Isoflurane-induced cognitive impairment measured by Barnes maze and fear conditioning.

<p>Eighteen-month-old Fisher 344 rats were exposed to or were not exposed to 1.2% isoflurane for 2 h. They were subjected to Barnes maze 2 weeks later or fear conditioning 27 days later. A: performance in the training sessions of Barnes maze test. There is a significant effect of training sessions on the latency to identify the target hole (P<0.001 by two-way repeated measures analysis of variance). B: latency to identify the target hole at 1 day or 8 days after the training sessions. C: number of other hole searched before identifying the target hole at 1 day or 8 days after the training sessions. D: performance in fear conditioning test. Results are mean±S.D. (n = 6). *P<0.05 compared with the corresponding control in panels B, C and D by t-test.</p

Isoflurane effects on the expression of interleukin 6 (IL-6), activated/cleaved caspase 3 and cluster of differentiation 11b (CD-11b) in rat brain tissues.

<p>Eighteen-month-old Fisher 344 rats were exposed to or were not exposed to 1.2% isoflurane in the presence or absence of lidocaine for 2 h. Hippocampus and cerebral cortex were harvested at 6 h after anesthetic exposure for Western blotting. A: representative Western blot images. B, C and D: graphic presentation of the IL-6, cleaved caspase 3 and CD-11b protein abundance quantified by integrating the volume of autoradiograms from 4 rats for each experimental condition. Values in graphs are expressed as fold changes over the mean values of control animals and are presented as the means±S.D. *P<0.05 compared with the control group. ? P<0.05 compared to isoflurane alone. Statistical analysis was performed by one-way analysis of variance. C: control, I: isoflurane, I+L: isoflurane plus lidocaine.</p

Isoflurane effects on the expression of NeuN, drebrin and synaptophysin in rat brain tissues.

<p>Eighteen-month-old Fisher 344 rats had the training sessions of fear conditioning and 30 min later were exposed to or were not exposed to 1.2% isoflurane in the presence or absence of lidocaine for 2 h. Hippocampus and cerebral cortex were harvested at 48 h after anesthetic exposure for Western blotting. A: representative Western blot images. B, C and D: graphic presentation of the NeuN, drebrin and synaptophysin protein abundance quantified by integrating the volume of autoradiograms from 4 rats for each experimental condition. Values in graphs are expressed as fold changes over the mean values of control animals and are presented as the means±S.D. C: control, I: isoflurane, I+L: isoflurane plus lidocaine.</p

Isoflurane effects on cognitive functions assessed by fear conditioning.

<p>Ten-week old male C57BL/6J (wild-type) mice or interleukin 1β (IL-1β) deficient mice were exposed to 1.4% isoflurane for 2 h and then subjected to the fear conditioning test 48 h later. Results are means±S.D. (n = 15 for the wild-type mice and 6 for the IL-1β deficient mice). *P<0.05 compared with the corresponding control group. # P<0.05 compared to the wild-type control mice. Statistical analysis was performed by t-test.</p

Isoflurane-induced learning impairment measured by fear conditioning test.

<p>A: freezing behavior during training sessions for 18-month old Fisher 344 rats that were exposed to isoflurane in the presence or absence of lidocaine 27 days ago. Results are means±S.D. (n = 6 for control and isoflurane only groups and  = 7 for isoflurane plus lidocaine group). There is a significant effect of training trial (P<0.001, among the control animals and animals exposed to isoflurane plus lidocaine), isoflurane use (P = 0.002, control animals vs. animals exposed to isoflurane only) and lidocaine use (P = 0.003, animals exposed to isoflurane only vs. animals exposed to isoflurane plus lidocaine) on the freezing behavior. Statistical analysis was performed by two-way analysis of variance. B: freezing behavior during the context- and tone-related fear conditioning tests for 18-month old Fisher 344 rats that first had the training sessions and were exposed to isoflurane in the presence or absence of lidocaine at 30 min after the training sessions. Results are means±S.D. (n = 4 for control group and  = 5 for the isoflurane only and isoflurane plus lidocaine groups).</p

Isoflurane effects on the expression of interleukin 6 (IL-6), activated/cleaved caspase 3 and cluster of differentiation 11b (CD-11b) in rat brain tissues.

