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1.
PLoS Pathog ; 16(10): e1008999, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33057424

RESUMO

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus known to cause epidemics resulting in predominantly symptomatic infections, which in rare cases cause long term debilitating arthritis and arthralgia. Significant progress has been made in understanding the roles of canonical RNA sensing pathways in the host recognition of CHIKV; however, less is known regarding antagonism of CHIKV by cytosolic DNA sensing pathways like that of cyclic GMP-AMP synthase (cGAS) and Stimulator of Interferon Genes (STING). With the use of cGAS or STING null cells we demonstrate that the pathway restricts CHIKV replication in fibroblasts and immune cells. We show that DNA accumulates in the cytoplasm of infected cells and that CHIKV blocks DNA dependent IFN-ß transcription. This antagonism of DNA sensing is via an early autophagy-mediated degradation of cGAS and expression of the CHIKV capsid protein is sufficient to induce cGAS degradation. Furthermore, we identify an interaction of CHIKV nsP1 with STING and map the interaction to 23 residues in the cytosolic loop of the adaptor protein. This interaction stabilizes the viral protein and increases the level of palmitoylated nsP1 in cells. Together, this work supports previous publications highlighting the relevance of the cGAS-STING pathway in the early detection of (+)ssRNA viruses and provides direct evidence that CHIKV interacts with and antagonizes cGAS-STING signaling.


Assuntos
Vírus Chikungunya/imunologia , Interferon Tipo I/imunologia , Proteínas de Membrana/imunologia , Nucleotidiltransferases/imunologia , Aedes , Animais , Autofagia/imunologia , Técnicas de Cultura de Células , Vírus Chikungunya/fisiologia , Células HEK293 , Humanos , Imunidade Inata , Interferon Tipo I/metabolismo , Interferon beta/imunologia , Interferon beta/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Transcrição Gênica , Proteínas Virais/metabolismo , Replicação Viral
2.
Ann Vasc Surg ; 73: 86-96, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33493590

RESUMO

OBJECTIVES: To analyze the outcome of vascular procedures performed in patients with COVID-19 infection during the 2020 pandemic. METHODS: This is a multicenter, prospective observational cohort study. We analyzed data from 75 patients with COVID-19 infection undergoing vascular surgery procedures in 17 hospitals across Spain and Andorra between March and May 2020. The primary end point was 30-day mortality. Clinical Trials registry number NCT04333693. RESULTS: The mean age was 70.9 (45-94) and 58 (77.0%) patients were male. Around 70.7% had postoperative complications, 36.0% of patients experienced respiratory failure, 22.7% acute renal failure, and 22.7% acute respiratory distress syndrome (ARDS). All-cause 30-days mortality rate was 37.3%. Multivariate analysis identified age >65 years (P = 0.009), American Society of Anesthesiologists (ASA) classification IV (P = 0.004), preoperative lymphocyte count <0.6 (×109/L) (P = 0.001) and lactate dehydrogenase (LDH) >500 (UI/L) (P = 0.004), need for invasive ventilation (P = 0.043), postoperative acute renal failure (P = 0.001), ARDS (P = 0.003) and major amputation (P = 0.009) as independent variables associated with mortality. Preoperative coma (P = 0.001), quick Sepsis Related Organ Failure Assessment (qSOFA) score ≥2 (P = 0.043), lymphocytes <0.6 (×109/L) (P = 0.019) leucocytes >11.5 (×109/L) (P = 0.007) and serum ferritin >1800 mg/dL (P = 0.004), bilateral lung infiltrates on thorax computed tomography (P = 0.025), and postoperative acute renal failure (P = 0.009) increased the risk of postoperative ARDS. qSOFA score ≥2 was the only risk factor associated with postoperative sepsis (P = 0.041). CONCLUSIONS: Patients with COVID-19 infection undergoing vascular surgery procedures showed poor 30-days survival. Age >65 years, preoperative lymphocytes <0.6 (x109/L) and LDH >500 (UI/L), and postoperative acute renal failure, ARDS and need for major amputation were identified as prognostic factors of 30-days mortality.


