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The Journal of Infectious Diseases Feb 1993Events were examined that might contribute to mortality in acute murine cytomegalovirus (MCMV) infection after intraperitoneal inoculation. Specifically, viral... (Comparative Study)
Comparative Study
Events were examined that might contribute to mortality in acute murine cytomegalovirus (MCMV) infection after intraperitoneal inoculation. Specifically, viral replication in the liver, spleen, and pancreas and the concomitant biochemical abnormalities induced by MCMV during lethal and nonlethal acute viral infection were compared. Mortality was limited to susceptible strains of mice infected by the intraperitoneal (ip) route. In addition, the virus content of the lung, liver, spleen, and pancreas was 100- to 1000-fold greater with lethal infection in the ip-infected group than in those with nonlethal infection. Serum transaminase and lipase levels were markedly elevated in susceptible mice inoculated with MCMV ip. Histopathologic and immunocytochemical changes in the liver, coupled with elevated serum transaminase levels indicating severe hepatitis, appear sufficient to explain the early mortality seen with the ip route of infection.
Topics: Acute Disease; Animals; Cytomegalovirus; Cytomegalovirus Infections; Female; Hepatitis, Viral, Animal; Immunohistochemistry; Lipase; Liver; Lung; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Pancreas; Spleen; Transaminases; Virus Replication
PubMed: 8380608
DOI: 10.1093/infdis/167.2.264 -
Diabetologia May 2019In type 1 diabetes, pancreatic beta cells are destroyed by chronic autoimmune responses. The disease develops in genetically susceptible individuals, but a role for... (Review)
Review
In type 1 diabetes, pancreatic beta cells are destroyed by chronic autoimmune responses. The disease develops in genetically susceptible individuals, but a role for environmental factors has been postulated. Viral infections have long been considered as candidates for environmental triggers but, given the lack of evidence for an acute, widespread, cytopathic effect in the pancreas in type 1 diabetes or for a closely related temporal association of diabetes onset with such infections, a role for viruses in type 1 diabetes remains unproven. Moreover, viruses have rarely been isolated from the pancreas of individuals with type 1 diabetes, mainly (but not solely) due to the inaccessibility of the organ. Here, we review past and recent literature to evaluate the proposals that chronic, recurrent and, possibly, persistent enteroviral infections occur in pancreatic beta cells in type 1 diabetes. We also explore whether these infections may be sustained by different virus strains over time and whether multiple viral hits can occur during the natural history of type 1 diabetes. We emphasise that only a minority of beta cells appear to be infected at any given time and that enteroviruses may become replication defective, which could explain why they have been isolated from the pancreas only rarely. We argue that enteroviral infection of beta cells largely depends on the host innate and adaptive immune responses, including innate responses mounted by beta cells. Thus, we propose that viruses could play a role in type 1 diabetes on multiple levels, including in the triggering and chronic stimulation of autoimmunity and in the generation of inflammation and the promotion of beta cell dysfunction and stress, each of which might then contribute to autoimmunity, as part of a vicious circle. We conclude that studies into the effects of vaccinations and/or antiviral drugs (some of which are currently on-going) is the only means by which the role of viruses in type 1 diabetes can be finally proven or disproven.
Topics: Adaptive Immunity; Antiviral Agents; Autoimmunity; Biological Specimen Banks; Diabetes Mellitus, Type 1; Enterovirus Infections; Humans; Immunity, Innate; Insulin-Secreting Cells; Pancreas; Viral Vaccines
PubMed: 30675626
DOI: 10.1007/s00125-019-4811-7 -
Current Gastroenterology Reports Apr 2006Infectious complications are the most common cause of morbidity and mortality in patients suffering from severe acute pancreatitis. Approximately 25% of patients develop... (Meta-Analysis)
Meta-Analysis Review
Infectious complications are the most common cause of morbidity and mortality in patients suffering from severe acute pancreatitis. Approximately 25% of patients develop pancreatic necrosis. In these patients with severe disease complicated by necrosis, there is evidence that preventing infection of the pancreatic necrosis decreases morbidity and mortality. Whereas sterile necrosis is often treated conservatively, surgical debridement is required when the necrosis becomes infected. Although surgery is necessary in patients with infected necrosis, for a variety of reasons surgical intervention increases the morbidity and mortality of the disease. Preventing infectious complications, such as infected necrosis, through the use of prophylactic antibiotics is controversial. Despite reviewing the same evidence, different authors and organizations have formed different conclusions. In this review, we perform a critical analysis of the studies. Overall, the use of antibiotics in patients with necrotizing pancreatitis appears to decrease infectious complications and mortality.
