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1.
Medicine (Baltimore) ; 99(42): e22645, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080703

RESUMO

RATIONALE: Pancreatic cancer (PC) has the worst prognosis among all carcinomas. However, patients with carcinoma in situ (CIS) of the pancreas, usually, have a good prognosis. Many previous reports have mentioned the high frequency of fibrosis around CIS. In some cases, the fibrosis is detected on endoscopic ultrasonography (EUS), but there are few past reports of fibrosis detected on computed tomography (CT). PATIENT CONCERNS: We encountered a case of fibrosis around CIS detected by CT. A 74-year-old man was being followed for chronic hepatitis C. On a contrast-enhanced CT (CE-CT), a space-occupied lesion (7 mm in size) in the pancreatic head was identified in the delayed phase. DIAGNOSIS: It was shown to be a hypo echoic lesion in EUS, and EUS-fine-needle aspiration was performed. Cytological examination revealed abnormal cells suspicious for a neuroendocrine tumor. INTERVENTIONS: Consequently, a pancreaticoduodenectomy was performed. Histopathological examination showed CIS in the branch duct with 10 mm of fibrosis around CIS. The fibrotic area corresponded to the mass detected by preoperative CE-CT. OUTCOMES: He had no relapse of PC but died 2 years later from another cause. LESSONS: This case highlights the importance of identifying the enhanced area in the delayed phase on CE-CT, as this can be fibrosis around CIS.


Assuntos
Carcinoma in Situ/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Idoso , Endossonografia , Fibrose , Humanos , Imagem por Ressonância Magnética , Masculino , Pâncreas/diagnóstico por imagem
3.
Intern Med ; 59(19): 2383-2389, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32999265

RESUMO

Follow-up computed tomography revealed a 40-mm pancreatic tail cyst in a 59-year-old man with type 1 diabetes mellitus. An intraductal papillary mucinous neoplasm was suspected; mucinous cystic neoplasm (MCN) was not considered because the patient was a man. During follow-up, cyst infection occurred but was improved by conservative treatment. At the 24-month follow up examination, cyst nodules had developed, corresponding to an increase in the carbohydrate antigen 19-9 level. Mucinous cystadenocarcinoma (MCC) was diagnosed pathologically based on distal pancreatectomy. A diagnosis of male MCN/MCC is often delayed, which may lead to a poor prognosis. MCN infection is also rare and poorly recognized. We observed an atypical male case of MCN/MCC.


Assuntos
Cistadenocarcinoma Mucinoso/patologia , Cisto Pancreático/patologia , Neoplasias Pancreáticas/patologia , Antígeno CA-19-9/sangue , Cistadenocarcinoma Mucinoso/diagnóstico , Cistadenocarcinoma Mucinoso/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico , Tomografia Computadorizada por Raios X
4.
S Afr Med J ; 110(7): 642-645, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32880340

RESUMO

We present an unusual case of syphilitic pancreatitis and ascending aortitis in a 41-year-old HIV-negative male patient presenting to a tertiary institution with obstructive jaundice. After a battery of investigations that included computed tomography (CT) and 18F-labelled fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) imaging, syphilis serology and histology, a diagnosis of tertiary syphilis was made. The patient responded favourably to antibiotics, with resolution of all lesions on FDG PET/CT 13 weeks after initiation of therapy. Even though tertiary syphilis is a rare entity, it should be earmarked as a mimicker of other pathological conditions, including, in this case, primary pancreatic malignancy.


Assuntos
Pancreatite/diagnóstico , Pancreatite/microbiologia , Sífilis/diagnóstico , Adulto , Aneurisma da Aorta Torácica/diagnóstico por imagem , Biópsia , Angiografia por Tomografia Computadorizada , Meios de Contraste , Diagnóstico Diferencial , Humanos , Icterícia Obstrutiva/microbiologia , Masculino , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico , Sífilis Cardiovascular/diagnóstico , Tomografia Computadorizada por Raios X
5.
Anticancer Res ; 40(10): 5845-5851, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988914

