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EBioMedicine Aug 2017Type 1 diabetes (T1D) has been associated with both genetic and environmental factors. Increasing incidence of T1D worldwide is prompting researchers to adopt different... (Review)
Review
Type 1 diabetes (T1D) has been associated with both genetic and environmental factors. Increasing incidence of T1D worldwide is prompting researchers to adopt different approaches to explain the biology of T1D, beyond the presence and activity of autoreactive lymphocytes. In this review, we propose inflammatory pathways as triggers for T1D. Within the scope of those inflammatory pathways and in understanding the pathogenesis of disease, we suggest that viruses, in particular Coxsackieviruses, act by causing a type 1 interferonopathy within the pancreas and the microenvironment of the islet. As such, this connection and common thread represents an exciting platform for the development of new diagnostic, treatment and/or prevention options.
Topics: Animals; Cellular Microenvironment; Coxsackievirus Infections; Diabetes Mellitus, Type 1; Immunity, Innate; Interferons; Islets of Langerhans; Pancreatic Diseases; Signal Transduction
PubMed: 28663145
DOI: 10.1016/j.ebiom.2017.06.014 -
AJR. American Journal of Roentgenology Aug 2021The purpose of this study was to evaluate the safety and efficacy of percutaneous drainage of peripancreatic fluid collections after pancreas transplant and to...
The purpose of this study was to evaluate the safety and efficacy of percutaneous drainage of peripancreatic fluid collections after pancreas transplant and to determine factors predicting a successful clinical outcome. This single-center retrospective study included 28 patients who underwent percutaneous drainage for peripancreatic collections after transplant between January 2008 and December 2018. Clinical success was defined as drainage resulting in resolution of symptoms. Primary clinical success was defined as symptom resolution after the initial drainage procedure, and secondary success was defined as symptom resolution after additional drainage procedures. Operative intervention or death was considered clinical failure. Patient, collection, and procedural factors were assessed for their potential impact on the clinical outcome. Clinical success was achieved in 23 of 28 drainage procedures (82.1%), with primary success in 15 procedures. Of the five patients with failed drainage procedures, three required pancreatectomies, one required surgical washout, and one died from a disseminated infection. The median duration of drainage in the clinical success group was 25 days (range, 3-136 days), and patients with longer drainage periods had more successful outcomes ( = .04). Graft pancreatitis was diagnosed in five patients (17.9%) and was not associated with drainage outcome ( = .21). Collections were positive for bacterial growth in 13 patients (46.4%) and were high in amylase in 12 (42.9%). We observed drainage failure in collections with polymicrobial growth and in the presence of fistulas ( = .05 and = .07, respectively). Patients with successful outcomes had smaller collection volumes ( = .045). No complications attributed to drainage were encountered. Percutaneous drainage is safe and effective for management of peripancreatic fluid collections after pancreas transplant.
Topics: Adult; Body Fluids; Drainage; Female; Humans; Male; Pancreas; Pancreas Transplantation; Postoperative Complications; Retrospective Studies; Treatment Outcome
PubMed: 34036810
DOI: 10.2214/AJR.20.23059 -
Journal of Immunology (Baltimore, Md. :... Nov 2023Environmental factors and host microbiota strongly influence type 1 diabetes (T1D) progression. We report that neonatal immunization with group A Streptococcus...
Environmental factors and host microbiota strongly influence type 1 diabetes (T1D) progression. We report that neonatal immunization with group A Streptococcus suppresses T1D development in NOD mice by promoting clonal expansion of N-acetyl-d-glucosamine (GlcNAc)-specific B-1 B cells that recognize pancreatic β cell-derived Ags bearing GlcNAc-containing posttranslational modifications. Early exposure to Lancefield group A cell-wall carbohydrate Ags increased production of GlcNAc-reactive serum Abs and enhanced localization of innate-like GlcNAc-specific B cells to pancreatic tissue during T1D pathogenesis. We show that B-1 B cell-derived GlcNAc-specific IgM engages apoptosis-associated β cell Ags, thereby suppressing diabetogenic T cell activation. Likewise, adoptively transferring GlcNAc-reactive B-1 B cells significantly delayed T1D development in naive recipients. Collectively, these data underscore potentially protective involvement of innate-like B cells and natural Abs in T1D progression. These findings suggest that previously reported associations of reduced T1D risk after GAS infection are B cell dependent and demonstrate the potential for targeting the natural Ab repertoire in considering therapeutic strategies for T1D.
