Role of mitochondrial uncoupling protein-4 in energy supply during neuronal differentiation

OBJECTIVES: Neuronal differentiation is involved in brain development. Stimulation of all-trans-retinoic acid (RA) in neuroblastoma cells results in growth inhibition, increased neuron-specific enolase (NSE) activity, and promoted axonal growth. Mitochondrial uncoupling protein-4 (UCP4) is ...published_or_final_versionThe 16th Medical Research Conference (MRC), Department of Medicine, the University of Hong Kong, Hong Kong, 22 January 2011. In Hong Kong Medical Journal, 2011, v. 17 suppl. 1, p. 31, abstract no. 4

Central Nervous System Inflammatory Demyelinating Disorders in the Hong Kong Chinese

Central nervous system inflammatory demyelinating disorders (CNS IDD) include classical multiple sclerosis, neuromyelitis optica (NMO) spectrum disorders, a single attack of/recurrent acute disseminated encephalomyelitis, a single attack of idiopathic acute transverse myelitis, optic neuritis (ON) and brainstem encephalitis. CNS IDD are potentially serious disorders with risks of mortality and significant disability. Typical relapsing forms of CNS IDD are relapsing remitting multiple sclerosis and relapsing NMO. Relapsing NMO is typified by recurrent longitudinally extensive transverse myelitis and severe unilateral or bilateral ON. Early diagnosis of CNS IDD is important as long-term treatment for different forms varies. Recognition of clinical, radiological and serological characteristics of different forms of CNS IDD facilitates early diagnoses. A significant proportion of NMO patients are seropositive for autoantibodies against aquaporin-4, the most abundant water channel in the CNS; this supports the hypothesis that NMO is an autoimmune disorder. Is NMO an autoantibody-mediated disorder sharing similar pathogenesis with myasthenia gravis (MG), a classical autoantibody-mediated autoimmune disease? An interesting observation is that paraneoplastic NMO associated various tumours is recognised recently, suggesting similarity with MG which is associated with thymoma in about 15 to 20% of patients.published_or_final_versio

Clinical outcome of relapsing remitting multiple sclerosis among Hong Kong Chinese

PosterBACKGROUND: Many relapsing remitting multiple sclerosis (RRMS) patients develop irreversible progressive neurological disability. Reported clinical outcome varied. We aimed to study clinical outcome of Chinese RRMS patients. METHODS: Only RRMS patients …published_or_final_versio

Plasma amyloid beta peptides and oligomers antibodies in Alzheimer's disease

INTRODUCTION: Various forms of amyloid beta (Aβ) including Aβ peptides, oligomers, protofibrils and fibrils are thought to be pathogenic in Alzheimer’s disease (AD). The exact pathophysiological role of endogenous Aβ autoantibodies (Ab) in healthy subjects and AD patients are uncertain. Potential protective role ...published_or_final_versio

Introduction of an electronic monitoring system for monitoring compliance with Moments 1 and 4 of the WHO "My 5 Moments for Hand Hygiene" methodology