RESUMO

BACKGROUND: Pancreatic mass sampling has historically been performed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). However, its sensitivity has been reported to be within a wide range, which limits its reliability. Fine needle biopsy (FNB) has been shown to have superior diagnostic performance and is increasingly replacing fine needle aspiration. In FNA, 25 gauge (G) needles appear to outperform 22G. Data comparing these sizes in FNB platforms is limited. We aimed to prospectively compare the performance of 22G and 25G Franseen-tip core biopsy needles in the sampling of solid pancreatic lesions. PATIENTS AND METHODS: Patients who underwent EUS-FNB of pancreatic lesions at the Indiana University Hospital using 2 needle sizes: 25G (Study group) and 22G (Control group) using the Acquire needle (Boston Scientific Co., Natick, MA, USA) were enrolled. Needle choice was left to the discretion of the endosonographer. Tissue specimens were evaluated onsite, and underwent touch and smear and cellblock preparation. Specimens were independently evaluated by 2 expert cytopathologists blinded to diagnosis. Cytopathologists assessed cytological yield (on smears) and histological yield (on cellblock) using a validated scoring system reached by a consensus among our cytopathologists as we have previously published. RESULTS: A total of 75 patients (42 males, median=65 years) underwent EUS-FNB during the study period (2017-2018): 50 using 25G and 25 using 22G needle. Diagnostic yield was numerically higher in 25G (98% vs. 88%, p=0.105). Number of passes for smears were similar, however the 25G group required additional passes for cell-block (1.6 vs. 0.4, p=0.001). 25G was used more frequently for pancreatic head and uncinate process sampling (70% vs. 52%, p=0.126). Four patients had self-limited adverse events in the 22G group, but none in the 25G group. CONCLUSION: We report no difference in the diagnostic yield between 25G FNB vs. 22G sampling device with Franseen style tip, however, the 25G needle use was associated with the need of additional passes to collect a sufficient cell block.


Assuntos
Biópsia com Agulha de Grande Calibre , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pancreáticas/diagnóstico , Idoso , Endossonografia , Feminino , Humanos , Indiana , Masculino , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Manejo de Espécimes
6.
Nat Commun ; 11(1): 4516, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908137

RESUMO

Acinar metaplasia is an initial step in a series of events that can lead to pancreatic cancer. Here we perform single-cell RNA-sequencing of mouse pancreas during the progression from preinvasive stages to tumor formation. Using a reporter gene, we identify metaplastic cells that originated from acinar cells and express two transcription factors, Onecut2 and Foxq1. Further analyses of metaplastic acinar cell heterogeneity define six acinar metaplastic cell types and states, including stomach-specific cell types. Localization of metaplastic cell types and mixture of different metaplastic cell types in the same pre-malignant lesion is shown. Finally, single-cell transcriptome analyses of tumor-associated stromal, immune, endothelial and fibroblast cells identify signals that may support tumor development, as well as the recruitment and education of immune cells. Our findings are consistent with the early, premalignant formation of an immunosuppressive environment mediated by interactions between acinar metaplastic cells and other cells in the microenvironment.


Assuntos
Células Acinares/patologia , Carcinoma Ductal Pancreático/genética , Regulação Neoplásica da Expressão Gênica , Pâncreas/patologia , Neoplasias Pancreáticas/genética , Lesões Pré-Cancerosas/genética , Animais , Animais Geneticamente Modificados , Biópsia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Diferenciação Celular , Modelos Animais de Doenças , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Heterogeneidade Genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Estimativa de Kaplan-Meier , Masculino , Metaplasia/genética , Camundongos , Mutação , Pâncreas/citologia , Pâncreas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Lesões Pré-Cancerosas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , RNA-Seq , Análise de Célula Única , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Microambiente Tumoral/genética
7.
Clin Nucl Med ; 45(11): 921-922, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32910042

RESUMO

A 55-year-old woman underwent FDG PET/CT to evaluate a pancreatic mass. The images showed elevated FDG activity in the uncinated process of the pancreas, suggestive of malignancy. However, pathological examination from the resected lesion demonstrated pancreatic schwannoma.


