genetics
- Chemical and Drug Induced Liver Injury/metabolism
- Chemical and Drug Induced Liver Injury/psychology
- Cholangitis/chemically induced
- Cholangitis/genetics
- Cholangitis/metabolism
- Cholangitis/psychology
- Colitis/chemically induced
- Colitis/genetics
- Colitis/metabolism
- Exploratory Behavior
- Genetic Predisposition to Disease
- Grooming
- Hepatic Stellate Cells/metabolism
- Hepatic Stellate Cells/pathology
- Hyperalgesia/chemically induced
- Hyperalgesia/genetics
- Hyperalgesia/metabolism
- Lithiasis/chemically induced
- Lithiasis/genetics
- Lithiasis/metabolism
- Lithiasis/psychology
- Liver/metabolism
- Liver/pathology
- Liver Cirrhosis, Experimental/chemically induced
- Liver Cirrhosis, Experimental/genetics
- Liver Cirrhosis, Experimental/metabolism
- Liver Cirrhosis, Experimental/psychology
- Mice, Knockout
- Organotin Compounds
- Pain Perception
- Pancreas/metabolism
- Pancreas/pathology
- Pancreatic Stellate Cells/metabolism
- Pancreatic Stellate Cells/pathology
- Pancreatitis/genetics
- Pancreatitis/metabolism
- Pancreatitis/psychology
- Phenotype
- Receptors, Tumor Necrosis Factor, Type I/deficiency
- Receptors, Tumor Necrosis Factor, Type I/genetics
- Receptors, Tumor Necrosis Factor, Type II/deficiency
- Receptors, Tumor Necrosis Factor, Type II/genetics
- Spleen/metabolism
- Spleen/pathology
- Weight Loss
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Meng GG, Ren DY, Zhang YX. P38 pathway regulates iNOS and PGE2 expression in hippocampal neurons in rats with severe acute pancreatitis. Shijie Huaren Xiaohua Zazhi 2015; 23:5620-5627. [DOI: 10.11569/wcjd.v23.i35.5620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of P38 mitogen-activated protein kinase (P38MAPK) pathway on the expression of inducible nitric oxide synthase (iNOS) and prostaglandin E2 (PGE2) in hippocampal neurons of rats with severe acute pancreatitis (SAP).
METHODS: Healthy male Sprague-Dawley rats were randomly divided into three groups: a control group, a model group, and an SB203580 (an inhibitor of P38MAPK pathway) group. The pathological changes in brain tissue were observed. By immunohistochemistry and Western blot, expression of iNOS and PGE2 and phosphorylation of P38MAPK were detected to observe the changes of positive cell numbers and the expression levels in the hippocampus.
RESULTS: Compared with the control group, the numbers of p-P38 (20.4 ± 2.2 vs 2.1 ± 1.3), iNOS (33.6 ± 4.4 vs 3.7 ± 0.4), and PGE2 (34.7 ± 4.0 vs 2.4 ± 1.0) immunoreactive cells increased markedly in the hippocampal CA1 region (P < 0.05). After treatment with SB203580, the numbers of p-P38 (12.8 ± 0.7), iNOS (14.4 ± 4.9), and PGE2 (18.3 ± 0.5) immunoreactive cells were reduced significantly as compared with the model group (P < 0.05). The inhibitor group had significantly improved pancreatic cell pathology compared to the SAP group, which had ultrastructural changes such as rough endoplasmic network degranulation and mitochondrial swelling expansion.
CONCLUSION: P38MAPK pathway regulates the expression of iNOS and PGE2 in the hippocampus, and inhibition of the pathway has a neuroprotective effect in rats with SAP.
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Greenwood-Van Meerveld B, Prusator DK, Johnson AC. Animal models of gastrointestinal and liver diseases. Animal models of visceral pain: pathophysiology, translational relevance, and challenges. Am J Physiol Gastrointest Liver Physiol 2015; 308:G885-903. [PMID: 25767262 DOI: 10.1152/ajpgi.00463.2014] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2014] [Accepted: 03/11/2015] [Indexed: 02/08/2023]
Abstract
Visceral pain describes pain emanating from the thoracic, pelvic, or abdominal organs. In contrast to somatic pain, visceral pain is generally vague, poorly localized, and characterized by hypersensitivity to a stimulus such as organ distension. Animal models have played a pivotal role in our understanding of the mechanisms underlying the pathophysiology of visceral pain. This review focuses on animal models of visceral pain and their translational relevance. In addition, the challenges of using animal models to develop novel therapeutic approaches to treat visceral pain will be discussed.
