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1.
Medicine (Baltimore) ; 100(15): e25374, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847635

RESUMO

ABSTRACT: The pathogenesis of hepatocellular carcinoma (HCC) can be divided into viral infection (VIR) and nonviral (NVIR) infection. Two types of HCC performed different tumor immune microenvironment (TIME) which directly affected prognosis of HCC. This study aimed to identify an effective 2 types of HCC prognostic gene signature that related to immune TIME.The differential expression genes (DEGs) were analyzed by Limma R package from the Cancer Genome Atlas. Immune related genes getting from IMMport database were matched to DEGs for testing prognosis. Prognostic index (PI) consisted of prognostic immune related genes was calculated in different types of HCC by COX regression and the correlation with the abundance of immune infiltrates, including 6 type cells, via gene modules. Tumor immune estimation resource database was applied to analyze TIME. Finally, the correlations between PI of DEGs and TIICs were analyzed by the Spearman method.Results showed that PI consisted of 11 messenger RNAs in VIR and 12 messenger RNAs in NVIR groups. The PI related to HCC prognosis has different correlations with immune infiltrating cells in VIR and NVIR groups. The PI value of DEGs has significant correlations with neutrophils (R = 0.22, P-value = .029) and dendritic (R = 0.21, P-value = .036) infiltration levels in VIR group. However, in NVIR group, the result showed there were no significant correlations between PI and other 5 type cell infiltration levels (P-value > .05).The 11-gene signature in VIR and 12-gene signature in NVIR group selected based on data from the Cancer Genome Atlas database had a different correlation with immune infiltrating cells of HCC patients.


Assuntos
Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/genética , Hepatite/complicações , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/genética , Microambiente Tumoral/genética , Biomarcadores Tumorais , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Hepatite/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/biossíntese , Microambiente Tumoral/imunologia
2.
Niger J Clin Pract ; 24(3): 452-455, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33723123

RESUMO

Transcatheter aortic valve implantation (TAVI) is widely used in high-risk patients with severe symptomatic aortic valve stenosis (AS). The use of traditional surgical aortic valve replacement (SAVR) significantly increases the risk of complications in chronic liver failure with the release of many vasoactive and cytotoxic substrates. In patients with ischemic hepatitis or liver dysfunction along with the severe AS, TAVI may be advantageous due to its minimally invasive nature. However, there is limited information about the outcome of TAVI in a patient with both hepatic and multisystem dysfunction. We report this case demonstrating dramatic result of TAVI in a patient in extremely poor clinical condition due to ischemic hepatitis and hyperbilirunemia.


Assuntos
Estenose da Valva Aórtica , Hepatite , Substituição da Valva Aórtica Transcateter , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Hepatite/complicações , Humanos , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
4.
BMC Cancer ; 21(1): 314, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761922

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICI) have become standard treatment in different tumor entities. However, safe treatment with ICI targeting the PD-1/PD-L1 axis requires early detection of immune-related adverse events (irAE). There exist different questionnaires of drug manufacturers for the detection of irAE that have not been validated so far. METHODS: The prospective non-interventional ST-ICI trial studied treatment with PD-1/PD-L1 ICI alone or combined with radiotherapy. In the current analysis, the detection rate of self-reported irAE with a patient questionnaire containing 41 different questions was compared to clinician-reported irAE. RESULTS: Between April 2017 and August 2019, a total of 104 patients were prospectively enrolled. NSCLC (44%) and HNSCC (42%) were the most frequent tumor entities. A total of 784 questionnaires were collected. A total of 29 irAE were reported by clinicians. The most frequent irAE was hypothyroidism (9%), followed by skin reactions (5%), hepatitis (4%), diarrhea (3%), and pneumonitis (3%). Questions that became significantly more often positive at time points of clinician-reported irAE were "weight change", "difficulty to grip things", "bloody or mucous stool" and "insomnia". Self-reported organ-specific questions detected at least 50% of clinician-reported irAE of gastrointestinal, lung, endocrine, and skin irAE. It was not possible to detect hepatic irAE with the questionnaire. CONCLUSION: Questionnaires can help to detect gastrointestinal, lung, endocrine, or skin irAE, but not hepatic irAE. Questions on "weight change" and "insomnia" may help to increase the detection rate of irAE, besides organ-specific questions. These results are a valuable contribution to the future development of a specific and practicable questionnaire for early self-reported detection of irAE during ICI therapy in cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03453892 . Registered on 05 March 2018.