Topics: Mice; Animals; Diabetes Mellitus, Type 1; Mice, Inbred NOD; Glucosamine; Acetylglucosamine; Pancreas
PubMed: 37747293
DOI: 10.4049/jimmunol.2300264 -
Frontiers in Cellular and Infection... 2023
Topics: Humans; Pancreatitis; Acute Disease; Pancreas; Infections
PubMed: 37026058
DOI: 10.3389/fcimb.2023.1175195 -
Acta Physiologica (Oxford, England) Dec 2021The molecular link between SARS-CoV-2 infection and susceptibility is not well understood. Nonetheless, a bi-directional relationship between SARS-CoV-2 and diabetes has... (Review)
Review
The molecular link between SARS-CoV-2 infection and susceptibility is not well understood. Nonetheless, a bi-directional relationship between SARS-CoV-2 and diabetes has been proposed. The angiotensin-converting enzyme 2 (ACE2) is considered as the primary protein facilitating SARS-CoV and SARS-CoV-2 attachment and entry into the host cells. Studies suggested that ACE2 is expressed in the endocrine cells of the pancreas including beta cells, in addition to the lungs and other organs; however, its expression in the islets, particularly beta cells, has been met with some contradiction. Importantly, ACE2 plays a crucial role in glucose homoeostasis and insulin secretion by regulating beta cell physiology. Given the ability of SARS-CoV-2 to infect human pluripotent stem cell-derived pancreatic cells in vitro and the presence of SARS-CoV-2 in pancreatic samples from COVID-19 patients strongly hints that SARS-CoV-2 can invade the pancreas and directly cause pancreatic injury and diabetes. However, more studies are required to dissect the underpinning molecular mechanisms triggered in SARS-CoV-2-infected islets that lead to aggravation of diabetes. Regardless, it is important to understand the function of ACE2 in the pancreatic islets to design relevant therapeutic interventions in combatting the effects of SARS-CoV-2 on diabetes pathophysiology. Herein, we detail the function of ACE2 in pancreatic beta cells crucial for regulating insulin sensitivity, secretion, and glucose metabolism. Also, we discuss the potential role played by ACE2 in aiding SARS-COV-2 entry into the pancreas and the possibility of ACE2 cooperation with alternative entry factors as well as how that may be linked to diabetes pathogenesis.
Topics: Angiotensin-Converting Enzyme 2; COVID-19; Diabetes Mellitus; Humans; Insulin-Secreting Cells; SARS-CoV-2
PubMed: 34561952
DOI: 10.1111/apha.13733 -
Scientific Reports Jul 2020Infection by hepatitis E virus (HEV) via the oral route causes acute hepatitis. Extra-hepatic manifestations of HEV infection may stem from various causes; however, its...
Infection by hepatitis E virus (HEV) via the oral route causes acute hepatitis. Extra-hepatic manifestations of HEV infection may stem from various causes; however, its distribution in organs such as the liver, as well as the mechanisms underlying HEV-induced cell injury, remain unclear. The objective of this study was to determine the chronological distribution of HEV in various tissues of HEV-challenged miniature pigs and to investigate the mechanisms underlying HEV-induced cell death in the pancreas and liver. Virological and serological analyses were performed on blood and faecal samples. Histopathology of the liver and extra-hepatic tissues was analysed. Cell death pathways and immune cell characterisation in inflammatory lesions were analysed using immunohistochemistry. The liver and pancreas displayed inflammation and cellular injury, and a large amount of HEV was observed in the lesions. The liver was infiltrated by T and natural killer cells. HEV was identified in all organs except the heart, and was associated with immune cells. Although the liver and the pancreas strongly expressed TNF-α and TRAIL, TUNEL assay results were negative. RIP3 and pMLKL were expressed in the pancreas. RIP3, but not pMLKL, was expressed in the liver. Pancreatitis induced in HEV-infected miniature pigs is associated with necroptosis.
