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1.
PLoS One ; 15(3): e0229463, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32214355

RESUMO

Food and feeds contaminated with mycotoxins have been a threat to the rearing industry by causing some of the most fatal toxic reactions not only in the farm animals but also in humans who consume them. Toxicity to juvenile goats was induced by feed contamination with T-2 toxin (at 10 and 20 ppm dosage; group I and II, respectively). The toxicity impact was assessed on days 15 and 30 post treatment with respect to growth performance, oxidative stress, apoptotic studies and detailed pathomorphology. The study revealed that apart from the obvious clinical toxicosis (weakness, lethargy, and retardation in growth), the toxin fed groups also exhibited significant haematological (reduced hemoglobin, total leukocyte and thrombocyte counts) and biochemical changes (increased levels of oxidative stress markers with concomitant decrease in levels of serum and tissue catalase and superoxide dismutase). The pathomorphological and histological alterations suggested that the liver and intestine were the most affected organs. Ultra-structurally, varying degrees of degeneration, cytoplasmic vacuolations and pleomorphic mitochondria were observed in the hepatocytes and the enterocytes of the intestine. Kidney also revealed extensive degeneration of the cytoplasmic organelles with similar condensation of the heterochromatin whereas the neuronal degeneration was characterized by circular, whirling structures. In addition, the central vein and portal triad of the hepatocytes, cryptic epithelial cells of the intestine, MLNs in the lymphoid follicles, PCT and DCT of the nephronal tissues and the white pulp of the spleen exhibited extensive apoptosis. In this study, it was also observed that the expression of HSPs, pro-apoptotic proteins and pro-inflammatory cytokines were significantly upregulated in response to the toxin treatment. These results suggest that the pathogenesis of T-2 toxicosis in goats employs oxidative, apoptotic and inflammatory mechanisms.


Assuntos
Apoptose , Regulação da Expressão Gênica/efeitos dos fármacos , Cabras/fisiologia , Mediadores da Inflamação/metabolismo , Fígado/patologia , Estresse Oxidativo/efeitos dos fármacos , Toxina T-2/toxicidade , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Citocinas/metabolismo , Proteínas de Choque Térmico/metabolismo , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Linfonodos/efeitos dos fármacos , Linfonodos/metabolismo , Linfonodos/patologia , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/patologia
2.
PLoS Pathog ; 16(3): e1008339, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32163523

RESUMO

Despite the success of antiretroviral therapy (ART) to halt viral replication and slow disease progression, this treatment is not curative and there remains an urgent need to develop approaches to clear the latent HIV reservoir. The human IL-15 superagonist N-803 (formerly ALT-803) is a promising anti-cancer biologic with potent immunostimulatory properties that has been extended into the field of HIV as a potential "shock and kill" therapeutic for HIV cure. However, the ability of N-803 to reactivate latent virus and modulate anti-viral immunity in vivo under the cover of ART remains undefined. Here, we show that in ART-suppressed, simian-human immunodeficiency virus (SHIV)SF162P3-infected rhesus macaques, subcutaneous administration of N-803 activates and mobilizes both NK cells and SHIV-specific CD8+ T cells from the peripheral blood to lymph node B cell follicles, a sanctuary site for latent virus that normally excludes such effector cells. We observed minimal activation of memory CD4+ T cells and no increase in viral RNA content in lymph node resident CD4+ T cells post N-803 administration. Accordingly, we found no difference in the number or magnitude of plasma viremia timepoints between treated and untreated animals during the N-803 administration period, and no difference in the size of the viral DNA cell-associated reservoir post N-803 treatment. These results substantiate N-803 as a potent immunotherapeutic candidate capable of activating and directing effector CD8+ T and NK cells to the B cell follicle during full ART suppression, and suggest N-803 must be paired with a bona fide latency reversing agent in vivo to facilitate immune-mediated modulation of the latent viral reservoir.


