Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections

PubMed Central

Noel, Pawan; Patel, Krutika; Durgampudi, Chandra; Trivedi, Ram N; de Oliveira, Cristiane; Crowell, Michael D; Pannala, Rahul; Lee, Kenneth; Brand, Randall; Chennat, Jennifer; Slivka, Adam; Papachristou, Georgios I; Khalid, Asif; Whitcomb, David C; DeLany, James P; Cline, Rachel A; Acharya, Chathur; Jaligama, Deepthi; Murad, Faris M; Yadav, Dhiraj; Navina, Sarah; Singh, Vijay P

2016-01-01

Background and aims Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. Methods We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. Results NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. Conclusions UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP. PMID:25500204

Pancreatic Necrosis and Gas in the Retroperitoneum: Treatment with Antibiotics Alone.

PubMed

Rasslan, Roberto; da Costa Ferreira Novo, Fernando; Rocha, Marcelo Cristiano; Bitran, Alberto; de Souza Rocha, Manoel; de Oliveira Bernini, Celso; Rasslan, Samir; Utiyama, Edivaldo Massazo

2017-02-01

To present our experience in the management of patients with infected pancreatic necrosis without drainage. The records of patients with pancreatic necrosis admitted to our facility from 2011 to 2015 were retrospectively reviewed. We identified 61 patients with pancreatic necrosis. Six patients with pancreatic necrosis and gas in the retroperitoneum were treated exclusively with clinical support without any type of drainage. Only 2 patients had an APACHE II score >8. The first computed tomography scan revealed the presence of gas in 5 patients. The Balthazar computed tomography severity index score was >9 in 5 of the 6 patients. All patients were treated with antibiotics for at least 3 weeks. Blood cultures were positive in only 2 patients. Parenteral nutrition was not used in these patients. The length of hospital stay exceeded three weeks for 5 patients; 3 patients had to be readmitted. A cholecystectomy was performed after necrosis was completely resolved; pancreatitis recurred in 2 patients before the operation. No patients died. In selected patients, infected pancreatic necrosis (gas in the retroperitoneum) can be treated without percutaneous drainage or any additional surgical intervention. Intervention procedures should be performed for patients who exhibit clinical and laboratory deterioration.

Pancreatic necrosis in New World camelids: 11 cases (1990-1998).

PubMed

Pearson, E G; Snyder, S P

2000-07-15

To determine clinical, clinicopathologic, and postmortem abnormalities in New World camelids with pancreatic necrosis. Retrospective study. 10 llamas and 1 alpaca. Medical records of animals in which a diagnosis of pancreatic necrosis had been made on the basis of histologic examination of necropsy specimens or on the basis of clinical signs and results of clinicopathologic testing were reviewed. The initial owner complaint varied, and various other conditions were diagnosed. Clinical and clinicopathologic abnormalities were vague. Amylase activity was higher in abdominal fluid than in serum in 5 of 7 animals, and lipase activity was higher in abdominal fluid than in serum in all 7. Four animals survived, and 7 died or were euthanatized. Only 1 of the animals that died had marked inflammation of the pancreatic parenchyma. All 7 had necrosis and saponification of fat in and surrounding the pancreas. Results suggest that pancreatic necrosis may develop in New World camelids, but clinical signs are vague, and the condition may easily be confused with other diseases. The only laboratory test that appeared to be helpful in the antemortem diagnosis of pancreatic necrosis was comparison of amylase and lipase activities in abdominal fluid and serum.

Sequence analysis of infectious pancreatic necrosis virus isolated from Iranian reared rainbow trout (Oncorhynchus mykiss) in 2012.

PubMed

Dadar, Maryam; Peyghan, Rahim; Memari, Hamid Rajabi; Shapouri, Masod Reza Seifi Abad; Hasanzadeh, Reza; Goudarzi, Laleh Moazzami; Vakharia, Vikram N

2013-12-01

Infectious pancreatic necrosis virus (IPNV) is the causal agent of a highly contagious disease that affects many species of fish and shellfish. This virus causes economically significant diseases of farmed rainbow trout, Oncorhynchus mykiss (Walbaum), in Iran, which is often associated with the transmission of pathogens from European resources. In this study, moribund rainbow trout fry samples were collected during an outbreak of IPNV in three different fish farms in north and west provinces of Iran in 2012; and we investigated the full genome sequence of Iranian IPNV and compared it with previously identified IPNV sequences. The sequences of different structural and nonstructural-protein genes were compared to those of other aquatic birnaviruses sequenced to date. Our results show that the Iranian isolate falls within genogroup 5, serotype A2 strain SP, having 99% identity with the strain 1146 from Spain. These results suggest that the Iranian isolate may have originated from Europe.

Complete genomic sequence of an infectious pancreatic necrosis virus isolated from rainbow trout (Oncorhynchus mykiss) in China.

PubMed

Ji, Feng; Zhao, Jing-Zhuang; Liu, Miao; Lu, Tong-Yan; Liu, Hong-Bai; Yin, Jiasheng; Xu, Li-Ming

2017-04-01

Infectious pancreatic necrosis (IPN) is a significant disease of farmed salmonids resulting in direct economic losses due to high mortality in China. However, no gene sequence of any Chinese infectious pancreatic necrosis virus (IPNV) isolates was available. In the study, moribund rainbow trout fry samples were collected during an outbreak of IPN in Yunnan province of southwest China in 2013. An IPNV was isolated and tentatively named ChRtm213. We determined the full genome sequence of the IPNV ChRtm213 and compared it with previously identified IPNV sequences worldwide. The sequences of different structural and non-structural protein genes were compared to those of other aquatic birnaviruses sequenced to date. The results indicated that the complete genome sequence of ChRtm213 strain contains a segment A (3099 nucleotides) coding a polyprotein VP2-VP4-VP3, and a segment B (2789 nucleotides) coding a RNA-dependent RNA polymerase VP1. The phylogenetic analyses showed that ChRtm213 strain fell within genogroup 1, serotype A9 (Jasper), having similarities of 96.3% (segment A) and 97.3% (segment B) with the IPNV strain AM98 from Japan. The results suggest that the Chinese IPNV isolate has relative closer relationship with Japanese IPNV strains. The sequence of ChRtm213 was the first gene sequence of IPNV isolates in China. This study provided a robust reference for diagnosis and/or control of IPNV prevalent in China.

Genetic inhibition of protein kinase Cε attenuates necrosis in experimental pancreatitis

PubMed Central

Liu, Yannan; Tan, Tanya; Jia, Wenzhuo; Lugea, Aurelia; Mareninova, Olga; Waldron, Richard T.; Pandol, Stephen J.

2014-01-01

Understanding the regulation of death pathways, necrosis and apoptosis, in pancreatitis is important for developing therapies directed to the molecular pathogenesis of the disease. Protein kinase Cε (PKCε) has been previously shown to regulate inflammatory responses and zymogen activation in pancreatitis. Furthermore, we demonstrated that ethanol specifically activated PKCε in pancreatic acinar cells and that PKCε mediated the sensitizing effects of ethanol on inflammatory response in pancreatitis. Here we investigated the role of PKCε in the regulation of death pathways in pancreatitis. We found that genetic deletion of PKCε resulted in decreased necrosis and severity in the in vivo cerulein-induced pancreatitis and that inhibition of PKCε protected the acinar cells from CCK-8 hyperstimulation-induced necrosis and ATP reduction. These findings were associated with upregulation of mitochondrial Bak and Bcl-2/Bcl-xL, proapoptotic and prosurvival members in the Bcl-2 family, respectively, as well as increased mitochondrial cytochrome c release, caspase activation, and apoptosis in pancreatitis in PKCε knockout mice. We further confirmed that cerulein pancreatitis induced a dramatic mitochondrial translocation of PKCε, suggesting that PKCε regulated necrosis in pancreatitis via mechanisms involving mitochondria. Finally, we showed that PKCε deletion downregulated inhibitors of apoptosis proteins, c-IAP2, survivin, and c-FLIPs while promoting cleavage/inactivation of receptor-interacting protein kinase (RIP). Taken together, our findings provide evidence that PKCε activation during pancreatitis promotes necrosis through mechanisms involving mitochondrial proapoptotic and prosurvival Bcl-2 family proteins and upregulation of nonmitochondrial pathways that inhibit caspase activation and RIP cleavage/inactivation. Thus PKCε is a potential target for prevention and/or treatment of acute pancreatitis. PMID:25035113

First evidence of infectious hematopoietic necrosis virus (IHNV) in the Netherlands.

PubMed

Haenen, O L M; Schuetze, H; Cieslak, M; Oldenburg, S; Spierenburg, M A H; Roozenburg-Hengst, I; Voorbergen-Laarman, M; Engelsma, M Y; Olesen, N J

2016-08-01

In spring 2008, infectious hematopoietic necrosis virus (IHNV) was detected for the first time in the Netherlands. The virus was isolated from rainbow trout, Oncorhynchus mykiss (Walbaum), from a put-and-take fishery with angling ponds. IHNV is the causative agent of a serious fish disease, infectious hematopoietic necrosis (IHN). From 2008 to 2011, we diagnosed eight IHNV infections in rainbow trout originating from six put-and-take fisheries (symptomatic and asymptomatic fish), and four IHNV infections from three rainbow trout farms (of which two were co-infected by infectious pancreatic necrosis virus, IPNV), at water temperatures between 5 and 15 °C. At least one farm delivered trout to four of these eight IHNV-positive farms. Mortalities related to IHNV were mostly <40%, but increased to nearly 100% in case of IHNV and IPNV co-infection. Subsequent phylogenetic analysis revealed that these 12 isolates clustered into two different monophyletic groups within the European IHNV genogroup E. One of these two groups indicates a virus-introduction event by a German trout import, whereas the second group indicates that IHNV was already (several years) in the Netherlands before its discovery in 2008. © 2016 John Wiley & Sons Ltd.

Role of bedside pancreatic scores and C-reactive protein in predicting pancreatic fluid collections and necrosis.

PubMed

Vinish, Doraiswami Babu; Abishek, Vishnu; Sujatha, K; Arulprakash, S; Solomon, Rajkumar; Ganesh, P

2017-01-01

Acute pancreatitis is a disease with variable outcome; the course of the disease can be modified by early aggressive management in patients with severe pancreatitis. Easily calculable pancreatic scores and investigations can help to triage these patients. We aimed to determine the role of bedside index for severity in acute pancreatitis (BISAP), harmless acute pancreatitis score (HAPS), and systemic inflammatory response syndrome (SIRS) scores on day of admission and C-reactive protein (CRP) at 48 h for predicting the presence of pancreatic fluid collection (PFC) and necrosis on CT scans done at 72 h. Of a total of 114 consecutively seen patients of pancreatitis, 64 with acute pancreatitis were enrolled in the study. All individuals had the pancreatitis predicting scores calculated at the time of admission, CRP at 48 h, and contrast-enhanced computed tomography (CECT) abdomen at 72 h from admission. The study population of 64 (55 male) had a mean (+SD) age of 37.7 ± 13 years. Alcohol was the most common (68.8%) etiology in these patients. Based on CECT, patients were divided into 2 groups; group 1 with 41 patients who had mild pancreatitis and group 2 with 23 patients who had pancreatic fluid collection with or without necrosis (PFCN). PFCN were seen in 19 (29.7%) of patients with 2 or more SIRS criteria, 17 (26.6%) of patients with BISAP score ≥3, and 16 patients (25.0%) with HAPS >0 respectively. All three scores were able to predict PFCN significantly. CRP >150 mg/L was noted in 23 patients and was able to predict the presence of fluid collections (p=0.0002) and pancreatic necrosis (p = 0.0004) on CT. BISAP, HAPS, and SIRS scores and CRP of 150 mg/L all correlated significantly with the occurrence of fluid collections and pancreatic necrosis on CT at 72 h. None of the scores was superior to the other in this respect.

Tumour necrosis factor α secretion induces protease activation and acinar cell necrosis in acute experimental pancreatitis in mice.

PubMed

Sendler, Matthias; Dummer, Annegret; Weiss, Frank U; Krüger, Burkhard; Wartmann, Thomas; Scharffetter-Kochanek, Karin; van Rooijen, Nico; Malla, Sudarshan Ravi; Aghdassi, Ali; Halangk, Walter; Lerch, Markus M; Mayerle, Julia

2013-03-01

Acute pancreatitis has long been considered a disorder of pancreatic self-digestion, in which intracellular activation of digestive proteases induces tissue injury. Chemokines, released from damaged pancreatic cells then attract inflammatory cells, whose systemic action ultimately determines the disease severity. In the present work the opposite mechanism is investigated; that is, whether and how inflammatory cells can activate intracellular proteases. Using mice either deficient for the CD18-α subunit of the membrane attack complex-1 (MAC-1) complex or tumour necrosis factor (TNF)α, as well as after depletion of leucocyte subpopulations, pancreatitis was induced by 7-hourly caerulein injections (50 μg/kg, intraperitoneally). Pancreatic acini were coincubated in vitro from wild-type and cathepsin-B-deficient animals with phorbol-12-myristate-13-acetate (PMA)-activated neutrophils and macrophages, caerulein or TNFα, and activities of trypsin, cathepsin-B and caspase-3 were measured, as well as necrosis using fluorogenic substrates. TNFα was inhibited with monospecific antibodies. Deletion of CD18 prevented transmigration of leucocytes into the pancreas during pancreatitis, greatly reduced disease severity and abolished digestive protease activation. Depletion of neutrophils and macrophages equally reduced premature trypsinogen activation and disease severity. In vitro activated neutrophils and macrophages directly induced premature protease activation and cell death in pancreatic acini and stimulation of acini with TNFα induced caspase-3 activation and necrosis via a cathepsin-B and calcium-dependent mechanism. Neutralising antibodies against TNFα and genetic deletion of TNFα prevented leucocyte-induced trypsin activity and necrosis in isolated acini. The soluble inflammatory cell mediator TNFα directly induces premature protease activation and necrosis in pancreatic acinar cells. This activation depends on calcium and cathepsin-B activity. The findings

Infectious pancreatic necrosis virus triggers antiviral immune response in rainbow trout red blood cells, despite not being infective

PubMed Central

Nombela, Ivan; Carrion, Aurora; Puente-Marin, Sara; Chico, Verónica; Mercado, Luis; Perez, Luis; Coll, Julio; Ortega-Villaizan, Maria del Mar

2017-01-01

Background: Some fish viruses, such as piscine orthoreovirus and infectious salmon anemia virus, target red blood cells (RBCs), replicate inside them and induce an immune response. However, the roles of RBCs in the context of infectious pancreatic necrosis virus (IPNV) infection  have not been studied yet. Methods: Ex vivo rainbow trout RBCs were obtained from peripheral blood, Ficoll purified and exposed to IPNV in order to analyze infectivity and immune response using RT-qPCR, immune fluorescence imaging, flow cytometry and western-blotting techniques. Results: IPNV could not infect RBCs; however, IPNV increased the expression of the INF1-related genes ifn-1, pkr and mx genes. Moreover, conditioned media from IPNV-exposed RBCs conferred protection against IPNV infection in CHSE-214 fish cell line. Conclusions: Despite not being infected, rainbow trout RBCs could respond to IPNV with increased expression of antiviral genes. Fish RBCs could be considered as mediators of the antiviral response and therefore targets of new strategies against fish viral infections. Further research is ongoing to completely understand the molecular mechanism that triggers this antiviral response in rainbow trout RBCs. PMID:29333244

Infectious pancreatic necrosis virus triggers antiviral immune response in rainbow trout red blood cells, despite not being infective.

PubMed

Nombela, Ivan; Carrion, Aurora; Puente-Marin, Sara; Chico, Verónica; Mercado, Luis; Perez, Luis; Coll, Julio; Ortega-Villaizan, Maria Del Mar

2017-01-01

Background : Some fish viruses, such as piscine orthoreovirus and infectious salmon anemia virus, target red blood cells (RBCs), replicate inside them and induce an immune response. However, the roles of RBCs in the context of infectious pancreatic necrosis virus (IPNV) infection  have not been studied yet. Methods : Ex vivo rainbow trout RBCs were obtained from peripheral blood, Ficoll purified and exposed to IPNV in order to analyze infectivity and immune response using RT-qPCR, immune fluorescence imaging, flow cytometry and western-blotting techniques. Results : IPNV could not infect RBCs; however, IPNV increased the expression of the INF1-related genes ifn-1 , pkr and mx genes. Moreover, conditioned media from IPNV-exposed RBCs conferred protection against IPNV infection in CHSE-214 fish cell line. Conclusions : Despite not being infected, rainbow trout RBCs could respond to IPNV with increased expression of antiviral genes. Fish RBCs could be considered as mediators of the antiviral response and therefore targets of new strategies against fish viral infections. Further research is ongoing to completely understand the molecular mechanism that triggers this antiviral response in rainbow trout RBCs.

Survival of the salmonid viruses infectious hematopoietic necrosis (IHNV) and infectious pancreatic necrosis (IPNV) in ozonated, chlorinated, and Untreated waters

USGS Publications Warehouse

Wedemeyer, Gary A.; Nelson, Nancy C.; Smith, Cathy A.

1978-01-01

Ozone and chlorine inactivation curves were determined in three water types at 10 °C for the fish pathogenic viruses infectious hematopoietic necrosis (IHNV) and infectious pancreatic necrosis (IPNV). In phosphate-buffered, distilled water (PBDW) an ozone dose of 0.01 mg/L for 30 or 60 s inactivated IHNV or IPNV, respectively, suspended at a tissue culture 50% infective dose (TCID50) of 104–105/mL. In hard (120 mg/L as CaCO3) and soft water (30 mg/L) lake waters, an ozone application rate of 70 mg∙h−1∙L−1 for 10 min destroyed IHNV. IPNV inactivation in hard water required 90 mg∙O3∙h−1∙L−1 for 10 min but only a 30-s contact time in soft water. The IPNV was also somewhat more resistant to chlorine. In PBDW, a residual of 0.1 mg/L with contact times of 30 and 60 s, respectively, destroyed IHNV and IPNV. In soft lake water IHNV was destroyed within 5 min at 0.5 mg/L, while in hard water a 10-min contact time was required. For IPNV disinfection in soft water, 0.2 mg/L for 10 min was sufficient but this chlorine residual had essentially no effect on IPNV in hard water. Increasing this dose to 0.7 mg/L destroyed IPNV in hard water within 2 min. In untreated waters, IPNV was stable for at least 8 wk in either distilled, soft, or hard lake waters. However, IHNV survived only about 2 wk in distilled and 7 wk in the soft or hard lake waters. We suggest the serious consideration of ozone as a fish disease control agent. Key words: ozone, chlorine disinfection, fish pathogens, viruses

Imaging of endoscopic cystogastrostomy in pancreatic walled-off necrosis: what the radiologist needs to know.

PubMed

Abou Karam, Anthony; Bagherpour, Arya; Calleros, Jesus; Laks, Shaked

2018-04-04

Acute pancreatitis is a frequent entity encountered by radiologists. In 2012, the Atlanta criteria were revised to help radiologists use a common nomenclature when describing acute pancreatitis and its complications. One delayed complication of acute necrotizing pancreatitis in walled-off necrosis, a collection seen at least 4 weeks after an episode of acute pancreatic necrosis and/or acute peripancreatic necrosis. Multiple treatments have been adapted in the setting of walled-off necrosis, including endoscopic cystogastrostomy. The focus of this article is to familiarize the radiologist with the imaging appearance of this procedure as well as, review the outcomes and potential complications of endoscopic cystogastrostomy.

A novel quantitative immunomagnetic reduction assay for Nervous necrosis virus.

PubMed

Yang, Shieh Yueh; Wu, Jen Leih; Tso, Chun Hsi; Ngou, Fang Huar; Chou, Hsin Yiu; Nan, Fan Hua; Horng, Herng Er; Lu, Ming Wei

2012-09-01

Rapid, sensitive, and automatic detection platforms are among the major approaches of controlling viral diseases in aquaculture. An efficient detection platform permits the monitoring of pathogen spread and helps to enhance the economic benefits of commercial aquaculture. Nervous necrosis virus (NNV), the cause of viral encephalopathy and retinopathy, is among the most devastating aquaculture viruses that infect marine fish species worldwide. In the present study, a highly sensitive magnetoreduction assay was developed for detecting target biomolecules with a primary focus on NNV antigens. A standard curve of the different NNV concentrations that were isolated from infected Malabar grouper (Epinephelus malabaricus) was established before experiments were conducted. The test solution was prepared by homogeneous dispersion of magnetic nanoparticles coated with rabbit anti-NNV antibody. The magnetic nanoparticles in the solution were oscillated by magnetic interaction with multiple externally applied, alternating current magnetic fields. The assay's limit of detection was approximately 2 × 10(1) TCID(50)/ml for NNV. Moreover, the immunomagnetic reduction readings for other aquatic viruses (i.e., 1 × 10(7) TCID(50)/ml for Infectious pancreatic necrosis virus and 1 × 10(6.5) TCID(50)/ml for grouper iridovirus) were below the background noise in the NNV solution, demonstrating the specificity of the new detection platform.

Infectious haematopoietic necrosis virus: Chapter 2

USGS Publications Warehouse

Leong, Jo-Ann; Kurath, Gael

2017-01-01

Infectious haematopoietic necrosis virus (IHNV) is a Rhabdovirus that causes significant disease in Pacific salmon (Oncorhynchus spp.), Atlantic salmon (Salmo salar), and rainbow and steelhead trout (O. mykiss). IHNV causes necrosis of the haematopoietic tissues, and consequently it was named infectious haematopoietic necrosis. This virus is waterborne and may transmit horizontally and vertically through virus associated with seminal and ovarian fluids. The clinical signs of disease and diagnosis; pathology; pathophysiology; and control strategies against IHNV are discussed.

Infectious pancreatic necrosis virus isolated from farmed rainbow trout and tilapia in Kenya is identical to European isolates.

PubMed

Mulei, I R; Nyaga, P N; Mbuthia, P G; Waruiru, R M; Njagi, L W; Mwihia, E W; Gamil, A A A; Evensen, Ø; Mutoloki, S

2018-05-28

Infectious pancreatic necrosis virus (IPNV) is an aquabirnavirus that causes serious diseases in a variety of fish species worldwide. It has been isolated from a large number of healthy fresh and marine water fish. Prior to this study, there was no record of the presence of IPNV infection in Kenya. Here, the presence of IPNV in farmed rainbow trout and tilapia was examined in Nyeri County of central Kenya. Head kidney samples taken from five rainbow trout and three tilapia farms and stored in RNALater ® were processed by PCR followed by sequencing of a segment A fragment covering nucleotide positions 2,120-2,343 bp. IPNV was detected in all the farms sampled with infection ratios ranging from 0.3 to 0.78 although the infections were not associated with any specific clinical signs of disease. These findings were supported by immunohistochemistry staining of the virus in the kidney and exocrine pancreas of rainbow trout. Sequence alignment and phylogenetic analysis revealed that the Kenyan isolates were identical to European isolates, suggesting a common origin. These findings highlight the need for better biosecurity procedures with more stringent surveillance programmes and control for fish diseases, especially focusing on imported breeding materials to Kenya. © 2018 John Wiley & Sons Ltd.

Development of a subunit vaccine for infectious pancreatic necrosis virus using a baculovirus insect/larvae system

USGS Publications Warehouse

Shivappa, R.B.; McAllister, P.E.; Edwards, G.H.; Santi, N.; Evensen, O.; Vakharia, V.N.; ,

2005-01-01

Various attempts to develop a vaccine against infectious pancreatic necrosis virus (IPNV) have not yielded consistent results. Thus, at present, no commercial vaccine is available that can be used with confidence to immunize fry of salmon and trout. We generated a cDNA clone of the large genome segment A of an IPNV Sp strain and expressed all structural protein genes in insect cells and larvae using a baculovirus expression system. Green fluorescent protein was also co-expressed as a reporter molecule. High yields of IPNV proteins were obtained and the structural proteins self assembled to form virus-like particles (VLPs). We tested the immunogenicity of the putative VLP antigen in immersion vaccine experiments (two concentrations) in rainbow trout (Oncorhynchus mykiss) fry, and by intraperitoneal immunisation of Atlantic salmon (Salmo salar) pre-smolts using an oil adjuvant formulation. Rainbow trout were challenged by immersion using either the Sp or the VR-299 strain of IPNV two or three weeks post-vaccination, while Atlantic salmon were bath challenged with Sp strain after two months, after parr-smolt transformation. In the rainbow trout fry challenged two weeks post-immunization, cumulative mortality rates three weeks post challenge were 14 % in the fry that had received the highest dose versus 8 % in the control groups. No indication of protection was seen in repeated trials using a lower dose of antigen and challenge three weeks post-immunisation. The cumulative mortality rate of intraperitoneally immunised Atlantic salmon post-smolts four weeks post challenge was lower (56 %) than in the control fish (77 %), showing a dose-response pattern.

One-step cross-genogroup multiplex RT-qPCR with an internal control system for the detection of infectious pancreatic necrosis virus (IPNV).

PubMed

Hoferer, Marc; Braun, Anne; Skrypski, Julia; Bock, Sabine; Thalheim, Sabine; Sting, Reinhard

2017-09-01

Infectious pancreatic necrosis virus (IPNV) causes great losses in fish hatcheries world-wide. The detection of IPNV can be challenging in certain circumstances, particularly due to low viral load and the genetic variability of this RNA virus. For the first time, this project created a quantitative triplex real-time reverse transcription PCR (RT-qPCR), including an endogenous control system, for specific, sensitive and rapid detection of IPNV in routine diagnostics. Multiple sequence alignment of 46 nucleotide sequences of the segment A genome obtained from the NCBI database allowed the design of two RT-qPCR systems covering the IPNV genogroup 1 and genogroups 2-5, respectively. The completed triplex RT-qPCR including a salmonid-specific endogenous control showed high specificity and an analytical sensitivity of 20-40 oligonucleotide copies. Testing of dilution series of virus-loaded cell culture suspensions proved equality of the triplex RT-qPCR with virus detection in cell culture and a higher sensitivity than conventional RT-PCR in field samples. In comparative studies of a total of 77 field samples tested, 51 showed identical positive and 19 identical negative results in cell culture and the triplex RT-qPCR. However, seven other samples yielded positive results in the triplex RT-qPCR, but negative results in cell culture. Copyright © 2017 Elsevier B.V. All rights reserved.

Intestinal Fatty Acid Binding Protein as a Marker of Necrosis and Severity in Acute Pancreatitis.

PubMed

Kupčinskas, Juozas; Gedgaudas, Rolandas; Hartman, Hannes; Sippola, Tomi; Lindström, Outi; Johnson, Colin D; Regnér, Sara

2018-07-01

The aim of this study was to study intestinal fatty acid binding protein (i-FABP) as a potential biomarker in predicting severity of acute pancreatitis (AP). In a prospective multicenter cohort study, plasma levels of i-FABP were measured in 402 patients with AP. Severity of AP was determined based on the 1992 Atlanta Classification. Admission levels of plasma i-FABP were significantly higher in patients with pancreatic necrosis, in patients having systemic complications, in patients treated invasively, in patients treated in the intensive care unit, in patients with severe AP, and in deceased patients. Plasma i-FABP levels on admission yielded an area under curve (AUC) of 0.732 in discriminating patients with or without pancreatic necrosis and AUC of 0.669 in predicting severe AP. Combination of levels of i-FABP and venous lactate on the day of admission showed higher discriminative power in severe AP-AUC of 0.808. Higher i-FABP levels on admission were associated with pancreatic necrosis, systemic complications, and severe AP. Low levels of i-FABP had a high negative predictive value for pancreatic necrosis and severe AP. Combination of levels of i-FABP and venous lactates on admission were superior to either of markers used alone in predicting severe AP.

Virus inhibition of RIP3-dependent necrosis.

PubMed

Upton, Jason W; Kaiser, William J; Mocarski, Edward S

2010-04-22

Viral infection activates cytokine expression and triggers cell death, the modulation of which is important for successful pathogenesis. Necroptosis is a form of programmed necrosis dependent on two related RIP homotypic interaction motif (RHIM)-containing signaling adaptors, receptor-interacting protein kinases (RIP) 1 and 3. We find that murine cytomegalovirus infection induces RIP3-dependent necrosis. Whereas RIP3 kinase activity and RHIM-dependent interactions control virus-associated necrosis, virus-induced death proceeds independently of RIP1 and is therefore distinct from TNFalpha-dependent necroptosis. Viral M45-encoded inhibitor of RIP activation (vIRA) targets RIP3 during infection and disrupts RIP3-RIP1 interactions characteristic of TNFalpha-induced necroptosis, thereby suppressing both death pathways. Importantly, attenuation of vIRA mutant virus in wild-type mice is normalized in RIP3-deficient mice. Thus, vIRA function validates necrosis as central to host defense against viral infections and highlights the benefit of multiple virus-encoded cell-death suppressors that inhibit not only apoptotic, but also necrotic mechanisms of virus clearance. Copyright 2010 Elsevier Inc. All rights reserved.

Antimicrobial activity of a multispecies probiotic (Ecologic 641) against pathogens isolated from infected pancreatic necrosis.

PubMed

Ridwan, B U; Koning, C J M; Besselink, M G H; Timmerman, H M; Brouwer, E C; Verhoef, J; Gooszen, H G; Akkermans, L M A

2008-01-01

Although probiotic prophylaxis has been suggested to prevent small bowel bacterial overgrowth, bacterial translocation and infection of pancreatic necrosis in severe acute pancreatitis, limited data are available on their antimicrobial activity. Using the well-diffusion method, we studied the antimicrobial properties of a multispecies probiotic product (Ecologic 641) against a collection of pathogens cultured from infected pancreatic necrosis. All individual probiotic strains included in the multispecies preparation were able to inhibit the growth of the pathogens to some extent. However, the combination of the individual strains (i.e. the multispecies preparation) was able to inhibit all pathogenic isolates. Probiotic-free supernatants adjusted to pH 7 were not able to inhibit pathogen growth. Ecologic 641 is capable of inhibiting growth of a wide variety of pathogens isolated from infected pancreatic necrosis. The antimicrobial properties are to a large extent explained by the production of organic acids. Ecologic 641 is currently being used in a Dutch nationwide double-blind, placebo-controlled, randomized multicentre trial in patients with predicted severe acute pancreatitis.

Phytoceuticals in Acute Pancreatitis: Targeting the Balance between Apoptosis and Necrosis

PubMed Central

Gaman, Laura; Robu, Georgiana Catalina; Radoi, Mugurel Petrinel; Stroica, Laura; Badea, Mihaela

2018-01-01

Despite recent advances in understanding the complex pathogenesis of pancreatitis, the management of the disease remains suboptimal. The use of phytoceuticals (plant-derived pleiotropic multitarget molecules) represents a new research trend in pancreatology. The purpose of this review is to discuss the phytoceuticals with pancreatoprotective potential in acute pancreatitis and whose efficacy is based, at least in part, on their capacity to modulate the acinar cell death. The phytochemicals selected, belonging to such diverse classes as polyphenols, flavonoids, lignans, anthraquinones, sesquiterpene lactones, nitriles, and alkaloids, target the balance between apoptosis and necrosis. Activation of apoptosis via various mechanisms (e.g., inhibition of X-linked inhibitor of apoptosis proteins by embelin, upregulation of FasL gene expression by resveratrol) and/or inhibition of necrosis seem to represent the essential key for decreasing the severity of the disease. Apart from targeting the apoptosis/necrosis balance, the phytochemicals displayed other specific protective activities: inhibition of inflammasome (e.g., rutin), suppression of neutrophil infiltration (e.g., ligustrazine, resveratrol), and antioxidant activity. Even though many of the selected phytoceuticals represent a promising therapeutic alternative, there is a shortage of human evidence, and further studies are required to provide solid basis to justify their use in the treatment of pancreatitis. PMID:29686719

Management of Inflammatory Fluid Collections and Walled-Off Pancreatic Necrosis.

PubMed

Shah, Apeksha; Denicola, Richard; Edirisuriya, Cynthia; Siddiqui, Ali A

2017-12-01

Pancreatic fluid collections are a frequent complication of acute pancreatitis. The revised Atlanta criterion classifies chronic fluid collections into pseudocysts and walled-off pancreatic necrosis (WON). Symptomatic PFCs require drainage options that include surgical, percutaneous, or endoscopic approaches. With the advent of newer and more advanced endoscopic tools and expertise, minimally invasive endoscopic drainage has now become the preferred approach. An endoscopic ultrasonography (EUS)-guided approach for pancreatic fluid collection drainage is now the preferred endoscopic approach. Both plastic stents and metal stents are efficacious and safe; however, metal stents may offer an advantage, especially in infected pseudocysts and in WON. Direct endoscopic necrosectomy is often required in WON. Lumen apposing metal stents allow for direct endoscopic necrosectomy and debridement through the stent lumen and are now preferred in these patients. Endoscopic retrograde cholangiopancreatography with pancreatic duct exploration should be performed concurrent to PFC drainage in patients with suspected PD disruption. PD disruption is associated with an increased severity of pancreatitis, an increased risk of recurrent attacks of pancreatitis and long-term complications, and a decreased rate of PFC resolution after drainage. Ideally, pancreatic ductal disruption should be bridged with endoscopic stenting.

[Dekasan application in treatment of infected pancreatic necrosis and its complications].

PubMed

Nichitaĭlo, M E

2010-03-01

The experience of the use of domestic antiseptic dekasan for topical use in patients over the infected pancreatic necrosis and its complications. There was significant improvement in the results of patients treatment.

Pathophysiology of infectious hematopoietic necrosis virus disease in rainbow trout (Salmo gairdneri): early changes in blood and aspects of the immune Response after Injection of IHN Virus

USGS Publications Warehouse

Amend, Donald F.; Smith, Lynnwood

1974-01-01

Juvenile rainbow trout (Salmo gairdneri) were injected with infectious hematopoietic necrosis (IHN) virus and various hematological and blood chemical changes were monitored over 9 days. The packed cell volume, hemoglobin, red blood cell count, and plasma bicarbonate were significantly depressed by day 4. Plasma chloride, calcium, phosphorus, total protein, and blood cell types did not change during the 9 days. Furthermore, plasma  LDH isozyme was significantly increased by the fourth day, and fish infected with infectious pancreatic necrosis virus, Vibrio anguillarum, Aeromonas salmonicida, and redmouth bacterium did not show specific LDH isozyme alterations. Acid-base alterations occurred at 10 C but not at 18 C. The acid-base imbalance and elevation of the  LDH isozyme were consistently associated with the early development of the disease.The immune response after injection of IHN virus was determined and protection from disease was tested by passive immunization. Actively immunized fish developed IHN-neutralizing antibodies within 54 days after injection of virus, and the antibodies were protective when juvenile fish were passively immunized and experimentally challenged with IHN virus.

[Protocol for the treatment of severe acute pancreatitis with necrosis].

PubMed

Barreda, Luis; Targarona, Javier; Rodriguez, César

2005-01-01

The Severe Acute Pancreatic Unit of Edgardo Rebagliati Martins National Hospital was officially created in the year 2000. Up to date, we have cared for more than 195 patients with Pancreatic Necrosis. All of them have been treated under a management protocol presented by us. This has helped us to standardize treatment and also to compare results with work groups around the world. This Protocol comes from our own experience and that of our colleagues abroad with a wide knowledge in this kind of pathology abroad, with whom we maintain close ties.

Comparative evaluation of structural and functional changes in pancreas after endoscopic and surgical management of pancreatic necrosis.

PubMed

Rana, Surinder Singh; Bhasin, Deepak Kumar; Rao, Chalapathi; Sharma, Ravi; Gupta, Rajesh

2014-01-01

Patients with acute necrotizing pancreatitis may develop pancreatic insufficiency and this is commonly seen in patients who have undergone surgery for pancreatic necrosis. Owing to the paucity of relative data, we retrospectively evaluated the structural and functional changes in the pancreas after endoscopic and surgical management of pancreatic necrosis. The records of patients who underwent endoscopic transmural drainage of walled off pancreatic necrosis (WOPN) over the last 3 years and who completed at least 6 months of follow up were analyzed. Structural and functional changes in these patients were compared with 25 historical surgical controls (operated in 2005-2006). Twenty six patients (21 M; mean age 35.4±8.1 years) who underwent endoscopic drainage for WOPN were followed up for 22.3±8.6 months. During the follow up, five (19.2%) patients developed diabetes with 3 patients requiring insulin and 1 patient with steatorrhea requiring pancreatic enzyme supplementation. The pancreatic fluid collection (PFC) recurred in 1 patient whose stents spontaneously migrated out. On follow up, in the surgery group, 2 (8%) patients developed steatorrhea and 11 (44%) developed diabetes. Five (20%) of these patients had recurrence of PFC. On comparison of follow up results of endoscopic drainage with surgery, recurrence rates as well as frequency of endocrine and exocrine insufficiency was lower in the endoscopic group but difference was not significant. Structural and functional impairment of pancreas is seen less frequently in patients with pancreatic necrosis treated endoscopically compared to patients undergoing surgery, although the difference was insignificant. Further studies with large sample size are needed to confirm these initial results.

Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium-driven bile uptake.

PubMed

Ferdek, Pawel E; Jakubowska, Monika A; Gerasimenko, Julia V; Gerasimenko, Oleg V; Petersen, Ole H

2016-11-01

Acute biliary pancreatitis is a sudden and severe condition initiated by bile reflux into the pancreas. Bile acids are known to induce Ca 2+ signals and necrosis in isolated pancreatic acinar cells but the effects of bile acids on stellate cells are unexplored. Here we show that cholate and taurocholate elicit more dramatic Ca 2+ signals and necrosis in stellate cells compared to the adjacent acinar cells in pancreatic lobules; whereas taurolithocholic acid 3-sulfate primarily affects acinar cells. Ca 2+ signals and necrosis are strongly dependent on extracellular Ca 2+ as well as Na + ; and Na + -dependent transport plays an important role in the overall bile acid uptake in pancreatic stellate cells. Bile acid-mediated pancreatic damage can be further escalated by bradykinin-induced signals in stellate cells and thus killing of stellate cells by bile acids might have important implications in acute biliary pancreatitis. Acute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca 2+ signals and necrosis in acinar cells. However, bile acid-elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells). Sodium cholate and taurocholate induced cytosolic Ca 2+ elevations in stellate cells, larger than those elicited simultaneously in the neighbouring acinar cells. In contrast, taurolithocholic acid 3-sulfate (TLC-S), known to induce Ca 2+ oscillations in acinar cells, had only minor effects on stellate cells in lobules. The dependence of the Ca 2+ signals on extracellular Na + and the presence of sodium-taurocholate cotransporting polypeptide (NTCP) indicate a Na + -dependent bile acid

Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium‐driven bile uptake

PubMed Central

Jakubowska, Monika A.; Gerasimenko, Julia V.; Gerasimenko, Oleg V.; Petersen, Ole H.

2016-01-01

Key points Acute biliary pancreatitis is a sudden and severe condition initiated by bile reflux into the pancreas.Bile acids are known to induce Ca2+ signals and necrosis in isolated pancreatic acinar cells but the effects of bile acids on stellate cells are unexplored.Here we show that cholate and taurocholate elicit more dramatic Ca2+ signals and necrosis in stellate cells compared to the adjacent acinar cells in pancreatic lobules; whereas taurolithocholic acid 3‐sulfate primarily affects acinar cells.Ca2+ signals and necrosis are strongly dependent on extracellular Ca2+ as well as Na+; and Na+‐dependent transport plays an important role in the overall bile acid uptake in pancreatic stellate cells.Bile acid‐mediated pancreatic damage can be further escalated by bradykinin‐induced signals in stellate cells and thus killing of stellate cells by bile acids might have important implications in acute biliary pancreatitis. Abstract Acute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca2+ signals and necrosis in acinar cells. However, bile acid‐elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells). Sodium cholate and taurocholate induced cytosolic Ca2+ elevations in stellate cells, larger than those elicited simultaneously in the neighbouring acinar cells. In contrast, taurolithocholic acid 3‐sulfate (TLC‐S), known to induce Ca2+ oscillations in acinar cells, had only minor effects on stellate cells in lobules. The dependence of the Ca2+ signals on extracellular Na+ and the presence of sodium–taurocholate cotransporting polypeptide (NTCP) indicate a Na

The effect of non-steroidal anti-inflammatory drugs on severity of acute pancreatitis and pancreatic necrosis.

PubMed

Baxter, K A; Pucher, P H; Berry, D P; Elberm, H; Abu-Hilal, M; Marangoni, G; Hamady, Zzr

2018-03-01

Introduction Acute pancreatitis (AP) is a common emergency presentation and can be disabling. There is significant morbidity and mortality associated with AP, and it places a considerable burden on the healthcare system. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to have a protective effect in some elective contexts. This retrospective study aimed to evaluate the effect of NSAIDs on the course of AP and the severity of the disease. Methods A retrospective analysis was carried out of 324 patients admitted as an emergency with a diagnosis of AP to two UK hospitals. Patients were divided into two groups: those already taking NSAIDs for other co-morbidities and those not taking NSAIDs. Variables compared included: admission to a high dependency or intensive care unit; pancreatic necrosis; pseudocyst development; need for surgery; serum inflammatory markers; modified early warning scores on days 1, 3 and 5; length of stay; and mortality. Results Patients not taking NSAIDs were more likely to have a C-reactive protein level of ≥150mg/l (p=0.007). Patients in the NSAID group experienced less pancreatic necrosis (p=0.019) and lower rates of pseudocyst formation (p=0.010). Other variables showed no difference between the two groups, specifically length of stay and mortality. Conclusions Routine NSAID use may exert a protective effect on the development of AP, its severity, and complications. Therapeutic use of NSAIDs in acute presentations with pancreatitis should be further evaluated.

Purtscher's retinopathy and renal cortical necrosis: two rare vaso-occlusive complications in a patient with acute pancreatitis: a case report.

PubMed

Haque, Wasim Md Mohosin Ul; Ananna, Mehruba Alam; Haque, Hasna Fahmima; Rahim, Muhammad Abdur; Samad, Tabassum; Iqbal, Sarwar

2016-11-15

Purtscher's retinopathy and renal cortical necrosis are two rare vaso-occlusive complications of acute pancreatitis. Purtscher's retinopathy causes sudden impairment of vision, which was first reported in a patient with head trauma. Subsequently, it was also reported as a complication of acute pancreatitis and few other clinical conditions. Acute pancreatitis also rarely causes renal cortical necrosis leading to acute kidney injury. However, the simultaneous presence of both complications is rarely reported. A 20-year-old Bengali man presented to our hospital with a history of acute upper abdominal pain, vomiting, anuria, and disorientation. He was ultimately found to have bilateral complete blindness due to Purtscher's retinopathy and acute kidney injury due to renal cortical necrosis, as sequelae of acute pancreatitis. He became dialysis-dependent, his vision did not recover, and he died 16 months after diagnosis. This case highlights Purtscher's retinopathy and renal cortical necrosis might be considered as a recognized pair complication of acute pancreatitis.

Experimental Transmission of Infectious Pancreatic Necrosis Virus from the Blue Mussel, Mytilus edulis, to Cohabitating Atlantic Salmon (Salmo salar) Smolts

PubMed Central

Pietrak, Michael R.; Bricknell, Ian

2013-01-01

Integrated multitrophic aquaculture (IMTA) reduces the environmental impacts of commercial aquaculture systems by combining the cultivation of fed species with extractive species. Shellfish play a critical role in IMTA systems by filter-feeding particulate-bound organic nutrients. As bioaccumulating organisms, shellfish may also increase disease risk on farms by serving as reservoirs for important finfish pathogens such as infectious pancreatic necrosis virus (IPNV). The ability of the blue mussel (Mytilus edulis) to bioaccumulate and transmit IPNV to naive Atlantic salmon (Salmo salar) smolts was investigated. To determine the ability of mussels to filter and accumulate viable IPNV, mussels were held in water containing log 4.6 50% tissue culture infective dose(s) (TCID50) of the West Buxton strain of IPNV ml−1. Viable IPNV was detected in the digestive glands (DGs) of IPNV-exposed mussels as early as 2 h postexposure. The viral load in mussel DG tissue significantly increased with time and reached log 5.35 ± 0.25 TCID50 g of DG tissue−1 after 120 h of exposure. IPNV titers never reached levels that were significantly greater than that in the water. Viable IPNV was detected in mussel feces out to 7 days postdepuration, and the virus persisted in DG tissues for at least 18 days of depuration. To determine whether IPNV can be transmitted from mussels to Atlantic salmon, IPNV-exposed mussels were cohabitated with naive Atlantic salmon smolts. Transmission of IPNV did occur from mussels to smolts at a low frequency. The results demonstrate that a nonenveloped virus, such as IPNV, can accumulate in mussels and be transferred to naive fish. PMID:23872575

Inguinoscrotal region as an unusual site of extra-pancreatic collections in infected pancreatic necrosis.

PubMed

Kalia, Saurabh; Gupta, Rahul; Shenvi, Sunil D; Kumar, Hemanth; Gupta, Rajesh; Kang, Mandeep; Rana, Surinder Singh; Bhasin, Deepak Kumar; Singh, Rajinder

2016-08-01

Severe acute pancreatitis often leads to pancreatic and peripancreatic collections but, rarely, it can lead to collections at sites remote from the pancreas. Three male patients presented with abdominal pain and inguinoscrotal swelling. They were initially misdiagnosed with obstructed inguinal hernia, epididymo-orchitis and hydrocele, respectively. Later, their diagnosis of acute pancreatitis was revealed on laparotomy in one patient and on computed tomography (CT) in the remaining two patients. All these cases had extensive peripancreatic necrosis and paracolic collections tracking along the psoas muscle, downwards towards the pelvis. These collections were initially managed by percutaneous drainage and saline irrigation as a part of the 'step-up' approach. Two of these patients required open necrosectomy, while all required incision and drainage of inguinoscrotal collections. All the patients were discharged in satisfactory condition. Inguinoscrotal swelling is unusual as a first presentation of acute pancreatitis. A high index of suspicion, with careful study of patient's history and examination along with CT, may provide an accurate diagnosis. Local drainage may be required to control sepsis and also provide an egress route for intra-abdominal collections. © The Author(s) 2015. Published by Oxford University Press and the Digestive Science Publishing Co. Limited.

Surgical management of pancreatic necrosis: A practice management guideline from the Eastern Association for the Surgery of Trauma.

PubMed

Mowery, Nathan T; Bruns, Brandon R; MacNew, Heather G; Agarwal, Suresh; Enniss, Toby M; Khan, Mansoor; Guo, Weidun Alan; Cannon, Jeremy W; Lissauer, Matthew E; Duane, Therese M; Hildreth, Amy N; Pappas, Peter A; Gries, Lynn M; Kaiser, Meghann; Robinson, Bryce R H

2017-08-01

Pancreatic or peripancreatic tissue necrosis confers substantial morbidity and mortality. New modalities have created a wide variation in approaches and timing of interventions for necrotizing pancreatitis. As acute care surgery evolves, its practitioners are increasingly being called upon to manage these complex patients. A systematic review of the MEDLINE database using PubMed was performed. English language articles regarding pancreatic necrosis from 1980 to 2014 were included. Letters to the editor, case reports, book chapters, and review articles were excluded. Topics of investigation included operative timing, the use of adjuvant therapy and the type of operative repair. Grading of Recommendations, Assessment, Development and Evaluations methodology was applied to question development, outcome prioritization, evidence quality assessments, and recommendation creation. Eighty-eight studies were included and underwent full review. Increasing the time to surgical intervention had an improved outcome in each of the periods evaluated (72 hours, 12-14 days, 30 days) with a significant improvement in outcomes if surgery was delayed 30 days. The use of percutaneous and endoscopic procedures was shown to postpone surgery and potentially be definitive. The use of minimally invasive surgery for debridement and drainage has been shown to be safe and associated with reduced morbidity and mortality. Acute Care Surgeons are uniquely trained to care for those with pancreatic necrosis due their training in critical care and complex surgery with ongoing shock. In adult patients with pancreatic necrosis, we recommend that pancreatic necrosectomy be delayed until at least day 12. During the first 30 days of symptoms with infected necrotic collections, we conditionally recommend surgical debridement only if the patients fail to improve after radiologic or endoscopic drainage. Finally, even with documented infected necrosis, we recommend that patients undergo a step-up approach to

Infectious pancreatic necrosis virus in fish by-products is inactivated with inorganic acid (pH 1) and base (pH 12).

PubMed

Myrmel, M; Modahl, I; Nygaard, H; Lie, K M

2014-04-01

The aquaculture industry needs a simple, inexpensive and safe method for the treatment of fish waste without heat. Microbial inactivation by inorganic acid (HCl) or base (KOH) was determined using infectious pancreatic necrosis virus (IPNV) as a model organism for fish pathogens. Salmonella and spores of Clostridium perfringens were general hygiene indicators in supplementary examinations. IPNV, which is considered to be among the most chemical- and heat-resistant fish pathogens, was reduced by more than 3 log in 4 h at pH 1.0 and pH 12.0. Salmonella was rapidly inactivated by the same treatment, whereas spores of C. perfringens were hardly affected. The results indicate that low and high pH treatment could be particularly suitable for fish waste destined for biogas production. pH treatment at aquaculture production sites could reduce the spread of fish pathogens during storage and transportation without disturbing the anaerobic digestion process. The treatment could also be an alternative to the current energy-intensive steam pressure sterilization of fish waste to be used by the bioenergy, fertilizer and soil improver industries. © 2013 John Wiley & Sons Ltd.

Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome: MRI features of intraosseous fat necrosis involving the feet and knees.

PubMed

Kang, Dong Joo; Lee, Sun Joo; Choo, Hye Jung; Her, Minyoung; Yoon, Hye Kyoung

2017-02-01

Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome is extremely rare and presents as a triad of the three diseases. The patient usually presents with mild or absent abdominal symptoms. Here, we report on a case of a 66-year-old male who presented with pain and swelling in both legs and mild abdominal pain. He was diagnosed with acute pancreatitis by pancreatic enzyme analysis and abdominal computed tomography (CT) and with skin lesions of panniculitis through a biopsy. Magnetic resonance imaging (MRI) revealed multifocal intraosseous fat necrosis and arthritis involving both the feet and the knees. Therefore, we report a case of PPP syndrome with intraosseous fat necrosis involving both the feet and the knees.

Carrot yellow leaf virus is associated with carrot internal necrosis.

PubMed

Adams, Ian P; Skelton, Anna; Macarthur, Roy; Hodges, Tobias; Hinds, Howard; Flint, Laura; Nath, Palash Deb; Boonham, Neil; Fox, Adrian

2014-01-01

Internal necrosis of carrot has been observed in UK carrots for at least 10 years, and has been anecdotally linked to virus infection. In the 2009 growing season some growers had up to 10% of yield with these symptoms. Traditional diagnostic methods are targeted towards specific pathogens. By using a metagenomic approach with high throughput sequencing technology, other, as yet unidentified causes of root necrosis were investigated. Additionally a statistical analysis has shown which viruses are most closely associated with disease symptoms. Carrot samples were collected from a crop exhibiting root necrosis (102 Affected: 99 Unaffected) and tested for the presence of the established carrot viruses: Carrot red leaf virus (CtRLV), Carrot mottle virus (CMoV), Carrot red leaf associated viral RNA (CtRLVaRNA) and Parsnip yellow fleck virus (PYFV). The presence of these viruses was not associated with symptomatic carrot roots either as single viruses or in combinations. A sub-sample of carrots of mixed symptom status was subjected to MiSeq sequencing. The results from these tests suggested Carrot yellow leaf virus (CYLV) was associated with symptomatic roots. Additionally a novel Torradovirus, a novel Closterovirus and two novel Betaflexiviradae related plant viruses were detected. A specific diagnostic test was designed for CYLV. Of the 102 affected carrots, 98% were positive for CYLV compared to 22% of the unaffected carrots. From these data we conclude that although we have yet to practically demonstrate a causal link, CYLV appears to be strongly associated with the presence of necrosis of carrots.

Carrot yellow leaf virus Is Associated with Carrot Internal Necrosis

PubMed Central

Adams, Ian P.; Skelton, Anna; Macarthur, Roy; Hodges, Tobias; Hinds, Howard; Flint, Laura; Nath, Palash Deb; Boonham, Neil; Fox, Adrian

2014-01-01

Internal necrosis of carrot has been observed in UK carrots for at least 10 years, and has been anecdotally linked to virus infection. In the 2009 growing season some growers had up to 10% of yield with these symptoms. Traditional diagnostic methods are targeted towards specific pathogens. By using a metagenomic approach with high throughput sequencing technology, other, as yet unidentified causes of root necrosis were investigated. Additionally a statistical analysis has shown which viruses are most closely associated with disease symptoms. Carrot samples were collected from a crop exhibiting root necrosis (102 Affected: 99 Unaffected) and tested for the presence of the established carrot viruses: Carrot red leaf virus (CtRLV), Carrot mottle virus (CMoV), Carrot red leaf associated viral RNA (CtRLVaRNA) and Parsnip yellow fleck virus (PYFV). The presence of these viruses was not associated with symptomatic carrot roots either as single viruses or in combinations. A sub-sample of carrots of mixed symptom status was subjected to MiSeq sequencing. The results from these tests suggested Carrot yellow leaf virus (CYLV) was associated with symptomatic roots. Additionally a novel Torradovirus, a novel Closterovirus and two novel Betaflexiviradae related plant viruses were detected. A specific diagnostic test was designed for CYLV. Of the 102 affected carrots, 98% were positive for CYLV compared to 22% of the unaffected carrots. From these data we conclude that although we have yet to practically demonstrate a causal link, CYLV appears to be strongly associated with the presence of necrosis of carrots. PMID:25365290

Long-term results and quality of life of patients undergoing sequential surgical treatment for severe acute pancreatitis complicated by infected pancreatic necrosis.

PubMed

Cinquepalmi, Lorenza; Boni, Luigi; Dionigi, Gianlorenzo; Rovera, Francesca; Diurni, Mario; Benevento, Angelo; Dionigi, Renzo

2006-01-01

Infected pancreatic necrosis (IPN) is one of the most severe complications of acute pancreatitis (AP). Sequential surgical debridement represents one of the most effective treatments in terms of morbidity and mortality. The aim of this paper is to describe the quality of life and long-term results (e.g., nutritional, muscular, and pancreatic function) of patients treated by sequential necrosectomy at the Department of Surgery of the University of Insubria (Varese, Italy). Data were collected on patients undergoing sequential surgical debridement as treatment for IPN. The severity of AP was evaluated using the Ranson criteria, the Acute Physiology and Chronic Health Evaluation (APACHE II) Score, and the Sepsis Score, as well as the extent of necrosis. The surgical approach was through a midline or subcostal laparotomy, followed by exploration of the peritoneal cavity, wide debridement, and peritoneal lavage. The abdomen was either left open or closed partially with a surgical zipper, with multiple re-laparotomies scheduled until debridement of necrotic tissue was complete. The long-term evaluation focused on late morbidity, performance status, and abdominal wall function. In the majority of patients (68%), mixed flora were isolated. Pseudomonas aeruginosa was the microorganism identified most commonly (59%), often associated with Candida albicans or C. glabrata. The mean total hospital stay was 71+/-38 days (range 13-146 days), of which 24+/-19 days (range 0-66 days) were in the intensive care unit. Eight patients died, the deaths being caused by multiple organ dysfunction syndrome in seven patients and hemorrhage from the splenic artery in one. Normal exocrine and endocrine pancreatic function was observed in 28 patients (88%). At discharge, four patients had steatorrhea, which was temporary. Eight patients (23%) developed pancreatic pseudocysts, and in six, cystogastostomy was performed. Most patients (29/32, 91%) developed a post-operative hernia, but only five

Enhanced detection of infectious hematopoietic necrosis virus by pretreatment of cell monolayers with polyethylene glycol

USGS Publications Warehouse

Batts, W.N.; Winton, J.R.

1989-01-01

To improve quantification of very low levels of infectious hematopoietic necrosis virus (IHNV) in samples of tissue, ovarian fluid, or natural water supplies, we tested the ability of polyethylene glycol (PEG) to enhance the sensitivity and speed of the plaque assay system. We compared 4, 7, and 10% solutions of PEG of molecular weight 6,000, 8,000, or 20,000 applied at selected volumes and for various durations. When cell monolayers of epithelioma papulosum cyprini (EPC), fathead minnow (FHM), chinook salmon embryo (CHSE-214), and bluegill fry (BF2) were pretreated with 7% PEG-20,000, they produced 4-17-fold increases in plaque assay titers of IHNV. The plaque assay titers of viral hemorrhagic septicemia virus, chum salmon reovirus, and chinook salmon paramyxovirus were also enhanced by exposure of CHSE-214 cells to PEG, but the titers of infectious pancreatic necrosis virus and Oncorhynchus masou virus were not substantially changed. Plaques formed by IHNV on PEG-treated EPC cells incubated at 15°C had a larger mean diameter at 6 d than those on control cells at 8 d; this suggests the assay could be shortened by use of PEG. Pretreatment of EPC cell monolayers with PEG enabled detection of IHNV in some samples that appeared negative with untreated cells. For example, when ovarian fluid samples from chinook salmon Oncorhynchus tshawytscha were inoculated onto untreated monolayers of EPC cells, IHNV was detected in only 11 of 51 samples; 17 of the samples were positive when PEG-treated EPC cells were used.PDF

The Association of Viral Hepatitis and Acute Pancreatitis

PubMed Central

Geokas, Michael C.; Olsen, Harvey; Swanson, Virginia; Rinderknecht, Heinrich

1972-01-01

The histological features of 24 pancreases obtained from patients who died of causes other than hepatitis, pancreatitis or pancreatic tumors, included a variable degree of autolysis, rare foci of inflammatory reaction but no hemorrhagic fat necrosis or destruction of elastic tissue in vessel walls (elastolysis). Assays of elastase in extracts of these pancreases showed no free enzyme, but varying amounts of proelastase. A review of autopsy findings in 33 patients with fatal liver necrosis attributed to halothane anesthesia, demonstrated changes of acute pancreatitis only in two. On the other hand, a review of 16 cases of fulminant viral hepatitis revealed changes characteristic of acute pancreatitis in seven – interstitial edema, hemorrhagic fat necrosis, inflammatory reaction and frequently elastolysis in vessel walls. Determination of elastase in extracts of one pancreas showed the bulk of the enzyme in free form. Furthermore, assays of urinary amylase in 44 patients with viral hepatitis showed increased levels of this enzyme (2583 ± 398 mean value ± standard error, Somogyi units per 100 ml in 13, or 29.5 percent). The evidence suggests that acute pancreatitis may at times complicate viral hepatitis. Although direct proof of viral pancreatic involvement is not feasible at present, a rational hypothesis is advanced which underlines similar mechanisms of tissue involvement in both liver and pancreas that may be brought about by the hepatitis viruses. PMID:5070694

Adsorption to Fish Sperm of Vertically Transmitted Fish Viruses

NASA Astrophysics Data System (ADS)

Mulcahy, Dan; Pascho, Ronald J.

1984-07-01

More than 99 percent of a vertically transmitted fish rhabdovirus, infectious hematopoietic necrosis virus, was removed from suspension in less than 1 minute by adsorption to the surface membrane of sperm from two genera of salmonid fishes. The vertically transmitted, infectious pancreatic necrosis virus adsorbed to a lesser degree, but no adsorption occurred with a second fish rhabdovirus that is not vertically transmitted. Such adsorption may be involved in vertical transmission of these viruses.

Adsorption to fish sperm of vertically transmitted fish viruses

USGS Publications Warehouse

Mulcahy, D.; Pascho, R.J.

1984-01-01

More than 99 percent of a vertically transmitted fish rhabdovirus, infectious hematopoietic necrosis virus, was removed from suspension in less than 1 minute by adsorption to the surface membrane of sperm from two genera of salmonid fishes. The vertically transmitted, infectious pancreatic necrosis virus adsorbed to a lesser degree, but no adsorption occurred with a second fish rhabdovirus that is not vertically transmitted. Such adsorption may be involved in vertical transmission of these viruses.

Immunodiagnosis of groundnut and watermelon bud necrosis viruses using polyclonal antiserum to recombinant nucleocapsid protein of Groundnut bud necrosis virus.

PubMed

Jain, R K; Pandey, Amar N; Krishnareddy, M; Mandal, Bikash

2005-12-01

In vitro gene expression strategy was used for the production of polyclonal antiserum to the nucleocapsid protein (NP) of Groundnut bud necrosis virus (GBNV). The GBNV NP gene from cowpea isolate was cloned into 6x His-tagged UA cloning vector and expressed in Escherichia coli [M15] cells. The fusion protein was detected in insoluble fraction and was purified by using Ni-NTA agarose resin. The purified 6x His-fusion protein ( approximately 32 kDa) was used for immunisation to produce a high titre polyclonal antiserum. The antiserum to the NP of GBNV at 1:4000 dilution detected successfully natural infection of GBNV and Watermelon bud necrosis virus in a wide range of cucurbitaceous, leguminous and solanaceous hosts from different locations.

Biliary versus alcohol-related infected pancreatic necrosis: similarities and differences in the follow-up.

PubMed

Reszetow, Jacek; Hać, Stanisław; Dobrowolski, Sebastian; Stefaniak, Tomasz; Wajda, Zdzisław; Gruca, Zbigniew; Sledziński, Zbigniew; Studniarek, Michał

2007-10-01

Infected pancreatic necrosis (IPN) is a serious complication of acute pancreatitis. Data concerning survivors' quality of life and pancreatic functions are scarce. Follow-up of the patients with alcohol and biliary etiology of IPN treated with open necrosectomy was performed. Twenty-eight survivors after operative treatment (Bradley procedure) of IPN were followed up 24 to 96 months after discharge from the hospital (10 biliary and 18 alcohol patients). Their exocrine and endocrine pancreatic functions and quality of life (Functional Assessment of Chronic Illness Therapy scale) were evaluated. Pancreatic tissue remaining after necrosectomy was visualized by use of contrast-enhanced computed tomography (CT). In 44.4% of alcohol-induced IPN patients, the presence of the whole pancreas was shown on the follow-up CT, contrary to the biliary group, where the partial lack of the pancreas was observed in all cases. Pancreatic tissue calcifications were present on CT in 8 patients of alcohol-induced acute pancreatitis group only. Median stool elastase 1 concentrations were 318.1 U/mL in the biliary group and 238.3 U/mL in the alcohol-induced group (not significant). The Functional Assessment of Chronic Illness Therapy scale showed significantly higher social/family and emotional well-being in patients with biliary acute necrotizing pancreatitis. Patients after alcohol-induced IPN had lower quality of life compared with biliary etiology. Biliary and alcohol-induced IPN patients after surgical treatment have nonsignificant differences of endocrine and exocrine pancreatic functions.

Hepatitis viruses causing pancreatitis and hepatitis: a case series and review of literature.

PubMed

Bhagat, Sandeep; Wadhawan, Manav; Sud, Randhir; Arora, Anil

2008-05-01

Association between acute pancreatitis and acute viral hepatitis (AVH) is more frequent than previously thought. Most cases are hepatitis A or B virus related. Only 6 cases of acute pancreatitis with acute hepatitis E virus (HEV)-related hepatitis has been reported so far. We analyzed the hospital records of 334 patients of acute pancreatitis admitted from December 2004 to March 2006. Seven patients had an associated AVH. Of these, 4 had HEV-related and 3 had hepatitis A virus-related AVH. All but one were young males who presented with abdominal pain during the second to third week of hepatitis illness. None had a history of biliary colic, alcoholism, abdominal trauma, or intake of drugs causing pancreatitis or a family history of pancreatitis. Mean bilirubin was 10.74 mg/dL; alanine aminotransferase levels, 482.85 IU/L; and serum amylase, 1263.57 IU/L. All patients had an imaging evidence of pancreatitis. Two patients with HEV-related disease had grades D to E pancreatitis. All were managed conservatively and recovered completely. Association between acute pancreatitis and nonfulminant viral hepatitis is now more frequently recognized. Seen more commonly in young males during the second and third week of hepatitis illness, HEV might be associated with severe pancreatitis.

Gastrointestinal Fistulas in Acute Pancreatitis With Infected Pancreatic or Peripancreatic Necrosis

PubMed Central

Jiang, Wei; Tong, Zhihui; Yang, Dongliang; Ke, Lu; Shen, Xiao; Zhou, Jing; Li, Gang; Li, Weiqin; Li, Jieshou

2016-01-01

Abstract Gastrointestinal (GI) fistula is a well-recognized complication of acute pancreatitis (AP). However, it has been reported in limited literature. This study aimed to evaluate the incidence and outcome of GI fistulas in AP patients complicated with infected pancreatic or peripancreatic necrosis (IPN). Between 2010 and 2013 AP patients with IPN who diagnosed with GI fistula in our center were analyzed in this retrospective study. And we also conducted a comparison between patients with and without GI fistula regarding the baseline characteristics and outcomes. Over 4 years, a total of 928 AP patients were admitted into our center, of whom 119 patients with IPN were diagnosed with GI fistula and they developed 160 GI fistulas in total. Colonic fistula found in 72 patients was the most common form of GI fistula followed with duodenal fistula. All duodenal fistulas were managed by nonsurgical management. Ileostomy or colostomy was performed for 44 (61.1%) of 72 colonic fistulas. Twenty-one (29.2%) colonic fistulas were successfully treated by percutaneous drainage or continuous negative pressure irrigation. Mortality of patients with GI fistula did not differ significantly from those without GI fistula (28.6% vs 21.9%, P = 0.22). However, a significantly higher mortality (34.7%) was observed in those with colonic fistula. GI fistula is a common finding in patients of AP with IPN. Most of these fistulas can be successfully managed with different procedures depending on their sites of origin. Colonic fistula is related with higher mortality than those without GI fistula. PMID:27057908

[Identifying the severe acute pancreatitis].

PubMed

Acevedo Tizón, Anais; Targarona Modena, Javier; Málaga Rodríguez, Germán; Barreda Cevasco, Luis

2011-01-01

To compare patients with acute necrotizing pancreatitis without any additional complications during their hospital stay (Group A) versus patients with Acute Necrotizing Pancreatitis with additional complications during their hospital stay (Group B). Data obtained from a pre-existing base from hospitalized patients with diagnosis of acute necrotizing pancreatitis in the specialized unit of "Unidad de Pancreatitis Aguda Grave del Hospital Nacional Edgardo Rebagliati Martins" between 2000 and 2010. Data included patients with diagnosis of acute necrotizing pancreatitis, of ages 18 and over. Data from 215 patients with acute necrotizing pancreatitis was included. Patients from Group A represented 32% (68) and from Group B 68% (147). Group A had a average of 39 hospitalized days and Group B had an average of 56 days (p=0.01). From Group A 22% had more than 50% of necrosis while 43% of Group B had this extension of necrosis (p <0.05, OR 3.4, IC (1.12-10)). Of the 14 deaths of the population, all part of Group B, 12 of them had more than 50% of necrosis. Not every patient classified as severe acute pancreatitis, based on the presence of necrosis, behave likewise. It is an extended necrosis, described as more than 50% of pancreatic necrosis, and not the presence itself which will determine additional complications during the course of disease and a greater mortality.

VP2 (PTA motif) encoding DNA vaccine confers protection against lethal challenge with infectious pancreatic necrosis virus (IPNV) in trout.

