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.     

Prevalence of dental trauma in Pan American Games athletes

Abstract – The aim of this cross‐sectional epidemiological survey was to assess the prevalence of dental trauma in athletes representing 42 countries competing at the most recent Pan American Games (XV Pan Am) held in Rio de Janeiro, Brazil in July of 2007, and to determine prior use and type of mouthguard among this group of athletes. The examiners participated in standardization and calibration training sessions before the field phase began. Invitations were sent to >5500 participating athletes competing in 41 sports and to the Medical Committee of the Pan American Sports Organization before and during the XV PAN. A convenience sample of 409 athletes was recruited. After signing an informed consent, all athletes answered a questionnaire. Data were collected at the clinical examination and recorded on a specific trauma form. The mean age of the athletes was 24.4 ± 5.3 years. Males comprised 55% of the sample; females 45%. The prevalence of dental trauma among the athletes was 49.6% (n = 203) with no gender‐based differences. Most of these injuries (63.6%) were related to activities during training or competition. Sports with the highest injury prevalence were wrestling (83.3%), boxing (73.7%), basketball (70.6%) and karate (60%). The most common injury was enamel fracture (39.8%); root fracture was the least common (0.4%). The teeth most affected were the maxillary permanent central incisors (n = 113), followed by the mandibular central incisors (n = 19). Based on the results of this study, nearly one‐half of the subjects had experienced previous dental trauma; the majority related to sports activities. Furthermore, only 17% of the athletes reported prior mouthguard use; the most frequent mouthguards reported were boil‐and‐bite. These results suggest the importance of enhanced educational efforts and the use of properly fitted mouthguards to reduce dental trauma among athletes in international sports competition, especially in sports where mouthguards are not mandatory.     

Busulfan and melphalan as consolidation therapy with autologous peripheral blood stem cell transplantation following Children's Oncology Group (COG) induction platform for high‐risk neuroblastoma: Early results from a single institution

Bu‐Mel as preparative therapy prior to autologous stem cell rescue was recently shown to be superior to the conventional CEM regimen for HR NBL in Europe. There are no data available on the feasibility and toxicity of Bu‐Mel as consolidation therapy following the COG‐type induction regimens used in North America. We report early complications and outcomes of patients with HR NBL who received Bu‐Mel for consolidation following COG‐based induction. Retrospective analysis of all patients who had received Bu‐Mel as preparative regimen prior to stem cell rescue for HR NBL was carried out. Toxicity, outcomes, and any delays to receiving radiation or anti‐GD2 antibody therapy were analyzed. Six patients undergoing PBSCT had received Bu‐Mel. The treatment was well tolerated. Mucositis was the main toxicity; three patients had developed neutropenia fever and none developed pulmonary toxicity. One patient had developed moderate SOS that responded to conservative management. All patients were able to receive and tolerate post‐transplant local radiotherapy and ch.14.18 anti‐GD2 antibody therapy without any delays. All patients are alive with no disease recurrence. The Bu‐Mel regimen is well tolerated and is feasible post‐COG‐type induction platform.     

Identification of Novel ROR2 Gene Mutations in Indian Children with Robinow Syndrome

Ob­jec­ti­ve: Robinow syndrome (RS) is an extremely rare genetic disorder characterized by short-limbed dwarfism, defects in vertebral segmentation and abnormalities in the head, face and external genitalia. Mutations in the ROR2 gene cause autosomal recessive RS (RRS) whereas mutations in WNT5A are responsible for the autosomal dominant (AD) form of RS. In AD Robinow patients, oral manifestations are more prominent, while hemivertebrae and scoliosis rarely occur and facial abnormalities tend to be milder.Methods: Three unrelated patients from different parts of India were studied. These patients were diagnosed as RRS due to presence of characteristic fetal facies, mesomelia, short stature, micropenis, hemivertebrae and rib abnormalities. One of the patients had fetal facies and micropenis but unusually mild skeletal features. This patient’s mother had mild affection in the form of short stature and prominent eyes. Testosterone response to human chorionic gonadotropin was investigated in two patients and were normal. The exons and exon-intron boundaries of the ROR2 gene were sequenced for all probands. Bioinformatics analysis was done for putative variants using SIFT, PolyPhen2 and Mutation Taster.Results: Patients 1, 2 and 3 were homozygous for c.G545A or p.C182Y in exon 5, c.227G>A or p.G76D in exon 3 and c.668G>A or p.C223Y in exon 6 respectively. Prenatal diagnosis could be performed in an ongoing pregnancy in one family and the fetus was confirmed to be unaffected. Conclusion: ROR2 mutations were documented for the first time in the Indian population. Knowledge of the molecular basis of the disorder served to provide accurate counseling and prenatal diagnosis to the families.     

Adaptations of Mouthguards for Patients with Special Needs

The adaptations and applications of mouthguard appliances are many and varied, with uses ranging from protective to therapeutic. These modifications serve the individual needs of patients. This requires problem‐solving based on combining form and function with the skills of the dentist.     

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.