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1.
Molecules ; 25(21)2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33147850

RESUMO

Zebrafish has been a reliable model system for studying human viral pathologies. SARS-CoV-2 viral infection has become a global chaos, affecting millions of people. There is an urgent need to contain the pandemic and develop reliable therapies. We report the use of a humanized zebrafish model, xeno-transplanted with human lung epithelial cells, A549, for studying the protective effects of a tri-herbal medicine Coronil. At human relevant doses of 12 and 58 µg/kg, Coronil inhibited SARS-CoV-2 spike protein, induced humanized zebrafish mortality, and rescued from behavioral fever. Morphological and cellular abnormalities along with granulocyte and macrophage accumulation in the swim bladder were restored to normal. Skin hemorrhage, renal cell degeneration, and necrosis were also significantly attenuated by Coronil treatment. Ultra-high-performance liquid chromatography (UHPLC) analysis identified ursolic acid, betulinic acid, withanone, withaferine A, withanoside IV-V, cordifolioside A, magnoflorine, rosmarinic acid, and palmatine as phyto-metabolites present in Coronil. In A549 cells, Coronil attenuated the IL-1ß induced IL-6 and TNF-α cytokine secretions, and decreased TNF-α induced NF-κB/AP-1 transcriptional activity. Taken together, we show the disease modifying immunomodulatory properties of Coronil, at human equivalent doses, in rescuing the pathological features induced by the SARS-CoV-2 spike protein, suggesting its potential use in SARS-CoV-2 infectivity.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Sacos Aéreos/efeitos dos fármacos , Sacos Aéreos/virologia , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Cromatografia Líquida de Alta Pressão/métodos , Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Modelos Animais de Doenças , Febre/tratamento farmacológico , Febre/etiologia , Hemorragia/prevenção & controle , Humanos , Interleucina-6/metabolismo , Rim/efeitos dos fármacos , Necrose/patologia , Necrose/prevenção & controle , Pandemias , Fitoterapia , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologia , Mucosa Respiratória/transplante , Ativação Transcricional/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Peixe-Zebra
2.
Nat Cell Biol ; 22(9): 1042-1048, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32868903

RESUMO

Ferroptosis is a regulated form of necrotic cell death that is caused by the accumulation of oxidized phospholipids, leading to membrane damage and cell lysis1,2. Although other types of necrotic death such as pyroptosis and necroptosis are mediated by active mechanisms of execution3-6, ferroptosis is thought to result from the accumulation of unrepaired cell damage1. Previous studies have suggested that ferroptosis has the ability to spread through cell populations in a wave-like manner, resulting in a distinct spatiotemporal pattern of cell death7,8. Here we investigate the mechanism of ferroptosis execution and discover that ferroptotic cell rupture is mediated by plasma membrane pores, similarly to cell lysis in pyroptosis and necroptosis3,4. We further find that intercellular propagation of death occurs following treatment with some ferroptosis-inducing agents, including erastin2,9 and C' dot nanoparticles8, but not upon direct inhibition of the ferroptosis-inhibiting enzyme glutathione peroxidase 4 (GPX4)10. Propagation of a ferroptosis-inducing signal occurs upstream of cell rupture and involves the spreading of a cell swelling effect through cell populations in a lipid peroxide- and iron-dependent manner.


Assuntos
Ferroptose/fisiologia , Osmose/fisiologia , Morte Celular/fisiologia , Linhagem Celular Tumoral , Células HeLa , Humanos , Ferro/metabolismo , Células MCF-7 , Necrose/metabolismo , Necrose/patologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Células U937
4.
Medicine (Baltimore) ; 99(27): e21112, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629745

