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1.
J Hazard Mater ; 421: 126704, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34325292

RESUMO

Cadmium (Cd) is a toxic environmental pollutant and induces toxic effects to organism. Nevertheless, the mechanism of Cd-induced toxicity in swine remains obscure. To explore this, 10 healthy 6-week-old weaned swine were placed into two groups stochastically, the Cd group was treated with a commercial diet containing 20 mg/kg Cd for 40 days. The results of histopathological and ultrastructural observations showed typical necrosis features and inflammatory cell infiltration in Cd group. Excessive Cd suppressed T-AOC and SOD activities, increased MDA content and ROS levels. Cd diet elevated the expression of RIPK1, RIPK3, and MLKL to activate the RIPK3-dependent necroptosis pathway. Results of Th1 and Th2 cytokines indicated that the levels of IL-4, IL-6 and IL10 was increased, while the level of IFN-γ was decreased, illustrating Th1/Th2 immune imbalance leads to aggravate inflammatory responses. Cd activated the TNF-α/NF-κB pathway and induced inflammatory responses via increasing the expression of HO-1, IL-1ß, iNOS, COX2. Heat shock proteins were notably elevated in response to inflammatory reactions. And these effects were inhibited by necrostatin-1 (Nec-1) and N-acetyl-cysteine (NAC). Altogether, these data demonstrated that Cd induced necroptosis and inflammation to aggravate small intestine injury in swine by increasing the excessive accumulation of ROS and imbalanced Th1/Th2, respectively.


Assuntos
NF-kappa B , Necroptose , Animais , Cádmio/toxicidade , Inflamação/induzido quimicamente , Intestino Delgado/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo , Suínos , Fator de Necrose Tumoral alfa
2.
J Coll Physicians Surg Pak ; 31(12): 1487-1493, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34794293

RESUMO

OBJECTIVES: To describe the spectrum of small intestine gastrointestinal stromal tumour (GIST) cases; and to analyse prognostic factors. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Kartal Dr. Lütfi Kirdar City Hospital, Istanbul, Turkey, from 2010 to 2020. METHODOLOGY: Forty patients with small intestine GIST followed up between 2010-2020 were included in this study. The demographic information and clinical laboratory, histopathology, and radiology findings of all patients were analysed and compared. Five-year overall survival (OS) rate and five-year disease-free survival (DFS)were calculated. RESULTS: The mean patient age at diagnosis was 58.9 ± 12.6 years (34-79 years). Thirty-seven (92.5%) tumours were in the jejunum and ileum, and three (7.5%) were in the duodenum. The most common symptoms were bleeding (50%) and pain (37.5%). A total of 5% of the patients were asymptomatic, and 67.5% were in the high-risk group. Two patients (5%) died within a 30-day postoperative period, and 13 (32.5%) died during the follow-up period. The five-year overall survival (OS) rate was 54.2%. The mean five-year OS and five-year disease-free survival (DFS) were 47.5 ± 16.8 months and 40.9 ± 25.0 months, respectively. The mortality risk was calculated as 4.5-fold increased in the patients aged over 60 years and as 3.556-fold increased in those with recurrence/metastasis detected in their follow-ups. CONCLUSION: The OS ratio and OS duration were not as high as expected for small intestine GIST cases. Tumour diameter, mitotic index, and risk classification may not provide sufficient information for prognosis prediction in some cases. The frequency of recurrence and/or metastasis was higher than expected - although complete resection was achieved. Key Words: Gastrointestinal stromal tumours, Small intestine, Tumour diameter, Mitotic index.


Assuntos
Tumores do Estroma Gastrointestinal , Neoplasias Intestinais , Idoso , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Neoplasias Intestinais/cirurgia , Intestino Delgado , Prognóstico , Estudos Retrospectivos
3.
Surg Clin North Am ; 101(6): 1045-1052, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34774267

RESUMO

This article highlights the quagmire of the surgeon who encounters a small bowel obstruction in the absence of previous abdominopelvic surgery. Historic literature implies urgent surgical intervention is required; however, there is no current standard of care to guide management. Key principles of general surgery apply, and definitive management is based on the provider's clinical judgment after synthesizing key clinical history and additional diagnostic imaging studies.