Assuntos
Quimiorradioterapia/efeitos adversos , Monitoramento de Medicamentos/métodos , Neoplasias/terapia , Autorrelato/estatística & dados numéricos , Idoso , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Quimiorradioterapia/métodos , Diarreia/induzido quimicamente , Diarreia/diagnóstico , Diarreia/epidemiologia , Diarreia/imunologia , Erupção por Droga/diagnóstico , Erupção por Droga/epidemiologia , Erupção por Droga/imunologia , Monitoramento de Medicamentos/estatística & dados numéricos , Feminino , Hepatite/diagnóstico , Hepatite/epidemiologia , Hepatite/imunologia , Humanos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/diagnóstico , Hipotireoidismo/epidemiologia , Hipotireoidismo/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Pneumonia/induzido quimicamente , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Pneumonia/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Estudos Prospectivos
6.
Zhonghua Gan Zang Bing Za Zhi ; 29(1): 13-15, 2021 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-33541018

RESUMO

Cytomegalovirus hepatitis, especially infants with cholestatic liver disease or abnormal liver function, is of great concern to pediatricians. Previously, cytomegalovirus infection was the recognized cause of the disease. Therefore, a comprehensive scientific understanding of cytomegalovirus hepatitis requires an understanding of the basic knowledge of cytomegalovirus infection. Concurrently, it is necessary to standardize the indications of antiviral treatment in combination with the child's age, immune status and other potential diseases to avoid the abuse of antiviral drugs.


Assuntos
Antivirais , Infecções por Citomegalovirus , Hepatite , Antivirais/uso terapêutico , Criança , Citomegalovirus , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Ganciclovir/uso terapêutico , Humanos , Lactente
7.
Br J Radiol ; 94(1121): 20201377, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33635729

RESUMO

Chronic liver disease (CLD) has rapidly increased in prevalence over the past two decades, resulting in significant morbidity and mortality worldwide. Historically, the clinical gold standard for diagnosis, assessment of severity, and longitudinal monitoring of CLD has been liver biopsy with histological analysis, but this approach has limitations that may make it suboptimal for clinical and research settings. Magnetic resonance (MR)-based biomarkers can overcome the limitations by allowing accurate, precise, and quantitative assessment of key components of CLD without the risk of invasive procedures. This review briefly describes the limitations associated with liver biopsy and the need for non-invasive biomarkers. It then discusses the current state-of-the-art for MRI-based biomarkers of liver iron, fat, and fibrosis, and inflammation.


Assuntos
Hepatopatias/diagnóstico por imagem , Hepatopatias/patologia , Imagem por Ressonância Magnética/métodos , Biomarcadores/análise , Biópsia , Doença Crônica , Técnicas de Imagem por Elasticidade , Fígado Gorduroso/diagnóstico por imagem , Hepatite/diagnóstico por imagem , Humanos , Ferro/análise , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Imagem por Ressonância Magnética/economia , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem
8.
Medicine (Baltimore) ; 100(6): e24723, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578617

