RESUMO
A traumatic iliacus hematoma is rare and usually occurs in patients after a fall involving a lower back injury. Although the hematoma may compress the femoral nerve causing femoral nerve palsy, the gold standard treatment for this condition has not been established. Here we report transcatheter arterial embolisation as a useful treatment strategy for a traumatic iliacus hematoma.
RESUMO
Environmental radioactive contamination caused by the Fukushima Dai-ichi Nuclear Power Plant accident has aroused great concern regarding a possible increase in the incidence of childhood thyroid cancer. The ultrasound examinations were conducted immediately after the accident as part of the Fukushima Health Management Survey (FHMS), which is divided into the preliminary baseline survey (PBLS) and the full-scale survey (FSS). Some of their outcomes are reported regularly and made available to the public. We have detailed measurements of the air-dose rates and radioactive elements in soil in many places all over the Fukushima prefecture. To study the dose-response relationship, we begin with the assumption that the external and internal doses are correlated with the air-dose rate and the amount of 131I in soil, respectively. We then investigate the relationship between these estimated doses and the PBLS and FSS thyroid cancer cases. Our analysis shows that the dose-response curve with the FSS data clearly differs from that with the PBLS data. Finally, we consider the potential mitigating effects of evacuation from highly contaminated areas in both external and internal exposure scenarios.
Assuntos
Poluição Ambiental/efeitos adversos , Acidente Nuclear de Fukushima , Inquéritos Epidemiológicos , Radioisótopos do Iodo/efeitos adversos , Neoplasias Induzidas por Radiação/epidemiologia , Monitoramento de Radiação , Neoplasias da Glândula Tireoide/epidemiologia , Criança , Humanos , Japão/epidemiologia , Neoplasias Induzidas por Radiação/etiologia , Doses de Radiação , Neoplasias da Glândula Tireoide/etiologiaRESUMO
NAD+ (oxidized form of NAD:nicotinamide adenine dinucleotide)-reducing soluble [NiFe]-hydrogenase (SH) is phylogenetically related to NADH (reduced form of NAD+):quinone oxidoreductase (complex I), but the geometrical arrangements of the subunits and Fe-S clusters are unclear. Here, we describe the crystal structures of SH in the oxidized and reduced states. The cluster arrangement is similar to that of complex I, but the subunits orientation is not, which supports the hypothesis that subunits evolved as prebuilt modules. The oxidized active site includes a six-coordinate Ni, which is unprecedented for hydrogenases, whose coordination geometry would prevent O2 from approaching. In the reduced state showing the normal active site structure without a physiological electron acceptor, the flavin mononucleotide cofactor is dissociated, which may be caused by the oxidation state change of nearby Fe-S clusters and may suppress production of reactive oxygen species.
Assuntos
Proteínas de Bactérias/química , Hidrogenase/química , NAD/química , Sítios de Ligação , Oxirredução , Conformação Proteica , Subunidades Proteicas/química , SolubilidadeRESUMO
PURPOSE: This study was conducted to evaluate changes in liver stiffness, volume, and function before and after occlusion of spontaneous portosystemic shunt. MATERIALS & METHODS: Twenty-four patients (13 men and 11 women) with a mean age of 68.2 years±10.1 (SD) (age range, 49-82 years) underwent percutaneous occlusion of spontaneous portosystemic shunt because of gastric varices (n=17) or hepatic encephalopathy (n=7) from March 2011 to June 2013. The liver fibrosis index indicating liver stiffness was calculated by using ultrasound elastography before and after shunt occlusion. Liver volume and liver profile were also evaluated. RESULTS: Spontaneous portosystemic shunt occlusion was uneventfully performed in all patients. The mean liver fibrosis index was significantly decreased from 2.7±1.0 before shunt occlusion to 2.0±0.9 (P<0.001) at 1 month, 2.2±1.0 at 3 months (P=0.004), and 1.6±0.7 at 6 months (P=0.001) afterwards. A significant increase in the liver volume was observed from 1035.3±340.1mL before shunt occlusion to 1116.8±298.4mL (P=0.006) at 1 month and 1174.2±354.1mL (P<0.001) at 3 months afterwards. Significant improvement in the Child-Pugh score was also found at 1 month (6.2±1.4, P<0.001), 3 months (6.5±1.1, P=0.022), and 6 months (6.0±0.9, P=0.004) after shunt occlusion as compared with that (7.2±1.9) before. CONCLUSION: The liver stiffness decreases along with an increase in liver volume and improvement in liver function after spontaneous portosystemic shunt occlusion.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Encefalopatia Hepática/diagnóstico por imagem , Encefalopatia Hepática/terapia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/terapia , Derivação Portossistêmica Cirúrgica , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Ácidos Oleicos/uso terapêutico , Tamanho do Órgão/fisiologia , Prognóstico , Estudos RetrospectivosRESUMO
Specific components of the intestinal microbiota are capable of influencing immune responses such that a mutualistic relationship is established. In mice, colonization with segmented filamentous bacteria (SFB) induces T-helper-17 (Th17) cell differentiation in the intestine, yet the effector functions of interleukin (IL)-17A in response to SFB remain incompletely understood. Here we report that colonization of mice with SFB-containing microbiota induced IL-17A- and CXCR2-dependent recruitment of neutrophils to the ileum. This response required adaptive immunity, as Rag-deficient mice colonized with SFB-containing microbiota failed to induce IL-17A, CXCL1 and CXCL2, and displayed defective neutrophil recruitment to the ileum. Interestingly, neutrophil depletion in wild-type mice resulted in significantly augmented Th17 responses and SFB expansion, which correlated with impaired expression of IL-22 and antimicrobial peptides. These data provide novel insight into a dynamic IL-17A-CXCR2-neutrophil axis during acute SFB colonization and demonstrate a central role for neutrophils in limiting SFB expansion.
Assuntos
Bactérias/imunologia , Microbioma Gastrointestinal/imunologia , Íleo/imunologia , Interleucina-17/metabolismo , Neutrófilos/imunologia , Receptores de Interleucina-8B/metabolismo , Células Th17/imunologia , Imunidade Adaptativa/genética , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Bactérias/crescimento & desenvolvimento , Diferenciação Celular , Movimento Celular/genética , Células Cultivadas , Proteínas de Homeodomínio/genética , Íleo/microbiologia , Interleucinas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Interleucina 22RESUMO
Catechins are ingested as food components and supplements. It is known that catechins are transformed to dinitrosocatechins by nitrite under acidic conditions, suggesting the possibility of their formation in the stomach because saliva contains nitrite. This paper deals with nitrite-induced transformation of (+)-catechin in methanol extracts of adzuki bean into 6,8-dinitrosocatechin in acidified saliva (pH ≈ 1.9). As the mechanism of its formation, addition of nitric oxide (NO) to (+)-catechin semiquinone radical, both of which were produced in nitrous acid/(+)-catechin systems, was proposed. The dinitrosocatechin was oxidized to the quinone by nitrous acid, and the quinone reacted with a salivary component thiocyanate producing 6'-thiocyanato-6,8-dinitrosocatechin. Since quinones are toxic, we propose a function of thiocyanate as a scavenger of the o-quinone formed from dinitrosocatechins in the stomach.
