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1.
J Environ Pathol Toxicol Oncol ; 39(3): 235-245, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865915

RESUMO

Ulcerative colitis (UC) is an intractable ailment, in which may chronic inflammations/ulcerations may develop in the mucosal lining of the colon with multiple recurrences. Various drugs such as steroids, immunosuppressants, and antibiotics are extensively used to treat UC. The patients suffer from adverse effects of these advanced drugs. So, they need a harmless therapeutic agent from natural sources. The therapeutic D-carvone has an anti-inflammatory action against the investigational colon cancer models. Therefore, we analyzed the effect of D-carvone on dextran sulfate sodium (DSS) provoked colitis model in mice as follows: Group I: noncolitis healthy control mice; Group II: ulcerative colitis mice models; Group III: D-carvone (40 mg/kg) + ulcerative colitis models; Group IV: sulfasalazine (50 mg/kg) + ulcerative colitis models. On the 8th day, the experimental study was terminated and serum samples and colon tissues were processed for further analysis. The effect of D-carvone at different concentration was studied on the LPS challenged RAW 264.7 cell lines. The D-carvone (40 mg/kg) treatment maintained the colon length and decreased disease activity index (DAI) score in UC animals. The increased antioxidant enzymes status and decreased oxidative stress and pro-inflammatory markers were noted in the D-carvone (40 mg/ kg) + UC mice. Histopathological study of colon tissue of D-carvone (40 mg/kg) treated UC mice displayed less mucosal damage and improved crypt integrity and goblet cells compared with DSS only provoked mice. The im-munohistochemical expression of iNOS and COX-2 was drastically diminished in the D-carvone treated UC mice. D-carvone (40 mg/kg) treatment appreciably diminished the LPS provoked NO production and pro-inflammatory modulators in the RAW 264.7 macrophage cell lines. These findings proved that D-carvone has a potential therapeutic effect to prevent LPS induced inflammation in in vitro cells and chemically induced ulcerative colitis in vivo models.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Monoterpenos Cicloexânicos/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Macrófagos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue , Animais , Anti-Inflamatórios/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Colo/efeitos dos fármacos , Colo/imunologia , Colo/patologia , Monoterpenos Cicloexânicos/administração & dosagem , Sulfato de Dextrana , Modelos Animais de Doenças , Lipopolissacarídeos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7
2.
Anticancer Res ; 40(10): 5611-5620, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988885

RESUMO

BACKGROUND/AIM: Cancer stem cell characteristics and drug resistance of colorectal cancer are associated with failure of cancer treatment. In this study, we investigated the effects of PrPC on cancer stem cell characteristics, migration, invasion, and drug resistance of 5FU-resistant CRC cells. MATERIALS AND METHODS: PrPC negative and PrPC positive cells were isolated from 5FU-resistant CRC cells using magnetic activated cell sorting. Sphere formation, cancer stem cell marker expression, migration, invasion, and drug resistance were analyzed. RESULTS: PrPC positive cells showed increased sphere formation capacity and increased expression of cancer stem cell markers compared to PrPC negative cells. In addition, PrPC positive cells showed increased migration, invasion and drug resistance compared to PrPC negative cells. Furthermore, knockdown of PrPC abolished these effects. CONCLUSION: PrPC expression is important in CRC cell behavior, such as sphere formation, migration, invasion, and drug resistance. PrPC is an important therapeutic target for the treatment of CRC.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/farmacologia , Proteínas Priônicas/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/genética , Colo/patologia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos
3.
Tokai J Exp Clin Med ; 45(3): 131-135, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32901901

RESUMO

Retained products of conception (RPOC) refer to the persistence of placental or fetal tissue in the uterus following delivery or miscarriage. RPOC may cause massive postpartum or post-abortion hemorrhage. Arterial embolization (AE) is an effective choice of management for postpartum hemorrhage including RPOC. We report a case of hemorrhagic RPOC, in which uterine artery embolization with transcervical resection did not achieve hemostasis, and laparotomy with uterine compression sutures was subsequently required. The RPOC was apparently fed by an aberrant branch derived from the inferior mesenteric artery (IMA). AE of IMA was not performed because of possible necrosis of the descending colon and rectum. A physician should be aware that AE is not an all-encompassing hemostatic technique for postpartum bleeding, such as with RPOC, and should keep alternatives in mind.