PubMed

Ahmadivand, Sohrab; Soltani, Mehdi; Behdani, Mahdi; Evensen, Øystein; Alirahimi, Ehsan; Soltani, Elahe; Hassanzadeh, Reza; Ashrafi-Helan, Javad

2018-02-01

IPNV in Atlantic salmon is represented by various strains with different virulence and immunogenicity linked to various motifs of the VP2 capsid. IPNV variant with P 217 , T 221 , A 247 (PTA) motif is found to be avirulent in Atlantic salmon, but virulent in rainbow trout, and other salmonid species. This study describes a DNA vaccine delivered intramuscularly encoding the VP2 protein of infectious pancreatic necrosis virus (IPNV) with PTA motif that confers high protection in rainbow trout (Oncorhynchus mykiss). Intramuscular injection of 2, 5 and 10 μg of DNA (pcDNA3.1-VP2) in rainbow trout fry (4-5 g), confers relative protection of 75-83% in the different vaccine groups at 30 days post vaccination (450° days). The VP2 gene is expressed in spleen, kidney, muscle and liver at day 30 post-vaccination (RT-PCR), and IFN-1 and Mx-1 mRNA are upregulated at early time post vaccination, and so also for IgM, IgT, CD4 and CD8 in the head kidney of vaccinated fish compared to controls, 15 and 30 days post vaccination. Significant increase of serum anti-IPNV antibodies was found 30-90 days post-vaccination that was correlated with protection levels. Mortality corresponded with viral VP4 gene expression were significantly decreased in vaccinated and challenged fish. This shows for the first time that a VP2-encoding DNA vaccine delivered intramuscularly elicits a high level of protection alongside with high levels of circulating antibodies in rainbow trout and a lowered viral replication. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dendritic Cells Promote Pancreatic Viability in Mice with Acute Pancreatitis

PubMed Central

Bedrosian, Andrea S.; Nguyen, Andrew H.; Hackman, Michael; Connolly, Michael K.; Malhotra, Ashim; Ibrahim, Junaid; Cieza-Rubio, Napoleon E.; Henning, Justin R.; Barilla, Rocky; Rehman, Adeel; Pachter, H. Leon; Medina-Zea, Marco V.; Cohen, Steven M.; Frey, Alan B.; Acehan, Devrim; Miller, George

2011-01-01

Background & Aims Acute pancreatitis increases morbidity and mortality from organ necrosis by mechanisms that are incompletely understood. Dendritic cells (DCs) can promote or suppress inflammation, depending on their subtype and context. We investigated the roles of DC in development of acute pancreatitis. Methods Acute pancreatitis was induced in CD11c.DTR mice using caerulein or L-arginine; DCs were depleted by administration of diphtheria toxin. Survival was analyzed using Kaplan-Meier analysis. Results Numbers of MHC II+CD11c+DC increased 100-fold in pancreas of mice with acute pancreatitis, to account for nearly 15% of intra-pancreatic leukocytes. Intra-pancreatic DC acquired an immune phenotype in mice with acute pancreatitis; they expressed higher levels of MHC II and CD86 and increased production of interleukin-6, membrane cofactor protein (MCP)-1, and tumor necrosis factor (TNF)-α. However, rather than inducing an organ-destructive inflammatory process, DC were required for pancreatic viability; the exocrine pancreas died in mice that were depleted of DC and challenged with caerulein or L-arginine. All mice with pancreatitis that were depleted of DC died from acinar cell death within 4 days. Depletion of DC from mice with pancreatitis resulted in neutrophil infiltration and increased levels of systemic markers of inflammation. However, the organ necrosis associated with depletion of DC did not require infiltrating neutrophils, activation of NF-κB, or signaling by mitogen-activated protein kinase or TNF-α. Conclusions DC are required for pancreatic viability in mice with acute pancreatitis and might protect organs against cell stress. PMID:21801698

Molecular characterization of infectious pancreatic necrosis virus strains isolated from the three types of salmonids farmed in Chile.

PubMed

Manríquez, René A; Vera, Tamara; Villalba, Melina V; Mancilla, Alejandra; Vakharia, Vikram N; Yañez, Alejandro J; Cárcamo, Juan G

2017-01-31

The infectious pancreatic necrosis virus (IPNV) causes significant economic losses in Chilean salmon farming. For effective sanitary management, the IPNV strains present in Chile need to be fully studied, characterized, and constantly updated at the molecular level. In this study, 36 Chilean IPNV isolates collected over 6 years (2006-2011) from Salmo salar, Oncorhynchus mykiss, and Oncorhynchus kisutch were genotypically characterized. Salmonid samples were obtained from freshwater, estuary, and seawater sources from central, southern, and the extreme-south of Chile (35° to 53°S). Sequence analysis of the VP2 gene classified 10 IPNV isolates as genogroup 1 and 26 as genogroup 5. Analyses indicated a preferential, but not obligate, relationship between genogroup 5 isolates and S. salar infection. Fifteen genogroup 5 and nine genogroup 1 isolates presented VP2 gene residues associated with high virulence (i.e. Thr, Ala, and Thr at positions 217, 221, and 247, respectively). Four genogroup 5 isolates presented an oddly long VP5 deduced amino acid sequence (29.6 kDa). Analysis of the VP2 amino acid motifs associated with clinical and subclinical infections identified the clinical fingerprint in only genogroup 5 isolates; in contrast, the genogroup 1 isolates presented sequences predominantly associated with the subclinical fingerprint. Predictive analysis of VP5 showed an absence of transmembrane domains and plasma membrane tropism signals. WebLogo analysis of the VP5 BH domains revealed high identities with the marine birnavirus Y-6 and Japanese IPNV strain E1-S. Sequence analysis for putative 25 kDa proteins, coded by the ORF between VP2 and VP4, exhibited three putative nuclear localization sequences and signals of mitochondrial tropism in two isolates. This study provides important advances in updating the characterizations of IPNV strains present in Chile. The results from this study will help in identifying epidemiological links and generating specific

Effects of Erdosteine on Experimental Acute Pancreatitis Model.

PubMed

Karapolat, Banu; Karapolat, Sami; Gurleyik, Emin; Yasar, Mehmet

2017-10-01

To create acute pancreatitis condition experimentally in rats using cerulein, and to reveal histopathological effects in pancreatic tissue with erdosteine. An experimental study. Department of General Surgery, Duzce University, Turkey, from June to October 2014. Thirty male Wistar albino rats were divided into three groups. No procedures were applied to Group 1. The rats in Group 2 and Group 3 were injected cerulein, to establish an experimental pancreatitis model and the blood amylase and lipase values were examined. The rats in Group 3 were given 10 mg/kg erdosteine. This treatment was continued for another 2 days and the rats were sacrificed. The pancreatic tissues were examined histopathologically for edema, inflammation, acinar necrosis, fat necrosis, and vacuolization. The lipase and amylase values and the histopathological examination of pancreatic tissues evidenced that the experimental acute pancreatitis model was established and edema, inflammation, acinar necrosis, fat necrosis, and vacuolization were observed in the pancreatic tissues. The statistical results suggest that erdosteine can decrease the edema, inflammation, acinar necrosis, fat necrosis and vacuolization scores in the tissues. The severity of acute pancreatitis, induced by cerulein in rats, is reduced with the use of erdosteine.

Endocrine and exocrine pancreatic insufficiency after acute pancreatitis: long-term follow-up study.

PubMed

Tu, Jianfeng; Zhang, Jingzhu; Ke, Lu; Yang, Yue; Yang, Qi; Lu, Guotao; Li, Baiqiang; Tong, Zhihui; Li, Weiqin; Li, Jieshou

2017-10-27

Patients could develop endocrine and exocrine pancreatic insufficiency after acute pancreatitis (AP), but the morbidity, risk factors and outcome remain unclear. The aim of the present study was to evaluate the incidence of endocrine and exocrine pancreatic insufficiency after AP and the risk factors of endocrine pancreatic insufficiency through a long-term follow-up investigation. Follow-up assessment of the endocrine and exocrine function was conducted for the discharged patients with AP episodes. Oral Glucose Tolerance Test (OGTT) and faecal elastase-1(FE-1) test were used as primary parameters. Fasting blood-glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin HBA1c, 2-h postprandial blood glucose (2hPG), Homa beta cell function index (HOMA-β), homeostasis model assessment of insulin resistance (HOMA-IR) and FE-1 were collected. Abdominal contrast-enhanced computed tomography (CECT) was performed to investigate the pancreatic morphology and the other related data during hospitalization was also collected. One hundred thirteen patients were included in this study and 34 of whom (30.1%) developed diabetes mellitus (DM), 33 (29.2%) suffered impaired glucose tolerance (IGT). Moreover, 33 patients (29.2%) developed mild to moderate exocrine pancreatic insufficiency with 100μg/gpancreatic insufficiency with FE-1<100μg/g. The morbidity of DM and IGT in patients with pancreatic necrosis was significant higher than that in the non-pancreatic necrosis group (X 2  = 13.442,P = 0.001). The multiple logistic regression analysis showed that extent of pancreatic necrosis<30% (P = 0.012, OR = 0.061) were the protective factors of endocrine pancreatic insufficiency. HOMA-IR (P = 0.002, OR = 6.626), Wall-off necrosis (WON) (P = 0.013, OR = 184.772) were the risk factors. The integrated morbidity of DM and IGT after AP was 59.25%, which was higher than exocrine pancreatic

[Latest advances in acute pancreatitis].

PubMed

de-Madaria, Enrique

2015-09-01

The present article analyses the main presentations on acute pancreatitis at Digestive Disease Week 2015. Arterial pseudoaneurysm is an uncommon complication of acute pancreatitis (incidence 0.7%) and mortality from this cause is currently anecdotal. Diabetes mellitus has little impact on the clinical course of acute pancreatitis, unlike cirrhosis, which doubles the risk of mortality. Intake of unsaturated fat could be associated with an increased severity of acute pancreatitis and is a confounding factor in studies evaluating the relationship between obesity and morbidity and mortality. PET-CT (positron emission tomography-computed tomography) could be a non-invasive tool to detect infection of collections in acute pancreatitis. Peripancreatic fat necrosis is less frequent than pancreatic fat necrosis and is associated with a better clinical course. If the clinical course is poor, increasing the calibre of the percutaneous drains used in the treatment of infected necrosis can avoid surgery in 20% of patients. The use of low molecular-weight heparin in moderate or severe pancreatitis could be associated with a better clinical course, specifically with a lower incidence of necrosis. In acute recurrent pancreatitis, simvastatin is a promising drug for prophylaxis of new episodes of acute pancreatitis. Nutritional support through a nasogastric tube does not improve clinical course compared with oral nutrition. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Osteomyelitis: A rare complication of pancreatitis and PPP-syndrome.

PubMed

Langenhan, Ronny; Reimers, Niklas; Probst, Axel

2016-03-01

Pancreatic diseases can be accompanied by periarthritis with bone necrosis and panniculitis (PPP-syndrome). It is postulated that this is caused by systemic activity of pancreatic enzymes leading to microcirculatory disturbances and fat necrosis. The morbidity and mortality of the PPP-syndrome is high. Successful treatment of pancreatitis can lead to resolution of accompanying panniculitis and periarthritis without adverse sequelae, but weeks or months after pancreatitis, asymptomatic necrosis of the bone may become symptomatic by fracturing spontaneously. In this report, we also describe osteomyelitis as a severe septic complication of bone necrosis caused by pancreatitis, in one case as acute tissue necrosis and in another case months after pancreatitis spread haematogenously. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Lactobacillus plantarum reduces infection of pancreatic necrosis in experimental acute pancreatitis.

PubMed

Mangiante, G; Colucci, G; Canepari, P; Bassi, C; Nicoli, N; Casaril, A; Marinello, P; Signoretto, C; Bengmark, S

2001-01-01

Infection is the commonest cause of death in acute pancreatitis. Early reduction of commensal flora (particularly Lactobacillus species) and, at the same time, overgrowth of Enterobacteriaceae, especially Escherichia coli, have recently been described during acute pancreatitis. Lactobacillus plantarum has been shown to be effective in reducing the egress of endotoxin and microbial translocation in several experimental models such as chemically induced hepatitis and ulcerative colitis. The aim of the study was to determine whether L. plantarum 299v (Lp 299v) is capable of effectively reducing microbial translocation in experimental pancreatitis. Acute pancreatitis was induced by isolation and ligation of the biliopancreatic duct in Lewis rats weighing 250-350 g. The animals were divided into 3 groups: group A, sham operation; group B, induction of pancreatitis and no further treatment, and group C, induction of pancreatitis + daily administration by gavage of a 5-ml/day suspension of Lp 299v at 0.5-1.0 x 10(9) bacteria/ml for 8 days, 4 days before and 4 days after induction of pancreatitis. All animals were sacrificed after 96 h. Histological studies and microbiological analyses were performed. At sacrifice, 40/55 animals showed signs of severe pancreatitis. Since acute pancreatitis was the specific disease investigated, only these animals were subjected to further study. In group B, we found pathogenic micro-organisms in the mesenteric lymph nodes in 14/20 animals and in the pancreatic tissue in 10/20. The bacterial flora consisted predominantly of E. coli, Enterococcus faecalis, Pseudomonas and Proteus species. In contrast, when the animals were kept under an 'umbrella' of Lp 299v, growth of E. faecalis or E. coli were detected only in 4/20 mesenteric lymph node cultures and in 3/20 pancreatic tissue cultures. Lp 299v is effective in reducing microbial translocation in experimental pancreatitis. Treatment with probiotic bacteria seems to be a promising alternative

Endothelial markers are associated with pancreatic necrosis and overall prognosis in acute pancreatitis: A preliminary cohort study.

PubMed

Chen, Yizhe; Ke, Lu; Meng, Lei; Yang, Qi; Tong, Zhihui; Pan, Yiyuan; Li, Weiqin; Li, Jieshou

Endothelial injury is believed to play an important role in the evolution of pancreatic microcirculatory dysfunction and pancreatic necrosis (PN) in patients with acute pancreatitis (AP). The aim of this study was to investigate the role of three endothelial markers (von Willebrand factor, vWF; E-selectin; endothelial protein C receptor, EPCR) in the early phase of AP, especially the relationship between endothelial markers and PN. From March 2015 to March 2016, 57 AP patients admitted within 72 h of symptom onset in our hospital were included for this study. Blood samples were taken on admission and the clinical characteristics and outcomes of these patients were recorded. The levels of vWF, E-selectin and EPCR were measured using ELISA for analysis and compared with other severity markers of AP. All the three markers were significantly different in healthy control, mild, moderate and severe AP patients. Moreover, the endothelial markers, especially vWF, also showed significant difference in patients with different extent of PN, as well as those with or without MODS. Additionally, the levels of endothelial markers correlated well with other commonly used markers of AP severity. Elevated endothelium-related mediators (vWF, E-selectin and EPCR) appear to participate in the development of PN and may be a potential indicator of overall prognosis. Our results may help clinicians better understand the pathophysiological process of the development of PN. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Virucidal activity of two Iodophors to salmonid viruses

USGS Publications Warehouse

Amend, Donald F.; Pietsch, John P.

1972-01-01

Wescodyne® and Betadine®, organic iodine complexes, were compared in vitro for virucidal activity against infectious hematopoietic necrosis (IHN), infectious pancreatic necrosis (IPN), and viral hemorrhagic septicemia (VHS) viruses. Both iodophors were about equally effective on all three viruses. Each iodophor completely destroyed IHN virus within 30 sec at 12 ppm iodine, and was not affected by water hardness. Virucidal activity, however, was reduced at pH levels above 8.0 and in the presence of organic matter. Wescodyne was also compared with seven disinfectants commonly used in fish hatcheries, for virucidal properties against IHN virus. Wescodyne and chlorine were the only disinfectants to completely destroy the virus. Either Wescodyne or Betadine would effectively destroy the salmonid viruses at less than 25 ppm iodine within 5 min in solutions near neutrality.

Oral DNA vaccines based on CS-TPP nanoparticles and alginate microparticles confer high protection against infectious pancreatic necrosis virus (IPNV) infection in trout.

PubMed

Ahmadivand, Sohrab; Soltani, Mehdi; Behdani, Mahdi; Evensen, Øystein; Alirahimi, Ehsan; Hassanzadeh, Reza; Soltani, Ellahe

2017-09-01

Infectious pancreatic necrosis virus (IPNV) is the etiological agent of a contagious viral disease causing remarkable mortalities in different fish species. Despite the availability of commercial vaccines against IPN, the disease still constitutes one of the main threats to the aquaculture industry worldwide. In this study, we developed a DNA vaccine encoding the VP2 gene of IPNV and evaluated its ability to induce protective immunity in rainbow trout fry (3 g) at doses of 10 and 25 μg/fish and boosting with the same doses two weeks later through the oral route using chitosan/tripolyphosphate (CS-TPP) nanoparticles and alginate microparticles incorporated into fish feed. The distribution of the administered vaccines in different organs and transcription of VP2 gene were confirmed by RT-PCR assay at day 30 post boost-vaccination. Transcript levels of IFN-1, Mx-1, IgM, IgT and CD4 genes was dependent on vaccine dose and was significantly up-regulated in head kidney of all orally vaccinated fish groups compared to controls (pcDNA3.1). Cumulative mortalities post-challenge with virulent isolate of the virus were lower in the vaccinated fish and a relative percentage survival (RPS) of 59% and 82% were obtained for the 10 and 25 μg/fish pcDNA3.1-VP2 groups, respectively. Vaccination with the same amount of pcDNA3.1-VP2 encapsulated with CS-TPP nanoparticles resulted in RPS of 47 %and 70%, respectively. Detectable anti-IPNV antibodies were shown until 90 days postvaccination. The orally administrated vaccines significantly decreased VP4 transcripts thus contributing to reducing viral load in surviving fish on day 45 post-challenge. In conclusion, these results show good to high protection post-vaccination alongside with significant up-regulation of key immune genes and detectable levels of circulating antibodies after oral administration of the DNA vaccine formulated in CS-TPP nanoparticles and alginate microparticles in fish feed. Copyright © 2017 Elsevier Ltd. All

Patients With Sentinel Acute Pancreatitis of Alcoholic Etiology are at Risk for Organ Failure and Pancreatic Necrosis: A Dual-Center Experience

PubMed Central

Easler, Jeffrey J.; de-Madaria, Enrique; Nawaz, Haq; Moya-Hoyo, Neftalí; Koutroumpakis, Efstratios; Rey-Riveiro, Mónica; Singh, Vijay P.; Acevedo-Piedra, Nelly G.; Whitcomb, David C.; Yadav, Dhiraj; Papachristou, Georgios I.

2016-01-01

Objectives Assess the relationship between alcoholic etiology, tobacco use and severe acute pancreatitis (SAP). Methods Smoking and alcohol exposure were recorded upon admission in a cohort of acute pancreatitis patients within the United States (U.S.). Patients with first, “sentinel” attack of acute pancreatitis (AP) were identified for analysis. Associations between alcohol, smoking and SAP were validated in an independent cohort of patients from Spain. Results U.S. cohort (n=222): Thirty-five% developed organ failure (OF), 35% Pancreatic Necrosis (PNec), and 7% died. OF (54% vs. 33%, p=0.03), PNec (62% vs. 31%, p=0.006), intensive care (ICU) admission (58% vs. 36%, p=0.03) and length of stay (LOS) (20 vs. 8 days, p= 0.007) were greater in alcoholic when compared to other etiologies. Spanish cohort (n=366): Similar differences in outcomes were also found with between alcoholic and non-alcoholic etiologies: OF (24% vs. 8%, p=0.001), PNec (38% vs. 14%, p<0.001), ICU admission (20% vs. 3%, p<0.001), and LOS (17 vs. 11 days, p=0.04). Multivariable analysis confirmed alcoholic etiology to be independently associated with OF and PNec in both cohorts. Conclusions Alcoholic etiology is independently associated with OF and PNec in patients with sentinel AP and is important when evaluating risk for severe disease in AP. PMID:27101573

Protein A from orange-spotted nervous necrosis virus triggers type I interferon production in fish cell.

PubMed

Huang, Runqing; Zhou, Qiong; Shi, Yan; Zhang, Jing; He, Jianguo; Xie, Junfeng

2018-05-04

Family Nodaviridae consists of two genera: Alphanodavirus and Betanodavirus, and the latter is classified into four genotypes, including red-spotted grouper nervous necrosis virus, tiger puffer nervous necrosis virus, striped jack nervous necrosis virus, and barfin flounder nervous necrosis virus. Type I interferons (IFNs) play a central role in the innate immune system and antiviral responses, and the interactions between IFN and NNV have been investigated in this study. We have found that the RNA-dependent RNA polymerase (RdRp) from orange-spotted nervous necrosis virus (OGNNV), named protein A, was capable of activating IFN promoter in fathead minnow (FHM) cells. Transient expression of protein A was found to induce IFN expression and secretion, endowing FHM cells with anti-tiger frog virus ability. Protein A from SJNNV can also induce IFN expression in FHM cells but that from Flock House virus (FHV), a well-studied representative species of genus Alphanodavirus, cannot. RdRp activity and mitochondrial localization were shown to be required for protein A to induce IFN expression by means of activating IRF3 but not NFκB. Furthermore, DsRNA synthesized in vitro transcription and poly I:C activated IFN promoter activity when transfected into FHM cells, and dsRNA were also detected in NNV-infected cells. We postulated that dsRNA, a PAMP, was produced by protein A, leading to activation of innate immune response. These results suggest that protein As from NNV are the agonists of innate immune response. This is the first work to demonstrate the interaction between NNV protein A and innate immune system, and may help to understand pathogenesis of NNV. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pathogenesis of infectious hematopoietic necrosis virus in adult sockeye salmon (Oncorhynchus nerka)

USGS Publications Warehouse

Mulcahy, D.M.; Burke, J.; Pascho, R.J.; Jenes, C.K.

1982-01-01

The concentration of infectious hematopoietic necrosis (IHN) virus was determined in eight organs and two body fluids from each of 60 adult sockeye salmon (Oncorhynchus nerka). Included in the sample were 4 males and 56 prespawning, spawning, or spent female fish. All fish were infected, and virus was present in nearly all organs. There was an overall tendency for the mean concentration to increase in many of the organs over time as the fish progressed in ripeness. In prespawning females, IHN virus could be detected in all organs and in ovarian fluid but not in serum; the incidences were highest in the gills, spleen, and pyloric ceca, and the titers were highest in the pyloric ceca and liver. Incidences of infection in the organs were higher in spawning than in prespawning females and higher still in spent females in which the incidence of virus was 100% in all organs except brains (78%) and sera (67%). Virus concentrations in organs or fluids ranged from 5 to 4.0 × 109 plaque-forming units per millilitre. In males, the highest incidences of virus were found in gills, pyloric ceca, and liver. The gills were the only organ in which the virus concentration in males exceeded that of females.Key words: infectious hematopoietic necrosis, IHN, fish virus, viral pathogenesis, sockeye salmon

Antiviral function of tilapia hepcidin 1-5 and its modulation of immune-related gene expressions against infectious pancreatic necrosis virus (IPNV) in Chinook salmon embryo (CHSE)-214 cells.

PubMed

Rajanbabu, Venugopal; Chen, Jyh-Yih

2011-01-01

Antimicrobial peptides, small cysteine-rich molecules, play vital roles in host defense mechanisms against pathogen infection. Recently, tilapia hepcidin (TH)1-5, was characterized, and its antimicrobial functions against several pathogens were reported. Herein, we investigated the antiviral functions of TH1-5 against infectious pancreatic necrosis virus (IPNV) in Chinook salmon embryo (CHSE)-214 cells. The presence of TH1-5 enhanced the survival of CHSE-214 cells infected with IPNV. Additionally, the number of plaques formed by the cytopathic effect of IPNV in CHSE-214 cells decreased when IPNV was preincubated with TH1-5. This observation demonstrates the antiviral function of TH1-5. Real-time PCR studies showed the modulation of interleukin, annexin, and other viral-responsive gene expressions by TH1-5. When TH1-5 and IPNV were used to co-treat CHSE-214 cells, then cells were re-challenged with IPNV at 24h, the cells did not survive the IPNV infection. This shows that in the absence of TH1-5, viral re-challenge killed CHSE-214 cells. In conclusion TH1-5 protected CHSE-214 cells against IPNV by direct antimicrobial and immunomodulatory functions. Copyright © 2010 Elsevier Ltd. All rights reserved.

Reduced lymphocyte count as an early marker for predicting infected pancreatic necrosis.

PubMed

Shen, Xiao; Sun, Jing; Ke, Lu; Zou, Lei; Li, Baiqiang; Tong, Zhihui; Li, Weiqin; Li, Ning; Li, Jieshou

2015-10-26

Early occurrence of immunosuppression is a risk factor for infected pancreatic necrosis (IPN) in the patients with acute pancreatitis (AP). However, current measures for the immune systems are too cumbersome and not widely available. Significantly decreased lymphocyte count has been shown in patients with severe but not mild type of AP. Whereas, the correlation between the absolute lymphocyte count and IPN is still unknown. We conduct this study to reveal the exact relationship between early lymphocyte count and the development of IPN in the population of AP patients. One hundred and fifty-three patients with acute pancreatitis admitted to Jinling Hospital during the period of January 2012 to July 2014 were included in this retrospective study. The absolute lymphocyte count and other relevant parameters were measured on admission. The diagnosis of IPN was based on the definition of the revised Atlanta classification. Patients were divided into two groups according to the presence of IPN. Thirty patients developed infected necrotizing pancreatitis during the disease course. The absolute lymphocyte count in patients with IPN was significantly lower on admission (0.62 × 10(9)/L, interquartile range [IQR]: 0.46-0.87 × 10(9)/L vs. 0.91 × 10(9)/L, IQR: 0.72-1.27 × 10(9)/L, p < 0.001) and throughout the whole clinical course than those without IPN. Logistic regression indicated that reduced lymphocyte count was an independent risk factor for IPN. The optimal cut-offs from ROC curve was 0.66 × 10(9)/L giving sensitivity of 83.7 % and specificity of 66.7 %. Reduced lymphocyte count within 48 h of AP onset is significantly and independently associated with the development of IPN.

A hematopoietic virus disease of rainbow trout and sockeye salmon

USGS Publications Warehouse

Amend, Donald F.; Yasutake, William T.; Mead, Robert W.

1969-01-01

A previously undescribed virus disease epizootic of hatchery rainbow trout (Salmo gairdneri) in British Columbia, Canada is presented. In the same locality, a similar virus disease was experienced among hatchery sockeye salmon (Oncorhynchus nerka). Typical symptoms included flashing, fecal casts, hemorrhagic areas at the base of fins, and petechial hemorrhages on the visceral fat and membranes in the abdominal cavity. Histopathologic changes were typified by extensive degeneration and necrosis in the hematopoietic tissues of the kidney and spleen. A virus was isolated from both species of fish on tissue culture and the viruses showed cross-infectivity. Based upon the pathological changes in the hematopoietic tissue and the demonstration of a vital infection, a tentative descriptive name was designated Infectious Hematopoietic Necrosis. The isolated viruses were distinctly different from the infectious pancreatic necrosis or viral hemorrhagic septicemia viruses of trout, but did show similarities to the Oregon sockeye and Sacramento River chinook viruses. Positive identification awaits further tests. The significance of these observations is the reporting of a new viral disease of rainbow trout and the extension of the geographic range of sockeye salmon viruses.

Chaiqinchengqi decoction regulates necrosis-apoptosis via regulating the release of mitochondrial cytochrome c and caspase-3 in rats with acute necrotizing pancreatitis.

PubMed

Lin, Ziqi; Guo, Jia; Xue, Ping; Huang, Lei; Deng, Lihui; Yang, Xiaonan; Xia, Qing

2014-04-01

To explore the effect and the mechanism of Chaiqinchengqi decoction (CQCQD) on the apoptosis-necrosis switch of pancreatic acinar cells in acute necrotizing pancreatitis (ANP) in rats. Sixty Sprague-Dawley rats were randomized into the control group, the ANP group and the CQCQD group. The acute pancreatitis (AP) model was induced by intraperitoneal injections of 4 g/kg 8% L-Arginine (PH 7.0) twice with a 1 h interval. Rats in the CQCQD group were intragastrically administered CQCQD (20 mL/kg every 2 h, 3 times, then 20 mL/kg every 6 h, 3 times). Rats were killed at the 6 and 24 h after the induction of AP. The pancreatic tissues were collected for pathology and to isolate pancreatic acinar cells and mitochondria. CQCQD significantly ameliorated the severity of ANP by reducing the pancreatic histopathology score, indicated by lactate dehydrogenase levels at the 6 and 24 h. The CQCQD group promoted the apoptosis of pancreatic acinar cells by raising the apoptosis index compared with the ANP group and the control group. Mitochondrial cytochrome c at the 6 and 24 h in the ANP group were lower than that in the control group or the CQCQD group (0.67 +/- 0.13 vs 1.54 +/- 0.03 vs 0.81 +/- 0.09; 0.71 +/- 0.08 vs 1.55 +/- 0.09 vs 0.89 +/- 0.16, P < 0.01). The cytochrome c levels in the cytoplasm at the 6 and 2 h in the CQCQD group were higher than in the control group (1.36 +/- 0.15 vs 0.67 +/- 0.04, 1.46 +/- 0.08 vs 0.59 +/- 0.09, P < 0.01), or the ANP group (0.96 +/- 0.13, P > 0.05; 0.97 +/- 0.09, P < 0.05). CQCQD increased caspase-3 activity over the ANP group at the 6 h. CQCQD can induce apoptosis and relieve the necrosis of pancreatic acinar cells via promoting the release of mitochondrial cytochrome c and increasing pancreatic caspase-3 activity in ANP rats.

The role of transpapillary drainage in management of patients with pancreatic fluid collections and pancreatic duct disruption as a consequences of severe acute pancreatitis.

PubMed

Jagielski, Mateusz; Smoczyński, Marian; Adrych, Krystian

In last thirty years we have been observing significant development of an endoscopic treatment of pancreatic fluid collections, including transmural drainage of walled-off pancreatic necrosis. Simultaneously, the use of endotherapy in treatment of main pancreatic ducts disruptions has increased. Despite many publications available in current literature, concerning the endoscopic treatment of consequences of acute necrotizing pancreatitis, the role of transpapillary drainage in management of patients with pancreatic fluid collections and pancreatic duct disruption as an after-effect of severe acute pancreatitis remains unclear and is still a current problem. This publication includes comment on the article entitled 'Early dual drainage combining transpapillary endotherapy and percutaneous catheter drainage in patients with pancreatic fistula associated with severe acute pancreatitis' published by Yokoi et al. in the July-August 2016 issue of Pancreatology together with questions to the authors. Furthermore, in the article we did pay particular attention to the role of transpapillary drainage in management of pancreatic fluid collections, especially of walled-of pancreatic necrosis. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Morphology of certain viruses of Salmonid fishes. II. In vivo studies of infectious Hematopoietic Necrosis Virus

USGS Publications Warehouse

Amend, Donald F.; Chambers, Velma C.

1970-01-01

Juvenile sockeye salmon (Oncorhynchus nerka) were injected with the infectious hematopoietic necrosis (IHN) virus, and tissue samples from the anterior kidney, spleen, liver, intestine, and pyloric caeca of moribund fish were prepared for electron microscopy. Bullet-shaped virus particles measuring 158 × 90 mμ were observed in the hematopoietic tissues of the anterior kidney and spleen. Virus particles were also observed in the outer connective tissues of the pancreas or pyloric caeca, or both. No virus was found in the intestine or liver. The healthy appearance of erythrocytes, reticular cells, and endothelial cells in necrotic areas of the spleen and anterior kidney, and the absence of lymphocytes in these areas, suggested that lymphocytes might be one source of the virus.

Robotic transgastric cystgastrostomy and pancreatic debridement in the management of pancreatic fluid collections following acute pancreatitis.

PubMed

Kirks, Russell C; Sola, Richard; Iannitti, David A; Martinie, John B; Vrochides, Dionisios

2016-01-01

Pancreatic and peripancreatic fluid collections may develop after severe acute pancreatitis. Organized fluid collections such as pancreatic pseudocyst and walled-off pancreatic necrosis (WOPN) that mature over time may require intervention to treat obstructive or constitutional symptoms related to the size and location of the collection as well as possible infection. Endoscopic, open surgical and minimally invasive techniques are described to treat post-inflammatory pancreatic fluid collections. Surgical intervention may be required to treat collections containing necrotic pancreatic parenchyma or in locations not immediately apposed to the stomach or duodenum. Comprising a blend of the surgical approach and the clinical benefits of minimally invasive surgery, the robot-assisted technique of pancreatic cystgastrostomy with pancreatic debridement is described.

Endoscopic pancreatic necrosectomy.

PubMed

Fogel, Evan L

2011-07-01

Traditionally, patients with symptomatic sterile pancreatic necrosis or infected necrosis have been managed by open surgical debridement and removal of necrotic tissue. Within the last decade, however, reports of endoscopic pancreatic necrosectomy, an alternative minimally invasive approach, have demonstrated high success rates and low mortality rates. This report describes the indications, technique, and study outcome data of the procedure. While our experience with this technique has recently increased, better selection criteria are needed to identify patients who are most suitable for endoscopic therapy.

Morphology of certain viruses of Salmonid Fishes. I. in vitro studies of some viruses causing Hematopoietic Necrosis

USGS Publications Warehouse

Amend, Donald F.; Chambers, Velma C.

1970-01-01

An electron microscope study was performed on three virus isolates that caused hematopoietic necrosis in salmonid fishes: infectious hematopoietic necrosis (IHN), Oregon Sockeye Disease (OSD), and Sacramento River Chinook Salmon Disease (SRCD). All three isolates were examined by negative staining of fathead minnow (FHM) monolayer tissue culture concentrates and IHN virus was also examined in thin sections of FHM cells. Viruslike particles were observed in infected tissues, but similar structures were not found in uninfected cultures. All three isolates were bullet-shaped, but oval and truncated forms were also observed. Mean measurements of particles from IHN-virus-infected tissue were 158 × 90 mμ. They consisted of an outer coat 15 mμ thick, a core 60 mμ in diameter, subunits about 5 mμ, and an axial pore about 20 mμ in diameter. These particles also were seen budding from the cytoplasmic membrane. Similar particles from SRCD were 159 × 90 mμ and isolates from OSD were 181 × 91 mμ. The three isolates were morphologically indistinguishable from one another and the greater length of OSD was considered insignificant. IHN, SRCD, and OSD viruses were tentatively placed in the rhabdovirus group, but serological studies are needed to determine if they are antigenically identical or should be included as separate members. Biochemical and physical characteristics of these viruses and a comparison with other salmonid viruses is also discussed.

First Complete Genome Sequence of Bean common mosaic necrosis virus from East Timor

PubMed Central

Maina, Solomon; Edwards, Owain R.; de Almeida, Luis; Ximenes, Abel

2016-01-01

We present here the first complete Bean common mosaic necrosis virus (BCMNV) genomic sequence isolated from virus-infected common bean (Phaseolus vulgaris) in East Timor, and compare it with six complete BMCNV genomes from the Netherlands, and one each from the United States, Tanzania, and an unspecified country. It most resembled the Netherlands strain NL-8 genome. PMID:27688343

Johnsongrass mosaic virus contributes to maize lethal necrosis in East Africa

USDA-ARS?s Scientific Manuscript database

Maize lethal necrosis (MLN), a severe virus disease of maize, has emerged in East Africa in recent years with devastating effects on production and food security where maize is a staple subsistence crop. In extensive surveys of MLN-symptomatic plants in East Africa, sequences of Johnsongrass mosaic ...

Cholecystokinin induces caspase activation and mitochondrial dysfunction in pancreatic acinar cells. Roles in cell injury processes of pancreatitis.

PubMed

Gukovskaya, Anna S; Gukovsky, Ilya; Jung, Yoon; Mouria, Michelle; Pandol, Stephen J

2002-06-21

Apoptosis and necrosis are critical parameters of pancreatitis, the mechanisms of which remain unknown. Many characteristics of pancreatitis can be studied in vitro in pancreatic acini treated with high doses of cholecystokinin (CCK). We show here that CCK stimulates apoptosis and death signaling pathways in rat pancreatic acinar cells, including caspase activation, cytochrome c release, and mitochondrial depolarization. The mitochondrial dysfunction is mediated by upstream caspases (possibly caspase-8) and, in turn, leads to activation of caspase-3. CCK causes mitochondrial alterations through both permeability transition pore-dependent (cytochrome c release) and permeability transition pore-independent (mitochondrial depolarization) mechanisms. Caspase activation and mitochondrial alterations also occur in untreated pancreatic acinar cells; however, the underlying mechanisms are different. In particular, caspases protect untreated acinar cells from mitochondrial damage. We found that caspases not only mediate apoptosis but also regulate other parameters of CCK-induced acinar cell injury that are characteristic of pancreatitis; in particular, caspases negatively regulate necrosis and trypsin activation in acinar cells. The results suggest that the observed signaling pathways regulate parenchymal cell injury and death in CCK-induced pancreatitis. Protection against necrosis and trypsin activation by caspases can explain why the severity of pancreatitis in experimental models correlates inversely with the extent of apoptosis.

Susceptibility of cultured juveniles of several marine fish to the sevenband grouper nervous necrosis virus.

PubMed

Tanaka, S; Kuriyama, I; Nakai, T; Miyazaki, T

2003-02-01

Piscine nodaviruses (betanodaviruses) have been tentatively divided into four genotypes (SJNNV, RGNNV, TPNNV and BFNNV) and it is suggested that host specificity is different among these genotypes. In the present study, a betanodavirus [sevenband grouper nervous necrosis virus (SGNNV)] belonging to the redspotted grouper nervous necrosis virus (RGNNV) genotype, to which most betanodaviruses from warm water fish are identified, was evaluated for its pathogenicity to hatchery-reared juveniles of several marine fish species. When challenged with the virus by a bath method (10(5.1) TCID50 mL(-1)), sevenband grouper, Epinephelus septemfasciatus, Japanese flounder, Paralichthys olivaceus, and tiger puffer, Takifugu rubripes, displayed behavioural abnormalities and mortalities with distinct histopathological signs of viral nervous necrosis and heavily immunostained cells were observed in the central nervous tissues and retina. Bath-challenged rock fish, Sebastiscus marmoratus, and a hybrid of sevenband grouper and kelp grouper, E. moara, did not display any behavioural abnormality or mortality during the experimental period, although many fish showed slight signs of viral infection in nerve cells. Kelp grouper and red sea bream, Pagrus major, showed no behavioural abnormality, mortality or immunohistopathological changes after the virus challenge. These results are, in part, consistent with the natural host range of RGNNV, indicating the complexity in the host specificity of betanodaviruses.

Acute Pancreatitis: Etiology, Pathology, Diagnosis, and Treatment.

PubMed

Majidi, Shirin; Golembioski, Adam; Wilson, Stephen L; Thompson, Errington C

2017-11-01

Acute pancreatitis is a fascinating disease. In the United States, the two most common etiologies of acute pancreatitis are gallstones and excessive alcohol consumption. The diagnosis of acute pancreatitis is made with a combination of history, physical examination, computed tomography scan, and laboratory evaluation. Differentiating patients who will have a benign course of their pancreatitis from patients who will have severe pancreatitis is challenging to the clinician. C-reactive protein, pro-calcitonin, and the Bedside Index for Severity of Acute Pancreatitis appeared to be the best tools for the early and accurate diagnosis of severe pancreatitis. Early laparoscopic cholecystectomy is indicated for patients with mild gallstone pancreatitis. For patients who are going to have a prolonged hospitalization, enteral nutrition is preferred. Total parenteral nutrition should be reserved for patients who cannot tolerate enteral nutrition. Prophylactic antibiotics are not indicated for patients with pancreatic necrosis. Surgical intervention for infected pancreatic necrosis should be delayed as long as possible to improve patient outcomes.

Epidemiological characteristics of infectious hematopoietic necrosis virus (IHNV): a review.

PubMed

Dixon, Peter; Paley, Richard; Alegria-Moran, Raul; Oidtmann, Birgit

2016-06-10

Infectious hematopoietic necrosis virus (IHNV, Rhabdoviridae), is the causative agent of infectious hematopoietic necrosis (IHN), a disease notifiable to the World Organisation for Animal Health, and various countries and trading areas (including the European Union). IHNV is an economically important pathogen causing clinical disease and mortalities in a wide variety of salmonid species, including the main salmonid species produced in aquaculture, Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). We reviewed the scientific literature on IHNV on a range of topics, including geographic distribution; host range; conditions required for infection and clinical disease; minimum infectious dose; subclinical infection; shedding of virus by infected fish; transmission via eggs; diagnostic tests; pathogen load and survival of IHNV in host tissues. This information is required for a range of purposes including import risk assessments; parameterisation of disease models; for surveillance planning; and evaluation of the chances of eradication of the pathogen to name just a few. The review focuses on issues that are of relevance for the European context, but many of the data summarised have relevance to IHN globally. Examples for application of the information is presented and data gaps highlighted.

Oxidative stress alters mitochondrial bioenergetics and modifies pancreatic cell death independently of cyclophilin D, resulting in an apoptosis-to-necrosis shift

PubMed Central

Armstrong, Jane A.; Cash, Nicole J.; Ouyang, Yulin; Morton, Jack C.; Chvanov, Michael; Latawiec, Diane; Awais, Muhammad; Tepikin, Alexei V.; Sutton, Robert; Criddle, David N.

2018-01-01

Mitochondrial dysfunction lies at the core of acute pancreatitis (AP). Diverse AP stimuli induce Ca2+-dependent formation of the mitochondrial permeability transition pore (MPTP), a solute channel modulated by cyclophilin D (CypD), the formation of which causes ATP depletion and necrosis. Oxidative stress reportedly triggers MPTP formation and is elevated in clinical AP, but how reactive oxygen species influence cell death is unclear. Here, we assessed potential MPTP involvement in oxidant-induced effects on pancreatic acinar cell bioenergetics and fate. H2O2 application promoted acinar cell apoptosis at low concentrations (1–10 μm), whereas higher levels (0.5–1 mm) elicited rapid necrosis. H2O2 also decreased the mitochondrial NADH/FAD+ redox ratio and ΔΨm in a concentration-dependent manner (10 μm to 1 mm H2O2), with maximal effects at 500 μm H2O2. H2O2 decreased the basal O2 consumption rate of acinar cells, with no alteration of ATP turnover at <50 μm H2O2. However, higher H2O2 levels (≥50 μm) diminished spare respiratory capacity and ATP turnover, and bioenergetic collapse, ATP depletion, and cell death ensued. Menadione exerted detrimental bioenergetic effects similar to those of H2O2, which were inhibited by the antioxidant N-acetylcysteine. Oxidant-induced bioenergetic changes, loss of ΔΨm, and cell death were not ameliorated by genetic deletion of CypD or by its acute inhibition with cyclosporine A. These results indicate that oxidative stress alters mitochondrial bioenergetics and modifies pancreatic acinar cell death. A shift from apoptosis to necrosis appears to be associated with decreased mitochondrial spare respiratory capacity and ATP production, effects that are independent of CypD-sensitive MPTP formation. PMID:29626097

Phylogeography of infectious haematopoietic necrosis virus in North America

USGS Publications Warehouse

Kurath, Gael; Garver, Kyle A.; Troyer, Ryan M.; Emmenegger, Eveline J.; Einer-Jensen, Katja; Anderson, Eric D.

2003-01-01

Infectious hematopoietic necrosis virus (IHNV) is a rhabdoviral pathogen that infects wild and cultured salmonid fish throughout the Pacific Northwest of North America. IHNV causes severe epidemics in young fish and can cause disease or occur asymptomatically in adults. In a broad survey of 323 IHNV field isolates, sequence analysis of a 303 nucleotide variable region within the glycoprotein gene revealed a maximum nucleotide diversity of 8.6 %, indicating low genetic diversity overall for this virus. Phylogenetic analysis revealed three major virus genogroups, designated U, M and L, which varied in topography and geographical range. Intragenogroup genetic diversity measures indicated that the M genogroup had three- to fourfold more diversity than the other genogroups and suggested relatively rapid evolution of the M genogroup and stasis within the U genogroup. We speculate that factors influencing IHNV evolution may have included ocean migration ranges of their salmonid host populations and anthropogenic effects associated with fish culture.

Growth promotion in plants by rice necrosis mosaic virus.

PubMed

Ghosh, S K

1982-08-01

Ludwigia perennis L. infected with rice necrosis mosaic virus (RNMV) showed an increase in both shoot growth and leaf size, along with characteristic chlorotic lesions on leaves. The promotion of growth over the controls extended over a considerable period of time (70 d). Inoculation with RNMV resulted in increased plant height, leaf size, stem diameter, and number and size of fiber bundles in Corchorus olitorius L., C. capsularis L., Hibiscus sabdariffa L. and H. cannabinus L.

Outcome of Acute Pancreatic and Peripancreatic Collections Occurring in Patients With Acute Pancreatitis.

PubMed

Manrai, Manish; Kochhar, Rakesh; Gupta, Vikas; Yadav, Thakur Deen; Dhaka, Narendra; Kalra, Naveen; Sinha, Saroj K; Khandelwal, Niranjan

2018-02-01

To study the outcome of acute collections occurring in patients with acute pancreatitis BACKGROUND:: There are limited data on natural history of acute collections arising after acute pancreatitis (AP). Consecutive patients of AP admitted between July 2011 and December 2012 were evaluated by imaging for development of acute collections as defined by revised Atlanta classification. Imaging was repeated at 1 and 3 months. Spontaneous resolution, evolution, and need for intervention were assessed. Of the 189 patients, 151 patients (79.9%) had acute collections with severe disease and delayed hospitalization being predictors of acute collections. Thirty-six patients had acute interstitial edematous pancreatitis, 8 of whom developed acute peripancreatic fluid collections, of which 1 evolved into pseudocyst. Among the 153 patients with acute necrotizing pancreatitis, 143 (93.4%) developed acute necrotic collection (ANC). Twenty-three of 143 ANC patients died, 21 had resolved collections, whereas 84 developed walled-off necrosis (WON), with necrosis >30% (P = 0.010) and Computed Tomographic Severity Index score ≥7 (P = 0.048) predicting development of WON. Of the 84 patients with WON, 8 expired, 53 patients required an intervention, and 23 were managed conservatively. Independent predictors of any intervention among all patients were Computed Tomographic Severity Index score ≥7 (P < 0.001) and interval between onset of pain to hospitalization >7 days (P = 0.04). Patients with severe AP and delayed hospitalization more often develop acute collections. Pancreatic pseudocysts are a rarity in acute interstitial pancreatitis. A majority of patients with necrotising pancreatitis will develop ANC, more than half of whom will develop WON. Delay in hospitalization and higher baseline necrosis score predict need for intervention.

Epidural anaesthesia restores pancreatic microcirculation and decreases the severity of acute pancreatitis

PubMed Central

Demirag, Alp; Pastor, Catherine M; Morel, Philippe; Jean-Christophe, Copin; Sielenkämper, Andreas W; Güvener, Nilgun; Mai, Gang; Berney, Thierry; Frossard, Jean-Louis; Bühler, Leo H

2006-01-01

AIM: To investigate the effect of epidural anaesthesia (EA) on pancreatic microcirculation during acute pancreatitis (AP). METHODS: AP was induced by injection of sodium taurocholate into the pancreatic duct of Sprague-Dawley rats. To realize EA, a catheter was introduced into the epidural space between T7 and T9 and bupivacaine was injected. Microcirculatory flow was measured by laser Doppler flowmetry. Arterial blood gas analyses were performed. At the end of the experiment (≤ 5 h), pancreas was removed for histology. The animals were divided into three groups: Group 1 (n = 9), AP without EA; Group 2 (n = 4), EA without AP; and Group 3 (n = 6), AP treated by EA. RESULTS: In Group 1, pancreatic microcirculatory flow prior to AP was 141 ± 39 perfusion units (PU). After AP, microcirculatory flow obviously decreased to 9 ± 6 PU (P < 0.05). Metabolic acidosis developed with base excess (BE) of - 14 ± 3 mmol/L. Histology revealed extensive edema and tissue necrosis. In Group 2, EA did not significantly modify microcirculatory flow. BE remained unchanged and histological analysis showed normal pancreatic tissue. In Group 3, AP initially caused a significant decrease in microcirculatory flow from 155 ± 25 to 11 ± 7 PU (P < 0.05). After initiation of EA, microcirculatory flow obviously increased again to 81 ± 31 PU (P < 0.05). BE was -6 ± 4 mmol/L, which was significantly different compared to Group 1 (P < 0.05). Furthermore, histology revealed less extensive edema and necrosis in pancreatic tissue in Group 3 than that in Group 1. CONCLUSION: AP caused dramatic microcirculatory changes within the pancreas, with development of metabolic acidosis and tissue necrosis. EA allowed partial restoration of microcirculatory flow and prevented development of tissue necrosis and systemic complications. Therefore, EA should be considered as therapeutic option to prevent evolution from edematous to necrotic AP. PMID

Sequential tests for infectious hematopoietic necrosis virus in individuals and populations of sockeye salmon

USGS Publications Warehouse

Mulcahy, Daniel M.; Pascho, Ron

1986-01-01

The incidence and titer distribution of infectious hematopoietic necrosis virus in cavity fluid from spent female sockeye salmon (Oncorhynchus nerka) varied little when fish from a naturally spawning population were sampled three times on alternate days. However, when prespawning female sockeye salmon from a second population were individually tagged, penned, and sampled daily, the incidence and proportion of fish with high virus titer rose over a 6-d period. In 10 instances, consecutive cavity fluid samples from the same fish reverted from virus-positive to virus-negative. We suggest that spent fish should be sampled when accurate and quantitative data on the incidence and level of the virus are required.

Mortality indicators and risk factors for intra-abdominal hypertension in severe acute pancreatitis.

PubMed

Zhao, J G; Liao, Q; Zhao, Y P; Hu, Y

2014-01-01

This study assessed the risk factors associated with mortality and the development of intra-abdominal hypertension (IAH) in patients with severe acute pancreatitis (SAP). To identify significant risk factors, we assessed the following variables in 102 patients with SAP: age, gender, etiology, serum amylase level, white blood cell (WBC) count, serum calcium level, Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, computed tomography severity index (CTSI) score, pancreatic necrosis, surgical interventions, and multiple organ dysfunction syndrome (MODS). Statistically significant differences were identified using the Student t test and the χ (2) test. Independent risk factors for survival were analyzed by Cox proportional hazards regression. The following variables were significantly related to both mortality and IAH: WBC count, serum calcium level, serum amylase level, APACHE-II score, CTSI score, pancreatic necrosis, pancreatic necrosis >50%, and MODS. However, it was found that surgical intervention had no significant association with mortality. MODS and pancreatic necrosis >50% were found to be independent risk factors for survival in patients with SAP. Mortality and IAH from SAP were significantly related to WBC count, serum calcium level, serum amylase level, APACHE-II score, CTSI score, pancreatic necrosis, and MODS. However, Surgical intervention did not result in higher mortality. Moreover, MODS and pancreatic necrosis >50% predicted a worse prognosis in SAP patients.

Development a of multiplex TaqMan real-time RT-PCR assay for simultaneous detection of Asian prunus viruses, plum bark necrosis stem pitting associated virus, and peach latent mosaic virus

USDA-ARS?s Scientific Manuscript database

Asian prunus viruses (APV 1, APV 2 and APV 3) and Plum bark necrosis stem pitting associated virus (PBNSPaV) are two recently described viruses infecting Prunus spp., and Peach latent mosaic viroid (PLMVd) is a viroid that infects the same species. A single-tube multiplex, TaqMan real-time RT-PCR as...

Recent advances in detection and control of infectious hematopoietic necrosis virus in aquaculture

USGS Publications Warehouse

Winton, James R.

1991-01-01

Infectious hematopoietic necrosis (IHN) is one of the most important viral diseases of salmon and trout reared in culture. The disease remains untreatable with avoidance being the only control measure. Much has been learned about the chemical, physical, and serological characteristics of the rhabdovirus causing IHN, but critical gaps exist in our understanding of the biology of the virus in nature. The tools of molecular biology have provided improved methods for detection of pathogens and new strategies for control of viral diseases. This paper reviews several recent improvements in methods for detecting infectious hematopoietic necrosis virus including the application of enzyme-linked immunosorbent assays, development of monoclonal antibodies and DNA probes, and use of the polymerase chain reaction. New strategies for control of IHN through the use of better water treatment, more resistant fish, antiviral drugs or chemicals, and new generation vaccines are discussed.

Effect of overweight and obesity on weight loss and length of stay in patients with walled-off pancreatic necrosis.

PubMed

Rysgaard, Sisse; Rasmussen, Ditlev; Novovic, Srdan; Schmidt, Palle N; Gluud, Lise L

2017-06-01

The aim of this study was to assess the association between admission weight, weight loss, and length of stay (LOS) in patients with walled-off pancreatic necrosis. We classified the admission body mass index (BMI) of 18.5 to <25 kg/m 2 as normal weight, 25 to <30 kg/m 2 as overweight, and ≥30 kg/m 2 as obesity. The Nutritional Risk Screening score-2002 was calculated to identify patients at risk for undernutrition. We included 38 patients (61% men, 68% with infected necrosis; 40% normal weight; 60% overweight/obesity). Four patients (11%) required treatment at the semi-intensive care unit, 11 (29%) developed pneumonia, and 10 (26%) developed septicemia. One patient died due to respiratory failure and hemorrhage. The remaining patients were discharged after a median of 49 d (36-64 d). During admission, 14 patients (38%) achieved an energy-protein intake of at least 75% and 17 (46%) achieved ≥70% coverage. The percentage weight loss was different (P < 0.01) for patients with normal weight (4%), overweight (9%), and obesity (14%). There was no difference between groups regarding percentage of energy or protein coverage. Patients with overweight/obesity had a longer hospital LOS (P = 0.016). In univariable regression analysis, overweight, obesity, energy, and protein coverage predicted weight loss. LOS did not predict weight loss. In multivariable regression analysis, overweight and obesity were the only remaining significant predictors of weight loss. Patients with walled-off pancreatic necrosis are at considerable risk for undernutrition. A BMI >25 kg/m 2 predicts greater weight loss and longer LOS. Copyright © 2017 Elsevier Inc. All rights reserved.

Lipotoxicity Causes Multisystem Organ Failure and Exacerbates Acute Pancreatitis in Obesity

PubMed Central

Navina, Sarah; Acharya, Chathur; DeLany, James P.; Orlichenko, Lidiya S.; Baty, Catherine J.; Shiva, Sruti S.; Durgampudi, Chandra; Karlsson, Jenny M.; Lee, Kenneth; Bae, Kyongtae T.; Furlan, Alessandro; Behari, Jaideep; Liu, Shiguang; McHale, Teresa; Nichols, Larry; Papachristou, Georgios Ioannis; Yadav, Dhiraj; Singh, Vijay P.

2012-01-01

Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid–mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis. PMID:22049070

Progressive outer retinal necrosis: manifestation of human immunodeficiency virus infection

PubMed Central

Lo, Phey Feng; Lim, Rongxuan; Antonakis, Serafeim N; Almeida, Goncalo C

2015-01-01

We present the case of a 54-year-old man who developed progressive outer retinal necrosis (PORN) as an initial manifestation of HIV infection without any significant risk factors for infection with HIV. PORN is usually found as a manifestation of known AIDS late in the disease. Our patient presented with transient visual loss followed by decrease in visual acuity and facial rash. Subsequent investigation revealed anterior chamber tap positive for varicella zoster virus (VZV), as well as HIV positivity, with an initial CD4 count of 48 cells/µL. Systemic and intravitreal antivirals against VZV, and highly active antiretroviral therapy against HIV were started, which halted further progression of retinal necrosis. This case highlights the importance of suspecting PORN where there is a rapidly progressive retinitis, and also testing the patient for HIV, so appropriate treatment can be started. PMID:25948844

PKD signaling and pancreatitis

PubMed Central

Yuan, Jingzhen; Pandol, Stephen J.

2016-01-01

Background Acute pancreatitis is a serious medical disorder with no current therapies directed to the molecular pathogenesis of the disorder. Inflammation, inappropriate intracellular activation of digestive enzymes, and parenchymal acinar cell death by necrosis are the critical pathophysiologic processes of acute pancreatitis. Thus, it is necessary to elucidate the key molecular signals that mediate these pathobiologic processes and develop new therapeutic strategies to attenuate the appropriate signaling pathways in order to improve outcomes for this disease. A novel serine/threonine protein kinase D (PKD) family has emerged as key participants in signal transduction, and this family is increasingly being implicated in the regulation of multiple cellular functions and diseases. Methods This review summarizes recent findings of our group and others regarding the signaling pathway and the biological roles of the PKD family in pancreatic acinar cells. In particular, we highlight our studies of the functions of PKD in several key pathobiologic processes associated with acute pancreatitis in experimental models. Results Our findings reveal that PKD signaling is required for NF-κB activation/inflammation, intracellular zymogen activation, and acinar cell necrosis in rodent experimental pancreatitis. Novel small-molecule PKD inhibitors attenuate the severity of pancreatitis in both in vitro and in vivo experimental models. Further, this review emphasizes our latest advances in the therapeutic application of PKD inhibitors to experimental pancreatitis after the initiation of pancreatitis. Conclusions These novel findings suggest that PKD signaling is a necessary modulator in key initiating pathobiologic processes of pancreatitis, and that it constitutes a novel therapeutic target for treatments of this disorder. PMID:26879861

Histopathological changes in the pancreas of cattle with abdominal fat necrosis

PubMed Central

TANI, Chikako; PRATAKPIRIYA, Watanyoo; TANI, Mineto; YAMAUCHI, Takenori; HIRAI, Takuya; YAMAGUCHI, Ryoji; ANO, Hitoshi; KATAMOTO, Hiromu

2016-01-01

The association between pancreatic disorder and abdominal fat necrosis in cattle remains unclear. The pancreases of 29 slaughtered cattle with or without fat necrosis were collected to investigate pathological changes. Japanese Black (JB) cattle were classified into the FN group (with abdominal fat necrosis; n=9) and N group (without fat necrosis; n=5). The pancreases were also collected from 15 Holstein Friesian (HF) cows. All JB cattle showed high body condition scores. Regarding the pathological findings, fatty pancreas which involves adipocyte infiltration into the pancreas and fat necrosis (saponification) were observed in 25 and 27 cases, respectively. Immunohistochemical staining with anti-Iba-1 antibody showed large numbers of macrophages surrounding the saponified fat in the pancreas. CD3-positive T cells were significantly more common in the pancreas of both the FN and N groups compared with the HF group (P<0.05). Furthermore, fibrosis in the pancreas exhibited a correlative tendency with the formation of necrotic fat mass in the peritoneal cavity (P<0.1). These results indicate that obesity leads to increased severity of pancreatic disorder, including fatty pancreas and pancreatitis. The pathological lesions in the pancreas may play a key role in abdominal fat necrosis through the inflammatory process. PMID:27795463

Histopathological changes in the pancreas of cattle with abdominal fat necrosis.

PubMed

Tani, Chikako; Pratakpiriya, Watanyoo; Tani, Mineto; Yamauchi, Takenori; Hirai, Takuya; Yamaguchi, Ryoji; Ano, Hitoshi; Katamoto, Hiromu

2017-01-20

The association between pancreatic disorder and abdominal fat necrosis in cattle remains unclear. The pancreases of 29 slaughtered cattle with or without fat necrosis were collected to investigate pathological changes. Japanese Black (JB) cattle were classified into the FN group (with abdominal fat necrosis; n=9) and N group (without fat necrosis; n=5). The pancreases were also collected from 15 Holstein Friesian (HF) cows. All JB cattle showed high body condition scores. Regarding the pathological findings, fatty pancreas which involves adipocyte infiltration into the pancreas and fat necrosis (saponification) were observed in 25 and 27 cases, respectively. Immunohistochemical staining with anti-Iba-1 antibody showed large numbers of macrophages surrounding the saponified fat in the pancreas. CD3-positive T cells were significantly more common in the pancreas of both the FN and N groups compared with the HF group (P<0.05). Furthermore, fibrosis in the pancreas exhibited a correlative tendency with the formation of necrotic fat mass in the peritoneal cavity (P<0.1). These results indicate that obesity leads to increased severity of pancreatic disorder, including fatty pancreas and pancreatitis. The pathological lesions in the pancreas may play a key role in abdominal fat necrosis through the inflammatory process.

Fatal hemorrhagic-necrotizing pancreatitis associated with pancreatic and hepatic lipidosis in an obese Asian palm civet (Paradoxurus hermaphroditus).

PubMed

Laura, Bongiovanni; Nicola, Di Girolamo; Alessandro, Montani; Leonardo, Della Salda; Paolo, Selleri

2014-05-01

Asian palm civets (Paradoxurus hermaphroditus), or toddy cats, belong to the family Viverridae. Little is known about the pathology of these animals and few articles have been published, mainly concerning their important role as wild reservoir hosts for severe infectious diseases of domestic animals and human beings. A 4-year-old, female Asian palm civet was found dead by the owner. At necropsy, large amount of adipose tissue was found in the subcutis and in the peritoneal cavity. Most of the pancreas appeared red, translucent. Hepatomegaly, discoloration of the liver were evident, with multifocal areas of degeneration, characterized by white nodular lesions. Histologically, the pancreas showed severe interstitial and perilobular necrosis and extensive haemorrhages, with separation of the interstitium, mild reactive inflammation at the periphery of the pancreatic lobules. Liver showed multifocal foci of vacuolar degeneration, lipidic accumulation, sometimes associated to hepatocyte necrosis. A diagnosis of acute severe hemorrhagic-necrotizing pancreatitis (or acute pancreatic necrosis) associated with pancreatic and hepatic lipidosis was made. To the best of our knowledge, this represents the first case report of acute lethal pancreatitis in an Asian palm civet. Although the exact cause of the disease remains undetermined, a hypothesis of the cause and pathogenesis is discussed, pointing out dietary indiscretion and consequent overweight as possible important risk factors.

Corexit 9500 inactivates two enveloped viruses of aquatic animals but enhances the infectivity of a nonenveloped fish virus.

PubMed

Pham, P H; Huang, Y J; Chen, C; Bols, N C

2014-02-01

The effects of Corexit 9500, a dispersant used to clean up oil spills, on invertebrates, lower vertebrates, birds, and human health have been examined, but there is a significant lack of study of the effect of this dispersant on aquatic viruses. In this study, the effects of Corexit 9500 on four aquatic viruses of differing structural composition were examined. Corexit 9500 reduced the titer of the enveloped viral hemorrhagic septicemia virus (VHSV) at all concentrations (10% to 0.001%) examined. The titer of frog virus 3 (FV3), a virus with both enveloped and nonenveloped virions, was reduced only at the high Corexit 9500 concentrations (10% to 0.1%). Corexit 9500 was unable to reduce the titer of nonenveloped infectious pancreatic necrosis virus (IPNV) but enhanced the titer of chum salmon reovirus (CSV) by 2 to 4 logs. With the ability to inactivate enveloped viruses and possibly enhance some nonenveloped viruses, Corexit 9500 has the potential to alter the aquatic virosphere.

Protective immunity against nervous necrosis virus in convict grouper Epinephelus septemfasciatus following vaccination with virus-like particles produced in yeast Saccharomyces cerevisiae.

PubMed

Wi, Ga Ram; Hwang, Jee Youn; Kwon, Mun-Gyeong; Kim, Hyoung Jin; Kang, Hyun Ah; Kim, Hong-Jin

2015-05-15

Infection with nervous necrosis virus (NNV) causes viral nervous necrosis, which inflicts serious economic losses in marine fish cultivation. Virus-like particles (VLPs) are protein complexes consisting of recombinant virus capsid proteins, whose shapes are similar to native virions. VLPs are considered a novel vaccine platform because they are not infectious and have the ability to induce neutralizing antibodies efficiently. However, there have been few studies of protective immune responses employing virus challenge following immunization with NNV VLPs, and this is important for evaluating the utility of the vaccine. In the present study, we produced red-spotted grouper (Epinephelus akaara) NNV (RGNNV) VLPs in Saccharomyces cerevisiae and investigated protective immune responses in convict grouper (Epinephelus septemfasciatus) following intraperitoneal injection and oral immunization with the RGNNV VLPs. The parenterally administered VLPs elicited neutralizing antibody with high efficacy, and provided the fish with full protection against RGNNV challenge: 100% of the immunized fish survived compared with only 37% of the control fish receiving phosphate-buffered saline. RGNNV VLPs administered orally provoked neutralizing antibody systemically and conferred protective immunity against virus challenge: however only 57% of the fish survived. Our results demonstrate that RGNNV VLP produced in yeast has great potential as vaccine in fish. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of recombinant Yarrowia lipolytica producing virus-like particles of a fish nervous necrosis virus.

PubMed

Luu, Van-Trinh; Moon, Hye Yun; Hwang, Jee Youn; Kang, Bo-Kyu; Kang, Hyun Ah

2017-08-01

Nervous necrosis virus (NNV) causes viral encephalopathy and retinopathy, a devastating disease of many species of cultured marine fish worldwide. In this study, we used the dimorphic non-pathogenic yeast Yarrowia lipolytica as a host to express the capsid protein of red-spotted grouper nervous necrosis virus (RGNNV-CP) and evaluated its potential as a platform for vaccine production. An initial attempt was made to express the codon-optimized synthetic genes encoding intact and N-terminal truncated forms of RGNNV-CP under the strong constitutive TEF1 promoter using autonomously replicating sequence (ARS)-based vectors. The full-length recombinant capsid proteins expressed in Y. lipolytica were detected not only as monomers and but also as trimers, which is a basic unit for formation of NNV virus-like particles (VLPs). Oral immunization of mice with whole recombinant Y. lipolytica harboring the ARS-based plasmids was shown to efficiently induce the formation of IgG against RGNNV-CP. To increase the number of integrated copies of the RGNNV-CP expression cassette, a set of 26S ribosomal DNA-based multiple integrative vectors was constructed in combination with a series of defective Ylura3 with truncated promoters as selection markers, resulting in integrants harboring up to eight copies of the RGNNV-CP cassette. Sucrose gradient centrifugation and transmission electron microscopy of this high-copy integrant were carried out to confirm the expression of RGNNV-CPs as VLPs. This is the first report on efficient expression of viral capsid proteins as VLPs in Y. lipolytica, demonstrating high potential for the Y. lipolytica expression system as a platform for recombinant vaccine production based on VLPs.

Progressive outer retinal necrosis: manifestation of human immunodeficiency virus infection.

PubMed

Lo, Phey Feng; Lim, Rongxuan; Antonakis, Serafeim N; Almeida, Goncalo C

2015-05-06

We present the case of a 54-year-old man who developed progressive outer retinal necrosis (PORN) as an initial manifestation of HIV infection without any significant risk factors for infection with HIV. PORN is usually found as a manifestation of known AIDS late in the disease. Our patient presented with transient visual loss followed by decrease in visual acuity and facial rash. Subsequent investigation revealed anterior chamber tap positive for varicella zoster virus (VZV), as well as HIV positivity, with an initial CD4 count of 48 cells/µL. Systemic and intravitreal antivirals against VZV, and highly active antiretroviral therapy against HIV were started, which halted further progression of retinal necrosis. This case highlights the importance of suspecting PORN where there is a rapidly progressive retinitis, and also testing the patient for HIV, so appropriate treatment can be started. 2015 BMJ Publishing Group Ltd.

Course of alcoholic chronic pancreatitis: a prospective clinicomorphological long-term study.