RESUMO

RATIONALE: Lupus miliaris disseminatus faciei (LMDF) is an inflammatory granulomatous skin disease without a clear etiology that frequently involves the middle area of the face and the upper eyelids. Pathological features of the disease include caseation necrosis and epithelioid granuloma. Consensus treatment for LMDF is currently unavailable. PATIENT CONCERNS: A 47-year-old Chinese female patient who presented with facial pruritic, erythematous papules 8 months before this study. She was diagnosed with skin tuberculosis at another hospital and given antituberculosis medication. However, the treatment was not efficacious. DIAGNOSES: In this study, the diagnosis of Demodex-induced LMDF was made by a dermatologist according to physical examination, skin biopsy pathology, and microscopic examination. INTERVENTIONS: The patient was given ornidazole tablets (500 mg twice a day) and recombinant bovine basic fibroblast growth factor gel (0.2 g/cm twice a day) for an 8-week period. OUTCOMES: Eight weeks after the treatment, the facial erythematous papules were improved, and no new skin lesions were observed. The patient showed no signs of recurrence during the 6-month follow-up. LESSONS SUBSECTIONS: This case showed that ornidazole combined with recombinant bovine basic fibroblast growth factor gel might be useful in treatment of Demodex-induced LMDF. In addition, the results suggested that pathological caseation necrosis was caused by a series of inflammatory and immune responses to Demodex infection.


Assuntos
Dermatoses Faciais/etiologia , Rosácea/parasitologia , Pele/parasitologia , Amebicidas/administração & dosagem , Amebicidas/uso terapêutico , Animais , Grupo com Ancestrais do Continente Asiático/etnologia , Erros de Diagnóstico , Dermatoses Faciais/patologia , Feminino , Fatores de Crescimento de Fibroblastos/administração & dosagem , Fatores de Crescimento de Fibroblastos/uso terapêutico , Granuloma/patologia , Humanos , Pessoa de Meia-Idade , Ácaros/parasitologia , Necrose/patologia , Ornidazol/administração & dosagem , Ornidazol/uso terapêutico , Rosácea/tratamento farmacológico , Pele/patologia , Pele/ultraestrutura , Resultado do Tratamento , Tuberculose Cutânea/diagnóstico , Tuberculose Cutânea/tratamento farmacológico
5.
Neurology ; 95(10): e1392-e1403, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32631922

RESUMO

OBJECTIVE: To develop and validate a nomogram to predict epilepsy in patients with radiation-induced brain necrosis (RN). METHODS: The nomogram was based on a retrospective analysis of 302 patients who were diagnosed with symptomatic RN from January 2005 to January 2016 in Sun Yat-sen Memorial Hospital using the Cox proportional hazards model. Discrimination of the nomogram was assessed by the concordance index (C index) and the calibration curve. The results were internally validated using bootstrap resampling and externally validated using 128 patients with RN from 2 additional hospitals. RESULTS: A total of 302 patients with RN with a median follow-up of 3.43 years (interquartile range 2.54-5.45) were included in the training cohort; 65 (21.5%) developed symptomatic epilepsy during follow-up. Seven variables remained significant predictors of epilepsy after multivariable analyses: MRI lesion volume, creatine phosphokinase, the maximum radiation dose to the temporal lobe, RN treatment, history of hypertension and/or diabetes, sex, and total cholesterol level. In the validation cohort, 28 out of 128 (21.9%) patients had epilepsy after RN within a median follow-up of 3.2 years. The nomogram showed comparable discrimination between the training and validation cohort (corrected C index 0.76 [training] vs 0.72 [95% confidence interval 0.62-0.81; validation]). CONCLUSION: Our study developed an easily applied nomogram for the prediction of RN-related epilepsy in a large RN cohort. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a nomogram predicts post-RN epilepsy.


Assuntos
Irradiação Craniana/efeitos adversos , Epilepsia/diagnóstico , Epilepsia/etiologia , Nomogramas , Lesões por Radiação/complicações , Encéfalo/patologia , Encéfalo/efeitos da radiação , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Necrose/etiologia , Necrose/patologia , Lesões por Radiação/diagnóstico , Lesões por Radiação/patologia , Estudos Retrospectivos , Fatores de Risco
6.
Presse Med ; 49(3): 104039, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32650042