Assuntos
Hemostasia Cirúrgica/métodos , Laparotomia/métodos , Artéria Mesentérica Inferior , Complicações do Trabalho de Parto/etiologia , Complicações do Trabalho de Parto/cirurgia , Placenta Retida/cirurgia , Hemorragia Pós-Parto/etiologia , Hemorragia Pós-Parto/cirurgia , Técnicas de Sutura , Útero/cirurgia , Adulto , Colo/patologia , Contraindicações , Feminino , Humanos , Angiografia por Ressonância Magnética , Necrose , Complicações do Trabalho de Parto/diagnóstico por imagem , Placenta Retida/diagnóstico por imagem , Hemorragia Pós-Parto/diagnóstico por imagem , Gravidez , Reto/patologia , Tomografia Computadorizada por Raios X , Embolização da Artéria Uterina/efeitos adversos
4.
Nat Commun ; 11(1): 4766, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958778

RESUMO

Germline telomere maintenance defects are associated with an increased incidence of inflammatory diseases in humans, yet whether and how telomere dysfunction causes inflammation are not known. Here, we show that telomere dysfunction drives pATM/c-ABL-mediated activation of the YAP1 transcription factor, up-regulating the major pro-inflammatory factor, pro-IL-18. The colonic microbiome stimulates cytosolic receptors activating caspase-1 which cleaves pro-IL-18 into mature IL-18, leading to recruitment of interferon (IFN)-γ-secreting T cells and intestinal inflammation. Correspondingly, patients with germline telomere maintenance defects exhibit DNA damage (γH2AX) signaling together with elevated YAP1 and IL-18 expression. In mice with telomere dysfunction, telomerase reactivation in the intestinal epithelium or pharmacological inhibition of ATM, YAP1, or caspase-1 as well as antibiotic treatment, dramatically reduces IL-18 and intestinal inflammation. Thus, telomere dysfunction-induced activation of the ATM-YAP1-pro-IL-18 pathway in epithelium is a key instigator of tissue inflammation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , Inflamação/patologia , Telômero/patologia , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Antibacterianos/uso terapêutico , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Caspase 1/metabolismo , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Criança , Colo/metabolismo , Colo/microbiologia , Colo/patologia , Gastroenteropatias/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/microbiologia , Interleucina-18/genética , Interleucina-18/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Camundongos , Camundongos Mutantes , Fosforilação , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Transdução de Sinais , Telomerase/genética , Telomerase/metabolismo
6.
PLoS One ; 15(8): e0236657, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760089

RESUMO

Crohn's disease is a pathological condition of the gastro-intestinal tract, causing severe transmural inflammation in the ileum and/or colon. Cigarette smoking is one of the best known environmental risk factors for the development of Crohn's disease. Nevertheless, very little is known about the effect of prolonged cigarette smoke exposure on inflammatory modulators in the gut. We examined the effect of cigarette smoke on cytokine profiles in the healthy and inflamed gut of human subjects and in the trinitrobenzene sulphonic acid mouse model, which mimics distal Crohn-like colitis. In addition, the effect of cigarette smoke on epithelial expression of transient receptor potential channels and their concurrent increase with cigarette smoke-augmented cytokine production was investigated. Active smoking was associated with increased IL-8 transcription in ileum of controls (p < 0,001; n = 18-20/group). In the ileum, TRPV1 mRNA levels were decreased in never smoking Crohn's disease patients compared to healthy subjects (p <0,001; n = 20/group). In the colon, TRPV1 mRNA levels were decreased (p = 0,046) in smoking healthy controls (n = 20/group). Likewise, healthy mice chronically exposed to cigarette smoke (n = 10/group) showed elevated ileal Cxcl2 (p = 0,0075) and colonic Kc mRNA levels (p = 0,0186), whereas TRPV1 mRNA and protein levels were elevated in the ileum (p = 0,0315). Although cigarette smoke exposure prior to trinitrobenzene sulphonic acid administration did not alter disease activity, increased pro-inflammatory cytokine production was observed in the distal colon (Kc: p = 0,0273; Cxcl2: p = 0,104; Il1-ß: p = 0,0796), in parallel with the increase of Trpv1 mRNA (p < 0,001). We infer that CS affects pro-inflammatory cytokine expression in healthy and inflamed gut, and that the simultaneous modulation of TRPV1 may point to a potential involvement of TRPV1 in cigarette smoke-induced production of inflammatory mediators.


