30 research outputs found
Multidrug resistance 1 gene polymorphisms may determine Crohn's disease behavior in patients from Rio de Janeiro
OBJECTIVES: Conflicting data from studies on the potential role of multidrug resistance 1 gene polymorphisms in inflammatory bowel disease may result from the analysis of genetically and geographically distinct populations. Here, we investigated whether multidrug resistance 1 gene polymorphisms are associated with inflammatory bowel diseases in patients from Rio de Janeiro. METHODS: We analyzed 123 Crohn's disease patients and 83 ulcerative colitis patients to determine the presence of the multidrug resistance 1 gene polymorphisms C1236T, G2677T and C3435T. In particular, the genotype frequencies of Crohn's disease and ulcerative colitis patients were analyzed. Genotype-phenotype associations with major clinical characteristics were established, and estimated risks were calculated for the mutations. RESULTS: No significant difference was observed in the genotype frequencies of the multidrug resistance 1 G2677T/A and C3435T polymorphisms between Crohn's disease and ulcerative colitis patients. In contrast, the C1236T polymorphism was significantly more common in Crohn's disease than in ulcerative colitis (pâ=â0.047). A significant association was also found between the multidrug resistance 1 C3435T polymorphism and the stricturing form of Crohn's disease (OR: 4.13; pâ=â0.009), whereas no association was found with penetrating behavior (OR: 0.33; pâ=â0.094). In Crohn's disease, a positive association was also found between the C3435T polymorphism and corticosteroid resistance/refractoriness (OR: 4.14; pâ=â0.010). However, no significant association was found between multidrug resistance 1 gene polymorphisms and UC subphenotypic categories. CONCLUSION: The multidrug resistance 1 gene polymorphism C3435T is associated with the stricturing phenotype and an inappropriate response to therapy in Crohn's disease. This association with Crohn's disease may support additional pathogenic roles for the multidrug resistance 1 gene in regulating gut-microbiota interactions and in mediating fibrosis. Understanding the effects of several drugs associated with multidrug resistance 1 gene variants may aid in the selection of customized therapeutic regimens
COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study
Background:
The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms.
Methods:
International, prospective observational study of 60â109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms.
Results:
âTypicalâ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (â€â18 years: 69, 48, 23; 85%), older adults (â„â70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each Pâ<â0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country.
Interpretation:
This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men
Inhibitory effect of ischemic preconditioning distance on migration of neutrophils: Mechanisms and mediators.
IntroduĂĂo:O prĂ-condicionamento isquĂmico (PCI) vem sendo considerado como um potente mecanismo endĂgeno capaz de inibir a resposta inflamatĂria. A migraĂĂo de neutrĂfilos (mn) Ă um evento central no desenvolvimento da reaĂĂo inflamatĂria. Nosso grupo tem demonstrado que o PCI inibe a mn em modelos experimentais, entretanto os mecanismos e mediadores envolvidos ainda nĂo sĂo conhecidos.Objetivo:Estudar a participaĂĂo dos mediadores Ăxido nĂtrico e MonĂxido de carbono, proteĂnas de adesĂo (ICAM-1 e β2-integrina) e da expressĂo de CXCR2 no efeito inibitĂrio do PCI a distĂncia sobre a mn. MĂtodos:O modelo de PCI a distĂncia foi realizado com um torniquete no membro posterior direito de camundongos durante 10 minutos seguidos de 30 de reperfusĂo. ParticipaĂĂo do NO e CO foi investigada atravĂs de inibidores de iNOS (1400 W, 3 mg/kg ou Aminoguanidina (Amg), 50 mg/kg) e HO-1 (ZnPPIX, 10 mg/kg) como prĂ-tratamento de 30 min. Posteriormente, induziu-se peritonite comCarragenina(Cg) (500 mg /cav). Quatro horas apĂs, a cavidade peritoneal (cp) era lavada e leucĂcitos eram contados. ApĂs aquele mesmo procedimento, os animais foram submetidos a microscopia intravital (miv) para avaliar os efeitos do NO e CO nas vĂnulas mesentĂricas de 3Ă ordem.NeutrĂfilos de animais prĂ-condicionados e prĂ-tratados ou nĂo, foram utilizados para o ensaio de quimiotaxiain vitro, usandocomo estĂmulo a quimiocina KC(30ng/ml). AexpressĂo de CXCR2 e GRK2 dos neutrĂfilos foi determinada por citometria de fluxo e imunofluorescĂncia, respectivamente.AsparticipaĂĂes de ICAM-1/CD54 e β2-integrina/CD11b foram investigadas em camundongos nocautes para os genes dessas molĂculas. A mn nesses animais foi avaliada segundo protocolo jĂ descrito pelo lavado peritonela.Na investigaĂĂo do papel do NO e CO na modulaĂĂo da proteĂna de