Assuntos
Antirretrovirais/administração & dosagem , Linfócitos B/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Interleucina-15/antagonistas & inibidores , Células Matadoras Naturais/efeitos dos fármacos , Proteínas/administração & dosagem , Animais , Linfócitos B/citologia , Linfócitos B/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Interleucina-15/genética , Interleucina-15/imunologia , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Macaca mulatta , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/fisiopatologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vírus da Imunodeficiência Símia/fisiologia , Latência Viral/efeitos dos fármacos
3.
Nat Med ; 26(3): 430-440, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32066977

RESUMO

Adjuvants are central to the efficacy of subunit vaccines. Aluminum hydroxide (alum) is the most commonly used vaccine adjuvant, yet its adjuvanticity is often weak and mechanisms of triggering antibody responses remain poorly understood. We demonstrate that site-specific modification of immunogens with short peptides composed of repeating phosphoserine (pSer) residues enhances binding to alum and prolongs immunogen bioavailability. The pSer-modified immunogens formulated in alum elicited greatly increased germinal center, antibody, neutralizing antibody, memory and long-lived plasma cell responses compared to conventional alum-adsorbed immunogens. Mechanistically, pSer-immunogen:alum complexes form nanoparticles that traffic to lymph nodes and trigger B cell activation through multivalent and oriented antigen display. Direct uptake of antigen-decorated alum particles by B cells upregulated antigen processing and presentation pathways, further enhancing B cell activation. These data provide insights into mechanisms of action of alum and introduce a readily translatable approach to significantly improve humoral immunity to subunit vaccines using a clinical adjuvant.


Assuntos
Adjuvantes Imunológicos/farmacologia , Hidróxido de Alumínio/farmacologia , Imunidade Humoral/efeitos dos fármacos , Peptídeos/imunologia , Engenharia de Proteínas , Animais , Apresentação do Antígeno/efeitos dos fármacos , Antígenos/metabolismo , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Endocitose/efeitos dos fármacos , Epitopos/imunologia , Imunização , Memória Imunológica/efeitos dos fármacos , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Ativação Linfocitária/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Nanopartículas/química , Peptídeos/química , Fosfosserina/metabolismo
4.
Food Chem Toxicol ; 136: 110954, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31707033

RESUMO

Due to the growing number of applications of cadmium oxide nanoparticles (CdO NPs), there is a concern about their potential deleterious effects. The objective of our study was to investigate the effect of CdO NPs on the immune response, renal and intestine oxidative stress, blood antioxidant defence, renal fibrotic response, bone density and mineral content. Six-week-old female ICR mice were exposed to CdO NPs for 6 weeks by inhalation (particle size: 9.82 nm, mass concentration: 31.7 µg CdO/m3, total deposited dose: 0.195 µg CdO/g body weight). CdO NPs increased percentage of thymus CD3e+CD8a+ cells and moderately enhanced splenocyte proliferation and production of cytokines and chemokines. CdO NPs elevated pro-fibrotic factors (TGF-ß2, α-SMA and collagen I) in the kidney, and concentrations of AGEs in the intestine. The ratio of GSH and GSSG in blood was slightly reduced. Exposure to CdO NPs resulted in 10-fold higher Cd concentration in tibia bones. No differences were found in bone mass density, mineral content, bone area values, bone concentrations of Ca, P, Mg and Ca/P ratio. Our findings indicate stimulation of immune/inflammatory response, oxidative stress in the intestine, starting fibrotic response in kidneys and accumulation of CdO NPs in bones of mice.


Assuntos
Compostos de Cádmio/toxicidade , Fibrose/induzido quimicamente , Imunidade Celular/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Óxidos/toxicidade , Tíbia/efeitos dos fármacos , Administração por Inalação , Animais , Compostos de Cádmio/administração & dosagem , Citocinas/metabolismo , Feminino , Intestinos/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Linfonodos/efeitos dos fármacos , Nanopartículas Metálicas/administração & dosagem , Camundongos Endogâmicos ICR , Óxidos/administração & dosagem , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos
5.
Am J Pathol ; 190(1): 125-133, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669306

RESUMO

Neuroinflammation plays an important role in the pathogenesis of ocular surface disease, including dry eye disease (DED), but little is known about the contribution of substance P (SP) to DED. In this study, we investigated the expression of SP at the ocular surface and evaluated its effect on maturation of antigen-presenting cells (APCs), the key cell component involved in the induction of type 17 helper T-cell (Th17) response in DED. The effect of topical blockade of SP signaling was further investigated using neurokinin-1 receptor (NK1R) inhibitors on APC maturation, Th17 cell activation, and disease severity in a mouse model of DED. The results demonstrate that SP is constitutively expressed at the ocular surface, and trigeminal ganglion neurons are the major source of SP in DED. SP derived from trigeminal ganglion enhanced the expression of major histocompatibility complex class II maturation marker by bone marrow-derived dendritic cells, an effect that is abrogated by blockade of SP signaling using NK1R antagonist spantide. Finally, using a well-established murine model of DED, topical treatment of DED mice with NK1R antagonists CP-99,994 and L-733,060 suppressed APC acquisition of major histocompatibility complex class II, reduced Th17 cell activity, and ameliorated DED severity. These findings are of translational value, as they suggest that antagonizing NK1R-mediated SP signaling may be an effective strategy in suppressing Th17-mediated ocular surface disease.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Modelos Animais de Doenças , Síndromes do Olho Seco/prevenção & controle , Antagonistas do Receptor de Neuroquinina-1/farmacologia , Receptores da Neurocinina-1/química , Células Th17/imunologia , Animais , Células Apresentadoras de Antígenos/efeitos dos fármacos , Córnea/efeitos dos fármacos , Córnea/imunologia , Síndromes do Olho Seco/imunologia , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/patologia , Feminino , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Células Th17/efeitos dos fármacos
6.
Planta Med ; 86(2): 160-168, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31745939

