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2.
World J Gastroenterol ; 27(35): 5796-5802, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34629803

RESUMO

Drug-induced pancreatitis is a gastrointestinal adverse effect concerning about 2% of drugs. The majority of cases are mild to moderate but severe episodes can also occur, leading to hospitalization or even death. Unfortunately, the mechanisms of this adverse reaction are still not clear, hindering its prevention, and the majority of data available of this potentially life-threatening adverse effect are limited to case reports leading to a probable underestimation of this event. In particular, in this editorial, special attention is given to thiopurine-induced pancreatitis (TIP), an idiosyncratic adverse reaction affecting around 5% of inflammatory bowel disease (IBD) patients taking thiopurines as immunosuppressants, with a higher incidence in the pediatric population. Validated biomarkers are not available to assist clinicians in the prevention of TIP, also because of the inaccessibility of the pancreatic tissue, which limits the possibility to perform dedicated cellular and molecular studies. In this regard, induced pluripotent stem cells (iPSCs) and the exocrine pancreatic differentiated counterpart could be a great tool to investigate the cellular and molecular mechanisms underlying the development of this undesirable event. This particular type of stem cells is obtained by reprogramming adult cells, including fibroblasts and leukocytes, with a set of transcription factors known as the Yamanaka's factors. Maintaining unaltered the donors' genetic heritage, iPSCs represent an innovative model to study the mechanisms of adverse drug reactions in individual patients' tissues not easily obtainable from human probands. Indeed, iPSCs can differentiate under adequate stimuli into almost any somatic lineage, opening a new world of opportunities for researchers. Several works are already available in the literature studying liver, central nervous system and cardiac cells derived from iPSCs and adverse drug effects. However, to our knowledge no studies have been performed on exocrine pancreas differentiated from iPSCs and drug-induced pancreatitis, so far. Hence, in this editorial we focus specifically on the description of the study of the mechanisms of TIP by using IBD patient-specific iPSCs and exocrine pancreatic differentiated cells as innovative in vitro models.


Assuntos
Células-Tronco Pluripotentes Induzidas , Pancreatite , Preparações Farmacêuticas , Diferenciação Celular , Criança , Humanos , Pâncreas , Pancreatite/induzido quimicamente
3.
Phytother Res ; 35(11): 6472-6485, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34661951

RESUMO

Acute pancreatitis (AP) is an acute inflammatory condition of the pancreas. Previous studies have shown that rutaecarpine (RUT), an important alkaloid component of Evodia rutaecarpa, exhibits certain protective effects against AP in rats by upregulating calcitonin gene-related peptide (CGRP). However, the molecular mechanism of RUT in AP remains unknown. This study aimed to investigate the effects of RUT on cerulein-induced AP in vivo and in vitro, and to explore the underlying molecular mechanisms. In cerulein/LPS-treated wild-type mice, but not CGRP gene knock-out mice, RUT significantly ameliorated pancreatic inflammation by alleviating histopathological changes, reducing IL-6 and TNF-α levels, and increasing in IL-10 levels. Moreover, RUT improved AP by suppressing the MAPK and NF-κB signaling pathways. These effects were mostly mediated through CGRP. Cell-based studies revealed that RUT significantly improved cell viability while suppressing the apoptosis of AR42J cells with cerulein-induced AP, downregulating IL-6 and TNF-α, stimulating IL-10 release, and inhibiting MAPK, NF-κB, and STAT3 signaling activation, all in a CGRP-dependent manner. RUT ameliorated cerulein/LPS-induced AP inflammatory responses in mice and AR42J cells in a CGRP-dependent manner and thus may represent a potential therapeutic option for AP patients. Our study provides valuable insights for AP drug development.