RESUMO

ABSTRACT: This study objected to evaluate the accuracy of the gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aspartate aminotransferase-to-platelet ratio index (APRI), red cell distribution width (RDW), and fibrosis-4 index (FIB4) index, compared with liver biopsy (LB), in predicting the severity of inflammation in drug-induced liver injury (DILI) patients.We evaluated patients with DILI who were followed at the First Hospital of Jilin University and underwent LB. Accuracy of each method was analyzed using ROC analysis. Classifications of liver inflammation included G0-4.One hundred fifty six DILI patients were included with LB and complete medical records. 62.8% (98), 39.1% (61), and 16.7% (26) were classified as ≥G2, ≥G3, or G4, respectively. The AUROCs, by degree of inflammation, were: ≥G2: GPR: 0.654, RDW: 0.635, APRI: 0.728, and FIB4: 0.739; ≥G3: GPR: 0.623, RDW: 0.703, APRI: 0.777, and FIB4: 0.781; and G4: GPR: 0.556, RDW: 0.647, APRI: 0.729, and FIB4: 0.714. To predict ≥G2 inflammation, there were no differences between the AUROCs for GPR, RDW, APRI, and FIB4. To predict ≥G3 inflammation, the AUROCs for FIB4 and APRI were higher than that for GPR (0.781 vs 0.623, P < .01; 0.777 vs 0.623, P < .05). As for G4 inflammation, the AUROCs for FIB4 and APRI were also higher than GPR (0.714 vs 0.556, P < .05, 0.729 vs 0.556, P < .05).When the level of inflammation was higher than G2 in patients with DILI, it could be predicted using APRI and FIB4 as non-invasive markers for this condition.


Assuntos
Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Índices de Eritrócitos , Índice de Gravidade de Doença , gama-Glutamiltransferase/sangue , Adulto , Biomarcadores/sangue , Biópsia , Doença Hepática Induzida por Substâncias e Drogas/complicações , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Feminino , Hepatite/etiologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas
11.
Nihon Shokakibyo Gakkai Zasshi ; 118(2): 161-167, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33563856

RESUMO

A 44-year-old man was admitted because of general malaise, jaundice, and epigastric pain. The patient had no significant medical history. However, the patient visited a brothel 3 months ago and noticed initial induration on his penis 2 months ago. Physical examination revealed swelling surface lymph nodes in the inguinals. Laboratory examination showed moderate hepatic disorder and jaundice. Hepatitis virus markers and various types of autoantibodies were negative, but serological test for syphilis was positive. The symptoms and abnormal data improved immediately after the patient was treated with amoxicillin (3000mg/day) and probenecid (750mg/day). Thus, a diagnosis of early syphilitic hepatitis was established. In addition, syphilis is not just a genital disease. This disease should be thought of in a patient with liver dysfunction, especially among people of high sexual activity.


Assuntos
Hepatite , Icterícia , Sífilis , Adulto , Amoxicilina , Hepatite/complicações , Hepatite/tratamento farmacológico , Humanos , Masculino , Probenecid , Sífilis/complicações , Sífilis/diagnóstico , Sífilis/tratamento farmacológico
12.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(1): 55-63, 2021 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-33509753