Assuntos
Fluordesoxiglucose F18 , Neurilemoma/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Feminino , Humanos , Pessoa de Meia-Idade , Neurilemoma/patologia , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/patologia
8.
Rom J Morphol Embryol ; 61(1): 209-218, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32747912

RESUMO

We are reporting a case of natural evolution and pathological data from a young person that was diagnosed with coronavirus disease 2019 (COVID-19). All data has been collected from the autopsy of a 30-year-old female, which was performed by the Department of Forensic Medicine from Emergency County Hospital, Drobeta Turnu Severin, Mehedinti County, Romania. The infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed by reverse transcription polymerase chain reaction (RT-PCR) on the lung tissue which was obtained during autopsy. This case provides the opportunity to study the natural evolution of COVID-19 pneumonia in a young person with clinical signs of pneumonia but without associated comorbidities. The patient had not received any treatment. The histopathological examination of the lung revealed a process of productive proliferation, proteinaceous and fibrin-macrophagic interalveolar spaces exudate, and lesions consistent with vasculitis. In the heart, we identified a cardiac thrombus. These changes are likely to suggest an advanced natural evolution of SARS-CoV-2 virus infection.


Assuntos
Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Pulmão/virologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Adulto , Autopsia , Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Rim/patologia , Fígado/patologia , Pulmão/patologia , Miocárdio/patologia , Pâncreas/patologia , Pandemias , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Romênia , Trombose/patologia , Trombose/virologia
9.
Nat Commun ; 11(1): 4286, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855403

RESUMO

Intracellular galectins are carbohydrate-binding proteins capable of sensing and repairing damaged lysosomes. As in the physiological conditions glycosylated moieties are mostly in the lysosomal lumen but not cytosol, it is unclear whether galectins reside in lysosomes, bind to glycosylated proteins, and regulate lysosome functions. Here, we show in gut epithelial cells, galectin-9 is enriched in lysosomes and predominantly binds to lysosome-associated membrane protein 2 (Lamp2) in a Asn(N)-glycan dependent manner. At the steady state, galectin-9 binding to glycosylated Asn175 of Lamp2 is essential for functionality of lysosomes and autophagy. Loss of N-glycan-binding capability of galectin-9 causes its complete depletion from lysosomes and defective autophagy, leading to increased endoplasmic reticulum (ER) stress preferentially in autophagy-active Paneth cells and acinar cells. Unresolved ER stress consequently causes cell degeneration or apoptosis that associates with colitis and pancreatic disorders in mice. Therefore, lysosomal galectins maintain homeostatic function of lysosomes to prevent organ pathogenesis.


Assuntos
Galectinas/metabolismo , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Lisossomos/metabolismo , Pâncreas/patologia , Celulas de Paneth/patologia , Células Acinares/metabolismo , Células Acinares/patologia , Animais , Autofagia/fisiologia , Colite/metabolismo , Colite/patologia , Estresse do Retículo Endoplasmático , Galectinas/genética , Células HT29 , Humanos , Proteína 2 de Membrana Associada ao Lisossomo/genética , Lisossomos/genética , Lisossomos/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pâncreas/metabolismo , Pancreatite/metabolismo , Pancreatite/patologia , Celulas de Paneth/metabolismo
10.
Surgery ; 168(3): 448-456, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32620306