RESUMO

Lung involvement is one of the most common clinical features in ANCA-associated vasculitides (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). In this review, we detail the five main presentations of pulmonary involvement in AAV: necrotizing granulomatous inflammation, tracheobronchial inflammation, pulmonary capillaritis, interstitial lung disease (ILD) and asthma with their clinical, radiological and therapeutic characteristics. The prevalence of these manifestations is variable according to the subtype of AAV, necrotizing granulomatous inflammation and tracheobronchial inflammation being defining features of GPA whereas ILD is primarily seen in patients with MPA, especially in association with ANCA directed against myeloperoxydase (MPO-ANCA), and asthma is characteristic of EGPA. Despite recent progresses in the diagnosis and management of these conditions, several questions remain and are discussed here, including local treatments for subglottic stenosis, the uncertain efficacy of plasma exchanges for alveolar hemorrhage, the potential role of antifibrotic agents in ILD associated with MPA, and the use of novel anti-IL-5 strategies in EGPA.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Doenças Pulmonares Intersticiais/etiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Asma/etiologia , Asma/patologia , Asma/terapia , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/patologia , Síndrome de Churg-Strauss/terapia , Granuloma/etiologia , Granuloma/patologia , Granuloma/terapia , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/patologia , Granulomatose com Poliangiite/terapia , Humanos , Inflamação/etiologia , Inflamação/patologia , Inflamação/terapia , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/terapia , Poliangiite Microscópica/complicações , Poliangiite Microscópica/patologia , Poliangiite Microscópica/terapia , Necrose/etiologia , Necrose/patologia , Necrose/terapia
7.
Cells ; 9(6)2020 06 02.
Artigo em Inglês | MEDLINE | ID: covidwho-459483

RESUMO

The COVID-19 pandemic is progressing worldwide with an alarming death toll. There is an urgent need for novel therapeutic strategies to combat potentially fatal complications. Distinctive clinical features of severe COVID-19 include acute respiratory distress syndrome, neutrophilia, and cytokine storm, along with severe inflammatory response syndrome or sepsis. Here, we propose the putative role of enhanced neutrophil infiltration and the release of neutrophil extracellular traps, complement activation and vascular thrombosis during necroinflammation in COVID-19. Furthermore, we discuss how neutrophilic inflammation contributes to the higher mortality of COVID-19 in patients with underlying co-morbidities such as diabetes and cardiovascular diseases. This perspective highlights neutrophils as a putative target for the immunopathologic complications of severely ill COVID-19 patients. Development of the novel therapeutic strategies targeting neutrophils may help reduce the overall disease fatality rate of COVID-19.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Armadilhas Extracelulares/imunologia , Neutrófilos/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Animais , Betacoronavirus/fisiologia , Doenças Cardiovasculares/complicações , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Complicações do Diabetes/virologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Necrose/imunologia , Necrose/patologia , Neutrófilos/metabolismo , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico
8.
Cells ; 9(6)2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32498376

RESUMO

The COVID-19 pandemic is progressing worldwide with an alarming death toll. There is an urgent need for novel therapeutic strategies to combat potentially fatal complications. Distinctive clinical features of severe COVID-19 include acute respiratory distress syndrome, neutrophilia, and cytokine storm, along with severe inflammatory response syndrome or sepsis. Here, we propose the putative role of enhanced neutrophil infiltration and the release of neutrophil extracellular traps, complement activation and vascular thrombosis during necroinflammation in COVID-19. Furthermore, we discuss how neutrophilic inflammation contributes to the higher mortality of COVID-19 in patients with underlying co-morbidities such as diabetes and cardiovascular diseases. This perspective highlights neutrophils as a putative target for the immunopathologic complications of severely ill COVID-19 patients. Development of the novel therapeutic strategies targeting neutrophils may help reduce the overall disease fatality rate of COVID-19.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Armadilhas Extracelulares/imunologia , Neutrófilos/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Animais , Betacoronavirus/fisiologia , Doenças Cardiovasculares/complicações , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Complicações do Diabetes/virologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Necrose/imunologia , Necrose/patologia , Neutrófilos/metabolismo , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico
9.
J Laryngol Otol ; 134(5): 404-408, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32498734