adesĂo celular (β2-integrina), utilizou-se inibidores da iNOS (1400W, 3 mg/kg ou Amg, 50 mg/kg, sc), HO-1 (ZnPPIX, 10 mg/kg, sc) eGuanilato Ciclase (ODQ (5 Ămol/kg, ip)) em prĂ-tratamento de 30 min antes do PCI. ApĂs peritonite, o sangue foi colhido e a expressĂo de CD11bem neutrĂfilos foi determinada por citometria de fluxo. Para anĂlise estatĂstica, utilizou-se ANOVA/Bonferroni. P<0,05 foi aceito. Resultados:Os inibidores de CO e NO preveniram o efeito inibitĂrio do PCIsobre a mn (p <0,05). AlĂm disso, os neutrĂfilos de animais prĂ-condicionados apresentaram reduĂĂo de quimiotaxia (p <0,05),achado que se correlacionou com a diminuiĂĂo da expressĂode CXCR2 na membrana dos neutrĂfilos (p <0,05) e comaumento da expressĂo de GRK2. NĂo houve alteraĂĂo da quimiotaxia, nem da expressĂo de GRK2 quando os neutrĂfilos foram obtidos a partir de animais prĂ-condicionados e prĂ-tratados com inibidores de de CO, NO e GCs. Os animais prĂ-condicionados apresentaram reduĂĂo nos neutrĂfilos circulantes e da aderĂnciana miv, as quais foram prevenidas pelo prĂ-tratamento com os inibidores (p <0,05). O efeito inibitĂrio do PCI persistiu em animais nocautes para β2-integrina, o que nĂo se observou nos animais nocautes para ICAM-1. AlĂm disso, os neutrĂfilos de animais prĂ-condicionados apresentaram reduĂĂo significativa na expressĂo de CD11b, que foi prevenida nos animais prĂ-tratados com os inibidores de iNOS, HO-1 e GCs.ConclusĂes: Os resultados sugerem que o NO e CO atuam no efeito inibitĂrio do PCI via iNOS e HO-1 em sitio distante, modulando ICAM-1, β2-integrina e CXCR2 via GRK2.Introduction: Ischemic preconditioning (IPC) has been considered as a potent endogenous mechanism capable of inhibiting the inflammatory response. The migration of neutrophils (mn) is a central event in the development of inflammation. Our group has demonstrated that PCI inhibits mn in experimental models, however the mechanisms and mediators involved are not yet known. Aim: To study the involvement of mediators nitric oxide and carbon monoxide, adhesion proteins (ICAM-1 and β2-integrin) and expression of CXCR2 in the inhibitory effect of PCI on the distance min. Methods: The model of distance PCI was performed with a tourniquet in the right hind limb of mice for 10 minutes followed by 30 reperfusion. Involvement of NO and CO was investigated using inhibitors of iNOS (1400 W, 3 mg/kg or aminoguanidine (Amg), 50 mg/kg) and HO-1 (ZnPPIX, 10 mg/kg) as pretreatment 30 min. Later, peritonitis was induced by carrageenan (Cg) (500 mg/cav). Four hours later the peritoneal cavity (pc) was washed and leukocytes were counted. After that same procedure, the animals were subjected to intravital microscopy (IVM) to evaluate the effects of NO and CO in the mesenteric venules of 3rd order. Neutrophils from animals preconditioned and pre-treated or untreated, were used for testing chemotaxis in vitro, using the stimulus to chemokine KC (30ng/ml). The expression of GRK2 and CXCR2 in neutrophils was determined by flow cytometry and immunohistochemistry, respectively. The stakes and ICAM-1/CD54 β2-integrina/CD11b been investigated in knockout mice for genes of these molecules. The mn in these animals was evaluated according to protocol previously described by washed peritonela. In the investigation of the role of NO and CO in the modulation of cell adhesion protein (β2-integrin), we used iNOS inhibitor (1400W, 3 mg/kg or Amg, 50 mg/kg, sc), HO-1 (ZnPPIX, 10 mg/kg, sc) and guanylate cyclase (ODQ (5 Ămol/kg, ip)) in pre-treatment 30 min before PCI. After peritonitis, blood was collected and the expression of CD11b on neutrophils was determined by flow cytometry. For statistical analysis, we used ANOVA/Bonferroni. P<0,05 was accepted. Results: The CO and NO inhibitors prevented the inhibitory effect of PCI on mn (P<0,05). Moreover, neutrophils from animals preconditioned showed reduced chemotaxis (p<0,05), a finding that correlated with decreased expression of CXCR2 in the membrane of neutrophils (p<0,05) and increased expression of GRK2. There was no change in chemotaxis or the expression of GRK2 when neutrophils were obtained from animals pre-conditioned and pretreated with inhibitors of CO, NO and sGC. Preconditioned animals showed a reduction in circulating neutrophils and the grip on IVM, which were prevented by pretreatment with inhibitors (P<0,05). The inhibitory effect of PCI was shown in knockout animals for β2-integrin, which was not observed in the knockout animals to ICAM-1. Moreover, neutrophils from animals preconditioned showed a significant reduction in the expression of CD11b, which was prevented in animals pretreated with inhibitors of iNOS, HO-1 and GCs. Conclusions: The results suggest that NO and CO act in the inhibitory effect of PCI via iNOS and HO-1 in place apart by modulating ICAM-1, β2-integrin and CXCR2 via GRK2