RESUMO

This study investigated the effect of hawthorn (Crataegus monogyna) phenolic extract on lymphocyte subsets in the lymphoid organs in nonimmunized mice and on humoral immune response in sheep red blood cell-immunized mice. Hawthorn phenolic extract (50, 100, 200 mg/kg) was administered orally five or ten times. Sheep red blood cells were injected 24 h after administration of the last extract dose. The lymphocyte subsets were assessed 24 and 72 h after the last dose. Humoral immune response was determined 4 and 7 days after immunization. Five doses of the extract decreased the percentage of CD4-CD8- and CD4+ thymocytes but elevated the percentage of CD4+CD8+ and CD8+ thymic cells. The extract increased the total number, percentage, and absolute count of T and B splenocytes. When administered five times, it lowered the percentage of T lymphocytes, but boosted the population of B lymphocytes of mesenteric lymph nodes (after 24 h). However, a rise in the population of T lymphocytes was observed 72 h after five and ten doses. The extract administered ten times elevated the number of plaque-forming cells and total anti-sheep red blood cell hemagglutinin titer but reduced the 2-ME-resistant antibody titer (day 7). At the same time, five doses of the extract increased antibody titers. Considering its impact on lymphocyte subsets and humoral immune response, hawthorn extract may be used as an immunomodulator.


Assuntos
Crataegus/química , Imunidade Humoral/efeitos dos fármacos , Subpopulações de Linfócitos/efeitos dos fármacos , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Animais , Relação Dose-Resposta a Droga , Feminino , Linfonodos/efeitos dos fármacos , Contagem de Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fenóis/isolamento & purificação , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos
7.
Surg Clin North Am ; 100(1): 91-107, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31753118

RESUMO

In this article we provide a critical review of the evidence available for surgical management of the nodal basin in melanoma, with an aim to ensure an understanding of risks and benefits for all lymph node surgery offered to patients, and alternatives to surgical management where appropriate.


Assuntos
Linfonodos/efeitos dos fármacos , Melanoma/patologia , Neoplasias Cutâneas/patologia , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática , Melanoma/diagnóstico por imagem , Melanoma/tratamento farmacológico , Melanoma/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/terapia
8.
Acta Cir Bras ; 34(10): e201901002, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31826148

RESUMO

PURPOSE: To evaluate the effect of garlic on formation of postoperative adhesions in rats. METHODS: Twenty-four Sprague dawley rats were divided into three groups. In Group 1 (sham), laparotomy was performed and stitched up. In Group 2 (control), after laparotomy was performed, punctate hemorrhage was induced by cecal abrasion in the cecum and 2 cc of saline was intraperitoneally administered to each rat. In Group 3 (experimental), after laparotomy was performed, punctate hemorrhage was induced by cecal abrasion in the cecum and each rat was intraperitoneally administered a sterile Allium sativum derivative. The rats in all groups were re-laparotomized on postoperative day 7; samples were obtained from the peritoneal tissue surrounding the cecum. RESULTS: In Group 3, there was a statistically significant difference in terms of inflammation, lymph node size, and free oxygen radicals; these parameters tended to increase. In terms of fibrosis evaluated using H&E and MT, there was no significant difference between groups 2 and 3. CONCLUSIONS: No positive outcomes indicating that Allium sativum reduces intra-abdominal adhesions were obtained. However, it caused severe inflammation in the tissue. Additionally, in immunohistochemical analyses conducted to detect oxidative stress, allium sativum increased the production of free oxygen radicals in the tissue.