Assuntos
Obstrução Intestinal , Intestino Delgado , Idoso , Raciocínio Clínico , Feminino , Humanos , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Obstrução Intestinal/terapia , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/cirurgia , Laparoscopia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/diagnóstico , Tomografia Computadorizada por Raios X
4.
Surg Clin North Am ; 101(6): 1081-1096, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34774270

RESUMO

Incidental findings are common in the evaluation of surgical patients. Understanding the appropriate assessment and management of these frequent occurrences is important for the provision of comprehensive quality care. This review details the epidemiology, considerations, and recommendations for management of common incidental manifestations in surgical patients, including Meckel diverticulum, adrenal incidentaloma, thyroid nodule, solitary pulmonary nodule, small bowel intussusception, gallstones, and incidental appendectomy.


Assuntos
Neoplasias das Glândulas Suprarrenais , Apendicectomia , Cálculos Biliares , Divertículo Ileal , Nódulo Pulmonar Solitário , Nódulo da Glândula Tireoide , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/terapia , Cálculos Biliares/diagnóstico , Cálculos Biliares/terapia , Humanos , Achados Incidentais , Intestino Delgado , Intussuscepção/diagnóstico , Intussuscepção/terapia , Divertículo Ileal/diagnóstico , Divertículo Ileal/terapia , Nódulo Pulmonar Solitário/diagnóstico , Nódulo Pulmonar Solitário/terapia , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/terapia
5.
Intern Med ; 60(22): 3517-3523, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776464

RESUMO

Objective Antithrombotic drugs are being used increasingly frequently to prevent cardiovascular diseases. Few studies have evaluated small bowel mucosal injury induced by dual antiplatelet therapy (DAPT). The aim of the present study was to evaluate small bowel mucosal injury induced by DAPT compared with other antithrombotics using video capsule endoscopy (VCE). Methods The study included chronic users of antithrombotics who underwent VCE for obscure gastrointestinal bleeding between January 2007 and July 2018. We evaluated the instances of small bowel injury classified into erosions and ulcers. Results Overall, 183 patients (114 men and 69 women; mean age, 73.6 years old) were enrolled, and the study groups comprised 49 patients taking low-dose aspirin (LDA) only, 50 taking anticoagulants only, 37 being treated with DAPT, 33 on combined LDA and anticoagulants, and 14 taking P2Y12 inhibitors. Small bowel erosions and ulcers were most frequently observed in the DAPT group, with frequencies of 78.4% and 37.8%, respectively. Exacerbating factors of small bowel ulcers were DAPT [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.2-7.7] and age over 80 years old (OR 2.4, 95% CI 1.1-5.4). Conclusion P2Y12 inhibitors seem to exacerbate LDA-induced small bowel injury. Preventive strategies for small bowel injury induced by LDA, especially DAPT, are urgently required.


Assuntos
Endoscopia por Cápsula , Enteropatias , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Feminino , Humanos , Intestino Delgado , Masculino , Inibidores da Agregação Plaquetária/efeitos adversos
6.
J Med Case Rep ; 15(1): 545, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34724972

RESUMO

INTRODUCTION: Dieulafoy's lesion, first found by Paul Georges Dieulafoy, is an infrequent but important cause of recurrent upper gastrointestinal bleeding. The bleeding is usually severe, but patients rarely present with chronic, occult gastrointestinal bleeding. CASE PRESENTATION: In this article, we discuss the case of a 68-year-old caucasian man with a history of recurrent hematemesis and chronic anemia with evidence of extravasation of contrast in the lumen of the bowel loop on computed tomography angiography. The patient was taken to the operating room, and a laparotomy procedure was performed. CONCLUSION: Due to the infrequency of Dieulafoy's lesion compared with other causes of gastrointestinal bleeding, it is often missed in the process of differential diagnosis. In this article, we have demonstrated the importance of this disease and different approaches to the treatment of this lesion, considering the location of the lesion among other factors.


Assuntos
Hemorragia Gastrointestinal , Hematemese , Idoso , Angiografia , Hemorragia Gastrointestinal/etiologia , Hematemese/etiologia , Humanos , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/cirurgia , Masculino
7.
Zhonghua Yi Xue Za Zhi ; 101(41): 3411-3416, 2021 Nov 09.
Artigo em Chinês | MEDLINE | ID: mdl-34758545