RESUMO

BACKGROUND: We describe the use of pancreatic retrograde venous infusion in an orthotopic murine model of pancreatic ductal adenocarcinoma and hypothesize that pancreatic retrograde venous infusion delivery of gemcitabine will increase concentrations of gemcitabine in the tumor and the subsequent tumor response to treatment. METHODS: Murine pancreatic ductal adenocarcinoma (KPC4580P) was transplanted onto the pancreatic tail of C57BL/6J mice. Groups (n = 15) of mice were assigned to sham laparotomy and 100 mg/kg intraperitoneal infusion of gemcitabine (systemic gemcitabine), pancreatic venous isolation with pancreatic retrograde venous infusion of 100 mg/kg gemcitabine, or pancreatic retrograde venous infusion with saline infusion. Tumor pressures were recorded during pancreatic retrograde venous infusion. Mice were killed at 1 hour or 7 days after infusion. RESULTS: Baseline tumor pressures were 45 ± 8 mm Hg, and pancreatic retrograde venous infusion increased tumor pressures by 29 ± 6 mm Hg (P < .01). Pancreatic retrograde venous infusion gemcitabine mice had greater tumor gemcitabine concentrations compared with systemic gemcitabine (127 vs 19 ng/mg; P < .01) and lesser tumor volumes compared with both systemic gem and pancreatic retrograde venous infusion with saline (274 vs 857 vs 629 mm3; P < .01). CONCLUSION: Pancreatic retrograde venous infusion increased tumor pressures greater than baseline, improved gemcitabine delivery, and increased the treatment response. These findings suggest that pressurized, regional delivery overcomes the increased pressure barrier in pancreatic ductal adenocarcinoma. Additional preclinical studies with cytotoxic and immunotherapeutic agents and clinical trials using pressure-enabled drug delivery with pancreatic retrograde venous infusion devices are underway.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Infusões Intralesionais/métodos , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Antimetabólitos Antineoplásicos/farmacocinética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral/transplante , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacocinética , Modelos Animais de Doenças , Humanos , Infusões Intravenosas/métodos , Masculino , Camundongos , Pâncreas/irrigação sanguínea , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Pressão , Distribuição Tecidual
11.
Hum Cell ; 33(4): 1006-1016, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32524326

RESUMO

In chronic pancreatitis, PSCs are activated by proinflammatory cytokines to induce pancreatic fibrogenesis. HDAC inhibition protected against the pancreatic fibrosis and the apoptosis of PSCs through induced apoptosis and depressed inflammation. In our study, we found that miR-15 and miR-16 decreased significantly in chronic pancreatitis and HDAC inhibition could recover the levels of these two miRNAs. HDAC regulated the transcription of miR-15 and miR-16, which then modulate the apoptosis and fibrosis of PSCs. And we proved that Bcl-2 and Smad5 were the target genes of miR-15 and miR-16, which illustrated how HDAC inhibition alleviated the apoptosis and fibrogenesis of PSCs in chronic pancreatitis. These results suggested that HDAC inhibition protects against CP by promoting apoptosis and TGF-ß/Smads signaling pathways, and indicated that HDAC inhibition is a potential therapy to alleviate CP patients in clinic, and these need to be explored further.


Assuntos
Apoptose/genética , Inibidores de Histona Desacetilases/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Pâncreas/patologia , Células Estreladas do Pâncreas/patologia , Pancreatite Crônica/tratamento farmacológico , Pancreatite Crônica/genética , Pancreatite Crônica/patologia , Regulação para Cima/efeitos dos fármacos , Células Cultivadas , Fibrose , Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Pâncreas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo
12.
Biochim Biophys Acta Rev Cancer ; 1874(1): 188387, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32579889

RESUMO

Late detection, compromised immune system, and chemotherapy resistance underlie the poor patient prognosis for pancreatic ductal adenocarcinoma (PDAC) patients, making it the 3rd leading cause of cancer-related deaths in the United States. Cooperation between the tumor cells and the immune system leads to the immune escape and eventual establishment of the tumor. For more than 20 years, sincere efforts have been made to intercept the tumor-immune crosstalk and identify the probable therapeutic targets for breaking self-tolerance toward tumor antigens. However, the success of these studies depends on detailed examination and understanding of tumor-immune cell interactions, not only in the primary tumor but also at distant systemic niches. Innate and adaptive arms of the immune system sculpt tumor immunogenicity, where they not only aid in providing an amenable environment for their survival but also act as a driver for tumor relapse at primary or distant organ sites. This review article highlights the key events associated with tumor-immune communication and associated immunosuppression at both local and systemic microenvironments in PDAC. Furthermore, we discuss the approaches and benefits of targeting both local and systemic immunosuppression for PDAC patients. The present articles integrate data from clinical and genetic mouse model studies to provide a widespread consensus on the role of local and systemic immunosuppression in undermining the anti-tumor immune responses against PDAC.


