68 research outputs found
Renal macrophage infiltration is associated with a poor outcome in IgA nephropathy
OBJECTIVES: The objectives of our study were as follows: 1) to analyze the prognostic value of macrophage infiltration in primary IgA nephropathy (IgAN) and 2) to study the relationship between macrophages and other factors associated with the development of renal fibrosis, including mast cells, TGF-β1, α-SMA and NF-kB. METHODS: We analyzed 62 patients who had been diagnosed with IgAN between 1987 and 2003. Immunohistochemical staining was performed with monoclonal antibodies against CD68 and mast cell tryptase and polyclonal antibodies against TGF-β1, α-SMA and NF-kB p65. We also used Southwestern histochemistry for the in situ detection of activated NF-kB. RESULTS: The infiltration of macrophages into the tubulointerstitial compartment correlated with unfavorable clinical and histological parameters, and a worse clinical course of IgAN was significantly associated with the number of tubulointerstitial macrophages. Kaplan-Meier curves demonstrated that increased macrophage infiltration was associated with decreased renal survival. Moreover, the presence of macrophages was associated with mast cells, tubulointerstitial α-SMA expression and NF-kB activation (IH and Southwestern histochemistry). In the multivariate analysis, the two parameters that correlated with macrophage infiltration, proteinuria and tubulointerstitial injury, were independently associated with an unfavorable clinical course. CONCLUSION: An increased number of macrophages in the tubulointerstitial area may serve as a predictive factor for poor prognosis in patients with IgAN, and these cells were also associated with the expression of pro-fibrotic factors
Long-term follow-up of patients with chronic hepatitis C with sustained virologic response to interferon
BACKGROUND AND AIM: The durability of the sustained virologic response (SVR) in patients with chronic hepatitis C after treatment and the ideal follow-up time for these patients remains undefined. The objective of the study was to evaluate the durability of the virologic response in patients with chronic hepatitis C followed up for at least 12 months after SVR at HCFMRP-USP. METHODS: The study was conducted on 174 patients with chronic hepatitis C treated with different antiviral regimens who had achieved SVR. Qualitative serum HCV-RNA was determined by the commercial kit (COBAS AMPLICOR HCV, v2.0). RESULTS: There was predominance of male (73%) with a mean age of 45.6 ± 10 years. Liver cirrhosis was present in 16.1% of the study subjects. Mean follow-up time after SVR was 47 months (12-156 months). Twenty-two patients received monotherapy with interferon; 94 received interferon plus ribavirin, and 58 received pegylated interferon plus ribavirin. A total of 134 patients (77.0%) received one treatment course, 29 (16.7%) received two courses, and 11 (6.3%) received three courses. The distribution of HCV genotypes was: genotype 1 (40.2%), genotype 3 (40.8%) and genotype 2 (10.3%). Genotype was undetermined in 8.7% of cases. None of the 174 patients had recurrence of HCV infection. Two cirrhotic patients developed hepatocellular carcinoma (HCC) during follow-up. CONCLUSIONS: Among patients with SVR there was no recurrence of HCV infection or evidence of liver disease progression in any patient followed up for a mean of 47 months after SVR, except for patients with advanced hepatic disease before treatment, who may develop HCC despite SVR. Therefore, one can assume that SVR is associated with long term good prognosis.(FAEPA) Fundação de Apoio ao Ensino Pesquisa e Assistênci
Functional Characterization of an Aspergillus fumigatus Calcium Transporter (PmcA) that Is Essential for Fungal Infection