RESUMO

OBJECTIVE: To investigate the role of NDUFA13 inactivation in the pathogenesis of spontaneous hepatitis in mice and explore the possible mechanisms. METHODS: Hepatocyte-specific NDUFA13 knockout (NDUFA13fl/-) mice were generated by intercrossing NDUFA13fl/fl and Alb-Cre mice based on Cre/loxP transgenic technology, and tail and liver DNA of the mice was genotyped by PCR analysis. Ten NDUFA13fl/- mice and 10 littermate control NDUFA13fl/fl mice were housed, and in each group, 5 mice were euthanized at the age of 4 weeks and the other 5 at two years for pathological examination of the liver tissues with HE staining. Immunohistochemistry was used to verify the expression levels of NDUFA13, NF-κB/p65, NF-κB/p-p65 and inflammasome NLRP3. The total intracellular ROS and mitochondrial ROS levels were measured with a ROS staining kit. The expressions of the inflammatory cell markers (CD45, MPO, and F4/80) and inflammatory cytokines (IL1ß and IL33) in the liver were detected with immunohistochemistry and immunofluorescence assay. RESULTS: Liver-specific NDUFA13 heterozygous knockout mice were successfully constructed as verified by PCR results. HE staining revealed severe liver damage in both 4- week-old and 2-year-old NDUFA13fl/- mice as compared with their littermate controls. Immunohistochemistry showed a significant decrease of NDUFA13 expression in both 4-week-old and 2-year-old NDUFA13fl/- mice (P < 0.05). The expression levels of NF-κB signals p65, p-p65 and NLRP3 inflammasomes were all significantly increased in NDUFA13fl/- mice (P < 0.05). The total intracellular ROS and mitochondrial ROS levels in NDUFA13fl/- mice were also significantly increased. NDUFA13 knockout obviously promoted the expression of the inflammatory cell markers (CD45, MPO and F4/80) and the secretion of IL-1ß and IL-33 in the liver tissue of the mice (P < 0.05). CONCLUSIONS: Hepatocytes-specific NDUFA13 ablation can trigger spontaneous hepatitis in mice possibly mediated by the activation of ROS/NF-κB/NLRP3 signaling.


Assuntos
Hepatite , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Inflamassomos , Camundongos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Transdução de Sinais
13.
AJR Am J Roentgenol ; 216(3): 812-823, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33439049

RESUMO

OBJECTIVE. The purpose of this article is to review the spectrum, etiopathogenesis, clinical presentation, imaging features, differential diagnoses, and management of emphysematous infections of the abdomen and pelvis. CONCLUSION. Emphysematous infections are associated with high morbidity and mortality and thus need urgent medical and surgical interventions. CT is the most sensitive modality to detect gas; CT provides definitive diagnosis in most cases and can depict the extent of involvement.


Assuntos
Enfisema/diagnóstico por imagem , Gases , Tomografia Computadorizada por Raios X , Parede Abdominal/diagnóstico por imagem , Parede Abdominal/microbiologia , Abscesso/diagnóstico por imagem , Abscesso/microbiologia , Aortite/diagnóstico por imagem , Aortite/microbiologia , Cistite/diagnóstico por imagem , Cistite/microbiologia , Enfisema/microbiologia , Colecistite Enfisematosa/diagnóstico por imagem , Colecistite Enfisematosa/microbiologia , Feminino , Gangrena de Fournier/diagnóstico por imagem , Gangrena de Fournier/microbiologia , Gangrena Gasosa/diagnóstico por imagem , Gangrena Gasosa/microbiologia , Gastrite/diagnóstico por imagem , Gastrite/microbiologia , Hepatite/diagnóstico por imagem , Hepatite/microbiologia , Humanos , Masculino , Pancreatite/diagnóstico por imagem , Pancreatite/microbiologia , Doenças Prostáticas/diagnóstico por imagem , Doenças Prostáticas/microbiologia , Abscesso do Psoas/diagnóstico por imagem , Abscesso do Psoas/microbiologia , Pielite/diagnóstico por imagem , Pielite/microbiologia , Pielonefrite/diagnóstico por imagem , Pielonefrite/microbiologia , Doenças Uterinas/diagnóstico por imagem , Doenças Uterinas/microbiologia
14.
Clin Immunol ; 224: 108662, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33412294

RESUMO

X-linked severe combined immunodeficiency (X-SCID) is a disorder of adaptive immunity caused by mutations in the IL-2 receptor common gamma chain gene resulting in deficiencies of T and natural killer cells, coupled with severe dysfunction in B cells. X-SCID is lethal without allogeneic stem cell transplant or gene therapy due to opportunistic infections. An infant with X-SCID became infected with SARS-CoV-2 while awaiting transplant. The patient developed severe hepatitis without the respiratory symptoms typical of COVID-19. He was treated with convalescent plasma, and thereafter was confirmed to have SARS-CoV-2 specific antibodies, as detected with a microfluidic antigen array. After resolution of the hepatitis, he received a haploidentical CD34 selected stem cell transplant, without conditioning, from his father who had recovered from COVID-19. SARS CoV-2 was detected via RT-PCR on nasopharyngeal swabs until 61 days post transplantation. He successfully engrafted donor T and NK cells, and continues to do well clinically.