Assuntos
Colo/metabolismo , Doença de Crohn/metabolismo , Íleo/metabolismo , Canais de Cátion TRPV/metabolismo , Fumar Tabaco/efeitos adversos , Adulto , Idoso , Animais , Células CACO-2 , Colo/patologia , Doença de Crohn/induzido quimicamente , Doença de Crohn/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Células HT29 , Humanos , Íleo/patologia , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Pesquisa Médica Translacional , Ácido Trinitrobenzenossulfônico
7.
Life Sci ; 259: 118356, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32861798

RESUMO

Curculigoside (CUR) is natural ingredient from Curculigo orchioides Gaertn with multiple biological activities. However, whether CUR protects from ulcerative colitis (UC) and underlying mechanisms are unclear. Herein, mice challenged with dextran sulfate sodium (DSS) were established and administrated with CUR for 7 days. Then histological pathologies and ferroptosis regulators were determined in vivo. The ferroptotic IEC-6 cells were prepared to investigate the underlying mechanism of CUR. Results showed that CUR inhibited the disease activity index, histological damage and cell death in mice with colitis. We also found that ferroptosis was induced in mice with colitis, as evidenced by iron overload, GSH depletion, ROS and MDA production, accompanied by decreased expression of SOD and GPX4. CUR treatment significantly reversed these alterations of ferroptotic features in DSS-induced mice. Furthermore, similar effects of CUR on ferroptosis were observed in IEC-6 cells under the combined treatment of H2O2 and iron chloride hexahydrate. Interestingly, we found that CUR could increase the selenium sensitivity and promote GPX4 transcription level in IEC-6 cells. Knockdown of GPX4 significantly blocked the protective effects of CUR on cell death, GSH and MDA contents as well as LDH activity in ferroptotic IEC-6 cells. Taken together, these findings suggest that CUR protects against ferroptosis in UC by the induction of GPX4, which presents a potential agent for UC treatment.


Assuntos
Benzoatos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Ferroptose/efeitos dos fármacos , Glucosídeos/uso terapêutico , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Animais , Western Blotting , Linhagem Celular , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Colo/química , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Ferro/análise , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Reação em Cadeia da Polimerase em Tempo Real
8.
Signal Transduct Target Ther ; 5(1): 121, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641705
9.
Zhonghua Zhong Liu Za Zhi ; 42(6): 507-512, 2020 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-32575949

RESUMO

Objective: To evaluate the safety, feasibility and short-term efficacy of totally laparoscopic left colectomy for left colon cancer by using overlapped delta-shaped anastomosis technique for digestive tract reconstruction. Methods: A retrospective cohort study was conducted to collect the clinical data of 86 patients with left colon cancer who underwent laparoscopic surgery in Cancer Hospital of Chinese Academy of Medical Sciences from October, 2017 to February, 2019. The patients were divided into totally laparoscopic left-sided colectomy (TLLC) (treatment group, n=25 cases) and laparoscopic-assisted left-sided colectomy (LALC) (control group, n=61 cases). The intraoperative and postoperative data were compared between the two groups. Results: There were no surgical-related deaths in both groups. All the patients in the TLLC group underwent laparoscopic resection, while one patient in the LALC group transfer to open surgery. The operation time in TLLC group and LALC group were (164.5±42.3) min and (171.0±43.1) min, respectively, without statistically significant difference (P=0.516). However, the intraoperative blood loss of patients in the TLLC group was (36.4±22.7) ml, which was significantly less than (52.9±32.2) ml in the LALC group (P=0.026). The anastomosis time in the TLLC group was (39.1±6.5) min, which was significantly longer than (24.9±5.4) min in the LALC group (P<0.001). Postoperative exhaust time in the TLLC group was (2.6±0.5) days, which was significantly shorter than (3.3±0.8) days in the LALC group (P<0.001). The incision length in the TLLC group was (4.2±2.2) cm, significantly shorter than (7.0±2.5) cm in the LALC group (P<0.001). The length of the resected bowel was (21.0±7.3) cm in the TLLC group, which was significantly longer than (17.5±5.4) cm in the LALC group (P=0.037). The length of hospital stay in the TLLC group was (6.2±1.9) days, which was significantly shorter than (7.9±1.5) days in the LALC group (P<0.001). The incidences of postoperative complications in the TLLC group and LALC group were 0 and 4.9% (3/61), respectively, without statistically significant (P=0.553). No anastomotic complications occurred in both groups. During the follow-up period, neither group of patients was hospitalized again, and no tumor metastasis or recurrence occurred. Conclusions: It is safe and feasible to apply the TLLC with overlapped delta-shaped anastomosis in patients with left colon cancer. It has better short-term effects such as shorter incisions, faster recovery, and shorter postoperative hospital stays, and is worthy of further promotion.