RESUMO

OBJECTIVE: To predict skull base osteomyelitis in patients with necrotising otitis externa using diffusion-weighted imaging. METHODS: A retrospective analysis was conducted of 25 necrotising otitis externa patients with skull base osteomyelitis (n = 10) or without skull base involvement (n = 14) who underwent a single-shot diffusion-weighted imaging of the skull base. RESULTS: The respective mean apparent diffusion coefficient values of the skull base, as determined by two reviewers, were 0.851 ± 0.15 and 0.841 ± 0.14 ×10-3mm2/s for the skull base osteomyelitis patients, and 1.065 ± 0.19 and 1.045 ± 0.20 ×10-3mm2/s for the necrotising otitis externa patients without skull base involvement. The difference in apparent diffusion coefficients between the groups was significant, for both reviewers (p = 0.008 and 0.012). The optimal threshold apparent diffusion coefficient for predicting skull base osteomyelitis in necrotising otitis externa patients was 0.945 ×10-3mm2/s and 0.915 ×10-3mm2/s, with an area under the curve of 0.825 and 0.800, accuracy of 87.5 and 83.3 per cent, sensitivity of 85.7 and 90.0 per cent, and specificity of 90.0 and 78.6 per cent, for each reviewer respectively. CONCLUSION: Apparent diffusion coefficient is a non-invasive imaging parameter useful for predicting skull base osteomyelitis in necrotising otitis externa patients.


Assuntos
Osteomielite/patologia , Otite Externa/complicações , Base do Crânio , Adulto , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/diagnóstico , Necrose/patologia , Osteomielite/complicações , Osso Petroso , Infecções por Pseudomonas/diagnóstico , Pseudomonas aeruginosa , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus
10.
Mycotoxin Res ; 36(3): 311-318, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32372256

RESUMO

Fusarium infections have been reported in aquatic animals, but are still poorly investigated in wild salmonids. The aim of the study was to determine the impact of the fungi and their toxins on the health status of brown trout (Salmo trutta morpha trutta) migrating from the Baltic Sea to the freshwater. Individuals from the wild brown trout population exhibiting ulcerative skin lesions were collected from the Slupia River in Poland and subjected to microbiological, histopathological, and hematological examinations, as well as toxicological analysis for a presence of mycotoxins. The results of microflora isolation from the brown trout skin samples revealed the presence of conditionally pathogenic bacteria and fungi classified by molecular techniques as Fusarium spp. Toxicological analysis allowed for detection of zearalenone (ZEN) in the liver, kidney, and gastrointestinal tract of the fish. In several cases, there was α-zearalenone (α-ZEL) identified at trace levels in the liver, as well as sterigmatocystin and enniatin B at low levels in the kidney and the liver. Histopathological examination revealed the presence of fungal hyphae disrupting the epidermis and penetrating into the necrotic dermis and hypodermis. The decreased values of the blood parameters, i.e., hemoglobin concentration (HGB), packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and white blood cell count (WBC), were indicative of osmoregulation failure being a consequence of the skin damage. The results of the study provide new information regarding Fusarium sp. infection in brown trout and serve as the basis for further research on the potential impact of the fungi and their mycotoxins on the Baltic salmonid population, including their role in ulcerative dermal necrosis.


Assuntos
Doenças dos Peixes/microbiologia , Fusarium/metabolismo , Micotoxinas/toxicidade , Necrose/veterinária , Dermatopatias/veterinária , Animais , Doenças dos Peixes/patologia , Fusarium/química , Micotoxinas/análise , Micotoxinas/metabolismo , Necrose/microbiologia , Necrose/patologia , Polônia , Pele/microbiologia , Dermatopatias/microbiologia , Dermatopatias/patologia , Truta/microbiologia
11.
Acta Cir Bras ; 35(2): e202000205, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428061

RESUMO

Purpose To investigate the effects of induction of selective liver hypothermia in a rodent model. Methods Seven male Wistar rats were subjected to 90 minutes of partial 70% liver ischemia and topic liver 26°C hypothermia (H group). Other seven male Wistar rats were subjected to 90 minutes of partial 70% normothermic liver ischemia (N group). Five additional rats underwent a midline incision and section of liver ligaments under normothermic conditions and without any liver ischemia (sham group). All animals were sacrificed 24-h after reperfusion, and livers were sampled for analyses. Pathology sections were scored for sinusoidal congestion, ballooning, hepatocelllular necrosis and the presence of neutrophilic infiltrates. Results At the end of the experiment, liver tissue expressions of TNF-ɑ, IL-1ß, iNOS and TNF-ɑ/IL-10 ratio were significantly reduced in the H group compared to N group, whereas IL-10 and eNOS were significantly increased in H group. Histopathological injury scores revealed a significant decrease in ischemia/reperfusion (I/R) injuries in H group. Conclusion Selective liver hypothermia prevented I/R injury by inhibiting the release of inflammatory cytokines, preserves microcirculation, prevents hepatocellular necrosis and leukocyte infiltration, allowing maintenance of the liver architecture.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Hipotermia Induzida/métodos , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Lesão Pulmonar Aguda/patologia , Animais , Temperatura Corporal , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Isquemia/patologia , Fígado/patologia , Masculino , Necrose/patologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fator de Necrose Tumoral alfa
12.
Wilderness Environ Med ; 31(3): 317-323, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32456876

