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The Journal of Nutrition Feb 2018The SLC39A family of metal transporters was identified through homologies with the Zrt- and Irt-like (ZIP) proteins from yeast and plants. Of all the ZIP transporters,... (Review)
Review
The SLC39A family of metal transporters was identified through homologies with the Zrt- and Irt-like (ZIP) proteins from yeast and plants. Of all the ZIP transporters, ZIP14 is arguably the most robustly characterized in terms of function at the integrative level. Mice with a global knockout of Zip14 are viable, thus providing the opportunity to conduct physiologic experiments. In mice, Zip14 expression is highly tissue specific, with the greatest abundance in the jejunum > liver > heart > kidney > white adipose tissue > skeletal muscle > spleen > pancreas. A unique feature of Zip14 is its upregulation by proinflammatory conditions, particularly increased interleukin 6 (IL-6) and nitric oxide. The transcription factors AP-1, ATF4, and ATF6α are involved in Zip14 regulation. ZIP14 does not appear to be zinc-regulated. The Zip14 knockout phenotype shows multiple sites of ZIP14 function, including the liver, adipose tissue, brain, pancreas, and bone. A prominent feature of the Zip14 ablation is a reduction in intestinal barrier function and onset of metabolic endotoxemia. Many aspects of the phenotype are accentuated with age and accompany increased circulating IL-6. Studies with 65Zn, 59Fe [nontransferrin-bound iron (NTBI)] and 54Mn show that ZIP14 transports these metals. At a steady state, the plasma concentrations of zinc, NTBI, and manganese are such that zinc ions are the major substrate available for ZIP14 at the cell surface. Upregulation of ZIP14 accounts for the hypozincemia and hepatic zinc accumulation associated with acute inflammation and sepsis and is required for liver regeneration and resistance to endoplasmic reticulum (ER) stress. Zip14 ablation in mice produces a defect in manganese excretion that leads to excess manganese accumulation in the brain that produces characteristics of Parkinsonism.
Topics: Adipose Tissue; Animals; Biological Transport; Bone and Bones; Brain; Cation Transport Proteins; Endotoxemia; Interleukin-6; Intestines; Iron; Liver; Manganese; Mice; Mice, Knockout; Neoplasms; Nitric Oxide; Pancreas; Tissue Distribution; Zinc
PubMed: 29490098
DOI: 10.1093/jn/nxx041 -
Journal of Molecular Medicine (Berlin,... Aug 2023Altered circulating hormone and metabolite levels have been reported during and post-COVID-19. Yet, studies of gene expression at the tissue level capable of identifying...
Altered circulating hormone and metabolite levels have been reported during and post-COVID-19. Yet, studies of gene expression at the tissue level capable of identifying the causes of endocrine dysfunctions are lacking. Transcript levels of endocrine-specific genes were analyzed in five endocrine organs of lethal COVID-19 cases. Overall, 116 autoptic specimens from 77 individuals (50 COVID-19 cases and 27 uninfected controls) were included. Samples were tested for the SARS-CoV-2 genome. The adrenals, pancreas, ovary, thyroid, and white adipose tissue (WAT) were investigated. Transcript levels of 42 endocrine-specific and 3 interferon-stimulated genes (ISGs) were measured and compared between COVID-19 cases (virus-positive and virus-negative in each tissue) and uninfected controls. ISG transcript levels were enhanced in SARS-CoV-2-positive tissues. Endocrine-specific genes (e.g., HSD3B2, INS, IAPP, TSHR, FOXE1, LEP, and CRYGD) were deregulated in COVID-19 cases in an organ-specific manner. Transcription of organ-specific genes was suppressed in virus-positive specimens of the ovary, pancreas, and thyroid but enhanced in the adrenals. In WAT of COVID-19 cases, transcription of ISGs and leptin was enhanced independently of virus detection in tissue. Though vaccination and prior infection have a protective role against acute and long-term effects of COVID-19, clinicians must be aware that endocrine manifestations can derive from virus-induced and/or stress-induced transcriptional changes of individual endocrine genes. KEY MESSAGES: • SARS-CoV-2 can infect adipose tissue, adrenals, ovary, pancreas and thyroid. • Infection of endocrine organs induces interferon response. • Interferon response is observed in adipose tissue independently of virus presence. • Endocrine-specific genes are deregulated in an organ-specific manner in COVID-19. • Transcription of crucial genes such as INS, TSHR and LEP is altered in COVID-19.