Assuntos
Anastomose Cirúrgica/métodos , Colectomia/métodos , Colo/cirurgia , Neoplasias do Colo/cirurgia , Laparoscopia/métodos , Colo/patologia , Neoplasias do Colo/patologia , Fístula do Sistema Digestório/epidemiologia , Fístula do Sistema Digestório/etiologia , Estudos de Viabilidade , Humanos , Incidência , Tempo de Internação , Recidiva Local de Neoplasia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
10.
Life Sci ; 256: 117960, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32534033

RESUMO

BACKGROUND: Intestinal GC-C/cGMP pathway may be involved in visceral hypersensitivity and fluid secretion in irritable bowel syndrome (IBS). The guanylcyclase C agonist linaclotide, approved for IBS- constipation, is contraindicated in children as it may cause severe diarrhea. In contrast, drugs increasing cGMP by inhibiting phosphodiesterase 5 (PDE-5) are well tolerated in children with pulmonary hypertension. Accordingly, we investigated whether beneficial effects of linaclotide in IBS might be shared by PDE-5inhibitor tadalafil without the severe diarrhea reported for linaclotide. Since depression is commonly comorbid with IBS and is implicated in its pathophysiology; and since tadalafil is absorbed systemically and crosses blood brain barrier, whereas linaclotide does not, impact of both drugs on behavioral changes in IBS was also investigated. METHODS: 72 rats were divided into 6groups (control naive, control tadalafil, control linaclotide, untreated IBS, IBS tadalafil, and IBS linaclotide-treated). IBS was induced by 0 to 4 °C intragastric saline for 14 days. RESULTS: Both drugs reduced visceral hypersensitivity and colonic C fos. Tadalafil, and to a greater extent, linaclotide increased colonic cGMP, fecal pellets (8.66 ± 4.6 (IBS),versus14.8 ± 3.3(tadalafil), 20 ± 1.2(linaclotide), fecal water content (29.8 ± 5.5 (IBS), versus 47.83 ± 12.6 (tadalafil), 63.58 ± 11.6 (linaclotide) and reduced intestinal transit time (% distance travelled: 29 ± 6.1(IBS), versus 40.58 + 7.5(tadalafil), 51.83 ± 8.3(linaclotide). Tadalafil, but not linaclotide, increased hippocampal cGMP, and improved behavioral tests scores compared to linaclotide (immobility time: 97.3 ± 12.5 s (IBS) versus 68 ± 12.8(tadalafil), 80 ± 17.06 (linaclotide). CONCLUSION: Systemic PDE-5 inhibitors might be alternatives to locally acting guanyl cyclase agonists in IBS, inducing less severe diarrhea and more beneficial effects on the associated behavioral changes.