Background: MedSense is an electronic hand hygiene compliance monitoring system that provides Infection Control Practitioners with continuous access to hand hygiene compliance information by monitoring Moments 1 and 4 of the WHO "My 5 Moments for Hand Hygiene" guidelines. Unlike previous electronic monitoring systems, MedSense operates in open cubicles with multiple beds and does not disrupt existing workflows.Methods: This study was conducted in a 6-bed neurosurgical intensive care unit with technical development and evaluation phases. Healthcare workers (HCWs) wore an electronic device in the style of an identity badge to detect hand hygiene opportunities and compliance. We compared the compliance determined by the system and an infection control nurse. At the same time, the system assessed compliance by time of day, day of week, work shift, professional category of HCWs, and individual subject, while the workload of HCWs was monitored by measuring the amount of time they spent in patient zones.Results: During the three-month evaluation phase, the system identified 13,694 hand hygiene opportunities from 17 nurses, 3 physiotherapists, and 1 healthcare assistant, resulting in an overall compliance of 35.1% for the unit. The per-indication compliance for Moment 1, 4, and simultaneous 1 and 4 were 21.3% (95%CI: 19.0, 23.6), 39.6% (95%CI: 37.3, 41.9), and 49.2% (95%CI: 46.6, 51.8), respectively, and were all statistically significantly different (p < 0.001). In the four 20-minute sessions when hand hygiene was monitored concurrently by the system and infection control nurse, the compliance were 88.9% and 95.6% respectively (p = 0.34), and the activity indices were 11.1 and 12.9 opportunities per hour, respectively. The hours from 12:00 to 14:00 had a notably lower compliance (21.3%, 95%CI: 17.2, 25.3) than nearly three quarters of the other periods of the day (p < 0.001). Nurses who used shared badges had significantly (p < 0.01) lower compliance (23.7%, 95%CI: 17.8, 29.6) than both the registered nurses (36.1%, 95%CI: 34.2, 37.9) and nursing officers (34.0%, 95%CI: 31.1, 36.9) who used named badges.Conclusion: MedSense provides an unobtrusive and objective measurement of hand hygiene compliance. The information is important for staff training by the infection control team and allocation of manpower by hospital administration. © 2011 Cheng et al; licensee BioMed Central Ltd.published_or_final_versio

Mitochondrial neuronal uncoupling proteins: a target for potential disease-modification in Parkinson's disease

This review gives a brief insight into the role of mitochondrial dysfunction and oxidative stress in the converging pathogenic processes involved in Parkinson's disease (PD). Mitochondria provide cellular energy in the form of ATP via oxidative phosphorylation, but as an integral part of this process, superoxides and other reactive oxygen species are also produced. Excessive free radical production contributes to oxidative stress. Cells have evolved to handle such stress via various endogenous anti-oxidant proteins. One such family of proteins is the mitochondrial uncoupling proteins (UCPs), which are anion carriers located in the mitochondrial inner membrane. There are five known homologues (UCP1 to 5), of which UCP4 and 5 are predominantly expressed in neural cells. In a series of previous publications, we have shown how these neuronal UCPs respond to 1-methyl-4-phenylpyridinium (MPP+; toxic metabolite of MPTP) and dopamine-induced toxicity to alleviate neuronal cell death by preserving ATP levels and mitochondrial membrane potential, and reducing oxidative stress. We also showed how their expression can be influenced by nuclear factor kappa-B (NF-kappaB) signaling pathway specifically in UCP4. Furthermore, we previously reported an interesting link between PD and metabolic processes through the protective effects of leptin (hormone produced by adipocytes) acting via UCP2 against MPP+-induced toxicity. There is increasing evidence that these endogenous neuronal UCPs can play a vital role to protect neurons against various pathogenic stresses including those associated with PD. Their expression, which can be induced, may well be a potential therapeutic target for various drugs to alleviate the harmful effects of pathogenic processes in PD and hence modify the progression of this disease.published_or_final_versio