Topics: Female; Humans; COVID-19; SARS-CoV-2; Interferons; Pancreas
PubMed: 37246981
DOI: 10.1007/s00109-023-02334-3 -
International Journal of Surgery... Apr 2016Acute pancreatitis may have a wide range of severity, from a clinically self-limiting to a quickly fatal course. Necrotizing pancreatitis (NP) is the most dreadful... (Review)
Review
Acute pancreatitis may have a wide range of severity, from a clinically self-limiting to a quickly fatal course. Necrotizing pancreatitis (NP) is the most dreadful evolution associated to a poor prognosis: mortality is approximately 15% and up to 30-39% in case of infected necrosis, which is the major cause of death. Intervention is generally required for infected pancreatic necrosis and less commonly in patients with sterile necrosis who are symptomatic (gastric or duodenal outlet or biliary obstruction). Traditionally the most widely used approach to infected necrosis has been open surgical necrosectomy, but it is burdened by high morbidity (34-95%) and mortality (11-39%) rates. In the last two decades the treatment of NP has significantly evolved from open surgery towards minimally invasive techniques (percutaneous catheter drainage, per-oral endoscopic, laparoscopy and rigid retroperitoneal videoscopy). The objective of this review is to summarize the current state of the art of the management of NP and to clarify some aspects about its diagnosis and treatment.
Topics: Debridement; Drainage; Humans; Laparoscopy; Pancreas; Pancreatitis, Acute Necrotizing; Postoperative Complications
PubMed: 26708848
DOI: 10.1016/j.ijsu.2015.12.038 -
Archivos Argentinos de Pediatria Feb 2023Pancreatic echinococcosis accounts for 0.2-0.6% of cases, with the pediatric population being at a higher risk. Most commonly, pancreatic lesions occur in the head of...
Pancreatic echinococcosis accounts for 0.2-0.6% of cases, with the pediatric population being at a higher risk. Most commonly, pancreatic lesions occur in the head of the pancreas (50-58%); and in the body and tail in 24-34% and 19% of cases, respectively. Given the potential complications, surgery is usually performed. Albendazole is recommended before and after the surgery due to the risks for rupture and dissemination of protoscolices. Here we describe the case of a 5-year-old girl with progressive abdominalpain and cystic lesion in the pancreas compatible with echinococcosis in the ultrasound. The computed tomography showed bile duct compression. Indirect hemagglutination was negative. She had elevated total bilirubin, with a clear predominance of direct bilirubin, and high liver enzymes. Exploratory laparotomy, cholecystectomy, and unroofing of the cyst were performed. The patient had a favorable course and continued with albendazole for 3 months after the surgery.
Topics: Female; Humans; Child; Child, Preschool; Albendazole; Pancreatic Diseases; Echinococcosis; Abdomen; Pancreas
PubMed: 36194666
DOI: 10.5546/aap.2021-02500.eng -
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 -
Asian Journal of Surgery Jan 2022This study is to assess immunological and graft survival outcomes after pancreas transplant at a single institute in Asia.
BACKGROUND/OBJECTIVE
This study is to assess immunological and graft survival outcomes after pancreas transplant at a single institute in Asia.
METHODS
Patients undergoing pancreas transplant with enteric drainage were included. Clinical data and outcomes were evaluated and compared between each subgroup.
RESULTS
There were 165 cases of pancreas transplant, including 38 (23 %) simultaneous pancreas-kidney transplant (SPK), 24 (15 %) pancreas after kidney transplant (PAK), 75 (46 %) pancreas transplant alone (PTA), and 28 (17 %) pancreas before kidney transplant (PBK). The overall surgical complication rate was 46.1 %, with highest (62.5 %) in PAK and lowest (32.0 %) in PTA, P = 0.008. The late complications included 32.7 % infection and 3.6 % malignancy. Overall rejection of pancreas graft was 24.8 % including 18.2 % acute and 9.7 % chronic rejection. Rejection was highest in PTA group (36.0 %) and lowest in PBK (3.6 %). There were 56 cases (33.9 %) with graft loss in total, with highest graft loss rate in PTA (38.7 %). The 1-year, 5-year and 10-year pancreas graft survivals for total patients were 98.0 %, 87.7 % and 70.9 % respectively.
CONCLUSIONS
Enteric drainage in pancreas transplant could be applied safely not only in SPK but also in other subgroups. Enteric drainage itself would not compromise the immunological and graft survival outcomes.
Topics: Drainage; Graft Rejection; Graft Survival; Humans; Pancreas; Pancreas Transplantation; Survival Rate
PubMed: 34364767
DOI: 10.1016/j.asjsur.2021.07.028 -
Le Infezioni in Medicina Dec 2020The gastrointestinal system may be affected by COVID-19 infection with an incidence variable from 3% up to 79%. Several works show that the pancreas, both in its... (Review)
Review
The gastrointestinal system may be affected by COVID-19 infection with an incidence variable from 3% up to 79%. Several works show that the pancreas, both in its exocrine and endocrine function, can be affected by this viral infection, although this organ has been poorly analyzed in this current epidemic context. This mini-review aims to provide a summary of available studies on exocrine pancreas involvement during COVID-19 infection. A search through MEDLINE/PubMed was conducted on the topic in hand. With regard to exocrine function, some studies highlight the presence of an associated hyperenzymemia (hyperamylasemia, hyperlipasemia), while others describe isolated and rare cases of acute pancreatitis. More attention should be paid to pancreatic impairment in subjects with COVID-19, as this may prove to be one of the elements aggravating its clinical course. Indeed, acute pancreatitis, especially when presenting in severe forms with hyperstimulation of the pro-inflammatory response, may represent a crucial factor in the progression of COVID-19, entailing both an increase in hospitalization days and in mortality rate.