Assuntos
Alho/química , Doenças Peritoneais/prevenção & controle , Animais , Fibrose , Radicais Livres/análise , Imuno-Histoquímica , Laparotomia , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Estresse Oxidativo/efeitos dos fármacos , Doenças Peritoneais/patologia , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/prevenção & controle , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Aderências Teciduais/patologia , Aderências Teciduais/prevenção & controle
9.
BMC Pharmacol Toxicol ; 20(1): 86, 2019 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864413

RESUMO

BACKGROUND: T lymphocytes play an important role in contact hypersensitivity. This study aims to explore the immunosuppressive activity of SBF-1, an analog of saponin OSW-1, against T lymphocytes in vitro and in vivo. METHODS: Proliferation of T lymphocytes from lymph nodes of mice was determined by MTT assay. Flow cytometry analysis was performed to assess T cell activation and apoptosis. Levels of cytokines were determined by PCR and ELISA. BALB/c mice were sensitized and challenged with picryl chloride and thickness of left and right ears were measured. RESULTS: SBF-1 effectively inhibited T lymphocytes proliferation induced by concanavalin A (Con A) or anti-CD3 plus anti-CD28 at a very low dose (10 nM) but exhibited little toxicity in non-activated T lymphocytes at concentrations up to 10 µM. In addition, SBF-1 inhibited the expression of CD25 and CD69, as well as he phosphorylation of AKT in Con A-activated T cells. SBF-1 also induced apoptosis of activated T cells. In addition, SBF-1 also downregulated the induction of the T cell cytokines, IL-2 and IFN-γ in a dose-dependent manner. Furthermore, SBF-1 significantly suppressed ear swelling and inflammation in a mouse model of picryl chloride-induced contact hypersensitivity. CONCLUSIONS: Our findings suggest that SBF-1 has an unique immunosuppressive activity both in vitro and in vivo mainly through inhibiting T cell proliferation and activation. Its mechanism appears to be related to the blockage of AKT signaling pathway.


Assuntos
Proliferação de Células/efeitos dos fármacos , Colestenonas/farmacologia , Dermatite de Contato/prevenção & controle , Linfonodos/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Saponinas/farmacologia , Linfócitos T/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Citocinas/biossíntese , Citocinas/genética , Dermatite de Contato/imunologia , Relação Dose-Resposta a Droga , Regulação para Baixo , Feminino , Linfonodos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T/imunologia
10.
BMJ Case Rep ; 12(11)2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31694828

RESUMO

We present two clinical cases of lymphadenopathy after vaccination with the human papillomavirus (HPV) 9-valent vaccine: an asymptomatic 11-year-old boy with inferior cervical and supraclavicular lymphadenopathy, and a 13-year-old girl who presented with lymphadenopathy. In both cases, medical history was unremarkable and there was no recent infection, or other clinical findings. Both adolescents had received the HPV 9-valent vaccine in the previous week. In the first case, blood tests, ultrasonography and biopsy were performed, while in the second, a watchful waiting strategy was adopted. In both cases, the lymphadenopathy resolved spontaneously. The boy received the second dose of the vaccine 6 months later and lymphadenopathy reappeared. The Naranjo scale was applied, classifying the events as definite (in the case of the boy) and probable (girl) adverse drug reactions. The vaccine is safe, but recognising this minor adverse event is important to prevent unnecessary investigation and reduce patient and parental anxiety.


Assuntos
Linfonodos/patologia , Linfadenopatia/induzido quimicamente , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/efeitos adversos , Criança , Feminino , Humanos , Injeções Intramusculares , Linfonodos/efeitos dos fármacos , Linfadenopatia/patologia , Masculino , Vacinas contra Papillomavirus/administração & dosagem , Vacinação
11.
Nutrients ; 11(10)2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31590415