Assuntos
COVID-19/complicações , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Injúria Renal Aguda/etiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Andorra/epidemiologia , COVID-19/mortalidade , Estudos de Coortes , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Prognóstico , Síndrome do Desconforto Respiratório/etiologia , Fatores de Risco , Espanha/epidemiologia , Resultado do Tratamento
3.
Nucleic Acids Res ; 43(1): 179-95, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25514925

RESUMO

Cleavage factor I (CFI) proteins are core components of the polyadenylation machinery that can regulate several steps of mRNA life cycle, including alternative polyadenylation, splicing, export and decay. Here, we describe the regulatory mechanisms that control two fungal CFI protein classes in Magnaporthe oryzae: Rbp35/CfI25 complex and Hrp1. Using mutational, genetic and biochemical studies we demonstrate that cellular concentration of CFI mRNAs is a limited indicator of their protein abundance. Our results suggest that several post-transcriptional mechanisms regulate Rbp35/CfI25 complex and Hrp1 in the rice blast fungus, some of which are also conserved in other ascomycetes. With respect to Rbp35, these include C-terminal processing, RGG-dependent localization and cleavage, C-terminal autoregulatory domain and regulation by an upstream open reading frame of Rbp35-dependent TOR signalling pathway. Our proteomic analyses suggest that Rbp35 regulates the levels of proteins involved in melanin and phenylpropanoids synthesis, among others. The drastic reduction of fungal CFI proteins in carbon-starved cells suggests that the pre-mRNA processing pathway is altered. Our findings uncover broad and multilayer regulatory mechanisms controlling fungal polyadenylation factors, which have profound implications in pre-mRNA maturation. This area of research offers new avenues for fungicide design by targeting fungal-specific proteins that globally affect thousands of mRNAs.


Assuntos
Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Poliadenilação , Fatores de Poliadenilação e Clivagem de mRNA/metabolismo , Regiões 5' não Traduzidas , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Magnaporthe/genética , Magnaporthe/crescimento & desenvolvimento , Magnaporthe/metabolismo , Fases de Leitura Aberta , Doenças das Plantas/microbiologia , Estrutura Terciária de Proteína , Proteólise , Serina-Treonina Quinases TOR/metabolismo , Fatores de Poliadenilação e Clivagem de mRNA/química , Fatores de Poliadenilação e Clivagem de mRNA/genética
4.
Am J Transplant ; 16(1): 72-82, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26317573

RESUMO

We examined intraepithelial lymphocytes (IELs) in 213 ileal biopsies from 16 bowel grafts and compared them with 32 biopsies from native intestines. During the first year posttransplantation, grafts exhibited low levels of IELs (percentage of CD103(+) cells) principally due to reduced CD3(+) CD8(+) cells, while CD103(+) CD3(-) cell numbers became significantly higher. Changes in IEL subsets did not correlate with histology results, isolated intestine, or multivisceral transplants, but CD3(-) IELs were significantly higher in patients receiving corticosteroids. Compared with controls, more CD3(-) IELs of the grafts expressed CD56, NKp44, interleukin (IL)-23 receptor, retinoid-related orphan receptor gamma t (RORγt), and CCR6. No difference was observed in granzyme B, and CD3(-) CD127(+) cells were more abundant in native intestines. Ex vivo, and after in vitro activation, CD3(-) IELs in grafts produced significantly more interferon (IFN)-γ and IL-22, and a double IFNγ(+) IL-22(+) population was observed. Epithelial cell-depleted grafts IELs were cytotoxic, whereas this was not observed in controls. In conclusion, different from native intestines, a CD3(-) IEL subset predominates in grafts, showing features of natural killer cells and intraepithelial ILC1 (CD56(+) , NKp44(+) , CCR6(+) , CD127(-) , cytotoxicity, and IFNγ secretion), ILC3 (CD56(+) , NKp44(+) , IL-23R(+) , CCR6(+) , RORγt(+) , and IL-22 secretion), and intermediate ILC1-ILC3 phenotypes (IFNγ(+) IL-22(+) ). Viability of intestinal grafts may depend on the balance among proinflammatory and homeostatic roles of ILC subsets.