Topics: Antibiotic Prophylaxis; Bacterial Infections; Bacterial Translocation; Colon; Disease Progression; Humans; Necrosis; Pancreas; Pancreatitis, Acute Necrotizing; Practice Guidelines as Topic; Prognosis
PubMed: 16533474
DOI: 10.1007/s11894-006-0007-7 -
Parasites & Vectors Jun 2021Zoonotic visceral leishmaniasis is caused by the protozoan Leishmania infantum and is highly lethal in humans and dogs if left untreated. The frequency of this parasite...
BACKGROUND
Zoonotic visceral leishmaniasis is caused by the protozoan Leishmania infantum and is highly lethal in humans and dogs if left untreated. The frequency of this parasite and associated histological changes in the pancreas of dogs are poorly studied. Therefore, the objectives of this study were to evaluate the frequency of detection and load of amastigotes in the pancreas of L. infantum-seropositive dogs and to identify the clinical signs and histological changes associated with parasitism of this organ.
METHODS
One hundred forty-three dogs from an endemic area in Brazil that tested seropositive for L. infantum were studied. The dogs were clinically examined, killed, and necropsied between 2013 and 2014. One fragment of the pancreas was randomly collected for histopathology and immunohistochemistry, and spleen and bone marrow were collected for culture.
RESULTS
Leishmania amastigotes were detected in the pancreas of 22 dogs (15.4%) by immunohistochemistry, all exhibiting L. infantum parasitism in the spleen and/or bone marrow. Poor body condition and cachexia were only associated with infection of the pancreas with Leishmania spp. (p = 0.021) and were found in 40.9% of dogs with pancreatic infection. Anorexia, vomiting, and/or diarrhea were observed in 9.2% of dogs with pancreatitis. The median parasite load in the pancreas was 1.4 infected macrophages/mm. Pancreatic histological changes and their frequencies were: granulomatous pancreatitis (28.0%), lymphoplasmacytic pancreatitis (23.8%), acinar cell degeneration (6.3%), fibrosis (5.6%), hemorrhage (2.1%), eosinophilic pancreatitis (0.7%), suppurative pancreatitis (0.7%), and necrosis (0.7%).
CONCLUSIONS
The present results demonstrate that L. infantum is one of the etiological agents of chronic pancreatitis in dogs; however, the frequency of detection and parasite load are low in this organ. The lack of an association of poor body condition and cachexia with pancreatitis and the low frequency of clinical signs commonly associated with pancreatitis suggest that a significant portion of the organ is not affected by this parasite. On the other hand, the association of poor body condition and cachexia with concomitant infection of the pancreas, spleen, and/or bone marrow with this parasite suggests that these manifestations are the result of a more advanced stage of canine visceral leishmaniasis.
Topics: Animals; Dog Diseases; Dogs; Female; Histological Techniques; Immunohistochemistry; Leishmania infantum; Leishmaniasis, Visceral; Male; Pancreas; Parasite Load
PubMed: 34118967
DOI: 10.1186/s13071-021-04813-3 -
Transplantation Oct 2005
Topics: Adult; Animals; Antinematodal Agents; Humans; Ivermectin; Male; Pancreas; Pancreas Transplantation; Strongyloides stercoralis; Strongyloidiasis; Thiabendazole; Transplantation, Homologous; Transplants
PubMed: 16249752
DOI: 10.1097/01.tp.0000173825.12681.eb -
The British Journal of Surgery Dec 1994
Topics: Bacterial Infections; Humans; Pancreas; Pancreatitis
PubMed: 7827923
DOI: 10.1002/bjs.1800811203 -
Pancreatology : Official Journal of the... Jul 2020
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Pancreas; Pancreatitis; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32498973
DOI: 10.1016/j.pan.2020.05.015 -
Journal of Virology Jul 2018Respiratory epithelial cell death by influenza virus infection is responsible for the induction of inflammatory responses, but the exact cell death mechanism is not...
Influenza A Virus Infection Triggers Pyroptosis and Apoptosis of Respiratory Epithelial Cells through the Type I Interferon Signaling Pathway in a Mutually Exclusive Manner.
