Liver tissue engineering and cell sources: issues and challenges

Liver diseases are of major concern as they now account for millions of deaths annually. As a result of the increased incidence of liver disease, many patients die on the transplant waiting list, before a donor organ becomes available. To meet the huge demand for donor liver, alternative approaches using liver tissue engineering principles are being actively pursued. Even though adult hepatocytes, the primary cells of the liver are most preferred for tissue engineering of liver, their limited availability, isolation from diseased organs, lack of in vitro propagation and deterioration of function acts as a major drawback to their use. Various approaches have been taken to prevent the functional deterioration of hepatocytes including the provision of an adequate extracellular matrix and co‐culture with non‐parenchymal cells of liver. Great progress has also been made to differentiate human stem cells to hepatocytes and to use them for liver tissue engineering applications. This review provides an overview of recent challenges, issues and cell sources with regard to liver tissue engineering.     

PROTEIN KINASE C AND TRANSMITTER RELEASE

1. Protein kinase C (PKC) is an important second messenger-activated enzyme. In noradrenergic nerves it appears to be tonically activated by diacylglycerol (DAG) to facilitate transmitter release and the steps in this involve activation of phospholipase C, generation of DAG and activation of PKC. It is suggested that the subsequent facilitation of transmitter release is due to the phosphorylation of proteins involved in the release process distal to Ca²⁺entry, presumably those involved in vesicle dynamics. 2. There are differences between central noradrenergic neurons and sympathetic nerves. In central neurons PKC appears to be tonically active and its inhibition results in a decrease in noradrenaline release under most, if not all, conditions. 3. In sympathetic nerves PKC inhibitors only decrease transmitter release during high-frequency stimulation and not during low-frequency stimulation. At high frequency there is a gradual increase in the effect of PKC inhibitors on transmitter release during the first 15 s of a stimulation train. It is suggested that this is due to a progressive rise in intracellular Ca²⁺ and a consequent activation of PKC. 4. Activation of PKC by phorbol esters produces a large enhancement in action potential-evoked noradrenaline release in both the central nervous system and in peripheral tissues. The structural requirements of the phorbol esters for maximal effect suggest that the phorbol esters must access the interior of the nerve terminal to activate PKC and the neural membrane acts as a barrier for highly lipophilic phorbol esters, thereby reducing their activity. Activation of PKC represents one of the most powerful ways to enhance transmitter release and may have therapeutic potential.     

血清白细胞介素-8与溃疡性结肠炎的关系

背景:炎症细胞因子在溃疡性结肠炎（UC）的发病中可能起一定作用。目的:检测UC患者的血清白细胞介素（IL）-8含量,并分析其与UC病变范围、病变程度和复发与否的关系。方法:收集64例经内镜检查证实的UC患者的血清标本,用酶联免疫吸附测定（ELISA）检测IL-8含量,并与正常对照组进口比较。结果:UC患者的血清IL-8含量为685pg/ml±790pg/ml,正常对照组为25pg/ml±21pg/ml（P<0.000）。不同病变范围UC的血清IL-8含量分别为:愈合期病变289pg/ml±373pg/ml,直肠病变499pg/ml±736pg/ml,直乙状结肠病变686pg/ml±755pg/ml,左半结肠病变 1407pg/ml±846pg/ml,全结肠病变815 pg/ml±926pg/ml;左半结肠病变者的IL-8含量最高,与愈合期和直肠病变者相比有显著差异（P<0.01）。不同病咎程度UC的血清IL-8含量分别为:0级267pg/ml±364pg/ml,1级332pg/ml±418pg/ml,2级999pg/ml±943pg/ml,3级894pg/ml±851pg/ml;2级和3级病变者的含量较0级和1级病变者明显增高（P<0.05和P<0.01）,0级者的含量亦高于正常对照组（P<0.01）。初发患者的血清IL-8含量为758pg/ml±833pg/ml,与复发患者（696pg/ml±803pg/ml）相比无显著差异（p=0.77）。19例患者在正规5-氨基水杨酸（5-ASA）制剂治疗前后分别测定了血清IL-8含量,治疗前的IL-8含     

Carotid artery stump pressure and associated neurological changes in predominantly symptomatic carotid artery disease patients undergoing awake carotid endarterectomy

Aim

To determine the mean carotid artery stump pressure (SP) at which patients develop neurological changes while undergoing awake carotid artery endarterectomy (CEA) under cervical block anaesthesia (CBA).