Assuntos
NF-kappa B , Pancreatite , Doença Aguda , Animais , Calcitonina , Peptídeo Relacionado com Gene de Calcitonina , Ceruletídeo , Humanos , Alcaloides Indólicos , Camundongos , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Quinazolinas , Ratos
4.
Ulus Travma Acil Cerrahi Derg ; 27(6): 605-612, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34710231

RESUMO

BACKGROUND: Acute pancreatitis is an inflammatory disease accompanied by pancreatic inflammation characterized by acinar cell damage and leukocyte infiltration in the tissue. At present, mortality and morbidity rates are high despite the current treatment of pancreatitis; therefore, new studies and treatment studies are needed. In this study, the effects of alpha-tocopherol on different doses of L-arginine-induced experimental acute pancreatitis model were investigated. METHODS: Thirty adult male Sprague-Dawley albino rats were randomly divided into four groups; control (sham) group (n=6), acute pancreatitis group (n=8), low-dose alpha-tocopherol (200 mg/kg once intraperitoneal [IP]) group (n=8), and high dose alpha-tocopherol (400 mg/kg once ip) group (n=8). Experimental acute pancreatitis model was created by a single IP dose of 5 g/kg of L-arginine. Alpha-tocopherol was administered in a single dose intraperitoneally, 30 min before the creation of the experimental model of acute pancreatitis induced by L-arginine induction in Groups 3 and 4. Tissue and blood samples were taken under anesthesia 72 h after L-arginine injection; then the rats were sacrificed by decapitation. Serum amylase, lipase, interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-alpha, and C-reactive protein (CRP) levels were examined. Pancreatic tissue samples were examined under a light microscope for histopathological examination. RESULTS: When the acute pancreatitis group (Group 2) was compared to the control group (Group 1), serum amylase, lipase, IL-1ß, IL-6, TNF-alpha, and CRP levels were all significantly increased (p<0.05 for all). Histopathological examination showed significant difference in edema (p<0.001) and inflammation (p=0.007) scores. When the low (Group 3) and high (Group 4) dose alpha-tocopherol groups were compared to Group 2, amylase, lipase, IL-1ß, IL-6, TNF-alpha, and CRP parameters were statistically significantly lower (p<0.05 for all). In the histopathological comparison of Groups 2, 3, and 4, edema and inflammation scores were decreased in Groups 3 and 4 compared to Group 2. Comparing Group 4 to Group 3, lipase (p<0.01), IL-6 (p=0.038), and TNF-alpha (p=0.002) levels were significantly decreased; no significant difference was observed in the histopathological evaluation. CONCLUSION: Alpha-tocopherol was found to reduce inflammation and pancreatic damage in acute pancreatitis and was more effective in high doses.


Assuntos
Pancreatite , Doença Aguda , Animais , Masculino , Pâncreas , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Fator de Necrose Tumoral alfa , alfa-Tocoferol/farmacologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-34586307

RESUMO

Acute pancreatitis (AP) is an inflammatory disease associated with abdominal pain and elevated serum pancreatic enzymes. The most common etiologies are gallstones and alcoholism. Drug-induced AP is quite rare, lacks a solid understanding and has been occasionally reported. The diagnosis requires a great suspicion and a careful exclusion of other causes. We present a case of a 37-year-old man, previously diagnosed with leprosy that developed acute pancreatitis after starting the multibacillary polychemotherapy (PCT/MB). After a month of treatment and the discontinuation of the PCT/MB, the therapy was restarted and a new episode of AP occurred. Three months after this last episode, the PCT/MB was reintroduced, changing one of the medications and the patient had no recurrence of AP or other reactions. Therefore, it is important to take into account that there is a risk of acute pancreatitis in patients on multidrug therapy (MDT) for leprosy.


Assuntos
Hanseníase Multibacilar , Hanseníase , Pancreatite , Doença Aguda , Adulto , Quimioterapia Combinada , Humanos , Hansenostáticos/efeitos adversos , Hanseníase/complicações , Hanseníase/tratamento farmacológico , Masculino , Pancreatite/induzido quimicamente
6.
Medicine (Baltimore) ; 100(35): e27182, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477177