Assuntos
Carcinoma Ductal Pancreático/terapia , Imunoterapia/métodos , Neoplasias Pancreáticas/terapia , Evasão Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/efeitos dos fármacos , Medula Óssea/imunologia , Medula Óssea/patologia , Vacinas Anticâncer/administração & dosagem , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Quimioterapia Adjuvante/métodos , Ensaios Clínicos como Assunto , Terapia Combinada/métodos , Modelos Animais de Doenças , Intervalo Livre de Doença , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Imunidade Inata/efeitos dos fármacos , Irinotecano/farmacologia , Irinotecano/uso terapêutico , Leucovorina/farmacologia , Leucovorina/uso terapêutico , Excisão de Linfonodo , Linfonodos/imunologia , Linfonodos/patologia , Linfonodos/cirurgia , Camundongos , Camundongos Transgênicos , Terapia Neoadjuvante/métodos , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Pâncreas/imunologia , Pâncreas/patologia , Pâncreas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Baço/imunologia , Baço/patologia , Baço/cirurgia , Esplenectomia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/transplante , Transplante Autólogo/métodos
13.
Cell Stem Cell ; 27(1): 125-136.e7, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32579880

RESUMO

SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. We present an experimental platform comprised of cell and organoid derivatives from human pluripotent stem cells (hPSCs). A Spike-enabled pseudo-entry virus infects pancreatic endocrine cells, liver organoids, cardiomyocytes, and dopaminergic neurons. Recent clinical studies show a strong association with COVID-19 and diabetes. We find that human pancreatic beta cells and liver organoids are highly permissive to SARS-CoV-2 infection, further validated using adult primary human islets and adult hepatocyte and cholangiocyte organoids. SARS-CoV-2 infection caused striking expression of chemokines, as also seen in primary human COVID-19 pulmonary autopsy samples. hPSC-derived cells/organoids provide valuable models for understanding the cellular responses of human tissues to SARS-CoV-2 infection and for disease modeling of COVID-19.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Modelos Biológicos , Organoides/virologia , Pneumonia Viral/virologia , Tropismo , Animais , Autopsia , Linhagem Celular , Infecções por Coronavirus/patologia , Hepatócitos/patologia , Hepatócitos/virologia , Humanos , Células-Tronco Pluripotentes Induzidas/virologia , Fígado/patologia , Camundongos , Pâncreas/patologia , Pâncreas/virologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/patologia , Internalização do Vírus
14.
Clin Imaging ; 67: 101-107, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32559679

RESUMO

Solid Pseudopapillary Neoplasms of the pancreas are rare pancreatic tumors with low-grade malignant potential, typically affecting young females. In this review, we discuss the surgical anatomy; the imaging characteristics, and image reporting essentials for proper surgical planning along with the atypical features which should caution the physician regarding the risk of malignancy. We also discuss the common surgical procedures and organ preservation surgeries along with a comprehensive review of the literature.


Assuntos
Neoplasias Epiteliais e Glandulares/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Adulto , Feminino , Humanos , Pâncreas/patologia , Pancreatectomia/métodos , Neoplasias Pancreáticas/patologia , Radiografia
15.
Life Sci ; 256: 118003, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32589998

RESUMO

INTRODUCTION AND AIMS: Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder affecting females. Mechanisms underlying PCOS complicated pathology remain largely unknown, making current treatment only symptomatic. Increasing reports suggest impaired PI3K/AKT/mTOR pathway and tumor necrosis factor-α (TNF-α) levels are involved in cellular proliferation and metabolism-related disorders. However, rare data explored their role in PCOS. Hence, this study investigated TNF-α and pancreatic PI3K/AKT/mTOR levels in PCOS animal model and evaluated their effects on developed pancreatic deficits. Secondly; we explored the impact of nanocurcumin as powerful anti-inflammatory supplement against these developed pancreatic pathologies. METHODS: PCOS was induced in rats using letrozole. Nanocurcumin was formulated to increase solubility and bioavailability of curcumin. Transmission electron microscopy (TEM), zeta potential and Infra-red spectroscopy (FT-IR) were used for characterization. Nanocurcumin was orally ingested for 15 days. FINDINGS: PCOS group exhibited significant disturbance in sex hormones, oxidative stress markers, and TNF-α levels as determined by immunoassay. Western blotting revealed significant reduction of PI3K/AKT/mTOR levels leading to impaired insulin sensitivity, decreased ß cells function and mass as confirmed by HOMA assessments and immunohistochemistry. Nanocurcumin significantly improved oxidative markers, glucose indices and TNF-α levels. It reinstated PI3K/AKT/mTOR levels, alleviated insulin resistance, and retained islets integrity consequently restoring normal sex hormonal levels. SIGNIFICANCE: To the best of our knowledge, the study is the first to report pancreatic role of PI3K/AKT/mTOR and TNF-α in PCOS and the first to demonstrate nanocurcumin promising potential against PCOS-related pancreatic molecular and histological pathologies that can indeed offer better control of the disease.