Respiratory epithelial cell death by influenza virus infection is responsible for the induction of inflammatory responses, but the exact cell death mechanism is not understood. Here we showed that influenza virus infection induces apoptosis and pyroptosis in normal or precancerous human bronchial epithelial cells. Apoptosis was induced only in malignant tumor cells infected with influenza virus. In human precancerous respiratory epithelial cells (PL16T), the number of apoptotic cells increased at early phases of infection, but pyroptotic cells were observed at late phases of infection. These findings suggest that apoptosis is induced at early phases of infection but the cell death pathway is shifted to pyroptosis at late phases of infection. We also found that the type I interferon (IFN)-mediated JAK-STAT signaling pathway promotes the switch from apoptosis to pyroptosis by inhibiting apoptosis possibly through the induced expression of the anti-apoptotic gene. Further, the inhibition of JAK-STAT signaling repressed pyroptosis but enhanced apoptosis in infected PL16T cells. Collectively, we propose that type I IFN signaling pathway triggers pyroptosis but not apoptosis in the respiratory epithelial cells in a mutually exclusive manner to initiate proinflammatory responses against influenza virus infection. Respiratory epithelium functions as a sensor of infectious agents to initiate inflammatory responses along with cell death. However, the exact cell death mechanism responsible for inflammatory responses by influenza virus infection is still unclear. We showed that influenza virus infection induced apoptosis and pyroptosis in normal or precancerous human bronchial epithelial cells. Apoptosis was induced at early phases of infection, but the cell death pathway was shifted to pyroptosis at late phases of infection under the regulation of type I IFN signaling to promote proinflammatory cytokine production. Taken together, our results indicate that the type I IFN signaling pathway plays an important role to induce pyroptosis but represses apoptosis in the respiratory epithelial cells to initiate proinflammatory responses against influenza virus infection.
Topics: Apoptosis; Apoptosis Regulatory Proteins; Cells, Cultured; Humans; Influenza A virus; Influenza, Human; Interferon Type I; Pancreas; Precancerous Conditions; Pyroptosis; Respiratory Mucosa; Signal Transduction
PubMed: 29743359
DOI: 10.1128/JVI.00396-18 -
The EMBO Journal Sep 2017Melanoma differentiation-associated protein 5 (MDA5) mediates the innate immune response to viral infection. Polymorphisms in , the gene coding for MDA5, correlate with...
Melanoma differentiation-associated protein 5 (MDA5) mediates the innate immune response to viral infection. Polymorphisms in , the gene coding for MDA5, correlate with the risk of developing type 1 diabetes (T1D). Here, we demonstrate that MDA5 is crucial for the immune response to enteric rotavirus infection, a proposed etiological agent for T1D. MDA5 variants encoded by minor alleles associated with lower T1D risk exhibit reduced activity against rotavirus infection. We find that MDA5 activity limits rotavirus infection not only through the induction of antiviral interferons and pro-inflammatory cytokines, but also by promoting cell death. Importantly, this MDA5-dependent antiviral response is specific to the pancreas of rotavirus-infected mice, similar to the autoimmunity associated with T1D. These findings imply that MDA5-induced cell death and inflammation in the pancreas facilitate progression to autoimmune destruction of pancreatic β-cells.
Topics: Animals; Cell Death; Cells, Cultured; Host-Pathogen Interactions; Inflammation; Interferon-Induced Helicase, IFIH1; Mice; Pancreas; Rotavirus; Rotavirus Infections
PubMed: 28851763
DOI: 10.15252/embj.201696273 -
Pancreas Mar 2003Frequent histologic changes (90%) in the pancreas suggesting protein-energy malnutrition were found in a previous necropsy study of pancreas morphology in patients with...
INTRODUCTION
Frequent histologic changes (90%) in the pancreas suggesting protein-energy malnutrition were found in a previous necropsy study of pancreas morphology in patients with AIDS. However, additional studies were required to clarify subcellular changes.
AIM
To ultrastructurally analyze pancreas changes in AIDS patients through transmission electron microscopy.
METHODOLOGY AND RESULTS
Pancreas specimens for necropsy were obtained from nine consecutive AIDS patients and four normal controls. A semiquantitative histologic and ultrastructural analysis of exocrine pancreas was carried out with the following findings: preserved pancreas structure with little autolysis, marked decrease in zymogen granules (100%), increased lipofuscin pigment (80%), augmented and dilated rough endoplasmic reticulum (100%), and increased number and size of mitochondria. The Golgi complex could be identified only in two cases. In all cases, acinar nuclei were decreased in size, with peripherally condensed chromatin and undulated membrane suggesting early apoptosis. In addition, immunohistochemical evaluation of the pancreas was carried out to detect opportunistic agents.
CONCLUSION
Decreased zymogen granules, acinar atrophy, increased lipofuscin pigment, and rarefying Golgi complex represent the morphologic substrate of protein-energy malnutrition in AIDS patients. The combination of rough endoplasmic reticulum and mitochondria changes could be due to the need for supplying vital plasma proteins rather than exportation protein synthesis associated, or not, with the deleterious effects of inflammatory cytokines and/or therapy for disease.
Topics: Acquired Immunodeficiency Syndrome; Adult; Autopsy; Female; Humans; Male; Microscopy, Electron; Pancreas
PubMed: 12604913
DOI: 10.1097/00006676-200303000-00011