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Affiliation(s)
- Beverley Greenwood-Van Meerveld
- Veterans Affairs Medical Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; and Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
| | - Dawn K Prusator
- Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
| | - Anthony C Johnson
- Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
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Kouzoukas DE, Meyer-Siegler KL, Ma F, Westlund KN, Hunt DE, Vera PL. Macrophage Migration Inhibitory Factor Mediates PAR-Induced Bladder Pain. PLoS One 2015; 10:e0127628. [PMID: 26020638 PMCID: PMC4447427 DOI: 10.1371/journal.pone.0127628] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Accepted: 04/17/2015] [Indexed: 12/13/2022] Open
Abstract
Introduction Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is constitutively expressed in urothelial cells that also express protease-activated receptors (PAR). Urothelial PAR1 receptors were shown to mediate bladder inflammation. We showed that PAR1 and PAR4 activator, thrombin, also mediates urothelial MIF release. We hypothesized that stimulation of urothelial PAR1 or PAR4 receptors elicits release of urothelial MIF that acts on MIF receptors in the urothelium to mediate bladder inflammation and pain. Thus, we examined the effect of activation of specific bladder PAR receptors on MIF release, bladder pain, micturition and histological changes. Methods MIF release was measured in vitro after exposing immortalized human urothelial cells (UROtsa) to PAR1 or PAR4 activating peptides (AP). Female C57BL/6 mice received intravesical PAR1- or PAR4-AP for one hour to determine: 1) bladder MIF release in vivo within one hour; 2) abdominal hypersensitivity (allodynia) to von Frey filament stimulation 24 hours after treatment; 3) micturition parameters 24 hours after treatment; 4) histological changes in the bladder as a result of treatment; 5) changes in expression of bladder MIF and MIF receptors using real-time RT-PCR; 6) changes in urothelial MIF and MIF receptor, CXCR4, protein levels using quantitative immunofluorescence; 7) effect of MIF or CXCR4 antagonism. Results PAR1- or PAR4-AP triggered MIF release from both human urothelial cells in vitro and mouse urothelium in vivo. Twenty-four hours after intravesical PAR1- or PAR4-AP, we observed abdominal hypersensitivity in mice without changes in micturition or bladder histology. PAR4-AP was more effective and also increased expression of bladder MIF and urothelium MIF receptor, CXCR4. Bladder CXCR4 localized to the urothelium. Antagonizing MIF with ISO-1 eliminated PAR4- and reduced PAR1-induced hypersensitivity, while antagonizing CXCR4 with AMD3100 only partially prevented PAR4-induced hypersensitivity. Conclusions Bladder PAR activation elicits urothelial MIF release and urothelial MIF receptor signaling at least partly through CXCR4 to result in abdominal hypersensitivity without overt bladder inflammation. PAR-induced bladder pain may represent an interesting pre-clinical model of Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) where pain occurs without apparent bladder injury or pathology. MIF is potentially a novel therapeutic target for bladder pain in IC/PBS patients.
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Affiliation(s)
- Dimitrios E. Kouzoukas
- Research and Development, Lexington Veterans Affairs Medical Center, Lexington, Kentucky, United States of America
- Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky, United States of America
- * E-mail:
| | - Katherine L. Meyer-Siegler
- Department of Natural Sciences, St. Petersburg College, St. Petersburg, Florida, United States of America
| | - Fei Ma
- Research and Development, Lexington Veterans Affairs Medical Center, Lexington, Kentucky, United States of America
- Department of Physiology, University of Kentucky, Lexington, Kentucky, United States of America
| | - Karin N. Westlund
- Research and Development, Lexington Veterans Affairs Medical Center, Lexington, Kentucky, United States of America
- Department of Physiology, University of Kentucky, Lexington, Kentucky, United States of America
| | - David E. Hunt
- Research and Development, Lexington Veterans Affairs Medical Center, Lexington, Kentucky, United States of America
| | - Pedro L. Vera
- Research and Development, Lexington Veterans Affairs Medical Center, Lexington, Kentucky, United States of America
- Department of Physiology, University of Kentucky, Lexington, Kentucky, United States of America
- Department of Surgery, University of Kentucky, Lexington, Kentucky, United States of America
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Zheng YQ, Huang J, Zeng FC, Zhou XY. Application of caerulein and lipopolysaccharides in creating mouse models of mild or severe acute pancreatitis. Shijie Huaren Xiaohua Zazhi 2014; 22:4068-4074. [DOI: 10.11569/wcjd.v22.i27.4068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To establish typical mouse models of mild or severe acute pancreatitis induced with caerulein (CAE) and/or lipopolysaccharides (LPS).