PubMed

Ammann, R W; Heitz, P U; Klöppel, G

1996-07-01

The pathogenesis of alcoholic chronic pancreatitis and its relationship to alcoholic acute pancreatitis are debated. According to our recent clinical long-term study, alcoholic chronic pancreatitis seems to evolve from severe acute pancreatits. The aim of this study was to correlate clinical findings to the pancreatic histopathology at early and advanced stages of the disease. Morphological changes (pseudocysts, autodigestive necrosis, calcification, and perilobular and intralobular fibrosis) were recorded in 37 surgical and 46 postmortem pancreas specimens of 73 patients from our long-term series, who progressed from clinically acute to chronic pancreatitis (mean follow-up, 12 years). Pancreatic function was monitored at yearly intervals. Surgical interventions were performed at a mean of 4.1 years from onset. Histologically, focal necrosis (49%) and mild perilobular fibrosis (54%) predominated, Pseudocysts (n = 41, mostly postnecrotic) occurred in 88% within 6 years from onset. Autopsy specimens were obtained at a mean of 12 years. These pancreata often showed severe perilobular and intralobular fibrosis (85%) and calcifications (74%), but rarely necrosis (4%). Fibrosis correlated with progressive pancreatic dysfunction (P < 0.001), particularly in the 10 patients with two histological assessments (mean interval between biopsy and autopsy, 8 years). The data support an evolution from severe alcoholic acute pancreatitis to chronic pancreatitis.

Inhibiting tumor necrosis factor-alpha diminishes desmoplasia and inflammation to overcome chemoresistance in pancreatic ductal adenocarcinoma.

PubMed

Zhao, Xianda; Fan, Wei; Xu, Zhigao; Chen, Honglei; He, Yuyu; Yang, Gui; Yang, Gang; Hu, Hanning; Tang, Shihui; Wang, Ping; Zhang, Zheng; Xu, Peipei; Yu, Mingxia

2016-12-06

Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancer death reasons. Anti-tumor necrosis factor-alpha (TNF-α) antibodies have shown promising effects in PDAC pre-clinical models. However, the prognostic values of TNF-α, underlying mechanisms by which anti-TNF-α treatments inhibit PDAC, and potential synergistic effects of anti-TNF-α treatments with chemotherapy are still unclear. To identify the targeting values of TNF-α in PDAC, we measured TNF-α expression in different stages of PDAC initiation and evaluated its prognostic significance in a pancreatic cancer cohort. We found that TNF-α expression elevated in PDAC initiation process, and high expression of TNF-α was an independent prognostic marker of poor survival. We further evaluated anti-tumor effects of anti-TNF-α treatments in PDAC. Anti-TNF-α treatments resulted in decreased cell viability in both PDAC tumor cells and pancreatic satellite cells in similar dose in vitro. In vivo, anti-TNF-α treatments showed effects in reducing desmoplasia and the tumor promoting inflammatory microenvironment in PDAC. Combination of anti-TNF-α treatments with chemotherapy partly overcame chemoresistance of PDAC tumor cells and prolonged the survival of PDAC mouse model. In conclusion, our findings indicated that TNF-α in PDAC can be a prognostic and therapeutic target. Inhibition of TNF-α synergized with chemotherapy in PDAC resulted in better pre-clinical responses via killing tumor cells as well as diminishing desmoplasia and inflammation in PDAC tumor stroma.

The effect of activated protein C on experimental acute necrotizing pancreatitis

PubMed Central

Yamenel, Levent; Mas, Mehmet Refik; Comert, Bilgin; Isik, Ahmet Turan; Aydin, Sezai; Mas, Nuket; Deveci, Salih; Ozyurt, Mustafa; Tasci, Ilker; Unal, Tahir

2005-01-01

Introduction Acute pancreatitis is a local inflammatory process that leads to a systemic inflammatory response in the majority of cases. Bacterial contamination has been estimated to occur in 30–40% of patients with necrotizing pancreatitis. Development of pancreatic necrosis depends mainly on the degree of inflammation and on the microvascular circulation of the pancreatic tissue. Activated protein C (APC) is known to inhibit coagulation and inflammation, and to promote fibrinolysis in patients with severe sepsis. We investigated the effects of APC on histopathology, bacterial translocation, and systemic inflammation in experimental acute necrotizing pancreatitis. Materials and method Forty-five male Sprague-Dawley rats were studied. Rats were randomly allocated to three groups. Acute pancreatitis was induced in group II (positive control; n = 15) and group III (treatment; n = 15) rats by retrograde injection of taurocholate into the common biliopancreatic duct. Group I rats (sham; n = 15) received an injection of normal saline into the common biliopancreatic duct to mimic a pressure effect. Group III rats were treated with intravenous APC 6 hours after induction of pancreatitis. Pancreatic tissue and blood samples were obtained from all animals for histopathological examination and assessment of amylase, tumor necrosis factor-α, and IL-6 levels in serum. Bacterial translocation to pancreas and mesenteric lymph nodes was measured. Results Acute pancreatitis developed in all groups apart from group I (sham), as indicated by microscopic parenchymal necrosis, fat necrosis and abundant turbid peritoneal fluid. Histopathological pancreatitis scores in the APC-treated group were lower than in positive controls (10.31 ± 0.47 versus 14.00 ± 0.52; P < 0.001). Bacterial translocation to mesenteric lymph nodes and to pancreas in the APC-treated group was significantly decreased compared with controls (P < 0.02 and P < 0.007, respectively). Serum amylase, tumor necrosis

Plaquing procedure for infectious hematopoietic necrosis virus

USGS Publications Warehouse

Burke, J.A.; Mulcahy, D.

1980-01-01

A single overlay plaque assay was designed and evaluated for infectious hematopoietic necrosis virus. Epithelioma papillosum carpio cells were grown in normal atmosphere with tris(hydroxymethyl)aminomethane- or HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid)-buffered media. Plaques were larger and formed more quickly on 1- to 3-day-old cell monolayers than on older monolayers. Cell culture medium with a 10% addition of fetal calf serum (MEM 10) or without serum (MEM 0) were the most efficient virus diluents. Dilution with phosphate-buffered saline, saline, normal broth, or deionized water reduced plaque numbers. Variations in the pH (7.0 to 8.0) of a MEM 0 diluent did not affect plaque numbers. Increasing the volume of viral inoculum above 0.15 ml (15- by 60-mm plate) decreased plaquing efficiency. Significantly more plaques occurred under gum tragacanth and methylcellulose than under agar or agarose overlays. Varying the pH (6.8 to 7.4) of methylcellulose overlays did not significantly change plaque numbers. More plaques formed under the thicker overlays of both methylcellulose and gum tragacanth. Tris(hydroxymethyl)aminomethane and HEPES performed equally well, buffering either medium or overlay. Plaque numbers were reduced when cells were rinsed after virus adsorption or less than 1 h was allowed for adsorption. Variation in adsorption time between 60 and 180 min did not change plaque numbers. The mean plaque formation time was 7 days at 16 degrees C. The viral dose response was linear when the standardized assay was used.

In vitro infection of salmonid epidermal tissues by infectious hematopoietic necrosis virus and viral hemorrhagic septicemia virus

USGS Publications Warehouse

Yamamoto, T.; Batts, W.N.; Winton, J.R.

1992-01-01

The ability of two rhabdoviruses, infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV), to infect fish skin was investigated by in vitro infection of excised tissues. Virus replication was determined by plaque assay of homogenized tissue extracts, and the virus antigen was detected by immunohistology of tissue sections. Gill, fin, and ventral abdominal skin tissues of rainbow trout Oncorhynchus mykiss that had been infected in vitro with a virulent strain of IHNV (193–110) produced substantial increases in virus titer within 24 h. Titers continued to increase up until day 3 of incubation; by this time, virus had increased 1,000-fold or more. This increase in IHNV titer occurred in epidermal tissues of fingerlings and of older fish. In another experiment, IHNV replicated in excised rainbow trout tissues whether the fish had been subject to prior infection with a virulent strain of IHNV (Western Regional Aquaculture Consortium isolate) or whether the fish had been infected previously with an attenuated strain of the virus (Nan Scott Lake, with 100 passes in culture). A virulent strain of VHSV (23/75) replicated effectively in excised gill tissues and epidermal tissues of rainbow trout and chinook salmon O. tshawytscha; however, the avirulent North American strain of VHSV (Makah) replicated poorly or not at all.

Fatal hemorrhagic-necrotizing pancreatitis associated with pancreatic and hepatic lipidosis in an obese Asian palm civet (Paradoxurus hermaphroditus)

PubMed Central

Laura, Bongiovanni; Nicola, Di Girolamo; Alessandro, Montani; Leonardo, Della Salda; Paolo, Selleri

2014-01-01

Asian palm civets (Paradoxurus hermaphroditus), or toddy cats, belong to the family Viverridae. Little is known about the pathology of these animals and few articles have been published, mainly concerning their important role as wild reservoir hosts for severe infectious diseases of domestic animals and human beings. A 4-year-old, female Asian palm civet was found dead by the owner. At necropsy, large amount of adipose tissue was found in the subcutis and in the peritoneal cavity. Most of the pancreas appeared red, translucent. Hepatomegaly, discoloration of the liver were evident, with multifocal areas of degeneration, characterized by white nodular lesions. Histologically, the pancreas showed severe interstitial and perilobular necrosis and extensive haemorrhages, with separation of the interstitium, mild reactive inflammation at the periphery of the pancreatic lobules. Liver showed multifocal foci of vacuolar degeneration, lipidic accumulation, sometimes associated to hepatocyte necrosis. A diagnosis of acute severe hemorrhagic-necrotizing pancreatitis (or acute pancreatic necrosis) associated with pancreatic and hepatic lipidosis was made. To the best of our knowledge, this represents the first case report of acute lethal pancreatitis in an Asian palm civet. Although the exact cause of the disease remains undetermined, a hypothesis of the cause and pathogenesis is discussed, pointing out dietary indiscretion and consequent overweight as possible important risk factors. PMID:25183148

IMMUNOMODULATION AND TREATMENT OF ACUTE DESTRUCTIVE PANCREATITIS IN A MULTIDISCIPLINARY SURGICAL HOSPITAL.

PubMed

Vinokurov, M M; Saveliev, V V; Gogolev, N M; Yalynskya, T V

2015-01-01

This work is based on the analysis of complex treatment of 497 patients with pancreatic necrosis treated at the surgical department of the Republican Hospital No2-Center for Emergency the Republic of Sakha (Yakutia) in the period from 2010 to 2015. The study was able to adapt and improve the two-tier immunocorretion in pancreatic necrosis in a multidisciplinary surgical hospital that along with the other constituents of intensive therapy has allowed a whole to reduce the amount of intra-abdominal and extraabdominal complications--sterile pancreatic necrosis phase--from 23.6% to 14.6 and 31 6% to 15.0% respectively, total lethality--from 17.6% to 7.2% lethality in patients with non-operated group--from 15.6% to 2.2% lethality in the group of patients operated--18.4% to 10.9%. In the phase of infectious complications of pancreatic necrosis lethality rate decreased from 45.8% to 37.7%.

Asparaginase-associated pancreatitis in children.

PubMed

Raja, Raheel Altaf; Schmiegelow, Kjeld; Frandsen, Thomas Leth

2012-10-01

l-asparaginase has been an element in the treatment for acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma since the late 1960s and remains an essential component of their combination chemotherapy. Among the major toxicities associated with l-asparaginase therapy are pancreatitis, allergic reactions, thrombotic events, hepatotoxicity and hyperlipidaemia. Acute pancreatitis is one of the most common reasons for stopping treatment with l-asparaginase. Short-term complications of asparaginase-associated pancreatitis include development of pseudocysts and pancreatic necrosis. Long-term complications include chronic pancreatitis and diabetes. The pathophysiology of asparaginase-associated pancreatitis remains to be uncovered. Individual clinical and genetic risk factors have been identified, but they are only weak predictors of pancreatitis. This review explores the definition, possible risk factors, treatment and complications of asparaginase-associated pancreatitis. © 2012 Blackwell Publishing Ltd.

Acute pancreatitis.

PubMed

Talukdar, Rupjyoti; Vege, Santhi S

2015-09-01

To summarize recent data on classification systems, cause, risk factors, severity prediction, nutrition, and drug treatment of acute pancreatitis. Comparison of the Revised Atlanta Classification and Determinant Based Classification has shown heterogeneous results. Simvastatin has a protective effect against acute pancreatitis. Young black male, alcohol, smoldering symptoms, and subsequent diagnosis of chronic pancreatitis are risk factors associated with readmissions after acute pancreatitis. A reliable clinical or laboratory marker or a scoring system to predict severity is lacking. The PYTHON trial has shown that oral feeding with on demand nasoenteric tube feeding after 72 h is as good as nasoenteric tube feeding within 24 h in preventing infections in predicted severe acute pancreatitis. Male sex, multiple organ failure, extent of pancreatic necrosis, and heterogeneous collection are factors associated with failure of percutaneous drainage of pancreatic collections. The newly proposed classification systems of acute pancreatitis need to be evaluated more critically. New biomarkers are needed for severity prediction. Further well designed studies are required to assess the type of enteral nutritional formulations for acute pancreatitis. The optimal minimally invasive method or combination to debride the necrotic collections is evolving. There is a great need for a drug to treat the disease early on to prevent morbidity and mortality.

Endoscopic and percutaneous drainage of symptomatic walled-off pancreatic necrosis reduces hospital stay and radiographic resources.

PubMed

Gluck, Michael; Ross, Andrew; Irani, Shayan; Lin, Otto; Hauptmann, Ellen; Siegal, Justin; Fotoohi, Mehran; Crane, Robert; Robinson, David; Kozarek, Richard A

2010-12-01

Walled-off pancreatic necrosis (WOPN), a complication of severe acute pancreatitis (SAP), can become infected, obstruct adjacent structures, and result in clinical deterioration of patients. Patients with WOPN have prolonged hospitalizations, needing multiple radiologic and medical interventions. We compared an established treatment of WOPN, standard percutaneous drainage (SPD), with combined modality therapy (CMT), in which endoscopic transenteric stents were added to a regimen of percutaneous drains. Symptomatic patients with WOPN between January 2006 and August 2009 were treated with SPD (n = 43, 28 male) or CMT (n = 23, 17 male) and compared by disease severity, length of hospitalization, duration of drainage, complications, and number of radiologic and endoscopic procedures. Patient age (59 vs 54 years), sex (77% vs 58% male), computed tomography severity index (8.0 vs 7.2), number of endoscopic retrograde cholangiopancreatographies (2.0 vs 2.6), and percentage with disconnected pancreatic ducts (50% vs 46%) were equivalent in the CMT and SPD arms, respectively. Patients undergoing CMT had significantly decreased length of hospitalization (26 vs 55 days, P < .0026), duration of external drainage (83.9 vs 189 days, P < .002), number of computed tomography scans (8.95 vs 14.3, P < .002), and drain studies (6.5 vs 13, P < .0001). Patients in the SPD arm had more complications. For patients with symptomatic WOPN, CMT provided a more effective and safer management technique, resulting in shorter hospitalizations and fewer radiologic procedures than SPD. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Inhibiting tumor necrosis factor-alpha diminishes desmoplasia and inflammation to overcome chemoresistance in pancreatic ductal adenocarcinoma

PubMed Central

Xu, Zhigao; Chen, Honglei; He, Yuyu; Yang, Gui; Yang, Gang; Hu, Hanning; Tang, Shihui; Wang, Ping; Zhang, Zheng; Xu, Peipei; Yu, Mingxia

2016-01-01

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancer death reasons. Anti-tumor necrosis factor-alpha (TNF-α) antibodies have shown promising effects in PDAC pre-clinical models. However, the prognostic values of TNF-α, underlying mechanisms by which anti-TNF-α treatments inhibit PDAC, and potential synergistic effects of anti-TNF-α treatments with chemotherapy are still unclear. Results and Methods To identify the targeting values of TNF-α in PDAC, we measured TNF-α expression in different stages of PDAC initiation and evaluated its prognostic significance in a pancreatic cancer cohort. We found that TNF-α expression elevated in PDAC initiation process, and high expression of TNF-α was an independent prognostic marker of poor survival. We further evaluated anti-tumor effects of anti-TNF-α treatments in PDAC. Anti-TNF-α treatments resulted in decreased cell viability in both PDAC tumor cells and pancreatic satellite cells in similar dose in vitro. In vivo, anti-TNF-α treatments showed effects in reducing desmoplasia and the tumor promoting inflammatory microenvironment in PDAC. Combination of anti-TNF-α treatments with chemotherapy partly overcame chemoresistance of PDAC tumor cells and prolonged the survival of PDAC mouse model. Conclusions In conclusion, our findings indicated that TNF-α in PDAC can be a prognostic and therapeutic target. Inhibition of TNF-α synergized with chemotherapy in PDAC resulted in better pre-clinical responses via killing tumor cells as well as diminishing desmoplasia and inflammation in PDAC tumor stroma. PMID:27835602

Laparoscopic necrosectomy in acute necrotizing pancreatitis: Our experience

PubMed Central

Mathew, Mittu John; Parmar, Amit Kumar; Sahu, Diwakar; Reddy, Prasanna Kumar

2014-01-01

CONTEXT: Pancreatic necrosis is a local complication of acute pancreatitis. The development of secondary infection in pancreatic necrosis is associated with increased mortality. Pancreatic necrosectomy is the mainstay of invasive management. AIMS: Surgical approach has significantly changed in the last several years with the advent of enhanced imaging techniques and minimally invasive surgery. However, there have been only a few case series related to laparoscopic approach, reported in literature to date. Herein, we present our experience with laparoscopic management of pancreatic necrosis in 28 patients. MATERIALS AND METHODS: A retrospective study of 28 cases [20 men, 8 women] was carried out in our institution. The medical record of these patients including history, clinical examination, investigations, and operative notes were reviewed. The mean age was 47.8 years [range, 23-70 years]. Twenty-one patients were managed by transgastrocolic, four patients by transgastric, two patients by intra-cavitary, and one patient by transmesocolic approach. RESULTS: The mean operating time was 100.8 min [range, 60-120 min]. The duration of hospital stay after the procedure was 10-18 days. Two cases were converted to open (7.1%) because of extensive dense adhesions. Pancreatic fistula was the most common complication (n = 8; 28.6%) followed by recollection (n = 3; 10.7%) and wound infection (n = 3; 10.7%). One patient [3.6%] died in postoperative period. CONCLUSIONS: Laparoscopic pancreatic necrosectomy is a promising and safe approach with all the benefits of minimally invasive surgery and is found to have reduced incidence of major complications and mortality. PMID:25013328

Infectious hematopoietic necrosis virus detected by separation and incubation of cells from salmonid cavity fluid.

USGS Publications Warehouse

Mulcahy, D.; Batts, W.N.

1987-01-01

Infectious hematopoietic necrosis (IHN) virus is usually detected by inoculating susceptible cell cultures with cavity ("ovarian") fluid (CF) from spawning females. We identified additional adult carriers of virus in spawning populations of steelhead trout (Salmo gairdneri) and sockeye salmon (Oncorhynchus nerka) by collecting nonerythrocytic cells from CF samples by low-speed centrifugation, culturing the cells for at least 7 d at 15 °C, and then testing the culture medium for virus. Virus appeared in the cultured cells from some samples of CF that remained negative during incubation. In additional samples of CF from these species, the virus titer increased in cultured cells compared with the titer in the original CF sample. With chinook salmon (O.tshawytscha), no negative samples converted to positive during incubation, but the virus titer was retained in incubated CF cells, but not in cell-free CF.

Fish Viruses: Buffers and Methods for Plaquing Eight Agents Under Normal Atmosphere

PubMed Central

Wolf, Ken; Quimby, M. C.

1973-01-01

A universal procedure was sought for plaque assay of eight fish viruses (bluegill myxovirus, channel catfish virus, eel virus, Egtved virus, infectious hematopoietic necrosis virus, infectious pancreatic necrosis virus, lymphocystis virus, and the agent of spring viremia of carp (Rhabdovirus carpio), in dish cultures of various fish cells. Eagle minimal essential medium with sodium bicarbonate-CO2 buffer (Earle’s salt solution) was compared with minimal essential medium buffered principally with tris (hydroxymethyl)aminomethane or N-2-hydroxyethylpiperazine-N′-2′-ethanesulfonic acid at a pH or in the range of 7.6 to 8.0 depending upon temperature. Five fish cell lines collectively capable of replicating all fish viruses thus far isolated were tested and quantitatively found to grow comparably well in the three media. Two-phase (gel-liquid) media incorporating the various buffer systems allowed plaquing at 15 to 33 C either in partial pressures of CO2 or in normal atmosphere, but greater efficiency and sensitivity were obtained with the organic buffers, and, overall, the best results were obtained with tris(hydroxymethyl)aminomethane. Epizootiological data, specific fish cell line response, and plaque morphology permit presumptive identification of most of the agents. At proper pH, use of organic buffers obviates the need for CO2 incubators. Images PMID:4349252

Endosonography guided management of pancreatic fluid collections

PubMed Central

Vilmann, Andreas S; Menachery, John; Tang, Shou-Jiang; Srinivasan, Indu; Vilmann, Peter

2015-01-01

The revised Atlanta classification of acute pancreatitis was adopted by international consensus, and is based on actual local and systemic determinants of disease severity. The local determinant is pancreatic necrosis (sterile or infected), and the systemic determinant is organ failure. Local complications of pancreatitis can include acute peri-pancreatic fluid collection, acute necrotic collection, pseudocyst formation, and walled-off necrosis. Interventional endoscopic ultrasound (EUS) has been increasing utilized in managing these local complications. After performing a PubMed search, the authors manually applied pre-defined inclusion criteria or a filter to identify publications relevant to EUS and pancreatic collections (PFCs). The authors then reviewed the utility, efficacy, and risks associated with using therapeutic EUS and involved EUS devices in treating PFCs. Due to the development and regulatory approval of improved and novel endoscopic devices specifically designed for transmural drainage of fluid and necrotic debris (access and patency devices), the authors predict continuing evolution in the management of PFCs. We believe that EUS will become an indispensable part of procedures used to diagnose PFCs and perform image-guided interventions. After draining a PFC, the amount of tissue necrosis is the most important predictor of a successful outcome. Hence, it seems logical to classify these collections based on their percentage of necrotic component or debris present when viewed by imaging methods or EUS. Finally, the authors propose an algorithm for managing fluid collections based on their size, location, associated symptoms, internal echogenic patterns, and content. PMID:26557008

Neutralizing monoclonal antibodies recognize antigenic variants among isolates of infectious hematopoietic necrosis virus

USGS Publications Warehouse

Winton, J.R.; Arakawa, C.N.; Lannan, C.N.; Fryer, J.L.

1988-01-01

eutralizing monoclonal antibodies were developed against strains of infectious hematopoietic necrosis virus (IHNV) from steelhead trout Salmo gairdneri in the Deschutes River of Oregon, chinook salmon Oncorhynchus tshawytscha in the Sacramento River of California, and rainbow trout Salmo gairdneri reared in the Hagerman Valley of Idaho, USA. These antibodies were tested for neutralization of 12 IHNV isolates obtained from salmonids in Japan, Alaska, Washington, Oregon, California, and Idaho. The antibodies recognized antigenic variants among the isolates and could be used to separate the viruses into 4 groups. The members of each group tended to be related by geographic area rather than by source host species, virulence, or date of isolation.

Genotyping of Korean isolates of infectious hematopoietic necrosis virus (IHNV) based on the glycoprotein gene

USGS Publications Warehouse

Kim, W.-S.; Oh, M.-J.; Nishizawa, T.; Park, J.-W.; Kurath, G.; Yoshimizu, M.

2007-01-01

Glycoprotein (G) gene nucleotide sequences of four Korean isolates of infectious hematopoietic necrosis virus (IHNV) were analyzed to evaluate their genetic relatedness to worldwide isolates. All Korean isolates were closely related to Japanese isolates of genogroup JRt rather than to those of North American and European genogroups. It is believed that Korean IHNV has been most likely introduced from Japan to Korea by the movement of contaminated fish eggs. Among the Korean isolates, phylogenetically distinct virus types were obtained from sites north and south of a large mountain range, suggesting the possibility of more than one introduction of virus from Japan. ?? 2007 Springer-Verlag.

Oncolytic Activity of Avian Influenza Virus in Human Pancreatic Ductal Adenocarcinoma Cell Lines

PubMed Central

Pizzuto, Matteo S.; Silic-Benussi, Micol; Pavone, Silvia; Ciminale, Vincenzo; Capua, Ilaria

2014-01-01

ABSTRACT Pancreatic ductal adenocarcinoma (PDA) is the most lethal form of human cancer, with dismal survival rates due to late-stage diagnoses and a lack of efficacious therapies. Building on the observation that avian influenza A viruses (IAVs) have a tropism for the pancreas in vivo, the present study was aimed at testing the efficacy of IAVs as oncolytic agents for killing human PDA cell lines. Receptor characterization confirmed that human PDA cell lines express the alpha-2,3- and the alpha-2,6-linked glycan receptor for avian and human IAVs, respectively. PDA cell lines were sensitive to infection by human and avian IAV isolates, which is consistent with this finding. Growth kinetic experiments showed preferential virus replication in PDA cells over that in a nontransformed pancreatic ductal cell line. Finally, at early time points posttreatment, infection with IAVs caused higher levels of apoptosis in PDA cells than gemcitabine and cisplatin, which are the cornerstone of current therapies for PDA. In the BxPC-3 PDA cell line, apoptosis resulted from the engagement of the intrinsic mitochondrial pathway. Importantly, IAVs did not induce apoptosis in nontransformed pancreatic ductal HPDE6 cells. Using a model based on the growth of a PDA cell line as a xenograft in SCID mice, we also show that a slightly pathogenic avian IAV significantly inhibited tumor growth following intratumoral injection. Taken together, these results are the first to suggest that IAVs may hold promise as future agents of oncolytic virotherapy against pancreatic ductal adenocarcinomas. IMPORTANCE Despite intensive studies aimed at designing new therapeutic approaches, PDA still retains the most dismal prognosis among human cancers. In the present study, we provide the first evidence indicating that avian IAVs of low pathogenicity display a tropism for human PDA cells, resulting in viral RNA replication and a potent induction of apoptosis in vitro and antitumor effects in vivo. These

Necrotizing pancreatitis: new definitions and a new era in surgical management.

PubMed

Rosenberg, Andrew; Steensma, Elizabeth A; Napolitano, Lena M

2015-02-01

Necrotizing pancreatitis is a challenging condition that requires surgical treatment commonly and is associated with substantial morbidity and mortality. Over the past decade, new definitions have been developed for standardization of severity of acute and necrotizing pancreatitis, and new management techniques have emerged based on prospective, randomized clinical trials. Review of English-language literature. A new international classification of acute pancreatitis has been developed by PANCREA (Pancreatitis Across Nations Clinical Research and Education Alliance) to replace the Atlanta Classification. It is based on the actual local (whether pancreatic necrosis is present or not, whether it is sterile or infected) and systemic determinants (whether organ failure is present or not, whether it is transient or persistent) of severity. Early management requires goal-directed fluid resuscitation (with avoidance of over-resuscitation and abdominal compartment syndrome), assessment of severity of pancreatitis, diagnostic computed tomography (CT) imaging to assess for necrotizing pancreatitis, consideration of endoscopic retrograde cholangiopancreatography (ERCP) for biliary pancreatitis and early enteral nutrition support. Antibiotic prophylaxis is not recommended. Therapeutic antibiotics are required for treatment of documented infected pancreatic necrosis. The initial treatment of infected pancreatic necrosis is percutaneous catheter or endoscopic (transgastric/transduodenal) drainage with a second drain placement as required. Lack of clinical improvement after these initial procedures warrants consideration of minimally invasive techniques for pancreatic necrosectomy including video-assisted retroperitoneal debridement (VARD), minimally invasive retroperitoneal pancreatectomy (MIRP), or transluminal direct endoscopic necrosectomy (DEN). Open necrosectomy is associated with substantial morbidity, but to date no randomized trial has documented superiority of either

Detection of infectious haematopoietic necrosis virus in river water and demonstration of waterborne transmission

USGS Publications Warehouse

Mulcahy, D.; Pascho, R.J.; Jenes, C.K.

1983-01-01

In a study of the possible role of waterborne infectious haematopoietic necrosis virus in transmission of the disease among spawning sockeye salmon, Oncorhynchus nerka (Walbaum), both infection rates and virus titres were higher in fish held at high density in a side channel than in fish in the adjacent river. Virus was never isolated from river water, but was found in water from the side channel at levels ranging from 32.5 to 1600 plaque-forming units (p.f.u.)/ml. Uninfected yearling sockeye salmon held in a box in the side channel developed localized gill infections with IHN virus. The disease did not progress to the viscera until a threshold titre of about 105 p.f.u./g was reached in the gill. The effectiveness of the gill as a barrier limiting development of systemic infections means that waterborne IHN virus probably does not greatly increase the infection rate in a sockeye salmon population during spawning.

Detection of infectious hematopoietic necrosis virus in river water and demonstration of waterborne transmission

USGS Publications Warehouse

Mulcahy, Daniel M.; Pascho, Ronald J.; Jenes, C.K.

1983-01-01

In a study of the possible role of waterborne infectious haematopoietic necrosis virus in transmission of the disease among spawning sockeye salmon, Oncorhynchus nerka (Walbaum), both infection rates and virus titres were higher in fish held at high density in a side channel than in fish in the adjacent river. Virus was never isolated from river water, but was found in water from the side channel at levels ranging from 32.5 to 1600 plaque-forming units (p.f.u.)/ml. Uninfected yearling sockeye salmon held in a box in the side channel developed localized gill infections with IHN virus. The disease did not progress to the viscera until a threshold titre of about 105 p.f.u./g was reached in the gill. The effectiveness of the gill as a barrier limiting development of systemic infections means that waterborne IHN virus probably does not greatly increase the infection rate in a sockeye salmon population during spawning.

Evaluation of the tepary bean (Phaseolus acutifolius) CIAT germplasm collection for response to common bacterial blight and bean common mosaic necrosis virus

USDA-ARS?s Scientific Manuscript database

Aphid-transmitted Bean Common Mosaic Necrosis Virus (BCMNV) and Bean Common Mosaic Virus (BCMV) are potyvirus that cause production losses in common and tepary beans. Developing resistance to viruses, specifically BCMV, BCMNV and BGYMV, will be critical for expanding tepary bean production. This stu...

Inactivation of infectious hematopoietic necrosis virus by low levels of iodine

USGS Publications Warehouse

Batts, William N.; Landolt, Marsha L.; Winton, James R.

1991-01-01

The fish rhabdovirus infectious hematopoietic necrosis virus (IHNV) was rapidly inactivated by extremely low concentrations of iodine in water. A 99.9% virus reduction was obtained in 7.5 s when virus (105PFU/ml) and iodine (0.1 mg/liter, final concentration) were combined in distilled-deionized or hatchery water. Iodine efficacy decreased at pHs greater than 7.5 or when proteinaceous material was added to the water. Bovine serum albumin blocked iodine inactivation of the virus more effectively than did equal concentrations of fetal bovine serum or river sediment. Sodium thiosulfate effectively neutralized free iodine. Powder, iodophor, and crystalline iodine solutions inactivated IHNV equally. Iodine rapidly inactivated IHNV isolates representing each of the five electropherotypes. Under the conditions used in this study, inactivation was not affected by temperature, salinity, or water hardness. When Dworshak National Fish Hatchery water was continuously treated to provide a free iodine concentration of 0.14 mg/liter, a 7.5-s exposure to iodine was sufficient to inactivate 99.9% of the IHNV. Iodine added to water that contained IHNV prevented infection of rainbow trout (Oncorhynchus mykiss) fry. These results suggest that the waterborne route of IHNV transmission can be blocked by adding low iodine concentrations to the water supplies of hatcheries.

P-HPB-21: Isolated pancreatic tuberculosis mimicking inoperable pancreatic cancer

PubMed Central

Sahu, Manoj Kumar; Singh, Ayashkanta; Behera, Debasmita; Behera, Manas; Narayan, Jimmy

2017-01-01

Background: Pancreatic tuberculosis is an uncommon disease, presenting as hypoechoic mass on imaging mimicking malignancy. Consequently, it represents a diagnostic challenge necessitating a tissue diagnosis. Case Report: A 75-year-old female presented with progressive jaundice and weight loss; imaging with computed tomography (CT) showed a large (5.8 cm × 4.6 cm) pancreatic head mass with encasement of portal and superior mesenteric veins, peripancreatic nodes, atrophic pancreatic parenchyma, and dilated main pancreatic duct. Cancer antigen 19-9 was moderately elevated. With a diagnosis of inoperable pancreatic malignancy, she was planned for tissue diagnosis and palliative chemotherapy. Endoscopic ultrasonography (EUS) showed a heterogeneous mass with vascular invasion as in the CT. Fine needle aspiration (FNA) and biliary decompression with a plastic stent performed in the same sitting. Cytology demonstrated granuloma with caseous necrosis and presence of acid-fast bacilli. Antituberculosis treatment was started, and repeat CT after 6 months showed resolution of the mass. Discussion and Conclusion: A diagnosis of isolated pancreatic tuberculosis is rare and is difficult by clinical presentation alone; in India, it should be considered as a differential diagnosis of a pancreatic tumor. Benign lesions can also present with vascular invasions mimicking inoperable malignancy. EUS FNA is a very useful tool in accurate diagnosis of pancreatic head mass avoiding unnecessary surgeries.

Occurrence and genetic typing of infectious hematopoietic necrosis virus in Kamchatka, Russia

USGS Publications Warehouse

Rudakova, S.L.; Kurath, G.; Bochkova, E.V.

2007-01-01

Infectious hematopoietic necrosis virus (IHNV) is a well known rhabdoviral pathogen of salmonid fish in North America that has become established in Asia and Europe. On the Pacific coast of Russia, IHNV was first detected in hatchery sockeye from the Kamchatka Peninsula in 2001. Results of virological examinations of over 10 000 wild and cultured salmonid fish from Kamchatka during 1996 to 2005 revealed IHNV in several sockeye salmon Oncorhynchus nerka populations. The virus was isolated from spawning adults and from juveniles undergoing epidemics in both hatchery and wild sockeye populations from the Bolshaya watershed. No virus was detected in 2 other water-sheds, or in species other than sockeye salmon. Genetic typing of 8 virus isolates by seguence analysis of partial glycoprotein and nucleocapsid genes revealed that they were genetically homogeneous and fell within the U genogroup of IHNV. In phylogenetic analyses, the Russian IHNV sequences were indistinguishable from the sequences of North American U genogroup isolates that occur throughout Alaska, British Columbia, Washington, and Oregon. The high similarity, and in some cases identity, between Russian and North American IHNV isolates suggests virus transmission or exposure to a common viral reservoir in the North Pacific Ocean. ?? Inter-Research 2007.

Pancreatitis, panniculitis and polyarthritis (PPP-) syndrome caused by post-pancreatitis pseudocyst with mesenteric fistula. Diagnosis and successful surgical treatment. Case report and review of literature.

PubMed

Dieker, Wulf; Derer, Johannes; Henzler, Thomas; Schneider, Alexander; Rückert, Felix; Wilhelm, Torsten J; Krüger, Bernd

2017-01-01

Pancreatitis, panniculitis and polyarthritis syndrome is a very rare extra-pancreatic complication of pancreatic diseases. While in most cases this syndrome is caused by acute or chronic pancreatitis, we report a case of a 62-year-old man presenting with extensive intraosseous fat necrosis, polyarthritis and panniculitis caused by a post-pancreatitis pseudocyst with a fistula to the superior mesenteric vein and extremely high blood levels of lipase. This became symptomatic 2.5 years after an episode of acute pancreatitis and as in most cases abdominal symptoms were absent. Treatment by surgical resection of the pancreatic head with the pseudocyst and mesenteric fistula led to complete remission of all symptoms. A review of the literature revealed that all publications are limited to case reports. Most authors hypothesize that an unspecific damage can cause a secretion of pancreatic enzymes to the bloodstream leading to a systemic lipolysis and fat tissue necrosis, especially of subcutaneous tissue, bone marrow, inducing panniculitis, polyarthritis and osteonecrosis. Even if caused by an acute pancreatitis abdominal symptoms are often mild or absent in most cases leading to misdiagnosis and poor prognosis. While symptomatic treatment with NSAR and cortisone showed poor to moderate response, causal treatment can be successful depending on the underlying pancreatic disease. Copyright © 2017. Published by Elsevier Ltd.

Necrosis of the tail of pancreas following proximal splenic artery embolization

PubMed Central

Talving, Peep; Rauk, Mariliis; Vipp, Liisa; Isand, Karl-Gunnar; Šamarin, Aleksandr; Põder, Kalle; Rätsep, Indrek; Saar, Sten

2016-01-01

The current case report presents a rare complication of a significant pancreatic tail necrosis following proximal splenic artery embolization in a 32-year-old male patient involved in a motorcycle accident. Proximal angiographic embolization of the splenic injury after trauma is a widely accepted method with excellent success rate; however, possible complications may occur and has been described in the literature. Nevertheless, only a few case reports pertinent to clinically significant pancreatic tail necrosis after the SAE has been reported. Thus, we add a case report to the scarce literature pertinent to this detrimental and rare complication. PMID:27177891

A necrosis-inducing elicitor domain encoded by both symptomatic and asymptomatic Plantago asiatica mosaic virus isolates, whose expression is modulated by virus replication.

PubMed

Komatsu, Ken; Hashimoto, Masayoshi; Maejima, Kensaku; Shiraishi, Takuya; Neriya, Yutaro; Miura, Chihiro; Minato, Nami; Okano, Yukari; Sugawara, Kyoko; Yamaji, Yasuyuki; Namba, Shigetou

2011-04-01

Systemic necrosis is the most destructive symptom induced by plant pathogens. We previously identified amino acid 1154, in the polymerase domain (POL) of RNA-dependent RNA polymerase (RdRp) of Plantago asiatica mosaic virus (PlAMV), which affects PlAMV-induced systemic necrosis in Nicotiana benthamiana. By point-mutation analysis, we show that amino acid 1,154 alone is not sufficient for induction of necrotic symptoms. However, PlAMV replicons that can express only RdRp, derived from a necrosis-inducing PlAMV isolate, retain their ability to induce necrosis, and transient expression of PlAMV-encoded proteins indicated that the necrosis-eliciting activity resides in RdRp. Moreover, inducible-overexpression analysis demonstrated that the necrosis was induced in an RdRp dose-dependent manner. In addition, during PlAMV infection, necrotic symptoms are associated with high levels of RdRp accumulation. Surprisingly, necrosis-eliciting activity resides in the helicase domain (HEL), not in the amino acid 1,154-containing POL, of RdRp, and this activity was observed even in HELs of PlAMV isolates of which infection does not cause necrosis. Moreover, HEL-induced necrosis had characteristics similar to those induced by PlAMV infection. Overall, our data suggest that necrotic symptoms induced by PlAMV infection depend on the accumulation of a non-isolate specific elicitor HEL (even from nonnecrosis isolates), whose expression is indirectly regulated by amino acid 1,154 that controls replication.

High incidence of coagualopathy in phase II studies of recombinant tumor necrosis factor in advanced pancreatic and gastric cancers.

PubMed

Muggia, F M; Brown, T D; Goodman, P J; Macdonald, J S; Hersh, E M; Fleming, T R; Leichman, L

1992-06-01

This multi-center trial was carried out to assess the therapeutic potential of recombinant tumor necrosis factor (rTNF) as the first form of systemic therapy for advanced carcinomas of gastric and pancreatic origin. To be eligible patients were required to have no overt sign of coagulopathy and hepatic function studies with enzymes less than two times beyond the normal range. Twenty nine patients with gastric cancer and 26 with pancreatic cancer were entered from various institutions in the Southwest Oncology Group with 27 and 22, respectively, meeting eligibility criteria. Drug treatment consisted of rTNF (Genentech) given at a dose of 150 micrograms intravenously for five consecutive days every 3 weeks; 50% dose reduction was made for acute intolerance such as hypotension or severe fever and chills. Although eight patients with gastric cancer and five patients with pancreatic cancer received four or more courses of treatment, no objective antitumor responses were recorded. As in other trials common toxicities of rTNF included nausea and vomiting, chills and fever, hypotension, headache, myalgias, fatigue and malaise. However, in this trial, other toxicities became prominent: four episodes of symptomatic disseminated intravascular clotting occurred among patients with pancreatic cancer. Eleven with this disease and five with gastric cancer manifested laboratory findings of abnormal amounts of fibrin split products, and/or hypofibrinogenemia, and/or thrombocytopenia after treatment began. Other laboratory abnormalities that were commonly encountered included hyperglycemia, hypertriglyceridemia, anemia, neutropenia and an elevation in liver enzymes. We conclude that rTNF does not demonstrate antitumor efficacy against adenocarcinomas of the stomach and the pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular epidemiology of infectious hematopoietic necrosis virus reveals complex virus traffic and evolution within southern Idaho aquaculture

USGS Publications Warehouse

Troyer, R.M.; Kurath, G.

2003-01-01

Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus which infects salmon and trout and may cause disease with up to 90% mortality. In the Hagerman Valley of Idaho, IHNV is endemic or epidemic among numerous fish farms and resource mitigation hatcheries. A previous study characterizing the genetic diversity among 84 IHNV isolates at 4 virus-endemic rainbow trout farms indicated that multiple lineages of relatively high diversity co-circulated at these facilities (Troyer et al. 2000 J Gen Virol. 81:2823-2832). We tested the hypothesis that high IHNV genetic diversity and co-circulating lineages are present in aquaculture facilities throughout this region. In this study, 73 virus isolates from 14 rainbow trout farms and 3 state hatcheries in the Hagerman Valley, isolated between 1978 and 1999, were genetically characterized by sequence analysis of a 303 nucleotide region of the glycoprotein gene. Phylogenetic and epidemiological analyses showed that multiple IHNV lineages co-circulate in a complex pattern throughout private trout farms and state hatcheries in the valley. IHNV maintained within the valley appears to have evolved significantly over the 22 yr study period.

Establishment of rat pancreatic endocrine cell lines by infection with simian virus 40.

PubMed Central

Niesor, E J; Wollheim, C B; Mintz, D H; Blondel, B; Renold, A E; Weil, R

1979-01-01

The feasibility of infection and transformation by SV40 (simian virus 40) of primary cell cultures derived from newborn-rat pancreas was investigated. As judged by the presence of intranuclear SV40 T-antigen, exposure to the virus resulted specifically in infection and transformation of epithelioid (predominantly endocrine) cells. The transformed cells were subcultured (more than 64 passages) and cloned. Culture medium and acid/ethanol extracts of the cells did not contain detectable amounts of immunoreactive insulin after the third subculture. However, inoculation of such SV40-transformed pancreatic cells into immunodeficient rats results in tumours in which insulin production was partially restored through the passage in vivo, since the tumour cells contained and synthesized small amounts of immunoreactive insulin which co-migrated with an insulin marker on gel chromatography. Interestingly, the transformed cells maintained under tissue-culture conditions produced a protein immunologically related to insulin, soluble in aqueous buffer but insoluble in acid/ethanol. This 3000-dalton protein is too large to be a translation product of the rat preproinsulin 9S mRNA. SV40-transformed pancreatic cells might prove useful in the investigation of the factors controlling and maintaining insulin biosynthesis. Images Fig. 1. PMID:222255

Experimental evidence of obesity as a risk factor for severe acute pancreatitis.

PubMed

Frossard, Jean-Louis; Lescuyer, Pierre; Pastor, Catherine M

2009-11-14

The incidence of acute pancreatitis, an inflammation of the pancreas, is increasing worldwide. Pancreatic injury is mild in 80%-90% of patients who recover without complications. The remaining patients may develop a severe disease with local complications such as acinar cell necrosis, abscess and remote organ injury including lung injury. The early prediction of the severity of the disease is an important goal for physicians in management of patients with acute pancreatitis in order to optimize the therapy and to prevent organ dysfunction and local complications. For that purpose, multiple clinical scale scores have been applied to patients with acute pancreatitis. Recently, a new problem has emerged: the increased severity of the disease in obese patients. However, the mechanisms by which obesity increases the severity of acute pancreatitis are unclear. Several hypotheses have been suggested: (1) obese patients have an increased inflammation within the pancreas; (2) obese patients have an increased accumulation of fat within and around the pancreas where necrosis is often located; (3) increase in both peri- and intra-pancreatic fat and inflammatory cells explain the high incidence of pancreatic inflammation and necrosis in obese patients; (4) hepatic dysfunction associated with obesity might enhance the systemic inflammatory response by altering the detoxification of inflammatory mediators; and (5) ventilation/perfusion mismatch leading to hypoxia associated with a low pancreatic flow might reduce the pancreatic oxygenation and further enhance pancreatic injury. Recent experimental investigations also show an increased mortality and morbidity in obese rodents with acute pancreatitis and the implication of the adipokines leptin and adiponectin. Such models are important to investigate whether the inflammatory response of the disease is enhanced by obesity. It is exciting to speculate that manipulation of the adipokine milieu has the potential to influence the

Susceptibility of Australian Redfin Perch Perca fluviatilis Experimentally Challenged with Epizootic Hematopoietic Necrosis Virus (EHNV).

PubMed

Becker, Joy A; Tweedie, Alison; Gilligan, Dean; Asmus, Martin; Whittington, Richard J

2016-06-01

The ranavirus epizootic hematopoietic necrosis virus (EHNV) is endemic to Australia and is listed by the Office International des Epizooties. Clinical outbreaks have only been observed in wild populations of Redfin Perch Perca fluviatilis (also known as Eurasian Perch) and farmed populations of Rainbow Trout Oncorhynchus mykiss. The initial outbreaks of EHNV describe all age-classes of Redfin Perch as being susceptible and can lead to epidemic fish kills. Subsequently, experimental challenge studies using either cohabitation with the virus or injection exposures resulted in mixed susceptibilities across various age-groupings of Redfin Perch. We used an experimental bath challenge model to investigate the susceptibility of Redfin Perch collected from areas with and without a history of EHNV outbreaks. The median survival time for fish from Blowering Dam in New South Wales, a zone with a history of EHNV outbreaks, was 35 d, compared with fish from other areas, which had a median survival between 12 and 28 d postexposure. Redfin Perch from Blowering Dam demonstrated an increased mortality associated with epizootic hematopoietic necrosis up to approximately day 14 after exposure, and then there was a significantly reduced risk of mortality until the end of the trial compared with all other fish. Redfin Perch from Blowering Dam had markedly decreased susceptibility to EHNV, and less than 40% became infected following a bath challenge. In contrast, Redfin Perch from neighboring (e.g., Bethungra Dam and Tarcutta Creek) and distant water bodies (e.g., in Western Australia) with no previous history of EHNVdisplayed moderate to high susceptibility when given a bath challenge. Potential factors for the observed changes in the host-pathogen relationship include intense positive selection pressure for resistant fish following epizootic hematopoietic necrosis outbreaks and subsequent attenuation of the virulence of the virus in resistant fish. Received August 22, 2015; accepted

Novel findings in the management of acute pancreatitis.

PubMed

Bolado, Federico; de-Madaria, Enrique

2016-09-01

Acute pancreatitis (AP) is a potentially serious disease whose incidence is on the increase. Pancreas divisum does not meet the required criteria to be considered an aetiological factor. Sphincter of Oddi dysfunction may be another cause of idiopathic AP. Less invasive methods cannot replace Sphincter of Oddi manometry in diagnosis. Almost half of patients with systemic inflammatory response syndrome develop organ failure, but the mechanisms involved are not completely understood. Obesity is a risk factor for severity in AP; the cause could be the presence of free unsaturated fatty acids, which have pro-inflammatory activity. Prognosis is better in patients with isolated extra-pancreatic necrosis than in those with parenchymal necrosis or with both. The mortality rate among those with infected pancreatic necrosis is 15-20%. The "moderately severe" group is widely heterogeneous and this category may require redefinition. Laparoscopic treatment of pseudocysts is an alternative to endoscopic drainage and could be the first-line option in patients requiring cholecystectomy. The use of lumen-apposing metal stents to treat pancreatic necrosis is cost-effective. Quality of life in some patients following an attack of AP is significantly impaired even at 1 year. Aggressive fluid therapy is not superior to standard fluid therapy in preventing post-ERCP AP. The role of statins in AP prevention is still unclear. Aggressive fluid resuscitation and the use of lactated Ringer solution seem to be beneficial in the treatment of AP. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Necrotizing pancreatitis: challenges and solutions.

PubMed

Bendersky, Victoria A; Mallipeddi, Mohan K; Perez, Alexander; Pappas, Theodore N

2016-01-01

Acute pancreatitis is a common disease that can progress to gland necrosis, which imposes significant risk of morbidity and mortality. In general, the treatment for pancreatitis is a supportive therapy. However, there are several reasons to escalate to surgery or another intervention. This review discusses the pathophysiology as well as medical and interventional management of necrotizing pancreatitis. Current evidence suggests that patients are best served by delaying interventions for at least 4 weeks, draining as a first resort, and debriding recalcitrant tissue using minimally invasive techniques to promote or enhance postoperative recovery while reducing wound-related complications.

Molecular identification of erythrocytic necrosis virus (ENV) from the blood of Pacific herring (Clupea pallasii)

USGS Publications Warehouse

Emmenegger, Eveline J.; Glenn, Jolene A.; Winton, James R.; Batts, William N.; Gregg, Jacob L.; Hershberger, Paul K.

2014-01-01

Viral erythrocytic necrosis (VEN) is a condition affecting the red blood cells of more than 20 species of marine and anadromous fishes in the North Atlantic and North Pacific Oceans. Among populations of Pacific herring (Clupea pallasii) on the west coast of North America the disease causes anemia and elevated mortality in periodic epizootics. Presently, VEN is diagnosed by observation of typical cytoplasmic inclusion bodies in stained blood smears from infected fish. The causative agent, erythrocytic necrosis virus (ENV), is unculturable and a presumed iridovirus by electron microscopy. In vivo amplification of the virus in pathogen-free laboratory stocks of Pacific herring with subsequent virus concentration, purification, DNA extraction, and high-throughput sequencing were used to obtain genomic ENV sequences. Fragments with the highest sequence identity to the family Iridoviridae were used to design four sets of ENV-specific polymerase chain reaction (PCR) primers. Testing of blood and tissue samples from experimentally and wild infected Pacific herring as well as DNA extracted from other amphibian and piscine iridoviruses verified the assays were specific to ENV with a limit of detection of 0.0003 ng. Preliminary phylogenetic analyses of a 1448 bp fragment of the putative DNA polymerase gene supported inclusion of ENV in a proposed sixth genus of the family Iridoviridae that contains other erythrocytic viruses from ectothermic hosts. This study provides the first molecular evidence of ENV's inclusion within the Iridoviridae family and offers conventional PCR assays as a means of rapidly surveying the ENV-status of wild and propagated Pacific herring stocks.

Acute and chronic pancreatitis: surgical management.

PubMed

Dzakovic, Alexander; Superina, Riccardo

2012-08-01

Pancreatitis is becoming increasingly prevalent in children, posing new challenges to pediatric health care providers. Although some general adult treatment paradigms are applicable in the pediatric population, diagnostic workup and surgical management of acute and chronic pancreatitis have to be tailored to anatomic and pathophysiological entities peculiar to children. Nonbiliary causes of acute pancreatitis in children are generally managed nonoperatively with hydration, close biochemical and clinical observation, and early initiation of enteral feeds. Surgical intervention including cholecystectomy or endoscopic retrograde cholangiopancreatography is often required in acute biliary pancreatitis, whereas infected pancreatic necrosis remains a rare absolute indication for pancreatic debridement and drainage via open, laparoscopic, or interventional radiologic procedure. Chronic pancreatitis is characterized by painful irreversible changes of the parenchyma and ducts, which may result in or be caused by inadequate ductal drainage. A variety of surgical procedures providing drainage, denervation, resection, or a combination thereof are well established to relieve pain and preserve pancreatic function. Copyright © 2012. Published by Elsevier Inc.

Pathogenesis of Pancreatitis in Chickens after Experimental Infection with 9a5b Newcastle Disease Virus Mutant Isolate.

PubMed

El-Bahrawy, A; Zaid, A; Sunden, Y; Sakurai, M; Ito, H; Ito, T; Morita, T

2015-11-01

The aim of this study was to investigate the effect of Newcastle disease virus (NDV) on the chicken pancreas. A virulent 9a5b mutant NDV isolate was inoculated intranasally into 32-day-old specific pathogen-free white Leghorn chickens. The pancreas was examined grossly and fixed for histopathological, immunohistochemical and electron microscopical investigations. Inflammatory changes were observed in the peripancreatic tissue at the early stage of infection (12 h post infection) and became more prevalent towards the end of the experiment. Multifocal areas of necrotizing inflammation were detected in the exocrine portion of the pancreas by 5 days post infection (dpi) and became more severe at 10 dpi. The endocrine islets were generally preserved, but slight degenerative changes were observed at 10 dpi. Immunohistochemically, NDV-nucleoprotein (NDV-NP) signals were detected in the peripancreatic tissues (associated with macrophages and other lymphoid cells) by 1 dpi. In the exocrine portion of the pancreas, NDV-NP signals were detected at 5 dpi and increased in intensity and distribution by 10 dpi. NDV particles were confirmed in the cytoplasm of exocrine acinar cells by transmission electron microscopy. CD3-positive cells were observed in the peripancreatic tissues earlier than in the pancreatic tissue. Moreover, in comparison with control chickens, insulin immunoexpression was unchanged, except on the last day of the experiment, when it was slightly reduced. The 9a5b NDV infection induced an inflammatory reaction and viral replication in the peripancreatic tissues earlier than in the pancreatic tissue. Furthermore, necrosis affected mainly the exocrine portion of the pancreas, while the endocrine portion was generally unaffected. Copyright © 2015 Elsevier Ltd. All rights reserved.

Viral fitness does not correlate with three genotype displacement events involving infectious hematopoietic necrosis virus

USGS Publications Warehouse

Kell, Alison M.; Wargo, Andrew R.; Kurath, Gael

2014-01-01

Viral genotype displacement events are characterized by the replacement of a previously dominant virus genotype by a novel genotype of the same virus species in a given geographic region. We examine here the fitness of three pairs of infectious hematopoietic necrosis virus (IHNV) genotypes involved in three major genotype displacement events in Washington state over the last 30 years to determine whether increased virus fitness correlates with displacement. Fitness was assessed using in vivo assays to measure viral replication in single infection, simultaneous co-infection, and sequential superinfection in the natural host, steelhead trout. In addition, virion stability of each genotype was measured in freshwater and seawater environments at various temperatures. By these methods, we found no correlation between increased viral fitness and displacement in the field. These results suggest that other pressures likely exist in the field with important consequences for IHNV evolution.

Modeling Virus Coinfection to Inform Management of Maize Lethal Necrosis in Kenya

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hilker, Frank M.; Allen, Linda J. S.; Bokil, Vrushali A.

Maize lethal necrosis (MLN) has emerged as a serious threat to food security in sub-Saharan Africa. MLN is caused by coinfection with two viruses, Maize chlorotic mottle virus and a potyvirus, often Sugarcane mosaic virus. To better understand the dynamics of MLN and to provide insight into disease management, we modeled the spread of the viruses causing MLN within and between growing seasons. The model allows for transmission via vectors, soil, and seed, as well as exogenous sources of infection. Following model parameterization, we predict how management affects disease prevalence and crop performance over multiple seasons. Resource-rich farmers with largemore » holdings can achieve good control by combining clean seed and insect control. However, crop rotation is often required to effect full control. Resource-poor farmers with smaller holdings must rely on rotation and roguing, and achieve more limited control. For both types of farmer, unless management is synchronized over large areas, exogenous sources of infection can thwart control. As well as providing practical guidance, our modeling framework is potentially informative for other cropping systems in which coinfection has devastating effects. Finally, our work also emphasizes how mathematical modeling can inform management of an emerging disease even when epidemiological information remains scanty.« less

Modeling Virus Coinfection to Inform Management of Maize Lethal Necrosis in Kenya

DOE PAGES

Hilker, Frank M.; Allen, Linda J. S.; Bokil, Vrushali A.; ...

2017-08-01

Maize lethal necrosis (MLN) has emerged as a serious threat to food security in sub-Saharan Africa. MLN is caused by coinfection with two viruses, Maize chlorotic mottle virus and a potyvirus, often Sugarcane mosaic virus. To better understand the dynamics of MLN and to provide insight into disease management, we modeled the spread of the viruses causing MLN within and between growing seasons. The model allows for transmission via vectors, soil, and seed, as well as exogenous sources of infection. Following model parameterization, we predict how management affects disease prevalence and crop performance over multiple seasons. Resource-rich farmers with largemore » holdings can achieve good control by combining clean seed and insect control. However, crop rotation is often required to effect full control. Resource-poor farmers with smaller holdings must rely on rotation and roguing, and achieve more limited control. For both types of farmer, unless management is synchronized over large areas, exogenous sources of infection can thwart control. As well as providing practical guidance, our modeling framework is potentially informative for other cropping systems in which coinfection has devastating effects. Finally, our work also emphasizes how mathematical modeling can inform management of an emerging disease even when epidemiological information remains scanty.« less

Factors and outcomes associated with pancreatic duct disruption in patients with acute necrotizing pancreatitis.

PubMed

Jang, Ji Woong; Kim, Myung-Hwan; Oh, Dongwook; Cho, Dong Hui; Song, Tae Jun; Park, Do Hyun; Lee, Sang Soo; Seo, Dong-Wan; Lee, Sung Koo; Moon, Sung-Hoon

Acute necrotizing pancreatitis (ANP) can affect main pancreatic duct (MPD) as well as parenchyma. However, the incidence and outcomes of MPD disruption has not been well studied in the setting of ANP. This retrospective study investigated 84 of 465 patients with ANP who underwent magnetic resonance cholangiopancreatography and/or endoscopic retrograde cholangiopancreatography. The MPD disruption group was subclassified into complete and partial disruption. MPD disruption was documented in 38% (32/84) of the ANP patients. Extensive necrosis, enlarging/refractory pancreatic fluid collections (PFCs), persistence of amylase-rich output from percutaneous drainage, and amylase-rich ascites/pleural effusion were more frequently associated with MPD disruption. Hospital stay was prolonged (mean 55 vs. 29 days) and recurrence of PFCs (41% vs. 14%) was more frequent in the MPD disruption group, although mortality did not differ between ANP patients with and without MPD disruption. Subgroup analysis between complete disruption (n = 14) and partial disruption (n = 18) revealed a more frequent association of extensive necrosis and full-thickness glandular necrosis with complete disruption. The success rate of endoscopic transpapillary pancreatic stenting across the stricture site was lower in complete disruption (20% vs. 92%). Patients with complete MPD disruption also showed a high rate of PFC recurrence (71% vs. 17%) and required surgery more often (43% vs. 6%). MPD disruption is not uncommon in patients with ANP with clinical suspicion on ductal disruption. Associated MPD disruption may influence morbidity, but not mortality of patients with ANP. Complete MPD disruption is often treated by surgery, whereas partial MPD disruption can be managed successfully with endoscopic transpapillary stenting and/or transmural drainage. Further prospective studies are needed to study these items. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Control of infectious Hematopoietic Necrosis virus disease by elevating the water temperature

USGS Publications Warehouse

Amend, Donald F.

1970-01-01

Studies were performed to determine if increasing water temperatures could control infectious hematopoietic necrosis virus (IHN) disease in sockeye salmon (Oncorhynchus nerka). Mortalities could be prevented if the water temperature was raised to at least 18 C within the first 24 hr after infection of the fish and if the fish were maintained at this temperature for 4–6 days. The disease did not recur after the elevated temperature treatment, but the fish would still contract the disease if they were reinfected. Reasons for the protecting action are discussed.

Severe acute pancreatitis and pregnancy.

PubMed

Robertson, K W; Stewart, I S; Imrie, C W

2006-01-01

For most patients with pregnancy-associated pancreatitis there is little maternal survival threat and only occasionally are there foetal deaths. We describe 4 young women with pregnancy-associated severe acute pancreatitis who each had gallstones. Their ages were 17, 18, 20 and 24 years. Each was a tertiary referral to our unit in Glasgow and each pursued a life-threatening course with hospital stays ranging from 37 to 90 days. One patient required pancreatic necrosectomy for infected necrosis, another had percutaneous management of a pancreatic abscess and 2 had cystogastrostomy as treatment for pancreatic pseudocyst. All underwent early endoscopic sphincterotomy and later cholecystectomy. It is important to be aware that pregnancy-associated acute pancreatitis may be severe, posing a survival threat even in the youngest patients. Gallstones, as we reported almost 20 years ago, are the most common aetiological factor in such patients. Copyright (c) 2006 S. Karger AG, Basel and IAP.

Molecular epidemiology of Epizootic haematopoietic necrosis virus (EHNV).

PubMed

Hick, Paul M; Subramaniam, Kuttichantran; Thompson, Patrick M; Waltzek, Thomas B; Becker, Joy A; Whittington, Richard J

2017-11-01

Low genetic diversity of Epizootic haematopoietic necrosis virus (EHNV) was determined for the complete genome of 16 isolates spanning the natural range of hosts, geography and time since the first outbreaks of disease. Genomes ranged from 125,591-127,487 nucleotides with 97.47% pairwise identity and 106-109 genes. All isolates shared 101 core genes with 121 potential genes predicted within the pan-genome of this collection. There was high conservation within 90,181 nucleotides of the core genes with isolates separated by average genetic distance of 3.43 × 10 -4 substitutions per site. Evolutionary analysis of the core genome strongly supported historical epidemiological evidence of iatrogenic spread of EHNV to naïve hosts and establishment of endemic status in discrete ecological niches. There was no evidence of structural genome reorganization, however, the complement of non-core genes and variation in repeat elements enabled fine scale molecular epidemiological investigation of this unpredictable pathogen of fish. Copyright © 2017 Elsevier Inc. All rights reserved.

Surveillance for nervous necrosis virus-specific antibodies in barramundi Lates calcarifer in Australian hatcheries.

PubMed

Jaramillo, Diana; Hick, Paul; Dyrting, Kitman; Anderson, Ian; Whittington, Richard J

2017-03-30

We conducted single point-in-time and repeated cross-sectional studies of the prevalence of antibodies against nervous necrosis virus (NNV) in populations of adult barramundi Lates calcarifer in Australia. Serum samples collected between 2002 and 2012 were analyzed with indirect ELISA (n = 468). Most of the samples were sourced from broodstock with unknown exposure history, and these were compared with reference populations with confirmed history of exposure to NNV. Non-lethally collected gonad fluid samples from economically valuable barramundi broodstock (n = 164) were tested for the presence of NNV using RT-quantitative PCR at the time of blood sampling to compare infectivity with serostatus, but no virus was detected. NNV-specific immunoreactivity in broodstock was significantly lower than that for immunized and persistently infected populations. Seroprevalence increased over time in broodstock sampled longitudinally, probably reflecting repeated exposure to NNV in a region where the virus was endemic. The seroprevalence for the broodstock was 23.8% over the entire sample period while a cross-sectional survey conducted in 2012 found a seroprevalence of 34.5% with no significant difference between populations based on the geographic region or the history of occurrence of viral nervous necrosis (VNN) disease in the progeny in the respective hatcheries. Although serological surveillance was useful for studying the history of exposure of barramundi to NNV, the lack of association between serostatus in broodstock and the subsequent occurrence of VNN disease in their progeny indicates that ELISA tests for anti-NNV antibodies are not suitable for the purpose of preventing vertical transmission of NNV in barramundi.

Redox signaling in acute pancreatitis

PubMed Central

Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

2015-01-01

Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis. PMID:25778551

Necrosis of the tail of pancreas following proximal splenic artery embolization.

PubMed

Talving, Peep; Rauk, Mariliis; Vipp, Liisa; Isand, Karl-Gunnar; Šamarin, Aleksandr; Põder, Kalle; Rätsep, Indrek; Saar, Sten

2016-05-13

The current case report presents a rare complication of a significant pancreatic tail necrosis following proximal splenic artery embolization in a 32-year-old male patient involved in a motorcycle accident. Proximal angiographic embolization of the splenic injury after trauma is a widely accepted method with excellent success rate; however, possible complications may occur and has been described in the literature. Nevertheless, only a few case reports pertinent to clinically significant pancreatic tail necrosis after the SAE has been reported. Thus, we add a case report to the scarce literature pertinent to this detrimental and rare complication. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2016.

The complete genome structure and phylogenetic relationship of infectious hematopoietic necrosis virus

USGS Publications Warehouse

Morzunov , Sergey P.; Winton, James R.; Nichol, Stuart T.

1995-01-01

Infectious hematopoietic necrosis virus (IHNV), a member of the family Rhabdoviridae, causes a severe disease with high mortality in salmonid fish. The nucleotide sequence (11, 131 bases) of the entire genome was determined for the pathogenic WRAC strain of IHNV from southern Idaho. This allowed detailed analysis of all 6 genes, the deduced amino acid sequences of their encoded proteins, and important control motifs including leader, trailer and gene junction regions. Sequence analysis revealed that the 6 virus genes are located along the genome in the 3′ to 5′ order: nucleocapsid (N), polymerase-associated phosphoprotein (P or M1), matrix protein (M or M2), surface glycoprotein (G), a unique non-virion protein (NV) and virus polymerase (L). The IHNV genome RNA was found to have highly complementary termini (15 of 16 nucleotides). The gene junction regions display the highly conserved sequence UCURUC(U)7RCCGUG(N)4CACR (in the vRNA sense), which includes the typical rhabdovirus transcription termination/polyadenylation signal and a novel putative transcription initiation signal. Phylogenetic analysis of M, G and L protein sequences allowed insights into the evolutionary and taxonomic relationship of rhabdoviruses of fish relative to those of insects or mammals, and a broader sense of the relationship of non-segmented negative-strand RNA viruses. Based on these data, a new genus, piscivirus, is proposed which will initially contain IHNV, viral hemorrhagic septicemia virus and Hirame rhabdovirus.

Natural History of Gas Configurations and Encapsulation in Necrotic Collections During Necrotizing Pancreatitis.

PubMed

van Grinsven, Janneke; van Brunschot, Sandra; van Baal, Mark C; Besselink, Marc G; Fockens, Paul; van Goor, Harry; van Santvoort, Hjalmar C; Bollen, Thomas L

2018-05-11

Decision-making on invasive intervention in patients with clinical signs of infected necrotizing pancreatitis is often related to the presence of gas configurations and the degree of encapsulation in necrotic collections on imaging. Data on the natural history of gas configurations and encapsulation in necrotizing pancreatitis are, however, lacking. A post hoc analysis was performed of a previously described prospective cohort in 21 Dutch hospitals (2004-2008). All computed tomography scans (CTs) performed during hospitalization for necrotizing pancreatitis were categorized per week (1 to 8, and thereafter) and re-assessed by an abdominal radiologist. A total of 639 patients with necrotizing pancreatitis were included, with median four (IQR 2-7) CTs per patient. The incidence of first onset of gas configurations varied per week without a linear correlation: 2-3-13-11-10-19-12-21-12%, respectively. Overall, gas configurations were found in 113/639 (18%) patients and in 113/202 (56%) patients with infected necrosis. The incidence of walled-off necrosis increased per week: 0-3-12-39-62-76-93-97-100% for weeks 1-8 and thereafter respectively. Clinically relevant walled-off necrosis (largely or fully encapsulated necrotic collections) was seen in 162/379 (43%) patients within the first 3 weeks. Gas configurations occur in every phase of the disease and develop in half of the patients with infected necrotizing pancreatitis. Opposed to traditional views, clinically relevant walled-off necrosis occurs frequently within the first 3 weeks.