RESUMO

Snakebites are a neglected and underestimated global health hazard. In the Brazilian Amazon, Bothrops snakebites are the most prevalent and may lead to severe complications. Here we describe a severe case of Bothrops atrox snakebite that, owing to delayed medical assistance, presented with renal and respiratory failure, compartment syndrome, and tissue necrosis. After several fasciotomy surgeries, the patient survived; however, he showed significant functional disability. Prompt management of snake envenomation would aid in the early diagnosis of local and systemic complications and, consequently, would result in a better functional outcome with improved quality of life.


Assuntos
Bothrops , Síndromes Compartimentais/fisiopatologia , Necrose/patologia , Qualidade de Vida , Mordeduras de Serpentes/complicações , Adulto , Animais , Brasil , Síndromes Compartimentais/etiologia , Cuidados Críticos , Fasciotomia , Humanos , Masculino , Necrose/etiologia , Necrose/cirurgia , Transplante de Tecidos
13.
Toxicology ; 439: 152464, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32315716

RESUMO

Mitochondrial injury and depolarization are primary events in acetaminophen hepatotoxicity. Previous studies have shown that restoration of mitochondrial function in surviving hepatocytes, which is critical to recovery, is at least partially accomplished via biogenesis of new mitochondria. However, other studies indicate that mitochondria also have the potential to spontaneously repolarize. Although repolarization was previously observed only at a sub-hepatotoxic dose of acetaminophen, we postulated that mitochondrial repolarization in hepatocytes outside the centrilobular regions of necrosis might contribute to recovery of mitochondrial function following acetaminophen-induced injury. Our studies utilized longitudinal intravital microscopy of millimeter-scale regions of the mouse liver to characterize the spatio-temporal relationship between mitochondrial polarization and necrosis early in acetaminophen-induced liver injury. Treatment of male C57BL/6J mice with a single intraperitoneal 250 mg/kg dose of acetaminophen resulted in hepatotoxicity that was apparent histologically within 2 h of treatment, leading to 20 and 60-fold increases in serum aspartate aminotransferase and alanine aminotransferase, respectively, within 6 h. Intravital microscopy of the livers of mice injected with rhodamine123, TexasRed-dextran, propidium iodide and Hoechst 33342 detected centrilobular foci of necrosis within extended regions of mitochondrial depolarization within 2 h of acetaminophen treatment. Although regions of necrosis were more apparent 6 h after acetaminophen treatment, the vast majority of hepatocytes with depolarized mitochondria did not progress to necrosis, but rather recovered mitochondrial polarization within 6 h. Recovery of mitochondrial function following acetaminophen hepatotoxicity thus involves not only biogenesis of new mitochondria, but also repolarization of existing mitochondria. These studies also revealed a spatial distribution of necrosis and mitochondrial depolarization whose single-cell granularity is inconsistent with the hypothesis that communication between neighboring cells plays an important role in the propagation of necrosis during the early stages of APAP hepatotoxicity. Small islands of healthy, intact cells were frequently found surrounded by necrotic cells, and small islands of necrotic cells were frequently found surrounded by healthy, intact cells. Time-series studies demonstrated that these "islands", consisting in some cases of single cells, are persistent; over a period of hours, injury does not spread from individual necrotic cells to their neighbors.