Assuntos
Catequina/análogos & derivados , Fabaceae/metabolismo , Mucosa Gástrica/metabolismo , Nitritos/química , Tiocianatos/química , Catequina/biossíntese , Humanos , Óxido Nítrico/metabolismo , Nitritos/metabolismo , Saliva/química , Saliva/metabolismo , Estômago/química , Tiocianatos/metabolismoRESUMO
Leptin is thought to be not only a satiety factor but also a stimulator of angiogenesis. We examined leptin, PPARγ2, and vascular endothelial growth factor (VEGF) expression in bovine intramuscular preadipocyte (BIP) cells during proliferation. The cells were seeded at 0.85 × 10(4) cells/cm(2) and collected every day until the fifth day after passage. Leptin mRNA was present in the cells between days 2 and 4, as indicated by RT-PCR analysis. Western blot analysis showed a band for leptin at approximately 16 kDa on all of the days during growth, and the cytoplasmic concentration of leptin was highest on day 2 and decreased gradually thereafter. A PPARγ2 band at approximately 54 kDa was also observed on all days. The concentration was highest on day 2 and decreased thereafter, which is similar to the expression pattern of leptin. In constant, the expression level of VEGF protein did not change while in culture. We have demonstrated that BIP cells can synthesize both leptin and PPARγ2, with maximal synthesis occurring during maximal proliferation. Given the role of leptin in angiogenesis, we speculate that leptin is involved in the neovascularization of adipose tissue, because new organization of adipose tissue requires the growth of new blood vessels.
Assuntos
Adipócitos/metabolismo , Bovinos/metabolismo , Leptina/biossíntese , Músculos/citologia , Tecido Adiposo/irrigação sanguínea , Indutores da Angiogênese , Animais , Linhagem Celular , Proliferação de Células , Expressão Gênica , Leptina/análise , Leptina/genética , PPAR gama/análise , PPAR gama/biossíntese , PPAR gama/genética , RNA Mensageiro/análise , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND: Clostridium difficile (Cdf) releases toxins (TcdA and TcdB) that damage the intestinal epithelial barrier. Ecto-5'-nucleotidase (CD73) is expressed on intestinal epithelial cells, and it is hypothesized to protect against toxin-induced epithelial damage through the cleavage of 5'-AMP to adenosine (Ado) and subsequent activation of adenosine receptors (AdoRs). Herein, we sought to assess the potential protective effects of CD73 and AdoR signaling on the injurious effects of Cdf toxins. METHODS: Barrier function was assessed with T84 colonocytes. Transepithelial electrical resistance (TEER), paracellular fluorescein isothiocyanate (FITC)-dextran flux, and tight junction protein (ZO-1) integrity were monitored. Intrarectal installation of Cdf toxin was used to assess epithelial damage in vivo. KEY RESULTS: TcdA/B caused reduced TEER and increased paracellular flux in vitro. Concurrent treatment with 5'-AMP attenuated these responses to Cdf toxin; an effect that was blocked with ZM241385 (AdoRA2 antagonist). APCP, a CD73 inhibitor, also suppressed the protective effects of 5'-AMP on paracellular flux. 5'-AMP reduced toxin-induced disruption of ZO-1, an effect that was abolished by APCP and ZM241385. Inhibition of CD73 with APCP during Cdf toxin exposure led to increased intestinal barrier permeability and epithelial damage in vivo. Intrarectal instillation of 5'-AMP had no effect on toxin-induced intestinal injury. CONCLUSIONS & INFERENCES: Our data suggest that CD73 has a protective role against TcdA/B-induced damage. 5'-AMP treatment attenuated the damaging effects of Cdf toxin in vitro, and inhibitors of CD73 (APCP) and AdoRs (ZM241385) revealed that the cleavage of 5'-AMP to Ado was necessary for the protective effects. Inhibition of CD73 in vivo increases colonic tissue damage and epithelial permeability during Cdf toxin exposure.