Assuntos
Constipação Intestinal/complicações , Constipação Intestinal/fisiopatologia , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/fisiopatologia , Peptídeos/uso terapêutico , Tadalafila/uso terapêutico , Animais , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Colo/fisiopatologia , Constipação Intestinal/tratamento farmacológico , GMP Cíclico/metabolismo , Fezes/química , Trânsito Gastrointestinal/efeitos dos fármacos , Hipocampo/metabolismo , Intestino Grosso/metabolismo , Masculino , Peptídeos/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Wistar , Reflexo/efeitos dos fármacos , Natação , Tadalafila/farmacologia , Água
11.
PLoS One ; 15(6): e0234989, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32598367

RESUMO

Alterations in glycosylation are seen in many types of cancer, including colorectal cancer (CRC). Glycans, the sugar moieties of glycoconjugates, are involved in many important functions relevant to cancer and can be of value as biomarkers. In this study, we have used mass spectrometry to analyze the N-glycan profiles of 35 CRC tissue samples and 10 healthy tissue samples from non-CRC patients who underwent operations for other reasons. The tumor samples were divided into groups depending on tumor location (right or left colon) and stage (II or III), while the healthy samples were divided into right or left colon. The levels of neutral and acidic N-glycan compositions and glycan classes were analyzed in a total of ten different groups. Surprisingly, there were no significant differences in glycan levels when all right- and left-sided CRC samples were compared, and few differences (such as in the abundance of the neutral N-glycan H3N5) were seen when the samples were divided according to both location and stage. Multiple significant differences were found in the levels of glycans and glycan classes when stage II and III samples were compared, and these glycans could be of value as candidates for new markers of cancer progression. In order to validate our findings, we analyzed healthy tissue samples from the right and left colon and found no significant differences in the levels of any of the glycans analyzed, confirming that our findings when comparing CRC samples from the right and left colon are not due to normal variations in the levels of glycans between the healthy right and left colon. Additionally, the levels of the acidic glycans H4N3F1P1, H5N4F1P1, and S1H5N4F1 were found to change in a cancer-specific but colon location-nonspecific manner, indicating that CRC affects glycan levels in similar ways regardless of tumor location.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Colorretais/metabolismo , Glicômica , Polissacarídeos/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Colo/patologia , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Glicosilação , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polissacarídeos/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Adulto Jovem
12.
Acta Cir Bras ; 35(5): e202000503, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578671

RESUMO

PURPOSE: To investigate the effect of hyperbaric oxygen therapy on colonic anastomosis healing with and without ischemia in rats. METHODS: Forty female rats underwent segmental resection of 1 cm of the left colon followed by end-to-end anastomosis. They were randomly assigned to four groups (n=10 each), a sham group; two groups were submitted to Hyperbaric Oxygen therapy (HBOT) with and without induced ischemia and the induced ischemia group without HBOT. The HBOT protocol evaluated was 100% O2 at 2.4 Atmosphere absolute pressure (ATA) for 60 minutes, two sessions before as a preconditioning protocol and three sessions after the operation. Clinical course and mortality were monitored during all experiment and on the day of euthanasia on the fourth day after laparotomy. Macroscopic appearance of the abdominal cavity were assessed and samples for breaking strength of the anastomosis and histopathological parameters were collected. RESULTS: There was no statistically significant difference in mortality or anastomosis leak between the four experimental groups. Anastomosis breaking strength was similar across groups. CONCLUSION: The HBOT protocol tested herein at 2.4 ATA did not affect histopathological and biomechanical parameters of colonic anastomotic healing, neither the clinical outcomes death and anastomosis leak on the fourth day after laparotomy.


Assuntos
Colo/irrigação sanguínea , Colo/cirurgia , Oxigenação Hiperbárica/métodos , Isquemia/patologia , Precondicionamento Isquêmico/métodos , Cicatrização , Anastomose Cirúrgica , Animais , Colo/patologia , Feminino , Isquemia/prevenção & controle , Período Pós-Operatório , Ratos Endogâmicos Lew , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
13.
Rev Col Bras Cir ; 47: e20202406, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32491029

RESUMO

OBJECTIVE: to evaluate the clinical characteristics of patients with colorectal cancer under the age of 50 treated at a public hospital in Brasilia over 5 years. METHODS: we conducted a longitudinal, retrospective study, with 184 patients undergoing surgical procedures at the Asa Norte Regional Hospital (HRAN), including those who underwent only biopsy, between January 2013 and January 2018. We divided the patients into two groups: under the age of 50 (n=39) and age equal to or greater than 50 years (n=145). We compared the groups as to age, sex, symptoms, time between symptom onset and diagnosis, family and personal history, tumor location, histopathological characteristics, applied surgical management, staging and mortality. RESULTS: the group of patients under the age of 50 had more individuals with stage III and IV (p=0.041), more frequent poorly differentiated tumors (10.25% versus 3.52%; p=0.153), and higher incidences of compromised surgical margins (p=0.368), angiolymphatic (p=0.07) and perineural (p=0.007) invasion, which denotes more advanced disease in this group of patients. CONCLUSIONS: the study showed the low effectiveness of population screening methods for colorectal cancer currently used in this population, given the high incidence of the disease and late diagnosis in both groups.