Methods

A prospective analysis was carried out of patients undergoing awake CEA under CBA between February 2004 and April 2007. All patients had mean SP measured, with selective shunting on those who developed neurological symptoms on carotid artery clamping regardless of stump pressure. A ball connected to a pressure sensor was put in the patient’s contra-lateral hand.

Results

Fifty-nine patients had awake CEA, 40 were males with a mean age of 64 years. Indications for CEA were asymptomatic high-grade stenosis in 12 (20%) patients and symptomatic stenosis in 47 (80%). Seven (12%) patients required shunting, one for transient ischaemic attack (TIA) and six for loss of consciousness. Six of these patients had presented with symptomatic disease.Taking the threshold of mean carotid SP of 50 mmHg as an indication for shunting, 22% (6/27) of patients with a mean SP of < 50 mmHg required shunting and only 3% (1/32) with a mean carotid SP of > 50 mmHg needed a shunt. This was not statistically significant. Using a mean carotid SP of ≤ 40 mmHg as the threshold for shunting, 40% (4/10) of patients required shunting and 3% (1/31) with a mean carotid SP of > 40 mmHg required shunting. This was statistically significant. Thirteen (22%) patients were complicated by transient hoarseness of voice. One (2%) had a haematoma that required re-exploration. None of these patients had any major postoperative neurological or cardiological complications.

Conclusion

Even though the sample in this study was small, awake CEA under local anaesthesia was seen as a safe procedure. It would appear to be safe to use the mean SP of 40 mmHg as a threshold for selective shunting in CEA under general anaesthesia.     

Suppression of transfusion-related alloimmunization in intensively treated cancer patients

A retrospective review of HLA antibody testing and transfusion records of 100 cancer patients who required extensive platelet support revealed that 27 of 100 patients exhibited positive HLA antibody tests; only 13 remained positive on repetitive examination, while 88% of aplastic anemia patients so tested were positive. Sixty-five patients with leukemia, 16 with Ewing's sarcoma, and 19 with recurrent undifferentiated lymphoma were studied. Each patient received at least 10 U of platelets (mean of 72). HLA antibodies were detected in 31% (20/65) of the leukemias, 12% (2/16) of the Ewing's, and 26% (5/19) of the lymphoma patients. Fourteen of the 27 patients who developed antibodies became antibody negative again within 2 mo and remained so. There were no significant differences in quantity of platelet transfusions between antibody-negative patients and alloimmunized patients. A smaller group (n = 8) of aplastic anemia patients followed at the NCl exhibited a frequency of alloimmunization of 88% (7/8) after a mean of 44 U of platelets were transfused. Granulocyte transfusions given therapeutically for granulocytopenia and documented infection did not appear to influence HLA antibody formation. These data indicate that significant immunosuppression occurs in intensively treated cancer patients, as measured by their ability to from antibodies to HLA antigens expressed on the surface of transfused platelets.     

Load transfer in tilted implants with varying cantilever lengths in an all‐on‐four situation

Background: The aim of this study was to evaluate if tilting of the distal implant at different angulations (30° and 40°) with different cantilever lengths (4 mm and 12 mm) affects the stress and strain distribution in an ‘all‐on‐four’ situation. Methods: A completely edentulous mandible was modelled with four tapered implants placed within the interforaminal region to receive an all acrylic fixed prosthesis. The two posterior implants were tilted at an angle of 30° and 40°. The prosthesis cantilever was given two different variables of 4 mm and 12 mm. For all models, the equivalent von Mises stress and strain was analysed using three‐dimensional finite element analysis. Results: Statistical significance (p < 0.05) was seen when a comparison was made for the stress developed on the implant and cortical bone between the 30° and 40° distally tilted posterior implants in both situations. No significance was seen in the trabecular bone and on the strain developed in these situations. Conclusions: The study shows that increasing the tilt of the distal implants does not increase the stress significantly. It also shows that the architecture of the mandible plays a major role during treatment planning of a completely edentulous patient.     

单道心电图机在社区医疗服务中的功能扩展

介绍了单道心电图机在社区医疗服务中功能扩展的设计思想,实施方案,并展望其应用前景。