Appearance and quantification of infectious hematopoietic necrosis virus in female sockeye salmon (Oncorhynchus nerka) during their spawning migration

USGS Publications Warehouse

Mulcahy, D.; Jenes, C.K.; Pascho, R.J.

1984-01-01

The incidence and amount of infectious hematopoietic necrosis (IHN) virus was determined in 10 organs and body fluids from each of 100 female sockeye salmon(Oncorhynchus nerka) before, during, and after their spawning migration into freshwater. Virus was found in high concentrations only in fish sampled during and after spawning. Infection rates increased from nil to 100 percent within 2 weeks. In spawning fish, incidences of IHN virus were high in all organs and fluids except brain and serum, and the highest concentrations were in the pyloric caeca and lower gut. Immediately before spawning, IHN virus was found most frequently in the gills, less frequently in the pyloric caeca and spleen, and rarely in other organs.

Vertical transmission of infectious hematopoietic necrosis virus in sockeye salmon (Oncorhynchus nerka): Isolation of virus from dead eggs and fry

USGS Publications Warehouse

Mulcahy, D.; Pascho, R.J.

1985-01-01

The control of epizootics of infectious haematopoietic necrosis (IHN) virus in salmonid fishes is presently based on examination and certification of adult brood fish to prevent the introduction of virus-infected eggs into hatcheries (Canadian Fisheries and Marine Service 1976; McDaniel 1979). This strategy is based on the assumption that the virus is vertically transmitted in association with the gametes. However, evidence for vertical transmission of IHN virus is circumstantial, based mostly on the appearance of the disease outside the enzootic area (the west coast of North America) in fish hatched from eggs obtained from within that area (Plumb 1972; Holway & Smith 1973; Wolf, Quimby, Pettijohn & Landolt 1973; Sano, Nishimura, Okamoto, Yamazaki, Hanada & Watanabe1977; Carlisle, Schat & Elston 1979). An indirect demonstration of vertical transmission was made by placing known virus-free fish in the water above and below raceways containing fish that suffered an IHN epizootic in an effort to eliminate waterborne virus as a source of infection (Wingfield & Chan 1970). The fish placed below the raceway developed IHN, due to waterborne virus released from the affected fish in the raceway, but the fish placed above the raceway failed to develop IHN. These results suggested that the source of infection of the fish in the raceway was not the water supply, although it is possible that the virus was no longer present in the water supply at the time the sentinel fish were exposed to the water.

The ORF1 Products of Tombusviruses Play a Crucial Role in Lethal Necrosis of Virus-Infected Plants

PubMed Central

Burgyán, József; Hornyik, Csaba; Szittya, György; Silhavy, Dániel; Bisztray, György

2000-01-01

Hybrids of cymbidium ringspot (CymRSV) and carnation Italian ringspot (CIRV) tombusviruses were used to identify viral symptom determinants responsible for the generalized necrosis in tombusvirus-infected plants. Surprisingly, symptoms of Nicotiana benthamiana infected with CymRSV/CIRV hybrids were distinctly different. It was demonstrated that not all chimeras expressing wild-type (wt) levels of p19 protein caused systemic necrosis as both parents CymRSV and CIRV did. We showed here that hybrids containing chimeric ORF1 were not able to induce lethal necrosis even if the viral replication of these constructs was not altered significantly. However, if a wt p33 (product of ORF1) of CymRSV was provided in trans in transgenic plants expressing p33 and its readthrough product p92, the lethal necrosis characteristic to tombusvirus infection was restored. In addition, the expression of p33 by a potato virus X viral vector in N. benthamiana caused severe chlorosis and occasionally necrosis, indicating the importance of p33 in wt symptoms of tombusviruses. Thus, our results provide evidence that elicitation of the necrotic phenotype requires the presence of the wt p33 in addition to the p19 protein of tombusviruses. PMID:11069981

Testing of male sockeye salmon (Oncorhynchus nerka) and steelhead trout (Salmo gairdneri) for infectious hematopoietic necrosis virus

USGS Publications Warehouse

Mulcahy, D.; Pascho, R.J.; Batts, W.N.

1987-01-01

Infectious hematopoietic necrosis (IHN) virus has been isolated only rarely from whole milt samples of male sockeye salmon (Oncorhynchus nerka). In 3 yr of testing, virus incidences in males ranged from 0 to 13% when milt was sampled but were 60–100% with spleen or kidney. When IHN virus was isolated from sockeye salmon milt at titers less than 3.00 log10 plaque-forming units (pfu)/mL, the level of virus in the kidney or spleen exceeded 7.00 log10 pfu/g. Higher rates of IHN virus isolation from kidney or spleen than from milt were also generally found in steelhead trout (Salmo gairdneri), although the differences were less pronounced than in sockeye salmon. Furthermore, virus was sometimes isolated from steelhead trout milt when the level of virus in kidney or spleen samples was very low, and was recovered from some milt samples when none was isolated from the corresponding spleen sample. When male salmonids are tested for IHN virus, kidney or spleen samples are superior to whole milt, but milt should be included for critical examinations.

Herpes Simplex Virus 1 (HSV-1) and HSV-2 Mediate Species-Specific Modulations of Programmed Necrosis through the Viral Ribonucleotide Reductase Large Subunit R1

PubMed Central

Yu, Xiaoliang; Li, Yun; Chen, Qin; Su, Chenhe; Zhang, Zili; Yang, Chengkui; Hu, Zhilin; Hou, Jue; Zhou, Jinying; Gong, Ling; Jiang, Xuejun

2015-01-01

ABSTRACT Receptor-interacting protein kinase 3 (RIP3) and its substrate mixed-lineage kinase domain-like protein (MLKL) are core regulators of programmed necrosis. The elimination of pathogen-infected cells by programmed necrosis acts as an important host defense mechanism. Here, we report that human herpes simplex virus 1 (HSV-1) and HSV-2 had opposite impacts on programmed necrosis in human cells versus their impacts in mouse cells. Similar to HSV-1, HSV-2 infection triggered programmed necrosis in mouse cells. However, neither HSV-1 nor HSV-2 infection was able to induce programmed necrosis in human cells. Moreover, HSV-1 or HSV-2 infection in human cells blocked tumor necrosis factor (TNF)-induced necrosis by preventing the induction of an RIP1/RIP3 necrosome. The HSV ribonucleotide reductase large subunit R1 was sufficient to suppress TNF-induced necrosis, and its RIP homotypic interaction motif (RHIM) domain was required to disrupt the RIP1/RIP3 complex in human cells. Therefore, this study provides evidence that HSV has likely evolved strategies to evade the host defense mechanism of programmed necrosis in human cells. IMPORTANCE This study demonstrated that infection with HSV-1 and HSV-2 blocked TNF-induced necrosis in human cells while these viruses directly activated programmed necrosis in mouse cells. Expression of HSV R1 suppressed TNF-induced necrosis of human cells. The RHIM domain of R1 was essential for its association with human RIP3 and RIP1, leading to disruption of the RIP1/RIP3 complex. This study provides new insights into the species-specific modulation of programmed necrosis by HSV. PMID:26559832

Herpes Simplex Virus 1 (HSV-1) and HSV-2 Mediate Species-Specific Modulations of Programmed Necrosis through the Viral Ribonucleotide Reductase Large Subunit R1.

PubMed

Yu, Xiaoliang; Li, Yun; Chen, Qin; Su, Chenhe; Zhang, Zili; Yang, Chengkui; Hu, Zhilin; Hou, Jue; Zhou, Jinying; Gong, Ling; Jiang, Xuejun; Zheng, Chunfu; He, Sudan

2016-01-15

Receptor-interacting protein kinase 3 (RIP3) and its substrate mixed-lineage kinase domain-like protein (MLKL) are core regulators of programmed necrosis. The elimination of pathogen-infected cells by programmed necrosis acts as an important host defense mechanism. Here, we report that human herpes simplex virus 1 (HSV-1) and HSV-2 had opposite impacts on programmed necrosis in human cells versus their impacts in mouse cells. Similar to HSV-1, HSV-2 infection triggered programmed necrosis in mouse cells. However, neither HSV-1 nor HSV-2 infection was able to induce programmed necrosis in human cells. Moreover, HSV-1 or HSV-2 infection in human cells blocked tumor necrosis factor (TNF)-induced necrosis by preventing the induction of an RIP1/RIP3 necrosome. The HSV ribonucleotide reductase large subunit R1 was sufficient to suppress TNF-induced necrosis, and its RIP homotypic interaction motif (RHIM) domain was required to disrupt the RIP1/RIP3 complex in human cells. Therefore, this study provides evidence that HSV has likely evolved strategies to evade the host defense mechanism of programmed necrosis in human cells. This study demonstrated that infection with HSV-1 and HSV-2 blocked TNF-induced necrosis in human cells while these viruses directly activated programmed necrosis in mouse cells. Expression of HSV R1 suppressed TNF-induced necrosis of human cells. The RHIM domain of R1 was essential for its association with human RIP3 and RIP1, leading to disruption of the RIP1/RIP3 complex. This study provides new insights into the species-specific modulation of programmed necrosis by HSV. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-κB activity

PubMed Central

Liu, Yong; Chen, Xiao-Dong; Yu, Jiang; Chi, Jun-Lin; Long, Fei-Wu; Yang, Hong-Wei; Chen, Ke-Ling; Lv, Zhao-Ying; Zhou, Bin; Peng, Zhi-Hai; Sun, Xiao-Feng; Li, Yuan; Zhou, Zong-Guang

2017-01-01

Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of l-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor-κB (NF-κB) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-κB activation and less release of TNF-α and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that

Universal reverse-transcriptase real-time PCR for infectious hematopoietic necrosis virus (IHNV)

USGS Publications Warehouse

Purcell, Maureen K.; Thompson, Rachel L.; Garver, Kyle A.; Hawley, Laura M.; Batts, William N.; Sprague, Laura; Sampson, Corie; Winton, James R.

2013-01-01

Infectious hematopoietic necrosis virus (IHNV) is an acute pathogen of salmonid fishes in North America, Europe and Asia and is reportable to the World Organization for Animal Health (OIE). Phylogenetic analysis has identified 5 major virus genogroups of IHNV worldwide, designated U, M, L, E and J; multiple subtypes also exist within those genogroups. Here, we report the development and validation of a universal IHNV reverse-transcriptase real-time PCR (RT-rPCR) assay targeting the IHNV nucleocapsid (N) gene. Properties of diagnostic sensitivity (DSe) and specificity (DSp) were defined using laboratory-challenged steelhead trout Oncorhynchus mykiss, and the new assay was compared to the OIE-accepted conventional PCR test and virus isolation in cell culture. The IHNV N gene RT-rPCR had 100% DSp and DSe and a higher estimated diagnostic odds ratio (DOR) than virus culture or conventional PCR. The RT-rPCR assay was highly repeatable within a laboratory and highly reproducible between laboratories. Field testing of the assay was conducted on a random sample of juvenile steelhead collected from a hatchery raceway experiencing an IHN epizootic. The RT-rPCR detected a greater number of positive samples than cell culture and there was 40% agreement between the 2 tests. Overall, the RT-rPCR assay was highly sensitive, specific, repeatable and reproducible and is suitable for use in a diagnostic setting.

Modeling Virus Coinfection to Inform Management of Maize Lethal Necrosis in Kenya.

PubMed

Hilker, Frank M; Allen, Linda J S; Bokil, Vrushali A; Briggs, Cheryl J; Feng, Zhilan; Garrett, Karen A; Gross, Louis J; Hamelin, Frédéric M; Jeger, Michael J; Manore, Carrie A; Power, Alison G; Redinbaugh, Margaret G; Rúa, Megan A; Cunniffe, Nik J

2017-10-01

Maize lethal necrosis (MLN) has emerged as a serious threat to food security in sub-Saharan Africa. MLN is caused by coinfection with two viruses, Maize chlorotic mottle virus and a potyvirus, often Sugarcane mosaic virus. To better understand the dynamics of MLN and to provide insight into disease management, we modeled the spread of the viruses causing MLN within and between growing seasons. The model allows for transmission via vectors, soil, and seed, as well as exogenous sources of infection. Following model parameterization, we predict how management affects disease prevalence and crop performance over multiple seasons. Resource-rich farmers with large holdings can achieve good control by combining clean seed and insect control. However, crop rotation is often required to effect full control. Resource-poor farmers with smaller holdings must rely on rotation and roguing, and achieve more limited control. For both types of farmer, unless management is synchronized over large areas, exogenous sources of infection can thwart control. As well as providing practical guidance, our modeling framework is potentially informative for other cropping systems in which coinfection has devastating effects. Our work also emphasizes how mathematical modeling can inform management of an emerging disease even when epidemiological information remains scanty. [Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Infectious hematopoietic necrosis virus virological and genetic surveillance 2000–2012

USGS Publications Warehouse

Breyta, Rachel; Brito, Ilana L.; Kurath, Gael; LaDeau, Shannon L.

2017-01-01

Surveillance records of the acute RNA pathogen of Pacific salmonid fish infectious hematopoietic necrosis virus are combined for the first time to enable landscape-level ecological analyses and modeling. The study area is the freshwater ecosystems of the large Columbia River watershed in the U.S. states of Washington, Oregon, and Idaho, as well as coastal rivers in Washington and Oregon. The study period is 2000–2012, and records were contributed by all five resource management agencies that operate conservation hatcheries in the study area. Additional records from wild fish were collected from the National Wild Fish Health Survey, operated by the U.S. Fish and Wildlife Survey. After curation and normalization, the data set consists of 6766 records, representing 1146 sample sites and 15 different fish hosts. The virus was found in an average of 12.4% of records, and of these 66.2% also have viral genetic analysis available. This data set is used to conduct univariate ecological and epidemiological analyses and develop a novel hierarchical landscape transmission model for an aquatic pathogen.

Pathogenic mechanisms of pancreatitis

PubMed Central

Manohar, Murli; Verma, Alok Kumar; Venkateshaiah, Sathisha Upparahalli; Sanders, Nathan L; Mishra, Anil

2017-01-01

Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in promoting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways (i.e., Transforming growth factor-β/SMAD, mitogen-activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8 IL-10, IL-18, IL-33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for

[Prevention and treatment of post-traumatic pancreatic necrosis in patients with blunt abdominal trauma].

PubMed

Cherdantsev, D V; Pervova, O V; Vinnik, Iu S; Kurbanov, D Sh

2016-01-01

High incidence of necrotic and suppurative complications is feature of acute post-traumatic pancreatitis. Severe trauma of the pancreas and post-traumatic pancreatitis lead to depressurization of ductal system that requires adequate drainage of damaged area and retroperitoneal fat. 95 patients in group 1 received standardized treatment. The victims of the 2nd group (44 patients) were treated using immunoreactive therapy (roncoleukin) and octreotide (the dose depended on the severity of pancreatitis) at early stages. The efficacy of treatment was assessed based on clinical, laboratory and instrumental parameters. Regardless severity of pancreatic injury overall mortality in groups 1 and 2 was 41% and 20.5% respectively. The main causes of adverse outcomes are severe destructive pancreatitis, postnecrotic suppurative complications. Adequacy rather radicalism of surgery should be preferred for blunt pancreatic trauma management. Minimally invasive surgical techniques and new methods of biological hemostasis may be applied. Timely use of anti-enzymatic and immunoactive therapy reduces the risk of severe post-traumatic pancreatitis, suppurative complications and improves outcomes in patients with blunt pancreatic trauma.

Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis.

PubMed

Ahmed Ali, Usama; Issa, Yama; Hagenaars, Julia C; Bakker, Olaf J; van Goor, Harry; Nieuwenhuijs, Vincent B; Bollen, Thomas L; van Ramshorst, Bert; Witteman, Ben J; Brink, Menno A; Schaapherder, Alexander F; Dejong, Cornelis H; Spanier, B W Marcel; Heisterkamp, Joos; van der Harst, Erwin; van Eijck, Casper H; Besselink, Marc G; Gooszen, Hein G; van Santvoort, Hjalmar C; Boermeester, Marja A

2016-05-01

episode of acute pancreatitis leads to recurrent pancreatitis in 17% of patients, and almost 8% of patients progress to CP within 5 years. Progression was associated independently with alcoholic etiology, smoking, and a history of pancreatic necrosis. Smoking is the predominant risk factor for recurrent disease, whereas the combination of alcohol abuse and smoking produces the highest cumulative risk for chronic pancreatitis. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Drug induced acute pancreatitis: incidence and severity.

PubMed Central

Lankisch, P G; Dröge, M; Gottesleben, F

1995-01-01

To determine the incidence and severity of drug induced acute pancreatitis, data from 45 German centres of gastroenterology were evaluated. Among 1613 patients treated for acute pancreatitis in 1993, drug induced acute pancreatitis was diagnosed in 22 patients (incidence 1.4%). Drugs held responsible were azathioprine, mesalazine/sulfasalazine, 2',3'-dideoxyinosine (ddI), oestrogens, frusemide, hydrochlorothiazide, and rifampicin. Pancreatic necrosis not exceeding 33% of the organ was found on ultrasonography or computed tomography, or both, in three patients (14%). Pancreatic pseudocysts did not occur. A decrease of arterial PO2 reflecting respiratory insufficiency, and an increase of serum creatinine, reflecting renal insufficiency as complications of acute pancreatitis were seen in two (9%) and four (18%) patients, respectively. Artificial ventilation was not needed, and dialysis was necessary in only one (5%) case. Two patients (9%) died of AIDS and tuberculosis, respectively; pancreatitis did not seem to have contributed materially to their death. In conclusion, drugs rarely cause acute pancreatitis, and drug induced acute pancreatitis usually runs a benign course. PMID:7489946

Vertical transmission of infectious haematopoietic necrosis virus in sockeye salmon, Oncorhynchus nerka (Walbaum): isolation of virus from dead eggs and fry

USGS Publications Warehouse

Mulcahy, D.; Pascho, R.J.

1985-01-01

The control of epizootics of infectious haematopoietic necrosis (IIHN) virus in salmonid fishes is presently based on examination and certification of adult brood fish to prevent the introduction of virus-infected eggs into hatcheries (Canadian Fisherics and Marine Service 1976; McDaniel 1979). This strategy is based on the assumption that the virus is vertically transmitted in association with the gametes. However, evidence for vertical transmission of lHN virus is circumstantial, based mostly on the appearance of the disease outside the enzootic area (the west coast of North America) in fish hatched from eggs obtained from within that area (Plumb 1972; Holway & Smith 1973; Wolf, Quimby, Pettijohn & Landolt 1973, Sano, Nishimura, Okamoto, Yamazaki, Hanada & Watanabe 1977. Carlisle, Schat & Elston 1979). An indirect demonstration of vertical transmission was made by placing known virus-free fish in the water above and below raceways containing fish that suffered an IEEN epizootic in an cffort to climinate waterborne virus as a source of infection (Wingficid & Chan 1970). The fish placed below the raceway developed IHN, due to waterborne virus released from the affected fish in the raceway, but the fish placed above the raceway failed to develop IHN. These results suggested that the source of infection of the fish in the raceway was not the water supply, although it is possible that the virus was no longer present in the water supply at the time the sentinel fish were exposed to the water.

The role of endoscopic intervention in the management of inflammatory pancreatic fluid collections.

PubMed

Parihar, Vikrant; Ridgway, Paul F; Conlon, Kevin C; Huggett, Matthew; Ryan, Barbara M

2017-04-01

Pancreatic fluid collections (PFCs) are a frequent complication of pancreatitis, or less commonly, pancreatic trauma or surgery. The revised Atlanta Classification categorizes PFCs as acute or chronic, with further subclassification of acute collections into acute peripancreatic collections and acute necrotic collections and of chronic fluid collections into pseudocysts and walled-off pancreatic necrosis. Acute PFCs are generally only subjected to an intervention when they are infected and not responding to antibiotics and are not managed endoscopically. Chronic PFCs, both pseudocysts and walled-off pancreatic necrosis, require intervention only when symptomatic or enlarging over time. Endoscopic ultrasound-guided drainage has become the mainstay of management for chronic PFCs that require intervention. Developments in medical devices over the past few years have significantly simplified and shortened the duration of the procedure itself, but the optimum choice of stent in different clinical scenarios remains to be defined, as does the place of endoscopic necrosectomy. To optimize outcomes, these patients should undergo a careful preprocedure workup and discussion in a multidisciplinary environment and procedures should be carried out in high-volume pancreatic units.

Comparison of genome size and synthesis of structural proteins of Hirame Rhabdovirus, infectious hematopoietic necrosis virus, and viral hemorrhagic Septicemia virus

USGS Publications Warehouse

Nishizawa, Toyohiko; Yoshimizu, Mamoru; Winton, James R.; Kimura, Takahisa

1991-01-01

Genomic RNA was extracted from purified virions of hirame rhabdovirus (HRV), infectious hematopoietic necrosis virus (IHNV), and viral hemorrhagic septicemia virus (VHSV). The full-length RNA was analyzed using formaldehyde agarose gel electrophoresis followed by ethidium bromide staining. Compared with an internal RNA size standard, all three viral genomic RNAs appeared to have identical relative mobilities and were estimated to be approximately 10.7 kilobases in length or about 3.7 megadaltons in molecular mass. Structural protein synthesis of HRV, IHNV, and VHSV was studied using cell cultures treated with actinomycin D. At 2 h intervals, proteins were labeled with 35S-methionine, extracted, and analyzed by SDS-polyacrylamide gel electrophoresis and autoradiography. The five structural proteins of each of the three viruses appeared in the following order : nucleoprotein (N), matrix protein 1 (M1), matrix protein 2 (M2), glycoprotein (G), and polymerase (L) reflecting both the approximate relative abundance of each protein within infected cells and the gene order within the viral genome.

Mitochondrial function and malfunction in the pathophysiology of pancreatitis.

PubMed

Gerasimenko, Oleg V; Gerasimenko, Julia V

2012-07-01

As a primary energy producer, mitochondria play a fundamental role in pancreatic exocrine physiology and pathology. The most frequent aetiology of acute pancreatitis is either gallstones or heavy alcohol consumption. Repeated episodes of acute pancreatitis can result in the development of chronic pancreatitis and increase the lifetime risk of pancreatic cancer 100-fold. Pancreatic cancer is one of the most common causes of cancer mortality with only about 3-4 % of patients surviving beyond 5 years. It has been shown that acute pancreatitis involves Ca²⁺ overload and overproduction of reactive oxygen species in pancreatic acinar cells. Both factors significantly affect mitochondria and lead to cell death. The pathogenesis of inflammation in acute and chronic pancreatitis is tightly linked to the induction of necrosis and apoptosis. There is currently no specific therapy for pancreatitis, but recent findings of an endogenous protective mechanism against Ca²⁺ overload--and particularly the potential to boost this protection--bring hope of new therapeutic approaches.

Animal models for investigating chronic pancreatitis

PubMed Central

2011-01-01

Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed. PMID:22133269

Pathology of natural infections by H5N1 highly pathogenic avian influenza virus in mute (Cygnus olor) and whooper (Cygnus cygnus) swans.

PubMed

Teifke, J P; Klopfleisch, R; Globig, A; Starick, E; Hoffmann, B; Wolf, P U; Beer, M; Mettenleiter, T C; Harder, T C

2007-03-01

Mortality in wild aquatic birds due to infection with highly pathogenic avian influenza viruses (HPAIV) is a rare event. During the recent outbreak of highly pathogenic avian influenza in Germany, mortality due to H5N1 HPAIV was observed among mute and whooper swans as part of a rapid spread of this virus. In contrast to earlier reports, swans appeared to be highly susceptible and represented the mainly affected species. We report gross and histopathology and distribution of influenza virus antigen in mute and whooper swans that died after natural infection with H5N1 HPAIV. At necropsy, the most reliable lesions were multifocal hemorrhagic necrosis in the pancreas, pulmonary congestion and edema, and subepicardial hemorrhages. Major histologic lesions were acute pancreatic necrosis, multifocal necrotizing hepatitis, and lymphoplasmacytic encephalitis with neuronal necrosis. Adrenals displayed consistently scattered cortical and medullary necrosis. In spleen and Peyer's patches, mild lymphocyte necrosis was present. Immunohistochemical demonstration of HPAIV nucleoprotein in pancreas, adrenals, liver, and brain was strongly consistent with histologic lesions. In the brain, a large number of neurons and glial cells, especially Purkinje cells, showed immunostaining. Occasionally, ependymal cells of the spinal cord were also positive. In the lungs, influenza virus antigen was identified in a few endothelial cells but not within pneumocytes. The infection of the central nervous system supports the view that the neurotropism of H5N1 HPAIV leads to nervous disturbances with loss of orientation. More investigations are necessary to clarify the mechanisms of the final circulatory failure, lung edema, and rapid death of the swans.

[Acute pancreatitis associated with hypercalcaemia].

PubMed

Tun-Abraham, Mauro Enrique; Obregón-Guerrero, Gabriela; Romero-Espinoza, Larry; Valencia-Jiménez, Javier

2015-01-01

Hypercalcaemia due to primary hyperparathyroidism is a rare cause of acute pancreatitis, with a reported prevalence of 1.5 to 8%. There is no clear pathophysiological basis, but elevated parathyroid hormone and high serum calcium levels could be responsible for calcium deposit in the pancreatic ducts and activation of pancreatic enzymes, which may be the main risk factor for developing acute pancreatitis. The aim of this report is to describe four cases. Four cases are reported of severe pancreatitis associated with hypercalcaemia secondary to primary hyperparathyroidism; three of them with complications (two pseudocysts and one pancreatic necrosis). Cervical ultrasound, computed tomography, and scintigraphy using 99mTc-Sestambi, studies showed the parathyroid adenoma. Surgical resection was the definitive treatment in all four cases. None of the patients had recurrent acute pancreatitis events during follow-up. Acute pancreatitis secondary to hypercalcaemia of primary hyperparathyroidism is rare; however, when it occurs it is associated with severe pancreatitis. It is suspected in patients with elevated serum calcium and high parathyroid hormone levels. Imaging techniques such as cervical ultrasound, computed tomography, and scintigraphy using 99mTc-Sestambi, should be performed, to confirm clinical suspicion. Surgical resection is the definitive treatment with excellent results. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Necroptosis: a potential, promising target and switch in acute pancreatitis.

PubMed

Wang, Gang; Qu, Feng-Zhi; Li, Le; Lv, Jia-Chen; Sun, Bei

2016-02-01

Pancreatic acinar cell death is the major pathophysiological change in early acute pancreatitis (AP), and the death modalities are important factors determining its progression and prognosis. During AP, acinar cells undergo two major modes of death, including necrosis and apoptosis. Acinar necrosis can lead to intensely local and systemic inflammatory responses, which both induce and aggravate the lesion. Necrosis has long been considered an unregulated, and passive cell death process. Since the effective interventions of necrosis are difficult to perform, its relevant studies have not received adequate attention. Necroptosis is a newly discovered cell death modality characterized by both necrosis and apoptosis, i.e., it is actively regulated by special genes, while has the typical morphological features of necrosis. Currently, necroptosis is gradually becoming an important topic in the fields of inflammatory diseases. The preliminary results from necroptosis in AP have confirmed the existence of acinar cell necroptosis, which may be a potential target for effectively regulating inflammatory injuries and improving its outcomes; however, the functional changes and mechanisms of necroptosis still require further investigation. This article reviewed the progress of necroptosis in AP to provide a reference for deeply understanding the pathogenic mechanisms of AP and identifying new therapeutic targets.

[Percutaneous ultrasound-guided drainage in the surgical treatment of acute severe pancreatitis].

PubMed

Delattre, J-F; Levy Chazal, N; Lubrano, D; Flament, J-B

2004-11-01

To report results of percutaneous ultrasound-guided drainage, performed by a surgeon, in the treatment of complications of acute pancreatitis (AP), and to determine the role of this technique in the therapeutic armamentarium of severe AP. From 1986 to 2001, 59 patients were included in this retrospective study. All patients initially had severe necrotizing AP (mean Ranson score = 4.1 ; range : 2-7). Anatomical lesions included pancreatic abscess in 6 patients and necrosis in 53 (17 stage D and 36 stage E according to Balthazar's classification). Necrosis was infected in 42 and sterile in 11 respectively. Drainage was performed under ultrasound guidance and local anaesthesia using small-diameter drains (7-14 French). Drainage was performed on average 23 days after onset of AP. Infection was proven by fine-needle aspiration in 47 (80 %) patients (41 infected necrosis and 6 localized abscess). In one patient, culture of aspirated fluid was negative but necrosis was infected (one false negative). Culture of aspirated fluid was negative and necrosis was sterile in 11 patients. Nineteen (32%) patients healed without subsequent surgery: 7 (16%) in the infected necrosis group, 6(55%) in the sterile necrosis group, and 6 (100%) in the abscess group. Forty (68%) patients had subsequent necrosectomy including 8 (14%) who died. Twenty (34 %) digestive fistulas healed spontaneously, except one treated by diversion stomia. Of the 16 (27 %) pancreatic fistulas, 6 needed subsequent interventional treatment. In selected patients, percutaneous drainage can represent an alternative to surgery with a 14% mortality rate. The high rate of subsequent necrosectomy suggests that drains with larger diameter, possibly associated with continuous irrigation, should be used.

Dextrans produced by lactic acid bacteria exhibit antiviral and immunomodulatory activity against salmonid viruses.

PubMed

Nácher-Vázquez, Montserrat; Ballesteros, Natalia; Canales, Ángeles; Rodríguez Saint-Jean, Sylvia; Pérez-Prieto, Sara Isabel; Prieto, Alicia; Aznar, Rosa; López, Paloma

2015-06-25

Viral infections in the aquaculture of salmonids can lead to high mortality and substantial economic losses. Thus, there is industrial interest in new molecules active against these viruses. Here we describe the production, purification, and the physicochemical and structural characterization of high molecular weight dextrans synthesized by Lactobacillus sakei MN1 and Leuconostoc mesenteroides RTF10. The purified dextrans, and commercial dextrans with molecular weights ranging from 10 to 2000kDa, were assayed in infected BF-2 and EPC fish cell-line monolayers for antiviral activity. Only T2000 and dextrans from MN1 and RTF10 had significant antiviral activity. This was similar to results obtained against infectious pancreatic necrosis virus. However the dextran from MN1 showed ten-fold higher activity against hematopoietic necrosis virus than T2000. In vivo assays using the MN1 polymer confirmed the in vitro results and revealed immunomodulatory activity. These results together with the high levels of dextran production (2gL(-1)) by Lb. sakei MN1, indicate the compounds potential utility as an antiviral agent in aquaculture. Copyright © 2015 Elsevier Ltd. All rights reserved.

Strains of infectious hematopoietic necrosis (IHN) virus may be identified by structural protein differences

USGS Publications Warehouse

Leong, J.C.; Hsu, Ya Li; Engelking, H. Mark; Mulcahy, Daniel M.; Anderson, D.P.

1981-01-01

The development of an effective vaccine to infectious hematopoietic necrosis virus (IHNV) in fish requires a knowledge of the virus serotypes in nature. At least two serotypes were found among three IHNV strains (12). Attempts in our laboratory to extend this study with additional virus strains by classical immunological techniques were unsatisfactory. Thus, we sought another method for comparing IHNV strains. We report here that different strains of IHNV can be distinguished by the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the viron polypeptides. Major strain differences were noted in the molecular weights of the envelope glycoprotein, G, and the nucleocapsid protein, N.The strains of IHNV were established from samples taken at several locations in California, Oregon, Washington, and Alaska. These strains were also characterized by growth rate at 15° and 18°C and average plaque size. Distinct differences in growth rate at the two temperatures were found for the California strains. The California strains were distinguished from the other strains by the production of minute plaques.

Effects of long term feeding of raw soya bean flour on virus-induced pancreatic carcinogenesis in guinea fowl.

PubMed

Kirev, T; Woutersen, R A; Kiril, A

1999-01-29

The effects of a diet enriched with 25% raw soya bean flour (RSF) on the pancreas and on the avian retrovirus Pts 56-induced pancreatic carcinogenesis in guinea fowl were studied. It has been shown that prolonged RSF feeding of new-hatched virus-infected and uninfected guinea fowl-poults induced enlargement of the pancreas, which was less pronounced when administration of the RSF supplemented diet started at the age of 75 days. Time-dependent multifocal inter- and intralobular hyperplasia of pleomorphic ducts lined by mucin-producing epithelium in the exocrine pancreas of virus-infected guinea fowls fed a RSF supplemented diet was regularly observed. Enlargement of virus-induced ductular neoplasms has been shown only after simultaneous RSF and virus administration.

Replication and shedding kinetics of infectious hematopoietic necrosis virus in juvenile rainbow trout

USGS Publications Warehouse

Wargo, Andrew R.; Scott, Robert J.; Kerr, Benjamin; Kurath, Gael

2017-01-01

Viral replication and shedding are key components of transmission and fitness, the kinetics of which are heavily dependent on virus, host, and environmental factors. To date, no studies have quantified the shedding kinetics of infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss), or how they are associated with replication, making it difficult to ascertain the transmission dynamics of this pathogen of high agricultural and conservation importance. Here, the replication and shedding kinetics of two M genogroup IHNV genotypes were examined in their naturally co-evolved rainbow trout host. Within host virus replication began rapidly, approaching maximum values by day 3 post-infection, after which viral load was maintained or gradually dropped through day 7. Host innate immune response measured as stimulation of Mx-1 gene expression generally followed within host viral loads. Shedding also began very quickly and peaked within 2 days, defining a generally uniform early peak period of shedding from 1 to 4 days after exposure to virus. This was followed by a post-peak period where shedding declined, such that the majority of fish were no longer shedding by day 12 post-infection. Despite similar kinetics, the average shedding rate over the course of infection was significantly lower in mixed compared to single genotype infections, suggesting a competition effect, however, this did not significantly impact the total amount of virus shed. The data also indicated that the duration of shedding, rather than peak amount of virus shed, was correlated with fish mortality. Generally, the majority of virus produced during infection appeared to be shed into the environment rather than maintained in the host, although there was more retention of within host virus during the post-peak period. Viral virulence was correlated with shedding, such that the more virulent of the two genotypes shed more total virus. This fundamental understanding of IHNV

Replication and shedding kinetics of infectious hematopoietic necrosis virus in juvenile rainbow trout.

PubMed

Wargo, Andrew R; Scott, Robert J; Kerr, Benjamin; Kurath, Gael

2017-01-02

Viral replication and shedding are key components of transmission and fitness, the kinetics of which are heavily dependent on virus, host, and environmental factors. To date, no studies have quantified the shedding kinetics of infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss), or how they are associated with replication, making it difficult to ascertain the transmission dynamics of this pathogen of high agricultural and conservation importance. Here, the replication and shedding kinetics of two M genogroup IHNV genotypes were examined in their naturally co-evolved rainbow trout host. Within host virus replication began rapidly, approaching maximum values by day 3 post-infection, after which viral load was maintained or gradually dropped through day 7. Host innate immune response measured as stimulation of Mx-1 gene expression generally followed within host viral loads. Shedding also began very quickly and peaked within 2days, defining a generally uniform early peak period of shedding from 1 to 4days after exposure to virus. This was followed by a post-peak period where shedding declined, such that the majority of fish were no longer shedding by day 12 post-infection. Despite similar kinetics, the average shedding rate over the course of infection was significantly lower in mixed compared to single genotype infections, suggesting a competition effect, however, this did not significantly impact the total amount of virus shed. The data also indicated that the duration of shedding, rather than peak amount of virus shed, was correlated with fish mortality. Generally, the majority of virus produced during infection appeared to be shed into the environment rather than maintained in the host, although there was more retention of within host virus during the post-peak period. Viral virulence was correlated with shedding, such that the more virulent of the two genotypes shed more total virus. This fundamental understanding of IHNV shedding

Replication and shedding kinetics of infectious hematopoietic necrosis virus in juvenile rainbow trout

PubMed Central

Wargo, Andrew R.; Scott, Robert J.; Kerr, Benjamin; Kurath, Gael

2016-01-01

Viral replication and shedding are key components of transmission and fitness, the kinetics of which are heavily dependent on virus, host, and environmental factors. To date, no studies have quantified the shedding kinetics of infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss), or how they are associated with replication, making it difficult to ascertain the transmission dynamics of this pathogen of high agricultural and conservation importance. Here, the replication and shedding kinetics of two M genogroup IHNV genotypes were examined in their naturally co-evolved rainbow trout host. Within host virus replication began rapidly, approaching maximum values by day 3 post-infection, after which viral load was maintained or gradually dropped through day 7. Host innate immune response measured as stimulation of Mx-1 gene expression generally followed within host viral loads. Shedding also began very quickly and peaked within 2 days, defining a generally uniform early peak period of shedding from 1 to 4 days after exposure to virus. This was followed by a post-peak period where shedding declined, such that the majority offish were no longer shedding by day 12 post-infection. Despite similar kinetics, the average shedding rate over the course of infection was significantly lower in mixed compared to single genotype infections, suggesting a competition effect, however, this did not significantly impact the total amount of virus shed. The data also indicated that the duration of shedding, rather than peak amount of virus shed, was correlated with fish mortality. Generally, the majority of virus produced during infection appeared to be shed into the environment rather than maintained in the host, although there was more retention of within host virus during the post-peak period. Viral virulence was correlated with shedding, such that the more virulent of the two genotypes shed more total virus. This fundamental understanding of IHNV

Legumain is activated in macrophages during pancreatitis

PubMed Central

Wartmann, Thomas; Fleming, Alicia K.; Gocheva, Vasilena; van der Linden, Wouter A.; Withana, Nimali P.; Verdoes, Martijn; Aurelio, Luigi; Edgington-Mitchell, Daniel; Lieu, TinaMarie; Parker, Belinda S.; Graham, Bim; Reinheckel, Thomas; Furness, John B.; Joyce, Johanna A.; Storz, Peter; Halangk, Walter; Bogyo, Matthew; Bunnett, Nigel W.

2016-01-01

Pancreatitis is an inflammatory disease of the pancreas characterized by dysregulated activity of digestive enzymes, necrosis, immune infiltration, and pain. Repeated incidence of pancreatitis is an important risk factor for pancreatic cancer. Legumain, a lysosomal cysteine protease, has been linked to inflammatory diseases such as atherosclerosis, stroke, and cancer. Until now, legumain activation has not been studied during pancreatitis. We used a fluorescently quenched activity-based probe to assess legumain activation during caerulein-induced pancreatitis in mice. We detected activated legumain by ex vivo imaging, confocal microscopy, and gel electrophoresis. Compared with healthy controls, legumain activity in the pancreas of caerulein-treated mice was increased in a time-dependent manner. Legumain was localized to CD68+ macrophages and was not active in pancreatic acinar cells. Using a small-molecule inhibitor of legumain, we found that this protease is not essential for the initiation of pancreatitis. However, it may serve as a biomarker of disease, since patients with chronic pancreatitis show strongly increased legumain expression in macrophages. Moreover, the occurrence of legumain-expressing macrophages in regions of acinar-to-ductal metaplasia suggests that this protease may influence reprogramming events that lead to inflammation-induced pancreatic cancer. PMID:27514475

Evidence for a carrier state of infectious hematopoietic necrosis virus in chinook salmon Oncorhynchus tshawytscha.

PubMed

St Hilaire, S; Ribble, C; Traxler, G; Davies, T; Kent, M L

2001-10-08

In British Columbia, Canada, infectious hematopoietic necrosis virus (IHNV) is prevalent in wild sockeye salmon Oncorhynchus nerka and has caused disease in seawater net-pen reared Atlantic salmon Salmo salar. In this study, chinook salmon Oncorhynchus tshawytscha experimentally exposed to an isolate of IHNV found in British Columbia became carriers of the virus. When Atlantic salmon were cohabited with these virus-exposed chinook salmon, IHNV was isolated from the Atlantic salmon. Identification of chinook salmon populations that have been exposed to IHNV may be difficult, as virus isolation was successful only in fish that were concurrently infected with either Renibacterium salmoninarum or Piscirickettisia salmonis. Also, IHNV-specific antibodies were detected in only 2 of the 70 fish experimentally exposed to the virus. Two samples collected from chinook salmon exposed to IHNV while at a salt water net-pen site had a seroprevalence of 19 and 22%; however, the inconsistencies between our laboratory and field data suggest that further research is required before we can rely on serological analysis for identifying potential carrier populations. Because of the difficulty in determining the exposure status of populations of chinook salmon, especially if there is no concurrent disease, it may be prudent not to cohabit Atlantic salmon with chinook salmon on a farm if there is any possibility that the latter have been exposed to the virus.

The coat protein of Alternanthera mosaic virus is the elicitor of a temperature-sensitive systemic necrosis in Nicotiana benthamiana, and interacts with a host boron transporter protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, Hyoun-Sub, E-mail: hyounlim@cnu.ac.kr; Nam, Jiryun, E-mail: jilyoon@naver.com; Seo, Eun-Young, E-mail: sey22@cnu.ac.kr

Different isolates of Alternanthera mosaic virus (AltMV; Potexvirus), including four infectious clones derived from AltMV-SP, induce distinct systemic symptoms in Nicotiana benthamiana. Virus accumulation was enhanced at 15 °C compared to 25 °C; severe clone AltMV 3-7 induced systemic necrosis (SN) and plant death at 15 °C. No interaction with potexvirus resistance gene Rx was detected, although SN was ablated by silencing of SGT1, as for other cases of potexvirus-induced necrosis. Substitution of AltMV 3-7 coat protein (CP{sub SP}) with that from AltMV-Po (CP{sub Po}) eliminated SN at 15 °C, and ameliorated symptoms in Alternanthera dentata and soybean. Substitution ofmore » only two residues from CP{sub Po} [either MN(13,14)ID or LA(76,77)IS] efficiently ablated SN in N. benthamiana. CP{sub SP} but not CP{sub Po} interacted with Arabidopsis boron transporter protein AtBOR1 by yeast two-hybrid assay; N. benthamiana homolog NbBOR1 interacted more strongly with CP{sub SP} than CP{sub Po} in bimolecular fluorescence complementation, and may affect recognition of CP as an elicitor of SN. - Highlights: • Alternanthera mosaic virus CP is an elicitor of systemic necrosis in N. benthamiana. • Virus-induced systemic necrosis is enhanced at 15 °C compared to 25 °C. • Induction of systemic necrosis is dependent on as few as two CP amino acid residues. • These residues are at subunit interfaces within the same turn of the virion helix. • Inducer/non-inducer CPs interact differentially with a boron transporter protein.« less

A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus

PubMed Central

Alejo, Alí; Ruiz-Argüello, M. Begoña; Ho, Yin; Smith, Vincent P.; Saraiva, Margarida; Alcami, Antonio

2006-01-01

Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis. PMID:16581912

A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus.

PubMed

Alejo, Alí; Ruiz-Argüello, M Begoña; Ho, Yin; Smith, Vincent P; Saraiva, Margarida; Alcami, Antonio

2006-04-11

Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis.

Characterization of infectious dose and lethal dose of two strains of infectious hematopoietic necrosis virus (IHNV)

USGS Publications Warehouse

McKenney, Douglas; Kurath, Gael; Wargo, Andrew

2016-01-01

The ability to infect a host is a key trait of a virus, and differences in infectivity could put one virus at an evolutionary advantage over another. In this study we have quantified the infectivity of two strains of infectious hematopoietic necrosis virus (IHNV) that are known to differ in fitness and virulence. By exposing juvenile rainbow trout (Oncorhynchus mykiss) hosts to a wide range of virus doses, we were able to calculate the infectious dose in terms of ID50 values for the two genotypes. Lethal dose experiments were also conducted to confirm the virulence difference between the two virus genotypes, using a range of virus doses and holding fish either in isolation or in batch so as to calculate LD50values. We found that infectivity is positively correlated with virulence, with the more virulent genotype having higher infectivity. Additionally, infectivity increases more steeply over a short range of doses compared to virulence, which has a shallower increase. We also examined the data using models of virion interaction and found no evidence to suggest that virions have either an antagonistic or a synergistic effect on each other, supporting the independent action hypothesis in the process of IHNV infection of rainbow trout.

Genetic analyses reveal unusually high diversity of infectious haematopoietic necrosis virus in rainbow trout aquaculture

USGS Publications Warehouse

Troyer, Ryan M.; LaPatra, Scott E.; Kurath, Gael

2000-01-01

Infectious haematopoietic necrosis virus (IHNV) is the most significant virus pathogen of salmon and trout in North America. Previous studies have shown relatively low genetic diversity of IHNV within large geographical regions. In this study, the genetic heterogeneity of 84 IHNV isolates sampled from rainbow trout (Oncorhynchus mykiss) over a 20 year period at four aquaculture facilities within a 12 mile stretch of the Snake River in Idaho, USA was investigated. The virus isolates were characterized using an RNase protection assay (RPA) and nucleotide sequence analyses. Among the 84 isolates analysed, 46 RPA haplotypes were found and analyses revealed a high level of genetic heterogeneity relative to that detected in other regions. Sequence analyses revealed up to 7·6% nucleotide divergence, which is the highest level of diversity reported for IHNV to date. Phylogenetic analyses identified four distinct monophyletic clades representing four virus lineages. These lineages were distributed across facilities, and individual facilities contained multiple lineages. These results suggest that co-circulating IHNV lineages of relatively high genetic diversity are present in the IHNV populations in this rainbow trout culture study site. Three of the four lineages exhibited temporal trends consistent with rapid evolution.

Simultaneous Occurrence of Varicella Zoster Virus-Induced Pancreatitis and Hepatitis in a Renal Transplant Recipient: A Case Report and Review of Literature

PubMed Central

Chhabra, Puneet; Ranjan, Priyadarshi; Bhasin, Deepak K

2017-01-01

Introduction: Gastrointestinal complications are common after renal transplantation, including oral lesions, esophagitis, gastritis, diarrhea, and colon carcinoma. The differential diagnosis is difficult in this scenario because multiple factors such as drugs, infections, and preexisting gastrointestinal disease come into play. Case Presentation: We report a case of varicella zoster virus-induced pancreatitis and hepatitis in a renal transplant recipient. The patient underwent renal transplantation 3 years earlier and now presented with severe pain in the epigastrium radiating to his back and had raised serum lipase levels and skin lesions characteristic of varicella. Liver enzyme levels were also elevated. He was started on a regimen of acyclovir. His pain improved in 24 hours, and liver enzyme levels returned to normal in 48 hours. Discussion: There is a paucity of literature on the simultaneous occurrence of varicella zoster virus-induced hepatitis and pancreatitis in both immunocompetent and immunocompromised patients. Our case highlights the gastrointestinal complications of varicella infection in immunocompromised patients that may precede the characteristic dermatologic manifestations, and the fact that rarely both hepatitis and pancreatitis may be seen. PMID:28333601

Acute retinal necrosis results in low vision in a young patient with a history of herpes simplex virus encephalitis.

PubMed

Shahi, Sanjeet K

2017-05-01

Acute retinal necrosis (ARN), secondary to herpes simplex encephalitis, is a rare syndrome that can present in healthy individuals, as well as immuno-compromised patients. Most cases are caused by a secondary infection from the herpes virus family, with varicella zoster virus being the leading cause of this syndrome. Potential symptoms include blurry vision, floaters, ocular pain and photophobia. Ocular findings may consist of severe uveitis, retinal vasculitis, retinal necrosis, papillitis and retinal detachment. Clinical manifestations of this disease may include increased intraocular pressure, optic disc oedema, optic neuropathy and sheathed retinal arterioles. A complete work up is essential to rule out cytomegalovirus retinitis, herpes simplex encephalitis, herpes virus, syphilis, posterior uveitis and other conditions. Depending on the severity of the disease, the treatment options consist of anticoagulation therapy, cycloplegia, intravenous acyclovir, systemic steroids, prophylactic laser photocoagulation and pars plana vitrectomy with silicon oil for retinal detachment. An extensive history and clinical examination is crucial in making the correct diagnosis. Also, it is very important to be aware of low vision needs and refer the patients, if expressing any sort of functional issues with completing daily living skills, especially reading. In this article, we report one case of unilateral ARN 20 years after herpetic encephalitis. © 2016 Optometry Australia.

Tomato chocolate spot virus, a member of a new torradovirus species that causes a necrosis-associated disease of tomato in Guatemala.

PubMed

Batuman, O; Kuo, Y-W; Palmieri, M; Rojas, M R; Gilbertson, R L

2010-06-01

Tomatoes in Guatemala have been affected by a new disease, locally known as "mancha de chocolate" (chocolate spot). The disease is characterized by distinct necrotic spots on leaves, stems and petioles that eventually expand and cause a dieback of apical tissues. Samples from symptomatic plants tested negative for infection by tomato spotted wilt virus, tobacco streak virus, tobacco etch virus and other known tomato-infecting viruses. A virus-like agent was sap-transmitted from diseased tissue to Nicotiana benthamiana and, when graft-transmitted to tomato, this agent induced chocolate spot symptoms. This virus-like agent also was sap-transmitted to Datura stramonium and Nicotiana glutinosa, but not to a range of non-solanaceous indicator plants. Icosahedral virions approximately 28-30 nm in diameter were purified from symptomatic N. benthamiana plants. When rub-inoculated onto leaves of N. benthamiana plants, these virions induced symptoms indistinguishable from those in N. benthamiana plants infected with the sap-transmissible virus associated with chocolate spot disease. Tomatoes inoculated with sap or grafted with shoots from N. benthamiana plants infected with purified virions developed typical chocolate spot symptoms, consistent with this virus being the causal agent of the disease. Analysis of nucleic acids associated with purified virions of the chocolate-spot-associated virus, revealed a genome composed of two single-stranded RNAs of approximately 7.5 and approximately 5.1 kb. Sequence analysis of these RNAs revealed a genome organization similar to recently described torradoviruses, a new group of picorna-like viruses causing necrosis-associated diseases of tomatoes in Europe [tomato torrado virus (ToTV)] and Mexico [tomato apex necrosis virus (ToANV) and tomato marchitez virus (ToMarV)]. Thus, the approximately 7.5 kb and approximately 5.1 kb RNAs of the chocolate-spot-associated virus corresponded to the torradovirus RNA1 and RNA2, respectively; however

Emergence of MD type infectious hematopoietic necrosis virus in Washington State coastal steelhead trout

USGS Publications Warehouse

Breyta, Rachel; Jones, Amelia; Stewart, Bruce; Brunson, Ray; Thomas, Joan; Kerwin, John; Bertolini, Jim; Mumford, Sonia; Patterson, Chris; Kurath, Gael

2013-01-01

Infectious hematopoietic necrosis virus (IHNV) occurs in North America as 3 major phylogenetic groups designated U, M, and L. In coastal Washington State, IHNV has historically consisted of U genogroup viruses found predominantly in sockeye salmon Oncorhynchus nerka. M genogroup IHNV, which has host-specific virulence for rainbow and steelhead trout O. mykiss, was detected only once in coastal Washington prior to 2007, in an epidemic among juvenile steelhead trout in 1997. Beginning in 2007 and continuing through 2011, there were 8 IHNV epidemics in juvenile steelhead trout, involving 7 different fish culture facilities in 4 separate watersheds. During the same time period, IHNV was also detected in asymptomatic adult steelhead trout from 6 coastal watersheds. Genetic typing of 283 recent virus isolates from coastal Washington revealed that the great majority were in the M genogroup of IHNV and that there were 2 distinct waves of viral emergence between the years 2007 and 2011. IHNV type mG110M was dominant in coastal steelhead trout during 2007 to 2009, and type mG139M was dominant between 2010 and 2011. Phylogenetic analysis of viral isolates indicated that all coastal M genogroup viruses detected in 1997 and 2007 to 2011 were part of the MD subgroup and that several novel genetic variants related to the dominant types arose in the coastal sites. Comparison of spatial and temporal incidence of coastal MD viruses with that of the rest of the Pacific Northwest indicated that the likely source of the emergent viruses was Columbia River Basin steelhead trout. 

The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer

PubMed Central

Martínez-Bosch, Neus; Guerrero, Pedro Enrique; Moreno, Mireia; José, Anabel; Iglesias, Mar; Munné-Collado, Jessica; Anta, Héctor; Gibert, Joan; Orozco, Carlos Alberto; Vinaixa, Judith; Fillat, Cristina; Viñals, Francesc; Navarro, Pilar

2016-01-01

Current treatments for pancreatic ductal adenocarcinoma (PDA) are ineffective, making this the 4th leading cause of cancer deaths. Sunitinib is a broad-spectrum inhibitor of tyrosine kinase receptors mostly known for its anti-angiogenic effects. We tested the therapeutic effects of sunitinib in pancreatic cancer using the Ela-myc transgenic mouse model. We showed that Ela-myc pancreatic tumors express PDGFR and VEGFR in blood vessels and epithelial cells, rendering these tumors sensitive to sunitinib by more than only its anti-angiogenic activity. However, sunitinib treatment of Ela-myc mice with either early or advanced tumor progression had no impact on either survival or tumor burden. Further histopathological characterization of these tumors did not reveal differences in necrosis, cell differentiation, angiogenesis, apoptosis or proliferation. In stark contrast, in vitro sunitinib treatment of Ela-myc– derived cell lines showed high sensitivity to the drug, with increased apoptosis and reduced proliferation. Correspondingly, subcutaneous tumors generated from these cell lines completely regressed in vivo after sunitinib treatments. These data point at the pancreatic tumor microenvironment as the most likely barrier preventing sunitinib treatment efficiency in vivo. Combined treatments with drugs that disrupt tumor fibrosis may enhance sunitinib therapeutic effectiveness in pancreatic cancer treatment. PMID:27374084

Effect of the disease severity on the risk of developing new-onset diabetes after acute pancreatitis.

PubMed

Tu, Jianfeng; Yang, Yue; Zhang, Jingzhu; Yang, Qi; Lu, Guotao; Li, Baiqiang; Tong, Zhihui; Ke, Lu; Li, Weiqin; Li, Jieshou

2018-06-01

Endocrine pancreatic insufficiency secondary to acute pancreatitis (AP) drew increasing attention in the recent years. The aim of the present study was to assess the impact of pancreatic necrosis and organ failure on the risk of developing new-onset diabetes after AP.The follow-up study was conducted for patients recovered from AP in the treatment center of Jinling Hospital. Endocrine function was evaluated by simplified oral glucose tolerance test (OGTT). Pancreatic necrosis was examined by abdominal contrast-enhanced CT (CECT) scan during hospitalization. The data including APACHE II score, Balthazar's score, organ failure (AKI and ARDS) was also collected from the medical record database. All patients were divided into group diabetes mellitus (DM) and group non-DM according to the endocrine function and group pancreatic necrosis (PN) and persistent organ failure (OF), group PN and non-OF, group non-PN and OF, and group non-PN and non-OF according to the occurrence of pancreatic necrosis and persistent organ failure.Around 256 patients were included for the final analysis. 154 patients (60.2%) were diagnosed with DM (include impaired glucose tolerance, IGT), while 102 patients (39.8%) were deemed as normal endocrine function. APACHE II score and Balthazar score of the patients in the group DM were significant higher than those in the non-DM group (F = 6.09, P = .01; F = 10.74, P = .001). The incidence of pancreatic necrosis in group DM and group non-DM was, respectively, 64.7% and 53.0% (χ = 3.506, P = .06). The patients underwent necrosis debridement by percutaneous catheter drainage (PCD) and/or the operative necrosectomy (ON) were more likely to developed new onset DM than the patients without PCD or ON (χ = 2.385, P = .02). The morbidity of new-onset DM after AP gradually increased from group non-PN and non-OF, group non-PN and OF, group PN and non-OF to group PN and OF in order (χ = 4.587, P = .03). The value of

Neutralization-resistant variants of infectious hematopoietic necrosis virus have altered virulence and tissue tropism

USGS Publications Warehouse

Kim, C.H.; Winton, J.R.; Leong, J.C.

1994-01-01

Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus that causes an acute disease in salmon and trout. In this study, a correlation between changes in tissue tropism and specific changes in the virus genome appeared to be made by examining four IHNV neutralization-resistant variants (RB-1, RB-2, RB-3, and RB-4) that had been selected with the glycoprotein (G)-specific monoclonal antibody RB/B5. These variants were compared with the parental strain (RB-76) for their virulence and pathogenicity in rainbow trout after waterborne challenge. Variants RB-2, RB-3, and RB-4 were only slightly attenuated and showed distributions of viral antigen in the livers and hematopoietic tissues of infected fish similar to those of the parental strain. Variant RB-1, however, was highly attenuated and the tissue distribution of viral antigen in RB-1-infected fish was markedly different, with more viral antigen in brain tissue. The sequences of the G genes of all four variants and RB-76 were determined. No significant changes were found for the slightly attenuated variants, but RB-1 G had two changes at amino acids 78 and 218 that dramatically altered its predicted secondary structure. These changes are thought to be responsible for the altered tissue tropism of the virus. Thus, IHNV G, like that of rabies virus and vesicular stomatitis virus, plays an integral part in the pathogenesis of viral infection.

Multiplication of infectious hematopoietic necrosis virus in rainbow trout following immersion infection: whole-body assay and immunohistochemistry

USGS Publications Warehouse

Yamamoto, T.; Batts, W.N.; Arakawa, C.K.; Winton, J.R.

1990-01-01

The sites of replication of infectious hematopoietic necrosis virus (IHNV) in infected tissues were detected in fingerling rainbow trout Oncorhynchus mykiss by in situ histologic techniques following immersion infection. Virus antigens in tissues were detected by a neutralizing mouse monoclonal antibody and a one-step anti-mouse biotin-streptavidin conjugated to horseradish peroxidase. The efficiency of infection and virulence of the virus determined by mortality rates showed high virulence of the selected IHNV isolates, and viral replication in individual fish showed that virus content of the fish increased rapidly from the second day to the seventh day postinfection. The earliest viral lesions following infection were detected in the epidermis of the pectoral fins, opercula, and ventral surface of the body. Virus lesions became evident in kidneys on the third day. By the fifth day, when there was a significant increase in virus titer, foci of viral replication were detected in gill tissue and in the anterior internal tissues below the epidermis. Subsequently, extensive virus replication and tissue destruction were observed in the spleen, dorsal adipose tissues, ventricle, and pseudobranch. Replication in the liver, the muscularis layers of the digestive tract, and the general body musculature followed later. These infection experiments indicated that the epidermis and gills of fish constitute important sites of early IHNV replication.

A Recombinant of Bean common mosaic virus Induces Temperature-Insensitive Necrosis in an I Gene-Bearing Line of Common Bean.

PubMed

Feng, Xue; Poplawsky, Alan R; Karasev, Alexander V

2014-11-01

The I gene is a single, dominant gene conferring temperature-sensitive resistance to all known strains of Bean common mosaic virus (BCMV) in common bean (Phaseolus vulgaris). However, the closely related Bean common mosaic necrosis virus (BCMNV) induces whole plant necrosis in I-bearing genotypes of common bean, and the presence of additional, recessive genes is required to prevent this severe whole plant necrotic reaction caused by BCMNV. Almost all known BCMNV isolates have so far been classified as having pathotype VI based on their interactions with the five BCMV resistance genes, and all have a distinct serotype A. Here, we describe a new isolate of BCMV, RU1M, capable of inducing whole plant necrosis in the presence of the I gene, that appears to belong to pathotype VII and exhibits B-serotype. Unlike other isolates of BCMV, RU1M was able to induce severe whole plant necrosis below 30°C in bean cultivar Jubila that carries the I gene and a protective recessive gene bc-1. The whole genome of RU1M was cloned and sequenced and determined to be 9,953 nucleotides long excluding poly(A), coding for a single polyprotein of 3,186 amino acids. Most of the genome was found almost identical (>98%) to the BCMV isolate RU1-OR (also pathotype VII) that did not induce necrotic symptoms in 'Jubila'. Inspection of the nucleotide sequences for BCMV isolates RU1-OR, RU1M, and US10 (all pathotype VII) and three closely related sequences of BCMV isolates RU1P, RU1D, and RU1W (all pathotype VI) revealed that RU1M is a product of recombination between RU1-OR and a yet unknown potyvirus. A 0.8-kb fragment of an unknown origin in the RU1M genome may have led to its ability to induce necrosis regardless of temperature in beans carrying the I gene. This is the first report of a BCMV isolate inducing temperature-insensitive necrosis in an I gene containing bean genotype.

Management of diseases caused by thrips-transmitted tospoviruses in subsistence agriculture: the case of Peanut bud necrosis virus in India

USDA-ARS?s Scientific Manuscript database

Among the tospoviruses (genus Tospovirus, family Bunyaviridae) reported in India, Peanut bud necrosis virus is by far the most economically significant for tomato production in subsistence agriculture. Management of PBNV has been a challenge for farmers due to the broad host-range of PBNV and its ve...

Resistance and Protective Immunity in Redfish Lake Sockeye Salmon Exposed to M Type Infectious Hematopoietic Necrosis Virus (IHNV)

USGS Publications Warehouse

Kurath, Gael; Garver, Kyle; Purcell, Maureen K.; LaPatra, Scott E.

2010-01-01

Differential virulence of infectious hematopoietic necrosis virus (IHNV) isolates from the U and M phylogenetic subgroups is clearly evident in the Redfish Lake (RFL) strain of sockeye salmon Oncorhynchus nerka. In these fish, experimental immersion challenges with U isolates cause extremely high mortality and M isolates cause low or no mortality. When survivors of M virus immersion challenges were exposed to a secondary challenge with virulent U type virus they experienced high mortality, indicating that the primary M challenge did not elicit protective immunity. Delivery of a moderate dose (2 × 104 plaque-forming units [PFU]/fish) of virus by intraperitoneal injection challenge did not overcome RFL sockeye salmon resistance to M type IHNV. Injection challenge with a high dose (5 × 106 PFU/fish) of M type virus caused 10% mortality, and in this case survivors did develop protective immunity against a secondary U type virus challenge. Thus, although it is possible for M type IHNV to elicit cross-protective immunity in this disease model, it does not develop after immersion challenge despite entry, transient replication of M virus to low levels, stimulation of innate immune genes, and development of neutralizing antibodies in some fish.

Differential virulence mechanisms of infectious hematopoietic necrosis virus in rainbow trout (Oncorhynchus mykiss) include host entry and virus replication kinetics

USGS Publications Warehouse

Penaranda, M.M.D.; Purcell, M.K.; Kurath, G.

2009-01-01

Host specificity is a phenomenon exhibited by all viruses. For the fish rhabdovirus infectious hematopoietic necrosis virus (IHNV), differential specificity of virus strains from the U and M genogroups has been established both in the field and in experimental challenges. In rainbow trout (Oncorhynchus mykiss), M IHNV strains are consistently more prevalent and more virulent than U IHNV. The basis of the differential ability of these two IHNV genogroups to cause disease in rainbow trout was investigated in live infection challenges with representative U and M IHNV strains. When IHNV was delivered by intraperitoneal injection, the mortality caused by U IHNV increased, indicating that the low virulence of U IHNV is partly due to inefficiency in entering the trout host. Analyses of in vivo replication showed that U IHNV consistently had lower prevalence and lower viral load than M IHNV during the course of infection. In analyses of the host immune response, M IHNV-infected fish consistently had higher and longer expression of innate immune-related genes such as Mx-1. This suggests that the higher virulence of M IHNV is not due to suppression of the immune response in rainbow trout. Taken together, the results support a kinetics hypothesis wherein faster replication enables M IHNV to rapidly achieve a threshold level of virus necessary to override the strong host innate immune response. ?? 2009 SGM.

[Necrotic acute pancreatitis in the intensive care unit: a comparison between conservative and surgical medical treatment].

PubMed

Milian J, William; Portugal S, José; Laynez Ch, Richard; Rodríguez A, Cesar; Targarona, Javier; Barreda C, Luis

2010-01-01

To determine the prognosis of patients with necrotic acute pancreatitis receiving medical and surgical treatments. The severe acute pancreatitis treatment is multidisciplinary and requires a daily evaluation of the patient that will allow to observe changes and apply therapy in due time. The treatment includes: Admission in the ICU, fluids, nutrition and antibiotics, as well as other life supports for high-risk patients. Thus, patients undergo conservative treatment or, if it is necessary, surgery. A retrospective study of patients with necrotic acute pancreatitis admitted to the ICU between January 2004 and August 2006. The patients with necrotic acute pancreatitis without signs of sepsis underwent a conservative medical treatment, while fine needle punction-aspiration was performed in all patients who were suffering from necrotic acute pancreatitis and persistent sepsis four weeks after their admission and after discarding and eradicating every non-pancreatic focus of infection. All Gram stain or culture positive patients underwent surgery immediately. Seventy patients with necrotic acute pancreatitis were included in the study. Thirty-six patients (51%) suffered acute pancreatitis with sterile necrosis and underwent a conservative treatment, while 34 patients (49%) developed acute pancreatic with infected necrosis and underwent surgery. The average age was 55.19 vs. 57.65 (p=0.57). The average amylase was 1421.74 vs. 1402.45. (p=0.96). The tomography severity index was 8.47 vs. 8.79 (p=0.36). The Apache II was 8.22 vs. 9 (p=0.46). The average number of failed organs was 0.39 vs. 0.68. (p=0.19). The ICU stay was 10.75 vs. 26.5 days (p<0.05) while the total hospital stay was 46.47 vs. 57.26 days (p<0.05). The mortality rate was (3/36) 8.3% vs. (9/34) 26.5% (p<0.05) for conservative medical treatment vs. surgical treatment, respectively. Between the first and the twelfth month the evaluated patients who attended consultation, after discharge, showed: pancreatic

Genotypes and phylogeographical relationships of infectious hematopoietic necrosis virus in California, USA

USGS Publications Warehouse

Kelley, G.O.; Bendorf, C.M.; Yun, S.C.; Kurath, G.; Hedrick, R.P.

2007-01-01

Infectious hematopoietic necrosis virus (IHNV) contains 3 major genogroups in North America with discreet geographic ranges designated as upper (U), middle (M), and lower (L). A comprehensive genotyping of 237 IHNV isolates from hatchery and wild salmonids in California revealed 25 different sequence types (a to y) all in the L genogroup; specifically, the genogroup contained 14 sequence types that were unique to individual isolates as well as 11 sequence types representing 2 or more identical isolates. The most evident trend was the phylogenetic and geographical division of the L genogroup into 2 distinct subgroups designated as LI and LII. Isolates within Subgroup LI were primarily found within waterways linked to southern Oregon and northern California coastal rivers. Isolates in Subgroup LII were concentrated within inland valley watersheds that included the Sacramento River, San Joaquin River, and their tributaries. The temporal and spatial patterns of virus occurrence suggested that infections among adult Chinook salmon in the hatchery or that spawn in the river are a major source of virus potentially infecting other migrating or resident salmonids in California. Serum neutralization results of the California isolates of IHNV corroborated a temporal trend of sequence divergence; specifically, 2 progressive shifts in which more recent virus isolates represent new serotypes. A comparison of the estimates of divergence rates for Subgroup LI (1 ?? ICT5 mutations per nucleotide site per year) indicated stasis similar to that observed in the U genogroup, while the Subgroup LII rate (1 ?? 10 3 mutations per nucleotide site per year) suggested a more active evolution similar to that of the M genogroup. ?? Inter-Research 2007.

