EGF促进RPE细胞β_2肾上腺能受体诱导的cAMP形成：受体间交互作用分析

研究证实表皮生长因子（ＥＧＦ）不影响培养人眼视网膜色素上皮（ＲＰＥ）细胞ｃＡＭＰ的基础水平，但促进异丙肾上腺素激活β＿２受体后诱导ｃＡＭＰ水平升高的效应，并呈量效依赖关系。ＥＧＦ对腺嘌呤核苷Ａ＿２受体激动剂ＮＥＣＡ诱导ｃＡＭＰ水平升高的效应没有明显影响。细胞增殖分析表明，ＥＧＦ刺激人眼ＲＰＥ细胞增殖，而ＤｉｂｕｔｙｒｙｌｃＡＭＰ和异丙肾上腺素抑制ＥＧＦ刺激增殖的效应。结果提示，在人眼ＲＰＥ细胞ＥＧＦ和β２受体之间存在受体间交互作用。     

Evaluating a computer system used as a microswitch for word utterances of persons with multiple disabilities

Purpose: To assess the effectiveness of a computer system used as a microswitch for word utterances of two adults with multiple disabilities. The system combined a new control software programme with a commercially available speech recognition programme. Method: Nine word utterances were targeted for each participant. The participant's emission of those utterances triggered the occurrence of related (favourite) stimuli during the intervention and the post-intervention check. Results: Intervention data showed that (1) the participants increased the frequencies of the target utterances and (2) the computer system recognized about 80% of those utterances correctly, providing the participants with high levels of favourite stimulation. The post-intervention check showed comparable data with both participants. Conclusions: The computer system proved an adequate microswitch for word utterances. Based on this evidence, microswitch programmes could be extended beyond the use of conventional motor responses.     

Are adverse events of nevirapine and efavirenz related to plasma concentrations?

OBJECTIVE: The relationships between adverse events (AEs) and plasma concentrations of nevirapine (NVP) and efavirenz (EFV) were investigated as part of the large, international, randomized 2NN study. METHODS: Treatment-naive, HIV-1-infected patients received NVP (once or twice daily), EFV or their combination, each in combination with lamivudine and stavudine. Blood samples were collected on day 3 and weeks 1, 2, 4, 24 and 48. Concentrations of NVP and EFV were quantitatively assessed by a validated HPLC assay. Individual Bayesian estimates of the area under the plasma concentration-time curve over 24 h (AUC24h), and minimum and maximum plasma concentrations (Cmin and Cmax) as measures for drug exposure of NVP and EFV, were generated using a previously developed population pharmacokinetic model. Pharmacokinetic parameters were compared for patients with and without central nervous system (CNS) and psychiatric AEs, hepatic events, liver enzyme elevations (LEEs) and rash. Furthermore, it was investigated whether a clear cut-off for a pharmacokinetic parameter could be identified above which the incidence of AEs was clearly increased. AEs were also related to demographic parameters and baseline characteristics. RESULTS: In total, from 1077 patients, NVP (3024 samples) and EFV (1694 samples) plasma concentrations and AE data (825 observations) were available. For all patients Cmin, Cmax and AUC24h were determined. When corrected for known covariates of gender, CD4 cell count at baseline, region, hepatitis coinfection and possible interactions between these factors, no significant associations between AEs and any tested exposure parameter of NVP was observed. Also, no target Cmin value, above which patients were at increased risk for AEs, could be established. On the other hand, geographical region, hepatitis coinfection, CD4 cell count and gender were found to be significantly related with the incidence of CNS and psychiatric AEs, hepatic events, LEEs and rash during the treatment with NVP. The occurrence of elevated liver enzymes during the first 6 weeks in the EFV-containing arm was significantly (P = 0.036) correlated to the exposure of EFV (Cmin). Only hepatitis coinfection impacted on LEEs during the first 6 weeks of treatment. With an EFV Cmin above 2.18 mg/l during the induction phase, patients were 4.4 (range 1.3-15.5) times more at risk for elevated liver enzymes. No other correlations between AEs and EFV pharmacokinetics or patient characteristics could be identified. CONCLUSIONS: Pharmacokinetic parameters of NVP did not have a relationship to AEs in the 2NN trial when corrected for known covariates. The value of periodical drug monitoring of NVP as a way to prevent toxicity is therefore limited. Treating physicians should instead focus on factors that are more predictive of AEs (gender, CD4 count and hepatitis coinfection). High EFV Cmin levels resulted in elevated liver enzyme values during the first 6 weeks of treatment. Regular measurement of EFV levels and liver enzymes at the start of therapy may therefore be advised.     