RESUMO

ABSTRACT: In this single-center retrospective study, we intended to evaluate the frequencies and characteristics of computed tomography findings of pancreatobiliary inflammation (PBI) in patients treated with lenvatinib and the relationship of these findings with treatment-planning changes.We included 78 patients (mean ±â€Šstandard deviation, 69.8 ±â€Š9.4 years, range: 39-84 years, 62 men) with hepatocellular carcinoma (n = 62) or thyroid carcinoma (n = 16) who received lenvatinib (June 2016-September 2020). Two radiologists interpreted the posttreatment computed tomography images and assessed the radiological findings of PBI (symptomatic pancreatitis, cholecystitis, or cholangitis). The PBI effect on treatment was statistically evaluated.PBI (pancreatitis, n = 1; cholecystitis, n = 7; and cholangitis, n = 2) was diagnosed in 11.5% (9/78) of the patients at a median of 35 days after treatment initiation; 6 of 9 patients discontinued treatment because of PBI. Three cases of cholecystitis and 1 of cholangitis were accompanied by gallstones, while the other 5 were acalculous. The treatment duration was significantly shorter in patients with PBI than in those without (median: 44 days vs. 201 days, P = .02). Overall, 9 of 69 patients without PBI showed asymptomatic gallbladder subserosal edema.Lenvatinib-induced PBI developed in 11.5% of patients, leading to a significantly shorter treatment duration. Approximately 55.6% of the PBI cases were acalculous. The recognition of this phenomenon would aid physicians during treatment planning in the future.


Assuntos
Antineoplásicos/efeitos adversos , Doenças Biliares/induzido quimicamente , Pancreatite/induzido quimicamente , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Biliares/diagnóstico por imagem , Doenças Biliares/epidemiologia , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pancreatite/diagnóstico por imagem , Pancreatite/epidemiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
7.
Environ Toxicol ; 36(12): 2392-2403, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34423886

RESUMO

Acute pancreatitis (AP) is one of the most common acute abdomen of digestive system and has the characteristics of dangerous condition and rapid development. Limonin has been confirmed to hold anti-inflammatory and antioxidant effects in various diseases. However, its potential beneficial effect on AP and the concrete mechanisms have never been revealed. Here, two mouse models were used to investigate the protective effects of limonin on AP, the caerulein-induced mild acute pancreatitis (MAP) model and L-arginine-induced severe AP (SAP) model. Firstly, it was found that limonin administration attenuated lipase and serum amylase levels and ameliorated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. Additionally, the amelioration of AP by limonin was associated with reduced levels of inflammation initiators (IL-6, IL-1ß, CCL2, and TNF-α). Mechanistically, we found that limonin suppressed the Janus Activating Kinase 2 (JAK2)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway, as evident by the decreased levels of JAK2 and p-STAT3. And activation of JAK2 using JAK2 activator rescued the protective effects of limonin on AP. Thus, our results demonstrate that limonin can ameliorate AP in two mice models via suppressing JAK2/STAT3 signaling pathway.


Assuntos
Limoninas , Pancreatite , Doença Aguda , Animais , Janus Quinase 2/metabolismo , Limoninas/toxicidade , Camundongos , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
8.
Paediatr Drugs ; 23(5): 457-463, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34351604

RESUMO

Asparaginase therapy is a vital agent in the treatment of acute lymphoblastic leukemia (ALL), with increasing evidence of its high importance in high-risk ALL populations. However, despite the clear clinical and biological benefits of asparaginase therapy, many patients experience toxicities. A well-known treatment-limiting toxicity is asparaginase-associated pancreatitis (AAP). If severe, it necessitates discontinuation of asparaginase therapy, which can lead to a higher risk of relapse in patients with ALL. New protocols for ALL therapy have increased overall total doses of asparaginase therapy in select high-risk populations and have incorporated longer half-life formulations of pegylated asparaginase. Treatment drug monitoring has also allowed assurance of adequate levels of asparagine depletion throughout treatment. It is currently unknown if these changes will increase rates of AAP. Interestingly, important pharmacogenomics data, such as single nucleotide polymorphisms, can identify patients at the highest risk for severe AAP. The incidence of AAP in recent trials, current pharmacogenomic data that could further our understanding of the disease, and the importance of cautiously re-exposing patients to further asparaginase treatment after an initial episode of AAP are discussed.


