SummaryApoptosis in the liver is generated mainly by the Fas system. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has been proposed recently as a new apoptotic inducer. In the liver environment hepatocytes and biliary epithelial cells express TRAIL receptors which are up-regulated by increased levels of bile acids and during viral hepatitis. As for FasL, a soluble form of TRAIL has been described. To explore the commitment and level of activation of these two apoptotic systems in patients affected by primary biliary cirrhosis (PBC) or chronic hepatitis C (CH-C), a comparative study was drawn. Thirty patients with PBC on ursodeoxycholic acid have been enrolled. This group was compared with 30 patients with CH-C and with 20 healthy subjects. Soluble Fas ligand (sFasL) and soluble TRAIL (sTRAIL) levels were evaluated by double determinant immune assay and enzyme-linked immunosorbent assay (ELISA), respectively. Soluble FasL molecules were higher in PBC compared to CH-C (P = 0·009). Soluble FasL was not detected in controls. Soluble TRAIL was significantly higher in CH-C patients compared to PBC (P = 0·0001). Soluble TRAIL levels were higher in PBC and in CH-C than in controls (P = 0·015 and P < 0·001, respectively). No correlation between sFasL and sTRAIL, stage of disease, liver histology in each disease and cytolysis was present. Our data show different levels of commitment of TRAIL and Fas apoptosis-inducing systems in CH-C and PBC. Thus a different prominent role of TRAIL and Fas systems in the pathogenesis of these two conditions can be speculated: the former by inducing the death of infected hepatocytes, the latter by mediating the disappearance of bile duct.
Antiviral treatment with pegylated interferon (PEG-IFN) and ribavirin for chronic hepatitis C improved the rates of viral clearance to 56%. An open issue is a better understanding of the factors responsible for the residual lack of response. Our aim was to investigate the effect of antiviral treatments on soluble tumor necrosis factor-related ligand (sTRAIL), which is capable of inducing apoptosis in virus-infected cells. We analyzed sTRAIL levels in 22 naive patients, randomly assigned to receive 6 months of treatment with IFN alone or in combination with amantadine or ribavirin, at baseline, at 6, 12, 24, 30, and 48 h, at days 3, 7, and 14, at 1, 3, and 6 months of treatment, and finally 6 months after the end of treatment. At baseline, the sTRAIL level was significantly higher in patients than in controls (p < 0.0001). The highest sTRAIL release was obtained within the first 12 h, followed by a second peak after the second dose of IFN. There was then a slow decline within the first month. Compared with baseline, high sTRAIL levels were present till day 7 in sustained responders (7 patients) and till the third month of treatment in relapsers or nonresponders (15 patients) (p < 0.02), with no differences related to the type of treatment. The IFN effect on sTRAIL is rapid and intense. The overexpression of TRAIL in viral hepatitis could be seen as a defense mechanism to eliminate infected cells and limit viral replication.
SUMMARY We have previously studied the effect of three different treatment regimens with interferon (IFN)‐α alone or in combination with amantadine or ribavirin on viral kinetics in the first month of therapy. To understand the regulation of cytokine immune response during early inhibition of HCV replication, we analysed the longitudinal profile of proinflammatory markers (soluble TNFRs), of type 1 cytokines [IFN‐γ and interleukin (IL‐12)], and of a type 2 cytokine (IL‐10). Twenty‐two chronic hepatitis C patients received daily therapy for 6 months. Sera were collected at baseline, at 6, 12, 24, 30 and 48 h and at the 3rd, 7th, 15th and 30th days of treatment. All cytokines and receptors were evaluated by enzyme linked immunosorbent assay (ELISA). At baseline, a correlation was found between the two soluble TNFRs (P < 0·0001) and between the soluble TNFRs and ALT levels (P < 0·003), as shown previously. Regardless of the type of treatment, lower levels of soluble TNFR‐p75 were present from day 3 in patients who had significant virus decay at day 30 (P < 0·01). Baseline IL‐10 levels correlated with TNFR‐p75 (P < 0·01) and with treatment response (P < 0·05) and a significant IL‐10 reduction from baseline was observed from day 3 among responders, irrespective of the type of treatments (P < 0·05). IL‐12 and IFN‐γ levels did not differ according to treatment or outcome. These findings suggest a pivotal role for IL‐10 in orchestrating the antiviral immune response. Its early decline can favour the shift from a Th2 to a Th1 immune response, which has been shown to be associated with a long‐term virological response to treatment.
La irrupción del teletrabajo en Argentina se dio de forma abrupta a partir del establecimiento del Aislamiento Social, Preventivo y Obligatorio (ASPO) como medida sanitaria para contener la pandemia de Covid-19. Hasta ese momento, esta modalidad de trabajo no tenía una regulación específica. Finalmente, fue debatida y aprobada entre los meses de junio y agosto de 2020. Este trabajo discute tres características del teletrabajo, las cuales están íntimamente relacionadas e incluso confundidas dentro de la noción de tiempo de trabajo: la relación tiempo-espacio, los límites de la jornada de trabajo y la oposición entre tiempo de trabajo mercantil y otros tiempos necesarios para la vida. Algunos de estos elementos fueron parcialmente incorporados a la nueva regulación.
La profundización del modelo aperturista a partir de 1991 introdujocambios profundos en la legislación laboral y dio lugar a una nueva generaciónde políticas sociales, las cuales, en el caso argentino, no contemplanla temporalidad social. A partir de esta premisa, el objetivo generalde esta tesis es indagar la incidencia que los programas de transferenciamonetaria condicionada implementados, tienen en moldear el uso deltiempo de los beneficiarios, a través del estudio del caso del ProgramaJefas y Jefes de Hogar Desocupados.Los programas diseñados para hacer frente a la desocupación a partirde los ’90 no resultan inocuos en términos de temporalidad social, ya queintroducen una serie de prescripciones y obligaciones que puede llegar aprofundizar la desestructuración temporal de las poblaciones asistidas. Elreconocimiento de esta situación a través de un estudio en profundidad constituye un aporte significativo, pues introduce una variable habitualmenteignorada y de fuerte incidencia en la aplicación de estos programas.La presente investigación de tipo exploratorio se propone como un estudiode caso único encastrado en la medida en que la indagación empírica secentra en describir y analizar un fenómeno social complejo y contemporáneodentro de su contexto en el mundo social. Al respecto, se indagarála temática en estudio con relación a la etapa final de aplicación del PJJHD(Programa Jefas y Jefes de Hogar Desocupados) en la ciudad de Rosario. Porsu parte, el abordaje metodológico reúne elementos tanto de la metodologíacualitativa como de la cuantitativa, con predominio de esta última.
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