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Pancreas Mar 2003The trigger for some cases of juvenile diabetes has been suggested to be an interaction between a virus and various trace elements. Infection with human coxsackievirus...
INTRODUCTION
The trigger for some cases of juvenile diabetes has been suggested to be an interaction between a virus and various trace elements. Infection with human coxsackievirus B3 (CB3) in the murine model results in viral replication and inflammation in the pancreas.
AIM
To determine how infection affects the trace element balance in the pancreas.
METHODOLOGY
Concentrations of the following trace elements were measured in the serum and pancreas during the early phase (days 1 and 3) of CB3 infection in female Balb/c mice: aluminium, arsenic, cadmium (Cd), calcium (Ca), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), magnesium (Mg), manganese (Mn), mercury (Hg), selenium, silver, vanadium (V), and zinc (Zn). The trace element concentrations were measured through inductively coupled plasma mass spectrometry. The histopathology was established by hematoxylin-eosin techniques and immunohistochemical staining of both CD4 and CD8 cells of the pancreas.
RESULTS
Infected mice developed expected clinical signs of disease. The only changes at day 1 occurred in the serum, with a pronounced decrease in the Zn concentration and a small increase in the V concentration. At day 3, concentrations of several trace elements, including Cu, Zn, Fe, Ca, V, and Mn, showed pronounced changes in both the serum and the pancreas. Ca, Cu, Mg, Mn, and V, but none of the potentially toxic elements, accumulated in the pancreas. Cu and V concentrations increased in the serum as well.
CONCLUSION
Several trace element changes, preceding the development of pancreatitis, occurred in the pancreas in this viral infection, the exact pathogenic interpretation of which warrants further studies.
Topics: Animals; Coxsackievirus Infections; Enterovirus; Female; HeLa Cells; Humans; Metals; Mice; Mice, Inbred BALB C; Pancreas; Time Factors
PubMed: 12604919
DOI: 10.1097/00006676-200303000-00017 -
Virology Jun 2000Coxsackievirus type B (CVB) infection of the pancreas induces a massive cellular infiltrate composed of natural killer cells, T cells, and macrophages and leads to the...
Coxsackievirus type B (CVB) infection of the pancreas induces a massive cellular infiltrate composed of natural killer cells, T cells, and macrophages and leads to the destruction of exocrine tissue. The physiological manifestations of pancreatic CVB infection are correlated with viral tropism; the virus infects acinar cells but spares the islets of Langerhans. Here we evaluate the mechanisms underlying pancreatic inflammation and destruction and identify the determinants of viral tropism. T-cell-mediated immunopathology has been invoked, along with direct virus-mediated cytopathicity, to explain certain aspects of CVB-induced pancreatic disease. However, we show here that in the pancreas, the extent of inflammation and tissue destruction appears unaltered in the absence of the cytolytic protein perforin; these findings exclude any requirement for perforin-mediated lysis by natural killer cells or cytotoxic T cells in CVB3-induced pancreatic damage. Furthermore, perforin-mediated cytotoxic T-cell activity does not contribute to the control of CVB infection in this organ. In addition, we demonstrate that the recently identified coxsackie-adenovirus receptor is expressed at high levels in acinar cells but is barely detectable in islets, which is consistent with its being a major determinant of virus tropism and, therefore, of disease. However, further studies using various cell lines of pancreatic origin reveal secondary determinants of virus tropism.
Topics: Animals; CD55 Antigens; Coxsackie and Adenovirus Receptor-Like Membrane Protein; Coxsackievirus Infections; Enterovirus B, Human; Gene Expression; HeLa Cells; Humans; Killer Cells, Natural; Male; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Pancreas; Perforin; Pore Forming Cytotoxic Proteins; RNA, Viral; Receptors, Virus; T-Lymphocytes, Cytotoxic; Tissue Distribution; Transfection; Tumor Cells, Cultured
PubMed: 10860882
DOI: 10.1006/viro.2000.0332 -
Nature Reviews. Endocrinology Apr 2021
Topics: COVID-19; Humans; Pancreas; Pancreas, Exocrine; SARS-CoV-2
PubMed: 33627835
DOI: 10.1038/s41574-021-00481-6 -
Frontiers in Cellular and Infection... 2021COVID-19 pandemic has infected more than 154 million people worldwide and caused more than 3.2 million deaths. It is transmitted by the Severe Acute Respiratory Syndrome...