Assuntos
Antígenos CD/metabolismo , Complexo CD3/metabolismo , Células Epiteliais/imunologia , Cadeias alfa de Integrinas/metabolismo , Enteropatias/cirurgia , Intestinos/transplante , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Aloenxertos , Estudos de Casos e Controles , Citocinas/metabolismo , Feminino , Humanos , Enteropatias/imunologia , Células Matadoras Naturais/imunologia , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Pediatr Transplant ; 18(6): 594-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25039398

RESUMO

Children are one of the groups with the highest mortality rate on the waiting list for LT. Primary closure of the abdominal wall is often impossible in the pediatric population, due to a size mismatch between a large graft and a small recipient. We present a retrospective cohort study of six pediatric patients, who underwent delayed abdominal wall closure with a biological mesh after LT, and in whom early closure was impossible. A non-cross-linked porcine-derived acellular dermal matrix (Strattice(™) Reconstructive Tissue Matrix; LifeCell Corp, Bridgewater, NJ, USA) was used in all of the cases of the series. After a mean follow-up of 26 months (21-32 months), all patients were asymptomatic, with a functional abdominal wall after physical examination. Non-cross-linked porcine-derived acellular dermal matrix (Strattice(™) ) is a good alternative for delayed abdominal wall closure after pediatric LT. Randomized controlled trials are necessary to determine the best moment and the best technique for abdominal wall closure.


Assuntos
Parede Abdominal/cirurgia , Derme Acelular , Transplante de Fígado , Animais , Pré-Escolar , Humanos , Lactente , Masculino , Estudos Retrospectivos , Telas Cirúrgicas , Suínos , Resultado do Tratamento
6.
Hernia ; 27(3): 677-685, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37138139

RESUMO

Abdominal compartment syndrome is a potentially life-threatening condition seen in critically ill patients, and most often caused by acute pancreatitis, postoperative abdominal vascular thrombosis or mesenteric ischemia. A decompressive laparotomy is sometimes required, often resulting in hernias, and subsequent definitive wall closure is challenging. AIM: This study aims to describe short term results after a modified Chevrel technique for midline laparotomies in patients witch abdominal hypertension. MATERIALS AND METHODS: We performed a modified Chevrel as an abdominal closure technique in 9 patients between January 2016 and January 2022. All patients presented varying degrees of abdominal hypertension. RESULTS: Nine patients were treated with new technique (6 male and 3 female), all of whom had conditions that precluded unfolding the contralateral side as a means for closure. The reasons for this were diverse, including presence of ileostomies, intraabdominal drainages, Kher tubes or an inverted T scar from previous transplant. The use of mesh was initially dismissed in 8 of the patients (88,9%) because they required subsequent abdominal surgeries or active infection. None of the patients developed a hernia, although two died 6 months after the procedure. Only one patient developed bulging. A decrease in intrabdominal pressure was achieved in all patients. CONCLUSION: The modified Chevrel technique can be used as a closure option for midline laparotomies in cases where the entire abdominal wall cannot be used.


Assuntos
Parede Abdominal , Técnicas de Fechamento de Ferimentos Abdominais , Pancreatite , Humanos , Masculino , Feminino , Estado Terminal , Doença Aguda , Herniorrafia , Pancreatite/etiologia , Pancreatite/cirurgia , Parede Abdominal/cirurgia , Laparotomia/efeitos adversos , Telas Cirúrgicas
7.
ESMO Open ; 6(4): 100215, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34325108

RESUMO

BACKGROUND: Young oncologists are at particular risk of professional burnout, and this could have a significant impact on their health and care of their patients. The coronavirus disease 2019 (COVID-19) pandemic has forced rapid changes in professionals' jobs and training, with the consequent physical and psychological effects. We aimed to characterize burnout levels and determinants in young oncologists, and the effects of the pandemic on their training and health. METHODS: Two online surveys were conducted among oncology residents and young oncology specialists in Spain. The first addressed professional burnout and its determinants before the COVID-19 pandemic, while the second analyzed the impact of the pandemic on health care organization, training, and physical and psychological health in the same population. RESULTS: In total, 243 respondents completed the first survey, and 263 the second; 25.1% reported significant levels of professional burnout. Burnout was more common among medical oncology residents (28.2%), mainly in their second year of training. It was significantly associated with a poor work-life balance, inadequate vacation time, and the burnout score. Nearly three-quarters of respondents (72%) were reassigned to COVID-19 care and 84.3% of residents missed part of their training rotations. Overall, 17.2% of this population reported that they had contracted COVID-19, 37.3% had scores indicating anxiety, and 30.4% moderate to severe depression. Almost a quarter of young oncologists (23.3%) had doubts about their medical vocation. CONCLUSIONS: Burnout affects a considerable number of young oncologists. The COVID-19 pandemic has had a profound impact on causes of burnout, making it even more necessary to periodically monitor it to define appropriate detection and prevention strategies.