Assuntos
/complicações , Hepatite/virologia , Imunodeficiência Combinada Severa/complicações , Humanos , Imunização Passiva/métodos , Lactente , Masculino
15.
Phytomedicine ; 81: 153426, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33341026

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, and it is closely associated to obesity, type 2 diabetes mellitus, and dyslipidemia. Medicinal cannabis and some neutral cannabinoids have been suggested as a potential therapy for liver diseases. HYPOTHESIS: Δ9-tetrahydrocannabinolic acid (Δ9-THCA), the non-psychotropic precursor of Δ9-THC, is one of the most abundant cannabinoids presents in Cannabis Sativa. However, its biological activities have been poorly investigated. Herein, we studied the antifibrotic and antiinflammatory activities of Δ9-THCA in two different animal models of liver injury, providing a rationale for additional studies on the medicinal use of this cannabinoid in the treatment of liver fibrosis and the management of NAFLD. STUDY DESIGN: The antifibrotic activity of Δ9-THCA in vitro was investigated in the cell lines LX-2 and NIH-3T3-Col1A2-luc. Non-alcoholic liver fibrosis was induced in mice by CCl4 treatment or, alternatively, by 23-week high fat diet (HFD) feeding. Δ9-THCA was administered daily intraperitoneally during the CCl4 treatment or during the last 3 weeks in HFD-fed mice. METHODS: TGFß-induced profibrotic gene expression was analyzed by luciferase and qPCR assays. Liver fibrosis and inflammation were assessed by immunochemistry and qPCR. Blood glucose, insulin, leptin and triglyceride levels were measured in HFD mice. RESULTS: Δ9-THCA inhibited the expression of Tenascin C (TNC) and Col3A1 induced by TGFß in LX-2 cells and the transcriptional activity of the Col1A2 promoter in fibroblasts. Δ9-THCA significantly attenuated CCl4-induced liver fibrosis and inflammation and reduced T cell and macrophage infiltration. Mice fed HFD for 23 weeks developed severe obesity (DIO), fatty liver and marked liver fibrosis, accompanied by immune cell infiltration. Δ9-THCA, significantly reduced body weight and adiposity, improved glucose tolerance, and drastically attenuated DIO-induced liver fibrosis and immune cell infiltration. CONCLUSIONS: Δ9-THCA prevents TGFß-induced fibrotic markers in vitro and liver inflammation and fibrogenesis in vivo, providing a rationale for additional studies on the medicinal use of this cannabinoid, as well as cannabis preparations containing it, for the treatment of liver fibrosis and the management of NAFLD.


Assuntos
Dronabinol/farmacologia , Hepatite/tratamento farmacológico , Cirrose Hepática/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Cannabis/química , Tetracloreto de Carbono/toxicidade , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatite/etiologia , Hepatite/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/complicações , Obesidade/etiologia
16.
Adv Exp Med Biol ; 1287: 69-80, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33034027

RESUMO

Interactions between liver cells are closely regulated by Notch signaling. Notch signaling has been reported clinically related to bile duct hypogenesis in Alagille syndrome, which is caused by mutations in the Jagged1 gene. Notch activation and hepatocarcinogenesis are closely associated since cancer signaling is affected by the development of liver cells and cancer stem cells. Gene expression and genomic analysis using a microarray revealed that abnormalities in Notch-related genes were associated with the aggressiveness of liver cancer. This pattern was also accompanied with α-fetoprotein- and EpCAM-expressing phenotypes in vitro, in vivo, and in clinical tissues. Hepatitis B or C virus chronic infection or alcohol- or steatosis-related liver fibrosis induces liver cancer. Previous reports demonstrated that HBx, a hepatitis B virus protein, was associated with Jagged1 expression. We found that the Jagged1 and Notch1 signaling pathways were closely associated with the transcription of covalently closed circular hepatitis B virus DNA, which regulated cAMP response element-binding protein, thereby affecting Notch1 regulation by the E3 ubiquitin ligase ITCH. This viral pathogenesis in hepatocytes induces liver cancer. In conclusion, Notch signaling exerts various actions and is a clinical signature associated with hepatocarcinogenesis and liver context-related developmental function.


