摘要:

The use of stem cells in cell replacement therapy for neurodegenerative diseases has received a great deal of scientific and public interest in recent years. This is due to the remarkable pace at which paradigm-changing discoveries have been made regarding the neurogenic potential of embryonic, fetal, and adult cells.Over the last decade, clinical fetal tissue transplants have demonstrated that dopaminergic neurons can survive long term and provide functional clinical benefits for patients with Parkinson's disease. Pluripotent embryonic stem cells and multipotent neural stem cells may provide renewable sources that could replace these primary fetal grafts. Considerable advancement has been made in generating cultures with high numbers of neurons in general and of dopaminergic neurons using a varied array of techniques. However, much of this encouraging progress still remains to be tested on long-term expanded human cultures. Further problems include the low survival rate of these cells following transplantation and the tumorigenic tendencies of embryo-derived cells. However, pre-differentiation or genetic modification of stem cell cultures prior to transplantation may help lead to the generation of high numbers of cells of the desired phenotype following grafting. Boosting particular factors or substrates in the culture media may also protect grafted neurons from oxidative and metabolic stress, and provide epigenetic trophic support.Possible endogenous sources of cells for brain repair include the transdifferentiation of various types of adult cells into neurons. Despite the excitement generated by examples of this phenomenon, further work is needed in order to identify the precise instructive cues that generate neural cells from many other tissue types, and whether or not the new cells are functionally normal. Furthermore, issues such as cell homogeneity and fusion need to be addressed further before the true potential of transdifferentiation can be known. Endogenous stem cells also reside in the neurogenic zones of the adult brain (ventricle lining and hippocampus). Further elucidation of the mechanisms that stimulate cell division and migration are required in order to learn how to amplify the small amount of new cells generated by the adult brain and to direct these cells to areas of injury or degeneration. Finally, a more fundamental understanding of brain injury and disease is required in order to circumvent local brain environmental restrictions on endogenous cell differentiation and survival.

ISSN:1173-8804    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

In patients with severe sepsis, thrombin has been implicated in the interrelationship between the coagulation and inflammation pathways. Thrombin is responsible for conversion of fibrinogen to fibrin (thrombus formation). Thrombin also activates endothelial cells, white blood cells and platelets. Regulation of both the coagulation and inflammation pathways is in part through the interaction of thrombin and activated protein C. Activated protein C has particular attributes that may inhibit microvascular thrombi, promote fibrinolysis and directly dampen the pro-inflammatory aspect of infection. In patients with severe sepsis, many investigators have demonstrated an active coagulopathic state, with low protein C levels. A phase III clinical trial has now demonstrated reduced mortality in patients with severe sepsis receiving activated protein C.

ISSN:1173-8804    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Microbial infection is sensed by Toll-like receptors (TLRs) on innate immune cells. Among the ten so far defined TLRs, TLR9 and its ligand are peculiar. TLR9 recognises bacterial DNA characterised by the abundance of unmethylated CpG dinucleotides, which distinguish bacterial DNA (CpG DNA) from mammalian DNA. Moreover, TLR9 shows a restricted cellular and subcellular pattern of expression. In contrast to other TLR agonists, CpG DNA is superior in activation of dendritic dells and induction of costimulatory cytokines such as interleukin (IL)-12 and IL-18. This qualifies CpG DNA as a Th1-promoting adjuvant. During infection, recognition of CpG DNA of intracellular pathogens skews and fine-tunes the ongoing immune response and induces long-lasting Th1 milieus. Thus, CpG DNA might play an important role in driving the immune system to a Th1 profile, preventing undesired Th2 milieus that might favour induction of allergic responses. Since CpG DNA can be synthesised with high purity and sequence fidelity, synthetic CpG DNA will become an important agent for Th1 instruction and be an effective adjuvant during vaccination.