Successful vaccination of immune suppressed recipients using Listeria vector HIV-1 vaccines in helminth infected mice

Vaccines for HIV, malaria and TB remain high priorities, especially for sub-Saharan populations. The question is: will vaccines currently in development for these diseases function in populations that have a high prevalence of helminth infection? Infection with helminth parasites causes immune suppression and a CD4+ Th2 skewing of the immune system, thereby impairing Th1-type vaccine efficacy. In this study, we conduct HIV vaccine trials in mice with and without chronic helminth infection to mimic the human vaccine recipient populations in Sub-Saharan Africa and other helminth parasite endemic regions of the world, as there is large overlap in global prevalence for HIV and helminth infection. Here, we demonstrate that Listeria monocytogenes functions as a vaccine vector to drive robust and functional HIV-specific cellular immune responses, irrespective of chronic helminth infection. This observation represents a significant advance in the field of vaccine research and underscores the concept that vaccines in the developmental pipeline should be effective in the target populations.     

Novel method for non-invasive induction of a middle-ear biofilm in the rat

Otitis media and other middle ear diseases are extremely common among all children worldwide. Chronic otitis media is strongly associated with the presence of a bacterial middle ear biofilm, which if left untreated, may result in hearing loss or delays in the development of speech and language. Many animal models and methods used to study the progression of various middle ear diseases exist. However, there are no reported approaches to biofilm induction in which this infectious process can be investigated. Here we report a unique, non-invasive method of biofilm induction in the rat through repeated bacterial inoculations and pressure changes within the ear.     

Serum hepatitis B surface antigen correlates with fibrosis and necroinflammation: A multicentre perspective in China

The kinetics of serum hepatitis B surface antigen (HBsAg) during the natural history of hepatitis B virus (HBV) infection has been studied, but the factors affecting them remain unclear. We aimed to investigate the factors affecting HBsAg titres, using data from multicentre, large‐sized clinical trials in China. The baseline data of 1795 patients in 3 multicentre trials were studied, and the patients were classified into 3 groups: hepatitis B early antigen (HBeAg)‐positive chronic HBV infection (n = 588), HBeAg‐positive chronic hepatitis B (n = 596), and HBeAg‐negative chronic hepatitis B (n = 611). HBsAg titres in the different phases were compared, and multiple linear progression analyses were performed to investigate the implicated factors. HBsAg titres varied significantly in different phases (P = .000), with the highest (4.60 log10 IU/mL [10%‐90% confidence interval: 3.52 log10 IU/mL‐4.99 log10 IU/mL]) in patients with HBeAg‐positive chronic HBV infection. In all phases, age and HBV DNA were correlated with serum HBsAg level. In HBeAg‐positive chronic hepatitis B patients, a negative correlation between HBsAg titres and fibrosis stage was observed. Alanine amonitransferase or necroinflammatory activity was also correlated with HBsAg titres in HBeAg‐negative chronic hepatitis B patients. In conclusion, decreased HBsAg titres may be associated with advancing fibrosis in HBeAg‐positive chronic hepatitis B patients or increased necroinflammation in those with HBeAg‐negative chronic hepatitis B. Our findings may help clinicians better understand the kinetics of HBsAg and provide useful insights into the management of this disease.