Assuntos
Esgotamento Profissional , COVID-19 , Oncologistas , Esgotamento Profissional/epidemiologia , Esgotamento Psicológico/epidemiologia , Esgotamento Psicológico/prevenção & controle , Humanos , Oncologia , Pandemias , SARS-CoV-2
8.
Transplant Proc ; 52(5): 1468-1471, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32204902

RESUMO

Abdominal wall transplant is developed in the context of intestinal and multivisceral transplant, in which it is often impossible to perform a primary wall closure. Despite the fact that abdominal wall closure is not as consequential in liver transplant, there are circumstances in which it might determine the success of the liver graft, especially in situations that compromise the abdominal cavity and facilitate an abdominal compartment syndrome. CASE 1: A 14-year-old girl suffering from cryptogenic cirrhosis with severe portal hypertension that causes ascites and severe malnutrition. Uneventful liver transplant, with a graft procured from a 14-year-old donor. At the time of wall closure it was decided to implant a nonvascularized fascia graft to supplement the right side of the transverse incision, with a 17 x 7 cm defect. This required reintervention after 4 months for biliary stricture. At that point, the wall graft was almost completely integrated into the native tissue. CASE 2: A 63-year-old man, transplanted for hepatitis C virus+ hepatocellular carcinoma+ nonocclusive portal thrombosis. Thirty-six hours after transplant the patient developed portal thrombosis. Thrombectomy and closure with biological mesh were performed. After 24 hours he was reoperated on for abdominal compartment syndrome and temporary closure with a Bogotá bag. Six days later he underwent omentectomy, intestinal decompression, and left components separation, identifying a 25 x 20 cm defect. For definitive closure, a nonvascularized fascia graft procured from a different donor was used, accomplishing a reduction in intra-abdominal pressure. Nonvascularized fascia transplantation is an interesting alternative in liver transplant recipients with abdominal wall closure difficulties.


Assuntos
Parede Abdominal , Técnicas de Fechamento de Ferimentos Abdominais , Fáscia/transplante , Transplante de Fígado/métodos , Procedimentos de Cirurgia Plástica/métodos , Parede Abdominal/cirurgia , Adolescente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Transplant Proc ; 51(1): 33-37, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30598229

RESUMO

BACKGROUND: The prevalence of obesity has increased dramatically, even in the population awaiting a liver transplantation. Despite their associated complications, we cannot consider morbid obesity any longer as an absolute contraindication to liver transplantation. Dietary approaches alone are usually completely ineffective. Bariatric surgery is the gold-standard treatment for morbid obesity and can be performed before, during, or after transplantation. MATERIALS AND METHODS: At our Liver Transplantation Unit, a single surgeon performed a sleeve gastrectomy in 8 patients with liver cirrhosis due to nonalcoholic steatohepatitis, alcohol, or HCV. The Child score was A in 6 patients and B in the remaining 2 patients. Two of our patients had portal hypertension with mild esophageal varices. The procedure was performed laparoscopically in 7 cases (87.5%); in the other case, it was performed by open approach due to portal hypertension and according to patient preferences. RESULTS: Patients showed no postoperative morbidity or mortality. The mean postoperative body mass index of our patients was 37.4, 33.3, and 30.3 kg/m2 at 3, 6, and 12 months after surgery, respectively. The mean percentage excess weight loss of our patients was 42.9%, 62.2%, and 76.3% at 3, 6, and 12 months. Two of the patients have already undergone a successful liver transplant. CONCLUSION: Bariatric surgery in selected patients with compensated cirrhosis and without significative portal hypertension is reasonable. There are not clear guidelines on the use of bariatric surgery in patients with cirrhosis. In our experience, the sleeve gastrectomy is safe and effective in the treatment of patients with compensated cirrhosis; in a short time, the sleeve gastrectomy can improve candidacy in morbidly obese patients awaiting transplantation.