RESUMO

Objective: To compare and evaluate the diagnostic performance of visual evaluation and CT maximal density relative enhancement value in the diagnosis of intestinal ischemia complication in patients with closed loop obstruction and to explore the feasibility of CT maximal density relative enhancement value in quantifying the degrees of intestinal ischemia. Methods: The clinical and CT imaging data of 82 patients, 46 males and 36 females, aged from 19 to 78(52±18) years, with closed loop obstruction were retrospectively analyzed in the First Affiliated Hospital of Zhengzhou University from July 2017 to July 2019. All patients were classified into three groups: necrosis group (28 cases), ischemia group (22 cases), non-ischemia group(32 cases) using clinicopathologic results as reference standard. CT visual evaluation was performed by two experienced radiologists. The sensitivity, specificity, positive and negative predictive values and accuracy of the two observers were calculated respectively. The inter-observer agreement was analyzed by kappa analysis. Maximal density relative enhancement value was defined as the difference CT value of an ROI at dilated obstructed loops between contrast-enhanced and unenhanced CT images. The differences among groups were compared by one-way analysis of variance. Diagnostic performances were evaluated by receiver operating characteristic (ROC) curve analysis. Results: The sensitivity, specificity, positive and negative predictive values and accuracy of observer1 were 62.0%, 87.5%, 88.6%, 59.6%, 72.0%, and 58.0%, 93.8%, 93.5%, 58.8%, 72.0%for observer2, respectively. The kappa value of inter-observer agreement was 0.747. The unenhanced CT value of necrosis group, ischemia group and non-ischemia group was (53.7±9.7), (45.7±7.2) and (44.7±7.0) HU, enhanced CT value was (60.5±10.1), (65.0±11.6) and (87.0±15.8) HU, relative enhancement value was(6.8±8.4), (19.2±12.4) and(44.7±16.2)HU, respectively. All had a statistical difference among three groups (all P<0.05). The unenhanced CT value of necrosis group was higher than that of ischemia group and un-ischemia group (both P<0.05). The enhanced CT value of non-ischemia group was higher than that of ischemia group and necrosis (both P<0.05). The relative enhancement value all had a significant difference between groups (all P<0.05). Taking maximal density relative enhancement value below 19.5 HU as diagnosis threshold, the sensitivity, specificity and area under curve(AUC) were 96.9%, 74.0% and 0.947, respectively. Taking enhanced CT value below 66.5 HU as diagnosis threshold, the sensitivity, specificity and AUC were 93.8%, 60.0% and 0.903, respectively; the sensitivity was higher than that of objective visual evaluation. Conclusion: Maximal density relative enhancement value can quantize the bowel wall enhancement, and is a more reliable way in the diagnosis of intestinal ischemia than visual evaluation.


Assuntos
Obstrução Intestinal , Isquemia Mesentérica , Meios de Contraste , Feminino , Humanos , Obstrução Intestinal/diagnóstico por imagem , Intestino Delgado , Isquemia/diagnóstico por imagem , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X
10.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638785

RESUMO

For a yet unknown reason, a substantial share of patients suffering from COVID-19 develop long-lasting neuropsychiatric symptoms ranging from cognitive deficits to mood disorders and/or an extreme fatigue. We previously reported that in non-neural cells, angiotensin-1 converting enzyme 2 (ACE2), the gene coding for the SARS-CoV2 host receptor, harbors tight co-expression links with dopa-decarboxylase (DDC), an enzyme involved in the metabolism of dopamine. Here, we mined and integrated data from distinct human expression atlases and found that, among a wide range of tissues and cells, enterocytes of the small intestine express the highest expression levels of ACE2, DDC and several key genes supporting the metabolism of neurotransmitters. Based on these results, we performed co-expression analyses on a recently published set of RNA-seq data obtained from SARS-CoV2-infected human intestinal organoids. We observed that in SARS-CoV2-infected enterocytes, ACE2 co-regulates not only with DDC but also with a specific group of genes involved in (i) the dopamine/trace amines metabolic pathway, (ii) the absorption of microbiota-derived L-DOPA and (iii) the absorption of neutral amino acids serving as precursors to neurotransmitters. We conclude that in patients with long COVID, a chronic infection and inflammation of small intestine enterocytes might be indirectly responsible for prolonged brain alterations.


Assuntos
Encéfalo/patologia , COVID-19/complicações , Regulação da Expressão Gênica , Intestino Delgado/patologia , Enzima de Conversão de Angiotensina 2/genética , Descarboxilases de Aminoácido-L-Aromático/genética , Encéfalo/metabolismo , COVID-19/genética , COVID-19/patologia , Células Cultivadas , Enterócitos/metabolismo , Enterócitos/patologia , Humanos , Intestino Delgado/metabolismo , SARS-CoV-2/isolamento & purificação
11.
Cir Cir ; 89(5): 588-594, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34665166