RESUMO

In preterm newborns the immaturity of the immune system is remarkable, with reduced innate and adaptive immune responses. Many bioactive compounds in breast milk, such as growth factors and adipokines, contribute to the immune system's maturation in early life. However, studies on the immunoregulatory activity in preterm neonates are practically nonexistent. The aim of the present study was to determine whether a nutritional supplementation in early life with leptin or epidermal growth factor (EGF) was able to promote the maturation of the systemic and intestinal immune system in preterm conditions. For this purpose, premature rats were daily supplemented by oral gavage with leptin or EGF. Term and Preterm groups receiving vehicle were used as controls. Preterm rats showed deficiencies compared to full-term ones, such as lower body weights, erythrocyte counts, plasma IgG and IgM concentrations and B cell percentages, and higher values of Th and Tc TCRαß+ cells in mesenteric lymph nodes, and intestinal permeability, among others. However, leptin and EGF supplementation were able to revert some of these deficiencies and to improve the premature immune system's development. These results suggest that leptin and EGF are involved in enhancing the maturation of the systemic and intestinal immune system in preterm conditions.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Suplementos Nutricionais , Fator de Crescimento Epidérmico/farmacologia , Imunidade Inata/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Lactação , Leptina/farmacologia , Linfonodos/efeitos dos fármacos , Nascimento Prematuro , Fatores Etários , Animais , Animais Lactentes , Feminino , Idade Gestacional , Imunidade nas Mucosas/efeitos dos fármacos , Imunoglobulinas/sangue , Intestino Delgado/crescimento & desenvolvimento , Intestino Delgado/imunologia , Intestino Delgado/metabolismo , Linfonodos/crescimento & desenvolvimento , Linfonodos/imunologia , Subpopulações de Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Permeabilidade , Fagócitos/imunologia , Fagocitose/efeitos dos fármacos , Gravidez , Ratos Wistar , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo
12.
Respir Res ; 20(1): 232, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651327

RESUMO

RATIONALE: Idiopathic Pulmonary Fibrosis (IPF) is thought to be triggered by repeated alveolar epithelial cell injury. Current evidence suggests that aberrant immune activation may contribute. However, the role of B-cell activation remains unclear. We determined the phenotype and activation status of B-cell subsets and evaluated the contribution of activated B-cells to the development of lung fibrosis both in humans and in mice. METHODS: B-cells in blood, mediastinal lymph node, and lung single-cell suspensions of IPF patients and healthy controls (HC) were characterized using 14-color flow cytometry. Mice were exposed to bleomycin to provoke pulmonary fibrosis. RESULTS: More IgA+ memory B-cells and plasmablasts were found in blood (n = 27) and lungs (n = 11) of IPF patients compared to HC (n = 21) and control lungs (n = 9). IPF patients had higher levels of autoreactive IgA in plasma, which correlated with an enhanced decline of forced vital capacity (p = 0.002, r = - 0.50). Bruton's tyrosine kinase expression was higher in circulating IPF B-cells compared to HC, indicating enhanced B-cell activation. Bleomycin-exposed mice had increased pulmonary IgA+ germinal center and plasma cell proportions compared to control mice. The degree of lung fibrosis correlated with pulmonary germinal center B-cell proportions (p = 0.010, r = 0.88). CONCLUSION: Our study demonstrates that IPF patients have more circulating activated B-cells and autoreactive IgA, which correlate with disease progression. These B-cell alterations were also observed in the widely used mouse model of experimental pulmonary fibrosis. Autoreactive IgA could be useful as a biomarker for disease progression in IPF.


Assuntos
Tirosina Quinase da Agamaglobulinemia/sangue , Linfócitos B/metabolismo , Progressão da Doença , Fibrose Pulmonar Idiopática/sangue , Imunoglobulina A/sangue , Idoso , Animais , Antibióticos Antineoplásicos/toxicidade , Autoanticorpos/sangue , Bleomicina/toxicidade , Feminino , Humanos , Fibrose Pulmonar Idiopática/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Linfonodos/efeitos dos fármacos , Linfonodos/metabolismo , Linfonodos/patologia , Masculino , Camundongos , Pessoa de Meia-Idade
13.
Ann Surg Oncol ; 26(13): 4337-4345, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31605348

RESUMO

BACKGROUND: The sentinel node biopsy following neoadjuvant chemotherapy (SN FNAC) study has shown that in node-positive (N+) breast cancer, sentinel node biopsy (SNB) can be performed following neoadjuvant chemotherapy (NAC), with a low false negative rate (FNR = 8.4%). A secondary endpoint of the SN FNAC study was to determine whether axillary ultrasound (AxUS) could predict axillary pathological complete response (ypN0) and increase the accuracy of SNB. METHODS: The SN FNAC trial is a study of patients with biopsy-proven N+ breast cancer who underwent SNB followed by completion node dissection. All patients had AxUS following NAC and the axillary nodes were classified as either positive (AxUS+) or negative (AxUS-). AxUS was compared with the final axillary pathology results. RESULTS: There was no statistical difference in the baseline characteristics of patients with AxUS+ versus those with AxUS-. Overall, 82.5% (47/57) of AxUS+ patients had residual positive lymph nodes (ypN+) at surgery and 53.8% (42/78) of AxUS- patients had ypN+. Post NAC AxUS sensitivity was 52.8%, specificity 78.3%, and negative predictive value 46.2%. AxUS FNR was 47.2%, versus 8.4% for SNB. If post-NAC AxUS- was used to select patients for SNB, FNR would decrease from 8.4 to 2.7%. However, using post-NAC AxUS in addition to SNB as an indication for ALND would have led to unnecessary ALND in 7.8% of all patients. CONCLUSION: AxUS is not appropriate as a standalone staging procedure, and SNB itself is sufficient to assess the axilla post NAC in patients who present with N+ breast cancer.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Linfonodos/patologia , Terapia Neoadjuvante/métodos , Ultrassonografia Mamária/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Axila , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/efeitos dos fármacos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Biópsia de Linfonodo Sentinela
14.
Anticancer Res ; 39(10): 5767-5772, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570480