Assuntos
5'-Nucleotidase/metabolismo , Proteínas de Bactérias/farmacologia , Toxinas Bacterianas/farmacologia , Enterotoxinas/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Receptores Purinérgicos P1/metabolismo , Linhagem Celular Tumoral , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Permeabilidade , Transdução de Sinais , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismoRESUMO
AIM: The influence of psychological disturbances in oral lichen planus (OLP) still bears some controversy. This study aimed at assessing levels of anxiety and depression in OLP patients and control subjects, using a self-report scale questionnaire. METHODS: This cross-sectional study comprised 91 consecutive OLP patients (71 female and 20 male; mean age 52.9 years) and 87 subjects as a control group (69 female and 18 male; mean age 52.7 years). Data collected of both groups included age, sex, race, medical records and systemic disease. Anxiety and depression levels were assessed using, respectively, the State-Trait Anxiety Inventory (STAI-T) and Center for Epidemiologic Studies Depression Scale (CES-D). Data were analyzed by Chi-square and Fisher's exact tests as appropriate, and by Logistic regression analysis. RESULTS: No statistically significant difference was found when the level of anxiety and depression was compared between the OLP and control using Chi-square and Fisher's tests (P>0.05). Logistic regression analysis showed that the score in 2 out of 20 items of the STAI-T scale (but none of the CES-D) was significantly higher in OLP patients (P<0.05). The analysis by gender showed that the female and male OLP patients presented a significantly higher score for one item in the STAI-T scale (respectively question 4 and 20) but none in the CES-D scale, as compared with that of the control group (P<0.05). CONCLUSION: Our findings do not support that either anxiety or depression has any role in the development of OLP lesions.
Assuntos
Ansiedade/complicações , Depressão/complicações , Líquen Plano Bucal/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/imunologia , Linfócitos T CD8-Positivos/imunologia , Causalidade , Comorbidade , Estudos Transversais , Depressão/imunologia , Feminino , Humanos , Líquen Plano Bucal/etiologia , Líquen Plano Bucal/imunologia , Masculino , Pessoa de Meia-Idade , Testes Psicológicos , Autorrelato , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Dietary salt restriction is believed to be a mainstay in the management of patients with heart failure. However, the effect of salt intake on heart failure has not been well evaluated in outpatient medical practice. AIMS: The aim of the present study was to assess the hypothesis that B-type natriuretic peptide (BNP) level, as an objective marker of heart failure, is associated with salt intake in patients with heart failure. METHODS: One hundred and thirteen consecutive patients with mild compensated heart failure (77 ± 10 years old, 51 female) were included. We estimated dietary salt intake by the concentration of sodium and creatinine in spot urine. We measured BNP at the time of urine sampling and assessed the relationship between the % changes in BNP levels (%ΔBNP) and the changes in the estimated daily salt excretion (ΔNaCl) during the follow-up period. RESULTS: The baseline median BNP level was 150 (interquartile range: 83-263) pg/mL and the estimated daily salt excretion was 162 ± 45 mmol/day. There was a positive correlation between %ΔBNP and ΔNaCl (r = 0.61, P < 0.01). Multiple regression analysis revealed that %ΔBNP was associated with ΔNaCl (P < 0.01), but not with changes in systolic blood pressure and bodyweight. CONCLUSIONS: Changes in BNP levels were associated with changes in the estimated daily salt excretion in outpatients with compensated heart failure. Salt restriction may be beneficial for the management of patients with heart failure.