Assuntos
Cirurgia Bariátrica/métodos , Cirrose Hepática/complicações , Transplante de Fígado , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Adulto , Feminino , Gastrectomia/métodos , Humanos , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade
10.
Springerplus ; 5: 276, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27006884

RESUMO

This article proposes the application of Laplace Transform-Homotopy Perturbation Method and some of its modifications in order to find analytical approximate solutions for the linear and nonlinear differential equations which arise from some variational problems. As case study we will solve four ordinary differential equations, and we will show that the proposed solutions have good accuracy, even we will obtain an exact solution. In the sequel, we will see that the square residual error for the approximate solutions, belongs to the interval [0.001918936920, 0.06334882582], which confirms the accuracy of the proposed methods, taking into account the complexity and difficulty of variational problems.

11.
Transplant Proc ; 48(2): 539-42, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27109996

RESUMO

BACKGROUND: Surgical complications in multivisceral transplantation (MVT) are frequent and always severe. Those related to technical issues are relevant as they have implications not only on the graft but also on patient survival. The aim of this study was to review our case-based data and experience with 5 MVT performed since December 2004. CASE REPORT: A 38 year-old woman presented with ultra-short bowel syndrome due to massive ischemia also affecting the celiac trunk. She also had moderate to severe hepatitis/steatosis with some degree of fibrosis on liver biopsy, due to long-term home parenteral nutrition (HPN). An MVT was carried out in September 2010 including the liver, stomach, pancreatoduodenal complex with the spleen, and small bowel. The postoperative course was complicated by a leak from the pyloromiotomy, requiring reoperation on postoperative day 13. She also had central line catheter infection and renal impairment, requiring renal replacement therapy, and was discharged on postoperative day 150. Fifteen days later she was hospitalized because of severe abdominal pain associated with an abdominal mass. Computed tomography showed an aortic donor graft pseudoaneurysm, so we decided to operate on the patient. A complete resection of the pseudoaneurysm using an interposed polytetrafluoroethylene graft was performed. Six months after the MVT, the patient died due to sepsis, despite a functional graft and complete digestive autonomy. CONCLUSIONS: Although this complication is rare, surgical complications in MVT are severe and may seriously impair graft and patient survival.


Assuntos
Falso Aneurisma/cirurgia , Aneurisma Infectado/etiologia , Aneurisma da Aorta Torácica/etiologia , Prótese Vascular/efeitos adversos , Intestino Delgado/transplante , Transplante de Fígado/efeitos adversos , Síndrome do Intestino Curto/cirurgia , Adulto , Falso Aneurisma/etiologia , Falso Aneurisma/microbiologia , Aneurisma Infectado/diagnóstico , Aneurisma Infectado/microbiologia , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/microbiologia , Prótese Vascular/microbiologia , Feminino , Humanos , Reoperação
12.
Transplant Proc ; 37(9): 3899-903, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16386578

RESUMO

INTRODUCTION: Portal vein thrombosis (PVT), which had been considered an absolute contraindication to orthotopic liver transplantation (OLT), is currently considered a risk factor that increases morbi-mortality. The objective of this study was to compare OLT outcomes in patients with vs without PVT. MATERIALS AND METHODS: Between April 1986 and December 2003, a sample of 83 patients with PVT was compared with another sample of 83 patients without PVT among 962 OLT performed in our department. RESULTS: Both groups were homogeneous in terms of epidemiological variables, surgical technique, immunosuppression, and donor-related variables. There were no differences with respect to graft function during the first week following surgery. Surgical time and anhepatic phase duration was longer in the PVT group, albeit the differences were not significant. PVT patients also required more transfusions; a strong statistical association was observed with respect to blood (P = .12) and plasma (P = .11) transfusions and statistically significant differences regarding platelet transfusions (P = .02). Time on mechanical ventilation and the length of stay in the ICU were longer but not significant among PVT patients. The only statistically significant difference was the incidence of portal rethrombosis (P = .02). With respect to mean and global patient and graft actuarial survivals after 1, 3, 5, and 10 years, we have observed no significant intergroup differences, although both patient (P = .48; NS) and graft (P = .96, NS) survivals were lower among PVT cases. CONCLUSIONS: PVT should not only cease to be considered a contraindication for OLT, but there were no significant differences between the outcomes despite this finding.


