RESUMEN
BACKGROUND: Tumor necrosis factor alpha (TNF-α) is important in promoting relative adrenal insufficiency (RAI) due to systemic inflammatory response syndrome (SIRS). We identified the TNF-α receptor involved in the inhibition of adrenal corticotrophin (ACTH)-stimulated hydrocortisone release by studying the expression of TNF-α receptors in adrenal cortex Y1 cells and the effect of downregulating TNF receptors on ACTH-stimulated hydrocortisone release. METHODS: We used real-time PCR and immunocytochemistry to evaluate the expression of TNF receptors on Y1 cells. TNF-receptor 1 (TNF-R1) DNA fragments corresponding to the short hairpin RNA (shRNA)-sequences were synthesized and cloned into pcDNA(TM) 6.2-GW/EmGFP expression vector. Knockdown efficiency of TNF-R1 expression was evaluated in miRNA transfected and mock-miRNA transfected Y1 cells by quantitative real-time PCR (Q-PCR). Hydro-cortisone expression levels were determined in TNF-R1-knockdown and control Y1 cells treated with TNF-α and ACTH. RESULTS: Mouse adrenal cortex Y1 cells were positive for type I TNF-R1, but not type II TNF-receptor (TNF-R2). Blocking TNF-R1 expression resulted in loss of TNF-α-mediated inhibition of ACTH-stimulated hydrocortisone expression, suggesting a role for the TNF-R1 related signaling pathway in ACTH-stimulated hydrocortisone synthesis. CONCLUSION: The inhibitory effect of TNF-α on ACTH-stimulated hydrocortisone synthesis was mediated via TNF-R1 in adrenal cortex.
Asunto(s)
Corteza Suprarrenal/efectos de los fármacos , Corteza Suprarrenal/metabolismo , Hidrocortisona/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Corteza Suprarrenal/citología , Animales , Línea Celular , Inmunohistoquímica , Ratones , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND/AIMS: Interferon (IFN) alpha has been used in the treatment of chronic hepatitis B for decades. Beneficial effects including hepatitis B e antigen (HBeAg)/HBV DNA seroclearance have been documented. However, it remains unclear whether interferon has long-term efficacy on inhibiting hepatitis B viral replication. So we conducted a meta-analysis of available literature to assess the evidence obtained on the efficacy of IFN treatment in chronic HBV infection. METHODS: Seven clinical controlled trials, including 1550 patients and comparing IFN to no treatment, were selected. Data on the incidence of HBV DNA seroclearance, HBeAg seroclearance, and HBsAg seroclearance in IFN treated and untreated patients were extracted from each study. The evaluation of effectiveness was performed with an intention-to-treat (ITT) method. We used the relative risk (RR) and 95% confidence interval (CI) of the main outcomes as the measure of efficacy. Meta-analysis was performed using fixed-effect or random-effect methods, depending on absence or presence of significant heterogeneity. Analyses were performed with STATA version 9.0 and Review Manager Version 4.2. RESULTS: Four studies including the data of HBeAg seroclearance with significant heterogeneity were analyzed by random-effect method; six studies including the data of HBsAg seroclearance without significant heterogeneity were analyzed by fixed-effect method. A different incidence of HBeAg seroclearance and HBsAg seroclearance was observed between treated and untreated patients. The RR of HBeAg seroclearance and HBsAg seroclearance was 0.66 (95% CI: 0.44, 0.99) and 0.28 (95% CI: 0.17, 0.46), respectively. CONCLUSIONS: In conclusion, the results of this meta-analysis indicate that IFN increases the incidence of HBeAg seroclearance and HBsAg seroclearance after long-term follow-up of three to seven years.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Ensayos Clínicos Controlados como Asunto , ADN Viral/sangre , Femenino , Estudios de Seguimiento , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Humanos , Masculino , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The use of hypertonic crystalloid solutions, including sodium chloride and bicarbonate, for treating severe sepsis has been much debated in previous investigations. We have investigated the effects of three crystalloid solutions on fluid resuscitation in severe sepsis patients with hypotension. METHODS: Ninety-four severe sepsis patients with hypotension were randomly assigned to three groups. The patients received the following injections within 15 min at initial treatment: Ns group (n = 32), 5 ml/kg normal saline; Hs group (n = 30), with 5 ml/kg 3.5% sodium chloride; and Sb group (n = 32), 5 ml/kg 5% sodium bicarbonate. Cardiac output (CO), systolic blood pressure, mean arterial pressure (MAP), body temperature, heart rate, respiratory rate and blood gases were measured. RESULTS: There were no differences among the three groups in CO, MAP, heart rate or respiratory rate during the 120 min trial or the 8 hour follow-up, and no significant differences in observed mortality rate after 28 days. However, improvement of MAP and CO started earlier in the Sb group than in the Ns and Hs groups. Sodium bicarbonate increased the base excess but did not alter blood pH, lactic acid or [HCO3]- values; and neither 3.5% hypertonic saline nor 5% sodium bicarbonate altered the Na+, K+, Ca2+ or Cl- levels. CONCLUSION: All three crystalloid solutions may be used for initial volume loading in severe sepsis, and sodium bicarbonate confers a limited benefit on humans with severe sepsis. TRIAL REGISTRATION: ISRCTN36748319.