Assuntos
Neoplasias Hepáticas , Receptores Notch/metabolismo , Transdução de Sinais , Hepatite/metabolismo , Hepatite/virologia , Vírus da Hepatite B/patogenicidade , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/virologia , Proteínas Repressoras/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
17.
Methods Mol Biol ; 2225: 275-292, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33108669

RESUMO

Ischemia-reperfusion injury (IRI) drives early and long-term damage to organs as well as compounding damage from acute transplant rejection and surgical trauma. IRI initiates an aggressive and prolonged inflammation leading to tissue injury, organ failure, and death. However, there are few effective therapeutic interventions for IRI. The destructive inflammatory cell activity in IRI is part of an aberrant innate immune response that triggers multiple pathways. Hence, immune-modulating treatments to control pathways triggered by IRI hold great therapeutic potential. Viruses, especially large DNA viruses, have evolved highly effective immune-modulating proteins for the purpose of immune evasion and to protect the virus from the host immune defenses. A number of these immune-modulating proteins have proven therapeutically effective in preclinical models, many with function targeting pathways known to be involved in IRI. The use of virus-derived immune-modulating proteins thus represents a promising source for new treatments to target ischemia-reperfusion injury. Laboratory small animal models of IRI are well established and are able to reproduce many aspects of ischemia-reperfusion injury seen in humans. This chapter will discuss the methods used to perform the IRI procedure in mice, as well as clinically relevant diagnostic tests to evaluate liver injury and approaches for assessing histological damage while testing novel immune modulating protein treatments.


Assuntos
Anti-Inflamatórios/farmacologia , Hepatite/prevenção & controle , Fatores Imunológicos/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Proteínas Virais/farmacologia , Isquemia Quente/métodos , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Animais , Anti-Inflamatórios/imunologia , Anti-Inflamatórios/metabolismo , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Biomarcadores/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Hepatite/genética , Hepatite/imunologia , Hepatite/patologia , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/biossíntese , Fatores Imunológicos/imunologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/imunologia , Fígado/patologia , Camundongos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/patologia , Coloração e Rotulagem/métodos , Proteínas Virais/biossíntese , Proteínas Virais/imunologia
18.
J Ethnopharmacol ; 264: 113287, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32858197