<p>Eighteen-month-old Fisher 344 rats had the training sessions of fear conditioning and 30 min later were exposed to or were not exposed to 1.2% isoflurane in the presence or absence of lidocaine for 2 h. Hippocampus and cerebral cortex were harvested at 48 h after anesthetic exposure for Western blotting. A: representative Western blot images. B, C and D: graphic presentation of the IL-6, cleaved caspase 3 and CD-11b protein abundance quantified by integrating the volume of autoradiograms from 4 rats for each experimental condition. Values in graphs are expressed as fold changes over the mean values of control animals and are presented as the means±S.D. *P<0.05 compared with the control group. ? P<0.05 compared to isoflurane alone. Statistical analysis was performed by one-way analysis of variance. C: control, I: isoflurane, I+L: isoflurane plus lidocaine.</p

Expression of interleukin 1β (IL-1β), IL-6 and activated/cleaved caspase 3 in rat brain tissues.

<p>Eighteen-month-old Fisher 344 rats were exposed to or were not exposed to 1.2% isoflurane for 2 h. Hippocampus was harvested at 48 h after isoflurane exposure for immunofluorescent staining of IL-1β (red), IL-6 (red), cleaved caspase 3 (red), NeuN (green), glial fibrillary acidic protein (GFAP, green) and ionized calcium binding adaptor molecule 1 (Iba1, green). The merged panels also include Hoechst staining (blue) to show cell nuclei. A: co-staining of IL-1β with GFAP, Iba1 and NeuN. B: co-staining of IL-6 with GFAP, Iba1 and NeuN. C: co-staining of cleaved caspase 3 with GFAP, Iba1 and NeuN. Con: control, Iso: isoflurane.</p

HBeAg Seroconversion in HBeAg-Positive Chronic Hepatitis B Patients Receiving Long-Term Nucleos(t)ide Analog Treatment: A Systematic Review and Network Meta-Analysis

<div><p>Background</p><p>HBeAg seroconversion is an important intermediate outcome in HBeAg-positive chronic hepatitis B (CHB) patients. This study aimed to compare the effect of nucleos(t)ide analogs (NAs) on HBeAg seroconversion in treating CHB with lamivudine, adefovir, telbivudine, entecavir, and tenofovir.</p><p>Methods</p><p>Network meta-analysis of NA treatment-induced HBeAg seroconversion after 1–2 years of treatment was performed. In addition, NA treatment-induced HBeAg seroconversion after 3–5 years of treatment was systematically evaluated.</p><p>Results</p><p>A total of 31 articles were included in this study. Nine and five studies respectively reporting on 1- and 2-year treatment were included in our network meta-analysis. In addition, 6, 5, and 5 studies, respectively reporting on 3-, 4-, and 5-year treatment were included in our systematic evaluation. Telbivudine showed a significantly higher HBeAg seroconversion rate after a 1 year treatment period compared to the other NAs (odds ratio (OR) = 3.99, 95% CI 0.68–23.6). This was followed by tenofovir (OR = 3.36, 95% CI 0.70–16.75). Telbivudine also showed a higher seroconversion rate compared to the other NAs after a 2 year treatment period, (OR = 1.38, 95% CI 0.92–2.22). This was followed by entecavir (OR = 1.14, 95% CI 0.72–1.72). No significant difference was observed between spontaneous induction and long-term telbivudine treatment-induced HBeAg seroconversion. However, entecavir and tenofovir treatment-induced HBeAg seroconversions were significantly lower than spontaneous seroconversion.</p><p>Conclusion</p><p>Long-term treatment with potent anti-HBV drugs, especially tenofovir and entecavir, may reduce HBeAg seroconversion compared with spontaneous HBeAg seroconversion rate. Telbivudine treatment, whether short term or long term, is associated with higher HBeAg seroconversion compared with the other NAs. However, the high rates of drug resistance likely limit the application of telbivudine.</p></div

Characteristics of HBeAg positive chronic hepatitis B patients following 5-year treatment with NAs.

<p>Characteristics of HBeAg positive chronic hepatitis B patients following 5-year treatment with NAs.</p

Flow diagram depicting the steps of this systematic review.

<p>Flow diagram depicting the steps of this systematic review.</p