RESUMO
Antimicrobial peptides (AMPs) are secreted in the airway and contribute to initial defence against inhaled pathogens. Infections of the respiratory tract are a major cause of morbidity and mortality in preterm newborns and in patients with cystic fibrosis (CF). In this latter group, the state of chronic lung infection is due to the ability of bacteria to grow as mucoid biofilm, a condition characterised by overproduction and release of polysaccharides (PSs). In this study, we investigate the effect of PSs produced by lung pathogens such as Pseudomonas aeruginosa, Klebsiella pneumoniae and members of the Burkholderia cepacia complex on the antibacterial activity of structurally different peptides. The AMPs tested in this study include the cathelicidin LL-37 and the beta-defensin hBD-3 from humans, both released at the alveolar level, as well as peptides from other mammals, i.e. SMAP-29, PG-1 and Bac7(1-35). Susceptibility assays, time killing and membrane permeabilization kinetics experiments were carried out to establish whether PSs produced by lung pathogens may be involved in the poor defence reaction of infected lungs and thus explain infection persistence. All the PSs investigated inhibited, albeit to a different extent, the antibacterial activity of the peptides tested, suggesting that their presence in the lungs of patients with CF may contribute to the decreased defence response of this district upon infection by PS-producing microorganisms. The results also show that inhibition of the antibacterial activity is not simply due to ionic interaction between the negatively charged PSs and the cationic AMPs, but it also involves other structural features of both interactors.
Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Bactérias/efeitos dos fármacos , Pneumopatias/microbiologia , Polissacarídeos Bacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/síntese química , Peptídeos Catiônicos Antimicrobianos/química , Infecções Bacterianas/microbiologia , Burkholderia mallei/efeitos dos fármacos , Burkholderia mallei/metabolismo , Catelicidinas/síntese química , Catelicidinas/química , Catelicidinas/farmacologia , Membrana Celular/efeitos dos fármacos , Fibrose Cística/microbiologia , Interações Medicamentosas , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Humanos , Cinética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/metabolismo , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismoRESUMO
To investigate the relationship among circulating cytokines, inflammation in the liver, and kind of response to interferon-alpha (IFN-alpha) in hepatitis C, we studied 63 consecutive patients (38 male, 25 female), treated with IFN for up to 1 year. Serum tumor necrosis factor-alpha (TNF-alpha) was measured at baseline and after 3 months of treatment. Transient (TR) or sustained response (SR) was observed in 29 and 16 patients, respectively. Baseline levels of TNF < or = 22 ng/L were observed in 69% of patients with SR, 55% of patients with TR, and 22% of nonresponders (p < 0.01). There was a significant correlation between baseline TNF levels and histologic grading score of hepatitis (p < 0.01). After 3 months of treatment, TNF levels >22 ng/L were observed in 63% of patients with SR, 69% of patients with TR, and 83% of nonresponders (p NS). Independent of the treatment outcome, TNF levels were lower at baseline and increased significantly with treatment in patients with lower histologic grading (p < 0.005). In conclusion, in patients with chronic hepatitis C, circulating TNF levels correlate with the degree of inflammation in the liver. Response to IFN is accompanied by an inflammatory response involving the release of TNF.
Assuntos
Antivirais/uso terapêutico , Citocinas/sangue , Hepatite C Crônica/tratamento farmacológico , Inflamação/sangue , Interferon-alfa/uso terapêutico , Adulto , Feminino , Hepatite C Crônica/sangue , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Resultado do TratamentoRESUMO
Serum iron indices are believed to be elevated in patients with hepatitis C virus (HCV) infection in connection to the presence of hepatic inflammation, though this hypothesis has never been formally tested. We studied 69 consecutive, unselected anti HCV antibody positive patients, aged 14 to 70 years. Iron, transferrin saturation and ferritin were measured in fasting serum samples. Histologically detectable iron (HDI) as well as histologic grading and staging were estimated semiquantitatively in liver biopsy samples. The median values for serum iron, transferrin saturation and serum ferritin were 24 micromol/l (range, 8-61), 29 percent (range, 6-77) and 170 microg/l (range, 1-954), respectively. At univariate analysis, all three serum iron indices were positively correlated with grading and staging scores, as well as with HDI in the liver; only serum iron was positively correlated with transaminases. At multivariate analysis, independent associations were found between serum iron and the grading score; ferritin and sinusoidal and portal HDI; transferrin saturation and total hepatic HDI. In conclusion, in hepatitis C, serum iron reflects the degree of current hepatic inflammation and necrosis, whereas the extent of progressive deposition of iron in sites of fibrosis is best reflected by serum ferritin. Transferrin saturation is the best predictor of the status of hepatic iron deposits.