Assuntos
Transplante de Fígado/efeitos adversos , Veia Porta , Trombose/complicações , Adolescente , Adulto , Ascite/complicações , Seguimentos , Sobrevivência de Enxerto/fisiologia , Encefalopatia Hepática/cirurgia , Humanos , Transplante de Fígado/mortalidade , Transplante de Fígado/fisiologia , Estudos Retrospectivos , Circulação Esplâncnica , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Varizes/cirurgia
13.
Transplant Proc ; 37(9): 3943-7, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16386592

RESUMO

INTRODUCTION: Partial liver transplantation has been consolidated to be a valid treatment option. We sought to understand the factors that modulate and may be harnessed to accelerate hepatocyte regeneration. We sought to determine the impact of heparin on m-hepatocyte growth factor (HGF) plasma concentrations. MATERIALS AND METHODS: Sixteen rats were assigned to four groups of four animals each: group A, without heparin; group B, 600 IU/kg; group C, 1000 IU/kg, group D, 1400 IU/kg. Blood samples (0.5 mL) were obtained from each rat at baseline and at 30, 60, 120, and 240 minutes. After the samples were centrifuged to separate supernates from the cell phase they were stored at -20 degrees C in the m-HGF reagent and subsequently tested using enzyme-linked immunosorbent assay. Results were analyzed using SPSS 11.5 statistical software. RESULTS: Among the 16 rats, one died at 110 minutes, just prior to the last extraction. The remaining rats were sacrificed. Mean weight was: 466 +/- 64.24 g with no intergroup differences (P = .149). The comparative results (using Student t test) were: baseline A(1-4) versus A(1-4) 30 minutes: P < .05; baseline A(1-4) versus A(1-4) 60 minutes: P < .05; baseline A(1-4) versus A(1-4) 120 minutes: P = .10 (NS); baseline A(1-4) versus A(1-4) 240 minutes: P = .15 (NS). No significant differences were found among group B: baseline C(1-4) versus C(1-4) 30 minutes and 60 minutes: NS; baseline C(1-4) versus C(1-4) 120 minutes: P < .001; baseline C(1-4) versus C(1-4) 240 minutes: P < .10 (NS). Finally, the results in group D were: baseline D(1-4) versus D(1-4) 30 minutes: NS; baseline D(1-4) versus D(1-4) 60 minutes and 120 minutes: P < .05; baseline D(1-4) versus D(1-4) 240 minutes: P < .0005. When we compared group A to C and D, we detected differences (albeit not when compared to B) with P values = .01. Peak values were obtained at 120 and 240 minutes (225.21 pg/mL and 221.78 pg/mL) among groups C and D. CONCLUSION: Heparin has a positive effect to increase serum HGF concentrations among rats. The effect was dependent on the administered dose and the time elapsed.


Assuntos
Heparina/farmacologia , Fator de Crescimento de Hepatócito/sangue , Animais , Relação Dose-Resposta a Droga , Fator de Crescimento de Hepatócito/biossíntese , Cinética , Fígado/fisiologia , Masculino , Modelos Animais , Ratos , Ratos Wistar , Valores de Referência , Fatores de Tempo
14.
J Interferon Cytokine Res ; 21(9): 763-73, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11576470

RESUMO

It has been shown that different types of pathogens induce different immune responses. Recovery from intracellular bacterial and viral infection is dependent on the secretion of Th1 cytokines, such as interferon-gamma (IFN-gamma), and on the generation of cytotoxic T cells. In contrast, responses to some parasitic invaders are of the Th2 type, characterized by secretion of interleukin-4 (IL-4). At present, it is not clear what directs this choice, and the most prevalent hypotheses are based on the dendritic cells (DC). In this work, we studied the immune responses generated in mice to a number of antigens, both replicating and nonreplicating, using bone marrow-derived DC as vehicles for immunization. We demonstrate that DC infected with influenza virus prime for a pure Th1 response in vivo devoid of IL-4 induction. This immune response correlates with the induction of DC maturation by the virus. In contrast, nonreplicating antigens, such as fetal bovine serum (FBS), beta-galactosidase, or inactivated influenza virus, do not mature the DC and prime for responses characterized by the secretion of large amounts of IL-4. These data support the hypothesis that myeloid DC are capable of eliciting both types of responses depending on the nature of the antigen.