RESUMO

BACKGROUND: The delay in surgical management of intestinal obstruction patients who did not respond to conservative management increases morbidity, mortality and days of hospital stay. OBJECTIVE: This study aimed to describe the clinical and tomographic features associated with surgical management in adhesive small bowel obstruction patients. METHOD: We conducted a retrospective review of the electronic medical records during a 5-year period with the diagnosis of adhesive small bowel obstruction. We divided patients in two, those who responded to medical management and those who required surgery. RESULTS: A total of 162 patients were included, with a mean age of 61.5 years. It was the first case of intestinal obstruction in 63% of the patients and 65.4% underwent surgery: 52.8% (n = 56) open surgery and 47.2% (n = 50) laparoscopic surgery. Multivariate analysis showed the following predictors of surgical treatment: abdominal rebound (odds ratio [OR]: 8.8; 95% confidence interval [95% CI]: 1.09-71.6), tomographic free fluid (OR: 4.62; 95% CI: 1.50-14.20) and transition zone (OR: 5.4; 95% CI: 1.59-18.80). The history of previous obstruction was a protective factor (OR: 0.33; 95% CI: 0.17-0.67). CONCLUSIONS: Abdominal rebound, free intrabdominal fluid and transition zone are related with the surgical management of adhesive small bowel obstruction.


Assuntos
Adesivos , Obstrução Intestinal , Humanos , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Aderências Teciduais/complicações , Aderências Teciduais/cirurgia
12.
Anticancer Res ; 41(10): 5147-5155, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593466

RESUMO

BACKGROUND/AIM: Metastatic small bowel adenocarcinoma (SBA) is a rare disease with poor prognosis. This study aimed to explore the efficacy and safety of second-line chemotherapy for patients with SBA. PATIENTS AND METHODS: We retrospectively reviewed the clinical characteristics of 27 metastatic patients with SBA after progression on first-line chemotherapy. The patients were divided into Cohort A, receiving second-line chemotherapy, and Cohort B, receiving best supportive care. RESULTS: Patients in Cohort B had higher age, worse performance status, and higher neutrophil-to-lymphocyte ratio compared with those in Cohort A. Cohort A showed significantly better overall survival (OS) compared with Cohort B (median OS, 15.6 vs. 3.4 months; p=0.002). Objective response rate, disease control rate, and median progression-free survival (PFS) for Cohort A were 7%, 74%, and 5.0 months, respectively. Patients who underwent irinotecan-based chemotherapy showed longer PFS and OS compared with those who underwent taxane-based chemotherapy. No significant adverse events were reported. CONCLUSION: Second-line chemotherapy for metastatic SBA demonstrated clinical activity with acceptable toxicities.


Assuntos
Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Intestinais/mortalidade , Intestino Delgado/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adulto , Idoso , Feminino , Seguimentos , Humanos , Neoplasias Intestinais/tratamento farmacológico , Neoplasias Intestinais/patologia , Intestino Delgado/efeitos dos fármacos , Irinotecano/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Taxoides/administração & dosagem
13.
Sensors (Basel) ; 21(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34641009

RESUMO

Acute intestinal ischemia is a life-threatening condition. The current gold standard, with evaluation based on visual and tactile sensation, has low specificity. In this study, we explore the feasibility of using machine learning models on images of the intestine, to assess small intestinal viability. A digital microscope was used to acquire images of the jejunum in 10 pigs. Ischemic segments were created by local clamping (approximately 30 cm in width) of small arteries and veins in the mesentery and reperfusion was initiated by releasing the clamps. A series of images were acquired once an hour on the surface of each of the segments. The convolutional neural network (CNN) has previously been used to classify medical images, while knowledge is lacking whether CNNs have potential to classify ischemia-reperfusion injury on the small intestine. We compared how different deep learning models perform for this task. Moreover, the Shapley additive explanations (SHAP) method within explainable artificial intelligence (AI) was used to identify features that the model utilizes as important in classification of different ischemic injury degrees. To be able to assess to what extent we can trust our deep learning model decisions is critical in a clinical setting. A probabilistic model Bayesian CNN was implemented to estimate the model uncertainty which provides a confidence measure of our model decisions.