ISSN:1173-8804    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

IntroductionThe increasing prevalence of antibiotic-resistant bacteria emphasises the need for new treatments that can replace traditional antibiotics. Oral immunotherapy with yolk antibodies from hyperimmunised hens is a new promising treatment strategy, primarily for infections in the mouth and gastrointestinal tract. Several studies show that bacterial and viral infections can be prevented with egg yolk immunoglobulin (IgY) in a dose-dependent manner. Oral treatment could potentially be used against many frequently encountered diseases (e.g. common cold, tonsillitis and caries).Group StudiedHealthy volunteers.Study DesignWe studied the presence of yolk anti-Pseudomonas aeruginosaantibodies in saliva from healthy volunteers over time after 1 or 2 minutes' mouth rinse, performed in the evening, with an aqueous IgY antibody preparation. The test persons rinsed the mouth with 8.0ml phosphate buffered saline before gargling with the antibody preparation 8 and 24 hours later. Statistical analysis was performed with the Mann-Whitney U test.MethodsThe antibody titres in the mouth rinses were tested for their specific activity againstP. aeruginosaby ELISA.Results and ConclusionThe next morning there were still active antibodies detected in the saliva from 18 of 19 subjects. After 24 hours, active antibodies could be detected in saliva from only a few of the subjects. A 2-minute mouth rinse resulted in higher mean ELISA absorbance values than a 1-minute rinse.

ISSN:1173-8804    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

The bilayered bioengineered skin substitute (BBSS) [Apligraf®] is used for the treatment of venous leg ulcers and diabetic foot ulcers. It has an epidermal layer formed from human keratinocytes and a dermal layer composed of human fibroblasts in a bovine type I collagen matrix. BBSS does not contain any antigen-presenting cells such as Langerhans cells, dermal dendritic cells, endothelial cells or leucocytes. In clinical trials, there was no evidence of clinical rejection and immunological tests indicated no humoral or cellular response to the keratinocytes or fibroblasts of BBSS. Further clinical trials are required to identify the exact mechanism of action of BBSS in chronic wounds.BBSS plus compression therapy was well tolerated and was superior in efficacy to compression therapy alone in a multicentre, randomised trial in patients with venous leg ulcers. At 6 months' follow-up, complete wound healing occurred in 63 versus 49% of patients and the median time to wound closure was 61 versus 181 days. In a subgroup of patients with hard-to-heal ulcers (>1 year's duration), wound healing was achieved in significantly more patients (47 vs 19%) and the median time to wound healing was significantly shorter (181 days vs not attained).In a multicentre, randomised trial, BBSS was well tolerated and effective in patients with full-thickness neuropathic diabetic foot ulcers. Ulcer healing occurred in significantly more patients (56 vs 38%) and the median time to wound healing was shorter (65 vs 90 days) with BBSS than with saline-moistened gauze at 12 weeks' follow-up. Patients in both groups also received standard diabetic foot care.The cost effectiveness of BBSS in patients with chronic ulcers has yet to be examined in well designed, prospective clinical trials. However, according to a modelled analysis incorporating data from a multicentre randomised trial, BBSS was cost effective in patients with hard-to-heal venous leg ulcers. The average annual medical cost of managing patients with ulcers of >1 year's duration was estimated to be $US20 041 per patient treated with BBSS plus compression therapy and $US27 493 per patient treated with compression therapy alone (1996 costs).ConclusionsClinical trials have shown that BBSS in conjunction with standard compression therapy was effective and well tolerated in patients with venous leg ulcers, especially patients with ulcers of >6 months' duration or that extended to the subcutaneous tissue. In addition, BBSS in conjunction with standard diabetic foot care was effective and well tolerated in patients with full-thickness neuropathic diabetic foot ulcers. BBSS represents a useful adjuvant to standard ulcer therapy in patients with venous leg ulcers or full-thickness neuropathic diabetic foot ulcers that do not respond to conventional ulcer therapy.

ISSN:1173-8804    

出版商:ADIS    

年代:2002

数据来源: ADIS