Assuntos
Acetaminofen/toxicidade , Analgésicos não Entorpecentes/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/patologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Fígado/enzimologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Necrose/patologia
14.
An Acad Bras Cienc ; 92(1): e20181120, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32321020

RESUMO

the focus ofthis study was to testthe hypothesisthatthere would be no difference betweenthe biocompatibility of silicon dioxide nanofilms used as antimicrobial agents. Sixty male Wistar rats were divided into 4 groups (n=15): Group C (Control,Polyethylene), Group AR (Acrylic Resin), Group NP (Acrylic Resin coated with NP-Liquid), Group BG (Acrylic Resin coated with Bacterlon).the animals were sacrificed with 7,15 and 30 days and tissues analyzed as regardsthe events of inflammatory infiltrate, edema, necrosis, granulation tissue, mutinucleated giant cells, fibroblasts and collagen. Kruskal-Wallis and Dunn tests was used (P<0.05). Intense inflammatory infiltrate was shown mainly in Groups BG and AR, with significant difference from Control Group inthe time interval of 7days (P=0.004). Necrosis demonstrated significant difference between Group BG and Control Group (P<0.05) inthe time intervals of 7 days. For collagen fibers,there was significant difference betweenthe Control Group and Groups AR and BG inthe time interval of 7 days (P=0.006), and between BG and Control Groups inthe time intervals of 15 days (P=0.010).the hypothesis was rejected. Bacterlon demonstratedthe lowest level, and NP-Liquid Glassthe highest level of tissue compatibility, and best cell repair.the coating with NP-Liquid Glass was demonstrated to be highly promising for clinical use.


Assuntos
Resinas Acrílicas/farmacologia , Materiais Biocompatíveis/farmacologia , Edema/induzido quimicamente , Necrose/induzido quimicamente , Dióxido de Silício/farmacologia , Tela Subcutânea/patologia , Resinas Acrílicas/química , Animais , Materiais Biocompatíveis/química , Edema/patologia , Masculino , Teste de Materiais , Modelos Animais , Necrose/patologia , Ratos , Ratos Wistar , Dióxido de Silício/química , Tela Subcutânea/efeitos dos fármacos
15.
BMC Surg ; 20(1): 54, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32192489

RESUMO

BACKGROUND: Distal gastrectomy with lymph node dissection, a standard operative technique for gastric cancer treatment, is safely performed because the stomach has a rich vascular supply. Gastric remnant necrosis caused by cholesterol crystal embolization following distal gastrectomy has not been described previously. We report a case of gastric remnant necrosis in a patient with cholesterol crystal embolization. CASE PRESENTATION: A 70-year-old man with a history of cholesterol crystal embolization presented to our surgery department with complaints of anorexia and dysphasia. He was diagnosed with gastric cancer invading the pyloric antrum and underwent distal gastrectomy with Billroth 2 reconstruction. On postoperative day 11, he developed abdominal pain without fever. Emergency laparotomy revealed that most parts of the remnant stomach were necrosed. Total gastrectomy with Roux-en-Y reconstruction and abscess drainage were performed. After surgery, anastomotic leakage occurred and was treated conservatively. However, the superior pancreaticoduodenal artery aneurysm suddenly ruptured and he expired. CONCLUSIONS: Gastric remnant necrosis after distal gastrectomy can be a gastrointestinal presentation of cholesterol crystal embolization. Perioperative/intraoperative risk assessments such as preventive total gastrectomy or intraoperative assessment with indocyanine green fluorescence angiography may be desirable to avoid this complication.


Assuntos
Gastrectomia/métodos , Coto Gástrico/patologia , Gastroenterostomia/métodos , Neoplasias Gástricas/cirurgia , Idoso , Anastomose em-Y de Roux , Embolia de Colesterol/complicações , Humanos , Excisão de Linfonodo , Masculino , Necrose/patologia , Período Pós-Operatório
16.
Clin Exp Metastasis ; 37(3): 425-434, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32185576