Assuntos
Antineoplásicos , Pancreatite , Leucemia-Linfoma Linfoblástico de Células Precursoras , Doença Aguda , Antineoplásicos/efeitos adversos , Asparaginase/efeitos adversos , Criança , Humanos , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
9.
Free Radic Biol Med ; 173: 29-40, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34246777

RESUMO

Acute pancreatitis (AP) is an inflammatory disorder associated with multiple organ failure. Pyroptosis and ferroptosis are two newly recognized cell death, and whether pyroptosis and ferroptosis are involved in AP remain largely elusive. The nature compound Wedelolactone (Wed) exhibits strong anti-inflammatory and antioxidant activities, the present study aims to investigate the effect of Wed on AP and unravel whether Wed could protect against AP and relevant lung injury against pyroptosis and ferroptosis. Our results showed that the pyroptosis inhibitor disulfiram or ferroptosis inhibitor ferrostatin-1 significantly alleviated AP and associated lung injury in the taurocholate or caerulein-induced murine AP model. Administration with Wed ameliorated AP and lung injury as evidenced by improved pathological injuries, reduced serum pancreatic digestive enzymes, and proinflammatory cytokines. The in vivo and in vitro data demonstrated that Wed broadly inhibited caspase1/caspase11 activation, reduced mature interleukin-1ß (IL-1ß) and N-terminal domain of gasdermin D (GSDMD-N) level. The oxidative stress and lipid peroxidation were also suppressed along with the up-regulation of the ferroptosis antagonism marker glutathione peroxidase-4 (GPX4) in Wed treatment group. Wed promoted the transcriptional activity and the selenium sensitivity of GPX4. Moreover, the protective effects of Wed in caerulein-stimulated pancreatic acinar cells were markedly abrogated by the down-regulation of GPX4. Collectively, our data suggest that pyroptosis and ferroptosis play crucial roles in AP. Wed mitigated AP and associated lung injury via GPX4 mediated suppression of pyroptosis and ferroptosis.


Assuntos
Ferroptose , Lesão Pulmonar , Pancreatite , Doença Aguda , Animais , Cumarínicos , Lesão Pulmonar/tratamento farmacológico , Camundongos , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Piroptose
10.
J Investig Med High Impact Case Rep ; 9: 23247096211035238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34293944

RESUMO

Drugs account for 2% of all the causes of acute pancreatitis. To date, there are approximately 26 reported cases of acute pancreatitis associated with the use of cannabis. We report the case of a 20-year-old male who presented with intractable nausea, vomiting, and epigastric pain and a lipase level of 1541 with reportedly no alcohol use, and no evidence of medication, biliary, or autoimmune etiology. However, the patient did endorse heavily smoking cannabis prior to symptom onset. He was instructed to abstain from cannabis use on discharge and has not presented to the hospital since this episode. The reporting of this case aims to increase awareness of cannabis as a differential diagnosis in cases of pancreatitis that is not due to typical etiologies such as gallstones, medications, and alcohol use. There has yet to be definitive evidence as to how cannabis can cause pancreatitis. Further studies must be conducted to better understand the association between cannabis use and acute pancreatitis and the mechanism by which cannabis affects the pancreas.


Assuntos
Cannabis , Pancreatite , Dor Abdominal , Doença Aguda , Adulto , Cannabis/efeitos adversos , Diagnóstico Diferencial , Humanos , Pancreatite/induzido quimicamente , Adulto Jovem
11.
J Vis Exp ; (172)2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34251363

RESUMO

Biliary acute pancreatitis induction by sodium taurocholate infusion has been widely used by the scientific community due to the representation of the human clinical condition and reproduction of inflammatory events corresponding to the onset of clinical biliary pancreatitis. The severity of pancreatic damage can be assessed by measuring the concentration, speed, and volume of the infused bile acid. This study provides an updated checklist of the materials and methods used in the protocol reproduction and shows the main results from this acute pancreatitis (AP) model. Most of the previous publications have limited themselves to reproducing this model in rats. We have applied this method in mice, which provides additional advantages (i.e., the availability of an arsenal of reagents and antibodies for these animals along with the possibility of working with genetically modified strains of mice) that may be relevant to the study. For acute pancreatitis induction in mice, we present a systematic protocol, with a defined dose of 2.5% sodium taurocholate at an infusion speed 10 µL/min for 3 min in C57BL/6 mice that reaches its maximal level of severity within 12 h of induction and highlight results with outcomes that validate the method. With practice and technique, the total estimated time, from the induction of anesthesia to the completion of the infusion, is 25 min per animal.