Assuntos
Carcinoma/patologia , Neoplasias Colorretais/patologia , Adulto , Fatores Etários , Brasil/epidemiologia , Carcinoma/epidemiologia , Carcinoma/cirurgia , Colo/patologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
14.
Chemosphere ; 258: 127255, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32554004

RESUMO

Trifluoromethanesulfonic acid (TFMS) is the shortest chain perfluorinated compound. Recently, it has been identified as a persistent and mobile organic chemical with a maximum concentration of 1 µg/L in the environment. However, its toxicological mechanism remains unclear. In this study, to evaluate the liver and intestinal toxicity of TFMS in mammals, male mice were orally exposed to 0, 1, 10 and 100 µg/kg for 12 weeks. Our results showed that TFMS exposure reduced the epididymal fat weight in mice, caused the decrease of serum and liver triglyceride (TG) level and the increase of serum low density lipoprotein (LDL) level. Also, we observed the inflammatory cell infiltration in the liver of mice exposed to 10 µg/kg and 100 µg/kg TFMS, which was coupled with the increased mRNA expression levels of inflammatory factors such as COX2, TNF-α, IL-1ß in the liver. In addition, the mRNA expression levels of lipid metabolism-related genes (PPAR-α, ACOX, SCD1, PPAR-γ, etc.) were significantly decreased in the liver of mice after exposure to both doses of TFMS. We also found TFMS exposure caused the imbalance of cecal gut microbiota and change of cecal microbiota diversity. KEGG pathway predictions showed that the exposure of 100 µg/kg TFMS changed the synthesis and degradation of ketone bodies, benzoate degradation and several other metabolic pathways. Our findings indicated that TFMS exposure disturbed the liver lipid metabolism possibly via altering the gut microbiota.


Assuntos
Poluentes Ambientais/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Mesilatos/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Ceco/efeitos dos fármacos , Ceco/microbiologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Disbiose , Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Triglicerídeos/sangue
15.
Ann R Coll Surg Engl ; 102(8): 594-597, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32538104

RESUMO

INTRODUCTION: The National Bowel Cancer Screening Programme guidelines advocate the use of endoscopic tattooing for suspected malignant lesions to assist identification and to facilitate laparoscopic resections. However, endoscopic tattooing practices are variable in endoscopic units, resulting in repeat endoscopy and delay in patient management. The aim of this study was to assess the adherence to tattoo protocol for significant colonic lesions at an endoscopy unit in a large district general hospital. MATERIALS AND METHODS: Prospectively collected data were analysed for 252 patients with significant colonic lesions between January 2017 and December 2018. Data were collected through reviewing patient's notes, histopathology findings and endoscopy reports. Data on lesions, complications, number and site of tattoo placed, and any repeat endoscopy for a tattoo were collected. RESULTS: Of the 252 patients, 88% (n = 222) had malignant and 12% (n = 30) had benign lesions. Only 58.7% (n = 148) of those patients who had colonoscopy had tattoo placement reported. Of these 148 cases, the report stated the distance of tattoo in relation to the lesion in only 46% (n = 68) of patients. Unfortunately, 14.3% (n = 36) of patients required repeat endoscopy to tattoo the lesions prior to surgery. CONCLUSIONS: Our study highlights the lack of uniformity of tattoo practice among endoscopists. Despite the National Bowel Cancer Screening Programme guidelines, a significant proportion of colorectal lesions are still not tattooed during their first endoscopy. Some patients had to have repeat endoscopy just for the purpose of tattooing. Active involvement and participation of all endoscopists in the colorectal and the complex polyp multidisciplinary teams may help to improve the tattoo service.