RESUMO

To compare the local control and brain radionecrosis in patients with brain metastasis primarily treated by single-fraction radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (HFSRT). Between January 2012 and December 2017, 179 patients with only 1-3 brain metastases (total: 287) primarily treated by SRS (14 Gy) or HFSRT (23.1 Gy in 3 fractions of 7.7 Gy, every other day) were retrospectively analyzed in a single center. Follow-up imaging data were available in 152 patients with 246 lesions. The corresponding Biological Effective Dose (BED) were 33.6 Gy and 40.9 Gy respectively for SRS and HFSRT group, assuming an α/ß of 10 Gy. Local control (LC) and risk of radionecrosis (RN) were calculated by the Kaplan-Meier method. The actuarial local control rates at 6 and 12 months were 94% and 88.1% in SRS group, and 87.6% and 78.4%, in HFSRT group (p = 0.06), respectively. Only the total volume of edema was associated with worse LC (p = 0.01, HR 1.02, 95% CI [1.004-1.03]) in multivariate analysis. Brain radionecrosis occurred in 1 lesion in SRS group and 9 in HFSRT group. Median time to necrosis was 5.5 months (range 1-9). Only the volume of GTV was associated with RN (p = 0.02, HR 1.09, 95% CI [1.01-1.18]) in multivariate analysis. Multi-fraction SRT dose of 23.31 Gy in 3 fractions has similar efficacy to single-fraction SRT dose of 14 Gy in patients with brain metastases. A slightly higher occurrence of radionecrosis appeared in HFSRT group.


Assuntos
Neoplasias Encefálicas/radioterapia , Encéfalo/patologia , Fracionamento da Dose de Radiação , Lesões por Radiação/epidemiologia , Radiocirurgia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Necrose/diagnóstico , Necrose/epidemiologia , Necrose/etiologia , Necrose/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Intervalo Livre de Progressão , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Carga Tumoral , Adulto Jovem
17.
Parasitol Int ; 76: 102098, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32120051

RESUMO

Sarcocistys -associated menigoencephalitis is virtually an unrecognized cause of neurological disease in chickens. An undescribed species of Sarcocystis cause fatal infection in two backyard chickens in the Midwest of Brazil. Infected chickens presented anorexia, weight loss, incoordination, ataxia and opisthotonos. Yellow necrotic foci in the gray and white matter of the telencephalon were the main gross lesion. Microscopically, necrotizing granulomatous and heterophilic meningoencephalitis with intralesional Sarcocystis -like schizonts and mezoites were observed in the central nervous system. Molecular analysis of frozen brain samples of the two chickens was identical and the protozoan was named Sarcocystis sp. Chicken-2016-DF-BR. Complete nested PCR- sequence of Sarcocystis sp. Chicken-2016-DF-BR was equally similar to Sarcocystis anasi (EU553477) and Sarcocystis albifronsi (EU502868). This is the first report of Sarcocistys -associated meningoencephalitis with molecular characterization in backyard chickens.


Assuntos
Galinhas , Meningoencefalite/veterinária , Doenças das Aves Domésticas/diagnóstico , Sarcocystis/classificação , Animais , Encéfalo/parasitologia , Encéfalo/patologia , Brasil , Feminino , Masculino , Meningoencefalite/diagnóstico , Meningoencefalite/parasitologia , Meningoencefalite/patologia , Necrose/diagnóstico , Necrose/parasitologia , Necrose/patologia , Necrose/veterinária , Reação em Cadeia da Polimerase/veterinária , Doenças das Aves Domésticas/parasitologia , Doenças das Aves Domésticas/patologia , Sarcocystis/fisiologia
18.
Curr Opin Cell Biol ; 63: 186-193, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32163825

RESUMO

Necroptosis and pyroptosis are inflammatory forms of regulated necrotic cell death as opposed to apoptosis that is generally considered immunologically silent. Recent studies revealed unexpected links in the pathways regulating and executing cell death in response to activation of signaling cascades inducing apoptosis, necroptosis, and pyroptosis. Emerging evidence suggests that receptor interacting protein kinase 1 and caspase-8 control the cross-talk between apoptosis, necroptosis, and pyroptosis and determine the type of cell death induced in response to activation of cell death signaling.