Topics: Animals; Disease Models, Animal; Feces; Hepatitis E; Hepatitis E virus; Killer Cells, Natural; Liver; Necroptosis; Pancreas; Pancreatitis; RNA, Viral; Reverse Transcriptase Polymerase Chain Reaction; Swine; Swine Diseases; Swine, Miniature; T-Lymphocytes
PubMed: 32694702
DOI: 10.1038/s41598-020-68959-3 -
Biochimica Et Biophysica Acta.... Apr 2018The pathophysiology of immunoglobulin G4-related disease (IgG4-RD) and its most common manifestations, IgG4-associated (sclerosing) cholangitis and autoimmune... (Review)
Review
The pathophysiology of immunoglobulin G4-related disease (IgG4-RD) and its most common manifestations, IgG4-associated (sclerosing) cholangitis and autoimmune pancreatitis, remains largely unknown, but IgG4 is presumably involved. IgG4 is a promiscuous antibody, which could be directly pathogenic, fulfill a protective role, or could just be a fortuitous marker of an aberrant inflammatory response. IgG4 antibodies possess exclusive structural and functional characteristics suggesting anti-inflammatory and tolerance-inducing effects. By studying the role of IgG4 in other inflammatory conditions, namely hypersensitivity and allergies, autoimmune and immune-mediated diseases, infections and malignancies, new insights can be obtained increasing our understanding of the role of IgG4 antibodies in IgG4-RD. Beekeepers, animal laboratory workers and individuals undergoing allergen immunotherapy possess high serum levels of allergen-specific IgG4, which exhibit immunosuppressive functions, protecting the individual from anaphylactic reactions. In autoimmune/immune-mediated diseases, such as pemphigus vulgaris, pemphigus foliaceus and MuSK-myasthenia gravis, IgG4 autoantibodies are pathogenic. Regarding malignancies such as melanoma and cholangiocarcinoma or helminthic infections, IgG4 antibodies inhibit clearance of tumor cells or the invader, respectively. Translating these findings to IgG4-RD, IgG4 alone can implement pathogenic effects and structural damage, but may also function as a protective antibody dampening the more harmful effects of IgG1 when directed against the same epitopes. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.
Topics: Autoantibodies; Autoimmune Diseases; Bile Duct Neoplasms; Bile Ducts; Cholangiocarcinoma; Cholangitis, Sclerosing; Helminthiasis; Humans; Hypersensitivity; Immunoglobulin G; Myasthenia Gravis; Pancreas; Pancreatitis
PubMed: 28782655
DOI: 10.1016/j.bbadis.2017.07.038 -
ANZ Journal of Surgery Jan 2021Pancreatic trauma is rare and complex. Non-operative management of pancreatic injuries is often appropriate, and when surgical intervention is required there may be a...
BACKGROUND
Pancreatic trauma is rare and complex. Non-operative management of pancreatic injuries is often appropriate, and when surgical intervention is required there may be a choice between resectional or more conservative approaches. This is especially true for distal injuries. Operative management of proximal pancreatic injuries is extremely challenging and has less room for conservatism. We sought to characterize the surgical treatment of pancreatic injuries, comparing outcomes for those undergoing formal resection (FR) versus those undergoing more conservative surgical treatment. Our hypothesis was that 'biting the bullet' and resecting is not associated with worse outcomes than less invasive approaches.
METHODS
All patients undergoing surgery for pancreatic injuries between June 2001 and June 2019 at the Alfred Hospital in Melbourne were included. Outcome measures including length of stay, return to theatre, total parenteral nutrition use, pancreatic fistula, intra-abdominal infection and mortality were compared between patients undergoing FR and those undergoing non-resectional procedures.