Assuntos
Pancreatite , Ácido Taurocólico , Doença Aguda , Animais , Camundongos , Camundongos Endogâmicos C57BL , Pâncreas , Pancreatite/induzido quimicamente , Ratos
13.
Medicine (Baltimore) ; 100(25): e26440, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160436

RESUMO

RATIONALE: Relapsed or refractory acute lymphoblastic leukemia poses a significant clinical challenge due to its poor prognosis, showing survival rates of less than a year even with the use of novel therapies. In this report, we describe the safe and effective use of trametinib combined with dasatinib in a patient with acute lymphoblastic leukemia (ALL). To the best of our knowledge, this is the first report on the successful use of 2 targeted drugs such as trametinib and dasatinib in a pediatric patient with Ph+ ALL and recurrent pancreatitis. PATIENT CONCERNS: A 6-year-old boy with ALL and Philadelphia chromosome (Ph+) who had recurrent asparaginase-associated pancreatitis. DIAGNOSIS: The patient was diagnosed with ALL, based on clinical features, laboratory analyses, bone marrow aspiration evaluation in morphology, immunology, cytogenetics, and molecular. INTERVENTIONS: The patient was treated with dasatinib combined with an intermediate risk-oriented chemotherapy. However, owing to recurrent asparaginase-associated pancreatitis, the patient has to abandon asparaginase in consolidation. Considering the high risk of relapse, we used trametinib and dasatinib combined with chemotherapy as maintenance chemotherapy. OUTCOMES: After 6 months, there were no obvious side effects or residual disease. LESSONS: We suggest that the combination of trametinib and dasatinib may represent a viable option to treat patients with potential relapsed/refractory Ph+ ALL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Dasatinibe/administração & dosagem , Pancreatite/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Piridonas/administração & dosagem , Pirimidinonas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Asparaginase/administração & dosagem , Asparaginase/efeitos adversos , Azatioprina/administração & dosagem , Azatioprina/efeitos adversos , Criança , Quimioterapia de Consolidação/métodos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Dasatinibe/efeitos adversos , Humanos , Quimioterapia de Manutenção/métodos , Masculino , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Piridonas/efeitos adversos , Pirimidinonas/efeitos adversos , Resultado do Tratamento
14.
Life Sci ; 280: 119704, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34111461

RESUMO

AIMS: The present study aimed to evaluate the protective action of thymol towards l-arginine-induced acute pancreatitis (AP) by studying the function of rat peritoneal immune cells. MAIN METHODS: Rat peritoneal exudate cells (PECs), obtained 24 h after the injection of l-arginine (350 mg/100 g of b.w.), were evaluated for mitochondrial activity (MTT assay), adherence capacity (methylene-blue assay), and phagocyte enzyme activity (myeloperoxidase, MPO, assay). The activity of α-amylase and free MPO, as well as the concentration of reactive oxygen species (ROS, i.e. O2-), were determined in the peritoneal exudate fluid. Also, serum α-amylase activity determination and pancreatic tissue pathohistological analysis were performed. KEY FINDING: The administered thymol (50 and 100 mg/kg, per os) caused a significant decrease in the PEC mitochondrial activity and adherence capacity when compared with these functions of PECs isolated from rats with AP. A decrease in cellular MPO activity, as well as in the levels of ROS, α-amylase, and free MPO in peritoneal exudates was found in animals treated with thymol compared to the control animals with AP. Additionally, thymol administration prevented an increase in serum α-amylase activity, accompanied by the decrease in pancreatic tissue damage that follows l-arginine application. SIGNIFICANCE: The present results showed that thymol exerts significant immunomodulatory properties and a potential to silence PEC functions in inflammatory conditions such as the AP induced by l-arginine.