Assuntos
Hepatite C Crônica/sangue , Ferro/sangue , Adolescente , Adulto , Idoso , Feminino , Ferritinas/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosAssuntos
Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/patologia , Artrite Reumatoide/complicações , Vasculite/complicações , Polipose Adenomatosa do Colo/cirurgia , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/fisiopatologia , Biópsia por Agulha , Colonoscopia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Radiografia , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Vasculite/diagnósticoRESUMO
UNLABELLED: A new case of tubulo-interstitial nephritis and uveitis (TINU) syndrome in a 14-y-old girl is described. In this patient unilateral mastitis was an associated feature. The aetiology of this rare syndrome, the prognosis for which is usually good, is still unknown. The most common theory supports a cell-mediated immune response induced by infectious/antigenic stimuli. CONCLUSION: The presence of acute unilateral mastitis in this patient may represent an additional localization in TINU syndrome.
Assuntos
Mastite/complicações , Nefrite Intersticial/complicações , Uveíte/complicações , Adolescente , Feminino , Humanos , Mastite/tratamento farmacológico , Nefrite Intersticial/patologia , Síndrome , Uveíte/tratamento farmacológicoRESUMO
Empyemas are usually of infectious origin. Noninfectious causes of empyema may be a considerable diagnostic challenge, as exemplified in the present case report. A 21-year-old male presented with high fever, sore throat and myalgias of 1 week duration. In the following days, bilateral pleural effusions developed, with cellular counts in the pleural fluid up to 117 x 10(9)/liter (98% neutrophils). Despite institution of empiric antibiotic therapy, spiking fever continued. All culture studies resulted in being negative. Following the report of a serum ferritin concentration of 6,975 microg/l, adult-onset Still's disease was diagnosed and successfully treated with anti-inflammatory drugs. This case adds adult-onset Still's disease to the list of noninfectious causes of empyema and underlies the value of measuring serum ferritin as a diagnostic tool.
Assuntos
Empiema Pleural/tratamento farmacológico , Empiema Pleural/etiologia , Doença de Still de Início Tardio/complicações , Doença de Still de Início Tardio/diagnóstico , Adulto , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Empiema Pleural/diagnóstico por imagem , Ferritinas/análise , Seguimentos , Humanos , Masculino , Metotrexato/uso terapêutico , Prednisona/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Because in experimental hepatocarcinogenesis apoptosis increases from normal to preneoplastic to carcinoma tissue, proapoptotic factors, such as activin-A, may represent useful markers for hepatocellular carcinoma (HCC). In this study, serum activin-A was measured in 99 cirrhotic patients, of whom 55 had HCC. Activin-A concentrations were higher in HCC patients (median, 2.33 ng/ml; range, 0.41-8.12) than in patients with nonmalignant cirrhosis (1.28 ng/ml; range, 0.35-6.25) (P < .05). All 12 patients with activin-A greater than 3 ng/ml and serum alpha-fetoprotein greater than 30 ng/ml had HCC, in comparison to 32 of 41 patients who had only one and to 11 of 46 patients who had both markers below these cutoffs (P < .0001). No correlation was found between activin-A and alpha-fetoprotein in the two groups, whereas in patients with HCC, activin-A was strictly correlated with serum aspartate aminotransferase (P < .001). Activin-A mRNA for inhibin betaA subunit was expressed both in tumor and nontumor liver tissues in a case of HCC superimposed on cirrhosis and was not expressed in a case of HCC without cirrhosis. In conclusion, cirrhotic patients with HCC have high serum activin-A, to the production of which both the cirrhotic liver and the liver tumor are likely to contribute.