METHODS: Fifty healthy adult male C57 mice were randomly divided into five groups (with 10 mice in each group): a control group (CON group), the caerulein 7 group (CAE 7 group), a caerulein 7 plus LPS group (CAE 7 + LPS group), a caerulein 13 group (CAE 13 group), and a caerulein 13 plus LPS group (CAE 13 + LPS group). All the animals were killed three hours after the last intraperitoneal injection. The pancreas was carefully removed for microscopic examination and further observed under a transmission electron microscope (TEM). Serum amylase and lipase concentrations were assayed.
RESULTS: Enzyme levels and pathological score in all the experimental groups were significantly higher than those in the CON group (amylase lowest CAE 7 group: 27020 U/dL ± 3443 U/dL vs CON group: 2696 U/dL ± 400 U/dL, P < 0.01; lipase content lowest CAE 7 group: 1379 U/L ± 283 U/L vs CON group: 33 U/L ± 13 U/L, P < 0.01; pathological score lowest CAE 7 group: 5.8 ± 0.9 vs CON group: 0.1 ± 0.3, P < 0.01). Compared with the CAE 7 group, the enzyme levels and pathological score in the CAE 13 + LPS group increased more significantly (CAE 13 + LPS group amylase: 46969 U/dL ± 11852 U/dL vs CAE 7 group amylase: 27020 U/dL ± 3443 U/dL, P < 0.01; CAE13 + LPS group lipase: 1962 U/dL ± 496 U/dL vs CAE 7 group lipase: 1379 U/dL ± 283 U/dL, P < 0.05; CAE13 + LPS group pathological score : 11.1 ± 1.1 vs CAE 7 group pathological score : 5.8 ± 0.9, P < 0.05). The grade of pathological changes in the CAE 13 + LPS group was significantly higher than that in the CAE 13 group (CAE 13 + LPS group: 11.1 ± 1.1 vs CAE 13 group: 10.1 ± 0.99, P < 0.05). The ultrastructure of acinar cells was damaged in the CAE 7 group, and the rough endoplasmic reticulum and mitochondria were markedly swollen. However, in the CAE 13 + LPS group, the acinar cells were seriously damaged.
CONCLUSION: Caerulein alone by intraperitoneal injection 7 times can be used to prepare a typical model of acute edematous pancreatitis, and caerulein by intraperitoneal injection 13 times plus LPS at the last time can be used to produce typical acute necrotizing pancreatitis.
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Gene expression changes in rat pancreas transplant model after long-term cold storage of the graft in perfluorohexyloctane. Transplant Proc 2013; 45:1729-33. [PMID: 23769033 DOI: 10.1016/j.transproceed.2012.11.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2012] [Accepted: 11/19/2012] [Indexed: 11/21/2022]
Abstract
BACKGROUND Perfluorohexyloctane (PFH) is a promising storage solution that has been successfully used for pancreas preservation before islet isolation. This hyperoxygen carrier has been designed to prevent ischemic injury to the pancreas graft during cold storage. In our storage, we aimed to evaluate the impact of this solution on long-term cold storage in a rat whole pancreas transplantation model. METHOD Brown-Norway rats were used for syngeneic heterotopic pancreas transplantation. The procured organs were cold-stored for 18 hours in preoxygenated PFH (PFH group; n = 8) or in the University of Wisconsin solution (UW group; n = 8), or were transplanted immediately in the control group (n = 8). Two hours after reperfusion, we obtained blood and pancreas tissue samples for biochemistry and gene analyses (real-time polymerase chain reaction). RESULTS A significant difference between the UW and PFH group was observed in the tumor necrosis factor (TNF)β and endothelin 1 genes, which was overexpressed more than twofold in the UW group. In the blood samples, the UW group compared with the PFH group showed significantly higher levels of pancreatic amylase and lipase (94.2 ± 25.2 vs 67.7 ± 13.4 μkat/L and 5.5 ± 2.8 vs 3 ± 0.7 μkat/L, respectively; P < .05). CONCLUSION We found significantly lower expression levels of the endothelin 1 and TNFβ genes and lower concentrations of pancreatic amylase and lipase in the PFH group. All these findings suggest lower rate of ischemic reperfusion injury in the PFH group. These findings may result in better post-transplant outcomes after long-term cold storage in PFH compared with the UW solution. Further research in this area is required.
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