Tetraodon nigroviridis as a nonlethal model of infectious spleen and kidney necrosis virus (ISKNV) infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu Xiaopeng; Huang Lichao; Weng Shaoping

Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus, family Iridoviridae. We have previously established a high mortality ISKNV infection model of zebrafish (Danio rerio). In this study, a nonlethal Tetraodon nigroviridis model of ISKNV infection was established. ISKNV infection did not cause lethal disease in Tetraodon but could infect almost all the organs of this species. Electron microscopy showed ISKNV particles were present in infected tissues. Immunofluorescence and quantitative real-time PCR analysis showed that nearly all the virions and infected cells were cleared at 14 d postinfection. The expression profiles of interferon-{gamma} andmore » tumor necrosis factor-{alpha} gene in response to ISKNV infection were significantly different in Tetraodon and zebrafish. The establishment of the nonlethal Tetraodon model of ISKNV infection can offer a valuable tool complementary to the zebrafish infection model for studying megalocytivirus disease, fish immune systems, and viral tropism.« less

Infectious hematopoietic necrosis virus: monophyletic origin of European isolates from North American genogroup M.

PubMed

Enzmann, P J; Kurath, G; Fichtner, D; Bergmann, S M

2005-09-23

Infectious hematopoietic necrosis virus (IHNV) was first detected in Europe in 1987 in France and Italy, and later, in 1992, in Germany. The source of the virus and the route of introduction are unknown. The present study investigates the molecular epidemiology of IHNV outbreaks in Germany since its first introduction. The complete nucleotide sequences of the glycoprotein (G) and non-virion (NV) genes from 9 IHNV isolates from Germany have been determined, and this has allowed the identification of characteristic differences between these isolates. Phylogenetic analysis of partial G gene sequences (mid-G, 303 nucleotides) from North American IHNV isolates (Kurath et al. 2003) has revealed 3 major genogroups, designated U, M and L. Using this gene region with 2 different North American IHNV data sets, it was possible to group the European IHNV strains within the M genogroup, but not in any previously defined subgroup. Analysis of the full length G gene sequences indicated that an independent evolution of IHN viruses had occurred in Europe. IHN viruses in Europe seem to be of a monophyletic origin, again most closely related to North American isolates in the M genogroup. Analysis of the NV gene sequences also showed the European isolates to be monophyletic, but resolution of the 3 genogroups was poor with this gene region. As a result of comparative sequence analyses, several different genotypes have been identified circulating in Europe.

Effect of inhibition of prostaglandin E2 production on pancreatic infection in experimental acute pancreatitis

PubMed Central

Coelho, Ana Maria M.; Sampietre, Sandra; Patzina, Rosely; Jukemura, Jose; Cunha, Jose Eduardo M.; Machado, Marcel C.C.

2007-01-01

Objective. Acute pancreatitis is one the important causes of systemic inflammatory response syndrome (SIRS). SIRS results in gut barrier dysfunction that allows bacterial translocation and pancreatic infection to occur. Indomethacin has been used to reduce inflammatory process and bacterial translocation in experimental models. The purpose of this study was to determine the effect of inhibition of prostaglandin E2 (PGE2) production on pancreatic infection. Materials and methods. An experimental model of severe acute pancreatitis (AP) was utilized. The animals were divided into three groups: sham (surgical procedure without AP induction); pancreatitis (AP induction); and indomethacin (AP induction plus administration of 3 mg/kg of indomethacin). Serum levels of interleukin (IL)-6 and IL-10, PGE2, and tumor necrosis factor (TNF)-α were measured 2 h after the induction of AP. We analyzed the occurrence of pancreatic infection with bacterial cultures performed 24 h after the induction of AP. The occurrence of pancreatic infection (considered positive when the CFU/g was >105), pancreatic histologic analysis, and mortality rate were studied. Results. In spite of the reduction of IL-6, IL-10, and PGE2 levels in the indomethacin group, TNF-α level, bacterial translocation, and pancreatic infection were not influenced by administration of indomethacin. The inhibition of PGE2 production did not reduce pancreatic infection, histologic score, or mortality rate. Conclusion. The inhibition of PGE2 production was not able to reduce the occurrence of pancreatic infection and does not have any beneficial effect in this experimental model. Further investigations will be necessary to discover a specific inhibitor that would make it possible to develop an anti-inflammatory therapy. PMID:18345325

Effects of metamizole, MAA, and paracetamol on proliferation, apoptosis, and necrosis in the pancreatic cancer cell lines PaTu 8988 t and Panc-1.

PubMed

Malsy, Manuela; Graf, Bernhard; Bundscherer, Anika

2017-12-06

Adenocarcinoma of the pancreas is one of the most aggressive cancer diseases affecting the human body. Recent research has shown the importance of the perioperative phase in disease progression. Particularly during this vulnerable phase, substances such as metamizole and paracetamol are given as general anesthetics and postoperative analgesics. Therefore, the effects of metamizole and paracetamol on tumor progression should be investigated in more detail because the extent to which these substances influence the carcinogenesis of pancreatic carcinoma is still unclear. This study analyzed the influence of metamizole and its active metabolites MAA (4-N-methyl-aminoantipyrine) and paracetamol on the proliferation, apoptosis, and necrosis of the pancreatic cancer cell lines PaTu 8988t and Panc-1 in vitro. Cell proliferation was measured by means of the ELISA BrdU assay and the rate of apoptosis by flow cytometry using the Annexin V assay. Metamizole and paracetamol significantly inhibited cell proliferation in pancreatic cancer cells. After the addition of metamizole to PaTu 8988t cells, the rate of apoptosis was reduced after 3 h of incubation but significantly increased after 9 h of incubation. The oncogenic potential of pancreatic adenocarcinoma is mainly characterized by its extreme growth rate. Non-opioid analgesics such as metamizole and paracetamol are given as general anesthetics and postoperative analgesics. The combination of metamizole or paracetamol with cytotoxic therapeutic approaches may achieve synergistic effects. Further studies are necessary to identify the underlying mechanisms so that new therapeutic options may be developed for the treatment of this aggressive tumor.

Pancreatic acinar cell carcinoma extending into the common bile and main pancreatic ducts.

PubMed

Yamaguchi, Rin; Okabe, Yoshinobu; Jimi, Atsuo; Shiota, Koji; Kodama, Takahito; Naito, Yoshiki; Yasunaga, Masafumi; Kinoshita, Hisafumi; Kojiro, Masamichi

2006-10-01

Acinar cell carcinoma (ACC) of the pancreas is relatively rare, accounting for only approximately 1% of all exocrine pancreatic tumors. A 69-year-old man was found to have a mass lesion measuring approximately 4 cm in diameter in the pancreatic head on ultrasound, abdominal dynamic CT, and percutaneous transhepatic cholangiography. Magnetic resonance cholangiopancreatography showed defect of the lower common bile duct (CBD) due to obstruction by the tumor cast. Histopathologically, the pancreatic head tumor invaded the main pancreatic duct (MPD) and CBD with extension into the CBD in a form of tumor cast. The tumor cells consisted of a solid proliferation with abundant eosinophilic cytoplasm and round nuclei in an acinar and trabecular fashion. A 55-year-old man with upper abdominal pain and nausea, had a cystic lesion approximately 3 cm in size in the pancreatic tail on CT. Histopathologically, the tumor was encapsulated by fibrous capsule and had extensive central necrosis with solid areas in the tumor periphery, and invaded with extension into the MPD in a form of tumor cast. The tumor cells resembled acinar cells in solid growths. Two resected cases of ACC with unusual tumor extension into the CBD and the MPD, respectively, are reported.

A zebrafish (Danio rerio) model of infectious spleen and kidney necrosis virus (ISKNV) infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu Xiaopeng; Zhang Lichun; Weng Shaoping

2008-06-20

Zebrafish is a model animal for studies of genetics, development, toxicology, oncology, and immunology. In this study, infectious spleen and kidney necrosis virus (ISKNV) was used to establish an infection in zebrafish, and the experimental conditions were established and characterized. Mortality of adult zebrafish infected with ISKNV by intraperitoneal (i.p.) injection exceeded 60%. ISKNV can be passed stably in zebrafish for over ten passages. The ailing zebrafish displayed petechial hemorrhaging and scale protrusion. Histological analysis of moribund fish revealed necrosis of tissue and enlarged cells in kidney and spleen. The real-time RT-PCR analysis of mRNA level confirmed that ISKNV wasmore » replicated in zebrafish. Immunohistochemistry and immunofluorescence analyses further confirmed the presence of ISKNV-infected cells in almost all organs of the infected fish. Electron microscope analyses showed that the ISKNV particle was present in the infected tissues. The establishment of zebrafish infection model of ISKNV can offer a valuable tool for studying the interactions between ISKNV and its host.« less

Chronic stress sensitizes rats to pancreatitis induced by cerulein: Role of TNF-α

PubMed Central

Binker, Marcelo G; Binker-Cosen, Andres A; Richards, Daniel; Gaisano, Herbert Y; de Cosen, Rodica H; Cosen-Binker, Laura I

2010-01-01

AIM: To investigate chronic stress as a susceptibility factor for developing pancreatitis, as well as tumor necrosis factor-α (TNF-α) as a putative sensitizer. METHODS: Rat pancreatic acini were used to analyze the influence of TNF-α on submaximal (50 pmol/L) cholecystokinin (CCK) stimulation. Chronic restraint (4 h every day for 21 d) was used to evaluate the effects of submaximal (0.2 μg/kg per hour) cerulein stimulation on chronically stressed rats. RESULTS: In vitro exposure of pancreatic acini to TNF-α disorganized the actin cytoskeleton. This was further increased by TNF-α/CCK treatment, which additionally reduced amylase secretion, and increased trypsin and nuclear factor-κB activities in a protein-kinase-C δ and ε-dependent manner. TNF-α/CCK also enhanced caspases’ activity and lactate dehydrogenase release, induced ATP loss, and augmented the ADP/ATP ratio. In vivo, rats under chronic restraint exhibited elevated serum and pancreatic TNF-α levels. Serum, pancreatic, and lung inflammatory parameters, as well as caspases’activity in pancreatic and lung tissue, were substantially enhanced in stressed/cerulein-treated rats, which also experienced tissues’ ATP loss and greater ADP/ATP ratios. Histological examination revealed that stressed/cerulein-treated animals developed abundant pancreatic and lung edema, hemorrhage and leukocyte infiltrate, and pancreatic necrosis. Pancreatitis severity was greatly decreased by treating animals with an anti-TNF-α-antibody, which diminished all inflammatory parameters, histopathological scores, and apoptotic/necrotic markers in stressed/cerulein-treated rats. CONCLUSION: In rats, chronic stress increases susceptibility for developing pancreatitis, which involves TNF-α sensitization of pancreatic acinar cells to undergo injury by physiological cerulein stimulation. PMID:21105189

Chronic stress sensitizes rats to pancreatitis induced by cerulein: role of TNF-α.

PubMed

Binker, Marcelo-G; Binker-Cosen, Andres-A; Richards, Daniel; Gaisano, Herbert-Y; de Cosen, Rodica-H; Cosen-Binker, Laura-I

2010-11-28

To investigate chronic stress as a susceptibility factor for developing pancreatitis, as well as tumor necrosis factor-α (TNF-α) as a putative sensitizer. Rat pancreatic acini were used to analyze the influence of TNF-α on submaximal (50 pmol/L) cholecystokinin (CCK) stimulation. Chronic restraint (4 h every day for 21 d) was used to evaluate the effects of submaximal (0.2 μg/kg per hour) cerulein stimulation on chronically stressed rats. In vitro exposure of pancreatic acini to TNF-α disorganized the actin cytoskeleton. This was further increased by TNF-α/CCK treatment, which additionally reduced amylase secretion, and increased trypsin and nuclear factor-κB activities in a protein-kinase-C δ and ε-dependent manner. TNF-α/CCK also enhanced caspases' activity and lactate dehydrogenase release, induced ATP loss, and augmented the ADP/ATP ratio. In vivo, rats under chronic restraint exhibited elevated serum and pancreatic TNF-α levels. Serum, pancreatic, and lung inflammatory parameters, as well as caspases'activity in pancreatic and lung tissue, were substantially enhanced in stressed/cerulein-treated rats, which also experienced tissues' ATP loss and greater ADP/ATP ratios. Histological examination revealed that stressed/cerulein-treated animals developed abundant pancreatic and lung edema, hemorrhage and leukocyte infiltrate, and pancreatic necrosis. Pancreatitis severity was greatly decreased by treating animals with an anti-TNF-α-antibody, which diminished all inflammatory parameters, histopathological scores, and apoptotic/necrotic markers in stressed/cerulein-treated rats. In rats, chronic stress increases susceptibility for developing pancreatitis, which involves TNF-α sensitization of pancreatic acinar cells to undergo injury by physiological cerulein stimulation.

Pleiotrophin promotes perineural invasion in pancreatic cancer.

PubMed

Yao, Jun; Hu, Xiu-Feng; Feng, Xiao-Shan; Gao, She-Gan

2013-10-21

Perineural invasion (PNI) in pancreatic cancer is an important cause of local recurrence, but little is known about its mechanism. Pleiotrophin (PTN) is an important neurotrophic factor. It is of interest that our recent experimental data showed its involvement in PNI of pancreatic cancer. PTN strongly presents in the cytoplasm of pancreatic cancer cells, and high expression of PTN and its receptor may contribute to the high PNI of pancreatic cancer. Correspondingly, PNI is prone to happen in PTN-positive tumors. We thus hypothesize that, as a neurite growth-promoting factor, PTN may promote PNI in pancreatic cancer. PTN is released at the time of tumor cell necrosis, and binds with its high-affinity receptor, N-syndecan on pancreatic nerves, to promote neural growth in pancreatic cancer. Furthermore, neural destruction leads to a distorted neural homeostasis. Neurons and Schwann cells produce more N-syndecan in an effort to repair the pancreatic nerves. However, the abundance of N-syndecan attracts further PTN-positive cancer cells to the site of injury, creating a vicious cycle. Ultimately, increased PTN and N-syndecan levels, due to the continuous nerve injury, may promote cancer invasion and propagation along the neural structures. Therefore, it is meaningful to discuss the relationship between PTN/N-syndecan signaling and PNI in pancreatic cancer, which may lead to a better understanding of the mechanism of PNI in pancreatic cancer.

Pleiotrophin promotes perineural invasion in pancreatic cancer

PubMed Central

Yao, Jun; Hu, Xiu-Feng; Feng, Xiao-Shan; Gao, She-Gan

2013-01-01

Perineural invasion (PNI) in pancreatic cancer is an important cause of local recurrence, but little is known about its mechanism. Pleiotrophin (PTN) is an important neurotrophic factor. It is of interest that our recent experimental data showed its involvement in PNI of pancreatic cancer. PTN strongly presents in the cytoplasm of pancreatic cancer cells, and high expression of PTN and its receptor may contribute to the high PNI of pancreatic cancer. Correspondingly, PNI is prone to happen in PTN-positive tumors. We thus hypothesize that, as a neurite growth-promoting factor, PTN may promote PNI in pancreatic cancer. PTN is released at the time of tumor cell necrosis, and binds with its high-affinity receptor, N-syndecan on pancreatic nerves, to promote neural growth in pancreatic cancer. Furthermore, neural destruction leads to a distorted neural homeostasis. Neurons and Schwann cells produce more N-syndecan in an effort to repair the pancreatic nerves. However, the abundance of N-syndecan attracts further PTN-positive cancer cells to the site of injury, creating a vicious cycle. Ultimately, increased PTN and N-syndecan levels, due to the continuous nerve injury, may promote cancer invasion and propagation along the neural structures. Therefore, it is meaningful to discuss the relationship between PTN/N-syndecan signaling and PNI in pancreatic cancer, which may lead to a better understanding of the mechanism of PNI in pancreatic cancer. PMID:24151381

Insights into Alternanthera mosaic virus TGB3 functions: Interactions with Nicotiana benthamiana PsbO correlate with chloroplast vesiculation and veinal necrosis caused by TGB3 overexpression

USDA-ARS?s Scientific Manuscript database

Alternanthera mosaic virus (AltMV) triple gene block 3 (TGB3) protein is involved in viral movement. AltMV TGB3 subcellular localization was previously shown to be distinct from that of Potato virus X (PVX) TGB3, and a chloroplast binding domain identified; veinal necrosis and chloroplast vesiculati...

Direct endoscopic necrosectomy versus step-up approach for walled-off pancreatic necrosis: comparison of clinical outcome and health care utilization.

PubMed

Kumar, Nitin; Conwell, Darwin L; Thompson, Christopher C

2014-11-01

Infected walled-off pancreatic necrosis (WOPN) is a complication of acute pancreatitis requiring intervention. Surgery is associated with considerable morbidity. Percutaneous catheter drainage (PCD), initial therapy in the step-up approach, minimizes complications. Direct endoscopic necrosectomy (DEN) has demonstrated safety and efficacy. We compared outcome and health care utilization of DEN versus step-up approach. This was a matched cohort study using a prospective registry. Twelve consecutive DEN patients were matched with 12 step-up approach patients. Outcomes were clinical resolution after primary therapeutic modality, new organ failure, mortality, endocrine or exocrine insufficiency, length of stay, and health care utilization. Clinical resolution in 11 of 12 patients after DEN versus 3 of 12 step-up approach patients after PCD (P < 0.01). Nine step-up approach patients required surgery; 7 of these experienced complications. Direct endoscopic necrosectomy resulted in less new antibiotic use, pulmonary failure, endocrine insufficiency, and shorter length of stay (P < 0.05). Health care utilization was lower after DEN by 5.2:1 (P < 0.01). Direct endoscopic necrosectomy may be superior to step-up approach for WOPN with suspected or established infection. Primary PCD generally delayed definitive therapy. Given the higher efficacy, shorter length of stay, and lower health care utilization, DEN could be the first-line therapy for WOPN, with primary PCD for inaccessible or immature collections.

Genomic analysis of the host response to nervous necrosis virus in Atlantic cod (Gadus morhua) brain.

PubMed

Krasnov, Aleksei; Kileng, Øyvind; Skugor, Stanko; Jørgensen, Sven Martin; Afanasyev, Sergey; Timmerhaus, Gerrit; Sommer, Ann-Inger; Jensen, Ingvill

2013-07-01

Genome sequencing combined with transcriptome profiling promotes exploration of defence against pathogens and discovery of immune genes. Based on sequences from the recently released genome of Atlantic cod, a genome-wide oligonucleotide microarray (ACIQ-1) was designed and used for analyses of gene expression in the brain during infection with nervous necrosis virus (NNV). A challenge experiment with NNV was performed with Atlantic cod juveniles and brain samples from virus infected and uninfected fish were used for microarray analysis. Expression of virus induced genes increased at 5 days post challenge and persisted at stable level to the last sampling at 25 days post challenge. A large fraction of the up-regulated genes (546 features) were known or expected to have immune functions and most of these have not previously been characterized in Atlantic cod. Transcriptomic changes induced by the virus involved strong activation of genes associated with interferon and tumour necrosis factor related responses and acute inflammation. Up-regulation of genes involved in adaptive immunity suggested a rapid recruitment of B and T lymphocytes to the NNV infected brain. QPCR analyses of 15 candidate genes of innate immunity showed rapid induction by poly(I:C) in Atlantic cod larvae cells suggesting an antiviral role. Earliest and greatest expression changes after poly I:C stimulation was observed for interferon regulatory factors IRF4 and IRF7. Comparative studies between teleost species provided new knowledge about the evolution of innate antiviral immunity in fish. A number of genes is present or responds to viruses only in fish. Innate immunity of Atlantic cod is characterized by selective expansion of several medium-sized multigene families with ribose binding domains. An interesting finding was the high representation of three large gene families among the early antiviral genes, including tripartite motif proteins (TRIM) and proteins with PRY-SPRY and NACHT domains. The

Atlantic salmon, Salmo salar L. are broadly susceptible to isolates representing the North American genogroups of infectious hematopoietic necrosis virus

USGS Publications Warehouse

Kurath, Gael; Winton, James R.; Dale, Ole B.; Purcell, Maureen K.; Falk, Knut; Busch, Robert D.

2016-01-01

Beginning in 1992, three epidemic waves of infectious hematopoietic necrosis, often with high mortality, occurred in farmed Atlantic salmon Salmo salar L. on the west coast of North America. We compared the virulence of eleven strains of infectious hematopoietic necrosis virus (IHNV), representing the U, M and L genogroups, in experimental challenges of juvenile Atlantic salmon in freshwater. All strains caused mortality and there was wide variation within genogroups: cumulative mortality for five U-group strains ranged from 20 to 100%, four M-group strains ranged 30-63% and two L-group strains varied from 41 to 81%. Thus, unlike Pacific salmonids, there was no apparent correlation of virulence in a particular host species with virus genogroup. The mortality patterns indicated two different phenotypes in terms of kinetics of disease progression and final per cent mortality, with nine strains having moderate virulence and two strains (from the U and L genogroups) having high virulence. These phenotypes were investigated by histopathology and immunohistochemistry to describe the variation in the course of IHNV disease in Atlantic salmon. The results from this study demonstrate that IHNV may become a major threat to farmed Atlantic salmon in other regions of the world where the virus has been, or may be, introduced.

Fish DNA vaccine against infectious hematopoietic necrosis virus: efficacy of various routes of immunization

USGS Publications Warehouse

Corbeil, Serge; Kurath, Gael; LaPatra, Scott E.

2000-01-01

The DNA vaccine, pIHNVw-G, contains the gene for the glycoprotein (G) of the rhabdovirus infectious hematopoietic necrosis virus (IHNV), a major pathogen of salmon and trout. The relative efficacy of various routes of immunisation with pIHNVw-G was evaluated using 1.8 g rainbow trout fry vaccinated via intramuscular injection, scarification of the skin, intraperitoneal injection, intrabuccal administration, cutaneous particle bombardment using a gene gun, or immersion in water containing DNA vaccine-coated beads. Twenty-seven days after vaccination neutralising antibody titres were determined, and 2 days later groups of vaccinated and control unvaccinated fish were subjected to an IHNV immersion challenge. Results of the virus challenge showed that the intramuscular injection and the gene gun immunisation induced protective immunity in fry, while intraperitoneal injection provided partial protection. Neutralising antibodies were not detected in sera of vaccinated fish regardless of the route of immunisation used, suggesting that cell mediated immunity may be at least partially responsible for the observed protection.

Significant inter-observer variation in the diagnosis of extrapancreatic necrosis and type of pancreatic collections in acute pancreatitis - An international multicenter evaluation of the revised Atlanta classification.

PubMed

Sternby, Hanna; Verdonk, Robert C; Aguilar, Guadalupe; Dimova, Alexandra; Ignatavicius, Povilas; Ilzarbe, Lucas; Koiva, Peeter; Lantto, Eila; Loigom, Tonis; Penttilä, Anne; Regnér, Sara; Rosendahl, Jonas; Strahinova, Vanya; Zackrisson, Sophia; Zviniene, Kristina; Bollen, Thomas L

2016-01-01

For consistent reporting and better comparison of data in research the revised Atlanta classification (RAC) proposes new computed tomography (CT) criteria to describe the morphology of acute pancreatitis (AP). The aim of this study was to analyse the interobserver agreement among radiologists in evaluating CT morphology by using the new RAC criteria in patients with AP. Patients with a first episode of AP who obtained a CT were identified and consecutively enrolled at six European centres backwards from January 2013 to January 2012. A local radiologist at each center and a central expert radiologist scored the CTs separately using the RAC criteria. Center dependent and independent interobserver agreement was determined using Kappa statistics. In total, 285 patients with 388 CTs were included. For most CT criteria, interobserver agreement was moderate to substantial. In four categories, the center independent kappa values were fair: extrapancreatic necrosis (EXPN) (0.326), type of pancreatitis (0.370), characteristics of collections (0.408), and appropriate term of collections (0.356). The fair kappa values relate to discrepancies in the identification of extrapancreatic necrotic material. The local radiologists diagnosed EXPN (33% versus 59%, P < 0.0001) and non-homogeneous collections (35% versus 66%, P < 0.0001) significantly less frequent than the central expert. Cases read by the central expert showed superior correlation with clinical outcome. Diagnosis of EXPN and recognition of non-homogeneous collections show only fair agreement potentially resulting in inconsistent reporting of morphologic findings. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Susceptibility of Koi and Yellow Perch to infectious hematopoietic necrosis virus by experimental exposure.

PubMed

Palmer, Alexander D; Emmenegger, Eveline J

2014-06-01

Infectious hematopoietic necrosis virus (IHNV) is a novirhabdoviral pathogen that originated in western North America among anadromous Pacific salmonids. Severe disease epidemics in the late 1970s resulting from IHNV's invasion into farmed Rainbow Trout Oncorhynchus mykiss in North America, Asia, and Europe emphasized IHNV's ability to adapt to new hosts under varying rearing conditions. Yellow Perch Perca flavescens and Koi Carp Cyprinus carpio (hereafter, "Koi") are aquaculture-reared fish that are highly valued in sport fisheries and the ornamental fish trade, respectively, but it is unknown whether these fish species are vulnerable to IHNV infection. In this study, we exposed Yellow Perch, Koi, and steelhead (anadromous Rainbow Trout) to IHNV by intraperitoneal injection (10(6) PFU/fish) and by immersion (5.7×10(5) PFU/mL) for 7 h, and monitored fish for 28 d. The extended immersion exposure and high virus concentrations used in the challenges were to determine if the tested fish had any level of susceptibility. After experimental exposure, Yellow Perch and Koi experienced low mortality (<6%) compared with steelhead (>35%). Virus was found in dead fish of all species tested and in surviving Yellow Perch by plaque assay and quantitative reverse transcription polymerase chain reaction (qPCR), with a higher prevalence in Yellow Perch than Koi. Infectious virus was also detected in Yellow Perch out to 5 d after bath challenge. These findings indicate that Yellow Perch and Koi are highly resistant to IHNV disease under the conditions tested, but Yellow Perch are susceptible to infection and may serve as possible virus carriers.

Susceptibility of Koi and Yellow Perch to infectious hematopoietic necrosis virus by experimental exposure

USGS Publications Warehouse

Palmer, Alexander D.; Emmenegger, Eveline J.

2014-01-01

Infectious hematopoietic necrosis virus (IHNV) is a novirhabdoviral pathogen that originated in western North America among anadromous Pacific salmonids. Severe disease epidemics in the late 1970s resulting from IHNV's invasion into farmed Rainbow Trout Oncorhynchus mykiss in North America, Asia, and Europe emphasized IHNV's ability to adapt to new hosts under varying rearing conditions. Yellow Perch Perca flavescens and Koi Carp Cyprinus carpio (hereafter, “Koi”) are aquaculture-reared fish that are highly valued in sport fisheries and the ornamental fish trade, respectively, but it is unknown whether these fish species are vulnerable to IHNV infection. In this study, we exposed Yellow Perch, Koi, and steelhead (anadromous Rainbow Trout) to IHNV by intraperitoneal injection (106 PFU/fish) and by immersion (5.7×105 PFU/mL) for 7 h, and monitored fish for 28 d. The extended immersion exposure and high virus concentrations used in the challenges were to determine if the tested fish had any level of susceptibility. After experimental exposure, Yellow Perch and Koi experienced low mortality (35%). Virus was found in dead fish of all species tested and in surviving Yellow Perch by plaque assay and quantitative reverse transcription polymerase chain reaction (qPCR), with a higher prevalence in Yellow Perch than Koi. Infectious virus was also detected in Yellow Perch out to 5 d after bath challenge. These findings indicate that Yellow Perch and Koi are highly resistant to IHNV disease under the conditions tested, but Yellow Perch are susceptible to infection and may serve as possible virus carriers.

Demonstration of helicase activity in the nonstructural protein, NSs, of the negative-sense RNA virus, groundnut bud necrosis virus.

PubMed

Bhushan, Lokesh; Abraham, Ambily; Choudhury, Nirupam Roy; Rana, Vipin Singh; Mukherjee, Sunil Kumar; Savithri, Handanahal Subbarao

2015-04-01

The nonstructural protein NSs, encoded by the S RNA of groundnut bud necrosis virus (GBNV) (genus Tospovirus, family Bunyaviridae) has earlier been shown to possess nucleic-acid-stimulated NTPase and 5' α phosphatase activity. ATP hydrolysis is an essential function of a true helicase. Therefore, NSs was tested for DNA helicase activity. The results demonstrated that GBNV NSs possesses bidirectional DNA helicase activity. An alanine mutation in the Walker A motif (K189A rNSs) decreased DNA helicase activity substantially, whereas a mutation in the Walker B motif resulted in a marginal decrease in this activity. The parallel loss of the helicase and ATPase activity in the K189A mutant confirms that NSs acts as a non-canonical DNA helicase. Furthermore, both the wild-type and K189A NSs could function as RNA silencing suppressors, demonstrating that the suppressor activity of NSs is independent of its helicase or ATPase activity. This is the first report of a true helicase from a negative-sense RNA virus.

N-acetylcysteine amid reduces pancreatic damage in a rat model of acute necrotizing pancreatitis.

PubMed

Turkyilmaz, Serdar; Usta, Arif; Cekic, Arif Burak; Alhan, Etem; Kural, Birgül Vanizor; Ercin, Cengiz

2016-06-15

Inflammatory explosion and oxidative stress are important mechanisms of injury in acute necrotizing pancreatitis (ANP). This study investigated the effects of N-acetylcysteine amid (NACA), a novel cell-permeant antioxidant with anti-inflammatory activity, on experimental ANP in rats. Fifty-two adult male Sprague-Dawley rats were used, and ANP was induced by cerulein. The animals were divided into four groups which were sham + saline, sham + NACA, ANP + saline, and ANP + NACA. NACA (2.2 mg/kg, i.p) was administered for 6 h, after the induction of ANP. The extent of acinar cell injury, mortality, systemic cardiorespiratory variables, functional capillary density, renal/hepatic functions, and changes in some enzyme markers for pancreas and lung tissues were investigated. Induction of ANP increased mortality from 0% in the sham group to 43.75% in the ANP + saline group (P < 0.05), and administration of NACA significantly reduced mortality to 12.5% (P < 0.05). Induction of ANP also caused increases in pancreatic necrosis, serum amylase, alanine aminotransferase (ALT), interleukin-6, LDH in bronchoalveolar lavage fluid, serum urea, tissue myeloperoxidase in pancreas and lung tissues and malondialdehyde. There was less pronounced increase in these parameters in NACA treated group. Compared with ANP group, ANP + NACA group had lower levels of pancreatic necrosis (0.5 ± 0.2 versus 1.45 ± 0.2, P < 0.05) and inflammation (0.6 ± 0.2 versus 1.29 ± 00.3, P < 0.05) scores. Administration of NACA significantly decreased the ANP-induced mortality and also provided significant improvements in hemodynamic changes. The obtained positive effects of NACA on the course of pancreatitis indicates its potential usefulness in the management of ANP. Copyright © 2016 Elsevier Inc. All rights reserved.

Isolation of infectious hematopoietic necrosis virus from a leech (Piscicola salmositica) and a copepod (Salmincola sp.), ectoparasites of sockeye salmon Oncorhynchus nerka

USGS Publications Warehouse

Mulcahy, Daniel M.; Klaybor, D.; Batts, W.N.

1990-01-01

Infectious haematopoietic necrosis (IHN) virus was isolated from freshwater leeches Piscicola salmositica and copepods Salmincola sp. removed from the gills of spawning sockeye salmon, Oncorhynchus nerka. This is the first report of the isolation of IHN virus from an animal other than salmonid fishes. High levels of IHN virus were also found in leeches taken from the bottom gravel of the spawning area. The prevalence of IHN virus in samples of individual leeches was as high as 100% and the virus was isolated from 95% of pooled samples of copepod and 1.5 × 108 pfu/g in the leech. The level of virus in leeches removed from fish gills was sometimes higher than the level of virus in the gill tissue itself. Virus persisted for at least 16 d in leeches held in the laboratory without feeding. Transmission of IHN virus by leeches probably increases the infection rate of spawning sockeye salmon.

Geography and host species shape the evolutionary dynamics of U genogroup infectious hematopoietic necrosis virus.

PubMed

Black, Allison; Breyta, Rachel; Bedford, Trevor; Kurath, Gael

2016-07-01

Infectious hematopoietic necrosis virus (IHNV) is a negative-sense RNA virus that infects wild and cultured salmonids throughout the Pacific Coastal United States and Canada, from California to Alaska. Although infection of adult fish is usually asymptomatic, juvenile infections can result in high mortality events that impact salmon hatchery programs and commercial aquaculture. We used epidemiological case data and genetic sequence data from a 303 nt portion of the viral glycoprotein gene to study the evolutionary dynamics of U genogroup IHNV in the Pacific Northwestern United States from 1971 to 2013. We identified 114 unique genotypes among 1,219 U genogroup IHNV isolates representing 619 virus detection events. We found evidence for two previously unidentified, broad subgroups within the U genogroup, which we designated 'UC' and 'UP'. Epidemiologic records indicated that UP viruses were detected more frequently in sockeye salmon ( Oncorhynchus nerka ) and in coastal waters of Washington and Oregon, whereas UC viruses were detected primarily in Chinook salmon ( Oncorhynchus tshawytscha ) and steelhead trout ( Oncorhynchus mykiss ) in the Columbia River Basin, which is a large, complex watershed extending throughout much of interior Washington, Oregon, and Idaho. These findings were supported by phylogenetic analysis and by F ST . Ancestral state reconstruction indicated that early UC viruses in the Columbia River Basin initially infected sockeye salmon but then emerged via host shifts into Chinook salmon and steelhead trout sometime during the 1980s. We postulate that the development of these subgroups within U genogroup was driven by selection pressure for viral adaptation to Chinook salmon and steelhead trout within the Columbia River Basin.

Molecular confirmation of infectious spleen and kidney necrosis virus (ISKNV) in farmed and imported ornamental fish in Australia.

PubMed

Mohr, Peter G; Moody, Nicholas J G; Williams, Lynette M; Hoad, John; Cummins, David M; Davies, Kelly R; StJ Crane, Mark

2015-10-16

Viruses of the genus Megalocytivirus have not been detected in wild populations of fish in Australia but circulate in imported ornamental fish. In 2012, detection of a megalocytivirus in healthy platys Xiphophorus maculatus was reported from a farm in Australia during surveillance testing as part of a research project undertaken at the University of Sydney. Confirmatory testing of the original samples at the AAHL Fish Diseases Laboratory verified the presence of an infectious spleen and kidney necrosis virus (ISKNV)-like virus. Additional sampling at the positive farm confirmed the persistence of the virus in the platys, with 39 of 265 (14.7%) samples testing positive. Comparison of 3 separate gene regions of the virus with those of ISKNV confirmed the detection of a virus indistinguishable from ISKNV. Subsequently, ISKNV was also detected in a range of imported ornamental fish from several countries between 2013 and 2014, by screening with real-time PCR and confirmation by conventional PCR and sequence analysis. Accordingly, the current importation of live ornamental fish acts as a potential perpetual source for the establishment of ISKNV viruses within Australia. The testing of the farmed and imported ornamental fish verified the utility of the probe-based real-time PCR assay for screening of ornamental fish for Megalocytivirus.

Protection of rainbow trout against infectious hematopoietic necrosis virus four days after specific or semi-specific DNA vaccination

USGS Publications Warehouse

LaPatra, S.E.; Corbeil, S.; Jones, G.R.; Shewmaker, W.D.; Lorenzen, N.; Anderson, E.D.; Kurath, G.

2001-01-01

A DNA vaccine against a fish rhabdovirus, infectious hematopoietic necrosis virus (IHNV), was shown to provide significant protection as soon as 4 d after intramuscular vaccination in 2 g rainbow trout (Oncorhynchus mykiss) held at 15??C. Nearly complete protection was also observed at later time points (7, 14, and 28 d) using a standardized waterborne challenge model. In a test of the specificity of this early protection, immunization of rainbow trout with a DNA vaccine against another fish rhabdovirus, viral hemorrhagic septicemia virus, provided a significant level of cross-protection against IHNV challenge for a transient period of time, whereas a rabies virus DNA vaccine was not protective. This indication of distinct early and late protective mechanisms was not dependent on DNA vaccine doses from 0.1 to 2.5 ??g. ?? 2001 Elsevier Science Ltd.

Estimation of Parameters Influencing Waterborne Transmission of Infectious Hematopoietic Necrosis Virus (IHNV) in Atlantic Salmon (Salmo salar)

PubMed Central

Garver, Kyle A; Mahony, Amelia A. M.; Stucchi, Dario; Richard, Jon; Van Woensel, Cecile; Foreman, Mike

2013-01-01

Understanding how pathogenic organisms spread in the environment is crucial for the management of disease, yet knowledge of propagule dispersal and transmission in aquatic environments is limited. We conducted empirical studies using the aquatic virus, infectious hematopoietic necrosis virus (IHNV), to quantify infectious dose, shedding capacity, and virus destruction rates in order to better understand the transmission of IHN virus among Atlantic salmon marine net-pen aquaculture. Transmission of virus and subsequent mortality in Atlantic salmon post-smolts was initiated with as low as 10 plaque forming units (pfu) ml−1. Virus shedding from IHNV infected Atlantic salmon was detected before the onset of visible signs of disease with peak shed rates averaging 3.2×107 pfu fish−1 hour−1 one to two days prior to mortality. Once shed into the marine environment, the abundance of free IHNV is modulated by sunlight (UV A and B) and the growth of natural biota present in the seawater. Virus decayed very slowly in sterilized seawater while rates as high as k =  4.37 d−1 were observed in natural seawater. Decay rates were further accelerated when exposed to sunlight with virus infectivity reduced by six orders of magnitude within 3 hours of full sunlight exposure. Coupling the IHNV transmission parameter estimates determined here with physical water circulation models, will increase the understanding of IHNV dispersal and provide accurate geospatial predictions of risk for IHNV transmission from marine salmon sites. PMID:24340016

Enterovirus strain and type-specific differences in growth kinetics and virus-induced cell destruction in human pancreatic duct epithelial HPDE cells.

PubMed

Smura, Teemu; Natri, Olli; Ylipaasto, Petri; Hellman, Marika; Al-Hello, Haider; Piemonti, Lorenzo; Roivainen, Merja

2015-12-02

Enterovirus infections have been suspected to be involved in the development of type 1 diabetes. However, the pathogenetic mechanism of enterovirus-induced type 1 diabetes is not known. Pancreatic ductal cells are closely associated with pancreatic islets. Therefore, enterovirus infections in ductal cells may also affect beta-cells and be involved in the induction of type 1 diabetes. The aim of this study was to assess the ability of different enterovirus strains to infect, replicate and produce cytopathic effect in human pancreatic ductal cells. Furthermore, the viral factors that affect these capabilities were studied. The pancreatic ductal cells were highly susceptible to enterovirus infections. Both viral growth and cytolysis were detected for several enterovirus serotypes. However, the viral growth and capability to induce cytopathic effect (cpe) did not correlate completely. Some of the virus strains replicated in ductal cells without apparent cpe. Furthermore, there were strain-specific differences in the growth kinetics and the ability to cause cpe within some serotypes. Viral adaptation experiments were carried out to study the potential genetic determinants behind these phenotypic differences. The blind-passage of non-lytic CV-B6-Schmitt strain in HPDE-cells resulted in lytic phenotype and increased progeny production. This was associated with the substitution of a single amino acid (K257E) in the virus capsid protein VP1 and the viral ability to use decay accelerating factor (DAF) as a receptor. This study demonstrates considerable plasticity in the cell tropism, receptor usage and cytolytic properties of enteroviruses and underlines the strong effect of single or few amino acid substitutions in cell tropism and lytic capabilities of a given enterovirus. Since ductal cells are anatomically close to pancreatic islets, the capability of enteroviruses to infect and destroy pancreatic ductal cells may also implicate in respect to enterovirus induced type 1

Endoscopic management of acute necrotizing pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) evidence-based multidisciplinary guidelines.

PubMed

Arvanitakis, Marianna; Dumonceau, Jean-Marc; Albert, Jörg; Badaoui, Abdenor; Bali, Maria Antonietta; Barthet, Marc; Besselink, Marc; Deviere, Jacques; Oliveira Ferreira, Alexandre; Gyökeres, Tibor; Hritz, Istvan; Hucl, Tomas; Milashka, Marianna; Papanikolaou, Ioannis S; Poley, Jan-Werner; Seewald, Stefan; Vanbiervliet, Geoffroy; van Lienden, Krijn; van Santvoort, Hjalmar; Voermans, Rogier; Delhaye, Myriam; van Hooft, Jeanin

2018-05-01

1:  ESGE suggests using contrast-enhanced computed tomography (CT) as the first-line imaging modality on admission when indicated and up to the 4th week from onset in the absence of contraindications. Magnetic resonance imaging (MRI) may be used instead of CT in patients with contraindications to contrast-enhanced CT, and after the 4th week from onset when invasive intervention is considered because the contents (liquid vs. solid) of pancreatic collections are better characterized by MRI and evaluation of pancreatic duct integrity is possible. Weak recommendation, low quality evidence. 2:  ESGE recommends against routine percutaneous fine needle aspiration (FNA) of (peri)pancreatic collections. Strong recommendation, moderate quality evidence. FNA should be performed only if there is suspicion of infection and clinical/imaging signs are unclear. Weak recommendation, low quality evidence. 3:  ESGE recommends initial goal-directed intravenous fluid therapy with Ringer's lactate (e. g. 5 - 10 mL/kg/h) at onset. Fluid requirements should be patient-tailored and reassessed at frequent intervals. Strong recommendation, moderate quality evidence. 4:  ESGE recommends against antibiotic or probiotic prophylaxis of infectious complications in acute necrotizing pancreatitis. Strong recommendation, high quality evidence. 5:  ESGE recommends invasive intervention for patients with acute necrotizing pancreatitis and clinically suspected or proven infected necrosis. Strong recommendation, low quality evidence.ESGE suggests that the first intervention for infected necrosis should be delayed for 4 weeks if tolerated by the patient. Weak recommendation, low quality evidence. 6:  ESGE recommends performing endoscopic or percutaneous drainage of (suspected) infected walled-off necrosis as the first interventional method, taking into account the location of the walled-off necrosis and local expertise. Strong recommendation, moderate quality evidence. 7: �

Endoscopic Management of Peri-Pancreatic Fluid Collections.

PubMed

Yip, Hon Chi; Teoh, Anthony Yuen Bun

2017-09-15

In the past decade, there has been a progressive paradigm shift in the management of peri-pancreatic fluid collections after acute pancreatitis. Refinements in the definitions of fluid collections from the updated Atlanta classification have enabled better communication amongst physicians in an effort to formulate optimal treatments. Endoscopic ultrasound (EUS)-guided drainage of pancreatic pseudocysts has emerged as the procedure of choice over surgical cystogastrostomy. The approach provides similar success rates with low complications and better quality of life compared with surgery. However, an endoscopic "step up" approach in the management of pancreatic walled-off necrosis has also been advocated. Both endoscopic and percutaneous drainage routes may be used depending on the anatomical location of the collections. New-generation large diameter EUS-specific stent systems have also recently been described. The device allows precise and effective drainage of the collections and permits endoscopic necrosectomy through the stents.

Evaluation of the tepary bean (Phaseolus acutifolius) diversity panel for response to the NL 3 strain of Bean Common Mosaic Necrosis Virus (BCMNV) and for biological nitrogen fixation with Bradyrhizobium strains

USDA-ARS?s Scientific Manuscript database

Aphid-transmitted Bean Common Mosaic Necrosis Virus (BCMNV) and Bean Common Mosaic Virus (BCMV) are potyviruses that are seed transmitted in tepary bean. Developing resistance to these viruses will be critical for expanding production in areas where they are endemic. Biological nitrogen fixation (BN...

Concentration of infectious hematopoietic necrosis virus from water samples by tangential flow filtration and polyethylene glycol precipitation

USGS Publications Warehouse

Batts, W.N.; Winton, J.R.

1989-01-01

Infectious hematopoietic necrosis virus (IHNV) was concentrated from water samples by polyethylene glycol (PEG) precipitation, tangential flow filtration (TFF), and by a combination of TFF followed by PEG precipitation of the retentate. Used alone, PEG increased virus titers more than 200-fold, and the efficiency of recovery was as great as 100%. Used alone, TFF concentrated IHNV more than 20-fold, and average recovery was 70%. When the two techniques were combined, 10-L water samples were reduced to about 300 mL by TFF and the virus was precipitated with PEG into a 1 to 2 g pellet; total recovery was as great as 100%. The combined techniques were used to isolate IHNV from water samples taken from a river containing adult sockeye salmon (Oncorhynchus nerka) and from a hatchery pond containing adult spring chinook salmon (O. tshawytscha). The combination of these methods was effective in concentrating and detecting IHNV from water containing only three infectious particles per 10-L sample.

Infectious hematopoietic necrosis virus: Monophyletic origin of European isolates from North American Genogroup M

USGS Publications Warehouse

Enzmann, P.-J.; Kurath, G.; Fichtner, D.; Bergmann, S.M.

2005-01-01

Infectious hematopoietic necrosis virus (IHNV) was first detected in Europe in 1987 in France and Italy, and later, in 1992, in Germany. The source of the virus and the route of introduction are unknown. The present study investigates the molecular epidemiology of IHNV outbreaks in Germany since its first introduction. The complete nucleotide sequences of the glycoprotein (G) and non-virion (NV) genes from 9 IHNV isolates from Germany have been determined, and this has allowed the identification of characteristic differences between these isolates. Phylogenetic analysis of partial G gene sequences (mid-G, 303 nucleotides) from North American IHNV isolates (Kurath et al. 2003) has revealed 3 major genogroups, designated U, M and L. Using this gene region with 2 different North American IHNV data sets, it was possible to group the European IHNV strains within the M genogroup, but not in any previously defined subgroup. Analysis of the full length G gene sequences indicated that an independent evolution of IHN viruses had occurred in Europe. IHN viruses in Europe seem to be of a monophyletic origin, again most closely related to North American isolates in the M genogroup. Analysis of the NV gene sequences also showed the European isolates to be monophyletic, but resolution of the 3 genogroups was poor with this gene region. As a result of comparative sequence analyses, several different genotypes have been identified circulating in Europe. ?? Inter-Research 2005.

Pathogenesis of acute viral disease induced in fish by carp interstitial nephritis and gill necrosis virus.

PubMed

Pikarsky, Eli; Ronen, Ariel; Abramowitz, Julia; Levavi-Sivan, Berta; Hutoran, Marina; Shapira, Yechiam; Steinitz, Michael; Perelberg, Ayana; Soffer, Dov; Kotler, Moshe

2004-09-01

A lethal disease of koi and common carp (species Cyprinus carpio) has afflicted many fish farms worldwide since 1998, causing severe financial losses. Morbidity and mortality are restricted to common carp and koi and appear in spring and autumn, when water temperatures are 18 to 28 degrees C. We have isolated the virus causing the disease from sick fish, propagated it in koi fin cell culture, and shown that virus from a single clone causes lethal disease in carp and koi upon infection. Intraperitoneal virus injection or bathing the fish in virus-containing water kills 85 to 100% of the fish within 7 to 21 days. This virus is similar to the previously reported koi herpesvirus; however, it has characteristics inconsistent with the herpesvirus family, and thus we have called it carp interstitial nephritis and gill necrosis virus. We examined the pathobiology of this disease in carp by using immunohistochemistry and PCR. We found large amounts of the virus in the kidneys of sick fish and smaller amounts in liver and brain. A rapid increase in the viral load in the kidneys was detected by using both immunofluorescence and semiquantitative PCR. Histological analyses of fish at various times after infection revealed signs of interstitial nephritis as early as 2 days postinfection, which increased in severity up to 10 days postinfection. There was severe gill disease evidenced by loss of villi with accompanying inflammation in the gill rakers. Minimal focal inflammation was noted in livers and brains. This report describes the etiology and pathology of a recently described viral agent in fish.

Pathogenesis of Acute Viral Disease Induced in Fish by Carp Interstitial Nephritis and Gill Necrosis Virus

PubMed Central

Pikarsky, Eli; Ronen, Ariel; Abramowitz, Julia; Levavi-Sivan, Berta; Hutoran, Marina; Shapira, Yechiam; Steinitz, Michael; Perelberg, Ayana; Soffer, Dov; Kotler, Moshe

2004-01-01

A lethal disease of koi and common carp (species Cyprinus carpio) has afflicted many fish farms worldwide since 1998, causing severe financial losses. Morbidity and mortality are restricted to common carp and koi and appear in spring and autumn, when water temperatures are 18 to 28°C. We have isolated the virus causing the disease from sick fish, propagated it in koi fin cell culture, and shown that virus from a single clone causes lethal disease in carp and koi upon infection. Intraperitoneal virus injection or bathing the fish in virus-containing water kills 85 to 100% of the fish within 7 to 21 days. This virus is similar to the previously reported koi herpesvirus; however, it has characteristics inconsistent with the herpesvirus family, and thus we have called it carp interstitial nephritis and gill necrosis virus. We examined the pathobiology of this disease in carp by using immunohistochemistry and PCR. We found large amounts of the virus in the kidneys of sick fish and smaller amounts in liver and brain. A rapid increase in the viral load in the kidneys was detected by using both immunofluorescence and semiquantitative PCR. Histological analyses of fish at various times after infection revealed signs of interstitial nephritis as early as 2 days postinfection, which increased in severity up to 10 days postinfection. There was severe gill disease evidenced by loss of villi with accompanying inflammation in the gill rakers. Minimal focal inflammation was noted in livers and brains. This report describes the etiology and pathology of a recently described viral agent in fish. PMID:15308746

Pathobiology of highly pathogenic avian influenza virus (H5N1) infection in mute swans (Cygnus olor).

PubMed

Pálmai, Nimród; Erdélyi, Károly; Bálint, Adám; Márton, Lázár; Dán, Adám; Deim, Zoltán; Ursu, Krisztina; Löndt, Brandon Z; Brown, Ian H; Glávits, Róbert

2007-06-01

The results of pathological, virological and polymerase chain reaction examinations carried out on 35 mute swans (Cygnus olor) that succumbed to a highly pathogenic avian influenza virus (H5N1) infection during an outbreak in Southern Hungary are reported. The most frequently observed macroscopic lesions included: haemorrhages under the epicardium, in the proventricular and duodenal mucosa and pancreas; focal necrosis in the pancreas; myocardial degeneration; acute mucous enteritis; congestion of the spleen and lung, and the accumulation of sero-mucinous exudate in the body cavity. Histopathological lesions comprised: lymphocytic meningo-encephalomyelitis accompanied by gliosis and occasional perivascular haemorrhages; multi-focal myocardial necrosis with lympho-histiocytic infiltration; pancreatitis with focal necrosis; acute desquamative mucous enteritis; lung congestion and oedema; oedema of the tracheal mucosa and, in young birds, the atrophy of the bursa of Fabricius as a result of lymphocyte depletion and apoptosis. The observed lesions and the moderate to good body conditions were compatible with findings in acute highly pathogenic avian influenza infections of other bird species reported in the literature. Skin lesions and lesions typical for infections caused by strains of lower pathogenicity (low pathogenic avian influenza virus) such as emaciation or fibrinous changes in the reproductive and respiratory organs, sinuses and airsacs were not observed. The H5N1 subtype avian influenza virus was isolated in embryonated fowl eggs from all cases and it was identified by classical and molecular virological methods.

[Determinant-based classification of acute pancreatitis severity. International multidisciplinary classification of acute pancreatitis severity: the 2013 German edition].

PubMed

Layer, P; Dellinger, E P; Forsmark, C E; Lévy, P; Maraví-Poma, E; Shimosegawa, T; Siriwardena, A K; Uomo, G; Whitcomb, D C; Windsor, J A; Petrov, M S

2013-06-01

The aim of this study was to develop a new international classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of published evidence, and worldwide consultation. The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of pancreatologists but suboptimal because these definitions are based on empiric descriptions of occurrences that are merely associated with severity. A personal invitation to contribute to the development of a new international classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensive medicine specialists, and radiologists who are currently active in clinical research on acute pancreatitis. The invitation was not limited to members of certain associations or residents of certain countries. A global Web-based survey was conducted and a dedicated international symposium was organised to bring contributors from different disciplines together and discuss the concept and definitions. The new international classification is based on the actual local and systemic determinants of severity, rather than descriptions of events that are correlated with severity. The local determinant relates to whether there is (peri)pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another such that the presence of both infected (peri)pancreatic necrosis and persistent organ failure have a greater effect on severity than either determinant alone. The derivation of a classification based on the above principles results in 4 categories of severity - mild, moderate, severe, and critical. This classification is the result of a consultative process amongst pancreatologists from 49 countries spanning North America, South America

High fat diet and GLP-1 drugs induce pancreatic injury in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rouse, Rodney, E-mail: rodney.rouse@fda.hhs.gov; Xu, Lin; Stewart, Sharron

Glucagon Like Peptide-1 (GLP-1) drugs are currently used to treat type-2 diabetes. Safety concerns for increased risk of pancreatitis and pancreatic ductal metaplasia have accompanied these drugs. High fat diet (HFD) is a type-2 diabetes risk factor that may affect the response to GLP-1 drug treatment. The objective of the present study was to investigate the effects of diet and GLP-1 based drugs on the exocrine pancreas in mice. Experiments were designed in a mouse model of insulin resistance created by feeding a HFD or standard diet (STD) for 6 weeks. The GLP-1 drugs, sitagliptin (SIT) and exenatide (EXE) weremore » administered once daily for additional 6 weeks in both mice fed HFD or STD. The results showed that body weight, blood glucose levels, and serum levels of pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly greater in HFD mice than in STD mice regardless of GLP-1 drug treatment. The semi-quantitative grading showed that pancreatic changes were significantly greater in EXE and SIT-treated mice compared to control and that HFD exacerbated spontaneous exocrine pancreatic changes seen in saline-treated mice on a standard diet. Exocrine pancreatic changes identified in this study included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. These findings support HFD as a risk factor to increased susceptibility/severity for acute pancreatitis and indicate that GLP-1 drugs cause pancreatic injury that can be exacerbated in a HFD environment.« less

Stability of Cucumber Necrosis Virus at the Quasi-6-Fold Axis Affects Zoospore Transmission.

PubMed

Sherman, Michael B; Kakani, Kishore; Rochon, D'Ann; Jiang, Wen; Voss, Neil R; Smith, Thomas J

2017-10-01

Cucumber necrosis virus (CNV) is a member of the genus Tombusvirus and has a monopartite positive-sense RNA genome. CNV is transmitted in nature via zoospores of the fungus Olpidium bornovanus As with other members of the Tombusvirus genus, the CNV capsid swells when exposed to alkaline pH and EDTA. We previously demonstrated that a P73G mutation blocks the virus from zoospore transmission while not significantly affecting replication in plants (K. Kakani, R. Reade, and D. Rochon, J Mol Biol 338:507-517, 2004, https://doi.org/10.1016/j.jmb.2004.03.008). P73 lies immediately adjacent to a putative zinc binding site (M. Li et al., J Virol 87:12166-12175, 2013, https://doi.org/10.1128/JVI.01965-13) that is formed by three icosahedrally related His residues in the N termini of the C subunit at the quasi-6-fold axes. To better understand how this buried residue might affect vector transmission, we determined the cryo-electron microscopy structure of wild-type CNV in the native and swollen state and of the transmission-defective mutant, P73G, under native conditions. With the wild-type CNV, the swollen structure demonstrated the expected expansion of the capsid. However, the zinc binding region at the quasi-6-fold at the β-annulus axes remained intact. By comparison, the zinc binding region of the P73G mutant, even under native conditions, was markedly disordered, suggesting that the β-annulus had been disrupted and that this could destabilize the capsid. This was confirmed with pH and urea denaturation experiments in conjunction with electron microscopy analysis. We suggest that the P73G mutation affects the zinc binding and/or the β-annulus, making it more fragile under neutral/basic pH conditions. This, in turn, may affect zoospore transmission. IMPORTANCE Cucumber necrosis virus (CNV), a member of the genus Tombusvirus , is transmitted in nature via zoospores of the fungus Olpidium bornovanus While a number of plant viruses are transmitted via insect vectors

Stability of Cucumber Necrosis Virus at the Quasi-6-Fold Axis Affects Zoospore Transmission

PubMed Central

Sherman, Michael B.; Kakani, Kishore; Rochon, D'Ann; Jiang, Wen; Voss, Neil R.

2017-01-01

ABSTRACT Cucumber necrosis virus (CNV) is a member of the genus Tombusvirus and has a monopartite positive-sense RNA genome. CNV is transmitted in nature via zoospores of the fungus Olpidium bornovanus. As with other members of the Tombusvirus genus, the CNV capsid swells when exposed to alkaline pH and EDTA. We previously demonstrated that a P73G mutation blocks the virus from zoospore transmission while not significantly affecting replication in plants (K. Kakani, R. Reade, and D. Rochon, J Mol Biol 338:507–517, 2004, https://doi.org/10.1016/j.jmb.2004.03.008). P73 lies immediately adjacent to a putative zinc binding site (M. Li et al., J Virol 87:12166–12175, 2013, https://doi.org/10.1128/JVI.01965-13) that is formed by three icosahedrally related His residues in the N termini of the C subunit at the quasi-6-fold axes. To better understand how this buried residue might affect vector transmission, we determined the cryo-electron microscopy structure of wild-type CNV in the native and swollen state and of the transmission-defective mutant, P73G, under native conditions. With the wild-type CNV, the swollen structure demonstrated the expected expansion of the capsid. However, the zinc binding region at the quasi-6-fold at the β-annulus axes remained intact. By comparison, the zinc binding region of the P73G mutant, even under native conditions, was markedly disordered, suggesting that the β-annulus had been disrupted and that this could destabilize the capsid. This was confirmed with pH and urea denaturation experiments in conjunction with electron microscopy analysis. We suggest that the P73G mutation affects the zinc binding and/or the β-annulus, making it more fragile under neutral/basic pH conditions. This, in turn, may affect zoospore transmission. IMPORTANCE Cucumber necrosis virus (CNV), a member of the genus Tombusvirus, is transmitted in nature via zoospores of the fungus Olpidium bornovanus. While a number of plant viruses are transmitted via insect

The role of melatonin in pancreatic protection: could melatonin be used in the treatment of acute pancreatitis?

PubMed

Jaworek, Jolanta; Leja-Szpak, Anna; Kot, Michalina; Jaworek, Andrzej; Nawrot-Porbka, Katarzyna; Bonior, Joanna; Szklarczyk, Joanna

2014-01-01

Acute pancreatitis is a disease, which could be manifested as either a mild edematous form or a more severe necrotizing pancreatitis which has a poor prognosis. The etiology and pathogenesis of this ailment is not completely clear. Melatonin is an indoleamine which is produced from L-tryptophan in the pineal gland and in the other tissue including gastrointestinal tract. Both melatonin and its precursor have been demonstrated to protect the pancreas against acute pancreatitis and to attenuate pancreatic tissue damage. In the pancreas melatonin and L-tryptophan activate complex mechanisms which involve direct scavenging of the radical oxygen and nitrogen species, activation of antioxidant enzymes (catalase, superoxide dysmutase, glutation peroxidase), reduction of pro-inflammatory cytokines and prostaglandins, activation of heat shock protein, and a decrease of necrosis and increase of regeneration in the pancreas. There are several arguments for the idea that endogenous melatonin produced in the pineal gland and in the gastrointestinal system could be the part of a native mechanisms for protecting the pancreas against acute damage: 1/ the melatonin precursor L-tryptophan exerts similar protective effect as melatonin, 2/ application of the melatonin receptor antagonist, luzindole aggravates acute pancreatitis, 3/ pinealectomy results in the exacerbation of acute pancreatitis, 4/ low melatonin plasma levels are associated with an increased risk of severe acute pancreatitis. These observations leads to the idea that perhaps melatonin could be used in clinical trials as supportive therapy in acute pancreatitis.

Biochemical and antigenic properties of the first isolates of infectious hematopoietic necrosis virus from salmonid fish in Europe

USGS Publications Warehouse

Arkush, K.D.; Bovo, G.; DeKinkelin, P.; Winton, J.R.; Wingfield, W.H.; Hedrick, R.P.

1989-01-01

The first isolates of infectious hematopoietic necrosis virus (IHNV) recovered from rainbow trout Oncorhynchus mykiss (formerly Salmo gairdneri) in France and Italy were compared to six representative strains from North America by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of virion polypeptides and neutralization by monoclonal antibodies (MAbs). All three IHNV isolates from Europe had similar polypeptide profiles when compared by SDS-PAGE. An analysis of the antigenic relatedness of the European isolates to representative strains from North America showed that they were clearly different from viruses obtained from salmonids in California. The RB/B5 MAb, which was developed against virus isolated from adult steelhead (anadromous rainbow trout) reared in central Oregon, neutralized all isolates examined. The 193–110/B4 MAb, developed against IHNV isolated from infected yearling rainbow trout in southern Idaho, neutralized all isolates tested except those from California. The SRCV/A4 MAb, developed against Sacramento River chinook virus (SRCV) isolated from adult spring chinook salmon O. tshawytscha in central California, was the least reactive, and strong neutralization was observed only with the SRCV strain of IHNV from California. However, partial reactivity of the virus isolates from France with the SRCV/A4 MAb distinguished them from the virus recovered from salmonids in Italy.

Prophylactic antibiotics in acute pancreatitis: endless debate.

PubMed

Mourad, M M; Evans, Rpt; Kalidindi, V; Navaratnam, R; Dvorkin, L; Bramhall, S R

2017-02-01

INTRODUCTION The development of pancreatic infection is associated with the development of a deteriorating disease with subsequent high morbidity and mortality. There is agreement that in mild pancreatitis there is no need to use antibiotics; in severe pancreatitis it would appear to be a logical choice to use antibiotics to prevent secondary pancreatic infection and decrease associated mortality. MATERIALS AND METHODS A non-systematic review of current evidence, meta-analyses and randomized controlled trials was conducted to assess the role of prophylactic antibiotics in acute pancreatitis and whether it might improve morbidity and mortality in pancreatitis. RESULTS Mixed evidence was found to support and refute the role of prophylactic antibiotics in acute pancreatitis. Most studies have failed to demonstrate much benefit from its routine use. Data from our unit suggested little benefit of their routine use, and showed that the mortality of those treated with antibiotics was significantly higher compared with those not treated with antibiotics (9% vs 0%, respectively, P = 0.043). In addition, the antibiotic group had significantly higher morbidity (36% vs 5%, respectively, P = 0.002). CONCLUSIONS Antibiotics should be used in patients who develop sepsis, infected necrosis-related systemic inflammatory response syndrome, multiple organ dysfunction syndrome or pancreatic and extra-pancreatic infection. Despite the many other factors that should be considered, prompt antibiotic therapy is recommended once inflammatory markers are raised, to prevent secondary pancreatic infection. Unfortunately, there remain many unanswered questions regarding the indications for antibiotic administration and the patients who benefit from antibiotic treatment in acute pancreatitis.

Vaccinia Virus Induces Rapid Necrosis in Keratinocytes by a STAT3-Dependent Mechanism

PubMed Central

He, Yong; Fisher, Robert; Chowdhury, Soma; Sultana, Ishrat; Pereira, Claudia P.; Bray, Mike; Reed, Jennifer L.

2014-01-01

Rationale Humans with a dominant negative mutation in STAT3 are susceptible to severe skin infections, suggesting an essential role for STAT3 signaling in defense against cutaneous pathogens. Methods To focus on innate antiviral defenses in keratinocytes, we used a standard model of cutaneous infection of severe combined immunodeficient mice with the current smallpox vaccine, ACAM-2000. In parallel, early events post-infection with the smallpox vaccine ACAM-2000 were investigated in cultured keratinocytes of human and mouse origin. Results Mice treated topically with a STAT3 inhibitor (Stattic) developed larger vaccinia lesions with higher virus titers and died more rapidly than untreated controls. Cultured human and murine keratinocytes infected with ACAM-2000 underwent rapid necrosis, but when treated with Stattic or with inhibitors of RIP1 kinase or caspase-1, they survived longer, produced higher titers of virus, and showed reduced activation of type I interferon responses and inflammatory cytokines release. Treatment with inhibitors of RIP1 kinase and STAT3, but not caspase-1, also reduced the inflammatory response of keratinocytes to TLR ligands. Vaccinia growth properties in Vero cells, which are known to be defective in some antiviral responses, were unaffected by inhibition of RIP1K, caspase-1, or STAT3. Conclusions Our findings indicate that keratinocytes suppress the replication and spread of vaccinia virus by undergoing rapid programmed cell death, in a process requiring STAT3. These data offer a new framework for understanding susceptibility to skin infection in patients with STAT3 mutations. Interventions which promote prompt necroptosis/pyroptosis of infected keratinocytes may reduce risks associated with vaccination with live vaccinia virus. PMID:25419841

Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by activating NF-κB pathway in experimental pancreatitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Ge; Wan, Rong; Hu, Yanling

2014-01-31

Highlights: • CypA is upregulated in experimental pancreatitis. • CCK induces expression and release of CypA in acinar cell in vitro. • rCypA aggravates CCK-induced acinar cell death and inflammatory cytokine production. • rCypA activates the NF-κB pathway in acinar cells in vitro. - Abstract: Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration ofmore » sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway.« less

VP08R from Infectious Spleen and Kidney Necrosis Virus Is a Novel Component of the Virus-Mock Basement Membrane

PubMed Central

Xu, Xiaopeng; Yan, Muting; Wang, Rui; Lin, Ting; Tang, Junliang; Li, Chaozheng; Weng, Shaoping

2014-01-01

ABSTRACT Infectious spleen and kidney necrosis virus (ISKNV), the type species of the genus Megalocytivirus, family Iridoviridae, brings great harm to fish farming. In infected tissues, ISKNV infection is characterized by a unique phenomenon, in that the infected cells are attached by lymphatic endothelial cells (LECs), which are speculated to wall off the infected cells from host immune attack. A viral membrane protein, VP23R, binds and recruits the host nidogen-1 protein to construct a basement membrane (BM)-like structure, termed virus-mock basement membrane (VMBM), on the surface of infected cells to provide attaching sites for LECs. VMBMs do not contain collagen IV protein, which is essential for maintenance of BM integrity and functions. In this study, we identified the VP08R protein encoded by ISKNV. VP08R was predicted to be a secreted protein with a signal peptide but without a transmembrane domain. However, immunofluorescence assays demonstrated that VP08R is located on the plasma membrane of infected cells and shows an expression profile similar to that of VP23R. Coimmunoprecipitation showed that VP08R interacts with both VP23R and nidogen-1, indicating that VP08R is a component of VMBM and is present on the cell membrane by binding to VP23R. Through formation of intermolecular disulfide bonds, VP08R molecules self-organized into a multimer, which may play a role in the maintenance of VMBM integrity and stability. Moreover, the VP08R multimer was easily degraded when the ISKNV-infected cells were lysed, which may be a mechanism for VMBM disassembly when necessary to free LECs and release the mature virions. IMPORTANCE Infectious spleen and kidney necrosis virus (ISKNV; genus Megalocytivirus, family Iridovirus) is most harmful to cultured fishes. In tissues, the ISKNV-infected cells are attached by lymphatic endothelial cells (LECs), which are speculated to segregate the host immune system. A viral membrane protein, VP23R, binds and recruits the host

Geography and host species shape the evolutionary dynamics of U genogroup infectious hematopoietic necrosis virus

USGS Publications Warehouse

Black, Allison; Breyta, Rachel; Bedford, Trevor; Kurath, Gael

2016-01-01

Infectious hematopoietic necrosis virus (IHNV) is a negative-sense RNA virus that infects wild and cultured salmonids throughout the Pacific Coastal United States and Canada, from California to Alaska. Although infection of adult fish is usually asymptomatic, juvenile infections can result in high mortality events that impact salmon hatchery programs and commercial aquaculture. We used epidemiological case data and genetic sequence data from a 303 nt portion of the viral glycoprotein gene to study the evolutionary dynamics of U genogroup IHNV in the Pacific Northwestern United States from 1971 to 2013. We identified 114 unique genotypes among 1,219 U genogroup IHNV isolates representing 619 virus detection events. We found evidence for two previously unidentified, broad subgroups within the U genogroup, which we designated ‘UC’ and ‘UP’. Epidemiologic records indicated that UP viruses were detected more frequently in sockeye salmon (Oncorhynchus nerka) and in coastal waters of Washington and Oregon, whereas UC viruses were detected primarily in Chinook salmon (Oncorhynchus tshawytscha) and steelhead trout (Oncorhynchus mykiss) in the Columbia River Basin, which is a large, complex watershed extending throughout much of interior Washington, Oregon, and Idaho. These findings were supported by phylogenetic analysis and by FST. Ancestral state reconstruction indicated that early UC viruses in the Columbia River Basin initially infected sockeye salmon but then emerged via host shifts into Chinook salmon and steelhead trout sometime during the 1980s. We postulate that the development of these subgroups within U genogroup was driven by selection pressure for viral adaptation to Chinook salmon and steelhead trout within the Columbia River Basin.