Assuntos
Insuficiência Cardíaca/dietoterapia , Insuficiência Cardíaca/urina , Peptídeo Natriurético Encefálico/urina , Cloreto de Sódio na Dieta/administração & dosagem , Cloreto de Sódio na Dieta/urina , Volume Sistólico/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Upregulation of lipogenesis is a hallmark of cancer and blocking the lipogenic pathway is known to cause tumor cell death by apoptosis. However, the exact role of lipogenesis in tumor initiation is as yet poorly understood. We examined the expression profile of key lipogenic genes in clinical samples of ductal carcinoma in situ (DCIS) of breast cancer and found that these genes were significantly upregulated in DCIS. We also isolated cancer stem-like cells (CSCs) from DCIS.com cell line using cell surface markers (CS24(-)CD44(+)ESA(+)) and found that this cell population has significantly higher tumor-initiating ability to generate DCIS compared with the non-stem-like population. Furthermore, the CSCs showed significantly higher level of expression of all lipogenic genes than the counterpart population from non-tumorigenic breast cancer cell line, MCF10A. Importantly, ectopic expression of SREBP1, the master regulator of lipogenic genes, in MCF10A significantly enhanced lipogenesis in stem-like cells and promoted cell growth as well as mammosphere formation. Moreover, SREBP1 expression significantly increased the ability of cell survival of CSCs from MCF10AT, another cell line that is capable of generating DCIS, in mouse and in cell culture. These results indicate that upregulation of lipogenesis is a pre-requisite for DCIS formation by endowing the ability of cell survival. We have also shown that resveratrol was capable of blocking the lipogenic gene expression in CSCs and significantly suppressed their ability to generate DCIS in animals, which provides us with a strong rationale to use this agent for chemoprevention against DCIS.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Lipogênese/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/prevenção & controle , Carcinoma Intraductal não Infiltrante/prevenção & controle , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lipogênese/efeitos dos fármacos , Camundongos , Camundongos Nus , Resveratrol , Células-Tronco/patologia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Estilbenos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
AIM: Objective of this study was to compare the skin-patch test with the clinical diagnosis of oral lichenoid contact reaction (OLCR) as indicators for amalgam replacement. METHODS: Of 53 patients (38 female and 15 male; mean age 48.7) with oral lichen planus (OLP), 26 were identified as having OLCR, and clinically graded according to the proximity of their lesions with amalgam fillings: class I (weak association), class II (moderate association), and class III (strong association). All OLCR patients were skin-patch tested for both standard (Brazilian) and specific allergens (TROLAB, Germany). Patients were considered skin-patch positive only if they developed positive skin reactions for thimerosal and/or amalgam components. Amalgam replacement was indicated in all class II and III patients. For class-I patients, amalgam replacement was indicated only if they were skin-patch test positive. Readings for the skin-patch test were made at 48h and 96h. RESULTS: Of the 26 patients with OLCR, two missed the follow-up and were excluded, leaving 24 cases. Of these, four were class-I, and all were negative for the skin-patch test. Twelve were class-II, of whom seven were skin-patch positive. Eight were class-III, of whom six were skin-patch positive. Following amalgam replacement in the 12 class-II patients, six showed improvement and six had complete resolution, while in the eight class-III patients, two showed improvement and six a complete resolution. CONCLUSION: Clinical diagnosis of OLCR lesions is a more reliable indicator for the question of amalgam replacement than is the skin-patch test.
Assuntos
Amálgama Dentário/efeitos adversos , Líquen Plano Bucal/induzido quimicamente , Líquen Plano Bucal/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes do EmplastroRESUMO
Notch signaling is often and aberrantly activated by hypoxia during tumor progression; however, the exact pathological role of hypoxia-induced Notch signaling in tumor metastasis is as yet poorly understood. In this study, we aimed to define the mechanism of Notch-ligand activation by hypoxia in both primary tumor and bone stromal cells in the metastatic niche and to clarify their roles in tumor progression. We have analyzed the expression profiles of various Notch ligands in 779 breast cancer patients in GEO database and found that the expression of Jagged2 among all five ligands is most significantly correlated with the overall- and metastasis-free survival of breast cancer patients. The results of our immunohistochemical (IHC) analysis for Jagged2 in 61 clinical samples also revealed that both Jagged2 and Notch signaling were strongly upregulated at the hypoxic invasive front. Activation of Jagged2 by hypoxia in tumor cells induced EMT and also promoted cell survival in vitro. Notably, a γ-secretase inhibitor significantly blocked Notch-mediated invasion and survival under hypoxia by promoting expression of E-cadherin and inhibiting Akt phosphorylation. Importantly, Jagged2 was also found to be upregulated in bone marrow stroma under hypoxia and promoted the growth of cancer stem-like cells by activating their Notch signaling. Therefore, hypoxia-induced Jagged2 activation in both tumor invasive front and normal bone stroma has a critical role in tumor progression and metastasis, and Jagged2 is considered to be a valuable prognostic marker and may serve as a novel therapeutic target for metastatic breast cancer.