Assuntos
Inteligência Artificial , Traumatismo por Reperfusão , Animais , Teorema de Bayes , Intestino Delgado , Redes Neurais de Computação , Projetos Piloto , Traumatismo por Reperfusão/diagnóstico , Suínos
14.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(10): 931-935, 2021 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-34674470

RESUMO

Intestinal obstruction is one of the most common diseases in abdominal surgery, and its prevention and treatment is a clinical difficulty. Although surgical operation can solve the symptoms of obstruction, there are many postoperative complications, and it is easy to develop re-obstruction due to postoperative abdominal adhesion. The internal fixation of small intestine with obstruction catheter provides a new idea for the prevention of postoperative adhesive bowel obstruction. The use of transanal ileus catheter provides the possibility of direct intestinal anastomosis after resection of malignant obstruction in the left hemicolon and can reduce the incidence of postoperative complications. However, sufficient attention should be paid to the related complications, and prevention and treatment should be planned. It is important to note that the use of obstruction catheter is only one of the conservative treatments for bowel obstruction, and it is not a complete replacement of surgery. Surgical treatment should still be considered, if the catheter fails to significantly move, if the obstructive symptoms do not significantly improve 5 days after catheterization.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Obstrução Intestinal , Cateteres , Humanos , Obstrução Intestinal/prevenção & controle , Obstrução Intestinal/cirurgia , Intestino Delgado , Aderências Teciduais
15.
World J Gastroenterol ; 27(37): 6332-6344, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34712036

RESUMO

BACKGROUND: Abdominal cocoon or "encapsulating peritoneal sclerosis" (EPS) is an uncommon and rare cause of intestinal obstruction. Only a few cases have been reported in paediatric patients. Typically, EPS is described as the primary form in young adolescent girls from tropical and subtropical countries because of viral peritonitis due to retrograde menstruation or a history of peritoneal dialysis. Most patients are asymptomatic or present with abdominal pain, which is likely to occur secondary to subacute bowel obstruction. Findings at imaging, such as ultrasound, computed tomography, and magnetic resonance imaging, are often nonspecific. When diagnosed, EPS is characterized by total or partial encasement of the bowel within a thick fibrocollagenous membrane that envelopes the small intestine in the form of a cocoon because of chronic intraabdominal fibroinflammatory processes. The membrane forms a fibrous tissue sheet that covers, fixes, and finely constricts the gut, compromising its motility. CASE SUMMARY: We present a case of EPS in a 12-year-old boy 8 wk after primary surgery for resection of symptomatic jejunal angiodysplasia. There was no history of peritoneal dialysis or drug intake. CONCLUSION: In this report, we sought to highlight the diagnostic, surgical, and histopathological characteristics and review the current literature on EPS in paediatric patients.


Assuntos
Obstrução Intestinal , Diálise Peritoneal , Fibrose Peritoneal , Peritonite , Adolescente , Criança , Feminino , Humanos , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Intestino Delgado/patologia , Masculino , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/diagnóstico por imagem , Fibrose Peritoneal/etiologia , Peritonite/diagnóstico por imagem , Peritonite/etiologia , Peritonite/cirurgia
16.
Arq Gastroenterol ; 58(3): 322-328, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34705966

RESUMO

BACKGROUND: Crohn's disease (CD) is an inflammatory bowel disease characterized by a chronic and recurrent inflammation of the gastrointestinal tract caused by an interaction of genetic and environmental factors. OBJECTIVE: To compare the quality and acceptance of two different oral contrast volumes for computed tomography enterography in Crohn's disease patients. METHODS: A cross-sectional study was conducted in 58 consecutive Crohn's disease patients who randomly received an oral contrast agent composed of 78.75 g polyethylene glycol diluted in either 1,000 mL or 2,000 mL of water. An examination was performed to evaluate the presence of inflammation or complications in the small bowel. The variables included the quality of intestinal segment filling and luminal distension, and oral contrast agent acceptance and tolerance in the patients. Statistical analysis included descriptive statistics and association tests. RESULTS: A total of 58 patients were assessed, in which 58.6% were female, 34.5% exhibited clinically-active disease, and 63.8% were receiving biologic therapy. As for comparative analysis between the two different volumes of oral contrast, no statistically significant difference was found regarding bowel loop filling (P=0.58) and adequate luminal distension (P=0.45). Patients who received a larger volume (2,000 mL) exhibited side-effects more frequently (51.7% vs 31.0%; P=0.06) and had greater difficulty ingesting the agent (65.5% vs 37.9%; P=0.07) compared with a volume of 1,000 mL. CONCLUSION: The quality of computed tomography enterography was not influenced by the contrast volume. However, acceptance and tolerance were better in the 1,000 mL group.