Aspergillus fumigatus is a primary and opportunistic pathogen, as well as a major allergen, of mammals. The Ca+2-calcineurin pathway affects virulence, morphogenesis and antifungal drug action in A. fumigatus. Here, we investigated three components of the A. fumigatus Ca+2-calcineurin pathway, pmcA,-B, and -C, which encode calcium transporters. We demonstrated that CrzA can directly control the mRNA accumulation of the pmcA-C genes by binding to their promoter regions. CrzA-binding experiments suggested that the 5′-CACAGCCAC-3′ and 5′-CCCTGCCCC-3′ sequences upstream of pmcA and pmcC genes, respectively, are possible calcineurin-dependent response elements (CDREs)-like consensus motifs. Null mutants were constructed for pmcA and -B and a conditional mutant for pmcC demonstrating pmcC is an essential gene. The ΔpmcA and ΔpmcB mutants were more sensitive to calcium and resistant to manganese and cyclosporin was able to modulate the sensitivity or resistance of these mutants to these salts, supporting the interaction between calcineurin and the function of these transporters. The pmcA-C genes have decreased mRNA abundance into the alveoli in the ΔcalA and ΔcrzA mutant strains. However, only the A. fumigatus ΔpmcA was avirulent in the murine model of invasive pulmonary aspergillosis
Effects of preoperative pelvic irradiation on colonic anastomosis healing: an experimental study in rats Efeito da radioterapia pélvica pré-operatória na cicatrização de anastomoses colônicas: estudo experimental em ratos
PURPOSE: Colorectal anastomosis is a constant worry-issue among surgeons because of high rates of complications, specially the dehiscence. The preoperative irradiation on cancer surgeries might interfere in the healing process, leading to an unfavorable outcome. METHODS: In the present study, two groups of rats were irradiated previously to a colorectal anastomosis surgery, with intervals of 4 and 8 weeks between the procedures. Seven days after the surgery, healing process was evaluated for dehiscence presence and histologic inflammatory characteristics. Also, levels of hydroxyproline, metalloproteinases and vascular endothelial growth factor were measured. RESULTS: Our results showed a higher incidence of dehiscences on the animals submitted to irradiation, compared to controls, with a reduced inflammatory activity in the healing tissue. DISCUSSION: Comparing both irradiated groups, those irradiated 8 weeks before surgery showed higher levels of hydroxyproline and metalloproteinases, indicating higher efficiency of the healing process. In conclusion, preoperative irradiation interferes with intestinal anastomosis healing and a larger time interval between both procedures is safer in terms of the healing quality.<br>INTRODUÇÃO: As anastomoses colorretais são motivos constante de preocupação por parte dos cirurgiões, em virtude do alto Ãndice de complicações, principalmente as deiscências. O uso da radioterapia previamente à cirurgia, nos casos de doença neoplásica, pode interferir no processo cicatricial das anastomoses, e levar a uma evolução desfavorável. MÉTODOS: Os autores estudaram dois grupos de ratos, submetidos a radioterapia e à confecção de uma anastomose no cólon, com intervalo de 04 e de 08 semanas entre os dois procedimentos, comparando com um grupo controle. Após 07 dias da cirurgia, estudaram-se vários aspectos do processo cicatricial: presença de deiscência, caracterÃsticas inflamatórias do tecido, dosagem de hidroxiprolina, de mateloproteinase e de VEGF. RESULTADOS: Os autores detectaram maior Ãndice de deiscência nos animais submetidos à radioterapia, com prejuÃzo da atividade inflamatória caracterÃstica de um tecido em cicatrização. DISCUSSÃO: Dentre os dois grupos irradiados, aquele com intervalo de oito semanas entre a radioterapia e a confecção da anastomose teve dosagem mais alta de hidroxiprolina e metaloproteinase, demonstrando maior eficiência do processo cicatricial. CONCLUSÃO: A radioterapia prévia interfere no processo de cicatrização das anastomoses intestinais, e que um maior intervalo de tempo entre os dois procedimentos é melhor para garantia de uma cicatrização satisfatória
HPV infection in Brazilian oral squamous cell carcinoma patients and its correlation with clinicopathological outcomes
Effect of thalidomide on the healing of colonic anastomosis, in rats Efeito da talidomida na cicatrização de anastomoses colônicas em ratos