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Hipóxia Celular , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Membrana/metabolismo , Metástase Neoplásica , Células-Tronco Neoplásicas/metabolismo , Receptores Notch/metabolismo , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Neoplasias da Mama/genética , Caderinas/biossíntese , Caderinas/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteína Jagged-2 , Proteínas de Membrana/genética , Células-Tronco Neoplásicas/patologia , Proteína Oncogênica v-akt/metabolismo , Fosforilação , Receptores Notch/genética , Células EstromaisRESUMO
BACKGROUND: Salvinorin A (SA) is the principal active ingredient of Salvia divinorum, with an established inhibitory action on gastrointestinal (GI) transit and colonic ion transport in mice. Under normal conditions, the effects of SA are mediated by kappa opioid (KOR) and cannabinoid (CB1 and CB2) receptors. However, the role of SA in pathophysiological conditions remains unresolved. The aim of this study was to characterize the in vitro and in vivo effects of SA on mouse ileum after endotoxin challenge. METHODS: Changes in GI motility were studied in vitro, using smooth muscle preparations from the mouse ileum. In vivo, the fecal pellet output and small intestinal fluid content were measured. Neurogenic ion transport and intestinal permeability were examined using Ussing chambers. In addition, Western blot analysis of mucosa was performed and plasma nitrite/nitrate levels were determined. KEY RESULTS: Salvinorin A inhibited endotoxin-induced ileal hypercontractility via KOR, CB1, and CB2 receptors. Neurogenic ion transport, which was significantly reduced after endotoxin challenge, was normalized by SA through a nitric oxide synthase (NOS)-dependent mechanism. Western blot analysis and plasma nitrite/nitrate level quantitation confirmed the involvement of NOS in the regulatory action of SA. CONCLUSIONS & INFERENCES: This is the first report showing differential effects of SA on motor and secretory activity in mouse GI during endotoxemia. The outcomes of our study imply possible novel applications of SA and its analogs in the treatment of GI disorders.
Assuntos
Diterpenos Clerodânicos/farmacologia , Endotoxinas/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Íleo/efeitos dos fármacos , Íleo/fisiologia , Transporte de Íons/efeitos dos fármacos , Animais , Defecação/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Contração Muscular/fisiologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Nitritos/metabolismoRESUMO
Intestinal mucosal integrity is dependent on epithelial function and a regulated immune response to injury. Fucosyltransferase VII (Fuc-TVII) is an essential enzyme required for the expression of the functional ligand for E- and P-selectin. Trefoil factor 3 (TFF3) is involved in both protecting the intestinal epithelium against injury as well as aiding in wound repair following injury. The aim of the present study was to assess the interplay between barrier function and leukocyte recruitment in intestinal inflammation. More specifically, we aimed to examine how targeted disruption of Fuc-TVII either in wild-type or TFF3(-/-) mice would alter their susceptibility to colonic injury. TFF3 and Fuc-TVII double-knockout mice (TFF3/Fuc-TVII(-/-) mice) were generated by mating TFF3(-/-) and Fuc-TVII(-/-) mice. Colitis was induced by administration of dextran sodium sulfate (DSS) (2.5% wt/vol) in the drinking water. Changes in baseline body weight, diarrhea, and fecal blood were assessed daily. Upon euthanasia, extents of colonic inflammation were assessed macroscopically, microscopically, and through quantification of myeloperoxidase (MPO) activity. Colonic lymphocyte subpopulations were assessed at 6 days after administration of DSS by flow cytometry and immunohistochemistry. No baseline intestinal inflammation was found in TFF3/Fuc-TVII(-/-), TFF3(-/-), Fuc-TVII(-/-), or wild-type mice. Loss of Fuc-TVII resulted in a reduction in disease severity whereas TFF3(-/-) mice were markedly more susceptible to DSS-induced colitis. Remarkably, the loss of Fuc-TVII in TFF3(-/-) mice markedly decreased the severity of DSS-induced colitis as evidenced by reduced weight loss, diarrhea, decreased colonic MPO levels and improved survival. Furthermore, the loss of TFF3 resulted in increased severity of spontaneous colitis in IL-2/beta-microglobulin-deficient mice. These studies highlight the importance of the interplay between factors involved in the innate immune response, mucosal barrier function, and genes involved in regulating leukocyte recruitment and other aspects of the immune response.
