Overcoming scarring in the urethra: Challenges for tissue engineering.

Urethral stricture disease is increasingly common occurring in about 1% of males over the age of 55. The stricture tissue is rich in myofibroblasts and multi-nucleated giant cells which are thought to be related to stricture formation and collagen synthesis. An increase in collagen is associated with the loss of the normal vasculature of the normal urethra. The actual incidence differs based on worldwide populations, geography, and income. The stricture aetiology, location, length and patient's age and comorbidity are important in deciding the course of treatment. In this review we aim to summarise the existing knowledge of the aetiology of urethral strictures, review current treatment regimens, and present the challenges of using tissue-engineered buccal mucosa (TEBM) to repair scarring of the urethra. In asking this question we are also mindful that recurrent fibrosis occurs in other tissues-how can we learn from these other pathologies

Aging is Associated with Reductions in Fascicle Length, Sarcomere Length and Serial Sarcomere Loss

Introduction: Aging is associated with decreased active force production leading to muscle weakness and subsequently decreased muscle performance. Aging also affects the muscle’s passive force properties; whereby in old age passive muscle force has been shown to be elevated above that of young, which may be related to increased muscle stiffness with age.  The purpose of this study was to investigate potential structural property changes that occur in aged muscle that may contribute to increased passive force. Methods: The muscle length where peak force occurred (i.e. plateau of the force-length relationship (FL); L0) was determined for the medial gastrocnemius muscle (MG) of young (n = 9) and old rats (n = 8) rats. Muscles were fixed at L0 in 10% formalin, fascicle length, sarcomere number and the sarcomere length were compared at L0. Results: Muscle from old rats showed a reduction of ~14% in fascicle length, ~4% in sarcomere length and  ~10% in sarcomere number, (P < 0.001). Discussion: Shorter fascicles and reduced sarcomeres in series in muscle from old rats may explain increased passive forces in older individuals. Reduced sarcomere number in series would lead to overstretched sarcomeres, leading to increased tension on sarcomere passive force structures and sarcomeres operating on the descending limb of FL relationship

An Improved In Vivo Methodology to Visualise Tumour Induced Changes in Vasculature Using the Chick Chorionic Allantoic Membrane Assay

Background/Aim: Decreasing the vascularity of a tumour has proven to be an effective strategy to suppress tumour growth and metastasis. Anti-angiogenic therapies have revolutionized the treatment of advanced-stage cancers, however there is still demand for further improvement. This necessitates new experimental models that will allow researchers to reliably study aspects of angiogenesis. The aim of this study was to demonstrate an in vivo technique in which the highly vascular and accessible chorioallantoic membrane (CAM) of the chick embryo is used to study tumour-induced changes in the macro and microvessels. Materials and Methods: Two cancer cell lines (human melanoma (C8161) and human prostate cancer (PC3)) were selected as model cells. Human dermal fibroblasts were used as a control. One million cells were labelled with green fluorescent protein and implanted on the CAM of the chick embryo at embryonic development day (EDD) 7 and angiogenesis was evaluated at EDDs 10, 12 and 14. A fluorescently-tagged lectin (lens culinaris agglutinin (LCA)) was injected intravenously into the chick embryo to label endothelial cells. The LCA is known to label the luminal surface of endothelial cells, or dextrans, in the CAM vasculature. Macrovessels were imaged by a hand-held digital microscope and images were processed for quantification. Microvessels were evaluated by confocal microscopy. Tumour invasion was assessed by histological and optical sectioning. Results: Tumour cells (C8161 and PC3) produced quantifiable increases in the total area covered by blood vessels, compared to fibroblasts when assessed by digital microscopy. Tumour invasion could be demonstrated by both histological and optical sectioning. The most significant changes in tumour vasculature observed were in the microvascular structures adjacent to the tumour cells, which showed an increase in the endothelial cell coverage. Additionally, tumour intravasation and tumour thrombus formation could be detected in the areas adjacent to tumour cells. The fragility of tumour blood vessels could be demonstrated when tumour cells seeded on a synthetic scaffold were grown on CAM. Conclusion: We report on a modification to a well-studied CAM in vivo assay, which can be effectively used to study tumour induced changes in macro and microvasculature

Psychological Morbidity and Expressed Motivation in Patients Requesting Rhinoplasties and Research Portfolio

Research was undertaken to assess psychological morbidity, expressed motivation and expectations of surgery in individuals (n=50) who had requested cosmetic rhinoplasties. Subjects participated in semi-structured interviews, completed three questionnaires and were categorised on their appearance by two means. Hypotheses were made for the total subject population and for differences according to gender and independently-rated severity of nasal disfigurement. Results supported some hypotheses, with subjects indicating higher anxiety and neuroticism, and lower extraversion and self-esteem than normed scores. Although less disfigured subjects appeared to show greater neuroticism and lower self-esteem, this relationship was not statistically significant (p<.05). Other hypotheses were not supported, as subjects did not meet clinical 'caseness' for depression, and males did not appear to be significantly more psychopathological on any measures and scored significantly lower neuroticism than females. Results should be interpreted with caution due to small subgroup sizes in the sample

Genetic effects from an Afrikaner, Bonsmara, and Nguni three-breed diallel and top-crosses of Angus and Simmental sires

Individual and maternal breed additive effects and heterosis exist for most economically important traits in cattle. Crossbreeding may therefore be valuable for emerging and commercial beef farmers in improving the productivity of their herds. Calves were produced by mating Afrikaner, Bonsmara and Nguni cows to Afrikaner, Bonsmara, Nguni, Angus and Simmental bulls. The cows used were from Vaalharts Research Station or were purchased from other herds. Data were collected over three years. Individual and maternal additive effects and individual heterosis were estimated simultaneously as continuous linear variates. The estimated genetic effects were then used to predict production levels that may be achieved through implementation of top-cross, two-breed rotation, and terminal sire crossbreeding systems. The individual estimates of the genetic effects were relatively small and in most cases were not different from zero, with the exception of the maternal additive effects of Nguni on preweaning traits and their individual additive effect on cow weight, which were less than those of Bonsmara. However, the alternative crossbreeding systems differed across traits. The straight-bred breeding system was least efficient, followed by the crisscross system (+2%) and the terminal sire system that utilized Simmental (+4%), with the terminal sire system utilizing Angus being on average most efficient (+8%). The inter-generational genetic differences in cow weight that resulted from the use of different breeds of sire increased its standard deviation by 5 to 6% in rotational crossing. Despite the relatively small magnitude of the genetic effects, advantages of crossbreeding systems became evident.Keywords: breed additive, crossbreeding, heterosis, post-weaning, pre-weanin