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Folk medicine reports have described the use of Chenopodium ambrosioides as an anti-inflammatory, analgesic, and anthelmintic herb. These effects, including its activity against intestinal worms, are already scientifically observed. However, the immunological mechanisms of this species in the treatment of Schistosoma mansoni infection are unknown. AIM OF THE STUDY: To evaluate the immunological and anti-Schistosoma mansoni effects of a crude Chenopodium ambrosioides hydro-alcoholic extract (HCE). MATERIALS AND METHODS: For the in vitro analysis, cercariae and adult worms were exposed to different concentrations (0 to 10,000 µg/mL) of the HCE. For the in vivo evaluation, Swiss mice were infected with 50 cercariae of S. mansoni and separated into groups according to treatment as follows: a negative control (without treatment), a positive control (treated with Praziquantel®), HCE1 Group (treated with HCE during the cutaneous phase), HCE2 Group (treated with HCE during the lung phase), HCE3 Group (treated with HCE during the young worm phase), and HCE4 Group (treated with HCE during the adult worm phase). The animals treated with HCE received daily doses of 50 mg/kg, by gavage, for seven days, corresponding to the different developmental stages of S. mansoni. For comparison, a clean control group (uninfected and untreated) was also included. All animals were euthanized 60 days post-infection to allow the following assessments to be performed: a complete blood cells count, counts of eggs in the feces and liver, the quantification of cytokines and IgE levels, histopathological evaluations of the livers, and the analysis of inflammatory mediators. RESULTS: HCE treatment increased the mortality of cercariae and adult worms in vitro. The HCE treatment in vivo reduced the eggs in feces and liver. The number and area of liver granulomas, independent of the phase of treatment, were also reduced. The treatment with HCE reduced the percentage of circulating eosinophils, IgE, IFN-γ, TNF-α, and IL-4. In contrast, the treatment with the HCE, dependent on the phase, increased IL-10 levels and the number of peritoneal and bone marrow cells, mainly of T lymphocytes, B lymphocytes, and macrophages. This effect could be due to secondary compounds presents in this extract, such as kaempferol, quercetin and derivatives. CONCLUSIONS: This study demonstrates that Chenopodium ambrosioides has antiparasitic and immunomodulatory activity against the different phases of schistosomiasis, reducing the granulomatous inflammatory profile caused by the infection and, consequently, improving the disease prognosis.


Assuntos
Antiparasitários/uso terapêutico , Chenopodium ambrosioides , Hepatite/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Esquistossomose mansoni/tratamento farmacológico , Animais , Antiparasitários/isolamento & purificação , Antiparasitários/farmacologia , Hepatite/metabolismo , Hepatite/parasitologia , Hepatite/patologia , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Distribuição Aleatória , Schistosoma mansoni/efeitos dos fármacos , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/metabolismo , Esquistossomose mansoni/patologia
19.
Med. clín (Ed. impr.) ; 155(12): 541-547, dic. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-198358

RESUMO

In recent years, immunotherapy has become an important pillar of cancer treatment, with high response rates regardless of tumour histology or baseline mutations. However, immune activation associated with check-point inhibitors is not selective and a large variety of immune-related adverse events have been associated with anti-PD1, anti-PD-1/L-1 and anti-CTLA-4 agents. Though diagnosis and treatment of these toxicities have been established according to the recommendations from clinical trials and in line with the autoimmune disorders that they mimic, increasing real-world data is coming up showing that these adverse events may have differential characteristics and management, especially in terms of the use of corticoids, second-line treatments, salvage therapy for life-threatening cases and reintroduction of immunotherapy. Herein we present a comprehensive review of current recommendations and real-world data on the main immune-related adverse events of immunotherapy


En los últimos años la inmunoterapia se ha convertido en un pilar fundamental para el tratamiento del cáncer, con altas tasas de respuesta, independientemente de la histología tumoral o de las mutaciones basales. Sin embargo, la activación inmune asociada a los inhibidores de control no es selectiva, habiéndose asociado una gran variedad de efectos adversos relacionados con la inmunidad a los agentes anti-PD1, anti-PD-1/L-1 y anti-CTLA-4. Aunque se han establecido el diagnóstico y el tratamiento de estas toxicidades en virtud de las recomendaciones de los ensayos clínicos, en consonancia con los trastornos autoinmunes que imitan, el incremento de los datos del mundo real refleja que dichos efectos adversos pueden tener características y manejos diferenciales, especialmente en términos de uso de corticoides, tratamientos de segunda línea, terapia de rescate para casos potencialmente letales, y reintroducción de la inmunoterapia. Presentamos aquí una revisión amplia de las recomendaciones actuales y los datos del mundo real sobre los principales efectos adversos de la inmunoterapia


Assuntos
Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Neoplasias/imunologia , Neoplasias/terapia , Ensaios Clínicos como Assunto , Imunoterapia/efeitos adversos , Hepatite/imunologia , Hepatite/terapia , Miosite/imunologia , Miosite/terapia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
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