Assuntos
Quimiotaxia de Leucócito , Colite/enzimologia , Fucosiltransferases/metabolismo , Imunidade Inata , Mucosa Intestinal/enzimologia , Leucócitos/enzimologia , Mucinas/metabolismo , Animais , Colite/induzido quimicamente , Colite/genética , Colite/imunologia , Colite/patologia , Colite/prevenção & controle , Sulfato de Dextrana , Diarreia/enzimologia , Diarreia/genética , Diarreia/imunologia , Modelos Animais de Doenças , Fucosiltransferases/deficiência , Fucosiltransferases/genética , Interleucina-2/deficiência , Interleucina-2/genética , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Leucócitos/imunologia , Leucócitos/patologia , Melena/enzimologia , Melena/genética , Melena/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mucinas/deficiência , Mucinas/genética , Peroxidase/metabolismo , Índice de Gravidade de Doença , Fatores de Tempo , Fator Trefoil-3 , Redução de Peso , Microglobulina beta-2/deficiência , Microglobulina beta-2/genéticaRESUMO
Regulatory T cells (T(reg)) have an essential role in maintaining immune tolerance in the gut. The functional CD4(+) T(reg) express the transcription factor forkhead box protein 3 (FoxP3) or a CD25(high) in humans. Further, depletion of elevated granulocytes/monocytes by extracorporeal adsorption (GMA) induces immunomodulation in patients with ulcerative colitis (UC). We investigated the impact of GMA on T(reg). Thirty-one UC patients, clinical activity index (CAI) 12.1 +/- 2.97, refractory to conventional medications including intravenous corticosteroid and 13 healthy controls (HC), were included. Patients received five GMA sessions over 5 weeks. Biopsies from the rectal mucosa and blood samples at baseline and post-GMA were immunostained with anti-CD4/FoxP3 and anti-CD4/CD25 antibodies for immunohistochemistry and flow cytometry. Following GMA, 22 of 31 patients achieved remission (CAI Assuntos
Antígenos CD4/análise
, Colite Ulcerativa/imunologia
, Fatores de Transcrição Forkhead/análise
, Subunidade alfa de Receptor de Interleucina-2/análise
, Linfócitos T Reguladores/imunologia
, Adsorção
, Adulto
, Estudos de Casos e Controles
, Colite Ulcerativa/tratamento farmacológico
, Colite Ulcerativa/terapia
, Feminino
, Citometria de Fluxo
, Glucocorticoides/uso terapêutico
, Granulócitos/fisiologia
, Humanos
, Imuno-Histoquímica
, Leucaférese
, Masculino
, Pessoa de Meia-Idade
, Monócitos/fisiologia
, Estatísticas não Paramétricas
, Resultado do Tratamento
RESUMO
OBJECTIVES: It remains to be fully clarified how adhesion of mast cells is regulated in vivo. We previously reported that PGE2-receptor EP4 stimulated the adhesion of mouse mastocytoma P-815 cells to plate-bound fibronectin. Our purpose in this study is to evaluate the adhesion using a system, which can mimic the in vivo adhesion. METHODS: P-815 cells were transplanted in an air pouch produced in the transplantable mice, CDF1. The number of cells that adhere to the subcutaneous tissues overlaying the inside cavity surface was determined. RESULTS: The number of adhered cells was decreased in mice administered with ibuprofen or an EP4 antagonist, ONO AE3-208. A local administration of PGE(2) or a phorbol ester, PMA, increased the number of adhered cells, which was also suppressed in the mice treated with ONO AE3-208. CONCLUSION: Our results suggest that PGE(2)-mediated adhesion of P-815 cells in the subcutaneous tissues of the air pouch is mediated by the EP4 subtype.
