275 research outputs found
Iron-Catalyzed, Highly Regioselective Synthesis of alpha-Aryl Carboxylic Acids from Styrene Derivatives and CO2
The relationship between food deprivation and blood glucose at induction of anaesthesia in juvenile pigs
The effect of recumbency and hindlimb position on the lumbosacral interlaminar distance in dogs: a cadaveric computed tomography study
Cellular and molecular mechanisms of liver regeneration
Improved understanding of how the liver regenerates would be of great value, particularly
given the dearth of therapies for end-stage liver disease. Currently, the only effective
treatment for total liver failure is transplantation. Such an invasive, costly and specialised
intervention is unable to address the enormous global impact from diseases of the liver.
Ironically, the liver has the greatest regenerative potential of any organ in the mammalian
body. However, this capacity for repair is overwhelmed in the face of massive or repeated
injury. Understanding the key factors driving or inhibiting successful liver regeneration offers
the potential for novel, targeted therapies to promote regeneration of a patientâs own liver.
Animal models are widely used when studying complex, dynamic, multicellular
processes such as liver injury and regeneration. Continued progress in transgenic
modification of mice, combined with ongoing advances in microscopy techniques, means that
the opportunity now exists to observe labelled cells, and subcellular structures, in real time
and in vivo, with previously unobtainable resolution and fidelity. Not only does this afford
the opportunity for novel insights into both normal physiology and the response to injury or
disease, it can vastly expand the amount of biologically relevant information that can be
obtained from each experimental animal. Hence, it is possible to advance scientific knowledge
and reduce experimental animal use simultaneously.
This thesis examines the role of αv integrins in liver regeneration. Integrins are expressed
on the surface of cells and can perform a range of functions, including signalling and
extracellular matrix adhesion. The most well-characterised role for αv integrins is activation
of transforming growth factor beta, a molecule which has been shown to inhibit hepatocyte
proliferation and liver regeneration. Partial hepatectomy was used as an experimental model
of liver injury and regeneration. It was performed in mice, in which one or more αv integrins
had been genetically depleted from specific cell types in the liver, namely hepatocytes, hepatic
stellate cells or liver sinusoidal endothelial cells. These investigations revealed that depletion
of integrin αvÎČ8 from hepatocytes led to increased hepatocyte proliferation and accelerated
liver regeneration. The possible mechanisms through which hepatocyte integrin αvÎČ8 may
exert its braking effect on liver regeneration following injury were also explored.
In parallel, a novel experimental system to permit intravital multiphoton microscopy of
the regenerating liver following partial hepatectomy in mice was developed and validated.
Intravital imaging of mouse liver was performed with a range of cellular labels, combined
with a fluorescent cell cycle reporter and label-free imaging modalities. This demonstrated the
enormous potential of the system to study the dynamics of hepatocytes and non-parenchymal
cells in the regenerative niche, reconstruct the sinusoidal vascular network in three
dimensions during angiogenesis, and measure sinusoidal blood flow and parenchymal lipid
deposition. Advances in experimental animal models such as this drive forward our
understanding of the cellular and molecular mechanisms of liver regeneration whilst refining
and reducing experimental animal use. Novel insights into the process of liver regeneration
will permit the development of innovative therapeutic strategies to allow this remarkable
organ to heal itself even in the face of massive or sustained insult
Premature recovery from general anaesthesia in an adult Limousin bull
This case report describes the premature and unanticipated recovery of a bull from general anaesthesia for penile surgery. Retrospective review revealed: (i) the elements of case management that contributed to this critical event; and (ii) other measures that allowed prompt control, thus minimising risk to the subject and personnel. The case highlights the challenges of monitoring depth of anaesthesia in large ruminants and illustrates that nonâsurgical stimuli such as hoisting can be equally, if not more, stimulating than surgery itself. Finally, practical recommendations are made to: (i) reduce the likelihood of this problem recurring; and (ii) limit the risk of harm to patient or personnel if it does
Premature recovery from general anaesthesia in an adult Limousin bull
This case report describes the premature and unanticipated recovery of a bull from general anaesthesia for penile surgery. Retrospective review revealed: (i) the elements of case management that contributed to this critical event; and (ii) other measures that allowed prompt control, thus minimising risk to the subject and personnel. The case highlights the challenges of monitoring depth of anaesthesia in large ruminants and illustrates that nonâsurgical stimuli such as hoisting can be equally, if not more, stimulating than surgery itself. Finally, practical recommendations are made to: (i) reduce the likelihood of this problem recurring; and (ii) limit the risk of harm to patient or personnel if it does
Iron-catalysed, hydride-mediated reductive cross-coupling of vinyl halides and Grignard reagents
An Exploratory Analysis of the Role of Adipose Characteristics in Fulltime Wheelchair Usersâ Pressure Injury History
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