Digital Rectal Examination Standardization for Inexperienced Hands: Teaching Medical Students
Objectives. To standardize digital rectal examination (DRE) and set how it correlates with the comprehensive evaluation of lower urinary tract symptoms (LUTS). Methods. After scaled standardization of DRE based on fingertips graphical schema: 10 cubic centimetersâcc for each fingertip prostate surface area on DRE, four randomly selected senior medical students examined 48 male patients presenting with LUTS in an outpatient clinical setting, totaling 12 DRE each. Standardized DRE, international prostate symptom score (IPSS), serum PSA, transabdominal ultrasound (US), urodynamic evaluation, and postvoid residue were compared. Results. The mean and median PVs were USâ45 and 34.7âcc (5.5 to 155) and DREâ39 and 37.5âcc (15 to 80). Comparing DRE and US by simple linear regression: US PV = 11.93 + 0.85 Ă (DRE PV); P=0.0009. Among patients classified as nonobstructed, inconclusive, and obstructed, the US PVs were 29.8, 43.2, and 53.6âcc (P=0.033), and DRE PVs were 20, 35, and 60âcc (P=0.026), respectively. Conclusion. This is the first attempt to DRE standardization focusing on teaching-learning process, establishing a linear correlation of DRE and US PVs with only 12 examinations by inexperienced hands, satisfactorily validated in an outpatient clinical setting
I Cardiovascular Prevention Guideline of the Brazilian Society of Cardiology - Executive Summary
Alternative techniques to reduce warm ischemia time in laparoscopic partial nephrectomy
Purpose: Demonstrate two alternatives that permit a warm ischemia time reduction during laparoscopic partial nephrectomy. Materials and Methods: In this video, two cases of intermediate complexity renal tumors according to the RENAL nephrometry renal scoring system illustrating the techniques and our preliminary experience: a 65 year old man with a 4 cm right, posterior renal tumor. This patient underwent an early unclamping and parenchymal suturing using a greek bar continuous suture with hem-o-lock clips attached to the respective extremities of the suture; The second patient is a 49 year old man with a 3 cm renal tumor. The technique utilized was no clamping resection following the ABC Medical School technique: dissection of renal hilum for eventual clamping if necessary, a frontal 360 degrees visualization of tumor limits, pneumoperitoneum pressure elevated to 25mmHg during tumor resection, spiral excavation of normal parenchyma around the tumor and resection with negative margins. Results: We previously performed 15 cases utilizing the early unclamping technique. The mean clamp time was 15 minutes with a mean blood loss of 285 mL. Only 1 patient had focal positive surgical margins, without recurrence demonstrated at 30 months. Fifteen partial nephrectomies were previously performed with on demand clamping. In 3 cases, clamping was necessary with a mean ischemia time of 11 minutes. The mean blood loss was 390 mL and 2 cases required a perioperative blood transfusion. One case presented with a positive focal margin without recurrence demonstrated at 24 months of follow-up. Renal function was preserved in all cases regardless of the technique applied. Conclusion: Warm ischemia time can be reduced and kidney function can be preserved during laparoscopic nephrectomy if either early unclamping or on demand clamping are selectively applied
UBE2C Is a Transcriptional Target of the Cell Cycle Regulator FOXM1
FOXM1 (forkhead box protein M1) is a transcription factor that participates in all stages of tumor development, mainly through the control of cell cycle and proliferation, regulating the expression of genes involved in G1/S and G2/M transition and M phase progression. The ubiquitin conjugating enzyme E2 (UBE2C) is a member of the anaphase promoting complex/cyclosome, promoting the degradation of several target proteins along cell cycle progression, during metaphase/anaphase transition. FOXM1 and UBE2C have been found overexpressed in a wide range of different solid tumors. Therefore, the aim of this study was to investigate whether UBE2C is a transcriptional target of FOXM1, using esophageal squamous cell carcinoma (ESCC) as a model, in addition to several cancer-deposited data. Our results show that FOXM1 and UBE2C expression present a positive correlation in normal tissues and in 25 distinct tumor types, including ESCC, where these genes are overexpressed. Moreover, FOXM1 binds to UBE2C promoter region in ESCC cell line and transcriptionally activates it, leading to UBE2C upregulation. In conclusion, this study provides evidences that FOXM1 transcriptionally regulates UBE2C expression in ESCC and their deregulation may be a general phenomenon in human neoplasias