Assuntos
Adesão Celular/fisiologia , Matriz Extracelular/metabolismo , Mastocitoma , Receptores de Prostaglandina E/metabolismo , Tela Subcutânea/metabolismo , Animais , Linhagem Celular Tumoral , Inibidores de Ciclo-Oxigenase/metabolismo , Matriz Extracelular/química , Ibuprofeno/metabolismo , Masculino , Mastócitos/citologia , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos , Naftalenos/metabolismo , Fenilbutiratos/metabolismo , Receptores de Prostaglandina E/genética , Receptores de Prostaglandina E Subtipo EP4 , Tela Subcutânea/anatomia & histologia , Acetato de Tetradecanoilforbol/metabolismoRESUMO
AIM: This study evaluated the effect of acupuncture on salivary flow rates in patients with radiation-induced xerostomia. METHODS: Twelve patients with severe xerostomia were treated with acupuncture after radiation therapy. The baseline data were obtained preceding acupuncture treatment, and used as reference values. Acupuncture was performed in 12 sessions, 20 min each, twice a week, during a 6-week period. Clinical response was evaluated objectively by saliva collection measuring resting and stimulated whole salivary flow rates, and subjectively by a visual analogue scale patients' self-evaluation questionnaire. Statistical analyses were performed with a repeated-measures analysis of variance by using a mixed-effect modeling procedure. RESULTS: The results showed a statistically significant improvement for salivary flow rates on both objective and subjective evaluations (P<0.05). On objective evaluation there was an increase for resting salivary flow of 142.2% (mean=0.04 mL/min to 0.12 mL/min) and of 73.5% (mean=0.09 mL/min to 0.21 mL/min) for stimulated salivary flow. On subjective evaluation, visual analogue scale raised 36 points (mean=18.4 to 53.8) for sensation of more saliva production. CONCLUSION: According to the results of the present study, acupuncture showed a significant effect on saliva production, suggesting this therapy as a useful treatment for patients suffering from radiation-induced xerostomia.
Assuntos
Terapia por Acupuntura , Lesões por Radiação/complicações , Salivação , Xerostomia/etiologia , Xerostomia/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Xerostomia/fisiopatologiaRESUMO
Several families exhibiting multiple gastrointestinal stromal tumours (GISTs) and germline c-kit gene mutations at exons 8, 11, 13, or 17 have been reported. These patients also exhibit diffuse hyperplasia of the interstitial cells of Cajal (ICCs) as a pre-existing lesion of multiple GISTs. We generated a mouse model of a family with germline c-kit gene mutation at exon 17, and compared the phenotypes between the mice and humans. The mouse counterpart (KIT-Asp818Tyr) of the human KIT-Asp820Tyr mutation was transmitted into germline by a knock-in strategy. Mating of male and female heterozygotes (KIT-Asp818Tyr/+) resulted in the generation of homozygotes (KIT-Asp818Tyr/KIT-Asp818Tyr). Histological examination revealed that all heterozygotes had both a small KIT-positive mesenchymal tumour at the caecum, consistent with GIST, and KIT-positive diffuse spindle-shaped cell proliferation in the distal oesophagus, stomach, proximal duodenum, and colon consistent with ICC hyperplasia. All homozygotes exhibited a larger caecal tumour and more prominent spindle-shaped cell proliferation compared with the heterozygous mice, and they usually died within 10 weeks after birth, likely due to ileus. The small intestine of both genotypes showed no apparent morphological abnormality, and autonomous contraction of the ileal segments appeared normal. Western blotting demonstrated that the caecal tumours expressed phosphorylated KIT, MAPK, Stat1, and Stat5. These mutant mice are considered to be useful for further investigation of the mechanism of GIST development as a result of ICC hyperplasia and for assessment of the in vivo effects of drugs against molecular targets.