Assuntos
Células Dendríticas/imunologia , Células Dendríticas/virologia , Orthomyxoviridae/patogenicidade , Células Th1/imunologia , Células Th2/imunologia , beta-Galactosidase/imunologia , Animais , Antígenos/imunologia , Linhagem Celular , Citocinas/imunologia , Cães , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Células Mieloides/imunologia , Linfócitos T Citotóxicos/imunologia
15.
Virus Res ; 28(2): 99-112, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-8317146

RESUMO

The influenza virus vRNA promoter was characterized: a complete set of single substitution mutants was generated in the fifteen 3' terminal nucleotides of a synthetic model RNA containing the reporter gene chloramphenicol acetyl transferase (CAT). The contribution of each nucleotide to the function of the promoter was tested by an in vitro assay. This system involves reconstitution of template (mutant) RNAs and purified viral polymerase; the system is primer-dependent and yields full-length complementary (c)RNA and not poly A-containing mRNA. The results of this in vitro replication assay suggest that (1) nucleotides 1 to 14 at the 3' terminus comprise the promoter sequence of the vRNA, (2) not all the mutations in the first 14 nucleotides affect vRNA promoter activity equally and (3) changes in positions 2 and 11 have the greatest effect on this promoter activity. In addition, the template (mutant) RNAs were examined in an in vivo assay. This system involves transfection of plasmid DNA-derived template (mutant) RNAs into helper virus-infected cells and measurement of levels of CAT activity. The expression of template RNAs was found to be highly sensitive to mutations in almost any of the first 14 positions. Differences in the results of the in vivo and the in vitro system are possibly due to the presence of overlapping cis-acting signals which are required for replication of vRNA and the expression of mRNA. Deletion and addition of nucleotides at the 3' end of the promoter resulted in a drastic reduction in template activity in both the in vitro and in vivo assays.


Assuntos
Vírus da Influenza A/genética , Regiões Promotoras Genéticas/genética , RNA Viral/genética , Sequência de Bases , Cloranfenicol O-Acetiltransferase/genética , Análise Mutacional de DNA , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida/genética , Moldes Genéticos
16.
Appl Environ Microbiol ; 64(10): 3948-53, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9758824

RESUMO

Many Pseudomonas syringae strains contain native plasmids that are important for host-pathogen interactions, and most of them contain several coexisting plasmids (pPT23A-like plasmids) that cross-hybridize to replication sequences from pPT23A, which also carries a gene cluster coding for the phytotoxin coronatine in P. syringae pv. tomato PT23. In this study, three functional pPT23A-like replicons were cloned from P. syringae pv. glycinea race 6, suggesting that the compatibility of highly related replicons is a common feature of P. syringae strains. Hybridization experiments using three separate incompatibility determinants previously identified from pPT23A and the rulAB (UV radiation tolerance) genes showed that the organization of the replication region among pPT23A-like plasmids from several P. syringae pathovars is poorly conserved. The putative repA gene from four pPT23A-like replicons from P. syringae pv. glycinea race 6 was amplified by using specific primers. The restriction profiles of the resulting PCR products for the race 6 plasmids were more similar to each other than they were to that of pPT23A. These data, together with the existence of other cross-hybridizing DNA regions around the replicon among the race 6 pPT23A-like plasmids, suggest that some of these plasmids may have originated from duplication events. Our results also imply that modifications of the repA sequences and the poor conservation of putative maintenance determinants contribute to the suppression of incompatibility among members of the pPT23A-like family, thus enhancing the genomic plasticity of P. syringae.

17.
Transplant Proc ; 35(5): 1898-9, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12962839

RESUMO

We report three cases of Kaposi's sarcoma after orthotopic liver transplantation performed for cirrhosis related to hepatitis C virus (one case), ethanol (one case), or both (one case). All patients displayed disease within the first year after liver transplantation, and only in one case was the diagnosis obtained before the patient died. All three patients were on tacrolimus-steroid therapy, and in one case mycophenolate mofetil was added to treat acute persistent rejection.


