Generation of therapeutic dendritic cells and regulatory T cells for preventing allogeneic cardiac graft rejection

Tolerogenic dendritic cells (Tol-DCs) and regulatory T cells (Treg) are key factors in the induction and maintenance of transplantation tolerance. We previously demonstrated that ex vivo-isolated Tol-DCs promote Treg generation, and vice versa, in an in vitro co-culture system. Here we demonstrate the occurrence of such an immune regulatory feedback loop in vivo. Tol-DC generated in vitro by treatment with LF 15-0195 exhibited features of immature DC and express low levels of MHC class II, CD86 and CD40. These Tol-DCs were capable of augmenting CD4⁺CD25⁺CTLA4⁺ and FoxP3⁺ Treg cell numbers and activity in cardiac allograft recipients. On the other hand, Tol-DCs possessed an ability to generate Treg cells in vitro. The adoptive transfer of these in vitro-generated Treg cells resulted in an increase of Tol-DC in vivo, suggesting that an immune regulatory feedback loop, between Tol-DC and Treg, exists in vivo. Furthermore, the administration of in vitro-generated Tol-DCs or Treg cells prevented rejection of allografts. Co-administration of Tol-DC and Treg synergized efficacy of promoting allograft survival heart transplantation. The present study highlights the therapeutic potential of preventing allograft rejection using in vitro-generated Tol-DCs and Treg.     

Mechanical evaluation of cervical glass-ionomer restorations: 3D finite element study

OBJECTIVES: The aim of this paper was to investigate the influence of lesion shape and depth as well as the direction of occlusal loading on the mechanical response of cervical GIC restorations. METHODS: A finite element model of a lower first premolar was created. Both wedged and rounded lesions were then modelled with incremental depth after which the tooth was loaded at different angles. First principal stress (tension) was employed as an indicator of material failure, by contrasting our calculated stresses with the ultimate tensile strength of the GIC and known values of bond strength between material and tooth substrate. RESULTS: Obliquely loaded teeth exhibited significantly higher tensile stress in the cervical region of the restoration. For forces inclined at angles of 30 degrees and higher to the vertical tooth axis, the tensile stresses in the cervical margin of the restoration exceeded the ultimate material and bond strength. In contrast, lesion shape and depth have only a minor influence on tensile stress development. CONCLUSIONS: Lesion depth and shape are not of primary concern from a mechanical perspective for a restorative treatment decision. By contrast, occlusal diagnosis and subsequent re-adjustments of tooth contacts do form a critical part of the treatment of non-carious cervical lesions (NCCLs).     

Lamotrigine Compared with Lithium in Mania: A Double-Blind Randomized Controlled Trial

Background: Preliminary data from case reports and small open trials suggest a role for lamotrigine in the treatment of bipolar disorder, although controlled data for the manic phase are lacking. Method: Thirty inpatients with a DSM-IV diagnosis of bipolar I disorder, currently manic, were randomly allocated to receive either lamotrigine (25 mg once daily for 1 week, 50 mg once daily for the second week, and 100 mg once daily for the last 2 weeks) or lithium (400 mg twice daily) in a 4-week randomized, double-blind, clinical trial. Results: Both treatments improved symptoms of mania, as assessed by the Mania Rating Scale, Brief Psychiatric Rating Scale, Clinical Global Impression severity and improvement scales, and the Global Assessment of Functioning scale. There were no significant differences between groups at any time point, suggesting that the dose escalation required for lamotrigine did not adversely affect its onset of action. Secondary outcome measures, including the use of lorazepam as rescue medication, did not differ between the groups. No significant adverse events were noted in either group. Conclusion: In this pilot study, lamotrigine was as effective as lithium in the treatment of patients with bipolar disorder hospitalised for acute mania.     