COVID-19 pandemic has infected more than 154 million people worldwide and caused more than 3.2 million deaths. It is transmitted by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and affects the respiratory tract as well as extra-pulmonary systems, including the pancreas, that express the virus entry receptor, Angiotensin-Converting Enzyme 2 (ACE2) receptor. Importantly, the endocrine and exocrine pancreas, the latter composed of ductal and acinar cells, express high levels of ACE2, which correlates to impaired functionality characterized as acute pancreatitis observed in some cases presenting with COVID-19. Since acute pancreatitis is already one of the most frequent gastrointestinal causes of hospitalization in the U.S. and the majority of studies investigating the effects of SARS-CoV-2 on the pancreas are clinical and observational, we utilized human iPSC technology to investigate the potential deleterious effects of SARS-CoV-2 infection on iPSC-derived pancreatic cultures containing endocrine and exocrine cells. Interestingly, iPSC-derived pancreatic cultures allow SARS-CoV-2 entry and establish infection, thus perturbing their normal molecular and cellular phenotypes. The infection increased a key cytokine, CXCL12, known to be involved in inflammatory responses in the pancreas. Transcriptome analysis of infected pancreatic cultures confirmed that SARS-CoV-2 hijacks the ribosomal machinery in these cells. Notably, the SARS-CoV-2 infectivity of the pancreas was confirmed in post-mortem tissues from COVID-19 patients, which showed co-localization of SARS-CoV-2 in pancreatic endocrine and exocrine cells and increased the expression of some pancreatic ductal stress response genes. Thus, we demonstrate that SARS-CoV-2 can directly infect human iPSC-derived pancreatic cells with strong supporting evidence of presence of the virus in post-mortem pancreatic tissue of confirmed COVID-19 human cases. This novel model of iPSC-derived pancreatic cultures will open new avenues for the comprehension of the SARS-CoV-2 infection and potentially establish a platform for endocrine and exocrine pancreas-specific antiviral drug screening.
Topics: Acute Disease; COVID-19; Humans; Pancreas; Pancreatitis; Pandemics; SARS-CoV-2
PubMed: 34282405
DOI: 10.3389/fcimb.2021.678482 -
Annals of Surgery Aug 1994Bacterial infection of pancreatic necrosis is thought to be a major determinant of outcome in acute necrotizing pancreatitis. The determinants and possibilities for...
BACKGROUND
Bacterial infection of pancreatic necrosis is thought to be a major determinant of outcome in acute necrotizing pancreatitis. The determinants and possibilities for prophylaxis are unknown and difficult to study in humans.
OBJECTIVE
The time course of bacterial infection of the pancreas in a rodent model of acute necrotizing pancreatitis was characterized. The authors ascertained if there is a correlation with the degree of necrosis.
METHODS
Acute pancreatitis (AP) of graded severity was induced under sterile conditions by an intravenous infusion of cerulein (5 micrograms/kg/hr) for 6 hours (mild AP), or a combination of intravenous cerulein with an intraductal infusion of 10-mM glycodeoxycholic acid (0.2 mL for 2 min for moderate AP, 0.5 mL for 10 min for severe AP). Sham-operated animals (intravenous and intraductal NaCl 0.9%) served as controls. Ninety-six hours after induction, animals were killed for quantitative bacterial examination and histologic scoring of necrosis. In addition, groups of animals with severe AP were investigated at 12, 24, 48, 96, and 144 hours.
RESULTS
No significant pancreatic necrosis was found in control animals (0.3 +/- 0.1) or animals with mild AP (0.6 +/- 0.1) killed at 96 hours. Necrosis scores were 1.1 +/- 0.2 for animals with moderate AP and 1.9 +/- 0.2 for animals with severe AP. Control animals did not develop significant bacterial infection of the pancreas (> or = 10(3) CFU/g). At 96 hours, the prevalence of infection was 37.5% in animals with mild AP and 50% in animals with moderate AP. In animals with severe AP, infection of the pancreas increased from 33% in the first 24 hours to 75% between 48 and 96 hours (p < 0.05). The bacterial counts and the number of different species increased with time and was maximal (> 10(11) CFU/g) at 96 hours.
CONCLUSION
Bacterial infection of the pancreas in rodent AP increases during the first several days, and its likelihood correlates with the severity of the disease. This model, which closely mimics the features of human acute pancreatitis, provides a unique opportunity to study the pathogenesis of infected necrosis and test therapeutic strategies.