RESUMO

BACKGROUND/AIM: To investigate the impact of inguinal lymph node dissection (ILND) following neoadjuvant chemoradiotherapy (NACRT) for rectal cancer patients with ILN metastasis. PATIENTS AND METHODS: Forty-three patients with rectal cancer underwent NACRT followed by curative surgery between January 2005 and December 2016. Seven patients underwent ILND after NACRT for clinically-positive ILN metastasis (ILND (+) group), while the remaining 36 did not receive ILND for clinically negative ILN metastasis (ILND (-) group). Their outcomes were retrospectively analyzed. RESULTS: Only one patient in the ILND (+) group had a local recurrence at six years after surgery. The 5-year recurrence-free survival was 100% and 65.4% in the ILND (+) and ILND (-) groups, respectively (p=0.09), and the 5-year overall survival was 100% and 83.2%, respectively (p=0.32). CONCLUSION: ILND following NACRT seems effective for rectal cancer patients with ILN metastasis.


Assuntos
Canal Inguinal/patologia , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Metástase Linfática/patologia , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adulto , Idoso , Biópsia/métodos , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Feminino , Humanos , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias Retais/patologia , Estudos Retrospectivos
15.
Acta cir. bras ; 34(10): e201901002, Oct. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1054669

RESUMO

Abstract Purpose: To evaluate the effect of garlic on formation of postoperative adhesions in rats. Methods: Twenty-four Sprague dawley rats were divided into three groups. In Group 1 (sham), laparotomy was performed and stitched up. In Group 2 (control), after laparotomy was performed, punctate hemorrhage was induced by cecal abrasion in the cecum and 2 cc of saline was intraperitoneally administered to each rat. In Group 3 (experimental), after laparotomy was performed, punctate hemorrhage was induced by cecal abrasion in the cecum and each rat was intraperitoneally administered a sterile Allium sativum derivative. The rats in all groups were re-laparotomized on postoperative day 7; samples were obtained from the peritoneal tissue surrounding the cecum Results: In Group 3, there was a statistically significant difference in terms of inflammation, lymph node size, and free oxygen radicals; these parameters tended to increase. In terms of fibrosis evaluated using H&E and MT, there was no significant difference between groups 2 and 3. Conclusions: No positive outcomes indicating that Allium sativum reduces intra-abdominal adhesions were obtained. However, it caused severe inflammation in the tissue. Additionally, in immunohistochemical analyses conducted to detect oxidative stress, allium sativum increased the production of free oxygen radicals in the tissue.


Assuntos
Animais , Doenças Peritoneais/prevenção & controle , Alho/química , Doenças Peritoneais/patologia , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/prevenção & controle , Fibrose , Imuno-Histoquímica , Aderências Teciduais/patologia , Aderências Teciduais/prevenção & controle , Reprodutibilidade dos Testes , Ratos Sprague-Dawley , Estresse Oxidativo/efeitos dos fármacos , Radicais Livres/análise , Laparotomia , Linfonodos/efeitos dos fármacos , Linfonodos/patologia
16.
Biomed Pharmacother ; 118: 109373, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545268