RESULTS
Of nearly 60 000 trauma presentations, 194 patients sustained pancreatic injury and 51 underwent surgical intervention. Over 70% were secondary to blunt trauma. There were 27 FR and 22 non-resectional procedures. No major outcome differences were detected. FR was not associated with worse outcomes.
CONCLUSION
In distal injuries, where there is doubt regarding parenchymal viability or ductal integrity, FR can safely be performed with non-inferior outcomes to more conservative surgery. Patients with high-grade proximal injuries will usually have multiple other injuries and require resuscitation, temporization and staged reconstruction.
Topics: Abdominal Injuries; Australia; Humans; Pancreas; Pancreatectomy; Pancreatic Fistula; Retrospective Studies; Wounds, Nonpenetrating
PubMed: 33369826
DOI: 10.1111/ans.16498 -
European Review For Medical and... Nov 2020Diabetes is a lifestyle disease and it has become an epidemic worldwide in recent decades. In the ongoing COVID-19 pandemic situation, diabetes has become a serious... (Review)
Review
OBJECTIVE
Diabetes is a lifestyle disease and it has become an epidemic worldwide in recent decades. In the ongoing COVID-19 pandemic situation, diabetes has become a serious health concern since large numbers of patients are vulnerable to die from the virus. Thus, diabetic patients affected by COVID-19 cause a major health crisis now. Reports show that large occurrence of diabetes makes it a serious comorbidity in COVID-19 patients.
MATERIALS AND METHODS
It is crucial to understand how COVID-19 affects diabetes patients. This paper has reviewed published literature extensively to understand the pattern, importance, care, and medication.
RESULTS
This review summarizes the association between COVID-19 and diabetes in terms of susceptibility for pneumonia and other diseases. It also discusses the harshness of COVID-19 with diabetes populations and immunological impacts. It further adds the ACE2 receptor role in diabetes with COVID-19 patients.
CONCLUSIONS
Finally, this paper illustrates different types of diabetes management techniques, such as blood glucose management, self-management, mental health management, and therapeutic management. It also summarizes the current knowledge about diabetic patients with COVID-19 to fight this pandemic.
Topics: Angiotensin-Converting Enzyme 2; Betacoronavirus; Blood Glucose; COVID-19; Comorbidity; Coronavirus Infections; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Susceptibility; Humans; Hypoglycemic Agents; Pancreas; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; SARS-CoV-2; Severity of Illness Index; Spike Glycoprotein, Coronavirus; Virus Replication
PubMed: 33215463
DOI: 10.26355/eurrev_202011_23634 -
The Journal of Endocrinology Dec 2021We review the current knowledge of pancreas pathology in type 1 diabetes. During the last two decades, dedicated efforts toward the recovery of pancreas from deceased... (Review)
Review
We review the current knowledge of pancreas pathology in type 1 diabetes. During the last two decades, dedicated efforts toward the recovery of pancreas from deceased patients with type 1 diabetes have promoted significant advances in the characterization of the pathological changes associated with this condition. The implementation of autoantibody screening among organ donors has also allowed examining pancreas pathology in the absence of clinical disease, but in the presence of serological markers of autoimmunity. The assessment of key features of pancreas pathology across various disease stages allows driving parallels with clinical disease stages. The main pathological abnormalities observed in the pancreas with type 1 diabetes are beta-cell loss and insulitis; more recently, hyperexpression of HLA class I and class II molecules have been reproduced and validated. Additionally, there are changes affecting extracellular matrix components, evidence of viral infections, inflammation, and ER stress, which could contribute to beta-cell dysfunction and the stimulation of apoptosis and autoimmunity. The increasing appreciation that beta-cell loss can be less severe at diagnosis than previously estimated, the coexistence of beta-cell dysfunction, and the persistence of key features of pancreas pathology for years after diagnosis impact the perception of the dynamics of this chronic process. The emerging information is helping the identification of novel therapeutic targets and has implications for the design of clinical trials.
Topics: Autoimmunity; Autopsy; Diabetes Mellitus, Type 1; Disease Progression; Endocrinology; History, 20th Century; History, 21st Century; Humans; Pancreas
PubMed: 34755679
DOI: 10.1530/JOE-21-0358