Assuntos
Transplante de Fígado/fisiologia , Sarcoma de Kaposi/diagnóstico , Adulto , Evolução Fatal , Hepatite C/complicações , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/cirurgia , Cirrose Hepática Alcoólica/cirurgia , Masculino , Pessoa de Meia-Idade
18.
Transplant Proc ; 35(5): 1869-70, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12962829

RESUMO

OBJECTIVE: Describe the results of liver transplantation after installing Transjugular Intrahepatic Portosystemic Shunt (TIPS) and compare them with those of a control group in a comparative, longitudinal, retrospective study. MATERIALS AND METHODS: Between April 1986 and October 2002, we performed 875 liver transplantations. Between January 1996 and October 2002, 26 transplantations were performed on TIPS carriers. This group was compared with a control cohort of 50 randomly selected patients who underwent transplantation in this period (non-TIPS carriers). Both groups were homogeneous with no significant differences between age, sex United Network for Organ Sharing (UNOS) score, Child stage, or etiology. RESULTS: Actuarial survival rates at 1 and 3 years: TIPS group 96.15% and 89.29% versus control cohort 87.8% and 81%, respectively. In 73.9%, the TIPS was clearly effective; in 88.9%, a postoperative Doppler revealed normal flow. There were no statistically significant differences compared with time on the waiting list for transplant, duration of the operation, ischemia times, intraoperative consumption of hemoderivates, vascular or nonvascular postoperative complications, duration of stay in the intensive care unit, hospital stay, or retransplantation rate. CONCLUSIONS: In our experience, TIPS insertion does not affect either the intraoperative or postoperative evolution and is not associated with an increased time on the liver transplant waiting list.


Assuntos
Transplante de Fígado/fisiologia , Derivação Portossistêmica Transjugular Intra-Hepática , Análise Atuarial , Adulto , Estudos de Coortes , Feminino , Humanos , Hipertensão Portal/terapia , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Derivação Portossistêmica Transjugular Intra-Hepática/mortalidade , Reoperação , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo
19.
Int Sch Res Notices ; 2014: 747098, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-27433526

RESUMO

The homotopy perturbation method (HPM) is coupled with versions of Laplace-Padé and Padé methods to provide an approximate solution to the nonlinear differential equation that describes the behaviour of a flow with a stretching flat boundary due to partial slip. Comparing results between approximate and numerical solutions, we concluded that our results are capable of providing an accurate solution and are extremely efficient.

20.
Transplant Proc ; 46(6): 2140-2, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25131125

RESUMO

BACKGROUND: Renal failure (RF) is a frequent complication in non-renal solid organ transplants. In the present study, we analyze our experience with intestinal transplants (ITx). METHODS: Between 2004 and 2012, we performed 21 ITx in 19 adult patients. Alemtuzumab was used as an induction agent followed by tacrolimus. Renal function was assessed before ITx and during the perioperative period. RESULTS: The main cause for transplants was non-resectable desmoids tumors (33.3%), followed by vascular thrombosis (19%) and others. Medical complications were frequent, especially infectious diseases, which were the most common (51%). Surgical complications were also frequent, but most of them (>50%) were mild but leading to a great number of re-operations and prolonged stays in hospital. Acute rejection is very frequent (66.6%) but mild in more than 70% of the cases. Finally, RF was very frequent (68.4%; 13/19 patients) and accounted for 15.6% of all medical complications. Causes were multiple. One patient is awaiting a kidney transplant, but no other patients need renal replacement therapy at the moment. Ileostomy closure was performed in 5 of 12 patients alive, showing improved renal function in 3 of them. CONCLUSIONS: RF is a problem in ITx and is always multifactorial. Increases in hospital stay, higher morbidity and is a cause for hospital readmission. Almost all patients had an impaired renal function when discharged. Immunosuppressants and ileostomy closure as soon as possible might prevent RF.


Assuntos
Enteropatias/cirurgia , Intestino Delgado/transplante , Transplante de Órgãos/efeitos adversos , Insuficiência Renal/etiologia , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/epidemiologia , Estudos Retrospectivos , Espanha/epidemiologia , Adulto Jovem
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