RESUMO

The effect of antigen-adjuvant associations on antigen uptake and antigen-specific humoral immunity is studied in detail. After formulation with a squalene-based double emulsion (referred to as PELC), the protein ovalbumin (OVA) was intramuscularly injected in mice, in either a separation (OVA-PELCSE), a surface attachment (OVA-PELCSA) or an encapsulation (OVA-PELCEN) manner. As an antigen delivery system, a significant increase of OVA-loaded cells migrating into draining lymph nodes (LNs) was detected in the PELC-formulated OVA groups, attachment and encapsulation as well. Additionally, OVA-PELCEN allowed the mice to induce a delayed but long-lasting OVA-specific antibodies production compared to OVA-PELCSA. In the extreme case where no antigen-adjuvant association at all (i.e., OVA-PELCSE), we found that even with the presence of PELC at the contralateral limb, an elevated level of OVA uptake was detected in ipsilateral draining CD11c+ LN cells, which subsequently augmented the production of OVA-specific IgG antibodies during early vaccination. The mouse study allows us to find out the optimal vaccine formulation and deepens our understandings on how antigen-adjuvant associations can govern the cellular uptake and transportation of protein antigen into the draining LNs and prolong antigen-specific humoral immunity, even if the antigen and the adjuvant are given separately.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/farmacologia , Antígenos/imunologia , Imunidade Humoral , Animais , Células Apresentadoras de Antígenos/metabolismo , Antígeno CD11c/metabolismo , Movimento Celular/efeitos dos fármacos , Emulsões/química , Feminino , Imunidade Humoral/efeitos dos fármacos , Injeções Intramusculares , Linfonodos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Vacinação
17.
Bull Exp Biol Med ; 167(4): 521-524, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31502124

RESUMO

The effects of inhalation exposure to a mixture containing acetone, acetaldehyde, and ethanol in concentrations typical of closed environment in space vehicles on the structure of mesenteric lymph nodes in F1 male mice were studied by histological technique. The long-term exposure to modeled atmosphere led to pronounced structural changes in these nodes that were clearly seen on day 22 and increased by day 36 of the experiment. The thickness of the capsule and trabeculae of mesenteric lymph nodes as well as diameter of lymphatic sinuses did not differ from the control values up to day 8, but then increased on days 22-70. Starting from day 22, the thickness of the medullary cords decreased and attained the minimum to the end of the experiments, which can indicate depletion of immunocytopoiesis and inhibition of humoral immunity. The present data are important for the space medicine, because they indicate structural changes in the peripheral lymphoid organs, the key elements of immune system.


Assuntos
Linfonodos/efeitos dos fármacos , Voo Espacial , Acetaldeído/toxicidade , Acetona/toxicidade , Animais , Etanol/toxicidade , Imunidade Humoral/efeitos dos fármacos , Masculino , Camundongos
18.
AAPS PharmSciTech ; 20(7): 292, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31428888

RESUMO

Mitoxantrone (MTO) is used to treat certain types of cancer, mostly metastatic cancer. While the drug has poor aqueous solubility and high side effects. Self-assembly nanocrystal is a novel lymphatic targeting delivery system. In our study, MTO self-assembly nanocrystal (MTO NC) was successfully prepared to improve lymphatic targeting ability and reduce its toxicity. MTO NCs had small size, stable potential, and uniform distribution. The average particle size of MTO NCs was less than 100 nm with the 0.218 PDI and - 6.6 mV the Zeta potential value. TEM images showed that MTO NCs had a sphere-like morphology with smooth surface and uniform distribution; Atomic force microscopy (AFM) images gave a 3D surface of MTO NCs. Polarizing microscope micrograph (PLM) of MTO NCs in lymph nodes demonstrated the crystal structure of MTO NCs when it was exposed to physiological condition. Transmission electron microscopy showed the presence of MTO NCs in mice lymph nodes. Pharmacokinetic parameters of MTO strongly demonstrated that MTO NCs could target the lymph nodes after subcutaneous injection. Moreover, tissue distribution results indicated that MTO NCs were mainly absorbed by the lymphatics and reduced system toxicity. Finally, a lymphatic metastasis mice model was established to precede the pharmacodynamics of MTO NCs, and using MTO liposomes as a reference preparation, the inhibitory effect of MTO NCs on lymphatic metastasis was markedly higher. Briefly, MTO NCs, as a novel self-assembled lymphatic targeting system, can accumulate in the metastatic lymph nodes and lead anticancer drug to kill cancer cells and control lymphatic metastasis with extremely low systemic toxicity.