Evaluation of the BISAP scoring system in prognostication of acute pancreatitis - A prospective observational study.

PubMed

Hagjer, Sumitra; Kumar, Nitesh

2018-04-21

Severe acute pancreatitis has a high mortality and its early identification is important for management and risk stratification. The bedside index for severity in acute pancreatitis (BISAP) is a simple scoring system done at admission which predicts the severity of pancreatitis. Procalcitonin is an inflammatory marker which is raised very early and helps in early prediction of the severity of disease. This study aims to evaluate the BISAP score and Procalcitonin in prognostication of acute pancreatitis. A prospective observational study of 60 patients presenting with acute pancreatitis was done at XXX Medical College and Hospital from July 2015 to June 2016. BISAP, APACHE-II, Ranson criteria, and CT severity index (CTSI) of all patients were calculated. Procalcitonin card test was done for all patients. The patients were stratified according by BISAP score and procalcitonin positivity into categories of severe pancreatitis, organ failure and pancreatic necrosis, as well as the number of deaths. The comparison of BISAP with other scoring systems, Procalcitonin (PCT), C-reactive protein (CRP), hematocrit, and body mass index (BMI) was done by the area under the receiver-operating curve (AUC) to prediction of severe acute pancreatitis, organ failure, necrosis, and death. Of the 60 patients, 14 (23.3%) developed severe acute pancreatitis, 11 (18.3%) Organ failure, 21 (35%) pancreatic necrosis and 7 (11.6%) died. A BISAP score of ≥3 was a statistically significant cutoff value. AUCs for predicting severe pancreatitis and death of BISAP were 0.875 and 0.740respectively, similar to those for Ranson criteria (0.802, 0.763) and APACHE-II (0.891, 0.769) and greater than AUCs for CTSI (0.641, 0.554). The AUC for prediction of organ failure were 0.906, 0.833, 0.874 and 0.623 for BISAP, Ranson criteria, APACHE-II, and CTSI respectively. AUCs for PCT predicting severity, organ failure, and death were 0.940, 0.923 and 0.769 respectively were similar to BISAP but greater than

Anti-inflammatory effect of α,β-amyrin, a triterpene from Protium heptaphyllum, on cerulein-induced acute pancreatitis in mice.

PubMed

Melo, Caroline M; Morais, Talita C; Tomé, Adriana R; Brito, Gerly Anne C; Chaves, Mariana H; Rao, Vietla S; Santos, Flávia A

2011-07-01

To evaluate the anti-inflammatory effect of α,β-amyrin, a pentacyclic triterpenoid from Protium heptaphyllum, on cerulein-induced acute pancreatitis in mice. Acute pancreatitis was induced in Swiss mice by five intraperitoneal injections of cerulein (50 μg/kg), at 1 h intervals. Mice received α,β-amyrin (10, 30 and 100 mg/kg), thalidomide (200 mg/kg), or vehicle (3% Tween 80) orally 1 h before and 12 h after the cerulein challenge. The severity of pancreatitis was evaluated 24 h after cerulein by assessing serum pro-inflammatory cytokines and amylase activity, pancreatic myeloperoxidase (MPO), and thiobarbituric acid-reactive substances (TBARS), as well as by histology. α,β-Amyrin and thalidomide significantly attenuated the cerulein-induced increase in tumor necrosis factor (TNF)-α, interleukin-6, lipase, amylase, MPO, and TBARS. Moreover, α,β-amyrin greatly suppressed the pancreatic edema, inflammatory cell infiltration, acinar cell necrosis, and expressions of TNFα and inducible nitric oxide synthase. α,β-Amyrin ameliorates cerulein-induced acute pancreatitis by acting as an anti-inflammatory and antioxidant agent.

Virulence of a chimeric recombinant infectious haematopoietic necrosis virus expressing the spring viraemia of carp virus glycoprotein in salmonid and cyprinid fish

USGS Publications Warehouse

Emmenegger, Eveline; Biacchesi, Stéphane; Mérour, Emilie; Glenn, Jolene. A; Palmer, Alexander D.; Brémont, Michel; Kurath, Gael

2018-01-01

Infectious haematopoietic necrosis virus (IHNV) and spring viraemia of carp virus (SVCV) are both rhabdoviruses of fish, listed as notifiable disease agents by the World Organization for Animal Health. Recombinant rhabdoviruses with heterologous gene substitutions have been engineered to study genetic determinants and assess the potential of these recombinant viruses for vaccine development. A recombinant IHNV (rIHNV), containing the full-length genome of a European IHNV strain, was modified by deleting the glycoprotein (G) gene and replacing it with a European SVCV G-gene to make the rIHNV-Gsvcv. The chimeric rIHNV-Gsvcv level of virulence in rainbow trout, common carp and koi was assessed, and its ability to induce a protective immune response in surviving koi against wild-type SVCV infection was tested. The rIHNV-Gsvcv infection of trout led to high mortality, ranging from 78% to 92.5%, after immersion. In contrast, no deaths occurred in juvenile common carp after infection with rIHNV-Gsvcv by either immersion or intraperitoneal (IP) injection. Similarly, koi infected with rIHNV-Gsvcv via IP injection had little to no mortality (≤9%). Koi that survived initial infection with a high dose of recombinant virus rIHNV-Gsvcv were protected against a virulent SVCV challenge resulting in a high relative per cent survival of 82.5%.

Peripancreatic collections in acute pancreatitis: Correlation between computerized tomography and operative findings

PubMed Central

Vege, Santhi Swaroop; Fletcher, Joel G; Talukdar, Rupjyoti; Sarr, Michael G

2010-01-01

AIM: To evaluate the ability of contrast-enhanced computerized tomography (CECT) to characterize the nature of peripancreatic collections. METHODS: Twenty five patients with peripancreatic collections on CECT and who underwent operative intervention for severe acute pancreatitis were retrospectively studied. The collections were classified into (1) necrosis without frank pus; (2) necrosis with pus; and (3) fluid without necrosis. A blinded radiologist assessed the preoperative CTs of each patient for necrosis and peripancreatic fluid collections. Peripancreatic collections were described in terms of volume, location, number, heterogeneity, fluid attenuation, wall perceptibility, wall enhancement, presence of extraluminal gas, and vascular compromise. RESULTS: Fifty-four collections were identified at operation, of which 45 (83%) were identified on CECT. Of these, 25/26 (96%) had necrosis without pus, 16/19 (84%) had necrosis with pus, and 4/9 (44%) had fluid without necrosis. Among the study characteristics, fluid heterogeneity was seen in a greater proportion of collections in the group with necrosis and pus, compared to the other two groups (94% vs 48% and 25%, P = 0.002 and 0.003, respectively). Among the wall characteristics, irregularity was seen in a greater proportion of collections in the groups with necrosis with and without pus, when compared to the group with fluid without necrosis (88% and 71% vs 25%, P = 0.06 and P < 0.01, respectively). The combination of heterogeneity and presence of extraluminal gas had a specificity and positive likelihood ratio of 92% and 5.9, respectively, in detecting pus. CONCLUSION: Most of the peripancreatic collections seen on CECT in patients with severe acute pancreatitis who require operative intervention contain necrotic tissue. CECT has a somewhat limited role in differentiating the different types of collections. PMID:20818812

Fulminant Epstein-Barr virus - infectious mononucleosis in an adult with liver failure, splenic rupture, and spontaneous esophageal bleeding with ensuing esophageal necrosis: a case report.

PubMed

Busch, Daniel; Hilswicht, Sarah; Schöb, Dominik S; von Trotha, Klaus T; Junge, Karsten; Gassler, Nikolaus; Truong, Son; Neumann, Ulf P; Binnebösel, Marcel

2014-02-05

Infectious mononucleosis is a clinical syndrome most commonly associated with primary Epstein-Barr virus infection. The majority of patients with infectious mononucleosis recovers without apparent sequelae. However, infectious mononucleosis may be associated with several acute complications. In this report we present a rare case of esophageal rupture that has never been described in the literature before. We present the case of an 18-year-old Caucasian man affected by severe infectious mononucleosis complicated by fulminant hepatic failure, splenic rupture and esophageal necrosis. Although primary Epstein-Barr virus infection is rarely fatal, fulminant infection may occur - in this case leading to hepatic failure, splenic rupture and esophageal necrosis, subsequently making several surgical interventions necessary. We show here that infectious mononucleosis is not only a strictly medical condition, but can also lead to severe surgical complications.

[Retrograde pancreatic duct imaging and surgical tactics in hemorrhagic necrotizing pancreatitis. Preliminary report].

PubMed

Gebhardt, C; Gall, F P; Lux, G; Riemann, J; Link, W

1983-12-01

In patients with haemorrhagic necrotizing pancreatitis who are scheduled for surgery we have been carrying out a preoperative retrograde investigation of the pancreatic duct system for the past months. The results in, to date, ten patients revealed four different morphological findings of importance for the surgical tactic: 1. A normal pancreatic duct system with no signs of fistulae: only peripancreatic necrosectomy is required. - 2. Contrast medium leaks via a ductal fistula: left resection including the removal of the fistulous area must be done. - 3. Normal duct system with complete segmental parenchymal staining, representing total necrosis in this region: left resection of the pancreas. - 4. Duodenoscopically demonstrable perforation into the duodenum of a necrotic cavity in the head of the pancreas: conservative management only, no surgery, since this lesion resulting in drainage of the necrotic cavity into the bowel permits self-healing, while the site of the perforation within the necrotic wall cannot be dealt with by surgery. - The experience gained so far indicates that the surgical tactic can be determined with greater selectivity by the use of ERP.

Triple Pancreatic Walled-off Fluid Collections Treated Simultaneously with Endoscopic Transmural Drainage.

PubMed

Khalid, Sameen; Abbass, Aamer; Nellis, Eric; Shah, Shashin; Shah, Hiral

2018-01-09

Pancreatic pseudocysts and walled-off pancreatic necrosis arise as a complication of pancreatitis. Multiple fluid collections are seen in 5-20% of the patients who have walled-off peripancreatic fluid collections. There is a paucity of data regarding the role of endoscopic transmural drainage in the management of multiple pancreatic fluid collections. In this case report, we present the case of a 72-year-old male with three walled-off pancreatic fluid collections in the setting of acute necrotizing pancreatitis. The patient underwent simultaneous endoscopic ultrasound-assisted cyst gastrostomy and cyst duodenostomy and aggressive irrigation without index endoscopic necrosectomy of the three peripancreatic fluid collections. Significant improvement in the size of the fluid collections was seen on the computed tomography scan, as well as a remarkable immediate clinical improvement after 24 hours of the endoscopic intervention.

Co-infections of infectious spleen and kidney necrosis virus and Siniperca chuatsi rhabdovirus in Chinese perch (Siniperca chuatsi).

PubMed

Lin, Qiang; Fu, Xiaozhe; Li, Ningqiu; Wan, Quanyuan; Chen, Wenjie; Huang, Yunmao; Huang, Zhibin; Li, Jun; Zhao, Lijuan; Lin, Li

2017-10-01

In spite of the quite common co-infections of viruses in the cultured fish, most of the previous studies have just simply focused on the infection of a single pathogen. In this report, we observed that about 13% of cultured Chinese perch have been co-infected by infectious spleen and kidney necrosis virus (ISKNV) and Siniperca chuatsi rhabdovirus (SCRV). Furthermore, Chinese perch could co-infected by ISKNV and SCRV by intraperitoneally injection with the two viruses. Interestingly, we revealed that the two viruses could even co-infect a single cell of Chinese perch in vivo and a single Chinese perch brain cells (CPB) cell in vitro. The dynamic co-infected viruses loads in the different tissues of Chinese perch showed dependent. When CPB cells were infected with the same 10 MOI of SCRV and ISKNV, the replication of SCRV overwhelmed the replication of ISKNV. When the MOI of ISKNV (10 MOI) was 10,000 times of MOI of SCRV (0.001 MOI), the dynamic virus loads of the two viruses in CPB cells indicated that co-infections could synergistically stimulate both viruses replication at the late time points but not at early time points. The co-infections of ISKNV and SCRV in the cultured Chinese perch will shed a new light on the prevention of the viral diseases of Chinese perch. The development of multivalent vaccine which could be effective for preventing against the co-infections of the viruses is highly needed. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Pathophysiology of hormonal, immune, metabolic changes in acute and chronic pancreatitis. Experimental and clinical studies].

PubMed

Trubitsyna, I E; Chikunova, B Z; Tkachenko, E V; Tsaregorodtseva, T M; Vinokurova, L V; Varvanina, G G

2008-01-01

There is literature review of the acute and chronic pancreatitis experimental models. Patogenetic necrosis mechanisms with fibrosis progress in pancreas were revealed. The stimulation of the proteolytic enzymes synthesis and secretion, that was examined in experiments were compared with clinical examinations. The patients with chronic pancreatitis were investigated in the Central Research Institute of Gastroenterology.

[Multidisciplinar international classification of the severity of acute pancreatitis: Italian version 2013].

PubMed

Uomo, G; Patchen Dellinger, E; Forsmark, C E; Layer, P; Lévy, P; Maravì-Poma, E; Shimosegawa, T; Siriwardena, A K; Whitcomb, D C; Windsor, J A; Petrov, M S

2013-12-01

The aim of this paper was to present the 2013 Italian edition of a new international classification of acute pancreatitis severity. The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of pancreatologists but suboptimal because these definitions are based on empiric description of occurrences that are merely associated with severity. A personal invitation to contribute to the development of a new international classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensivists, and radiologists who are currently active in clinical research on acute pancreatitis. A global web-based survey was conducted and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. The new international classification is based on the actual local and systemic determinants of severity, rather than description of events that are correlated with severity. The local determinant relates to whether there is (peri)pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another such that the presence of both infected (peri)pancreatic necrosis and persistent organ failure have a greater effect on severity than either determinant alone. The derivation of a classification based on the above principles results in 4 categories of severity-mild, moderate, severe, and critical. This classification provides a set of concise up-to-date definitions of all the main entities pertinent to classifying the severity of acute pancreatitis in clinical practice and research.

The North American strain of viral hemorrhagic septicemia virus is highly pathogenic for laboratory-reared Pacific herring (Clupea pallasi)

USGS Publications Warehouse

Kocan, R.; Bradley, M.; Elder, N.; Meyers, T.; Batts, W.; Winton, J.

1997-01-01

Specific-pathogen-free Pacific herring Clupea pallasi were reared in the laboratory from eggs and then challenged at 5, 9, and 13 months of age by waterborne exposure to low (101.5–2.5 plaque-forming units [PFU] per milliliter), medium (103.5–4.5 PFU/mL), or high (105.5–6.5 PFU/mL) levels of a North American isolate of viral hemorrhagic septicemia virus (VHSV). The fish were extremely susceptible to the virus, showing clinical disease, mortality approaching 100%, and only a limited increase in resistance with age. Mortality began 4–6 d after exposure and peaked at approximately day 7 in fish exposed to high levels of virus. Whereas the mean time to death showed a significant dose response (P < 0.001), the percent mortality and virus titers in dead fish were generally high in all groups regardless of initial challenge dose. External signs of disease were usually limited to 1–2-mm hemorrhagic areas on the lower jaw and isthmus and around the eye, but 2 of 130 infected fish exhibited extensive cutaneous hemorrhaging. Histopathologic examination of tissues from moribund fish sampled at 2–8 d after exposure revealed multifocal coagulative necrosis of hepatocytes, diffuse necrosis of interstitial hematopoietic tissues in the kidney, diffuse necrosis of the spleen, epidermis, and subcutis, and occasional necrosis of pancreatic acinar cells. Virus titers in tissues of experimentally infected herring were first detected 48 h after exposure and peaked 6-8 d after exposure at 107.7 PFU/g. Fish began shedding virus at 48 h after exposure with titers in the flow-through aquaria reaching 102.5 PFU/mL at 4–5 d after exposure, just before peak mortality. When the water flow was turned off for 3 h, titers in the water rose to 103.5 PFU/mL, and the amount of virus shed by infected fish (on average, greater than 106.5 PFU/h per fish) appeared sufficient to sustain a natural epizootic among schooling herring. Taken together, these data suggest that VHSV could be a

[Bilateral acute retinal necrosis in a patient with acquired immunodeficiency syndrome].

PubMed

Menerath, J M; Gerard, M; Laurichesse, H; Goldschmidt, P; Peigue-Lafeuille, H; Rozenberg, F; Beytout, J

1995-01-01

A case of bilateral progressive outer retinal necrosis occurred after herpes zoster ophthalmicus in a patient with acquired immunodeficiency syndrome. This case does not correspond to the classical picture of progressive outer retinal necrosis. The disease led to blindness despite intravenous therapy with acyclovir and foscarnet. PCR could not identify any virus in the aqueous humour, but VZV is evidenced in cerebrospinal fluid. Acute retinal necrosis is now clearly defined by the American Uveitis Society, which should allow to determine its incidence and risk factors. Herpes zoster usually precedes the acute outer retinal necrosis. The infectious theory (VZV, HSV, CMV) widely prevails over the immune theory. We prefer the virus genome identification in the aqueous humor or in the vitreous by PCR to confirm diagnosis rather than the specific antibody titration. Therapy consists in acyclovir, foscarnet and ganciclovir. But whatever the treatment, the visual prognosis is poor.

Genome organisation and sequence comparison suggest intraspecies incongruence in M RNA of Watermelon bud necrosis virus.

PubMed

Kumar, Rakesh; Mandal, B; Geetanjali, A S; Jain, R K; Jaiwal, P K

2010-08-01

Watermelon bud necrosis virus (WBNV), a member of the genus Tospovirus, family Bunyaviridae is an important viral pathogen in watermelon cultivation in India. The complete genome sequence properties of WBNV are not available. In the present study, the complete M RNA sequence and the genome organisation of a WBNV isolate infecting watermelon in Delhi (WBNV-wDel) were determined. The M RNA was 4,794 nucleotides (nt) long and potentially coded for a movement protein (NSm) of 34.22 kDa (307 amino acids) on the viral sense strand and a Gn/Gc glycoprotein precursor of 127.15 kDa (1,121 amino acids) on the complementary strand. The two open reading frames were separated by an intergenic region of 402 nt. The 5' and 3' untranslated regions were 55 and 47 nt long, respectively, containing complementary termini typical of tospoviruses. WBNV-wDel was most closely related (79.1% identity) to Groundnut bud necrosis virus, an important tospovirus that occurs in several crops in India, and was different (63.3-75.2% identity) from the other cucurbit-infecting tospoviruses known to occur in Taiwan and Japan. Sequence analysis of NSm and Gn/Gc revealed phylogenetic incongruence between WBNV-wDel and another isolate originating from central India (WBNV-Wm-Som isolate). The Wm-Som isolate showed evolutionary divergence from the wDel isolate in the Gn/Gc protein (74.6% identity) potentially due to recombination with the other tospoviruses that are known to occur in India. This is the first report of a comparison of complete sequences of M RNA of WBNV.

Transcriptome analysis of rainbow trout infected with high and low virulence strains of Infectious hematopoietic necrosis virus

USGS Publications Warehouse

Purcell, Maureen K.; Marjara, Inderjit Singh; Batts, William; Kurath, Gael; Hansen, John D.

2010-01-01

There are three main genetic lineages or genogroups of Infectious hematopoietic necrosis virus (IHNV) in N. America. Strains representing the M genogroup are more virulent in rainbow trout relative to the U genogroup. In this study, we used microarray analysis to evaluate potential mechanisms responsible for host-specific virulence in rainbow trout that were given intraperitoneal injections of buffer or a representative M or U type virus strain. Reverse transcriptase quantitative PCR (RT-qPCR) was used to assess viral load and gene expression of select immune genes. Viral load was significantly higher in trout infected with the M virus starting at 24 h post-infection (p.i.) and continuing until 72 h p.i. Microarray analysis of the 48 h time point revealed 153 up-regulated and 248 down-regulated features in response to M virus infection but only 62 up-regulated and 49 down-regulated features following U virus infection. Translation and transcription features were among the most frequent down-regulated features in response to M virus infection and may be associated with the host cell shutoff phenomenon. A greater host cell shutoff response by the M virus may facilitate subversion of the host cell transcriptional machinery and enhance viral replication, suggesting the M virus may be better optimized to manipulate the rainbow trout transcriptional and translational machinery. Anti-viral associated features were the most commonly up-regulated features. A common set of features were up-regulated in both the M and U infection groups, but were induced to a higher magnitude in the M infection group. Gene expression of the anti-viral genes Mx-1 and Vig-1 was correlated but not entirely dependent on viral load in the anterior kidney. Slower replication of the U virus may allow the host more time to induce protective anti-viral immune mechanisms.

Biological and genetic characterization of new and known necroviruses causing an emerging systemic necrosis disease of corn salad (Valerianella locusta L.) in France.

PubMed

Verdin, Eric; Marais, Armelle; Wipf-Scheibel, Catherine; Faure, Chantal; Pelletier, Brigitte; David, Perrine; Svanella-Dumas, Laurence; Poisblaud, Clement; Lecoq, Herve'; Candresse, Thierry

2018-02-28

An emerging systemic necrosis disease of corn salad was first observed in the Nantes region of France in the late 2000's. Classical virology and high-throughput sequencing approaches demonstrated that the disease is associated with four different necroviruses, tobacco necrosis virus A (TNVA), tobacco necrosis virus D (TNVD), olive mild mosaic virus (OMMV) and a novel recombinant Alphanecrovirus for which the name corn salad necrosis virus (CSNV) is proposed. Satellite tobacco necrosis virus (STNV) was also frequently observed. Koch's postulates were completed for all four agents, each one alone being able to cause systemic necrosis of varying severity in corn salad. OMMV was the most frequently observed virus and causes the most severe symptoms. TNVA was the second, both in terms of prevalence and symptom severity while TNVD and CSNV were only rarely observed and cause the less severe symptoms. The emergence of this systemic disease may have been favoured by the short and repeated cropping cycles used for corn salad, possibly allowing the selection of necrovirus isolates with an improved ability to systemically invade this specialty crop.

Lettuce chlorosis virus P23 Suppresses RNA Silencing and Induces Local Necrosis with Increased Severity at Raised Temperatures.

PubMed

Kubota, Kenji; Ng, James C K

2016-06-01

RNA silencing functions as an antivirus defense strategy in plants, one that plant viruses counter by producing viral suppressors of RNA silencing (VSRs). VSRs have been identified in three members of the genus Crinivirus but they do not all share identical suppression mechanisms. Here, we used Agrobacterium co-infiltration assays to investigate the suppressor activity of proteins encoded by Lettuce chlorosis virus (LCV). Of 7 LCV proteins (1b, P23, HSP70 homolog, P60, CP, CPm, and P27) tested for the suppression of silencing of green fluorescent protein (GFP) expression in wild-type Nicotiana benthamiana plants, only P23 suppressed the onset of local silencing. Small-interfering (si)RNA accumulation was reduced in leaves co-infiltrated with P23, suggesting that P23 inhibited the accumulation or enhanced the degradation of siRNA. P23 also inhibited the cell-to-cell and systemic movement of RNA silencing in GFP-expressing transgenic N. benthamiana plants. Expression of P23 via agroinfiltration of N. benthamiana leaves induced local necrosis that increased in severity at elevated temperatures, a novelty given that a direct temperature effect on necrosis severity has not been reported for the other crinivirus VSRs. These results further affirm the sophistication of crinivirus VSRs in mediating the evasion of host's antiviral defenses and in symptom modulation.

Immune response to synthetic peptides representing antigenic sites on the glycoprotein of infectious hematopoietic necrosis virus

USGS Publications Warehouse

Emmenegger, Eveline J.; Huang, C.; LaPatra, S.; Winton, James R.

1995-01-01

Summary ― Monoclonal antibodies against infectious hematopoietic necrosis virus have been used to react with recombinant expression products in immunoblots and to select neutralization-resistant mutants for sequence analysis. These strategies identified neutralizing and non-neutralizing antigenic sites on the viral glycoprotein. Synthetic peptides based upon the amino acid sequences of these antigenic sites were synthesized and were injected together with an adjuvant into rainbow trout. The constructs generally failed to stimulate neutralizing antibodies in the fish. These results indicate that we need to understand more about the ability of peptide antigens to stimulate fish immune systems.

Dendritic cell-based vaccines for pancreatic cancer and melanoma.

PubMed

Mulé, James J

2009-09-01

Based on leads from our recent animal studies, we are embarking on a series of new clinical trials to evaluate potential improvements in dendritic cell (DC)-based vaccines for melanoma and pancreatic cancer. The first new strategy involves the use of a powerful chemokine (denoted secondary lymphoid tissue chemokine; SLC/CCL-21), which can both create functioning lymph node-like structures at sites of vaccination with tumor-loaded DCs and dramatically enhance vaccine efficacy in animal tumor models. Using this strategy, we are embarking on a clinical trial in melanoma patients with the intent to create functioning, ectopic, lymph node-like structures to enhance host antitumor immunity. The second strategy, in the setting of pancreatic cancer, involves a gene therapy and immunotherapy combination of a locally administered tumor necrosis factor-alpha gene vector followed by radiation (to induce tumor apoptosis/necrosis) and intratumorally administered monocyte-derived DCs (to uptake and present antigens from dying tumor cells to elicit potent, systemic, antitumor immunity).

In vivo fitness correlates with host-specific virulence of Infectious hematopoietic necrosis virus (IHNV) in sockeye salmon and rainbow trout

USGS Publications Warehouse

Penaranda, M.M.D.; Wargo, A.R.; Kurath, G.

2011-01-01

The relationship between virulence and overall within-host fitness of the fish rhabdovirus Infectious hematopoietic necrosis virus (IHNV) was empirically investigated in vivo for two virus isolates belonging to different IHNV genogroups that exhibit opposing host-specific virulence. U group isolates are more virulent in sockeye salmon and M group isolates are more virulent in rainbow trout. In both single and mixed infections in the two fish hosts, the more virulent IHNV type exhibited higher prevalence and higher viral load than the less virulent type. Thus, a positive correlation was observed between higher in vivo fitness and higher host-specific virulence in sockeye salmon and rainbow trout. Comparisons of mean viral loads in single and mixed infections revealed no evidence for limitation due to competition effects between U and M viruses in either rainbow trout or sockeye salmon co-infections.

Acute pancreatitis at the beginning of the 21st century: The state of the art

PubMed Central

Tonsi, Alfredo F; Bacchion, Matilde; Crippa, Stefano; Malleo, Giuseppe; Bassi, Claudio

2009-01-01

Acute pancreatitis is an acute inflammatory disease of the pancreas which can lead to a systemic inflammatory response syndrome with significant morbidity and mortality in 20% of patients. Gallstones and alcohol consumption are the most frequent causes of pancreatitis in adults. The treatment of mild acute pancreatitis is conservative and supportive; however severe episodes characterized by necrosis of the pancreatic tissue may require surgical intervention. Advanced understanding of the pathology, and increased interest in assessment of disease severity are the cornerstones of future management strategies of this complex and heterogeneous disease in the 21st century. PMID:19554647

Evolution of infectious hematopoietic necrosis virus (IHNV), a fish rhabdovirus, in Europe over 20 years: implications for control.

PubMed

Enzmann, Peter-Joachim; Castric, Jeannette; Bovo, Giuseppe; Thiery, Richard; Fichtner, Dieter; Schütze, Heike; Wahli, Thomas

2010-02-24

The fish pathogenic rhabdovirus infectious hematopoietic necrosis virus (IHNV) causes substantial losses in European aquaculture. IHNV was first detected in Europe in 1987 and has since undergone considerable spread. Phylogenetic analyses of the full G-gene sequences of 73 isolates obtained from 4 countries in Europe (France, n = 18; Italy, 9; Switzerland, 4; Germany, 42) enable determination of the evolution of the virus in Europe since the first detection, and identification of characteristic changes within the G-genes of European strains. Further, the database allows us to analyse the pathways of distribution in Europe over time. The results suggest that in most of the recent cases, spread of IHNV was related to trade of infected fish. The data further demonstrate that knowledge of the sequence is required to determine the source of infections in farms.

Polyarthritis and bone lesions complicating traumatic pancreatitis in two children.

PubMed Central

Goluboff, N.; Cram, R.; Ramgotra, B.; Singh, A.; Wilkinson, G. W.

1978-01-01

The association of bone lesions, polyarthritis and cutaneous nodules with pancreatic disease is being recognized and reported more frequently. In adults all forms of pancreatitis and carcinoma of the pancreas have been involved, but in the few children described these complications have been associated with acute traumatic pancreatitis. This paper describes two cases of acute traumatic pancreatitis in which polyarthritis and limb pains were noted after 2 to 3 weeks. In one child osteolytic lesions and periostitis were seen on roentgenograms 7 weeks after the onset of pancreatitis. In the other child minor roentgenographic changes were not seen until 5 months after the onset; however, bone scans showed clear-cut abnormalities after 1 month. Almost complete resolution could be expected within a year. Serum lipase and amylase concentrations remained elevated during the acute illness. Disseminated fat necrosis is apparently related to the excess amounts of circulating lipase. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 PMID:647564

Surgical resection after TNFerade therapy for locally advanced pancreatic cancer.

PubMed

Chadha, Manpreet K; Litwin, Alan; Levea, Charles; Iyer, Renuka; Yang, Gary; Javle, Milind; Gibbs, John F

2009-09-04

Treatment of pancreatic cancer remains a major oncological challenge and survival is dismal. Most patients, present with advanced disease at diagnosis and are not candidates for curative resection. Preoperative chemoradiation may downstage and improve survival in locally advanced pancreatic cancer. This has prompted investigators to look for novel neoadjuvant therapies. Gene therapy for pancreatic cancer is a novel investigational approach that may have promise. TNFerade is a replication deficient adenovirus vector carrying the human tumor necrosis factor (TNF)-alpha gene regulated under control of a radiation-inducible gene promoter. Transfection of tumor cells with TNFerade maximizes the antitumor effect of TNF-alpha under influence of radiation leading to synergistic effects in preclinical studies. We describe a case of locally advanced unresectable pancreatic cancer treated with a novel multimodal approach utilizing gene therapy with TNFerade and concurrent chemoradiation that was followed by successful surgical resection. Neoadjuvant TNFerade based chemoradiation therapy may be a useful adjunct to treatment of locally advanced pancreatic cancer.

Role of Biomarkers in Diagnosis and Prognostic Evaluation of Acute Pancreatitis

PubMed Central

Meher, Susanta; Mishra, Tushar Subhadarshan; Sasmal, Prakash Kumar; Rath, Satyajit; Sharma, Rakesh; Rout, Bikram; Sahu, Manoj Kumar

2015-01-01

Acute pancreatitis is a potentially life threatening disease. The spectrum of severity of the illness ranges from mild self-limiting disease to a highly fatal severe necrotizing pancreatitis. Despite intensive research and improved patient care, overall mortality still remains high, reaching up to 30–40% in cases with infected pancreatic necrosis. Although little is known about the exact pathogenesis, it has been widely accepted that premature activation of digestive enzymes within the pancreatic acinar cell is the trigger that leads to autodigestion of pancreatic tissue which is followed by infiltration and activation of leukocytes. Extensive research has been done over the past few decades regarding their role in diagnosis and prognostic evaluation of severe acute pancreatitis. Although many standalone biochemical markers have been studied for early assessment of severity, C-reactive protein still remains the most frequently used along with Interleukin-6. In this review we have discussed briefly the pathogenesis and the role of different biochemical markers in the diagnosis and severity evaluation in acute pancreatitis. PMID:26345247

Transduction of rat pancreatic islets with pseudotyped adeno-associated virus vectors

PubMed Central

Craig, Anthony T; Gavrilova, Oksana; Dwyer, Nancy K; Jou, William; Pack, Stephanie; Liu, Eric; Pechhold, Klaus; Schmidt, Michael; McAlister, Victor J; Chiorini, John A; Blanchette-Mackie, E Joan; Harlan, David M; Owens, Roland A

2009-01-01

Background Pancreatic islet transplantation is a promising treatment for type I diabetes mellitus, but current immunosuppressive strategies do not consistently provide long-term survival of transplanted islets. We are therefore investigating the use of adeno-associated viruses (AAVs) as gene therapy vectors to transduce rat islets with immunosuppressive genes prior to transplantation into diabetic mice. Results We compared the transduction efficiency of AAV2 vectors with an AAV2 capsid (AAV2/2) to AAV2 vectors pseudotyped with AAV5 (AAV2/5), AAV8 (AAV2/8) or bovine adeno-associated virus (BAAV) capsids, or an AAV2 capsid with an insertion of the low density lipoprotein receptor ligand from apolipoprotein E (AAV2apoE), on cultured islets, in the presence of helper adenovirus infection to speed expression of a GFP transgene. Confocal microscopy and flow cytometry were used. The AAV2/5 vector was superior to AAV2/2 and AAV2/8 in rat islets. Flow cytometry indicated AAV2/5-mediated gene expression in approximately 9% of rat islet cells and almost 12% of insulin-positive cells. The AAV2/8 vector had a higher dependence on the helper virus multiplicity of infection than the AAV 2/5 vector. In addition, the BAAV and AAV2apoE vectors were superior to AAV2/2 for transducing rat islets. Rat islets (300 per mouse) transduced with an AAV2/5 vector harboring the immunosuppressive transgene, tgfβ1, retain the ability to correct hyperglycemia when transplanted into immune-deficient diabetic mice. Conclusion AAV2/5 vectors may therefore be useful for pre-treating donor islets prior to transplantation. PMID:19450275

Genetic diversity and epidemiology of infectious hematopoietic necrosis virus in Alaska

USGS Publications Warehouse

Emmenegger, E.G; Meyers, T.R.; Burton, T.O.; Kurath, G.

2000-01-01

Forty-two infectious hematopoietic necrosis virus (IHNV) isolates from Alaska were analyzed using the ribonuclease protection assay (RPA) and nucleotide sequencing. RPA analyses, utilizing 4 probes, N5, N3 (N gene), GF (G gene), and NV (NV gene), determined that the haplotypes of all 3 genes demonstrated a consistent spatial pattern. Virus isolates belonging to the most common haplotype groups were distributed throughout Alaska, whereas isolates in small haplotype groups were obtained from only 1 site (hatchery, lake, etc.). The temporal pattern of the GF haplotypes suggested a 'genetic acclimation' of the G gene, possibly due to positive selection on the glycoprotein. A pairwise comparison of the sequence data determined that the maximum nucleotide diversity of the isolates was 2.75% (10 mismatches) for the NV gene, and 1.99% (6 mismatches) for a 301 base pair region of the G gene, indicating that the genetic diversity of IHNV within Alaska is notably lower than in the more southern portions of the IHNV North American range. Phylogenetic analysis of representative Alaskan sequences and sequences of 12 previously characterized IHNV strains from Washington, Oregon, Idaho, California (USA) and British Columbia (Canada) distinguished the isolates into clusters that correlated with geographic origin and indicated that the Alaskan and British Columbia isolates may have a common viral ancestral lineage. Comparisons of multiple isolates from the same site provided epidemiological insights into viral transmission patterns and indicated that viral evolution, viral introduction, and genetic stasis were the mechanisms involved with IHN virus population dynamics in Alaska. The examples of genetic stasis and the overall low sequence heterogeneity of the Alaskan isolates suggested that they are evolutionarily constrained. This study establishes a baseline of genetic fingerprint patterns and sequence groups representing the genetic diversity of Alaskan IHNV isolates. This

Oxalate nephropathy associated with chronic pancreatitis.

PubMed

Cartery, Claire; Faguer, Stanislas; Karras, Alexandre; Cointault, Olivier; Buscail, Louis; Modesto, Anne; Ribes, David; Rostaing, Lionel; Chauveau, Dominique; Giraud, Patrick

2011-08-01

Enteric overabsorption of oxalate may lead to hyperoxaluria and subsequent acute oxalate nephritis (AON). AON related to chronic pancreatitis is a rare and poorly described condition precluding early recognition and treatment. We collected the clinical characteristics, treatment, and renal outcome of 12 patients with chronic pancreatitis-associated AON followed in four French renal units. Before AON, mild to moderate chronic kidney disease was present in all patients, diabetes mellitus in eight (insulin [n = 6]; oral antidiabetic drugs [n = 2]), and known chronic pancreatitis in only eight. At presentation, pancreas imaging showed gland atrophy/heterogeneity, Wirsung duct dilation, calcification, or pseudocyst. Renal findings consisted of rapidly progressive renal failure with tubulointerstitial profile. Acute modification of glomerular filtration preceded the AON (i.e., diarrhea and diuretics). Increase in urinary oxalate excretion was found in all tested patients and hypocalcemia in nine (<1.5 mmol/L in four patients). Renal biopsy showed diffuse crystal deposits, highly suggestive of oxalate crystals, with tubular necrosis and interstitial inflammatory cell infiltrates. Treatment consisted of pancreatic enzyme supplementation, oral calcium intake, and an oxalate-free diet in all patients and renal replacement therapy in five patients. After a median follow-up of 7 months, three of 12 patients reached end-stage renal disease. AON is an under-recognized severe crystal-induced renal disease with features of tubulointerstitial nephritis that may occur in patients with a long history of chronic pancreatitis or reveal the pancreatic disease. Extrinsic triggering factors should be prevented.

Pancreatic head cryosurgery: safety and efficiency in vivo--a pilot study.

PubMed

Li, Jialiang; Zhou, Liang; Chen, Jibing; Wu, Binghui; Zeng, Jianying; Fang, Gang; Deng, Chunjuan; Huang, Shengquan; Yao, Fei; Chen, Zhixian; Leng, Yin; Deng, Min; Deng, Chunmei; Zhang, Bo; Zhou, Gang; He, Lihua; Liao, Maoxin; Chiu, David; Niu, Lizhi; Zuo, Jiansheng; Xu, Kecheng

2012-11-01

Pancreatic cancer is the fourth leading cause of cancer-related death. Cryosurgery has emerged as a promising new technique for treatment. Although 80% of pancreatic cancers are located in the pancreatic head, no research has been conducted on the safety and efficacy of cryosurgery for these tumors. Two groups of Tibetan miniature pigs (n = 4 per group) underwent cryosurgery to the pancreatic head with either the deep freezing protocol (100% argon output) or shallow freezing protocol (10% argon output), and compared to sham-operated pigs. Serum inflammatory factors and amylase increased during the 5 days after cryoablation in both groups but acute pancreatitis did not occur. Adhesions were observed between the pancreatic head and adjacent organs, and only minor trauma was caused to the stomach, duodenum, small intestine, and liver. Ice balls with a radius of 0.5 cm beyond the tumor edge were sufficient to cause complete necrosis of the pancreatic tissue, and decreased the degree of cold injury to surrounding tissues. Shallow freezing protocol seemed to be safer than, and just as effective as, the deep freezing protocol. This preliminary study suggests that cryosurgery could potentially be an effective treatment of cancer of the pancreatic head.

Utility of CT classifications to predict unfavorable outcomes in children with acute pancreatitis.

PubMed

Izquierdo, Yojhan E; Fonseca, Eileen V; Moreno, Luz-Ángela; Montoya, Rubén D; Guerrero Lozano, Rafael

2018-02-21

Computed tomography (CT) is useful for the diagnosis of local complications in children with acute pancreatitis but its role as a prognostic tool remains controversial. To establish the correlation between the CT Severity Index and the Revised Atlanta Classification regarding unfavorable outcomes such as severe acute pancreatitis and need for Pediatric Special Care Unit attention in children with acute pancreatitis. We conducted a retrospective and concordance cohort study in which we obtained abdominal CT scans from 30 patients ages 0 to 18 years with acute pancreatitis. Two pediatric radiologists interpreted the results using the CT Severity Index and the Revised Atlanta Classification. The kappa coefficient was determined for each scale. The association among severe acute pancreatitis, need for admission to the Pediatric Special Care Unit and CT systems were established using chi-square or Mann-Whitney U tests. The best CT Severity Index value to predict the need for admission to the Pediatric Special Care Unit was estimated through a receiver operating characteristic (ROC) curve. Mean CT Severity Index was 5.1±2.8 (mean ± standard deviation on a scale of 0 to 10) for the severe acute pancreatitis group vs. 3.8±2.7 for the mild acute pancreatitis group (P=0.230). The CT Severity Index for the children who were not hospitalized at the Pediatric Special Care Unit was 2.2±2.2 vs. 5.6±2.4 for the group hospitalized at the Pediatric Special Care Unit (P=0.001). Only parenchymal necrosis >30% was associated with severe acute pancreatitis (P=0.021). A CT Severity Index ≥3 has a sensitivity of 89% and specificity of 72% to predict need for admission to the Pediatric Special Care Unit. None of the Revised Atlanta Classification categories was associated with severe acute pancreatitis or admission to the Pediatric Special Care Unit. A CT Severity Index ≥3 in children with acute pancreatitis who require CT assessment based on clinical criteria is associated with

Herpesviral Hematopoietic Necrosis in Goldfish in Switzerland: Early Lesions in Clinically Normal Goldfish (Carassius auratus).

PubMed

Giovannini, S; Bergmann, S M; Keeling, C; Lany, C; Schütze, H; Schmidt-Posthaus, H

2016-07-01

Cyprinid herpesvirus 2 is a pathogen of goldfish, inducing a disease referred to as herpesviral hematopoietic necrosis. The disease is described so far in Japan, North America, Taiwan, Australia, the United Kingdom, and recently also Italy. Here the authors describe histologic lesions in clinically affected fish in comparison with clinically normal but virus DNA-positive goldfish in Switzerland. While necrosis or enhanced single-cell necrosis in the hematopoietic tissue in the pronephros or mesonephros was evident in dead and sick animals, in clinically normal goldfish, only single-cell necrosis was observed. Virus DNA was demonstrated in dead as well as clinically affected and subclinically infected goldfish by polymerase chain reaction and in situ hybridization. This study identifies the presence of goldfish herpesvirus in Switzerland and highlights the fact that the virus might be more widespread than assumed, as clinically normal goldfish can also carry cyprinid herpesvirus 2, showing histologically similar lesions but of lesser extent and severity. © The Author(s) 2015.

Disease progression of acute pancreatitis in pediatric patients.

PubMed

Hao, Fabao; Guo, Hongjie; Luo, Qianfu; Guo, Chunbao

2016-05-15

Approximately 10% of patients with acute pancreatitis (AP) progress to chronic pancreatitis. Little is known about the factors that affect recurrence of pancreatitis after an initial episode. We retrospectively investigated patients with AP, focusing on their outcomes and the predictors for disease progression. Between July 2003 and June 2015, we retrospectively enrolled first-time AP patients with medical records on disease etiology, severity (according to the Atlanta classifications), and recurrence of AP. Independent predictors of recurrent AP (RAP) and chronic pancreatitis were identified using the logistic regression model. Of the total 159 patients, 45 (28.3%) developed RAP, including two episodes of RAP in 19 patients, and 9 (5.7%) developed chronic pancreatitis. The median duration from the time of AP to the onset of RAP was 5.6 ± 2.3 months. RAP patients were identified as more common among patients with idiopathic first-time AP. The presence of severe ascites, pancreatic necrosis, and systemic complications was independent predictors of RAP in pediatric patients. Experiencing over two RAP episodes was the predictor for developing chronic pancreatitis. No influence of age or number of AP episodes was found on the occurrence of abdominal pain, pain severity, and the prevalence of any pain. Severity of first-time AP and idiopathic first-time AP are related to RAP. Recurrence increases risk for progression to chronic pancreatitis. The risk of recurrence increased with increasing numbers of AP episodes. Copyright © 2016 Elsevier Inc. All rights reserved.

[International multidisciplinary classification of acute pancreatitis severity: the 2013 Spanish edition].

PubMed

Maraví-Poma, E; Patchen Dellinger, E; Forsmark, C E; Layer, P; Lévy, P; Shimosegawa, T; Siriwardena, A K; Uomo, G; Whitcomb, D C; Windsor, J A; Petrov, M S

2014-05-01

To develop a new classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of the published evidence, and worldwide consultation. The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of specialist in pancreatic diseases, but are suboptimal because these definitions are based on the empiric description of events not associated with severity. A personal invitation to contribute to the development of a new classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensivists and radiologists currently active in the field of clinical acute pancreatitis. The invitation was not limited to members of certain associations or residents of certain countries. A global web-based survey was conducted, and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. The new classification of severity is based on the actual local and systemic determinants of severity, rather than on the description of events that are non-causally associated with severity. The local determinant relates to whether there is (peri) pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another, whereby the presence of both infected (peri) pancreatic necrosis and persistent organ failure has a greater impact upon severity than either determinant alone. The derivation of a classification based on the above principles results in four categories of severity: mild, moderate, severe, and critical. This classification is the result of a consultative process among specialists in pancreatic diseases from 49 countries spanning North America, South America, Europe, Asia, Oceania and

The acquisition of molecular determinants involved in potato virus Y necrosis capacity leads to fitness reduction in tobacco plants.

PubMed

Rolland, Mathieu; Kerlan, Camille; Jacquot, Emmanuel

2009-01-01

The prevalence of necrotic potato virus Y (PVY) in natural populations could reflect increased fitness of necrotic isolates. In this paper, the effects of the acquisition of molecular determinants (A/G(2213) and A/C(2271)) involved in necrosis capacity on both the number of progeny produced and the competitiveness of PVY were characterized. The relationship between necrosis and fitness was tested using (i) Nicotiana tabacum cv. Xanthi and Nicotiana clevelandii, (ii) necrotic PVY(N)-605 and non-necrotic PVY(O)-139 isolates, (iii) single-mutated (PVY(KR) and PVY(ED)) and double-mutated (PVY(KRED)) versions of PVY(N)-605 and (iv) three quantitative PCR assays specific for nt A(2213), G(2213) and A(2271) of the PVY genome. The data demonstrated effects of both the genetic background and nt 2213 and 2271 on the fitness of PVY. Quantification of PVY RNA in singly infected plants revealed that both the PVY(N)-605 genetic background and the acquisition of necrotic capacity resulted in a decrease in the number of progeny produced. Competition experiments revealed that the genetic background of PVY(N) had a positive impact on competitiveness. In contrast, nucleotides involved in necrotic properties were associated with decreased fitness. Finally, in the host that did not respond to infection with necrosis, the benefit associated with the PVY(N)-605 genetic background was higher than the cost associated with the acquisition of molecular determinants involved in necrosis capacity. The opposite result was obtained in the host responding to the infection with necrosis. These results indicate that the emergence of necrotic isolates from a non-necrotic population is unlikely in tobacco.

Surveillance of Viruses in Wild Fish Populations in Areas around the Gulf of Cadiz (South Atlantic Iberian Peninsula)

PubMed Central

Moreno, Patricia; Olveira, José G.; Labella, Alejandro; Cutrín, Juan Manuel; Baro, Jorge C.; Borrego, Juan Jose

2014-01-01

This report describes a viral epidemiological study of wild fish around the Gulf of Cadiz (southwestern Iberian Peninsula) and is focused on infectious pancreatic necrosis virus (IPNV), viral hemorrhagic septicemia virus (VHSV), and viral nervous necrosis virus (VNNV). One fish species (Chelon labrosus) was sampled inside the gulf, at the mouth of the San Pedro River. Another 29 were sampled, in three oceanographic campaigns, at sites around the Bay of Cadiz. The fish were processed individually and subjected to isolation in cell culture and molecular diagnosis. VHSV was not isolated from any species. Thirteen IPNV-type isolates were obtained from barracuda (Sphyraena sphyraena), axillary seabream (Pagellus acarne), common two-banded seabream (Diplodus vulgaris), common pandora (P. erythrinus), Senegal seabream (D. bellottii), and surmullet (Mullus surmuletus). Six VNNV isolates were obtained from axillary seabream, common pandora, black seabream (Spondyliosoma cantharus), red mullet (Mullet barbatus), Lusitanian toadfish (Halobatrachus didactylus), and tub gurnard (Chelidonichtys lucerna). In the river mouth, viruses were detected only after reamplification, obtaining prevalence percentages of IPNV and VNNV (44.4 and 63.0%, respectively) much higher than those observed in the oceanographic campaigns (25.7 and 19.6%, respectively). The opposite results were obtained in the case of VHSV after reamplification: 11.1% in the river mouth and 43.6% in the oceanic locations. Analyzing the results with respect to the proximity of the sampling sites to the coast, an anthropogenic influence on wild fish is suggested and discussed. The type of viruses and the presence of natural reassortants are also discussed. PMID:25128341

Oxylipin Biosynthesis Genes Positively Regulate Programmed Cell Death during Compatible Infections with the Synergistic Pair Potato Virus X-Potato Virus Y and Tomato Spotted Wilt Virus

PubMed Central

García-Marcos, Alberto; Pacheco, Remedios; Manzano, Aranzazu; Aguilar, Emmanuel

2013-01-01

One of the most severe symptoms caused by compatible plant-virus interactions is systemic necrosis, which shares common attributes with the hypersensitive response to incompatible pathogens. Although several studies have identified viral symptom determinants responsible for systemic necrosis, mechanistic models of how they contribute to necrosis in infected plants remain scarce. Here, we examined the involvement of different branches of the oxylipin biosynthesis pathway in the systemic necrosis response caused either by the synergistic interaction of Potato virus X with Potato virus Y (PVX-PVY) or by Tomato spotted wilt virus (TSWV) in Nicotiana benthamiana. Silencing either 9-lipoxygenase (LOX), 13-LOX, or α-dioxygenase-1 (α-DOX-1) attenuated the programmed cell death (PCD)-associated symptoms caused by infection with either PVX-PVY or TSWV. In contrast, silencing of the jasmonic acid perception gene, COI1 (Coronatine insensitive 1), expedited cell death during infection with compatible viruses. This correlated with an enhanced expression of oxylipin biosynthesis genes and dioxygenase activity in PVX-PVY-infected plants. Moreover, the Arabidopsis thaliana double lox1 α-dox-1 mutant became less susceptible to TSWV infection. We conclude that oxylipin metabolism is a critical component that positively regulates the process of PCD during compatible plant-virus interactions but does not play a role in restraining virus accumulation in planta. PMID:23487466

Differential susceptibility in steelhead trout populations to an emergent MD strain of infectious hematopoietic necrosis virus

USGS Publications Warehouse

Breyta, R.; Jones, Amelia; Kurath, Gael

2014-01-01

A significant emergence of trout-adapted MD subgroup infectious hematopoietic necrosis virus (IHNV) began in the coastal region of Washington State, USA, in 2007. This emergence event lasted until 2011 and caused both asymptomatic adult fish infection and symptomatic epidemic disease and mortality in juvenile fish. Incidence of virus during this emergence demonstrated a heterogeneous distribution among rivers of the coastal region, leaving fish populations of some rivers apparently untouched while others suffered significant and recurrent infection and mortality (Breyta et. al. 2013; Dis Aquat Org 104:179-195). In this study, we examined the possible contribution of variations in susceptibility of fish populations, age-related resistance, and virus virulence to the observed landscape heterogeneity. We found that the most significant variable was host susceptibility: by controlled experimental challenge studies steelhead trout populations with no history of IHNV infection were 1 to 3 orders of magnitude more sensitive than a fish population with a long history of IHNV infection. In addition, 2 fish populations from the same river, which descended relatively recently from a common ancestral population, demonstrated 1 to 2 orders of magnitude difference in susceptibility. Fish age-related development of resistance was most evident in the more susceptible of 2 related fish populations. Finally, the strain of virus involved in the 2007 coastal Washington emergence had high virulence but was within the range of other known M group viruses tested. These results suggest that one major driver of landscape heterogeneity in the 2007 coastal Washington IHNV emergence was variation in fish population susceptibility and that this trait may have a heritable component.

Effects of thalidomide in experimental models of post-endoscopic retrograde cholangiopancreatography pancreatitis.

PubMed

Xiong, Guang-Su; Wu, Shu-Ming; Wang, Zhen-Hua; Mo, Jian-Zhong; Xiao, Shu-Dong

2007-03-01

Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the pathogenesis of acute pancreatitis and related systemic complications. The authors hypothesized that it may also play an important role in the development of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). The aim of the study was to evaluate the effectiveness of thalidomide, an immunomodulator that exerts an inhibitory action on TNF-alpha by enhancing mRNA degradation, in reducing post-ERCP pancreatitis in a rat model. A total of 200 mg/kg thalidomide was given intragastric once a day (total 8 days) before the experimental models of post-ERCP pancreatitis were established. After 24 h, histology and edema of pancreas, serum amylase, and TNF-alpha mRNA in the pancreatic tissue were evaluated. Intraductal contrast infusion caused increases in serum amylase, edema, histological grade, and TNF-alpha mRNA of pancreas. The prophylactic use of thalidomide significantly reduced serum amylase, pancreatic edema and the histologic grade of pancreatitis accompanied by a decrease in mRNA expression of TNF-alpha in the pancreatic tissue. Prophylactic intragastric administration of thalidomide provides a protective effect in post-ERCP pancreatitis. The mechanism of the protective effects of thalidomide seems to be the reduction of expression of TNF-alpha mRNA in pancreatic tissue.

Spatial and temporal heterogeneity of infectious hematopoietic necrosis virus in Pacific Northwest salmonids

USGS Publications Warehouse

Breyta, Rachel; Black, Allison; Kaufman, John; Kurath, Gael

2016-01-01

The aquatic rhaboviral pathogen infectious hematopoietic necrosis virus (IHNV) causes acute disease in juvenile fish of a number of populations of Pacific salmonid species. Heavily managed in both marine and freshwater environments, these fish species are cultured during the juvenile stage in freshwater conservation hatcheries, where IHNV is one of the top three infectious diseases that cause serious morbidity and mortality. Therefore, a comprehensive study of viral genetic surveillance data representing 2590 field isolates collected between 1958 and 2014 was conducted to determine the spatial and temporal patterns of IHNV in the Pacific Northwest of the contiguous United States. Prevalence of infection varied over time, fluctuating over a rough 5–7 year cycle. The genetic analysis revealed numerous subgroups of IHNV, each of which exhibited spatial heterogeneity. Within all subgroups, dominant genetic types were apparent, though the temporal patterns of emergence of these types varied among subgroups. Finally, the affinity or fidelity of subgroups to specific host species also varied, where UC subgroup viruses exhibited a more generalist profile and all other subgroups exhibited a specialist profile. These complex patterns are likely synergistically driven by numerous ecological, pathobiological, and anthropogenic factors. Since only a few anthropogenic factors are candidates for managed intervention aimed at improving the health of threatened or endangered salmonid fish populations, determining the relative impact of these factors is a high priority for future studies.

Characterization of the glycoprotein of infectious hematopoietic necrosis virus using neutralizing monoclonal antibodies

USGS Publications Warehouse

Huang, Chienjin; Chien, Maw-Sheng; Landolt, Marsha; Winton, James

1994-01-01

To study the antigenic nature of the glycoprotein (G protein) of infectious hematopoietic necrosis virus (IHNV), 31 neutralizing monoclonal antibodies (MAbs) were produced against a reference isolate of the virus. The MAbs were compared using a neutralization assay, an enzyme-linked immunosorbent assay (ELISA), and by immunoblotting of the G protein in the native, reduced, and deglycosylated forms. Hybridoma culture fluids of the various MAbs could be diluted from 1:2 to 1:512 and still completely neutralize 1 X 104 plaque-forming units of IHNV. Similarly, the end point dilutions that produced optical density readings of 0.1 or greater in the ELISA were 1:40 to 1:10240. Western blotting showed that all of the MAbs reacted with the G protein in the unreduced (i.e. native) conformation; however, only 9 nine of the MAbs were able to react with the G protein following reduction by 2-mercaptoethanol. Deglycosylation of the protein did not influence the binding ability of any of the MAbs. These data indicate that all the MAbs recognized amino acid sequences on the protein itself and that the IHNV glycoprotein contains linear as well as conformation-dependent neutralizing epitopes. When rainbow trout Oncorhynchus mykiss fingerlings were passively immunized with MAbs against either a linear or a conformation-dependent epitope, the fish were protected against challenge with wild-type IHNV.

Virulence correlates with fitness in vivo for two M group genotypes of Infectious hematopoietic necrosis virus (IHNV).

USGS Publications Warehouse

Wargo, Andrew R.; Garver, Kyle A.; Kurath, Gael

2010-01-01

The nature of the association between viral fitness and virulence remains elusive in vertebrate virus systems, partly due to a lack of in vivo experiments using statistically sufficient numbers of replicate hosts. We examined the relationship between virulence and fitness in Infectious hematopoietic necrosis virus (IHNV), in vivo, in intact living rainbow trout. Trout were infected with a high or low virulence genotype of M genogroup IHNV, or a mixture of the two genotypes, so as to calculate relative fitness and the effect of a competition environment on fitness. Fitness was measured as total viral load in the host at time of peak viral density, quantified by genotype-specific quantitative RT-PCR (qRT-PCR). The more virulent IHNV genotype reached higher densities in both single and mixed infections. There was no effect of competition on the performance of either genotype. Our results suggest a positive link between IHNV genotype fitness and virulence.

Determinant-based classification of acute pancreatitis severity: an international multidisciplinary consultation.

PubMed

Dellinger, E Patchen; Forsmark, Christopher E; Layer, Peter; Lévy, Philippe; Maraví-Poma, Enrique; Petrov, Maxim S; Shimosegawa, Tooru; Siriwardena, Ajith K; Uomo, Generoso; Whitcomb, David C; Windsor, John A

2012-12-01

To develop a new international classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of published evidence, and worldwide consultation. The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of pancreatologists but suboptimal because these definitions are based on empiric description of occurrences that are merely associated with severity. A personal invitation to contribute to the development of a new international classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensivists, and radiologists who are currently active in clinical research on acute pancreatitis. The invitation was not limited to members of certain associations or residents of certain countries. A global Web-based survey was conducted and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. The new international classification is based on the actual local and systemic determinants of severity, rather than description of events that are correlated with severity. The local determinant relates to whether there is (peri)pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another such that the presence of both infected (peri)pancreatic necrosis and persistent organ failure have a greater effect on severity than either determinant alone. The derivation of a classification based on the above principles results in 4 categories of severity-mild, moderate, severe, and critical. This classification is the result of a consultative process amongst pancreatologists from 49 countries spanning North America, South America, Europe, Asia, Oceania, and Africa. It provides

Diagnostic ultrasonography in cattle with abdominal fat necrosis.

PubMed

Tharwat, Mohamed; Buczinski, Sébastien

2012-01-01

This study describes the ultrasonographic findings in 14 cows with abdominal fat necrosis. Ultrasonography of the abdomen revealed the presence of heterogeneous hyperechoic masses and hyperechoic omentum with localized masses floating in a hypoechoic peritoneal fluid. A hyperechogenic rim was imaged around both kidneys. The intestines were coated with hyperechoic capsules and the intestinal lumens were constricted. Ultrasonographic examination of the pancreatic parenchyma showed an overall increased echogenicity which was homogenously distributed in 3 cases. A diagnosis of abdominal fat necrosis was made with ultrasound-guided biopsy of the echogenic masses, and thereafter at postmortem examination. Results from this study demonstrate the efficacy of ultrasonography as an imaging modality for antemortem diagnosis of abdominal lipomatosis in cattle. To the authors' knowledge, this study is the first that illustrates ultrasonographic findings in cattle affected with abdominal lipomatosis.

Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis by possible reduction of NLRP3 activation and up-regulation of NET expression.

PubMed

Li, Yong; Pan, Yiyuan; Gao, Lin; Lu, Guotao; Zhang, Jingzhu; Xie, Xiaochun; Tong, Zhihui; Li, Baiqiang; Li, Gang; Li, Weiqin

2018-01-22

Previous studies have shown that acute inflammation is associated with increased sympathetic activity, which in turn increases the inflammatory response and leads to organ damage. The present study aimed to investigate whether dexmedetomidine administration during acute pancreatitis (AP) lessens pancreatic pathological and functional injury and the inflammatory response, and to explore the underlying mechanisms. Mild pancreatitis was induced in mice with caerulein, and severe pancreatitis was induced with caerulein plus lipopolysaccharide (LPS). After pancreatitis induction, dexmedetomidine at 10 or 20 μg/kg was injected via the tail vein. Pancreatic pathological and functional injury was assessed by histology and serum levels of amylase and lipase, respectively. The inflammatory response was evaluated by determining serum levels of inflammatory factors. The expression of myeloperoxidase (MPO) was examined by immunohistochemistry. The expression of norepinephrine transporter (NET), NLRP3, pro-IL-1β, and interleukin (IL)-1β in pancreatic tissue was detected by Western blot and real-time PCR. Dexmedetomidine at 20 μg/kg significantly attenuated pancreatic pathological injury, reduced serum levels of amylase, lipase, IL-1β, IL-6, and tumor necrosis factor (TNF)-α, and decreased the expression of MPO in pancreatic tissue in both mouse models of pancreatitis. In addition, dexmedetomidine at 20 μg/kg significantly down-regulated the expression of NLRP3, pro-IL-1β, and IL-1β in pancreatic tissue, but up-regulated the expression of NET in both mouse models. Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis possibly by reducing NLRP3 activation and up-regulating NET expression. Copyright © 2018 Elsevier Inc. All rights reserved.

Molecular epizootiology and evolution of the glycoprotein and non-virion protein genes of infectious hematopoietic necrosis virus, a fish rhabdovirus

USGS Publications Warehouse

Nichol, Stuart T.; Rowe, Joan E.; Winton, James R.

1995-01-01

Infectious hematopoietic necrosis virus (IHNV) causes a highly lethal, economically important disease of salmon and trout. The virus is enzootic throughout western North America, and has been spread to Asia and Europe. The nucleotide sequences of the glycoprotein (G) and non-virion (NV) genes of 12 diverse IHNV isolates were determined in order to examine the molecular epizootiology of IHN, the primary structure and conservation of NV, and the evolution of the virus. The G and NV genes and their encoded proteins were highly conserved, with a maximum pairwise nucleotide divergence of 3.6 and 4.4.%, and amino acid divergence of 3.7 and 6.2%, respectively. Conservation of NV protein sequence (111 amino acids in length) confirms that the protein is functional and plays an important role in virus replication. The phylogenetic relationship of viruses was found to correlate with the geographic origin of virus isolates rather than with host species or time of isolation. These data are consistent with stable maintenance of virus in enzootic foci. Two main IHNV genetic lineages were identified; one in the Columbia River Basin (Oregon, Washington and Idaho), the other in the Sacramento River Basin (California). The first major IHNV outbreak in chinook salmon in 1973 in the Columbia River was genetically linked to importation of virus-infected fish eggs from the Sacramento River where outbreaks in chinook salmon are common. However, the introduced virus apparently did not persist, subsequent virus outbreaks in Columbia River chinook salmon being associated with Columbia River genetic lineages. In general, virus monoclonal antibody reactivity profiles and phylogenetic relationships correlated well.

Antibiotic prophylaxia in patients with severe acute pancreatitis.

PubMed

Zhou, Yan-Ming; Xue, Zuo-Liang; Li, Yu-Min; Zhu, You-Quan; Cao, Nong

2005-02-01

The prophylactic use of antibiotics in patients with severe acute pancreatitis remains contentious. This study was undertaken to review the current studies on antibiotic prophylaxis in patients with severe acute pancreatitis. All papers found by a Medline search were relevant to human trials of antibiotic prophylaxis in patients with severe acute pancreatitis. In the 1970s, three small randomized studies of prophylactic ampicillin in the treatment of acute pancreatitis showed no effect on mortality or morbidity, but the inclusion of patients at low risk for infection and the use of an ineffective antibiotic were insufficient to detect any differences. From 1993 to 2001, eight prospective clinical trials of antibiotic prophylaxis were conducted in patients with severe acute pancreatitis (SAP). Seven of the 8 trials showed significant effect of the prophylaxis in prevention of pancreatic infections, and one showed significant improvement of clinical course documented by the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. Only two trials did demonstrate the significance of the prophylaxis in lowering the mortality rate. Despite variations in drug agents, study size and patient selection, duration of treatment, and methodology (None of the studies was double-blinded), a meta-analysis showed the positive effect of antibiotics in reducing the mortality. We suggested that antibiotic prophylaxis with proven efficacy in necrotic pancreatic tissues should be given to all patients with acute necrotizing pancreatitis. In recent years, however, the first double-blind, placebo-controlled multicenter study from Germany detected no benefit of antibiotic prophylaxis with respect to the risk of developing infected pancreatic necrosis. Prophylactic antibiotics for severe acute pancreatitis is still a matter of discussion and further studies are required to provide adequate data to answer many questions and to define the role of antibiotic prophylaxis in patients

The genetic diversity and epizootiology of infectious hematopoietic necrosis virus

USGS Publications Warehouse

Oshima, Kevin H.; Arakawa, Cindy K.; Higman, Keith H.; Landolt, Marsha L.; Nichol, Stuart T.; Winton, James R.

1994-01-01

Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus which causes a serious disease in salmondd fish. The T1 ribonuclease fingerprinttin method was used to compare the RNA genomes of 26 isolates of IHNV recovered from sockeye salmon (Oncorhynchus nerka), chinook salmon (O. tshawytscha), and steelhead trout (O. mykiss) throughout the enzootic portion of western North America. Most of the isolates as a source of genetic variation. In from a single year (1987) to limit time of isolation as a source of genetic variation. In addition, isolates from different years collected at three sites were analyzed to investigate genetic drift or evolution of IHNV within specific locations. All of the isolates examined by T1 fingerprint analysis contained less than a 50% variation in spot location and were represented by a single fingerprint group. The observed variation was estimated to correspond to less than 5% variation in the nucleic acid sequence. However, sufficient variation was detected to separate the isolates into four subgroups which appeared to correlate to different geographic regions. Host species appeared not to be a significant source of variation. The evolutionary and epizootiologic significance of these findings and their relationship to other evidence of genetic variation in IHNV isolates are discussed.

Induction of necrosis via mitochondrial targeting of Melon necrotic spot virus replication protein p29 by its second transmembrane domain.

