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Laura Cisneros Maria-Carlota Londo?o Carmen Blasco Ramón Bataller Rosa Miquel Miquel Bruguera Pere Ginès Antoni Rimola 《Liver transplantation》2007,13(7):1017-1027
The pathogenic mechanisms of accelerated graft fibrosis in hepatitis C recurrence after liver transplantation (LT) are not well established. The aim of the study was to assess whether a greater activation of hepatic stellate cells (HSC), the major collagen-producing cells in the liver, can occur in these patients as compared to non-LT patients with chronic hepatitis C. We determined the amount of activated HSC by computer-based morphometric analysis of alpha-smooth muscle actin (alphaSMA)-positive cells and the hepatic TGFbeta(1) expression by immunohistochemistry in 46 LT patients with hepatitis C recurrence, 35 non-LT patients with chronic hepatitis C, and 16 controls. Hepatic alphaSMA and TGFbeta(1) expression was higher in LT patients with hepatitis C recurrence than in controls and was correlated with fibrosis stage and progression rate. No significant difference in alphaSMA and TGFbeta(1) expression was observed between LT and non-LT patients with hepatitis C, with the exception of a higher transforming growth factor beta-1 (TGFbeta(1)) expression in non-LT patients in the early stages of fibrosis. LT patients receiving cyclosporine (CsA) or tacrolimus (FK) had a similar fibrosis progression rate and alphaSMA and TGFbeta(1) expression. In conclusion, the accelerated fibrosis observed in LT patients with hepatitis C recurrence does not seem to be related to a greater amount of activated HSC and TGFbeta(1) expression in the grafts of these patients as compared to non-LT patients with chronic hepatitis C. In LT patients, the amount of activated HSC and TGFbeta(1) expression correlated with fibrosis stage and progression, without any apparent influence of the type of calcineurin inhibitor administered. 相似文献
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In the 12-day-old rat cochlea, the synthesis of inositol phosphates (IPs) can be activated via M3 cholinoceptors. This stimulation is blocked by ototoxins (mercury, ethacrynate, cisplatin, neomycin), drugs with side effects that lead to damage of hair cells and strial cells. As these toxic effects can be reversed in vivo by thiol molecules, we investigated whether modifications of thiol compounds could be involved in ototoxin-induced inhibition of the IP turnover in the cochlea. For this purpose, we assessed whether the sulphhydryl-modifying reagents N -ethylmaleimide and cadmium modify the carbachol-stimulated formation of IPs in the 12-day-old rat cochlea. Both molecules inhibit the carbachol effect on a dose-dependent way without altering the basal metabolism of IPs. As cadmium may block some calcium channels, the effect of verapamil, another calcium channel antagonist, was tested. Verapamil (1 –50 μM) does not alter carbachol-evoked IP formation, suggesting that the inhibitory effect of cadmium is not due to a calcium influx block. Binding experiments with the muscarinic ligand quinuclidinyl benzylate (QNB) showed that the sulphhydryl-modifying reagents do not displace QNB from binding sites. Combining ototoxins and reagents shows that N -ethylmaleimide acts synergistically with all ototoxins but ethacrynate while cadmium does so only with mercury. Both N -ethylmaleimide and cadmium have additive effects with ethacrynate. As a supplement, disulphide bond-modifying agents do not alter the carbachol-enhanced metabolism of IPs. These results suggest that molecules having thiol-modifying properties inhibit the carbachol-induced turnover of IPs without acting at the muscarinic sites. Since thiol modifiers and ethacrynate share similar features in both QNB binding and IP response it is hypothesized that they strike common targets, possibly G proteins. 相似文献
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P-fimbriae vaccines 总被引:3,自引:0,他引:3
M. Bernice Kaack Auli Pere Timo K. Korhonen Stefan B. Svenson James A. Roberts 《Pediatric nephrology (Berlin, Germany)》1989,3(4):386-390
To test for cross-protective capacity of two different P-fimbriae vaccines we vaccinated baboons with fimbriae purified from either Escherichia coli strain ER2 or strain JR1. The vaccinated animals showed elevated antibody titers to P-fimbriae from each of the E. coli strains used, suggesting cross-reactivity as was expected from the results of immunoprecipitation of the fimbriae. Enzyme-linked immunosorbent assay inhibition by heterologous P-fimbriae proved this to be true immunologic cross-reactivity. 相似文献
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A Pujol M F Berthault L Picon L Pénicaud 《International journal of obesity (2005)》1991,15(8):505-511
This study was undertaken to determine the changes which could occur in glucose homeostatis during the suckling-weaning transition in the genetically obese Zucker (fa/fa) rat. Glucose kinetics and glucose utilization in individual tissues were determined in 15-day-old suckling and 30-day-old weaned obese Zucker rats either in the post-absorptive state or during a glucose infusion. During suckling, glucose turnover rates in the basal state as well as glucose production and utilization during the glucose infusion were identical in lean and obese rats. Furthermore, individual tissue glucose utilizations were similar in the two groups of rats, except in brown adipose tissue where utilization was lower in obese than in lean rats during the glucose challenge. After weaning, glucose turnover rates and glucose utilization in individual tissues were identical in the two genotypes in the basal state. During the glucose infusion, hepatic glucose production was less suppressed in the obese. Furthermore, glucose utilization was significantly lower in muscles (extensor digitorum longus, tibialis anterior, diaphragm) and higher in white adipose tissue of obese rats. These data show that, before weaning, pre-obese Zucker rats present a perturbation only in the uptake of glucose in brown adipose tissue. Major defects in the regulation of glucose homeostatis occur after weaning. 相似文献
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Ana María Fortuna Marco Balleza Núria Calaf Mercedes González Teresa Feixas Pere Casan 《Archivos de bronconeumologia》2009,45(3):143-147
Nitric oxide (NO) production has been described using a 2-compartment model for the synthesis and movement of NO in both the alveoli and the airways. The alveolar concentration of NO (CaNO), an indirect marker of the inflammatory state of the distal portions of the lung, can be deduced through exhalation at multiple flow rates. Our objective was to determine reference values for CaNO. The fraction of exhaled NO (FeNO) was measured in 33 healthy individuals at a rate of 50 mL/s; the subjects then exhaled at 10, 30, 100, and 200 mL/s to calculate CaNO. A chemiluminescence analyzer (NIOX Aerocrine) was used to perform the measurements. The mean (SD) FeNO was 15 (6) ppb. The mean CaNO was 3.04 (1.30) ppb. These values of CaNO measured in healthy individuals will allow us to analyze alveolar inflammatory behavior in respiratory and systemic processes. 相似文献