Topics: COVID-19; Disease Progression; Humans; Hyperamylasemia; Lipase; Pancreas, Exocrine; Pancreatitis; SARS-CoV-2
PubMed: 33257624
DOI: No ID Found -
Gastroenterology May 2020
Topics: Channelopathies; Humans; Liver Cirrhosis; Macrophages; Pancreas; Pancreatitis, Chronic; Peritonitis; Phenotype
PubMed: 32205170
DOI: 10.1053/j.gastro.2020.03.027 -
Clinical Microbiology and Infection :... Sep 2014Solid organ transplantation (SOT) is an appropriate therapeutic option for HIV-infected patients with end-stage organ disease. Recent experience in North America and... (Review)
Review
Solid organ transplantation (SOT) is an appropriate therapeutic option for HIV-infected patients with end-stage organ disease. Recent experience in North America and Europe indicates that 3- to 5-year survival in HIV/HCV-coinfected liver recipients is lower than that of HCV-monoinfected recipients. Conversely, 3- to 5-year survival of non-HCV-coinfected transplant patients (liver, kidney and heart) was similar to that of non-HIV-infected patients. Preliminary experience with lung transplantation and combined kidney and pancreas transplantation is also satisfactory. Infections in HIV-infected recipients during the post-transplant period are similar to those seen in non-HIV-infected patients, although the incidence rates of tuberculosis and fungal infections seem to be higher. HIV-infected patients who are being evaluated for SOT should follow the same recommendations as those used for non-HIV-infected patients in order to prevent infections during the pre-transplant period. After transplantation, HIV-infected SOT recipients must follow recommendations on post-SOT and anti-HIV immunization and on antimicrobial prophylaxis. The recommended antiretroviral regimen is one based on raltegravir or dolutegravir plus two nucleos(t)ide reverse transcriptase inhibitors (tenofovir + emtricitabine or abacavir + lamivudine), because it can prevent pharmacokinetic interactions between antiretroviral drugs, immunosuppressive drugs and some of the antimicrobial agents used to treat or prevent post-transplant infections. In this manuscript, we review current recommendations for preventing infections both before and after transplantation. We also analyse the incidence, aetiology and clinical characteristics of opportunistic and non-opportunistic bacterial, mycobacterial, fungal and viral infections in HIV-infected SOT recipients during the post-transplant period.
Topics: Europe; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidence; Infection Control; North America; Opportunistic Infections; Organ Transplantation; Transplant Recipients
PubMed: 25040016
DOI: 10.1111/1469-0691.12754 -
Clinical and Experimental Immunology Jan 2019Enteroviruses (EV) have been historically associated to type 1 diabetes. Definitive proof for their implication in disease development is lacking, but growing evidence... (Review)
Review
Enteroviruses (EV) have been historically associated to type 1 diabetes. Definitive proof for their implication in disease development is lacking, but growing evidence suggests that they could be involved in beta cell destruction either directly by killing beta cells or indirectly by creating an exacerbated inflammatory response in the islets, capable of attracting autoreactive T cells to the 'scene of the crime'. Epidemiological and serological studies have been associated with the appearance of islet autoimmunity and EV RNA has been detected in prospective studies. In addition, the EV capsid protein has been detected in the islets of recent-onset type 1 diabetic donors, suggesting the existence of a low-grade EV infection that could become persistent. Increasing evidence in the field shows that a 'viral signature' exists in type 1 diabetes and involves interferon responses that could be sustained during prolonged periods. These include the up-regulation of markers such as protein kinase R (PKR), melanoma differentiation-associated protein 5 (MDA5), retinoic acid inducible gene I (RIG-I), myxovirus resistance protein (MxA) and human leukocyte antigen-I (HLA-I) and the release of chemokines able to attract immune cells to the islets leading to insulitis. In this scenario, the hyperexpression of HLA-I molecules would promote antigen presentation to autoreactive T cells, favoring beta cell recognition and, ultimately, destruction. In this review, an overview is provided of the standing evidence that implicates EVs in beta cell 'murder', the time-line of events is investigated from EV entry in the cell to beta cell death and possible accomplices are highlighted that might be involved in beta cell demise.
Topics: Animals; Apoptosis; Autoimmunity; Diabetes Mellitus, Type 1; Enterovirus; Enterovirus Infections; Gene Expression Regulation; Humans; Insulin-Secreting Cells; Interferons; T-Lymphocytes
PubMed: 30307605
DOI: 10.1111/cei.13223