Clinical Phenotypes and Cellular Mediators in Diabetic Retinopathy

The aim of this work was to establish meaningful clinical end-points and surrogate markers for diabetic macular ischaemia, a condition for which there is no treatment. The relationship between diabetic eye disease and circulating cellular mediators of angiogenesis and inflammation was further explored with a view to developing therapy in the longer term. Visual loss in diabetic macular ischaemia was observed to occur only in moderate to severe disease, progresses at a rate of 5-10% increase in area per year and associated with thinning of the retinal nerve fibre layer. Direct visualisation of cells in the vitreous was achieved using optical coherence tomography. Novel methods for this were further developed in inflammatory eye disease, with a view for application in diabetic eye disease. A method for in vivo labelling of cells using ICG to enhance visualisation was described. In the field of regenerative medicine, this technique may allow direct visualisation of cell-mediated inflammation regardless of the type of cell or tissue transplanted. EPC and monocyte profiles were analysed in the context of diabetic eye disease. Elevated levels of EPCs as defined by CD34+ CD309+ were observed in diabetes, but no associations were observed with progression. There were no initial associations between monocyte subsets and diabetic eye disease severity at the outset but differences were observed in the context of progression. Observations from this work support the notion that inflammation plays an important role in diabetic eye disease and will inform development of new treatments in this field

Wear debris pseudotumor following total knee arthroplasty: a case report

<p>Abstract</p> <p>Introduction</p> <p>In patients who have undergone a total joint replacement, any mass occurring in or adjacent to the joint needs thorough investigation and a wear debris-induced cyst should be suspected.</p> <p>Case presentation</p> <p>An 81-year-old man presented with a painful and enlarging mass at the popliteal fossa and calf of his right knee. He had had a total right knee replacement seven years previously. Plain radiographs showed narrowing of the medial compartment. Magnetic resonance imaging showed a cystic lesion at the postero-medial aspect of the knee joint mimicking popliteal cyst or soft tissue sarcoma. Fine needle aspiration was non-diagnostic. A core-needle biopsy showed metallosis. Intraoperative findings revealed massive metallosis related to extensive polyethylene wear, delamination and deformation. Revision knee and patella arthroplasty was carried out after a thorough debridement of the knee joint.</p> <p>Conclusion</p> <p>Long-term follow-up is critical for patients with total joint replacement for early detection of occult polyethylene wear and prosthesis loosening. In these cases, revision arthroplasty may provide a satisfactory knee function.</p

Role of UCP1 gene variants in interethnic differences in the development of cardio-metabolic diseases

Cardio-metabolic diseases (CMDs) comprise a cluster of risk factors that contribute to chronic pathological conditions with adverse consequences for cardiovascular function and metabolic processes. A wide range of CMD prevalence rates among different ethnic groups has been documented. In view of accumulated evidence, there is a trend toward increasing CMD prevalence rates in Eastern Europe and Western Asia. Numerous studies have revealed an association between uncoupling protein 1 (UCP1) gene variants and CMDs. UCP1 activity is essential for brown adipose tissue (BAT)-mediated thermogenesis. Experimental animal studies and epidemiological studies in humans highlight the significance of BAT-mediated thermogenesis in protecting against obesity and maintaining a lean phenotype. We hypothesize that the genetic variation in UCP1 gene expression observed among different ethnic groups could contribute to the ethnic-specific predisposition to CMD development. Constructing such prevalence maps of UCP1 gene variants could contribute significantly into identifying high-risk ethnic groups predisposed to the development of CMDs, and further shaping public health policies by the improvement of existing preventive and management strategies

Neuron specific reduction in CuZnSOD is not sufficient to initiate a full sarcopenia phenotype

Our previous studies showed that adult (8 month) mice lacking CuZn-superoxide dismutase (CuZnSOD, Sod1KO mice) have neuromuscular changes resulting in dramatic accelerated muscle atrophy and weakness that mimics age-related sarcopenia. We have further shown that loss of CuZnSOD targeted to skeletal muscle alone results in only mild weakness and no muscle atrophy. In this study we targeted deletion of CuZnSOD specifically to neurons (nSod1KO mice) and determined the effect on muscle mass and weakness. The nSod1KO mice show a significant loss of CuZnSOD activity and protein level in brain and spinal cord but not in muscle tissue. The masses of the gastrocnemius, tibialis anterior and extensor digitorum longus (EDL) muscles were not reduced in nSod1KO compared to wild type mice, even at 20 months of age, although the quadriceps and soleus muscles showed small but significant reductions in mass in the nSod1KO mice. Maximum isometric specific force was reduced 8% to 10% in the gastrocnemius and EDL muscle of nSod1KO mice, while soleus was not affected. Muscle mitochondrial ROS generation and oxidative stress measured by levels of reactive oxygen/nitrogen species (RONS) regulatory enzymes, protein nitration and F2-isoprostane levels were not increased in muscle from the nSod1KO mice. Although we did not find evidence of denervation in the nSOD1KO mice, neuromuscular junction morphology was altered and the expression of genes associated with denervation (acetylcholine receptor subunit alpha (AChRα) and the transcription factors Runx1 and GADD45α) was increased, supporting a role for neuronal loss of CuZnSOD initiating alterations at the neuromuscular junction. These results and our previous studies support the concept that deficits in either the motor neuron or muscle alone are not sufficient to initiate a full sarcopenic phenotype and that deficits in both tissues are required to recapitulate the loss of muscle observed in Sod1KO mice

CuZnSOD gene deletion targeted to skeletal muscle leads to loss of contractile force but does not cause muscle atrophy in adult mice

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154374/1/fsb2027009015.pd

Chronic l-menthol-induced browning of white adipose tissue hypothesis: A putative therapeutic regime for combating obesity and improving metabolic health

Obesity constitutes a serious global health concern reaching pandemic prevalence rates. The existence of functional brown adipose tissue (BAT) in adult humans has provoked intense research interest in the role of this metabolically active tissue in whole-body energy balance and body weight regulation. A number of environmental, physiological, pathological, and pharmacological stimuli have been proposed to induce BAT-mediated thermogenesis and functional thermogenic BAT-like activity in white adipose tissue (WAT), opening new avenues for therapeutic strategies based on enhancing the number of beige adipocytes in WAT

Association of the 894G>T polymorphism in the endothelial nitric oxide synthase gene with risk of acute myocardial infarction

Background: This study was designed to investigate the association of the 894G>T polymorphism in the eNOS gene with risk of acute myocardial infarction (AMI), extent of coronary artery disease (CAD) on coronary angiography, and in-hospital mortality after AMI. Methods: We studied 1602 consecutive patients who were enrolled in the GEMIG study. The control group was comprised by 727 individuals, who were randomly selected from the general adult population. Results: The prevalence of the Asp298 variant of eNOS was not found to be significantly and independently associated with risk of AMI (RR = 1.08, 95%CI = 0.77–1.51, P = 0.663), extent of CAD on angiography (OR = 1.18, 95%CI = 0.63–2.23, P = 0.605) and in-hospital mortality (RR = 1.08, 95%CI = 0.29–4.04, P = 0.908). Conclusion: In contrast to previous reports, homozygosity for the Asp298 variant of the 894G>T polymorphism in the eNOS gene was not found to be associated with risk of AMI, extent of CAD and in-hospital mortality after AM