Assuntos
Apoptose/genética , Caspase 8/fisiologia , Necroptose/genética , Piroptose/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/fisiologia , Animais , Caspase 8/genética , Caspase 8/metabolismo , Humanos , Necrose/genética , Necrose/patologia , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Transdução de Sinais/genética
19.
World Neurosurg ; 137: e462-e469, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32058117

RESUMO

BACKGROUND: There is no standard approach to differentiate cerebral radiation necrosis from tumor recurrence and no standard treatment pathway for symptomatic lesions. In addition, reports on histology-proven radiation necrosis and the underlying pathophysiology are scarce and highly relevant. METHODS: Our monocentric, retrospective analysis included 21 histology-proven cerebral radiation necroses. Our study focused on 1) potential risk factors for the development of radiation necrosis, 2) radiologic and histopathologic features of individual necroses, and 3) the suitability of previously reported magnetic resonance imaging (MRI)-based methods to identify radiation necroses based on specific structural image features. RESULTS: Average time between radiation treatment and development of necrosis was 4.68 years (95% confidence interval, 0.19-9.55 years). Matching available MRI data sets with those of patients with tumor lesions, we compared specificity and sensitivity of 3 previously reported methods to identify radionecrosis based on imaging criteria. In our hands, none of these methods reached a sensitivity ≥70%. Radionecrosis presented with large edema and showed increased levels of cell proliferation, as inferred by Ki-67 staining. Surgical removal of radiation necrosis proved to be a safe approach with low permanent morbidity (<5%) and no mortality. CONCLUSIONS: Although the overall incidence of cerebral radiation necrosis is low, our data suggest an increasing incidence over the last 2 decades, which is likely associated with the use of stereotactic radiotherapy. There are no imaging standards to identify radiation necrosis on standard MRI with structural sequences. Surgical removal of radiation necrosis is associated with low morbidity and mortality.


Assuntos
Neoplasias Encefálicas/radioterapia , Encéfalo/patologia , Glioma/radioterapia , Meningioma/radioterapia , Recidiva Local de Neoplasia/diagnóstico por imagem , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Adulto , Idoso , Encéfalo/efeitos da radiação , Diagnóstico Diferencial , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Necrose/diagnóstico por imagem , Necrose/etiologia , Necrose/patologia , Recidiva Local de Neoplasia/patologia , Lesões por Radiação/patologia , Estudos Retrospectivos
20.
BMC Vet Res ; 16(1): 63, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070340

RESUMO

BACKGROUND: Necrotic enteritis is a significant problem to the poultry industry globally and, in Norway up to 30% of Norwegian turkey grow-outs can be affected. However, despite an awareness that differences exist between necrotic enteritis in chickens and turkeys, little information exists concerning the pathogenesis, immunity, microbiota or experimental reproduction of necrotic enteritis in turkeys. In particular, it is important to determine the appearance of the gross lesions, the age dependency of the disease and the role of netB toxin of Clostridium perfringens. To this end, we report our findings in developing an in vivo experimental model of necrotic enteritis in turkeys. RESULTS: A four tier (0-3) scoring system with clearly defined degrees of severity of macroscopic intestinal lesions was developed, based on 2312 photographic images of opened intestines from 810 B.U.T. 10 or B.U.T. Premium turkeys examined in nine experiments. Loss of macroscopically recognizable villi in the anterior small intestine was established as the defining lesion qualifying for a score 3 (severe intestinal lesions). The developed scoring system was used to identify important factors in promoting high frequencies of turkeys with severe lesions: a combined Eimeria meleagrimitis and Clostridium perfringens challenge, challenge at five rather than 3 weeks of age, the use of an Eimeria meleagrimitis dose level of at least 5000 oocysts per bird and finally, examination of the intestines of 5-week-old turkeys at 125 to 145 h after Eimeria meleagrimitis inoculation. Numbers of oocysts excreted were not influenced by Clostridium perfringens inoculation or turkey age. Among three different lesion score outcomes tested, frequency of severe lesions proved superior in discriminating between impact of four combinations of Clostridium perfringens inoculation and turkey age at challenge. CONCLUSIONS: This study provides details for the successful establishment of an in vivo model of necrotic enteritis in turkeys.


Assuntos
Infecções por Clostridium/veterinária , Coccidiose/veterinária , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/parasitologia , Fatores Etários , Animais , Toxinas Bacterianas/metabolismo , Infecções por Clostridium/patologia , Clostridium perfringens/fisiologia , Coccidiose/patologia , Eimeria/fisiologia , Enterite/veterinária , Intestinos/patologia , Masculino , Modelos Teóricos , Necrose/patologia , Necrose/veterinária , Doenças das Aves Domésticas/patologia , Distribuição Aleatória , Perus
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