Topics: Acute Disease; Animals; Bacterial Infections; Ceruletide; Colony Count, Microbial; Disease Models, Animal; Edema; Enterococcus; Escherichia coli Infections; Glycodeoxycholic Acid; Gram-Positive Bacterial Infections; Leukocytes; Male; Necrosis; Pancreas; Pancreatitis; Rats; Rats, Sprague-Dawley; Staphylococcal Infections; Survival Rate; Time Factors
PubMed: 8053741
DOI: 10.1097/00000658-199408000-00011 -
International Journal of STD & AIDS Feb 2008One thousand and eighty-one evaluable HIV-infected patients were assessed for pancreatic abnormalities in a prospective case-control study including the whole follow-up...
One thousand and eighty-one evaluable HIV-infected patients were assessed for pancreatic abnormalities in a prospective case-control study including the whole follow-up period of each patient (minimum 12 months). The 435 patients (40.2%), who experienced at least one episode of confirmed pancreatic laboratory abnormality had a longer duration of seropositivity, exposure to protease inhibitors, a more frequent immunodeficiency, AIDS, chronic liver and/or biliary disease and hypertriglyceridaemia, while no relation was found with antiretroviral administration, and the duration of type of nucleoside analogues, when compared with the 646 controls. High and prolonged laboratory alterations eventually associated with signs of organ involvement occurred in 166 cases (38.2%), and were related to the administration of didanosine, stavudine, lamivudine, pentamidine, cotrimoxazole or antitubercular/antimycobacterial therapy, cytotoxic chemotherapy, illicit substance or alcohol abuse, opportunistic infections, chronic liver and/or biliary disease, a protease inhibitor-based highly active antiretroviral therapy (HAART) and hypertriglyceridaemia (usually associated with HAART administration). No difference was noticed between the 46 patients with clinical and/or imaging evidence of pancreatic involvement and the 120 asymptomatic subjects. Although recurrences of enzyme alterations involved 69.6% of patients, only in 30.1% of cases did a change of the underlying antiretroviral or antimicrobial therapy become necessary. An acute, uncomplicated pancreatitis occurred in nine of the 46 symptomatic subjects (19.6%). A two to four week gabexate and/or octreotide administration (performed in 79 cases of 166, 47.6%), achieved a significant laboratory, clinical and imaging cure or improvement in 82.3% of cases, with a better success rate of combined (gabexate mesilate plus octreotide) vs. single (gabexate mesilate or ocreotide) therapy. Reduced disease recurrences and a better tolerability of antiretroviral regimens, were also noticed.
Topics: Adult; Amylases; Anti-Bacterial Agents; Anti-Retroviral Agents; Antitubercular Agents; Case-Control Studies; Female; HIV Infections; Humans; Isoamylase; Lipase; Male; Pancreas; Pancreatic Diseases; Practice Guidelines as Topic; Prospective Studies; Risk Factors
PubMed: 18334062
DOI: 10.1258/ijsa.2007.007076 -
Cell Reports Mar 2022Concerns that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), may cause...
Concerns that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), may cause new-onset diabetes persist in an evolving research landscape, and precise risk assessment is hampered by, at times, conflicting evidence. Here, leveraging comprehensive single-cell analyses of in vitro SARS-CoV-2-infected human pancreatic islets, we demonstrate that productive infection is strictly dependent on the SARS-CoV-2 entry receptor ACE2 and targets practically all pancreatic cell types. Importantly, the infection remains highly circumscribed and largely non-cytopathic and, despite a high viral burden in infected subsets, promotes only modest cellular perturbations and inflammatory responses. Similar experimental outcomes are also observed after islet infection with endemic coronaviruses. Thus, the limits of pancreatic SARS-CoV-2 infection, even under in vitro conditions of enhanced virus exposure, challenge the proposition that in vivo targeting of β cells by SARS-CoV-2 precipitates new-onset diabetes. Whether restricted pancreatic damage and immunological alterations accrued by COVID-19 increase cumulative diabetes risk, however, remains to be evaluated.
Topics: COVID-19; Diabetes Mellitus; Humans; Insulin-Secreting Cells; Pancreas; SARS-CoV-2
PubMed: 35247306
DOI: 10.1016/j.celrep.2022.110508 -
Virulence Dec 2019Enteroviral infections are frequent, often asymptomatic in humans and during gravidity. The present study is an extension of our previous investigations where we had...