PURPOSE: Thalidomide, because of its anti-inflammatory properties, as re-emerged as an option for the treatment of Crohn's disease refractory to standard therapy. We studied the effect of thalidomide on the healing of colonic anastomosis. METHODS: Sixty male rats (Rattus norvegicus), were divided into 3 groups of 20 animals each, respectively receiving 0.5 or 1.0 mg/kg thalidomide by the oral route for 7 days, or saline solution (control). All animals were submitted to continuous end-to-end anastomosis with 6-0 Prolene sutures. After sacrifice the anastomoses were analyzed macroscopically and submitted to determination of hydroxyproline, to histology and to immunohistochemistry for metalloproteinase 1, metalloproteinase 1 inhibitor and vascular endothelial growth factor (VEGF). RESULTS: Statistical analysis of the data showed no significant difference in macroscopic aspect or hydroxyproline determination (p= 0.5403). In the immunohistochemical analysis, the following p values were obtained: p = 0.5817 for VEGF, p = 0.1854 for metalloproteinase 1, and p = 0.0023 for metalloproteinase 1 inhibitor, with this last value being considered statistically significant. CONCLUSION: We conclude that thalidomide influenced collagen maturation. There was a stronger action of metalloproteinases, possibly indicating a negative tendency for the healing process.<br>OBJETIVO: Sabe-se que agentes farmacológicos podem influenciar no processo de cicatrização. A talidomida, devido à s suas propriedades antiinflamatórias, tem ressurgido como uma opção no tratamento da doença de Cröhn refratária à terapêutica convencional. Neste trabalho, estudamos o efeito da talidomida na cicatrização de anastomoses colônicas no rato. MÉTODOS: Foram utilizados 60 animais Rattus norvegius, com peso médio de 300g. Organizou-se 3 grupos de 20 animais, sendo um grupo controle (AC), um grupo (BD), com administração de talidomida 0,5 mg/kg por 7 dias e um grupo (AD) com administração de talidomida 1,0 mg/kg por 7 dias. Foi realizada anastomose término-terminal contÃnua de prolene 6-0. O sacrifÃcio foi no 7º. dia pós operatório e as anastomoses foram analisadas quanto a aspecto macroscópico, dosagem de hidroxiprolina, histologia em hematoxilina-eosina e imuno-histoquÃmica para metaloproteinase 1, inibidor de metaloproteinase 1 e VEGF. RESULTADOS: Não houve diferença estatisticamente significante para a observação macroscópica e para dosagem de hidroxiprolina (p=0,5403). Na análise imunohistoquÃmica, para VEGF houve p=0,5817, para metaloproteinase 1, p=0,1854 e para inibidor de metaloproteinase, p=0,0023, considerado estatisticamente significante. CONCLUSÃO: ConcluÃmos que a talidomida influenciou na maturação do colágeno. Notou-se maior ação das metaloproteinases, que pode significar uma tendência negativa para o processo cicatricial
HCV virological response during treatment of chronic hepatitis C is associated with liver histological Improvement in patients with HCV/HIV co-infection
Liver histological improvement after treatment for chronic hepatitis C in patients co-infected with human immunodeficiency virus-1 (HIV-1) has been described. Paired liver biopsies in twenty six HCV/HIV co-infected patients were compared to determine factors possibly associated with histological improvement. The patients were submitted to a liver biopsy before treatment for hepatitis C and 25 months after the end of treatment. Fragments of the liver biopsy obtained before and after treatment were compared regarding the following parameters: histological activity index (HAI) and degree of fibrosis (Knodell); intensity of collagen deposits (Sirius Red staining) and degree of stellate cell activation (alpha-smooth muscle actin labeling). The ratios of the post and pre-treatment variables were related through logistic regression to body mass index (BMI), alcohol ingestion, HCV genotype, HCV viremia, presence of hepatic iron and pre-treatment hepatic steatosis. A negative RNA test in the 24th week of treatment was associated with improvement in fibrosis, collagen deposits and stellate cell numbers. The other variables analyzed did not correlate to an improvement in hepatic histology after hepatitis C treatment. Reduction in HCV viremia during treatment may result in reduced hepatic fibrosis even in patients without a sustained virological response
- …