Assuntos
Arginina/efeitos adversos , Imunidade Celular/efeitos dos fármacos , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Timol/uso terapêutico , Animais , Células Cultivadas , Granulócitos/efeitos dos fármacos , Granulócitos/imunologia , Granulócitos/patologia , Masculino , Pâncreas/efeitos dos fármacos , Pâncreas/imunologia , Pâncreas/patologia , Pancreatite/imunologia , Pancreatite/patologia , Cavidade Peritoneal/patologia , Ratos , Ratos Wistar
15.
Obes Surg ; 31(9): 4107-4117, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34152559

RESUMO

PURPOSE: Obesity is one of the most important risk factors for acute pancreatitis. Based on the effect of sleeve gastrectomy (SG) on improving body weight and blood lipids, we investigated whether SG is beneficial in improving pancreatitis in obese rats. MATERIALS AND METHODS: Two studies were used to evaluate the effect of SG on the first onset of pancreatitis and acute episodes of recurrent pancreatitis in obese rats. A high-fat diet (HFD) for 8 weeks resulted in obesity in rats. Study 1: Obese rats were treated with SG and sham surgery. Pancreatitis was induced by intraperitoneal injection of cerulein at 6 weeks after surgery. The severity of pancreatitis was assessed by histological examination, cytokines, and infiltration of inflammatory cells. Study 2 performed the same procedure as in study 1, except that rats were intraperitoneally injected with a small dose of cerulein three times a week for 6 weeks before surgery to induce recurrent pancreatitis. RESULTS: The body weight, food intake, and blood lipids of SG rats in study 1 and study 2 were significantly lower than those of sham rats during the 6 weeks after surgery. Compared with sham rats, SG rats in both studies had fewer inflammatory cytokines, inflammatory cell infiltration, and pathological injury in the pancreas after cerulein-induced acute pancreatitis. CONCLUSION: SG reduces the severity of the first onset of pancreatitis and the seriousness of acute episodes of recurrent pancreatitis. The improvement of lipid metabolism and body weight by SG may play an important role in this effect.


Assuntos
Obesidade Mórbida , Pancreatite , Doença Aguda , Animais , Ceruletídeo , Gastrectomia , Obesidade/cirurgia , Obesidade Mórbida/cirurgia , Pancreatite/induzido quimicamente , Ratos
16.
J Investig Med High Impact Case Rep ; 9: 23247096211026500, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34151624

RESUMO

IgG4 (immunoglobulin G4)-related systemic disease is an autoimmune process affecting multiple organ systems. This inflammatory process can present as but not limited to pancreatitis, cholangitis, or unspecified kidney disease. In this case, our patient developed IgG4-related kidney disease while already on a prolonged steroid course for IgG4-related pancreatitis. The patient ultimately had renal recovery after starting a higher dose of prednisone, but also developed steroid-related complications. This case further highlights the relationship between IgG4 diseases now termed IgG4-related systemic disease. This case brings to light the need for further investigative research into ideal steroid dosing, as well as steroid-sparing agents for IgG4-related systemic disease.


Assuntos
Doenças Autoimunes , Pancreatite Autoimune , Doença Relacionada a Imunoglobulina G4 , Pancreatite , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/tratamento farmacológico , Humanos , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/complicações , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico
17.
J Investig Med High Impact Case Rep ; 9: 23247096211028386, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34180257

RESUMO

Pancreatitis is inflammation of pancreas associated most commonly with chronic alcoholism and gallstones. Other less common causes of pancreatitis are hyperlipidemia, infections, surgery, trauma, post endoscopic retrograde cholangiopancreatography, and drugs. Drugs are now increasingly recognized as a cause of pancreatitis, and high suspicion and exclusion of other most common causes is required before considering drug-induced pancreatitis. There are few case reports of acute pancreatitis in the literature after statin use, but out of these, only 3 are after starting pravastatin. We are reporting a case of 49-year-old male who presented with nausea, vomiting, and abdominal pain. His laboratory findings were significant for lipase more than 10 000 on admission, and computed tomography scan of abdomen was showing peripancreatic fat stranding and inflammation. After exclusion of most common causes of pancreatitis, pravastatin was found probable culprit for his symptoms, which he started taking 2 weeks ago. We also reviewed the literature on statins-induced acute pancreatitis. With increased uses of statins, physician need to be vigilant to suspect statins as a culprit in cases of pancreatitis with unknown etiology. Prompt discontinuation of statins is required in these cases.