Assuntos
Curcumina/farmacologia , Resistência à Insulina , Nanopartículas , Pâncreas/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Animais , Curcumina/administração & dosagem , Modelos Animais de Doenças , Feminino , Pâncreas/patologia , Fosfatidilinositol 3-Quinase/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
16.
Khirurgiia (Mosk) ; (6): 31-37, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32573529

RESUMO

OBJECTIVE: To analyze the role of contrast-enhanced computed tomography in evaluation of pancreatic stump volume for prediction of significant pancreatic fistula. MATERIAL AND METHODS: A retrospective analysis enrolled 99 patients. Patients were divided into 2 groups depending on the course of postoperative period and development of clinically significant pancreatic fistula. The first group included 24 patients (25%) with clinically significant postoperative pancreatic fistula. The second group included 75 patients (75%) without postoperative complications. Pancreatic structure, pancreatic parenchyma thickness (mm), pancreatic duct diameter (mm) and volume of pancreatic stump (cm3) were preoperatively analyzed considering contrast-enhanced computed tomography data. RESULTS: The risk of postoperative pancreatic fistula is 10 times higher in case of soft structure of the pancreas, 1,7 times higher in decrease of pancreatic duct diameter, 9,3 times higher in increased volume of residual pancreatic parenchyma, 8.6 times higher in increase of pancreatic parenchyma thickness. CONCLUSION: Contrast-enhanced computed tomography is valuable for preoperative evaluation of the volume of residual pancreatic parenchyma and identification of patients with high risk of postoperative pancreatic fistula.


Assuntos
Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Fístula Pancreática/diagnóstico por imagem , Pancreaticoduodenectomia/efeitos adversos , Meios de Contraste , Humanos , Tamanho do Órgão , Pâncreas/patologia , Ductos Pancreáticos/diagnóstico por imagem , Ductos Pancreáticos/patologia , Ductos Pancreáticos/cirurgia , Fístula Pancreática/etiologia , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X
18.
Nat Commun ; 11(1): 2238, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382089

RESUMO

In type1 diabetes (T1D) autoreactive T-cells infiltrate the islets of Langerhans, depleting insulin-secreting ß-cells (insulitis). Insulitis arises during an asymptomatic phase, prior to clinical diagnosis of T1D. Methods to diagnose insulitis and ß-cell mass changes during this asymptomatic phase are limited, precluding early therapeutic intervention. During T1D the islet microvasculature increases permeability, allowing nanoparticles to access the microenvironment. Contrast enhanced ultrasound (CEUS) uses shell-stabilized gas bubbles to provide acoustic backscatter in vasculature. Here, we report that sub-micron sized 'nanobubble' ultrasound contrast agents can be used to measure increased islet microvasculature permeability and indicate asymptomatic T1D. Through CEUS and histological analysis, pre-clinical models of T1D show accumulation of nanobubbles specifically within pancreatic islets, correlating with insulitis. Importantly, accumulation is detected early in disease progression and decreases with successful therapeutic intervention. Thus, sub-micron sized nanobubble ultrasound contrast agents provide a predicative marker for disease progression and therapeutic reversal early in asymptomatic T1D.