Clinical and Pathological Findings in Women with Fabry Disease

Introduction. Fabry disease is a rare metabolic disorder caused by the genetic deficiency of the lysosomal hydrolase alpha-galactosidase A, located on chromosome X. Females with the defective gene are more than carriers and can develop a wide range of symptoms. Nevertheless, disease symptoms generally occur later and are less severe in women than in men. The enzyme deficiency manifests as a glycosphingolipidosis with progressive accumulation of glycosphingolipids and deposit of inclusion bodies in lysosomes giving a myelinlike appearance. Patients and Methods. Records of renal biopsies performed on adults from 1st January 2008 to 31st August 2011, were retrospectively examined at the Renal Pathology Laboratory. We retrieved biopsies diagnosed with Fabry disease and reviewed clinical and laboratory data and pathology findings. Results. Four female patients with a mean age of 49.3±4.5 (44-55) years were identified. The mean proteinuria was 0.75±0.3 g/24h (0.4-1.2) and estimated glomerular filtration rate (CKD EPI equation) was 71±15.7 ml/min/1.73m2 (48-83). Three patients experienced extra-renal organ involvement (cerebrovascular, cardiac, dermatologic, ophthalmologic and thyroid) with distinct severity degrees. Leukocyte α-GAL A activity was below normal range in the four cases but plasma and urinary enzymatic activity was normal. Light microscopy showed predominant vacuolisation of the podocyte cytoplasm and darkly staining granular inclusions on paraffin and plastic-embedded semi-thin sections. Electron microscopy showed in three patients the characteristic myelin-like inclusions in the podocyte cytoplasm and also focal podocyte foot process effacement. In one case the inclusions were also present in parietal glomerular cells, endothelial cells of peritubular capillary and arterioles. Conclusion. Clinical signs and symptoms are varied and can be severe among heterozygous females with Fabry disease. Intracellular accumulation of glycosphingolipids is a characteristic histologic finding of Fabry nephropathy. Since this disease is a potentially treatable condition, its early identification is imperative. We should consider it in the differential diagnosis of any patient presenting with proteinuria and/or chronic kidney disease, especially if there is a family history of kidney disease

Cerebral involvement in neuromyelitis optica spectrum disorders among Hong Kong Chinese

published_or_final_versionThe 16th Medical Resarch Conference (MRC), The University of Hong Kong, Hong Kong, China, 22 January 2011. In Hong Kong Medical Journal, 2011, v. 17, suppl. 1, p. 55, abstract no. 8

Successful control of vancomycin-resistant Enterococcus faecium outbreak in a neurosurgical unit at non-endemic region

Vancomycin-resistant enterococci (VRE) have emerged in many parts of the world, but have only been reported sporadically in Hong Kong. We report an outbreak of vancomycin-resistant Enterococcus faecium (VREfm) in a neurosurgical unit at a tertiary teaching hospital between 3 March and 3 April 2009 in Hong Kong. During the outbreak investigation, clinical samples from 193 (91.5%) of 211 patients who had stayed in the neurosurgical unit and 506 environmental samples were screened for VREfm. Besides the index case, another 3 (1.6%) out of 192 patients were found to be positive for VREfm. Two (0.4%) out of 506 environmental samples were positive for VREfm. All four clinical and two environmental isolates were found to be clonally related by pulse-field gel electrophoresis. The risk factors for nosocomial acquisition of VREfm included advanced age (P¼0.047), presence of nasogastric tubing (P¼0.002) and tracheostomy (Po0.001), and the use of b-lactam antibiotics (Po0.001) and vancomycin (P¼0.001). Contrary to other VRE outbreaks in which the spread was rapid, the neurosurgical patients’ immobilization because of coma and mechanical ventilation dependency, and the vigilant practice of hand hygiene by health-care workers successfully limited the number of secondary cases despite the delayed recognition of the index case. All patients with VREfm were labeled in the hospital network information system so that stringent infection control measures with contact precautions would be carried out once these patients were readmitted to prevent its spread in our locality.published_or_final_versio

Adiponectin is protective against oxidative stress-induced cytotoxicity in amyloid-beta neurotoxicity

Oral PresentationBeta-amyloid (Aβ) neurotoxicity is important in Alzheimer’s disease (AD) pathogenesis. Aβ neurotoxicity causes oxidative stress, inflammation, and mitochondrial damage resulting in neuronal degeneration and death. Oxidative stress, inflammation, and mitochondrial failure are also pathophysiological mechanisms of type 2 diabetes mellitus (T2DM) which is characterised by insulin resistance. Interestingly, T2DM increases risk to develop AD which is associated with reduced neuronal insulin sensitivity (central insulin resistance). We studied the potential protective effect of adipon…published_or_final_versio