Assuntos
Pancreatite , Pravastatina , Dor Abdominal , Doença Aguda , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/induzido quimicamente , Pravastatina/efeitos adversos , Tomografia Computadorizada por Raios X
18.
Sci Rep ; 11(1): 12614, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34131249

RESUMO

In the adult pancreas, the presence of progenitor or stem cells and their potential involvement in homeostasis and regeneration remains unclear. Here, we identify that SET domain-containing protein 4 (SETD4), a histone lysine methyltransferase, is expressed in a small cell population in the adult mouse pancreas. Genetic lineage tracing shows that during pancreatic development, descendants of SETD4+ cells make up over 70% of pancreatic cells and then contribute to each pancreatic lineage during pancreatic homeostasis. SETD4+ cells generate newborn acinar cells in response to cerulein-induced pancreatitis in acinar compartments. Ablation of SETD4+ cells compromises regeneration of acinar cells, in contrast to controls. Our findings provide a new cellular narrative for pancreatic development, homeostasis and response to injury via a small SETD4+ cell population. Potential applications may act to preserve pancreatic function in case of pancreatic disease and/or damage.


Assuntos
Metiltransferases/genética , Pâncreas/metabolismo , Pancreatite/genética , Regeneração/genética , Células Acinares/metabolismo , Células Acinares/patologia , Animais , Linhagem da Célula/genética , Ceruletídeo/toxicidade , Modelos Animais de Doenças , Homeostase/efeitos dos fármacos , Homeostase/genética , Humanos , Camundongos , Pâncreas/crescimento & desenvolvimento , Pâncreas/lesões , Pâncreas/patologia , Pancreatite/induzido quimicamente , Pancreatite/patologia , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos
19.
BMJ Case Rep ; 14(6)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34088696

RESUMO

A 57-year-old man with lung cancer, previously treated with the programmed death-1 inhibitor pembrolizumab, was evaluated for liver injury and acute pancreatitis. Serum IgG4 levels were not elevated. Contrast-enhanced CT showed pancreatic swelling, contrast unevenness in the liver and thickening of the common bile duct and gall bladder. Magnetic resonance cholangial pancreatography revealed beads in the left intrahepatic bile duct and localised narrowing of the head and body of the central pancreatic duct. Endoscopic ultrasound-guided fine-needle and liver needle biopsy showed CD8+ and CD4+ T lymphocyte aggregates, whereas immunostaining revealed greater infiltration by CD8+ cells than CD4+ cells. IgG4-related disease was ruled out based on serum and pathological findings. The patient simultaneously presented with immune-related adverse events, autoimmune pancreatitis-like features and sclerosing cholangitis, which were ameliorated by steroid therapy. CD8+ lymphocytes were the dominant infiltrating cells in autoimmune pancreatitis and sclerosing cholangitis.


Assuntos
Doenças Autoimunes , Pancreatite Autoimune , Colangite Esclerosante , Pancreatite , Doença Aguda , Anticorpos Monoclonais Humanizados , Doenças Autoimunes/induzido quimicamente , Colangite Esclerosante/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/induzido quimicamente
20.
Clin J Gastroenterol ; 14(4): 1269-1277, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33945068

RESUMO

Cocaine use continues to be an important global public health problem. As the use of cocaine remains pervasive so have a myriad of adverse events associated with this drug. These deleterious effects are well-studied, but gastrointestinal complications remain esoteric and the existing clinical evidence is scarce. Ischemia of the esophagus and small bowel, perforation, peptic ulceration, gastrointestinal bleeding, and ischemic colitis are among the reported complications. In specific, acute pancreatitis secondary to cocaine use is an exceedingly rare clinicopathologic entity. To date, only 7 cases of this condition have been reported in the English-language literature. We hereby delineate a rare case of a 29-year-old female who developed her first episode of cocaine-associated pancreatitis. The diagnosis was made based on a standard battery of investigations and meticulous exclusion of common etiologies of acute pancreatitis. To our knowledge, this case represents the first report of re-occurrence of acute pancreatitis upon subsequent crack cocaine insufflation, adding a higher level of evidence to a fallible association. We also present a systematic review of the existing literature on acute pancreatitis following cocaine use. An updated knowledge regarding this rare association is of paramount importance for early diagnosis and astute management.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Pancreatite , Doença Aguda , Adulto , Cocaína/efeitos adversos , Transtornos Relacionados ao Uso de Cocaína/complicações , Feminino , Hemorragia Gastrointestinal , Humanos , Pancreatite/induzido quimicamente
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