Assuntos
Meios de Contraste , Diabetes Mellitus Tipo 1/diagnóstico por imagem , Diabetes Mellitus Tipo 1/patologia , Animais , Feminino , Humanos , Células Secretoras de Insulina/patologia , Ilhotas Pancreáticas/diagnóstico por imagem , Ilhotas Pancreáticas/patologia , Camundongos , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Ultrassonografia
19.
Adv Clin Exp Med ; 29(5): 587-595, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32459401

RESUMO

BACKGROUND: Disturbances in pancreatic microcirculation, beginning with vasoconstriction, are crucial in early pancreatitis and progression to necrotizing pancreatitis. Thus, vascular-targeted treatment aiming to restore a sufficient level of microcirculation through vasodilation would possibly reduce the severity of pancreatitis. Lidocaine is an anti-arrhythmic and local anesthetic drug, which also acts as a vasodilator at higher concentrations. OBJECTIVES: To evaluate the efficacy of intra-arterial infusion of lidocaine into the celiac trunk in treatment of cerulein-induced acute pancreatitis. MATERIAL AND METHODS: Wistar rats (n = 20) were randomly divided into 2 equal groups: the control group (NaCl group, n = 10) and the study group (lidocaine group, n = 10). All subjects underwent surgical intervention with intra-arterial infusion of 0.9% NaCl (control group) or 1% lidocaine hydrochloride (study group) into the celiac trunk. Blood samples were collected 5 times at regular intervals from each rat for amylase and lipase measurements. Histopathological analysis of the pancreas was performed. RESULTS: A total number of 16 rats (control group n = 7, study group n = 9) were included. In the postoperative course, the study group (lidocaine group) revealed lower values of serum amylase and lipase levels compared to the control group (NaCl group), except the values at the 1st treatment point, which appeared 1 h after intraoperative drug injection. Significantly lower treatment endpoint levels of pancreatic enzymes were seen in the lidocaine group. Moreover, no differences were observed between the 1st and the last treatment point in the control group; however, these differences were significant for both enzymes in the study group. Histopathology revealed reduced pancreatitis severity in the study group compared to the controls. CONCLUSIONS: Intra-arterial lidocaine infusion into the celiac trunk decreases pancreatitis severity. What is more, this study demonstrates the relevance of early vasodilation in the therapy of acute pancreatitis.


Assuntos
Ceruletídeo/efeitos adversos , Lidocaína/administração & dosagem , Pancreatite/tratamento farmacológico , Doença Aguda , Animais , Ceruletídeo/uso terapêutico , Infusões Intra-Arteriais , Lidocaína/uso terapêutico , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pancreatite/induzido quimicamente , Pancreatite/patologia , Distribuição Aleatória , Ratos , Ratos Wistar , Resultado do Tratamento
20.
Am J Chin Med ; 48(4): 987-1003, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431181

RESUMO

Our previous report revealed that Gardenia jasminoides (GJ) has protective effects against acute pancreatitis. So, we examined whether aqueous extract of GJ has anti-inflammation and antifibrotic effects even against cerulein-induced chronic pancreatitis (CP). CP was induced in mice by an intraperitoneal injection of a stable cholecystokinin (CCK) analogue, cerulein, six times a day, four days per week for three weeks. GJ extract (0.1 or 1[Formula: see text]g/kg) or saline (control group) were intraperitoneally injected 1[Formula: see text]h before first cerulein injection. After three weeks of stimulation, the pancreas was harvested for the examination of several fibrotic parameters. In addition, pancreatic stellate cells (PSCs) were isolated using gradient methods to examine the antifibrogenic effects of GJ. In the cerulein-induced CP mice, the histological features of the pancreas showed severe tissue damage such as enlarged interstitial spaces, inflammatory cell infiltrate and glandular atrophy, and tissue fibrosis. However, treatment of GJ reduced the severity of CP such as pancreatic edema and inflammatory cell infiltration. Furthermore, treatment of GJ increased pancreatic acinar cell survival, and reduced pancreatic fibrosis and activation of PSC in vivo and in vitro. In addition, GJ treatment inhibited the activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) in the PSCs. These results suggest that GJ attenuated the severity of CP and the pancreatic fibrosis by inhibiting JNK and ERK activation during CP.


Assuntos
Ceruletídeo/efeitos adversos , Gardenia/química , Pancreatite Crônica/tratamento farmacológico , Pancreatite Crônica/prevenção & controle , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Animais , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Fibrose , Injeções Intraperitoneais , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Pâncreas/patologia , Células Estreladas do Pâncreas/patologia , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/patologia , Extratos Vegetais/isolamento & purificação
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