Enteroviral infections are frequent, often asymptomatic in humans and during gravidity. The present study is an extension of our previous investigations where we had shown pancreatitis in challenged pups of CVB4-E2-infected dams. Present investigation describes the effect of gestational infection with this virus on the pancreas of both dams and their challenged pups. Gravid CD1 outbred mice were orally infected with CVB4-E2 virus at different gestation times. Pups were challenged orally with the same virus after 25 days of birth. Organs were collected at selected intervals postinfection (p.i.), and replicating virus and viral-RNA copies were analyzed. Additional readouts included histopathology and immunohistochemical (IHC) analysis for localization and identification of Ly6G+ cells (neutrophils), CD11b+ cells (macrophages), and viral protein in pancreatic tissue sections of the infected dams and their challenged pups. Our results show the presence of replicating virus in the pancreas of infected dams and their challenged pups, with inflammation leading to chronic necrotizing pancreatitis and atrophy of pancreatic acini of the dams and their offspring. IHC analysis of the infiltrating cells showed pronounced Ly6G+ neutrophils in dams only, whereas CD11b+ macrophages were present in tissues of both, the pups and the dams. Time of infection during gravidity as well as the p.i. intervals when mice were sacrificed influenced the pancreatic pathophysiology in both groups. We conclude that coxsackievirus infection during pregnancy is a risk factor for chronic affliction of the exocrine tissue and could affect endocrine pancreas in the mother and child.
Topics: Animals; Coxsackievirus Infections; Disease Models, Animal; Female; Infectious Disease Transmission, Vertical; Mice; Pancreas; Pancreatitis; Pregnancy; RNA, Viral; Virus Replication
PubMed: 30829107
DOI: 10.1080/21505594.2019.1589364 -
The American Surgeon Jan 2002Infection remains the greatest risk for victims of penetrating abdominal injury with major infections occurring in 10 to 15 per cent. Attributable mortality is... (Review)
Review
Infection remains the greatest risk for victims of penetrating abdominal injury with major infections occurring in 10 to 15 per cent. Attributable mortality is approximately 30 per cent of those who develop major abdominal infections. In addition to this morbidity infection adds approximately $43,000.00 of hospital charges per infected patients. This article addresses two significant areas: risk factors and antibiotic utilization. The most important risk factor is the presence of hollow viscus injury; colonic wounding carries the highest incidence of infection relative to intra-abdominal organs injured. Pancreatic and liver injuries significantly increase infection risk when combined with hollow viscus wounds. The degree of injury as measured by the volume of hemorrhage and the presence of shock as well as the anatomic degree of injury likewise correlates with the incidence of septic morbidity. Antibiotic utilization is addressed by the three issues of antibiotic agents of choice, duration of administration, and optimal dosing. Regimens of choice should include anaerobic coverage. Twenty-four hours of antibiotic administration is satisfactory with currently available agents. Evidence-based medicine analyses from the Eastern Association for the Surgery of Trauma have addressed those two issues. There are few data on optimal dosing. Increased volumes of distribution and rates of excretion have been demonstrated in trauma patients. This would suggest that higher-than-normal doses should be used. Laboratory studies would support such an approach. However, significant clinical research is desirable to address issues of concentration-dependent bacterial killing and time-dependent killing. Those pharmacodynamic considerations are variable among antibiotic classes.
Topics: Abdominal Injuries; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Colon; Humans; Injury Severity Score; Liver; Pancreas; Risk Factors; Shock, Hemorrhagic; Wounds, Penetrating
PubMed: 12467313
DOI: No ID Found -
Parasitology Research Mar 2017The parasite Trypanosoma cruzi causes a persistent infection, Chagas disease, affecting millions of persons in endemic areas of Latin America. As a result of... (Review)
Review
The parasite Trypanosoma cruzi causes a persistent infection, Chagas disease, affecting millions of persons in endemic areas of Latin America. As a result of immigration, this disease has now been diagnosed in non-endemic areas worldwide. Although, the heart and gastrointestinal tract are the most studied, the insulin-secreting β cell of the endocrine pancreas is also a target of infection. In this review, we summarize available clinical and laboratory evidence to determine whether T. cruzi-infection-mediated changes of β cell function is likely to contribute to the development of hyperglycemia and diabetes. Our literature survey indicates that T. cruzi infection of humans and of experimental animals relates to altered secretory behavior of β cells. The mechanistic basis of these observations appears to be a change in stimulus-secretion pathway function rather than the loss of insulin-producing β cells. Whether this attenuated insulin release ultimately contributes to the pathogenesis of diabetes in human Chagas disease, however, remains to be determined. Since the etiologies of diabetes are multifactorial including genetic and lifestyle factors, the use of cell- and animal-based investigations, allowing direct manipulation of these factors, are important tools in testing if reduced insulin secretion has a causal influence on diabetes in the setting of Chagas disease. Long-term clinical investigations will be required to investigate this link in humans.
Topics: Animals; Chagas Disease; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Pancreas; Trypanosoma cruzi
PubMed: 28013375
DOI: 10.1007/s00436-016-5350-5