Assuntos
Colonoscopia/métodos , Neoplasias Colorretais/cirurgia , Laparoscopia/métodos , Tatuagem/métodos , Idoso , Idoso de 80 Anos ou mais , Carbono/uso terapêutico , Colo/patologia , Colo/cirurgia , Neoplasias Colorretais/patologia , Humanos , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos
17.
Am J Pathol ; 190(8): 1657-1666, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32380082

RESUMO

Increasingly, the ß-galactoside binding lectins, termed galectins, are being recognized as critical regulators of cell function and organismal homeostasis. Within the context of the mucosal surface, galectins are established regulators of innate and adaptive immune responses, microbial populations, and several critical epithelial functions, including cell migration, proliferation, and response to injury. However, given their complex tissue distribution and expression patterns, their role within specific processes remains poorly understood. We took a genetic approach to understand the role of endogenous galectin-9 (Gal-9), a mucosal galectin that has been linked to inflammatory bowel disease, within the context of the murine intestine. Gal-9-deficient (Gal9-/-, also known as Lgals9-/-) animals show increased sensitivity to chemically induced colitis and impaired proliferation in the setting of acute injury. Moreover, Gal9-/--derived enteroids showed impaired growth ex vivo. Consistent with a model in which endogenous Gal-9 controls epithelial growth and repair, Gal9-/- animals showed increased sensitivity to intestinal challenge in multiple models of epithelial injury, including acute irradiation injury and ectopic wound biopsies. Finally, regenerating crypts from patient biopsies showed increased expression of Gal-9, indicating these processes may be conserved in humans. Taken together, these studies implicate Gal-9 in the regulation of cellular proliferation and epithelial restitution after intestinal epithelial injury.


Assuntos
Colite/metabolismo , Colo/metabolismo , Galectinas/metabolismo , Mucosa Intestinal/metabolismo , Animais , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Colite/induzido quimicamente , Colite/genética , Colite/patologia , Colo/patologia , Galectinas/genética , Humanos , Mucosa Intestinal/patologia , Camundongos , Camundongos Knockout
19.
PLoS Pathog ; 16(5): e1008553, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32453761

RESUMO

IRGM and its mouse orthologue Irgm1 are dynamin-like proteins that regulate vesicular remodeling, intracellular microbial killing, and pathogen immunity. IRGM dysfunction is linked to inflammatory bowel disease (IBD), and while it is thought that defective intracellular killing of microbes underscores IBD susceptibility, studies have yet to address how IRGM/Irgm1 regulates immunity to microbes relevant to intestinal inflammation. Here we find that loss of Irgm1 confers marked susceptibility to Citrobacter rodentium, a noninvasive intestinal pathogen that models inflammatory responses to intestinal bacteria. Irgm1-deficient mice fail to control C. rodentium outgrowth in the intestine, leading to systemic pathogen spread and host mortality. Surprisingly, susceptibility due to loss of Irgm1 function was not linked to defective intracellular killing of C. rodentium or exaggerated inflammation, but was instead linked to failure to remodel specific colon lamina propria (C-LP) myeloid cells that expand in response to C. rodentium infection and are essential for C. rodentium immunity. Defective immune remodeling was most striking in C-LP monocytes, which were successfully recruited to the infected C-LP, but subsequently underwent apoptosis. Apoptotic susceptibility was induced by C. rodentium infection and was specific to this setting of pathogen infection, and was not apparent in other settings of intestinal inflammation. These studies reveal a novel role for Irgm1 in host defense and suggest that deficiencies in survival and remodeling of C-LP myeloid cells that control inflammatory intestinal bacteria may underpin IBD pathogenesis linked to IRGM dysfunction.


Assuntos
Citrobacter rodentium/imunologia , Colo/imunologia , Infecções por Enterobacteriaceae/imunologia , Proteínas de Ligação ao GTP/deficiência , Doenças Inflamatórias Intestinais/imunologia , Monócitos/imunologia , Animais , Colo/microbiologia , Colo/patologia , Infecções por Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/patologia , Proteínas de Ligação ao GTP/imunologia , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Camundongos , Camundongos Knockout , Monócitos/microbiologia , Monócitos/patologia , Membrana Mucosa/imunologia , Membrana Mucosa/microbiologia , Membrana Mucosa/patologia
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