Assuntos
Antineoplásicos/farmacologia , Linfonodos/efeitos dos fármacos , Metástase Linfática , Mitoxantrona/farmacologia , Nanopartículas , Animais , Antineoplásicos/química , Lipossomos/metabolismo , Camundongos , Mitoxantrona/química , Solubilidade , Distribuição Tecidual
19.
J Immunotoxicol ; 16(1): 155-163, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31403359

RESUMO

Exposure to the widely-used phthalate plasticizer di-(2-ethylhexyl)-phthalate (DEHP) has been shown to be closely related to an increased prevalence of allergic diseases in infants and juveniles. Earlier work in our laboratory found that DEHP-related anaphylactic responses could be ascribed to T-follicular helper (Tfh) cell hyperfunction directly. The Tfh cell, a newly identified CD4+ TH cell subset, until recently has been considered as a key player in humoral immunity. Tfh cells can respond to stimulation through various receptors. Signaling lymphocytic activation molecule family member-1 (SLAMF1, CD150) is a surface co-stimulatory receptor that can bind to an intracytoplasmic adaptor signaling lymphocytic activation molecule-associated protein (SAP) to initiate downstream signaling cascades, regulating some events of immune response. The present study explored the role of SLAMF1 in Tfh cell differentiation and cytokine secretion under the condition of DEHP exposure. Using a weanling mice model of DEHP gavage with ovalbumin (OVA) sensitization, it was found that DEHP acted as an immunoadjuvant to elevate SLAMF1 and SAP expression in host Tfh cells. Ex vivo studies of effects from DEHP exposure on Tfh cells from OVA-sensitized hosts showed that DEHP acted in an adjuvant-like manner to promote the expression of adaptor protein SAP, transcription factors Bcl-6 and c-MAF, and cytokines interleukin (IL)-21 and IL-4 in Tfh cells. Transfection of these Tfh cells with Slamf1 small interfering RNA prior to exposure to the DEHP attenuated the over-expression of these molecules that was caused by the DEHP. In conclusion, this study demonstrated that DEHP, via a SLAMF1-mediated pathway, can impact on Tfh cell differentiation and their ability to form select cytokines.


Assuntos
Anafilaxia/imunologia , Diferenciação Celular/efeitos dos fármacos , Dietilexilftalato/toxicidade , Plastificantes/toxicidade , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Administração Oral , Anafilaxia/induzido quimicamente , Animais , Animais Recém-Nascidos , Diferenciação Celular/imunologia , Criança , Dietilexilftalato/administração & dosagem , Modelos Animais de Doenças , Humanos , Interleucina-4/imunologia , Interleucina-4/metabolismo , Interleucinas/imunologia , Interleucinas/metabolismo , Linfonodos/citologia , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Camundongos , Ovalbumina/imunologia , Plastificantes/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Proteína Associada à Molécula de Sinalização da Ativação Linfocitária/imunologia , Proteína Associada à Molécula de Sinalização da Ativação Linfocitária/metabolismo , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária/imunologia , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Desmame
20.
Br J Radiol ; 92(1103): 20180734, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31430185

RESUMO

OBJECTIVE: The purpose of our study was to evaluate the visibility of the hilar lymph nodes (LNs) using advanced virtual monoenergetic low-keV images compared with early-phase contrast-enhanced CT. METHODS: Dual energy contrast-enhanced CT was performed for pre-operative evaluation of lung cancer at 20 and 60 s after administration of contrast media in 50 patients (32 males and 18 females; mean age, 69 years). Five kinds of images (A: 20 s/120 kV; B: 60 s/40 keV; C: 60 s/50 keV; D: 60 s/120 kV; E: 60 s/100 kV) were reconstructed. We measured the CT number of the bilateral main pulmonary arteries (PAs), pulmonary veins (PVs) and hilar LNs, and evaluated the differences in CT number (Hounsfield units, HUs) between the PA/PV and LNs (PA-LN and PV-LN contrast). Artifacts from the superior vena cava (SVC) were also evaluated. RESULTS: The mean PA-LN contrast (HU) was 415 in image group A, 299 in B, 180 in C, 80 in D, and 100 in E. The mean PV-LN contrasts in each group were 306, 287, 177, 78, and 99, respectively. Image group B showed the second highest PA-LN contrast following image group A. There was no significant difference in the PV-LN contrast between image groups A and B. The PA-LN and PV-LN contrasts of image groups B and C were significantly higher than those of E. SVC artifacts were lower in the delayed-phase images (Group B-E) than in Group A. CONCLUSION: To evaluate the hilar LNs with a single image series, advanced virtual monoenergetic 40-keV imaging at the delayed 60-s phase seems to be the most valuable. ADVANCES IN KNOWLEDGE: Advanced virtual monoenergetic image is useful for evaluation of both hilar LNs and tumors in the delayed phase without artifact derived from the streak artifact from dense contrast media in the SVC.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Linfonodos/efeitos dos fármacos , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores/métodos , Cuidados Pré-Operatórios/métodos , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos
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