PubMed

Mochizuki, Tomofumi; Hirai, Katsuyuki; Kanda, Ayami; Ohnishi, Jun; Ohki, Takehiro; Tsuda, Shinya

2009-08-01

The virulence factor of Melon necrotic spot virus (MNSV), a virus that induces systemic necrotic spot disease on melon plants, was investigated. When the replication protein p29 was expressed in N. benthamiana using a Cucumber mosaic virus vector, necrotic spots appeared on the leaf tissue. Transmission electron microscopy revealed abnormal mitochondrial aggregation in these tissues. Fractionation of tissues expressing p29 and confocal imaging using GFP-tagged p29 revealed that p29 associated with the mitochondrial membrane as an integral membrane protein. Expression analysis of p29 deletion fragments and prediction of hydrophobic transmembrane domains (TMDs) in p29 showed that deletion of the second putative TMD from p29 led to deficiencies in both the mitochondrial localization and virulence of p29. Taken together, these results indicated that MNSV p29 interacts with the mitochondrial membrane and that p29 may be a virulence factor causing the observed necrosis.

Induction of necrosis via mitochondrial targeting of Melon necrotic spot virus replication protein p29 by its second transmembrane domain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mochizuki, Tomofumi; Hirai, Katsuyuki; Kanda, Ayami

2009-08-01

The virulence factor of Melon necrotic spot virus (MNSV), a virus that induces systemic necrotic spot disease on melon plants, was investigated. When the replication protein p29 was expressed in N. benthamiana using a Cucumber mosaic virus vector, necrotic spots appeared on the leaf tissue. Transmission electron microscopy revealed abnormal mitochondrial aggregation in these tissues. Fractionation of tissues expressing p29 and confocal imaging using GFP-tagged p29 revealed that p29 associated with the mitochondrial membrane as an integral membrane protein. Expression analysis of p29 deletion fragments and prediction of hydrophobic transmembrane domains (TMDs) in p29 showed that deletion of the secondmore » putative TMD from p29 led to deficiencies in both the mitochondrial localization and virulence of p29. Taken together, these results indicated that MNSV p29 interacts with the mitochondrial membrane and that p29 may be a virulence factor causing the observed necrosis.« less

Two distinct phylogenetic clades of infectious hematopoietic necrosis virus overlap within the Columbia River basin

USGS Publications Warehouse

Garver, K.A.; Troyer, R.M.; Kurath, G.

2003-01-01

Infectious hematopoietic necrosis virus (IHNV), an aquatic rhabdovirus, causes a highly lethal disease of salmonid fish in North America. To evaluate the genetic diversity of IHNV from throughout the Columbia River basin, excluding the Hagerman Valley, Idaho, the sequences of a 303 nt region of the glycoprotein gene (mid-G) of 120 virus isolates were determined. Sequence comparisons revealed 30 different sequence types, with a maximum nucleotide diversity of 7.3% (22 mismatches) and an intrapopulational nucleotide diversity of 0.018. This indicates that the genetic diversity of IHNV within the Columbia River basin is 3-fold higher than in Alaska, but 2-fold lower than in the Hagerman Valley, Idaho. Phylogenetic analyses separated the Columbia River basin IHNV isolates into 2 major clades, designated U and M. The 2 clades geographically overlapped within the lower Columbia River basin and in the lower Snake River and tributaries, while the upper Columbia River basin had only U clade and the upper Snake River basin had only M clade virus types. These results suggest that there are co-circulating lineages of IHNV present within specific areas of the Columbia River basin. The epidemiological significance of these findings provided insight into viral traffic patterns exhibited by IHNV in the Columbia River basin, with specific relevance to how the Columbia River basin IHNV types were related to those in the Hagerman Valley. These analyses indicate that there have likely been 2 historical events in which Hagerman Valley IHNV types were introduced and became established in the lower Columbia River basin. However, the data also clearly indicates that the Hagerman Valley is not a continuous source of waterborne virus infecting salmonid stocks downstream.

Virulence comparisons of infectious hematopoietic necrosis virus U and M genogroups in sockeye salmon and rainbow trout

USGS Publications Warehouse

Garver, K.A.; Batts, W.N.; Kurath, G.

2006-01-01

Infectious hematopoietic necrosis virus (IHNV) is an aquatic rhabdovirus that infects salmonids in the Pacific Northwest of the United States, Europe, and Asia. Isolates of IHNV have been phylogenetically classified into three major viral genogroups, designated U, M, and L. To characterize virulence of IHNV in the context of these three viral genogroups, seven strains of IHNV (three U genogroup strains, three M strains, and one L strain) were compared for their pathogenicity in juvenile sockeye salmon Oncorhynchus nerka, kokanee (lacustrine sockeye salmon), and rainbow trout O. mykiss. Fish were waterborne-exposed to the different viral strains, and virulence was assessed by comparing mortality curves and final cumulative percent mortality (CPM) in both species of fish at 10??C and 15??C. In sockeye salmon and kokanee, the U genogroup virus types were extremely virulent, causing average CPMs of 69-100%, while the M genogroup virus types caused very little or no mortality (CPM = 0-4%). The endangered Redfish Lake sockeye salmon stock exhibited extreme differences in susceptibility to the U and M genogroups. Conversely, in two stocks of rainbow trout, the M genogroup virus types were more virulent, inducing average CPMs of 25-85%, while the U genogroup viruses caused lower mortality (CPM = 5-41%). In both fish species, the single L genogroup strain caused low to intermediate mortality (CPM = 13-53%). Viral glycoprotein sequence comparisons of the seven challenge strains revealed three amino acid sites (247, 256, and 270) that consistently differed between the U and M genogroups, possibly contributing to pathogenicity differences. ?? Copyright by the American Fisheries Society 2006.

Expression of human cationic trypsinogen (PRSS1) in murine acinar cells promotes pancreatitis and apoptotic cell death

PubMed Central

Athwal, T; Huang, W; Mukherjee, R; Latawiec, D; Chvanov, M; Clarke, R; Smith, K; Campbell, F; Merriman, C; Criddle, D; Sutton, R; Neoptolemos, J; Vlatković, N

2014-01-01

Hereditary pancreatitis (HP) is an autosomal dominant disease that displays the features of both acute and chronic pancreatitis. Mutations in human cationic trypsinogen (PRSS1) are associated with HP and have provided some insight into the pathogenesis of pancreatitis, but mechanisms responsible for the initiation of pancreatitis have not been elucidated and the role of apoptosis and necrosis has been much debated. However, it has been generally accepted that trypsinogen, prematurely activated within the pancreatic acinar cell, has a major role in the initiation process. Functional studies of HP have been limited by the absence of an experimental system that authentically mimics disease development. We therefore developed a novel transgenic murine model system using wild-type (WT) human PRSS1 or two HP-associated mutants (R122H and N29I) to determine whether expression of human cationic trypsinogen in murine acinar cells promotes pancreatitis. The rat elastase promoter was used to target transgene expression to pancreatic acinar cells in three transgenic strains that were generated: Tg(Ela-PRSS1)NV, Tg(Ela-PRSS1*R122H)NV and Tg(Ela-PRSS1*N29I)NV. Mice were analysed histologically, immunohistochemically and biochemically. We found that transgene expression is restricted to pancreatic acinar cells and transgenic PRSS1 proteins are targeted to the pancreatic secretory pathway. Animals from all transgenic strains developed pancreatitis characterised by acinar cell vacuolisation, inflammatory infiltrates and fibrosis. Transgenic animals also developed more severe pancreatitis upon treatment with low-dose cerulein than controls, displaying significantly higher scores for oedema, inflammation and overall histopathology. Expression of PRSS1, WT or mutant, in acinar cells increased apoptosis in pancreatic tissues and isolated acinar cells. Moreover, studies of isolated acinar cells demonstrated that transgene expression promotes apoptosis rather than necrosis. We therefore

Endocrine pancreatic insufficiency secondary to chronic herpesvirus pancreatitis in a cockatiel (Nymphicus hollandicus).

PubMed

Phalen, David N; Falcon, Michelle; Tomaszewski, Elizabeth K

2007-06-01

A cockatiel (Nymphicus hollandicus) examined because of weight loss, polydipsia, and polyuria was diagnosed with diabetes mellitus based on the presence of glucosuria and marked hyperglycemia. Medical attempts to manage the diabetes mellitus were unsuccessful, and the bird was euthanatized. Histopathologic examination of the pancreas revealed a chronic active pancreatitis with herpesviral inclusions in many of the pancreatic acinar and duct cells. Psittacid herpesvirus-1 (PsHV-1) DNA was amplified from the lesion by polymerase chain reaction. Sequencing of the amplicon showed it to be the genotype 1 variant, which is most commonly associated with Pacheco's disease, an acute rapidly fatal systemic infection. The findings in this case suggest that the PsHV-1 genotype may also cause a localized disease of the pancreas. Infection with this virus should be considered as a differential diagnosis in birds with pancreatitis with or without diabetes mellitus.

Clinical Study on Acute Pancreatitis in Pregnancy in 26 Cases

PubMed Central

Qihui, Cheng; Xiping, Zhang; Xianfeng, Ding

2012-01-01

Aim. This paper investigated the pathogenesis and treatment strategies of acute pancreatitis (AP) in pregnancy. Methods. We analyzed retrospectively the characteristics, auxiliary diagnosis, treatment strategies, and clinical outcomes of 26 cases of patients with AP in pregnancy. Results. All patients were cured finally. (1) Nine cases of 22 mild acute pancreatitis (MAP) patients selected automatic termination of pregnancy because of the unsatisfied therapeutic efficacy or those patients' requirements. (2) Four cases of all patients were complicated with severe acute pancreatitis (SAP); 2 cases underwent uterine incision delivery while one of them also received cholecystectomy, debridement and drainage of pancreatic necrosis, and percutaneous jejunostomy. One case had a fetal death when complicated with SAP; she had to receive extraction of bile duct stones and drainage of abdominal cavity after induced abortion. The other one case with hyperlipidemic pancreatitis was given induced abortion and hemofiltration. Conclusions. The first choice of MAP in pregnancy is the conventional therapy. Apart from the conventional therapy, we need to terminate pregnancy as early as possible for patients with SAP. Removing biliary calculi and drainage is supposed to be considered for acute biliary pancreatitis. Lowering blood lipids treatment should be applied to hyperlipidemic pancreatitis or given to hemofiltration when necessary. PMID:23213326

Interaction between Cucumber mosaic virus 2b protein and plant catalase induces a specific necrosis in association with proteasome activity.

PubMed

Murota, Katsunori; Shimura, Hanako; Takeshita, Minoru; Masuta, Chikara

2017-01-01

Cucumber mosaic virus (CMV) can induce a specific necrosis on Arabidopsis through the interaction between the CMV 2b protein and host catalase, in which the ubiquitin-proteasome pathway may be involved. We previously reported that the CMV 2b protein, the viral RNA silencing suppressor, interacted with the H 2 O 2 scavenger catalase (CAT3), leading to necrosis on CMV-inoculated Arabidopsis leaves. We here confirmed that CMV could more abundantly accumulate in the CAT3-knockout mutant (cat3), and that CAT3 makes host plants a little more tolerant to CMV. We also found that the necrosis severity is not simply explained by a high level of H 2 O 2 given by the lack of CAT3, because the recombinant CMV, CMV-N, induced much milder necrosis in cat3 than in the wild type, suggesting some specific mechanism for the necrosis induction. To further characterize the 2b-inducing necrosis in relation to its binding to CAT3, we conducted the agroinfiltration experiments to overexpress CAT3 and 2b in N. benthamiana leaves. The accumulation levels of CAT3 were higher when co-expressed with the CMV-N 2b (N2b) than with CMV-Y 2b (Y2b). We infer that N2b made a more stable complex with CAT3 than Y2b did, and the longevity of the 2b-CAT3 complex seemed to be important to induce necrosis. By immunoprecipitation (IP) with an anti-ubiquitin antibody followed by the detection with anti-CAT3 antibodies, we detected a higher molecular-weight smear and several breakdown products of CAT3 among the IP-proteins. In addition, the proteasome inhibitor MG132 treatment could actually increase the accumulation levels of CAT3. This study suggests that the host proteasome pathway is, at least partially, responsible for the degradation of CAT3, which is manifested in CMV-infected tissues.

Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2

PubMed Central

Peng, Shuang; Gerasimenko, Julia V.; Tsugorka, Tatiana; Gryshchenko, Oleksiy; Samarasinghe, Sujith; Gerasimenko, Oleg V.

2016-01-01

Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca2+ signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca2+ elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca2+ signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side-effect occurring in about 5–10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca2+ release followed by Ca2+ entry and also substantially reduced Ca2+ extrusion because of decreased intracellular ATP levels. The toxic Ca2+ signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca2+ signals and necrosis. We tested the effects of inhibiting the Ca2+ release-activated Ca2+ entry by the Ca2+ channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca2+ entry and also protected effectively against the development of necrosis. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377732

Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2.

PubMed

Peng, Shuang; Gerasimenko, Julia V; Tsugorka, Tatiana; Gryshchenko, Oleksiy; Samarasinghe, Sujith; Petersen, Ole H; Gerasimenko, Oleg V

2016-08-05

Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca(2+) signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca(2+) elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca(2+) signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side-effect occurring in about 5-10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca(2+) release followed by Ca(2+) entry and also substantially reduced Ca(2+) extrusion because of decreased intracellular ATP levels. The toxic Ca(2+) signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca(2+) signals and necrosis. We tested the effects of inhibiting the Ca(2+) release-activated Ca(2+) entry by the Ca(2+) channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca(2+) entry and also protected effectively against the development of necrosis.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. © 2016 The Authors.

Viral erythrocytic necrosis: Some physiological consequences of infection in chum salmon (Oncorhynchus keta)

USGS Publications Warehouse

MacMillan, John R.; Mulcahy, Daniel M.; Landolt, Marsha L.

1980-01-01

Erythroid cells in chum salmon (Oncorhynchus keta) susceptible to infection with erythrocytic necrosis virus (ENV) were examined by light and electron microscopy. Cells of stages II, III, IV, V, and VI contained complete eyrthrocytic necrosis virions in the cytoplasm. Viruses closely resembling ENV were also detected in the nuclei of some erythroblasts. Some secondary consequences of ENV infection were a threefold greater mortality rate from vibriosis, a significantly decreased tolerance to oxygen depletion, and a decreased ability to regulate serum sodium and potassium in saltwater.

Pancreaticoportal Fistula and Disseminated Fat Necrosis After Revision of a Transjugular Intrahepatic Portosystemic Shunt

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klein, Seth J., E-mail: kleins@mir.wustl.edu; Saad, Nael; Korenblat, Kevin

A 59-year old man with alcohol related cirrhosis and portal hypertension was referred for transjugular intrahepatic portosystemic shunt (TIPS) to treat his refractory ascites. Ten years later, two sequential TIPS revisions were performed for shunt stenosis and recurrent ascites. After these revisions, he returned with increased serum pancreatic enzyme levels and disseminated superficial fat necrosis; an iatrogenic pancreaticoportal vein fistula caused by disruption of the pancreatic duct was suspected. The bare area of the TIPS was subsequently lined with a covered stent-graft, and serum enzyme levels returned to baseline. In the interval follow-up period, the patient has clinically improved.

Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: A soluble, secreted CD30 homologue

PubMed Central

Panus, Joanne Fanelli; Smith, Craig A.; Ray, Caroline A.; Smith, Terri Davis; Patel, Dhavalkumar D.; Pickup, David J.

2002-01-01

Cowpox virus (Brighton Red strain) possesses one of the largest genomes in the Orthopoxvirus genus. Sequence analysis of a region of the genome that is type-specific for cowpox virus identified a gene, vCD30, encoding a soluble, secreted protein that is the fifth member of the tumor necrosis factor receptor family known to be encoded by cowpox virus. The vCD30 protein contains 110 aa, including a 21-residue signal peptide, a potential O-linked glycosylation site, and a 58-aa sequence sharing 51–59% identity with highly conserved extracellular segments of both mouse and human CD30. A vCD30Fc fusion protein binds CD153 (CD30 ligand) specifically, and it completely inhibits CD153/CD30 interactions. Although the functions of CD30 are not well understood, the existence of vCD30 suggests that the cellular receptor plays a significant role in normal immune responses. Viral inhibition of CD30 also lends support to the potential therapeutic value of targeting CD30 in human inflammatory and autoimmune diseases. PMID:12034885

Effects of urtica dioica extract on experimental acute pancreatitis model in rats.

PubMed

Yilmaz, Baris; Basar, Omer; Aktas, Bora; Altinbas, Akif; Ekiz, Fuat; Büyükcam, Fatih; Albayrak, Aynur; Ginis, Zeynep; Oztürk, Gülfer; Coban, Sahin; Ucar, Engin; Kaya, Oskay; Yüksel, Osman; Caner, Sedat; Delibasi, Tuncay

2014-01-01

Acute pancreatitis is the acute inflammation of pancreas and peripancreatic tissues, and distant organs are also affected. The aim of this study was to investigate the effect of Urtica dioica extract (UDE) treatment on cerulein induced acute pancreatitis in rats. Twenty-one Wistar Albino rats were divided into three groups: Control, Pancreatitis, and UDE treatment group. In the control group no procedures were performed. In the pancreatitis and treatment groups, pancreatitis was induced with intraperitoneal injection of cerulein, followed by intraperitoneal injection of 1 ml saline (pancreatitis group) and 1 ml 5.2% UDE (treatment group). Pancreatic tissues were examined histopathologically. Pro-inflammatory cytokines (tumor necrosis factor-α), amylase and markers of apoptosis (M30, M65) were also measured in blood samples. Immunohistochemical staining was performed with Caspase-3 antibody. Histopathological findings in the UDE treatment group were less severe than in the pancreatitis group (5.7 vs 11.7, p = 0.010). TNF-α levels were not statistically different between treated and control groups (63.3 vs. 57.2, p = 0.141). UDE treatment was associated with less apoptosis [determined by M30, caspase-3 index (%)], (1.769 vs. 0.288, p = 0.056; 3% vs. 2.2%, p = 0.224; respectively). UDE treatment of pancreatitis merits further study.

Effects of urtica dioica extract on experimental acute pancreatitis model in rats

PubMed Central

Yilmaz, Baris; Basar, Ömer; Aktas, Bora; Altinbas, Akif; Ekiz, Fuat; Büyükcam, Fatih; Albayrak, Aynur; Ginis, Zeynep; Öztürk, Gülfer; Coban, Sahin; Ucar, Engin; Kaya, Oskay; Yüksel, Osman; Caner, Sedat; Delibasi, Tuncay

2014-01-01

Acute pancreatitis is the acute inflammation of pancreas and peripancreatic tissues, and distant organs are also affected. The aim of this study was to investigate the effect of Urtica dioica extract (UDE) treatment on cerulein induced acute pancreatitis in rats. Twenty-one Wistar Albino rats were divided into three groups: Control, Pancreatitis, and UDE treatment group. In the control group no procedures were performed. In the pancreatitis and treatment groups, pancreatitis was induced with intraperitoneal injection of cerulein, followed by intraperitoneal injection of 1 ml saline (pancreatitis group) and 1 ml 5.2% UDE (treatment group). Pancreatic tissues were examined histopathologically. Pro-inflammatory cytokines (tumor necrosis factor-α), amylase and markers of apoptosis (M30, M65) were also measured in blood samples. Immunohistochemical staining was performed with Caspase-3 antibody. Histopathological findings in the UDE treatment group were less severe than in the pancreatitis group (5.7 vs 11.7, p = 0.010). TNF-α levels were not statistically different between treated and control groups (63.3 vs. 57.2, p = 0.141). UDE treatment was associated with less apoptosis [determined by M30, caspase-3 index (%)], (1.769 vs. 0.288, p = 0.056; 3% vs. 2.2%, p = 0.224; respectively). UDE treatment of pancreatitis merits further study. PMID:24995088

Percutaneous transgastric irrigation drainage in combination with endoscopic necrosectomy in necrotizing pancreatitis (with videos).

PubMed

Raczynski, Susanne; Teich, Niels; Borte, Gudrun; Wittenburg, Henning; Mössner, Joachim; Caca, Karel

2006-09-01

Endoscopic drainage of pancreatic acute and chronic pseudocysts and pancreatic necrosectomy have been shown to be beneficial for critically ill patients, with complete endoscopic resolution rates of around 80%. Our purpose was to describe an improved endoscopic technique used to treat pancreatic necrosis. Case report. University hospital. Two patients with large retroperitoneal necroses were treated with percutaneous transgastric retroperitoneal flushing tubes and a percutaneous transgastric jejunal feeding tube by standard percutaneous endoscopic gastrostomy access in addition to endoscopic necrosectomy. Intensive percutaneous transgastric flushing in combination with percutaneous normocaloric enteral nutrition and repeated endoscopic necrosectomy led to excellent outcomes in both patients. Small number of patients. The "double percutaneous endoscopic gastrostomy" approach for simultaneous transgastric drainage and normocaloric enteral nutrition in severe cases of pancreatic necroses is safe and effective. It could be a promising improvement to endoscopic transgastric treatment options in necrotizing pancreatitis.

Advances in the endoscopic management of pancreatic collections.

PubMed

Ruiz-Clavijo, David; de la Higuera, Belen González; Vila, Juan J

2015-04-16

Treatment of pancreatic collections has experienced great progress in recent years with the emergence of alternative minimally invasive techniques comparing to the classic surgical treatment. Such techniques have been shown to improve outcomes of morbidity vs surgical treatment. The recent emergence of endoscopic drainage is noteworthy. The advent of endoscopic ultrasonography has been crucial for treatment of these specific lesions. They can be characterized, their relationships with neighboring structures can be evaluated and the drainage guided by this technique has been clearly improved compared with the conventional endoscopic drainage. Computed tomography is the technique of choice to characterize the recently published new classification of pancreatic collections. For this reason, the radiologist's role establishing and classifying in a rigorously manner the collections according to the new nomenclature is essential to making therapeutic decisions. Ideal scenario for comprehensive treatment of these collections would be those centers with endoscopic ultrasound and interventional radiology expertise together with hepatobiliopancreatic surgery. This review describes the different types of pancreatic collections: acute peripancreatic fluid collection, pancreatic pseudocysts, acute necrotic collection and walled-off necrosis; the indications and the contraindications for endoscopic drainage, the drainage technique and their outcomes. The integrated management of pancreatic collections according to their type and evolution time is discussed.

Hypothermia induced by adenosine 5'-monophosphate attenuates injury in an L-arginine-induced acute pancreatitis rat model.

PubMed

Wang, Yunlong; Guo, Weiting; Li, Yuan; Pan, Xinting; Lv, Wenshan; Cui, Lingling; Li, Changgui; Wang, Yangang; Yan, Shengli; Zhang, Jidong; Liu, Bin

2014-04-01

This study sought to investigate the effects of hypothermia induced by adenosine 5'-monophosphate (5'-AMP) on L-arginine (L-Arg)-induced acute pancreatitis in rats. The rats were divided into four groups: the control group, the acute pancreatitis group, the 5'-AMP pretreatment group, and the 5'-AMP posttreatment group. Rats in all groups, except for the control group, received two injections of 2.5 g/kg body weight (intraperitoneally) L-Arg, with an interval of 1 h between the injections. Subsequently, the rats were observed to assess whether hypothermia induced by 5'-AMP could effectively inhibit inflammation associated with L-Arg-induced acute pancreatitis in rats. Hypothermia induced by 5'-AMP produced protective effects in our acute pancreatitis model. These effects exhibited the following manifestations: (i) a significant reduction in rat mortality rates; (ii) a significant decrease in the occurrence of pancreatic edema; (iii) significant reductions in serum amylase (P < 0.001), interleukin-6 (P < 0.001), interleukin-1β (P < 0.001) and tumor necrosis factor-α (P < 0.001); (iv) the significant inhibition of nuclear factor-κB (NF-κB) activation in rats that were pre- and posttreated with 5'-AMP compared with rats that were only injected with L-Arg; and (v) significant decreases in the occurrence of pancreatic interstitial edema, inflammatory cell infiltration, hemorrhage, and acinar cell necrosis. Hypothermia induced by 5'-AMP could inhibit the acute inflammatory reaction and NF-κB activation associated with acute pancreatitis. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Arginase-II Promotes Tumor Necrosis Factor-α Release From Pancreatic Acinar Cells Causing β-Cell Apoptosis in Aging.

PubMed

Xiong, Yuyan; Yepuri, Gautham; Necetin, Sevil; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong

2017-06-01

Aging is associated with glucose intolerance. Arginase-II (Arg-II), the type-II L -arginine-ureahydrolase, is highly expressed in pancreas. However, its role in regulation of pancreatic β-cell function is not known. Here we show that female (not male) mice deficient in Arg-II (Arg-II -/- ) are protected from age-associated glucose intolerance and reveal greater glucose induced-insulin release, larger islet size and β-cell mass, and more proliferative and less apoptotic β-cells compared with the age-matched wild-type (WT) controls. Moreover, Arg-II is mainly expressed in acinar cells and is upregulated with aging, which enhances p38 mitogen-activated protein kinase (p38 MAPK) activation and release of tumor necrosis factor-α (TNF-α). Accordingly, conditioned medium of isolated acinar cells from old WT (not Arg-II -/- ) mice contains higher TNF-α levels than the young mice and stimulates β-cell apoptosis and dysfunction, which are prevented by a neutralizing anti-TNF-α antibody. In acinar cells, our study demonstrates an age-associated Arg-II upregulation, which promotes TNF-α release through p38 MAPK leading to β-cell apoptosis, insufficient insulin secretion, and glucose intolerance in female rather than male mice. © 2017 by the American Diabetes Association.

Nature of the endogenous pyrogen (EP) induced by influenza viruses: lack of correlation between EP levels and content of the known pyrogenic cytokines, interleukin 1, interleukin 6 and tumour necrosis factor.

PubMed

Jakeman, K J; Bird, C R; Thorpe, R; Smith, H; Sweet, C

1991-03-01

Fever in influenza results from the release of endogenous pyrogen (EP) following virus-phagocyte interaction and its level correlates with the differing virulence of virus strains. However, the different levels of fever produced in ferrets by intracardial inoculation of EP obtained from the interaction of different virus strains with ferret of human phagocytes did not correlate with the levels of interleukin 1 (IL-1), IL-6 or tumour necrosis factor in the same samples as assayed by conventional in vitro methods. Hence, the EP produced by influenza virus appears to be different to these cytokines.

Cucumber Necrosis Virus Recruits Cellular Heat Shock Protein 70 Homologs at Several Stages of Infection

PubMed Central

Alam, Syed Benazir

2015-01-01

ABSTRACT RNA viruses often depend on host factors for multiplication inside cells due to the constraints of their small genome size and limited coding capacity. One such factor that has been exploited by several plant and animal viruses is heat shock protein 70 (HSP70) family homologs which have been shown to play roles for different viruses in viral RNA replication, viral assembly, disassembly, and cell-to-cell movement. Using next generation sequence analysis, we reveal that several isoforms of Hsp70 and Hsc70 transcripts are induced to very high levels during cucumber necrosis virus (CNV) infection of Nicotiana benthamiana and that HSP70 proteins are also induced by at least 10-fold. We show that HSP70 family protein homologs are co-opted by CNV at several stages of infection. We have found that overexpression of Hsp70 or Hsc70 leads to enhanced CNV genomic RNA, coat protein (CP), and virion accumulation, whereas downregulation leads to a corresponding decrease. Hsc70-2 was found to increase solubility of CNV CP in vitro and to increase accumulation of CNV CP independently of viral RNA replication during coagroinfiltration in N. benthamiana. In addition, virus particle assembly into virus-like particles in CP agroinfiltrated plants was increased in the presence of Hsc70-2. HSP70 was found to increase the targeting of CNV CP to chloroplasts during infection, reinforcing the role of HSP70 in chloroplast targeting of host proteins. Hence, our findings have led to the discovery of a highly induced host factor that has been co-opted to play multiple roles during several stages of the CNV infection cycle. IMPORTANCE Because of the small size of its RNA genome, CNV is dependent on interaction with host cellular components to successfully complete its multiplication cycle. We have found that CNV induces HSP70 family homologs to a high level during infection, possibly as a result of the host response to the high levels of CNV proteins that accumulate during infection

Genetic and serological typing of European infectious haematopoietic necrosis virus (IHNV) isolates

USGS Publications Warehouse

Johansson, T.; Einer-Jensen, K.; Batts, W.; Ahrens, P.; Bjorkblom, C.; Kurath, G.; Bjorklund, H.; Lorenzen, N.

2009-01-01

Infectious haematopoietic necrosis virus (IHNV) causes the lethal disease infectious haematopoietic necrosis (IHN) in juvenile salmon and trout. The nucleocapsid (N) protein gene and partial glycoprotein (G) gene (nucleotides 457 to 1061) of the European isolates IT-217A, FR-32/87, DE-DF 13/98 11621, DE-DF 4/99-8/99, AU-9695338 and RU-FR1 were sequenced and compared with IHNV isolates from the North American genogroups U, M and L. In phylogenetic studies the N gene of the Italian, French, German and Austrian isolates clustered in the M genogroup, though in a different subgroup than the isolates from the USA. Analyses of the partial G gene of these European isolates clustered them in the M genogroup close to the root while the Russian isolate clustered in the U genogroup. The European isolates together with US-WRAC and US-Col-80 were also tested in an enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies (MAbs) against the N protein. MAbs 136-1 and 136-3 reacted equally at all concentrations with the isolates tested, indicating that these antibodies identify a common epitope. MAb 34D3 separated the M and L genogroup isolates from the U genogroup isolate. MAb 1DW14D divided the European isolates into 2 groups. MAb 1DW14D reacted more strongly with DE-DF 13/98 11621 and RU-FR1 than with IT-217A, FR- 32/87, DE-DF 4/99-8/99 and AU-9695338. In the phylogenetic studies, the Italian, French, German and Austrian isolates clustered in the M genogroup, whereas in the serological studies using MAbs, the European M genogroup isolates could not be placed in the same specific group. These results indicate that genotypic and serotypic classification do not correlate. ?? 2009 Inter-Research.

Infectious haematopoietic necrosis virus genogroup-specific virulence mechanisms in sockeye salmon, Oncorhynchus nerka (Walbaum), from Redfish Lake, Idaho

USGS Publications Warehouse

Purcell, M.K.; Garver, K.A.; Conway, C.; Elliott, D.G.; Kurath, G.

2009-01-01

Characterization of infectious haematopoietic necrosis virus (IHNV) field isolates from North America has established three main genogroups (U, M and L) that differ in host-specific virulence. In sockeye salmon, Oncorhynchus nerka, the U genogroup is highly virulent, whereas the M genogroup is nearly non-pathogenic. In this study, we sought to characterize the virus-host dynamics that contribute to genogroup-specific virulence in a captive stock of sockeye salmon from Redfish Lake in Idaho. Juvenile sockeye salmon were challenged by immersion and injection with either a representative U or M viral strain and sampled periodically until 14 days post-infection (p.i.). Fish challenged with each strain had positive viral titre by day 3, regardless of challenge route, but the fish exposed to the M genogroup virus had significantly lower virus titres than fish exposed to the U genogroup virus. Gene expression analysis by quantitative reverse transcriptase PCR was used to simultaneously assess viral load and host interferon (IFN) response in the anterior kidney. Viral load was significantly higher in the U-challenged fish relative to M-challenged fish. Both viruses induced expression of the IFN-stimulated genes (ISGs), but expression was usually significantly lower in the M-challenged group, particularly at later time points (7 and 14 days p.i.). However, ISG expression was comparable with 3 days post-immersion challenge despite a significant difference in viral load. Our data indicated that the M genogroup virus entered the host, replicated and spread in the sockeye salmon tissues, but to a lesser extent than the U genogroup. Both virus types induced a host IFN response, but the high virulence strain (U) continued to replicate in the presence of this response, whereas the low virulence strain (M) was cleared below detectable levels. We hypothesize that high virulence is associated with early in vivo replication allowing the virus to achieve a threshold level, which the

Infectious haematopoietic necrosis virus genogroup-specific virulence mechanisms in sockeye salmon, Oncorhynchus nerka (Walbaum), from Redfish Lake, Idaho.

PubMed

Purcell, M K; Garver, K A; Conway, C; Elliott, D G; Kurath, G

2009-07-01

Characterization of infectious haematopoietic necrosis virus (IHNV) field isolates from North America has established three main genogroups (U, M and L) that differ in host-specific virulence. In sockeye salmon, Oncorhynchus nerka, the U genogroup is highly virulent, whereas the M genogroup is nearly non-pathogenic. In this study, we sought to characterize the virus-host dynamics that contribute to genogroup-specific virulence in a captive stock of sockeye salmon from Redfish Lake in Idaho. Juvenile sockeye salmon were challenged by immersion and injection with either a representative U or M viral strain and sampled periodically until 14 days post-infection (p.i.). Fish challenged with each strain had positive viral titre by day 3, regardless of challenge route, but the fish exposed to the M genogroup virus had significantly lower virus titres than fish exposed to the U genogroup virus. Gene expression analysis by quantitative reverse transcriptase PCR was used to simultaneously assess viral load and host interferon (IFN) response in the anterior kidney. Viral load was significantly higher in the U-challenged fish relative to M-challenged fish. Both viruses induced expression of the IFN-stimulated genes (ISGs), but expression was usually significantly lower in the M-challenged group, particularly at later time points (7 and 14 days p.i.). However, ISG expression was comparable with 3 days post-immersion challenge despite a significant difference in viral load. Our data indicated that the M genogroup virus entered the host, replicated and spread in the sockeye salmon tissues, but to a lesser extent than the U genogroup. Both virus types induced a host IFN response, but the high virulence strain (U) continued to replicate in the presence of this response, whereas the low virulence strain (M) was cleared below detectable levels. We hypothesize that high virulence is associated with early in vivo replication allowing the virus to achieve a threshold level, which the

The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lou, Hai-zhou; Weng, Xiao-chuan; Pan, Hong-ming

Highlights: • INK-128 inhibits the survival and growth of human pancreatic cancer cells. • INK-128 induced pancreatic cancer cell apoptosis and necrosis simultaneously. • INK-128 blocks mTORC1/2 activation simultaneously in pancreatic cancer cells. • INK-128 down-regulates cyclin D1 and causes pancreatic cancer cell cycle arrest. • INK-128 significantly increases sensitivity of pancreatic cancer cells to gemcitabine. - Abstract: Pancreatic cancer has one of worst prognosis among all human malignancies around the world, the development of novel and more efficient anti-cancer agents against this disease is urgent. In the current study, we tested the potential effect of INK-128, a novel mammalianmore » target of rapamycin (mTOR) complex 1 and 2 (mTORC1/2) dual inhibitor, against pancreatic cancer cells in vitro. Our results demonstrated that INK-128 concentration- and time-dependently inhibited the survival and growth of pancreatic cancer cells (both primary cells and transformed cells). INK-128 induced pancreatic cancer cell apoptosis and necrosis simultaneously. Further, INK-128 dramatically inhibited phosphorylation of 4E-binding protein 1 (4E-BP1), ribosomal S6 kinase 1 (S6K1) and Akt at Ser 473 in pancreatic cancer cells. Meanwhile, it downregulated cyclin D1 expression and caused cell cycle arrest. Finally, we found that a low concentration of INK-128 significantly increased the sensitivity of pancreatic cancer cells to gemcitabine. Together, our in vitro results suggest that INK-128 might be further investigated as a novel anti-cancer agent or chemo-adjuvant for pancreatic cancer treatment.« less

Outcome of video-assisted translumbar retroperitoneal necrosectomy and closed lavage for severe necrotizing pancreatitis.

PubMed

Ulagendra Perumal, Srinivasan; Pillai, Sastha Ahanatha; Perumal, Senthilkumar; Sathyanesan, Jeswanth; Palaniappan, Ravichandran

2014-04-01

Surgery for necrotizing pancreatitis is associated with a high rate of morbidity and mortality. We present a series of 26 patients who underwent video-assisted translumbar retroperitoneal necrosectomy and analyse their outcomes. Records of 26 patients who underwent video-assisted translumbar retroperitoneal necrosectomy and closed drainage for infected pancreatitic necrosis between January 2008 and March 2012 were reviewed, retrospectively. Twenty-three out of 26 patients were males, with a mean age of 38.6 (±9.9) years. Alcohol was the aetiology in 18 patients, gall stones in 7, and in 1 it was idiopathic. The mean duration of symptoms before patients were taken up for surgery was 47.2 (±34.8) days. The mean computed tomography severity index was 7.7 (±1.2). All patients had undergone video-assisted retroperitoneal necrosectomy through a limited left lumbar incision. Post-operative lavage was given through drains placed in the retroperitoneum. Three patients required re-exploration. Eleven patients developed complications and there were two mortalities. The median intensive care unit (ICU) stay was 4 days (range 2-14 days). The mean post-operative hospital stay was 22.5 (±6.6) days. Video-assisted translumbar retroperitoneal necrosectomy followed by closed lavage of infected pancreatic necrosis in select cases of infected pancreatic necrosis was associated with a low rate of ICU stay, hospital stay and need for re-entry. © 2013 The Authors. ANZ Journal of Surgery © 2013 Royal Australasian College of Surgeons.

Genetic characterization of infectious hematopoietic necrosis virus of coastal salmonid stocks in Washington State

USGS Publications Warehouse

Emmenegger, E.J.; Kurath, G.

2002-01-01

Infectious hematopoietic necrosis virus (IHNV) is a pathogen that infects many Pacific salmonid stocks from the watersheds of North America. Previous studies have thoroughly characterized the genetic diversity of IHNV isolates from Alaska and the Hagerman Valley in Idaho. To enhance understanding of the evolution and viral transmission patterns of IHNV within the Pacific Northwest geographic range, we analyzed the G gene of IHNV isolates from the coastal watersheds of Washington State by ribonuclease protection assay (RPA) and nucleotide sequencing. The RPA analysis of 23 isolates indicated that the Skagit basin IHNV isolates were relatively homogeneous as a result of the dominance of one G gene haplotype (S). Sequence analysis of 303 bases in the middle of the G gene (midG region) of 61 isolates confirmed the high frequency of a Skagit River basin sequence and identified another sequence commonly found in isolates from the Lake Washington basin. Overall, both the RPA and sequence analysis showed that the Washington coastal IHNV isolates are genetically homogeneous and have little genetic diversity. This is similar to the genetic diversity pattern of IHNV from Alaska and contrasts sharply with the high genetic diversity demonstrated for IHNV isolates from fish farms along the Snake River in Idaho. The high degree of sequence and haplotype similarity between the Washington coastal IHNV isolates and those from Alaska and British Columbia suggests that they have a common viral ancestor. Phylogenetic analyses of the isolates we studied and those from different regions throughout the virus's geographic range confirms a conserved pattern of evolution of the virus in salmonid stocks north of the Columbia River, which forms Washington's southern border.

Infectious hematopoietic necrosis (IHN) and viral hemorrhagic septicemia (VHS): Detection of the trout antibodies to the causative viruses by means of plaque neutralization, immunofluorescence, and enzyme-linked immunosorbent assay

USGS Publications Warehouse

Vestergard Jorgensen, P. E.; Olesen, N.J.; Lorenzen, N.; Winton, J.R.; Ristow, S.S.

1991-01-01

Sera collected from cultured rainbow trout Oncorhynchus mykiss surviving outbreaks of infectious hematopoietic necrosis (IHN) or viral hemorrhagic septicemia (VHS) were examined for the presence of antibodies to both of the causative viruses, infectious hematopoietic necrosis virus (IHNV) and Egtved virus (viral hemorrhagic septicemia virus: VHSV). Sera were screened with three serological tests: 50% plaque neutralization test (PNT), immunofluorescence (IF), and enzyme-linked immunosorbent assay (ELISA). In sera from 20 rainbow trout surviving IHN, antibodies to IHNV were detected in 9 fish by PNT, in 12 fish by IF, and in 9 fish by ELISA. In these sera, antibodies cross-reacting with VHSV were rare (detected in 0 fish by PNT, in 1 by IF, and in 1 by ELISA). In sera from 20 rainbow trout surviving VHS, antibodies to VHSV were detected in 9 fish by PNT, in 16 fish by IF, and in 18 fish by ELISA. A considerable percentage of the VHS-survivor sera contained antibodies that cross-reacted with IHNV, as detected by ELISA (16 fish) and 1F (7 fish) but not by PNT (0 fish). The three serological tests appear to be useful tools for IHNV and VHSV epidemiology; however, the presence of cross-reacting antibodies in some sera suggests caution when farms require specific pathogen-free certification for one of the viruses in the presence of the other.

Inhibitors of ORAI1 Prevent Cytosolic Calcium-Associated Injury of Human Pancreatic Acinar Cells and Acute Pancreatitis in 3 Mouse Models

PubMed Central

Wen, Li; Voronina, Svetlana; Javed, Muhammad A.; Awais, Muhammad; Szatmary, Peter; Latawiec, Diane; Chvanov, Michael; Collier, David; Huang, Wei; Barrett, John; Begg, Malcolm; Stauderman, Ken; Roos, Jack; Grigoryev, Sergey; Ramos, Stephanie; Rogers, Evan; Whitten, Jeff; Velicelebi, Gonul; Dunn, Michael; Tepikin, Alexei V.; Criddle, David N.; Sutton, Robert

2015-01-01

Background & Aims Sustained activation of the cytosolic calcium concentration induces injury to pancreatic acinar cells and necrosis. The calcium release–activated calcium modulator ORAI1 is the most abundant Ca2+ entry channel in pancreatic acinar cells; it sustains calcium overload in mice exposed to toxins that induce pancreatitis. We investigated the roles of ORAI1 in pancreatic acinar cell injury and the development of acute pancreatitis in mice. Methods Mouse and human acinar cells, as well as HEK 293 cells transfected to express human ORAI1 with human stromal interaction molecule 1, were hyperstimulated or incubated with human bile acid, thapsigargin, or cyclopiazonic acid to induce calcium entry. GSK-7975A or CM_128 were added to some cells, which were analyzed by confocal and video microscopy and patch clamp recordings. Acute pancreatitis was induced in C57BL/6J mice by ductal injection of taurolithocholic acid 3-sulfate or intravenous' administration of cerulein or ethanol and palmitoleic acid. Some mice then were given GSK-7975A or CM_128, which inhibit ORAI1, at different time points to assess local and systemic effects. Results GSK-7975A and CM_128 each separately inhibited toxin-induced activation of ORAI1 and/or activation of Ca2+ currents after Ca2+ release, in a concentration-dependent manner, in mouse and human pancreatic acinar cells (inhibition >90% of the levels observed in control cells). The ORAI1 inhibitors also prevented activation of the necrotic cell death pathway in mouse and human pancreatic acinar cells. GSK-7975A and CM_128 each inhibited all local and systemic features of acute pancreatitis in all 3 models, in dose- and time-dependent manners. The agents were significantly more effective, in a range of parameters, when given at 1 vs 6 hours after induction of pancreatitis. Conclusions Cytosolic calcium overload, mediated via ORAI1, contributes to the pathogenesis of acute pancreatitis. ORAI1 inhibitors might be developed

[Latest advances in acute pancreatitis].

PubMed

de-Madaria, Enrique

2013-10-01

The present article analyzes the main presentations on acute pancreatitis (AP) in Digestive Disease Week 2013. Perfusion computed tomography allows early diagnosis of pancreatic necrosis. Neutrophil gelatinase-associated lipocalin predicts the development of acute renal failure, severe AP and death. Factors associated with greater fluid sequestration in AP are alcoholic etiology, an elevated hematocrit, and the presence of criteria of systemic inflammatory response syndrome; fluid sequestration is associated with a worse outcome. True pseudocysts (fluid collections without necrosis for more than 4 weeks) are a highly infrequent complication in AP. Patients with necrotic collections have a poor prognosis, especially if associated with infection. A meta-analysis on fluid therapy suggests that early aggressive fluid administration is associated with higher mortality and more frequent respiratory complications. According to a meta-analysis, enteral nutrition initiated within 24 hours of admission improves the outcome of AP compared with later initiation of enteral nutrition. Pentoxifylline could be a promising alternative in AP; a double-blind randomized study showed that this drug reduced the length of hospital and intensive care unit stay, as well as the need for intensive care unit admission. The association of octreotide and celecoxib seems to reduce the frequency of organ damage compared with octreotide alone. Mild AP can be managed in the ambulatory setting through hospital-at-home units after a short, 24-hour admission. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Management of patients after recovering from acute severe biliary pancreatitis.

PubMed

Dedemadi, Georgia; Nikolopoulos, Manolis; Kalaitzopoulos, Ioannis; Sgourakis, George

2016-09-14

Cholelithiasis is the most common cause of acute pancreatitis, accounting 35%-60% of cases. Around 15%-20% of patients suffer a severe attack with high morbidity and mortality rates. As far as treatment is concerned, the optimum method of late management of patients with severe acute biliary pancreatitis is still contentious and the main question is over the correct timing of every intervention. Patients after recovering from an acute episode of severe biliary pancreatitis can be offered alternative options in their management, including cholecystectomy, endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy, or no definitive treatment. Delaying cholecystectomy until after resolution of the inflammatory process, usually not earlier than 6 wk after onset of acute pancreatitis, seems to be a safe policy. ERCP and sphincterotomy on index admission prevent recurrent episodes of pancreatitis until cholecystectomy is performed, but if used for definitive treatment, they can be a valuable tool for patients unfit for surgery. Some patients who survive severe biliary pancreatitis may develop pseudocysts or walled-off necrosis. Management of pseudocysts with minimally invasive techniques, if not therapeutic, can be used as a bridge to definitive operative treatment, which includes delayed cholecystectomy and concurrent pseudocyst drainage in some patients. A management algorithm has been developed for patients surviving severe biliary pancreatitis according to the currently published data in the literature.

Src kinases play a novel dual role in acute pancreatitis affecting severity but no role in stimulated enzyme secretion.

PubMed

Nuche-Berenguer, Bernardo; Ramos-Álvarez, Irene; Jensen, R T

2016-06-01

In pancreatic acinar cells, the Src family of kinases (SFK) is involved in the activation of several signaling cascades that are implicated in mediating cellular processes (growth, cytoskeletal changes, apoptosis). However, the role of SFKs in various physiological responses such as enzyme secretion or in pathophysiological processes such as acute pancreatitis is either controversial, unknown, or incompletely understood. To address this, in this study, we investigated the role/mechanisms of SFKs in acute pancreatitis and enzyme release. Enzyme secretion was studied in rat dispersed pancreatic acini, in vitro acute-pancreatitis-like changes induced by supramaximal COOH-terminal octapeptide of cholecystokinin (CCK). SFK involvement assessed using the chemical SFK inhibitor (PP2) with its inactive control, 4-amino-7-phenylpyrazol[3,4-d]pyrimidine (PP3), under experimental conditions, markedly inhibiting SFK activation. In CCK-stimulated pancreatic acinar cells, activation occurred of trypsinogen, various MAP kinases (p42/44, JNK), transcription factors (signal transducer and activator of transcription-3, nuclear factor-κB, activator protein-1), caspases (3, 8, and 9) inducing apoptosis, LDH release reflective of necrosis, and various chemokines secreted (monocyte chemotactic protein-1, macrophage inflammatory protein-1α, regulated on activation, normal T cell expressed and secreted). All were inhibited by PP2, not by PP3, except caspase activation leading to apoptosis, which was increased, and trypsin activation, which was unaffected, as was CCK-induced amylase release. These results demonstrate SFK activation is playing a dual role in acute pancreatitis, inhibiting apoptosis and promoting necrosis as well as chemokine/cytokine release inducing inflammation, leading to more severe disease, as well as not affecting secretion. Thus, our studies indicate that SFK is a key mediator of inflammation and pancreatic acinar cell death in acute pancreatitis, suggesting it

Tumour necrosis factor-alpha-induced protein 8 (TNFAIP8) expression associated with cell survival and death in cancer cell lines infected with canine distemper virus.

PubMed

Garcia, J A; Ferreira, H L; Vieira, F V; Gameiro, R; Andrade, A L; Eugênio, F R; Flores, E F; Cardoso, T C

2017-06-01

Oncolytic virotherapy is a novel strategy for treatment of cancer in humans and companion animals as well. Canine distemper virus (CDV), a paramyxovirus, has proven to be oncolytic through induction of apoptosis in canine-derived tumour cells, yet the mechanism behind this inhibitory action is poorly understood. In this study, three human mammary tumour cell lines and one canine-derived adenofibrosarcoma cell line were tested regarding to their susceptibility to CDV infection, cell proliferation, apoptosis, mitochondrial membrane potential and expression of tumour necrosis factor-alpha-induced protein 8 (TNFAIP8). CDV replication-induced cytopathic effect, decrease of cell proliferation rates, and >45% of infected cells were considered death and/or under late apoptosis/necrosis. TNFAIP8 and CDVM gene expression were positively correlated in all cell lines. In addition, mitochondrial membrane depolarization was associated with increase in virus titres (p < 0.005). Thus, these results strongly suggest that both human and canine mammary tumour cells are potential candidates for studies concerning CDV-induced cancer therapy. © 2015 John Wiley & Sons Ltd.

Mapping the neutralizing epitopes on the glycoprotein of infectious haematopoietic necrosis virus, a fish rhabdovirus

USGS Publications Warehouse

Huang, C.; Chien, M.S.; Landolt, M.L.; Batts, W.; Winton, J.

1996-01-01

Twelve neutralizing monoclonal antibodies (MAbs) against the fish rhabdovirus, infectious haematopoietic necrosis virus (IHNV), were used to select 20 MAb escape mutants. The nucleotide sequence of the entire glycoprotein (G) gene was determined for six mutants representing differing cross-neutralization patterns and each had a single nucleotide change leading to a single amino acid substitution within one of three regions of the protein. These data were used to design nested PCR primers to amplify portions of the G gene of the 14 remaining mutants. When the PCR products from these mutants were sequenced, they also had single nucleotide substitutions coding for amino acid substitutions at the same, or nearby, locations. Of the 20 mutants for which all or part of the glycoprotein gene was sequenced, two MAbs selected mutants with substitutions at amino acids 230-231 (antigenic site I) and the remaining MAbs selected mutants with substitutions at amino acids 272-276 (antigenic site II). Two MAbs that selected mutants mapping to amino acids 272-276, selected other mutants that mapped to amino acids 78-81, raising the possibility that this portion of the N terminus of the protein was part of a discontinuous epitope defining antigenic site II. CLUSTAL alignment of the glycoproteins of rabies virus, vesicular stomatitis virus and IHNV revealed similarities in the location of the neutralizing epitopes and a high degree of conservation among cysteine residues, indicating that the glycoproteins of three different genera of animal rhabdoviruses may share a similar three-dimensional structure in spite of extensive sequence divergence.

Pancreatic fluid collections: What is the ideal imaging technique?

PubMed

Dhaka, Narendra; Samanta, Jayanta; Kochhar, Suman; Kalra, Navin; Appasani, Sreekanth; Manrai, Manish; Kochhar, Rakesh

2015-12-28

Pancreatic fluid collections (PFCs) are seen in up to 50% of cases of acute pancreatitis. The Revised Atlanta classification categorized these collections on the basis of duration of disease and contents, whether liquid alone or a mixture of fluid and necrotic debris. Management of these different types of collections differs because of the variable quantity of debris; while patients with pseudocysts can be drained by straight-forward stent placement, walled-off necrosis requires multi-disciplinary approach. Differentiating these collections on the basis of clinical severity alone is not reliable, so imaging is primarily performed. Contrast-enhanced computed tomography is the commonly used modality for the diagnosis and assessment of proportion of solid contents in PFCs; however with certain limitations such as use of iodinated contrast material especially in renal failure patients and radiation exposure. Magnetic resonance imaging (MRI) performs better than computed tomography (CT) in characterization of pancreatic/peripancreatic fluid collections especially for quantification of solid debris and fat necrosis (seen as fat density globules), and is an alternative in those situations where CT is contraindicated. Also magnetic resonance cholangiopancreatography is highly sensitive for detecting pancreatic duct disruption and choledocholithiasis. Endoscopic ultrasound is an evolving technique with higher reproducibility for fluid-to-debris component estimation with the added advantage of being a single stage procedure for both diagnosis (solid debris delineation) and management (drainage of collection) in the same sitting. Recently role of diffusion weighted MRI and positron emission tomography/CT with (18)F-FDG labeled autologous leukocytes is also emerging for detection of infection noninvasively. Comparative studies between these imaging modalities are still limited. However we look forward to a time when this gap in literature will be fulfilled.

[Glutamate dehydrogenase activity in the pancreatic tissue in acute experimental pancreatitis and under the action of sodium thiosulphate].

PubMed

Simavorian, P S; Saakian, I L; Gevorkian, D A

1991-04-01

It has been established that the development of acute pancreatitis is accompanied by the reduced activity of glutamate dehydrogenase in the mitochondrial fraction of pancreas, pronounced in the focus of tissue necrosis and less expressed in the reactive inflammation focus. Besides this in the pancreas redistribution of enzyme, activity in the subcellular organelles takes place and enzyme activity emerges in the cytosol and further--in the blood and peritoneum liquid. Sodium thiosulfate has a marked correlation effect.

External pancreatic fistula as a sequel to management of acute severe necrotizing pancreatitis.

PubMed

Sikora, Sadiq S; Khare, Ritu; Srikanth, Gadiyaram; Kumar, Ashok; Saxena, Rajan; Kapoor, Vinay K

2005-01-01

External pancreatic fistula (EPF) is a common sequel to surgical or percutaneous intervention for infective complications of acute severe pancreatitis. The present study was aimed at studying the clinical profile, course and outcome of patients with EPF following surgical or percutaneous management of these infective complications. A retrospective analysis of clinical data of patients with EPF following intervention (surgical or percutaneous) for acute severe pancreatitis managed between January 1989 and April 2002 recorded on a prospective database was done. Univariate analysis of various factors (etiology, imaging findings prior to intervention, fistula characteristics and management) that could predict early closure of fistula was performed. Of 210 patients with acute severe pancreatitis, 43 (20%) patients developed EPF (mean age 38 (range 16-78) years, M:F ratio 5:1) following intervention for infected pancreatic necrosis (n=23) and pancreatic abscess (n=20) and constituted the study group. The fistula output was categorized as low (<200 ml), moderate (200-500 ml) and high (>500 ml) in 29 (67%), 11 (26%) and 3 (7%) patients, respectively. Fifteen patients (35%) had morbidity in the form of abscess (n=5), bleeding (n=1), pseudoaneurysm (n=2) and fever with no other focus of infection (n=7). Spontaneous closure of the fistula occurred in 38 (88%) patients. The average time to closure of fistula was 109+/- 26 (median 70) days. Fistula closed after intervention in 5 patients (2 after endoscopic papillotomy, 1 after fistulojejunostomy and 2 after downsizing the drains). Of the 38 patients with spontaneous closure, 9 (24%) patients developed a pseudocyst after a mean interval of 123 days of which 7 underwent surgical drainage of the cyst. Univariate analysis of various factors (etiology, imaging findings prior to intervention, fistula characteristics and management) failed to identify any factors that could predict early closure of fistula. EPF is a common sequel

Tomato yellow leaf curl virus infection of a resistant tomato line with a silenced sucrose transporter gene LeHT1 results in inhibition of growth, enhanced virus spread, and necrosis.

PubMed

Eybishtz, Assaf; Peretz, Yuval; Sade, Dagan; Gorovits, Rena; Czosnek, Henryk

2010-02-01

To identify genes involved in resistance of tomato to Tomato yellow leaf curl virus (TYLCV), cDNA libraries from lines resistant (R) and susceptible (S) to the virus were compared. The hexose transporter LeHT1 was found to be expressed preferentially in R tomato plants. The role of LeHT1 in the establishment of TYLCV resistance was studied in R plants where LeHT1 has been silenced using Tobacco rattle virus-induced gene silencing (TRV VIGS). Following TYLCV inoculation, LeHT1-silenced R plants showed inhibition of growth and enhanced virus accumulation and spread. In addition, a necrotic response was observed along the stem and petioles of infected LeHT1-silenced R plants, but not on infected not-silenced R plants. This response was specific of R plants since it was absent in infected LeHT1-silenced S plants. Necrosis had several characteristics of programmed cell death (PCD): DNA from necrotic tissues presented a PCD-characteristic ladder pattern, the amount of a JNK analogue increased, and production of reactive oxygen was identified by DAB staining. A similar necrotic reaction along stem and petioles was observed in LeHT1-silenced R plants infected with the DNA virus Bean dwarf mosaic virus and the RNA viruses Cucumber mosaic virus and Tobacco mosaic virus. These results constitute the first evidence for a necrotic response backing natural resistance to TYLCV in tomato, confirming that plant defense is organized in multiple layers. They demonstrate that the hexose transporter LeHT1 is essential for the expression of natural resistance against TYLCV and its expression correlates with inhibition of virus replication and movement.

Substance P is a determinant of lethality in diet-induced hemorrhagic pancreatitis in mice.

PubMed

Maa, J; Grady, E F; Yoshimi, S K; Drasin, T E; Kim, E H; Hutter, M M; Bunnett, N W; Kirkwood, K S

2000-08-01

The neuropeptide substance P (SP) induces plasma extravasation and neutrophil infiltration by activating the neurokinin 1-receptor (NK1-R). SP-induced neurogenic inflammation is terminated by the cell surface enzyme neutral endopeptidase (NEP), which degrades SP. We determined whether genetic deletion of the NK1-R reduces mortality and, conversely, whether genetic deletion of NEP increases mortality in a lethal model of hemorrhagic pancreatitis. Necrotizing pancreatitis was induced by feeding mice a diet deficient in choline and supplemented with ethionine. We determined the length of survival, the severity of pancreatitis (by measuring the neutrophil enzyme myeloperoxidase [MPO] and by histologic evaluation), and the severity of pancreatitis-associated lung injury (lung MPO and histology) in NK1-R (+/+)/(-/-) and NEP (+/+)/(-/-) mice. Genetic deletion of the NK1-R significantly improved survival (100% vs 8% at 120 hours, P <.001) and reduced pancreatic MPO and acinar cell necrosis. Conversely, genetic deletion of NEP significantly worsened survival (0% vs 90% at 120 hours, P <.001) and exacerbated pancreatic MPO and pancreatitis-associated lung injury. Substance P is an important determinant of lethality in this model of necrotizing pancreatitis. Defects in NEP expression could lead to uncontrolled inflammation.

Infections of nervous necrosis virus in wild and cage-reared marine fish from South China Sea with unexpected wide host ranges.

PubMed

Liu, X D; Huang, J N; Weng, S P; Hu, X Q; Chen, W J; Qin, Z D; Dong, X X; Liu, X L; Zhou, Y; Asim, M; Wang, W M; He, J G; Lin, L

2015-06-01

The concerns about the impact of the nervous necrosis virus (NNV) infections in wild fish have been raised. This paper presents the results of quarterly surveys of NNV in wild and cage-reared marine fish from South China Sea. Samples of 892 wild fish belonging to 69 species and 381 cage-reared fish belonging to 11 species were collected and were detected by seminested PCR and nested PCR. In the case of seminested PCR, the positive signal was detected in 3.0% and 3.1% samples of wild and cage-reared fish, respectively. However, by nested RT-PCR, the positive signal was observed in 42.3% and 63.0% samples of wild and cage-reared fish, respectively. If the fish species were considered, the positive signal was detected in 21.7% and 72.7% species of wild and cage-reared fish by seminested PCR assay, respectively. However, by nested RT-PCR, the positive signal was observed in 65.2% and 100% species of wild and cage-reared fish, respectively. The nucleotide sequences of the nested PCR products were determined. Phylogenetic tree showed that all the obtained viral isolates belonged to the red-spotted grouper nervous necrosis virus (RGNNV) genotype. Thirty-five species of the marine fish were the new hosts of NNV. © 2014 John Wiley & Sons Ltd.

Scolopendra subspinipes mutilans protected the cerulein-induced acute pancreatitis by inhibiting high-mobility group box protein-1.

PubMed

Jo, Il-Joo; Bae, Gi-Sang; Park, Kyoung-Chel; Choi, Sun Bok; Jung, Won-Seok; Jung, Su-Young; Cho, Jung-Hee; Choi, Mee-Ok; Song, Ho-Joon; Park, Sung-Joo

2013-03-14

To evaluate the inhibitory effects of Scolopendra subspinipes mutilans (SSM) on cerulein-induced acute pancreatitis (AP) in a mouse model. SSM water extract (0.1, 0.5, or 1 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein. Once AP developed, the stable cholecystokinin analogue, cerulein was injected hourly, over a 6 h period. Blood samples were taken 6 h later to determine serum amylase, lipase, and cytokine levels. The pancreas and lungs were rapidly removed for morphological examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. To specify the role of SSM in pancreatitis, the pancreatic acinar cells were isolated using collagenase method. Then the cells were pre-treated with SSM, then stimulated with cerulein. The cell viability, cytokine productions and high-mobility group box protein-1 (HMGB-1) were measured. Furthermore, the regulating mechanisms of SSM action were evaluated. The administration of SSM significantly attenuated the severity of pancreatitis and pancreatitis associated lung injury, as was shown by the reduction in pancreatic edema, neutrophil infiltration, vacuolization and necrosis. SSM treatment also reduced pancreatic weight/body weight ratio, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as tumor necrosis factor-α and interleukin-1β. In addition, treatment with SSM inhibited HMGB-1 expression in the pancreas during AP. In accordance with in vivo data, SSM inhibited the cerulein-induced acinar cell death, cytokine, and HMGB-1 release. SSM also inhibited the activation of c-Jun NH2-terminal kinase, p38 and nuclear factor (NF)-κB. These results suggest that SSM plays a protective role during the development of AP and pancreatitis associated lung injury via deactivating c-Jun NH2-terminal kinase, p38 and NF-κB.

Scolopendra subspinipes mutilans protected the cerulein-induced acute pancreatitis by inhibiting high-mobility group box protein-1

PubMed Central

Jo, Il-Joo; Bae, Gi-Sang; Park, Kyoung-Chel; Choi, Sun Bok; Jung, Won-Seok; Jung, Su-Young; Cho, Jung-Hee; Choi, Mee-Ok; Song, Ho-Joon; Park, Sung-Joo

2013-01-01

AIM: To evaluate the inhibitory effects of Scolopendra subspinipes mutilans (SSM) on cerulein-induced acute pancreatitis (AP) in a mouse model. METHODS: SSM water extract (0.1, 0.5, or 1 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein. Once AP developed, the stable cholecystokinin analogue, cerulein was injected hourly, over a 6 h period. Blood samples were taken 6 h later to determine serum amylase, lipase, and cytokine levels. The pancreas and lungs were rapidly removed for morphological examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. To specify the role of SSM in pancreatitis, the pancreatic acinar cells were isolated using collagenase method. Then the cells were pre-treated with SSM, then stimulated with cerulein. The cell viability, cytokine productions and high-mobility group box protein-1 (HMGB-1) were measured. Furthermore, the regulating mechanisms of SSM action were evaluated. RESULTS: The administration of SSM significantly attenuated the severity of pancreatitis and pancreatitis associated lung injury, as was shown by the reduction in pancreatic edema, neutrophil infiltration, vacuolization and necrosis. SSM treatment also reduced pancreatic weight/body weight ratio, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as tumor necrosis factor-α and interleukin-1β. In addition, treatment with SSM inhibited HMGB-1 expression in the pancreas during AP. In accordance with in vivo data, SSM inhibited the cerulein-induced acinar cell death, cytokine, and HMGB-1 release. SSM also inhibited the activation of c-Jun NH2-terminal kinase, p38 and nuclear factor (NF)-κB. CONCLUSION: These results suggest that SSM plays a protective role during the development of AP and pancreatitis associated lung injury via deactivating c-Jun NH2-terminal kinase, p38 and NF-κB. PMID:23539679

Herpes Simplex Encephalitis during Treatment with Tumor Necrosis Factor-α Inhibitors

PubMed Central

Bradford, Russell D.; Pettit, April C.; Wright, Patty W.; Mulligan, Mark J.; Moreland, Larry W.; McLain, David A.; Gnann, John W.; Bloch, Karen C.

2012-01-01

We report 3 cases of herpes simplex virus encephalitis in patients receiving tumor necrosis factor-alpha (TNF-α) inhibitors for rheumatologic disorders. Although TNF-α inhibitors have been reported to increase the risk of other infectious diseases, to our knowledge, an association between anti–TNF-α drugs and herpes simplex virus encephalitis has not been previously described. PMID:19681709

Kinetics of viral load and erythrocytic inclusion body formation in pacific herring artificially infected with erythrocytic necrosis virus

USGS Publications Warehouse

Glenn, Jolene A.; Emmenegger, Eveline J.; Grady, Courtney A.; Roon, Sean R.; Gregg, Jacob L.; Conway, Carla M.; Winton, James R.; Hershberger, Paul K.

2012-01-01

Viral erythrocytic necrosis (VEN) is a condition that affects marine and anadromous fish species, including herrings and salmonids, in the Atlantic and Pacific oceans. Infection is frequently associated with severe anemia and causes episodic mortality among wild and hatchery fish when accompanied by additional stressors; VEN can be presumptively diagnosed by (1) light microscopic identification of a single characteristic—a round, magenta-colored, 0.8-μm-diameter inclusion body (IB) within the cytoplasm of erythrocytes and their precursors on Giemsa-stained blood films; or (2) observation (via transmission electron microscopy [TEM]) of the causative iridovirus, erythrocytic necrosis virus (ENV), within erythrocytes or their precursors. To better understand the kinetics of VEN, specific-pathogen-free Pacific herring Clupea pallasii were infected with ENV by intraperitoneal injection. At 1, 4, 7, 10, 14, 21, and 28 d postexposure, samples of blood, spleen, and kidney were collected and assessed (1) via light microscopy for the number of intracytoplasmic IBs in blood smears and (2) via TEM for the number of virions within erythrocytes. The mean prevalence of intracytoplasmic IBs in the blood cells increased from 0% at 0–4 d postexposure to 94% at 28 d postexposure. Viral load within circulating red blood cells peaked at 7 d postexposure, fell slightly, and then reached a plateau. However, blood cells observed within the kidney and spleen tissues demonstrated high levels of ENV between 14 and 28 d postexposure. The results indicate that the viral load within erythrocytes does not correlate well with IB prevalence and that the virus can persist in infected fish for more than 28 d.

Long-term results after endoscopic drainage and necrosectomy of symptomatic pancreatic fluid collections.

PubMed

Seewald, Stefan; Ang, Tiing Leong; Richter, Hugo; Teng, Karl Yu Kim; Zhong, Yan; Groth, Stefan; Omar, Salem; Soehendra, Nib

2012-01-01

To determine the immediate and long-term results of endoscopic drainage and necrosectomy for symptomatic pancreatic fluid collections. The data of 80 patients with symptomatic pancreatic fluid collections (mean diameter: 11.7 cm, range 3-20; pseudocysts: 24/80, abscess: 20/80, infected walled-off necrosis: 36/80) referred for endoscopic management from October 1997 to March 2008 were analyzed retrospectively. Endoscopic drainage techniques included endoscopic ultrasound (EUS)-guided aspiration (2/80), EUS-guided transenteric drainage (70/80) and non-EUS-guided drainage across a spontaneous transenteric fistula (8/80). Endoscopic necrosectomy was carried out in 49/80 (abscesses: 14/20; infected necrosis: 35/36). Procedural complications were bleeding (12/80), perforation (7/80), portal air embolism (1/80) and Ogilvie Syndrome (1/80). Initial technical success was achieved in 78/80 (97.5%) and clinical resolution of the collections was achieved endoscopically in 67/80 (83.8%), with surgery required in 13/80 (perforation: four; endoscopically inaccessible areas: two; inadequate drainage: seven). Within 6 months five patients required surgery due to recurrent fluid collections; over a mean follow up of 31 months, surgery was required in four more patients due to recurrent collections as a consequence of underlying pancreatic duct abnormalities that could not be treated endoscopically. The long-term success of endoscopic treatment was 58/80 (72.5%). Endoscopic drainage of symptomatic pancreatic fluid collections is safe and effective, with excellent immediate and long-term results. Endoscopic necrosectomy has a risk of serious complications. The underlying pancreatic duct abnormalities must be addressed to prevent recurrence of fluid collections. © 2011 The Authors. Digestive Endoscopy © 2011 Japan Gastroenterological Endoscopy Society.