Assuntos
Meios de Contraste , Doença de Crohn , Doença de Crohn/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Intestino Delgado , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X
17.
Sci Rep ; 11(1): 21308, 2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34716391

RESUMO

The aim of this study was to present and evaluate novel oral vaccines, based on self-amplifying RNA lipid nanparticles (saRNA LNPs), saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum, to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) variants alpha and delta. After invitro evaluation of the oral vaccines on HEK293T/17 cells, we found that saRNA LNPs, saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum could express S-protein at both mRNA and protein levels. In the next step, BALB/c mice were orally vaccinated with saRNA LNPs, saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum at weeks 1 and 3. Importantly, a high titer of IgG and IgA was observed by all of them, sharply in week 6 (P < 0.05). In all study groups, their ratio of IgG2a/IgG1 was upper 1, indicating Th1-biased responses. Wild-type viral neutralization assay showed that the secreted antibodies in vaccinated mice and recovered COVID-19 patients could neutralize SARS-COV-2 variants alpha and delta. After oral administration of oral vaccines, biodistribution assay was done. It was found that all of them had the same biodistribution pattern. The highest concentration of S-protein was seen in the small intestine, followed by the large intestine and liver.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Lactobacillus plantarum/genética , Lipídeos/química , Nanopartículas/química , SARS-CoV-2/imunologia , Transfecção/métodos , Vacinação/métodos , Vacinas Sintéticas/administração & dosagem , Administração Oral , Adulto , Animais , COVID-19/sangue , COVID-19/virologia , Vacinas contra COVID-19/farmacocinética , Feminino , Células HEK293 , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Intestino Delgado/metabolismo , Lactobacillus plantarum/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Modelos Animais , Testes de Neutralização , RNA Mensageiro/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Distribuição Tecidual
18.
Nutrients ; 13(10)2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34684506

RESUMO

Functional gastrointestinal disorders (FGIDs) are characterized by abdominal pain, bloating and bowel disturbances. FGID therapy is primarily symptomatic, including treatment with herbal remedies. Flower extract of Tilia tomentosa Moench (TtM) is occasionally used as an anti-spasmodic in popular medicine. Since its effect on intestinal response is unknown, we evaluated the influence of TtM extract on small intestine contractility. Ileal preparations from C57BL/6J mice were mounted in organ baths to assess changes in muscle tension, following addition of TtM extract (0.5-36 µg/mL) or a vehicle (ethanol). Changes in contractile response to receptor- and non-receptor-mediated stimuli were assessed in ileal preparations pretreated with 12 µg/mL TtM. Alterations in the enteric nervous system neuroglial network were analyzed by confocal immunofluorescence. Increasing addition of TtM induced a marked relaxation in ileal specimens compared to the vehicle. Pretreatment with TtM affected cholinergic and tachykininergic neuromuscular contractions as well as K+-induced smooth muscle depolarization. Following incubation with TtM, a significant reduction in non-adrenergic non-cholinergic-mediated relaxation sensitive to Nω-Nitro-L-arginine methyl ester hydrochloride (pan-nitric oxide synthase inhibitor) was found. In vitro incubation of intestinal specimens with TtM did not affect the myenteric plexus neuroglial network. Our findings show that TtM-induced intestinal relaxation is mediated by nitric oxide pathways, providing a pharmacological basis for the use of TtM in FGIDs.


Assuntos
Intestino Delgado/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Extratos Vegetais/farmacologia , Tilia , Animais , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/fisiopatologia , Íleo/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL
20.
Nutrients ; 13(10)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34684302

RESUMO

As part of a whole egg, egg white proteins are embedded in a lipid matrix that could modify their presentation to the immune system and their allergenic properties. The present study examines the impact of the main egg lipid components, triacylglycerides and phospholipids, in the early events of sensitization to egg. To this end, BALB/c mice were exposed intragastrically to egg lipids and egg lipid fractions, alone and in mixtures with egg white proteins, and Th2-promoting and proinflammatory effects were investigated. Our results highlight that the egg lipid fraction is responsible for Th2 adjuvant effects and point at a different influence of triacylglycerides and phospholipids on the bioavailability and immunomodulating properties of egg white proteins. While triacylglycerides promote type 2 responses at the small intestine level, phospholipids reduce the solubility of EW proteins and induce Th2 skewing in lymphoid intestinal tissues, which may have a direct impact on the development of egg allergy.


Assuntos
Proteínas do Ovo/farmacologia , Gema de Ovo/química , Imunização , Fosfolipídeos/farmacologia , Triglicerídeos/farmacologia , Animais , Galinhas , Duodeno/efeitos dos fármacos , Duodeno/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Intestino Delgado/metabolismo , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Camundongos Endogâmicos BALB C , Solubilidade , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo
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