自体骨髓干细胞移植治疗心力衰竭的研究进展

细胞移植已为病损心脏细胞重建及衰竭心脏功能恢复提供了一种全新的治疗方法。骨髓干细胞具有自我更新、定向分化成为包括心肌细胞等多种组织细胞的潜能,其增殖分化能力能持续终生,已成为细胞移植治疗心力衰竭的主要细胞源。本文就自体骨髓干细胞治疗心力衰竭可行性、与其他移植细胞相比较的优势、临床应用现状及目前问题与展望作一综述。     

Analysis of experimental cranial skin wounding from screwdriver trauma

As part of a more extensive investigation of skin wounding mechanisms, we studied wounds created by five common screwdrivers (straight, star, square or Robertson, Posidriv and Phillips) on the shaven foreheads of 12 freshly slaughtered pigs. We fixed the different screwdriver heads to a 5-kg metal cylinder which was directed vertically onto each pig head by a droptube of 700 mm length. We examined skin lesions by photography and also by scanning electron microscopy (SEM). Our evaluation of differences in wound shape and size was based on geometric morphometric methods. Our results show that there are obvious morphological differences between the straight head and the other types. The straight-headed screwdriver penetrates the skin by a mode II crack which results in a compressed skin plug with bundles of collagen fibres forming skin tabs within the actual wound. The sharper-tipped screwdrivers wedge open the skin (mode I), with a clearly defined edge with no skin plugs. Geometric morphometric analysis indicates that shapes of skin wounds created by the five screwdriver types could be classified into three different groups. The straight head results in the most differentiated wound profile, with the Robertson or square and some specimens of star, and also the Posidriv and Phillips giving similar wound outlines. SEM evaluation of wounds created by a new and worn straight-head screwdrivers shows that the outline of the worn screwdriver head is reflected in the shape of the wound it created.     

Non-Hodgkin lymphoma response evaluation with MRI texture classification

Background

Liver cancer is a common malignancy with a high mortality rate. Given the poor prognosis associated with this cancer, many patients seek additional therapies that may improve quality of life or survival. Several Traditional Chinese Medicines (TCM) have been evaluated in clinical trials, but little is known about them outside of China.

Methods

We searched independently and in duplicate 8 electronic databases, including 2 Chinese language databases, until February 2009. We included any randomized clinical trials (RCT) evaluating a TCM oral preparation for the treatment of hepatocellular cancers. We abstracted data on survival, tumor response, and performance scores. We conducted a random-effects meta-analysis and applied a meta-regression analysis.

Results

We included 45 RCTs (n = 3,236). All studies employed an active control group. In general, the reporting of methodological issues was poor. We analyzed data from 37 trials reporting on complete response effects score (Relative Risk [RR] of 1.26 (95 CI, 1.04–1.52, P = 0.01, I² = 0%, P = 0.99). Products containing ginseng, astragalus and mylabris had a larger treatment effect (OR 1.34, 95% CI, 1.04–1.71, P = 0.01) than the pooled broad estimate, also the case for astragalus-based treatments (OR 1.35, 95% CI, 1.001–1.80. P = 0.048). We examined survival rates and pooled 15 studies reporting on 6 month outcomes (RR 1.10, 95% CI, 1.04–1.15, P = < 0.0001, I² = 0%, P = 0.60). This effect was consistent at other prospective dates, including 12 months (22 trials, RR 1.26, 95% CI, 1.17–1.36, P = < 0.0001, I² = 7%, P = 0.36), 24 months (15 trials, 1.72, 95% CI, 1.40–2.03, P = < 0.0001, I² = 0%, P = 0.75); and, at 36 months (8 trials, RR 2.40, 95% CI, 1.65–3.49, P = < 0.0001, I² = 0%, P = 0.62).

Limitations

All included trials were conducted in China where emerging evidence suggests many RCTs are not, in fact, randomized. Publication bias may exist, favouring positive reports.

Conclusion

Our meta-analysis displays compelling evidence of effectiveness for hepatocellular cancers that should be evaluated in high-quality and transparent clinical trials.