Low impact of infectious hypodermal and hematopoietic necrosis virus (IHHNV) on growth and reproductive performance of Penaeus monodon.

PubMed

Withyachumnarnkul, Boonsirm; Chayaburakul, Kanokporn; Lao-Aroon, Supak; Plodpai, Pornthep; Sritunyalucksana, Kallaya; Nash, Gary

2006-04-06

No controlled studies on the effect of infectous hypodermal and necrosis virus (IHHNV) on Penaeus monodon have been previously reported. Here we describe domesticated P. monodon that became positive for IHHNV and other viruses at variable levels of prevalence during cultivation in 16 open-air, earthen ponds. These were stocked with domesticated postlarvae (PL) that tested negative for 7 shrimp viruses including IHHNV at 6% prevalence in 3 checks using polymerase chain reaction (PCR) methods. These PL were derived from domesticated female broodstock that individually tested negative for the same viruses. At 4 mo of culture, the shrimp in some ponds without obvious mortality tested positive by PCR methods for IHHNV and 3 other viruses at variable levels of maximum estimated prevalence (MEP). Stained tissue sections showed no lesions typical of IHHNV, but in situ hybridization tests with an IHHNV-specific DNA probe were positive. There was no significant difference in mean body weight (i.e. ca. 25 g) between shrimp groups positive or negative for IHHNV. Similar results were obtained with IHHNV negative and positive adults at 1 yr. Adults that individually tested negative for all 7 viruses and some that tested lightly positive for IHHNV were bred for the next generation. There were no significant differences in the number of eggs (> 600 000) and nauplii (ca. 300,000) produced by females negative and positive for IHHNV. From these females, 11/49 (22%) IHHNV PCR-positive PL batches were obtained from PCR-negative spawners, while 8/11 (73%) were obtained from IHHNV PCR-positive spawners. The results suggested that IHHNV infection can be transmitted vertically but does not seriously retard growth of P. monodon or affect fecundity of lightly infected broodstock.

Bilateral central retinal artery occlusion associated with herpes simplex virus-associated acute retinal necrosis and meningitis: case report and literature review.

PubMed

Weissman, Heather M; Biousse, Valerie; Schechter, Marcos Coutinho; Del Rio, Carlos; Yeh, Steven

2015-02-01

A 60-year-old woman with a history of recurrent headaches and blurred vision presented with bilateral optic disc edema. Optic neuritis was suspected, and intravenous methylprednisonlone was administered. Her vision declined to hand motions in both eyes, and subsequent evaluation revealed bilateral acute retinal necrosis with bilateral central retinal artery occlusions (CRAO). Aqueous humor polymerase chain reaction analysis was positive for herpes simplex virus (HSV), establishing a diagnosis of HSV-associated bilateral acute retinal necrosis (ARN) and meningitis. CRAO has rarely been reported in association with ARN, and a fulminant course with bilateral CRAO in association with ARN has not been previously reported. This case emphasizes the importance of careful peripheral examination in patients with presumptive optic neuritis, judicious use of systemic corticosteroid in this context, and the retinal vaso-obliterative findings that may be observed in the pathogenesis of ARN. Copyright 2015, SLACK Incorporated.

Reduction of Decoy Receptor 3 Enhances TRAIL-Mediated Apoptosis in Pancreatic Cancer

PubMed Central

Wang, Wei; Yang, Shanmin; Su, Ying; Zhang, Hengshan; Liu, Chaomei; Li, Xinfeng; Lin, Ling; Kim, Sunghee; Okunieff, Paul; Zhang, Zhenhuan; Zhang, Lurong

2013-01-01

Most human pancreatic cancer cells are resistant to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. However, the mechanisms by which pancreatic cancer cells utilize their extracellular molecules to counteract the proapoptotic signaling mediated by the TNF family are largely unknown. In this study, we demonstrate for the first time that DcR3, a secreted decoy receptor that malignant pancreatic cancer cells express at a high level, acts as an extracellular antiapoptotic molecule by binding to TRAIL and counteracting its death-promoting function. The reduction of DcR3 with siRNA unmasked TRAIL and greatly enhanced TRAIL-induced apoptosis. Gemcitabine, a first-line drug for pancreatic cancer, also reduced the level of DcR3. The addition of DcR3 siRNA further enhanced gemcitabine-induced apoptosis. Notably, our in vivo study demonstrated that the therapeutic effect of gemcitabine could be enhanced via further reduction of DcR3, suggesting that downregulation of DcR3 in tumor cells could tip the balance of pancreatic cells towards apoptosis and potentially serve as a new strategy for pancreatic cancer therapy. PMID:24204567

Reduction of decoy receptor 3 enhances TRAIL-mediated apoptosis in pancreatic cancer.

PubMed

Wang, Wei; Zhang, Mei; Sun, Weimin; Yang, Shanmin; Su, Ying; Zhang, Hengshan; Liu, Chaomei; Li, Xinfeng; Lin, Ling; Kim, Sunghee; Okunieff, Paul; Zhang, Zhenhuan; Zhang, Lurong

2013-01-01

Most human pancreatic cancer cells are resistant to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. However, the mechanisms by which pancreatic cancer cells utilize their extracellular molecules to counteract the proapoptotic signaling mediated by the TNF family are largely unknown. In this study, we demonstrate for the first time that DcR3, a secreted decoy receptor that malignant pancreatic cancer cells express at a high level, acts as an extracellular antiapoptotic molecule by binding to TRAIL and counteracting its death-promoting function. The reduction of DcR3 with siRNA unmasked TRAIL and greatly enhanced TRAIL-induced apoptosis. Gemcitabine, a first-line drug for pancreatic cancer, also reduced the level of DcR3. The addition of DcR3 siRNA further enhanced gemcitabine-induced apoptosis. Notably, our in vivo study demonstrated that the therapeutic effect of gemcitabine could be enhanced via further reduction of DcR3, suggesting that downregulation of DcR3 in tumor cells could tip the balance of pancreatic cells towards apoptosis and potentially serve as a new strategy for pancreatic cancer therapy.

Pancreatic tuberculosis with acquired immunodeficiency syndrome: a case report and systematic review.

PubMed

Meesiri, Somchai

2012-02-21

Pancreatic tuberculosis (TB) is a relatively rare disease that can mimic carcinoma, lymphoma, cystic neoplasia, retroperitoneal tumors, pancreatitis or pseudocysts. Here, I report the case of a 31-year-old immigrant Burmese woman who exhibited epigastralgia, fever, weight loss and an epigastric mass. The patient was diagnosed with pancreatic TB and acquired immunodeficiency syndrome, and was treated with antituberculous drugs and percutaneous catheter drainage without a laparotomy. The clinical presentation, radiographic investigation and management of pancreatic TB are summarized in this paper to emphasize the importance of considering this rare disease in the differential diagnosis of pancreatic masses concomitant with human immunodeficiency virus infection. I also emphasize the need for both histopathological and microbiological diagnosis via fine-needle aspiration.

CLINICAL AND THERAPEUTIC CORRELATIONS IN PATIENTS WITH SLIGHT ACUTE PANCREATITIS

PubMed Central

MUNHOZ-FILHO, Clewis Henri; BATIGÁLIA, Fernando; FUNES, Hamilton Luiz Xavier

2015-01-01

Background Acute pancreatitis is an inflammatory disease of the pancreas due to enzymatic autodigestion which can cause necrosis or multiple organ failure; its pathophysiology is not fully known yet. Aim To evaluate the correlation between clinical and therapeutic data in patients with mild acute pancreatitis. Methods A retrospective study in 55 medical records of patients admitted with acute mild pancreatitis was realized to analyze the association between age, leukocytosis, serum glutamic-oxaloacetic transaminase and lactate dehydrogenase, glucose, antibiotics, time admission and Ranson´s scores. Results There was a positive association between less intensive care (strict hydration, analgesia and monitoring of vital signs), early antibiotic therapy (monotherapy), early return to diet after 48 hours and laboratory control of the serum amylase and lipase (high in the first week and decreasing after 10 days, without any prognostic value). Conclusions Changes in the management of patients with mild acute pancreatitis, such as enteral nutrition, rational use of lower spectrum antibiotics and intensive care, have contributed significantly to the reduction of hospitalization time and mortality. PMID:25861064

Ablation of Phosphoinositide 3-Kinase-γ Reduces the Severity of Acute Pancreatitis

PubMed Central

Lupia, Enrico; Goffi, Alberto; De Giuli, Paolo; Azzolino, Ornella; Bosco, Ornella; Patrucco, Enrico; Vivaldo, Maria Cristina; Ricca, Marco; Wymann, Matthias P.; Hirsch, Emilio; Montrucchio, Giuseppe; Emanuelli, Giorgio

2004-01-01

In pancreatic acini, the G-protein-activated phosphoinositide 3-kinase-γ (PI3Kγ) regulates several key pathological responses to cholecystokinin hyperstimulation in vitro. Thus, using mice lacking PI3Kγ, we studied the function of this enzyme in vivo in two different models of acute pancreatitis. The disease was induced by supramaximal concentrations of cerulein and by feeding mice a choline-deficient/ethionine-supplemented diet. Although the secretive function of isolated pancreatic acini was identical in mutant and control samples, in both models, genetic ablation of PI3Kγ significantly reduced the extent of acinar cell injury/necrosis. In agreement with a protective role of apoptosis in pancreatitis, PI3Kγ-deficient pancreata showed an increased number of apoptotic acinar cells, as determined by terminal dUTP nick-end labeling and caspase-3 activity. In addition, neutrophil infiltration within the pancreatic tissue was also reduced, suggesting a dual action of PI3Kγ, both in the triggering events within acinar cells and in the subsequent neutrophil recruitment and activation. Finally, the lethality of the choline-deficient/ethionine-supplemented diet-induced pancreatitis was significantly reduced in mice lacking PI3Kγ. Our results thus suggest that inhibition of PI3Kγ may be of therapeutic value in acute pancreatitis. PMID:15579443

Soluble CD163 is increased in patients with acute pancreatitis independent of disease severity.

PubMed

Karrasch, Thomas; Brünnler, Tanja; Hamer, Okka W; Schmid, Karin; Voelk, Markus; Herfarth, Hans; Buechler, Christa

2015-10-01

Macrophages are crucially involved in the pathophysiology of acute pancreatitis. Soluble CD163 (sCD163) is specifically released from macrophages and systemic levels are increased in inflammatory diseases. Here, sCD163 was measured in serum of 50 patients with acute pancreatitis to find out possible associations with disease activity. Admission levels of systemic sCD163 were nearly three-fold higher in patients with acute pancreatitis compared to controls. In patients sCD163 did not correlate with C-reactive protein and leukocyte count as established markers of inflammation. Levels were not associated with disease severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age, and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis score. Soluble CD163 was not related to complications of acute pancreatitis. These data show that serum sCD163 is increased in acute pancreatitis indicating activation of macrophages but is not associated with disease severity and outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Treatment of severe acute pancreatitis and its complications

PubMed Central

Zerem, Enver

2014-01-01

Severe acute pancreatitis (SAP), which is the most serious type of this disorder, is associated with high morbidity and mortality. SAP runs a biphasic course. During the first 1-2 wk, a pro-inflammatory response results in systemic inflammatory response syndrome (SIRS). If the SIRS is severe, it can lead to early multisystem organ failure (MOF). After the first 1-2 wk, a transition from a pro-inflammatory response to an anti-inflammatory response occurs; during this transition, the patient is at risk for intestinal flora translocation and the development of secondary infection of the necrotic tissue, which can result in sepsis and late MOF. Many recommendations have been made regarding SAP management and its complications. However, despite the reduction in overall mortality in the last decade, SAP is still associated with high mortality. In the majority of cases, sterile necrosis should be managed conservatively, whereas in infected necrotizing pancreatitis, the infected non-vital solid tissue should be removed to control the sepsis. Intervention should be delayed for as long as possible to allow better demarcation and liquefaction of the necrosis. Currently, the step-up approach (delay, drain, and debride) may be considered as the reference standard intervention for this disorder. PMID:25320523

Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis.

PubMed

Pendharkar, Sayali A; Drury, Marie; Walia, Monika; Korc, Murray; Petrov, Maxim S

2017-08-01

Gastrin-releasing peptide (GRP) is a pluripotent peptide that has been implicated in both gastrointestinal inflammatory states and classical chronic metabolic diseases such as diabetes. Abnormal glucose metabolism (AGM) after pancreatitis, an exemplar inflammatory disease involving the gastrointestinal tract, is associated with persistent low-grade inflammation and altered secretion of pancreatic and gut hormones as well as cytokines. While GRP is involved in secretion of many of them, it is not known whether GRP has a role in AGM. Therefore, we aimed to investigate the association between GRP and AGM following pancreatitis. Fasting blood samples were collected to measure GRP, blood glucose, insulin, amylin, glucagon, pancreatic polypeptide (PP), somatostatin, cholecystokinin, gastric-inhibitory peptide (GIP), gastrin, ghrelin, glicentin, glucagon-like peptide-1 and 2, oxyntomodulin, peptide YY (PYY), secretin, vasoactive intestinal peptide, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP)-1, and interleukin-6. Modified Poisson regression analysis and linear regression analyses were conducted. Four statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. A total of 83 individuals after an episode of pancreatitis were recruited. GRP was significantly associated with AGM, consistently in all four models (P -trend < 0.05), and fasting blood glucose contributed 17% to the variance of GRP. Further, GRP was significantly associated with glucagon (P < 0.003), MCP-1 (P < 0.025), and TNF-α (P < 0.025) - consistently in all four models. GRP was also significantly associated with PP and PYY in three models (P < 0.030 for both), and with GIP and glicentin in one model (P = 0.001 and 0.024, respectively). Associations between GRP and other pancreatic and gut hormones were not significant. GRP is significantly increased in patients with AGM after pancreatitis and is associated with increased levels of pro

Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis

PubMed Central

Pendharkar, Sayali A.; Drury, Marie; Walia, Monika; Korc, Murray; Petrov, Maxim S.

2017-01-01

Background Gastrin-releasing peptide (GRP) is a pluripotent peptide that has been implicated in both gastrointestinal inflammatory states and classical chronic metabolic diseases such as diabetes. Abnormal glucose metabolism (AGM) after pancreatitis, an exemplar inflammatory disease involving the gastrointestinal tract, is associated with persistent low-grade inflammation and altered secretion of pancreatic and gut hormones as well as cytokines. While GRP is involved in secretion of many of them, it is not known whether GRP has a role in AGM. Therefore, we aimed to investigate the association between GRP and AGM following pancreatitis. Methods Fasting blood samples were collected to measure GRP, blood glucose, insulin, amylin, glucagon, pancreatic polypeptide (PP), somatostatin, cholecystokinin, gastric-inhibitory peptide (GIP), gastrin, ghrelin, glicentin, glucagon-like peptide-1 and 2, oxyntomodulin, peptide YY (PYY), secretin, vasoactive intestinal peptide, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP)-1, and interleukin-6. Modified Poisson regression analysis and linear regression analyses were conducted. Four statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. Results A total of 83 individuals after an episode of pancreatitis were recruited. GRP was significantly associated with AGM, consistently in all four models (P -trend < 0.05), and fasting blood glucose contributed 17% to the variance of GRP. Further, GRP was significantly associated with glucagon (P < 0.003), MCP-1 (P < 0.025), and TNF-α (P < 0.025) - consistently in all four models. GRP was also significantly associated with PP and PYY in three models (P < 0.030 for both), and with GIP and glicentin in one model (P = 0.001 and 0.024, respectively). Associations between GRP and other pancreatic and gut hormones were not significant. Conclusion GRP is significantly increased in patients with AGM after pancreatitis and is

Cathepsin B Activity Initiates Apoptosis via Digestive Protease Activation in Pancreatic Acinar Cells and Experimental Pancreatitis*

PubMed Central

Sendler, Matthias; Maertin, Sandrina; John, Daniel; Persike, Maria; Weiss, F. Ulrich; Krüger, Burkhard; Wartmann, Thomas; Wagh, Preshit; Halangk, Walter; Schaschke, Norbert; Mayerle, Julia; Lerch, Markus M.

2016-01-01

Pancreatitis is associated with premature activation of digestive proteases in the pancreas. The lysosomal hydrolase cathepsin B (CTSB) is a known activator of trypsinogen, and its deletion reduces disease severity in experimental pancreatitis. Here we studied the activation mechanism and subcellular compartment in which CTSB regulates protease activation and cellular injury. Cholecystokinin (CCK) increased the activity of CTSB, cathepsin L, trypsin, chymotrypsin, and caspase 3 in vivo and in vitro and induced redistribution of CTSB to a secretory vesicle-enriched fraction. Neither CTSB protein nor activity redistributed to the cytosol, where the CTSB inhibitors cystatin-B/C were abundantly present. Deletion of CTSB reduced and deletion of cathepsin L increased intracellular trypsin activation. CTSB deletion also abolished CCK-induced caspase 3 activation, apoptosis-inducing factor, as well as X-linked inhibitor of apoptosis protein degradation, but these depended on trypsinogen activation via CTSB. Raising the vesicular pH, but not trypsin inhibition, reduced CTSB activity. Trypsin inhibition did not affect apoptosis in hepatocytes. Deletion of CTSB affected apoptotic but not necrotic acinar cell death. In summary, CTSB in pancreatitis undergoes activation in a secretory, vesicular, and acidic compartment where it activates trypsinogen. Its deletion or inhibition regulates acinar cell apoptosis but not necrosis in two models of pancreatitis. Caspase 3-mediated apoptosis depends on intravesicular trypsinogen activation induced by CTSB, not CTSB activity directly, and this mechanism is pancreas-specific. PMID:27226576

Cathepsin B Activity Initiates Apoptosis via Digestive Protease Activation in Pancreatic Acinar Cells and Experimental Pancreatitis.

PubMed

Sendler, Matthias; Maertin, Sandrina; John, Daniel; Persike, Maria; Weiss, F Ulrich; Krüger, Burkhard; Wartmann, Thomas; Wagh, Preshit; Halangk, Walter; Schaschke, Norbert; Mayerle, Julia; Lerch, Markus M

2016-07-08

Pancreatitis is associated with premature activation of digestive proteases in the pancreas. The lysosomal hydrolase cathepsin B (CTSB) is a known activator of trypsinogen, and its deletion reduces disease severity in experimental pancreatitis. Here we studied the activation mechanism and subcellular compartment in which CTSB regulates protease activation and cellular injury. Cholecystokinin (CCK) increased the activity of CTSB, cathepsin L, trypsin, chymotrypsin, and caspase 3 in vivo and in vitro and induced redistribution of CTSB to a secretory vesicle-enriched fraction. Neither CTSB protein nor activity redistributed to the cytosol, where the CTSB inhibitors cystatin-B/C were abundantly present. Deletion of CTSB reduced and deletion of cathepsin L increased intracellular trypsin activation. CTSB deletion also abolished CCK-induced caspase 3 activation, apoptosis-inducing factor, as well as X-linked inhibitor of apoptosis protein degradation, but these depended on trypsinogen activation via CTSB. Raising the vesicular pH, but not trypsin inhibition, reduced CTSB activity. Trypsin inhibition did not affect apoptosis in hepatocytes. Deletion of CTSB affected apoptotic but not necrotic acinar cell death. In summary, CTSB in pancreatitis undergoes activation in a secretory, vesicular, and acidic compartment where it activates trypsinogen. Its deletion or inhibition regulates acinar cell apoptosis but not necrosis in two models of pancreatitis. Caspase 3-mediated apoptosis depends on intravesicular trypsinogen activation induced by CTSB, not CTSB activity directly, and this mechanism is pancreas-specific. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Management of pancreatic fluid collections: A comprehensive review of the literature

PubMed Central

Tyberg, Amy; Karia, Kunal; Gabr, Moamen; Desai, Amit; Doshi, Rushabh; Gaidhane, Monica; Sharaiha, Reem Z; Kahaleh, Michel

2016-01-01

Pancreatic fluid collections (PFCs) are a frequent complication of pancreatitis. It is important to classify PFCs to guide management. The revised Atlanta criteria classifies PFCs as acute or chronic, with chronic fluid collections subdivided into pseudocysts and walled-off pancreatic necrosis (WOPN). Establishing adequate nutritional support is an essential step in the management of PFCs. Early attempts at oral feeding can be trialed in patients with mild pancreatitis. Enteral feeding should be implemented in patients with moderate to severe pancreatitis. Jejunal feeding remains the preferred route of enteral nutrition. Symptomatic PFCs require drainage; options include surgical, percutaneous, or endoscopic approaches. With the advent of newer and more advanced endoscopic tools and expertise, and an associated reduction in health care costs, minimally invasive endoscopic drainage has become the preferable approach. An endoscopic ultrasonography-guided approach using a seldinger technique is the preferred endoscopic approach. Both plastic stents and metal stents are efficacious and safe; however, metal stents may offer an advantage, especially in infected pseudocysts and in WOPN. Direct endoscopic necrosectomy is often required in WOPN. Lumen apposing metal stents that allow for direct endoscopic necrosectomy and debridement through the stent lumen are preferred in these patients. Endoscopic retrograde cholangio pancreatography with pancreatic duct (PD) exploration should be performed concurrent to PFC drainage. PD disruption is associated with an increased severity of pancreatitis, an increased risk of recurrent attacks of pancreatitis and long-term complications, and a decreased rate of PFC resolution after drainage. Any pancreatic ductal disruption should be bridged with endoscopic stenting. PMID:26900288

Viral-induced systemic necrosis in plants involves both programmed cell death and the inhibition of viral multiplication, which are regulated by independent pathways.

PubMed

Komatsu, Ken; Hashimoto, Masayoshi; Ozeki, Johji; Yamaji, Yasuyuki; Maejima, Kensaku; Senshu, Hiroko; Himeno, Misako; Okano, Yukari; Kagiwada, Satoshi; Namba, Shigetou

2010-03-01

Resistant plants respond rapidly to invading avirulent plant viruses by triggering a hypersensitive response (HR). An HR is accompanied by a restraint of virus multiplication and programmed cell death (PCD), both of which have been observed in systemic necrosis triggered by a successful viral infection. Here, we analyzed signaling pathways underlying the HR in resistance genotype plants and those leading to systemic necrosis. We show that systemic necrosis in Nicotiana benthamiana, induced by Plantago asiatica mosaic virus (PlAMV) infection, was associated with PCD, biochemical features, and gene expression patterns that are characteristic of HR. The induction of necrosis caused by PlAMV infection was dependent on SGT1, RAR1, and the downstream mitogen-activated protein kinase (MAPK) cascade involving MAPKKKalpha and MEK2. However, although SGT1 and RAR1 silencing led to an increased accumulation of PlAMV, silencing of the MAPKKKalpha-MEK2 cascade did not. This observation indicates that viral multiplication is partly restrained even in systemic necrosis induced by viral infection, and that this restraint requires SGT1 and RAR1 but not the MAPKKKalpha-MEK2 cascade. Similarly, although both SGT1 and MAPKKKalpha were essential for the Rx-mediated HR to Potato virus X (PVX), SGT1 but not MAPKKKalpha was involved in the restraint of PVX multiplication. These results suggest that systemic necrosis and HR consist of PCD and a restraint of virus multiplication, and that the latter is induced through unknown pathways independent from the former.

A prospective study of the Bedside Index for Severity in Acute Pancreatitis (BISAP) score in acute pancreatitis: an Indian perspective.

PubMed

Senapati, Debadutta; Debata, Prasanna Kumar; Jenasamant, Saumya Sekhar; Nayak, Anil Kumar; Gowda S, Manoj; Swain, Narendra Nath

2014-01-01

A simple and easily applicable system for stratifying patients with acute pancreatitis is lacking. The aim of our study was to evaluate the ability of BISAP score to predict mortality in acute pancreatitis patients from our institution and to predict which patients are at risk for development of organ failure, persistent organ failure and pancreatic necrosis. All patients with acute pancreatitis were included in the study. BISAP score was calculated within 24 h of admission. A Contrast CT was used to differentiate interstitial from necrotizing pancreatitis within seven days of hospitalization whereas Marshall Scoring System was used to characterize organ failure. Among 246 patients M:F = 153:93, most common aetiology among men was alcoholism and among women was gallstone disease. 207 patients had no organ failure and remaining 39 developed organ failure. 17 patients had persistent organ failure, 16 of those with BISAP score ≥3. 13 patients in our study died, out of which 12 patients had BISAP score ≥3. We also found that a BISAP score of ≥3 had a sensitivity of 92%, specificity of 76%, a positive predictive value of 17%, and a negative predictive value of 99% for mortality. The BISAP score is a simple and accurate method for the early identification of patients at increased risk for in hospital mortality and morbidity. Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Pancreatic tuberculosis with acquired immunodeficiency syndrome: A case report and systematic review

PubMed Central

Meesiri, Somchai

2012-01-01

Pancreatic tuberculosis (TB) is a relatively rare disease that can mimic carcinoma, lymphoma, cystic neoplasia, retroperitoneal tumors, pancreatitis or pseudocysts. Here, I report the case of a 31-year-old immigrant Burmese woman who exhibited epigastralgia, fever, weight loss and an epigastric mass. The patient was diagnosed with pancreatic TB and acquired immunodeficiency syndrome, and was treated with antituberculous drugs and percutaneous catheter drainage without a laparotomy. The clinical presentation, radiographic investigation and management of pancreatic TB are summarized in this paper to emphasize the importance of considering this rare disease in the differential diagnosis of pancreatic masses concomitant with human immunodeficiency virus infection. I also emphasize the need for both histopathological and microbiological diagnosis via fine-needle aspiration. PMID:22363146

Safety and Efficacy of AAV Retrograde Pancreatic Ductal Gene Delivery in Normal and Pancreatic Cancer Mice.

PubMed

Quirin, Kayla A; Kwon, Jason J; Alioufi, Arafat; Factora, Tricia; Temm, Constance J; Jacobsen, Max; Sandusky, George E; Shontz, Kim; Chicoine, Louis G; Clark, K Reed; Mendell, Joshua T; Korc, Murray; Kota, Janaiah

2018-03-16

Recombinant adeno-associated virus (rAAV)-mediated gene delivery shows promise to transduce the pancreas, but safety/efficacy in a neoplastic context is not well established. To identify an ideal AAV serotype, route, and vector dose and assess safety, we have investigated the use of three AAV serotypes (6, 8, and 9) expressing GFP in a self-complementary (sc) AAV vector under an EF1α promoter (scAAV.GFP) following systemic or retrograde pancreatic intraductal delivery. Systemic delivery of scAAV9.GFP transduced the pancreas with high efficiency, but gene expression did not exceed >45% with the highest dose, 5 × 10 12 viral genomes (vg). Intraductal delivery of 1 × 10 11 vg scAAV6.GFP transduced acini, ductal cells, and islet cells with >50%, ∼48%, and >80% efficiency, respectively, and >80% pancreatic transduction was achieved with 5 × 10 11 vg. In a Kras G12D -driven pancreatic cancer mouse model, intraductal delivery of scAAV6.GFP targeted acini, epithelial, and stromal cells and exhibited persistent gene expression 5 months post-delivery. In normal mice, intraductal delivery induced a transient increase in serum amylase/lipase that resolved within a day of infusion with no sustained pancreatic inflammation or fibrosis. Similarly, in PDAC mice, intraductal delivery did not increase pancreatic intraepithelial neoplasia progression/fibrosis. Our study demonstrates that scAAV6 targets the pancreas/neoplasm efficiently and safely via retrograde pancreatic intraductal delivery.

Acute Lipotoxicity Regulates Severity of Biliary Acute Pancreatitis without Affecting Its Initiation

PubMed Central

Durgampudi, Chandra; Noel, Pawan; Patel, Krutika; Cline, Rachel; Trivedi, Ram N.; DeLany, James P.; Yadav, Dhiraj; Papachristou, Georgios I.; Lee, Kenneth; Acharya, Chathur; Jaligama, Deepthi; Navina, Sarah; Murad, Faris; Singh, Vijay P.

2015-01-01

Obese patients have worse outcomes during acute pancreatitis (AP). Previous animal models of AP have found worse outcomes in obese rodents who may have a baseline proinflammatory state. Our aim was to study the role of acute lipolytic generation of fatty acids on local severity and systemic complications of AP. Human postpancreatitis necrotic collections were analyzed for unsaturated fatty acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to replicate the human variables by intraductal injection of the triglyceride glyceryl trilinoleate alone or with the chemically distinct lipase inhibitors orlistat or cetilistat. Parameters of AP etiology and outcomes of local and systemic severity were measured. Patients with postpancreatitis necrotic collections were obese, and 13 of 15 had biliary AP. Postpancreatitis necrotic collections were enriched in UFAs. Intraductal glyceryl trilinoleate with or without the lipase inhibitors resulted in oil red O–positive areas, resembling intrapancreatic fat. Both lipase inhibitors reduced the glyceryl trilinoleate–induced increase in serum lipase, UFAs, pancreatic necrosis, serum inflammatory markers, systemic injury, and mortality but not serum alanine aminotransferase, bilirubin, or amylase. We conclude that UFAs are enriched in human necrotic collections and acute UFA generation via lipolysis worsens pancreatic necrosis, systemic inflammation, and injury associated with severe AP. Inhibition of lipolysis reduces UFA generation and improves these outcomes of AP without interfering with its induction. PMID:24854864

[Inflammatory pancreatic disease due to enzyme autodigestion: an exceptional model of glandular crinophagy].

PubMed

Sánchez-Fayos Calabuig, P; Martín Relloso, M Jesús; González Guirado, Agustina; Porres Cubero, Juan Carlos

2007-01-01

The exocrine pancreas is a functionally dangerous structure since it is exposed to digestion by its most aggressive enzymes (proteases, etc) despite self-protective measures such as the synthesis of some of these enzymes in the form of inactive zymogens (trypsinogen, etc.). We review inflammatory pancreatic disease by separately analyzing its classical forms of onset: acute and chronic pancreatitis (AP and CP). There is general consensus that the initial pathogenic event in AP is intraacinar activation of trypsinogen into trypsin, followed by that of the remaining proenzymes, giving rise to an unusual model of autophagic inflammation. In contrast, consensus is lacking on the initial pathogenic event in CP (toxic-metabolic lesion, oxidative stress, ductal hypertension, etc.?), although in some cases a <necrosis-fibrosis> sequence due to recurrent episodes of AP seems evident. The pathogenic features shared by both forms of the disease and which justify some recent attempts to formulate an overall explanation of the pathogenesis of pancreatitis are discussed. Such an explanation would place both forms of pancreatitis within the conceptual framework of an pancreatic disease due to enzyme autodigestion>.

Early Assessment of Pancreatic Infections and Overall Prognosis in Severe Acute Pancreatitis by Procalcitonin (PCT)

PubMed Central

Rau, Bettina M.; Kemppainen, Esko A.; Gumbs, Andrew A.; Büchler, Markus W.; Wegscheider, Karl; Bassi, Claudio; Puolakkainen, Pauli A.; Beger, Hans G.

2007-01-01

Background: Pancreatic infections and sepsis are major complications in severe acute pancreatitis (AP) with significant impact on management and outcome. We investigated the value of Procalcitonin (PCT) for identifying patients at risk to develop pancreatic infections in severe AP. Methods: A total of 104 patients with predicted severe AP were enrolled in five European academic surgical centers within 96 hours of symptom onset. PCT was measured prospectively by a semi-automated immunoassay in each center, C-reactive protein (CRP) was routinely assessed. Both parameters were monitored over a maximum of 21 consecutive days and in weekly intervals thereafter. Results: In contrast to CRP, PCT concentrations were significantly elevated in patients with pancreatic infections and associated multiorgan dysfunction syndrome (MODS) who all required surgery (n = 10) and in nonsurvivors (n = 8) early after onset of symptoms. PCT levels revealed only a moderate increase in patients with pancreatic infections in the absence of MODS (n = 7), all of whom were managed nonoperatively without mortality. A PCT value of ≥3.5 ng/mL on 2 consecutive days was superior to CRP ≥430 mg/L for the assessment of infected necrosis with MODS or nonsurvival as determined by ROC analysis with a sensitivity and specificity of 93% and 88% for PCT and 40% and 100% for CRP, respectively (P < 0.01). The single or combined prediction of the two major complications was already possible on the third and fourth day after onset of symptoms with a sensitivity and specificity of 79% and 93% for PCT ≥3.8 ng/mL compared with 36% and 97% for CRP ≥430 mg/L, respectively (P = 0.002). Conclusion: Monitoring of PCT allows early and reliable assessment of clinically relevant pancreatic infections and overall prognosis in AP. This single test parameter significantly contributes to an improved stratification of patients at risk to develop major complications. PMID:17457167

Flavocoxid, a dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, reduces pancreatic damage in an experimental model of acute pancreatitis

PubMed Central

Polito, F; Bitto, A; Irrera, N; Squadrito, F; Fazzari, C; Minutoli, L; Altavilla, D

2010-01-01

BACKGROUND AND PURPOSE Acute pancreatitis is an autodigestive process resulting in acute inflammation of the pancreas. Accumulating evidence indicates the essential contribution of cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LOX) to acute pancreatitis. We studied the effects of flavocoxid, a plant-derived dual inhibitor of COX-2 and 5-LOX, in a model of caerulein (CER)-induced acute pancreatitis. EXPERIMENTAL APPROACH Rats were given CER (80 µg·kg−1 for each of four injections at hourly intervals) or vehicle (Sham-CER). Animals were then randomized to receive flavocoxid (20 mg·kg−1 i.p.) or vehicle, 30 min after the first CER injection. Two hours after the last CER injection, we evaluated damage to the pancreas by histological methods; serum levels of amylase, lipase, leukotriene (LT)B4 and prostaglandin (PG)E2; pancreatic expression of COX-2 and 5-LOX and tumour necrosis factor-α (TNF-α) gene expression by real-time polymerase chain reaction. KEY RESULTS Caerulein induced inflammatory changes in the pancreas and raised values of the other variables measured. In CER-treated animals, but not in those given saline, flavocoxid inhibited COX-2 and 5-LOX expression, reduced serum levels of lipase and amylase and the degree of pancreatic oedema. Treatment with flavocoxid blunted the increased pancreatic TNF-α mRNA expression, serum leukotriene B4 and prostaglandin E2 levels, and protected against histological damage in terms of vacuolization and leukocyte infiltration. CONCLUSIONS AND IMPLICATIONS Our results confirm the key role of both COX-2 and 5-LOX in the inflammatory response to acute pancreatitis. Flavocoxid may provide a potential therapeutic approach to the treatment of patients at high risk of developing this life-threatening condition. PMID:20977452

Flavocoxid, a dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, reduces pancreatic damage in an experimental model of acute pancreatitis.

PubMed

Polito, F; Bitto, A; Irrera, N; Squadrito, F; Fazzari, C; Minutoli, L; Altavilla, D

2010-11-01

Acute pancreatitis is an autodigestive process resulting in acute inflammation of the pancreas. Accumulating evidence indicates the essential contribution of cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LOX) to acute pancreatitis. We studied the effects of flavocoxid, a plant-derived dual inhibitor of COX-2 and 5-LOX, in a model of caerulein (CER)-induced acute pancreatitis. Rats were given CER (80 µg·kg⁻¹ for each of four injections at hourly intervals) or vehicle (Sham-CER). Animals were then randomized to receive flavocoxid (20 mg·kg⁻¹ i.p.) or vehicle, 30 min after the first CER injection. Two hours after the last CER injection, we evaluated damage to the pancreas by histological methods; serum levels of amylase, lipase, leukotriene (LT)B₄ and prostaglandin (PG)E₂ ; pancreatic expression of COX-2 and 5-LOX and tumour necrosis factor-α (TNF-α) gene expression by real-time polymerase chain reaction. Caerulein induced inflammatory changes in the pancreas and raised values of the other variables measured. In CER-treated animals, but not in those given saline, flavocoxid inhibited COX-2 and 5-LOX expression, reduced serum levels of lipase and amylase and the degree of pancreatic oedema. Treatment with flavocoxid blunted the increased pancreatic TNF-α mRNA expression, serum leukotriene B₄ and prostaglandin E₂ levels, and protected against histological damage in terms of vacuolization and leukocyte infiltration. Our results confirm the key role of both COX-2 and 5-LOX in the inflammatory response to acute pancreatitis. Flavocoxid may provide a potential therapeutic approach to the treatment of patients at high risk of developing this life-threatening condition. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.

Pancreatitis associated with the helminth Serpinema microcephalus (Nematoda: Camallanidae) in exotic red-eared slider turtles (Trachemys scripta elegans).

PubMed

Hidalgo-Vila, Judit; Martínez-Silvestre, Albert; Ribas, Alexis; Casanova, Joan Carles; Pérez-Santigosa, Natividad; Díaz-Paniagua, Carmen

2011-01-01

Pancreatitis associated with the helminth Serpinema microcephalus was found in three of 19 free-ranging red-eared slider turtles (Trachemys scripta elegans) captured between March 2003 and September 2004 in southern Spain. Microscopic changes were associated with parasite migrations and were characterized by central areas of necrosis surrounded by leukocytes and resulted in destruction of exocrine tissue. The blood profile of one of the three female turtles revealed eosinophilia and hyperglycemia, common in helminth infections and pancreatic disorders respectively. These are the first reported cases of pancreatitis caused by the nematode S. microcephalus in the exotic and newly colonized host T. s. elegans.

Animal model of alcoholic pancreatitis: role of viral infections.

PubMed

Jerrells, Thomas R; Chapman, Nora; Clemens, Dahn L

2003-11-01

Pancreatitis is clearly associated with alcohol abuse, but only a relatively small percentage of people who abuse alcohol develops obvious pancreatitis. These observations have led to the concept that the development of alcoholic pancreatitis requires cofactors. Although diet and smoking have been studied, a clear cofactor has not been identified. The study results presented in this paper were obtained to determine whether viral infection of the pancreas would be a cofactor for alcoholic pancreatitis similar to the role of hepatitis virus infections in the development of alcoholic liver disease. To test this hypothesis, mice were fed ethanol with a liquid diet protocol and infected with coxsackievirus B3 (CVB3). It was found that consumption of alcohol alone did not result in pancreatitis as determined by serum levels of amylase or histologic changes in the pancreas. Two strains of CVB3 that are tropic for the pancreas were used; a virulent and an avirulent strain. Infection of alcohol-fed animals with the virulent CVB3 strain 28 resulted in a more severe pancreatitis than the pancreatitis noted in control animals. Alcohol-fed mice infected with the avirulent strain (GA) showed severe pancreatitis, whereas the infection of control mice did not result in obvious pathologic effects in the pancreas. This model allows mechanistic studies to define the role of viral infection as a cofactor for alcoholic pancreatitis.

Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

PubMed

Warzecha, Zygmunt; Sendur, Paweł; Ceranowicz, Piotr; Cieszkowski, Jakub; Dembiński, Marcin; Sendur, Ryszard; Bonior, Joanna; Jaworek, Jolanta; Ambroży, Tadeusz; Olszanecki, Rafał; Kuśnierz-Cabala, Beata; Tomasz, Kaczmarzyk; Tomaszewska, Romana; Dembiński, Artur

2017-04-21

Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats.

Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

PubMed Central

Warzecha, Zygmunt; Sendur, Paweł; Ceranowicz, Piotr; Cieszkowski, Jakub; Dembiński, Marcin; Sendur, Ryszard; Bonior, Joanna; Jaworek, Jolanta; Ambroży, Tadeusz; Olszanecki, Rafał; Kuśnierz-Cabala, Beata; Tomasz, Kaczmarzyk; Tomaszewska, Romana; Dembiński, Artur

2017-01-01

Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Results: Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Conclusion: Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats. PMID:28430136

Lumen apposing metal stents for pancreatic fluid collections: Recognition and management of complications.

PubMed

DeSimone, Michael L; Asombang, Akwi W; Berzin, Tyler M

2017-09-16

For patients recovering from acute pancreatitis, the development of a pancreatic fluid collection (PFC) predicts a more complex course of recovery, and introduces difficult management decisions with regard to when, whether, and how the collection should be drained. Most PFCs resolve spontaneously and drainage is indicated only in pseudocysts and walled-off pancreatic necrosis when the collections are causing symptoms and/or local complications such as biliary obstruction. Historical approaches to PFC drainage have included surgical (open or laparoscopic cystgastrostomy or pancreatic debridement), and the placement of percutaneous drains. Endoscopic drainage techniques have emerged in the last several years as the preferred approach for most patients, when local expertise is available. Lumen-apposing metal stents (LAMS) have recently been developed as a tool to facilitate potentially safer and easier endoscopic drainage of pancreatic fluid collections, and less commonly, for other indications, such as gallbladder drainage. Physicians considering LAMS placement must be aware of the complications most commonly associated with LAMS including bleeding, migration, buried stent, stent occlusion, and perforation. Because of the patient complexity associated with severe pancreatitis, management of pancreatic fluid collections can be a complex and multidisciplinary endeavor. Successful and safe use of LAMS for patients with pancreatic fluid collections requires that the endoscopist have a full understanding of the potential complications of LAMS techniques, including how to recognize and manage expected complications.

Ablation of phosphoinositide 3-kinase-gamma reduces the severity of acute pancreatitis.

PubMed

Lupia, Enrico; Goffi, Alberto; De Giuli, Paolo; Azzolino, Ornella; Bosco, Ornella; Patrucco, Enrico; Vivaldo, Maria Cristina; Ricca, Marco; Wymann, Matthias P; Hirsch, Emilio; Montrucchio, Giuseppe; Emanuelli, Giorgio

2004-12-01

In pancreatic acini, the G-protein-activated phosphoinositide 3-kinase-gamma (PI3K gamma) regulates several key pathological responses to cholecystokinin hyperstimulation in vitro. Thus, using mice lacking PI3K gamma, we studied the function of this enzyme in vivo in two different models of acute pancreatitis. The disease was induced by supramaximal concentrations of cerulein and by feeding mice a choline-deficient/ethionine-supplemented diet. Although the secretive function of isolated pancreatic acini was identical in mutant and control samples, in both models, genetic ablation of PI3K gamma significantly reduced the extent of acinar cell injury/necrosis. In agreement with a protective role of apoptosis in pancreatitis, PI3K gamma-deficient pancreata showed an increased number of apoptotic acinar cells, as determined by terminal dUTP nick-end labeling and caspase-3 activity. In addition, neutrophil infiltration within the pancreatic tissue was also reduced, suggesting a dual action of PI3K gamma, both in the triggering events within acinar cells and in the subsequent neutrophil recruitment and activation. Finally, the lethality of the choline-deficient/ethionine-supplemented diet-induced pancreatitis was significantly reduced in mice lacking PI3K gamma. Our results thus suggest that inhibition of PI3K gamma may be of therapeutic value in acute pancreatitis.

Companion Animals as a Source of Viruses for Human Beings and Food Production Animals.

PubMed

Reperant, L A; Brown, I H; Haenen, O L; de Jong, M D; Osterhaus, A D M E; Papa, A; Rimstad, E; Valarcher, J-F; Kuiken, T

2016-07-01

Companion animals comprise a wide variety of species, including dogs, cats, horses, ferrets, guinea pigs, reptiles, birds and ornamental fish, as well as food production animal species, such as domestic pigs, kept as companion animals. Despite their prominent place in human society, little is known about the role of companion animals as sources of viruses for people and food production animals. Therefore, we reviewed the literature for accounts of infections of companion animals by zoonotic viruses and viruses of food production animals, and prioritized these viruses in terms of human health and economic importance. In total, 138 virus species reportedly capable of infecting companion animals were of concern for human and food production animal health: 59 of these viruses were infectious for human beings, 135 were infectious for food production mammals and birds, and 22 were infectious for food production fishes. Viruses of highest concern for human health included hantaviruses, Tahyna virus, rabies virus, West Nile virus, tick-borne encephalitis virus, Crimean-Congo haemorrhagic fever virus, Aichi virus, European bat lyssavirus, hepatitis E virus, cowpox virus, G5 rotavirus, influenza A virus and lymphocytic choriomeningitis virus. Viruses of highest concern for food production mammals and birds included bluetongue virus, African swine fever virus, foot-and-mouth disease virus, lumpy skin disease virus, Rift Valley fever virus, porcine circovirus, classical swine fever virus, equine herpesvirus 9, peste des petits ruminants virus and equine infectious anaemia virus. Viruses of highest concern for food production fishes included cyprinid herpesvirus 3 (koi herpesvirus), viral haemorrhagic septicaemia virus and infectious pancreatic necrosis virus. Of particular concern as sources of zoonotic or food production animal viruses were domestic carnivores, rodents and food production animals kept as companion animals. The current list of viruses provides an objective

Development of the PANVAC-VF vaccine for pancreatic cancer.

PubMed

Petrulio, Christian A; Kaufman, Howard L

2006-02-01

PANVAC-VF is a vaccine regimen composed of a priming dose of recombinant vaccinia virus and booster doses of recombinant fowlpox virus expressing carcinoembryonic antigen, mucin-1 and a triad of costimulatory molecules (TRICOM), which include B7.1, intercellular adhesion molecule-1 and leukocyte function-associated antigen-3. Vaccination is administered by subcutaneous injection followed by 4 days of local recombinant adjuvant granulocyte-macrophage colony-stimulating factor at the vaccination site. The vaccine has been developed for patients with advanced pancreatic cancer and has now entered a randomized Phase III clinical trial. This review will describe the background of recombinant poxvirus technology for tumor vaccine development, detail the key preclinical studies supporting the regimen, review the clinical trials supporting the current Phase III study, and highlight the key challenges and future obstacles to successful implementation of PANVAC-VF for pancreatic cancer.

Exosomes derived from pancreatic cancer cells induce activation and profibrogenic activities in pancreatic stellate cells.

PubMed

Masamune, Atsushi; Yoshida, Naoki; Hamada, Shin; Takikawa, Tetsuya; Nabeshima, Tatsuhide; Shimosegawa, Tooru

2018-01-01

Pancreatic cancer cells (PCCs) interact with pancreatic stellate cells (PSCs), which play a pivotal role in pancreatic fibrogenesis, to develop the cancer-conditioned tumor microenvironment. Exosomes are membrane-enclosed nanovesicles, and have been increasingly recognized as important mediators of cell-to-cell communications. The aim of this study was to clarify the effects of PCC-derived exosomes on cell functions in PSCs. Exosomes were isolated from the conditioned medium of Panc-1 and SUIT-2 PCCs. Human primary PSCs were treated with PCC-derived exosomes. PCC-derived exosomes stimulated the proliferation, migration, activation of ERK and Akt, the mRNA expression of α-smooth muscle actin (ACTA2) and fibrosis-related genes, and procollagen type I C-peptide production in PSCs. Ingenuity pathway analysis of the microarray data identified transforming growth factor β1 and tumor necrosis factor as top upstream regulators. PCCs increased the expression of miR-1246 and miR-1290, abundantly contained in PCC-derived exosomes, in PSCs. Overexpression of miR-1290 induced the expression of ACTA2 and fibrosis-related genes in PSCs. In conclusion, PCC-derived exosomes stimulate activation and profibrogenic activities in PSCs. Exosome-mediated interactions between PSCs and PCCs might play a role in the development of the tumor microenvironment. Copyright © 2017 Elsevier Inc. All rights reserved.

The preclinical evaluation of TIC10/ONC201 as an anti-pancreatic cancer agent.

PubMed

Zhang, Qiangbo; Wang, Hong; Ran, Lin; Zhang, Zongli; Jiang, Runde

2016-08-05

Here we evaluated the potential anti-pancreatic cancer activity by TIC10/ONC201, a first-in-class small-molecule inducer of tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL). The in vitro results showed that TIC10 induced potent cytotoxic and cytostatic activities in several human pancreatic cancer cell lines (Panc-1, Mia-PaCa2, AsPC-1 or L3.6). TIC10 activated both extrinsic (TRAIL-caspase-8-dependent) and endogenous/mitochondrial (caspase-9-dependent) apoptosis pathways in the pancreatic cancer cells. Molecularly, we showed that TIC10 inhibited Akt-Erk activation, yet induced TRAIL expression in pancreatic cancer cells. Significantly, TIC10, at a relatively low concentration, sensitized gemcitabine-induced growth inhibition and apoptosis against pancreatic cancer cells. Further, TIC10 and gemcitabine synergistically inhibited Panc-1 xenograft growth in SCID mice. The combination treatment also significantly improved mice survival. In addition, Akt-Erk in-activation and TRAIL/cleaved-caspase-8 induction were observed in TIC10-treated Panc-1 xenografts. Together, the preclinical results of the study demonstrate the potent anti-pancreatic cancer activity by TIC10, or with gemcitabine. Copyright © 2016 Elsevier Inc. All rights reserved.

Tumor necrosis factor α (TNF-α) receptor-I is required for TNF-α-mediated fulminant virus hepatitis caused by murine hepatitis virus strain-3 infection.

PubMed

Xu, Huan; Li, Hong; Cao, Dayan; Wu, Yuzhang; Chen, Yongwen

2014-01-01

TNF-α plays an essential role in the pathogenesis of fulminant virus hepatitis (FH) caused by infection with murine hepatitis virus strain-3 (MHV-3). However, the specific TNF-α receptors (TNFR) involved in this disease and how they mediate this effect are uncertain. Here, we showed that the expression of TNFR1 and TNFR2 in the liver and spleen was triggered by MHV-3. However, only TNFR1(-/-) mice were resistant to MHV-3 mediated FH, as displayed by a dramatic decrease in tissue necrosis and cell apoptosis in the infected spleens and livers from TNFR1(-/-) mice, as well as prolonged survival in these mice compared to wild type littermate controls. Mechanistically, TNFR1 deficiency directly impeded the serum and tissue levels of fibrinogen-like protein 2 (FGL2), a virus-induced procoagulant molecule that promotes cell apoptosis. Additionally, the expression of apoptosis-associated molecules, Fas and Fas ligand (FasL) in the infected organs from TNFR1(-/-) mice were also decreased. Moreover, the infiltration of neutrophils rather than Foxp3(+) regulatory T cells, which produce proinflammatory factors and FGL2 directly, into the infected liver and spleen tissues was also decreased in TNFR1(-/-) mice. These combined results indicate that signaling through TNFR1 plays an essential role in the pathogenesis of FH caused by MHV-3 infection, and interruption of this signaling pathway could be useful for clinical therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

Major histocompatibility complex loci are associated with susceptibility of Atlantic salmon to infectious hematopoietic necrosis virus

USGS Publications Warehouse

Miller, Kristina M.; Winton, James R.; Schulze, Angela D.; Purcell, Maureen K.; Ming, Tobi J.

2004-01-01

Infectious hematopoietic necrosis virus (IHNV) is one of the most significant viral pathogens of salmonids and is a leading cause of death among cultured juvenile fish. Although several vaccine strategies have been developed, some of which are highly protective, the delivery systems are still too costly for general use by the aquaculture industry. More cost effective methods could come from the identification of genes associated with IHNV resistance for use in selective breeding. Further, identification of susceptibility genes may lead to an improved understanding of viral pathogenesis and may therefore aid in the development of preventive and therapeutic measures. Genes of the major histocompatibility complex (MHC), involved in the primary recognition of foreign pathogens in the acquired immune response, are associated with resistance to a variety of diseases in vertebrate organisms. We conducted a preliminary analysis of MHC disease association in which an aquaculture strain of Atlantic salmon was challenged with IHNV at three different doses and individual fish were genotyped at three MHC loci using denaturing gradient gel electrophoresis (PCR-DGGE), followed by sequencing of all differentiated alleles. Nine to fourteen alleles per exon-locus were resolved, and alleles potentially associated with resistance or susceptibility were identified. One allele (Sasa-B-04) from a potentially non-classical class I locus was highly associated with resistance to infectious hematopoietic necrosis (p < 0.01). This information can be used to design crosses of specific haplotypes for family analysis of disease associations.

Interference in plant defense and development by non-structural protein NSs of Groundnut bud necrosis virus.

PubMed

Goswami, Suneha; Sahana, Nandita; Pandey, Vanita; Doblas, Paula; Jain, R K; Palukaitis, Peter; Canto, Tomas; Praveen, Shelly

2012-01-01

Groundnut bud necrosis virus (GBNV) infects a large number of leguminous and solanaceous plants. To elucidate the biological function of the non-structural protein encoded by the S RNA of GBNV (NSs), we studied its role in RNA silencing suppression and in viral pathogenesis. Our results demonstrated that GBNV NSs functions as a suppressor of RNA silencing using the agroinfiltration patch assay. An in silico analysis suggested the presence of pro-apoptotic protein Reaper-like sequences in the GBNV NSs, which were known to be present in animal infecting bunyaviruses. Utilizing NSs mutants, we demonstrated that a Leu-rich domain was required for RNA silencing suppression activity, but not the non-overlapping Trp/GH3 motif of the Reaper-like sequence. To investigate the role of NSs in symptom development we generated transgenic tomato expressing the GBNV NSs and showed that the expression of NSs in tomato mimics symptoms induced by infection with GBNV, such as leaf senescence and necrosis. As leaf senescence is controlled by miR319 regulation of the transcription factor TCP1, we assessed the accumulation of both RNAs in transgenic NSs-expressing and GBNV-infected tomato plants. In both types of plants the levels of miR319 decreased, while the levels of TCP1 transcripts increased. We propose that GBNV-NSs affects miRNA biogenesis through its RNA silencing suppressor activity and interferes with TCP1-regulated leaf developmental pathways. Copyright © 2011 Elsevier B.V. All rights reserved.

Assessment of biophysical tumor response to PDT in pancreatic cancer using localized reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Isabelle, Martin; Klubben, William; He, Ting; Laughney, Ashley M.; Glaser, Adam; Krishnaswamy, Venkataramanan; Hoopes, P. Jack; Hasan, Tayyaba; Pogue, Brian W.

2011-02-01

Biophysical changes such as inflammation and necrosis occur immediately following PDT and may be used to assess the treatment response to PDT treatment in-vivo. This study uses localized reflectance measurements to quantify the scatter changes in tumor tissue occurring in response to verteporfin-based PDT treatment in xenograft pancreas tumors. Nude mice were implanted with subcutaneous AsPC-1 pancreatic tumors cells in matrigel, and allowed to establish solid tumors near 100mm3 volume. The mice were sensitized with 1mg/kg of the active component of verteporfin (benzoporphryin derivative, BPD), one hour before light delivery. The optical irradiation was performed using a 1 cm cylindrical interstitial diffusing tip fiber with 20J of red light (690nm). Tumor tissue was excised progressively and imaged, from 1 day to 4 weeks, after PDT treatment. The tissue sections were stained and analyzed by an expert veterinary pathologist, who provided information on tissue regions of interest. This information was correlated with variations in scattering and absorption parameters elucidated from the spectral images and the degree of necrosis and inflammation involvement was identified. Areas of necrosis and dead cells exhibited the lowest average scatter irradiance signature (3.78 and 4.07 respectively) compared to areas of viable pancreatic tumor cells and areas of inflammation (5.81 and 7.19 respectively). Bilirubin absorbance parameters also showed a lower absorbance value in necrotic tissue and areas of dead cells (0.05 and 0.1 respectively) compared to tissue areas for viable pancreatic tumor cells and areas of inflammation (0.28 and 0.35). These results demonstrate that localized reflectance spectroscopy is an imaging modality that can be used to identify tissue features associated with PDT treatment (e.g. necrosis and inflammation) that can be correlated with histopathologically-reviewed H&E stained slides. Further study of this technique may provide means for automated

First outbreak of an infection with infectious spleen and kidney necrosis virus (ISKNV) in ornamental fish in Germany.

PubMed

Jung-Schroers, Verena; Adamek, Mikolaj; Wohlsein, Peter; Wolter, Jan; Wedekind, Helmut; Steinhagen, Dieter

2016-05-26

In 2014, infectious spleen and kidney necrosis virus (ISKNV), a member of the genus Megalocytivirus, was detected for the first time in ornamental fish in Germany. Since 2013, angelfish Pterophyllum spp. originating from Colombia have experienced significant epizootics in a number of German retailers' facilities. The diseased fish showed symptoms such as increased ventilation, swollen gills, and ulcerations of the skin. In 2014, diseased angelfish P. altum and platys Xiphophorus maculatus maintained in the same recirculating system were examined. Histopathological lesions included hypertrophic cells, single-cell necrosis, and an inflammatory infiltration of granulocytes, lymphocytes, and macrophages in liver, spleen, and kidney. Transmission electron microscopy revealed the presence of numerous polygonal viral particles (150 nm in diameter) within the cytoplasm of enlarged cells. A PCR assay for the detection of megalocytiviruses amplified 777 bp of major capsid protein gene that was 100% identical to ISKNV. This is the first report of an ISKNV outbreak in Germany that most probably was introduced by infected angelfish from Colombia. To our knowledge, this is the first report of ISKNV detected in fish imported from South America. Given the lethal nature of megalocytiviruses, proper biosecurity would seem prudent in countries like Germany where these emerging pathogens are not established.

Cytosolic Double-Stranded DNA as a Damage-Associated Molecular Pattern Induces the Inflammatory Response in Rat Pancreatic Stellate Cells: A Plausible Mechanism for Tissue Injury-Associated Pancreatitis

PubMed Central

Nakamura, Taichi; Ito, Tetsuhide; Igarashi, Hisato; Uchida, Masahiko; Hijioka, Masayuki; Oono, Takamasa; Fujimori, Nao; Niina, Yusuke; Suzuki, Koichi; Jensen, Robert T.; Takayanagi, Ryoichi

2012-01-01

Pancreatitis is an inflammatory disease of unknown causes. There are many triggers causing pancreatitis, such as alcohol, common bile duct stone, virus and congenital or acquired stenosis of main pancreatic duct, which often involve tissue injuries. Pancreatitis often occurs in sterile condition, where the dead/dying pancreatic parenchymal cells and the necrotic tissues derived from self-digested-pancreas were observed. However, the causal relationship between tissue injury and pancreatitis and how tissue injury could induce the inflammation of the pancreas were not elucidated fully until now. This study demonstrates that cytosolic double-stranded DNA increases the expression of several inflammatory genes (cytokines, chemokines, type I interferon, and major histocompatibility complex) in rat pancreatic stellate cells. Furthermore, these increase accompanied the multiple signal molecules genes, such as interferon regulatory factors, nuclear factor-kappa B, low-molecular-weight protein 2, and transporter associated with antigen processing 1. We suggest that this phenomenon is a plausible mechanism that might explain how cell damage of the pancreas or tissue injury triggers acute, chronic, and autoimmune pancreatitis; it is potentially relevant to host immune responses induced during alcohol consumption or other causes. PMID:22550608

Efficacy of an infectious hematopoietic necrosis (IHN) virus DNA vaccine in Chinook Oncorhynchus tshawytscha and sockeye O. nerka salmon.

PubMed

Garver, Kyle A; LaPatra, Scott E; Kurath, Gael

2005-04-06

The level of protective immunity was determined for Chinook Oncorhynchus tshawytscha and sockeye/kokanee salmon (anadromous and landlocked) O. nerka following intramuscular vaccination with a DNA vaccine against the aquatic rhabdovirus, infectious hematopoietic necrosis virus (IHNV). A DNA vaccine containing the glycoprotein gene of IHNV protected Chinook and sockeye/kokanee salmon against waterborne or injection challenge with IHNV, and relative percent survival (RPS) values of 23 to 86% were obtained under a variety of lethal challenge conditions. Although this is significant protection, it is less than RPS values obtained in previous studies with rainbow trout (O. mykiss). In addition to the variability in the severity of the challenge and inherent host susceptibility differences, it appears that use of a cross-genogroup challenge virus strain may lead to reduced efficacy of the DNA vaccine. Neutralizing antibody titers were detected in both Chinook and sockeye that had been vaccinated with 1.0 and 0.1 pg doses of the DNA vaccine, and vaccinated fish responded to viral challenges with higher antibody titers than mock-vaccinated control fish.

Efficacy of an infectious hematopoietic necrosis (IHN) virus DNA vaccine in Chinook Oncorhynchus tshawytscha and sockeye O. nerka salmon

USGS Publications Warehouse

Garver, K.A.; LaPatra, S.E.; Kurath, G.

2005-01-01

The level of protective immunity was determined for Chinook Oncorhynchus tshawytscha and sockeye/kokanee salmon (anadromous and landlocked) O. nerka following intramuscular vaccination with a DNA vaccine against the aquatic rhabdovirus, infectious hematopoietic necrosis virus (IHNV). A DNA vaccine containing the glycoprotein gene of IHNV protected Chinook and sockeye/kokanee salmon against waterborne or injection challenge with IHNV, and relative percent survival (RPS) values of 23 to 86% were obtained under a variety of lethal challenge conditions. Although this is significant protection, it is less than RPS values obtained in previous studies with rainbow trout (O. mykiss). In addition to the variability in the severity of the challenge and inherent host susceptibility differences, it appears that use of a cross-genogroup challenge virus strain may lead to reduced efficacy of the DNA vaccine. Neutralizing antibody titers were detected in both Chinook and sockeye that had been vaccinated with 1.0 and 0.1 ??g doses of the DNA vaccine, and vaccinated fish responded to viral challenges with higher antibody titers than mock-vaccinated control fish. ?? Inter-Research 2005.

Direct activation of RIP3/MLKL-dependent necrosis by herpes simplex virus 1 (HSV-1) protein ICP6 triggers host antiviral defense

PubMed Central

Wang, Xing; Li, Yun; Liu, Shan; Yu, Xiaoliang; Li, Lin; Shi, Cuilin; He, Wenhui; Li, Jun; Xu, Lei; Hu, Zhilin; Yu, Lu; Yang, Zhongxu; Chen, Qin; Ge, Lin; Zhang, Zili; Zhou, Biqi; Jiang, Xuejun; Chen, She; He, Sudan

2014-01-01

The receptor-interacting kinase-3 (RIP3) and its downstream substrate mixed lineage kinase domain-like protein (MLKL) have emerged as the key cellular components in programmed necrotic cell death. Receptors for the cytokines of tumor necrosis factor (TNF) family and Toll-like receptors (TLR) 3 and 4 are able to activate RIP3 through receptor-interacting kinase-1 and Toll/IL-1 receptor domain-containing adapter inducing IFN-β, respectively. This form of cell death has been implicated in the host-defense system. However, the molecular mechanisms that drive the activation of RIP3 by a variety of pathogens, other than the above-mentioned receptors, are largely unknown. Here, we report that human herpes simplex virus 1 (HSV-1) infection triggers RIP3-dependent necrosis. This process requires MLKL but is independent of TNF receptor, TLR3, cylindromatosis, and host RIP homotypic interaction motif-containing protein DNA-dependent activator of IFN regulatory factor. After HSV-1 infection, the viral ribonucleotide reductase large subunit (ICP6) interacts with RIP3. The formation of the ICP6–RIP3 complex requires the RHIM domains of both proteins. An HSV-1 ICP6 deletion mutant failed to cause effective necrosis of HSV-1–infected cells. Furthermore, ectopic expression of ICP6, but not RHIM mutant ICP6, directly activated RIP3/MLKL-mediated necrosis. Mice lacking RIP3 exhibited severely impaired control of HSV-1 replication and pathogenesis. Therefore, this study reveals a previously uncharacterized host antipathogen mechanism. PMID:25316792

Ruxolitinib and Polycation Combination Treatment Overcomes Multiple Mechanisms of Resistance of Pancreatic Cancer Cells to Oncolytic Vesicular Stomatitis Virus

PubMed Central

Felt, Sébastien A.; Droby, Gaith N.

2017-01-01

ABSTRACT Vesicular stomatitis virus (VSV) is a promising oncolytic virus (OV). Although VSV is effective against a majority of pancreatic ductal adenocarcinoma cell (PDAC) cell lines, some PDAC cell lines are highly resistant to VSV, and the mechanisms of resistance are still unclear. JAK1/2 inhibitors (such as ruxolitinib and JAK inhibitor I) strongly stimulate VSV replication and oncolysis in all resistant cell lines but only partially improve the susceptibility of resistant PDACs to VSV. VSV tumor tropism is generally dependent on the permissiveness of malignant cells to viral replication rather than on receptor specificity, with several ubiquitously expressed cell surface molecules playing a role in VSV attachment to host cells. However, as VSV attachment to PDAC cells has never been tested before, here we examined if it was possibly inhibited in resistant PDAC cells. Our data show a dramatically weaker attachment of VSV to HPAF-II cells, the most resistant human PDAC cell line. Although sequence analysis of low-density lipoprotein (LDL) receptor (LDLR) mRNA did not reveal any amino acid substitutions in this cell line, HPAF-II cells displayed the lowest level of LDLR expression and dramatically lower LDL uptake. Treatment of cells with various statins strongly increased LDLR expression levels but did not improve VSV attachment or LDL uptake in HPAF-II cells. However, LDLR-independent attachment of VSV to HPAF-II cells was dramatically improved by treating cells with Polybrene or DEAE-dextran. Moreover, combining VSV with ruxolitinib and Polybrene or DEAE-dextran successfully broke the resistance of HPAF-II cells to VSV by simultaneously improving VSV attachment and replication. IMPORTANCE Oncolytic virus (OV) therapy is an anticancer approach that uses viruses that selectively infect and kill cancer cells. This study focuses on oncolytic vesicular stomatitis virus (VSV) against pancreatic ductal adenocarcinoma (PDAC) cells. Although VSV is effective against

First report of Persimmon cryptic virus and Persimmon virus A in Korea

USDA-ARS?s Scientific Manuscript database

In 2014, a total of 77 persimmon (Diospyros kaki Thunb.) trees from Korean commercial persimmon orchards were surveyed for Persimmon cryptic virus (PeCV) and Persimmon virus A (PeVA). Leaf samples were collected from symptomatic trees with necrosis (two), or mosaic and leaf malformations (one) and 7...

Predictors of severity in childhood pancreatitis: correlation with nutritional status and racial demographics.

PubMed

Vasilescu, Alexandra; Cuffari, Carmen; Santo Domingo, Lisa; Scheimann, Ann O

2015-04-01

Acute pancreatitis is one of the leading causes of rising pediatric hospitalizations in North America. The aim of this study was to assess the role of nutritional status and racial influences on the severity of acute pancreatitis in children. The institutional review board approved this retrospective chart review of children with the diagnosis of acute pancreatitis between the ages of 0 and 18 years hospitalized at the Johns Hopkins Hospital between 1998 and 2008. Parameters studied included biochemical markers associated with pancreatitis, review of severity of illness reflected through the length of stay, and pediatric intensive care unit admission. The length of in-patient hospitalization was longer for children with imaging findings of pseudocyst or pancreatic necrosis (23.1 ± 26.4 days vs 4.4 ± 10.6 days; P = 0.0074) and malnourished children versus normal weight and obese children (16.5 days for malnourished vs 10.6 days for normal weight vs 10.7 days for obese; P = 0.04). There was also a significant difference in the need for pediatric intensive care unit admission across ethnic groups (18% African American vs 7% white) (P = 0.04). Ethnicity and nutritional status may influence the severity and duration of hospitalization among children with pancreatitis.

Pathogenesis of chronic pancreatitis: an evidence-based review of past theories and recent developments.