Upregulation of erythropoietin and its receptor expression in the rat carotid body during chronic and intermittent hypoxia

Proceeding of the XVIIth ISAC Meeting (International Society for Arterial Chemoreception Meeting), School of Medicine of Valladolid, Valladolid, Spain, July 1–5, 2008The carotid body (CB) plays important roles in cardiorespiratory changes in intermittent hypoxia (IH). Erythropoietin (EPO), a hypoxia-inducible factor (HIF)-1 target gene, is present in the chemoreceptive type-I cells in the CB but its expression and role in IH resembling sleep apnoeic conditions are not known. We hypothesized that IH upregulates the expression of EPO and its receptor (EPOr) in the rat CB. The CB expressions of EPO and EPOr were examined in rats breathing 10% O 2 (in isobaric chamber for CH, 24 hour/day) or in IH (cyclic between air and 5% O 2 per minute, 8 hour/day) for 3-28 days. Immunohistochemical studies revealed that the EPO and EPOr proteins were localized in CB glomic clusters. The proportional amount of cells with positive staining of EPO immunoreactivities was significantly increased in both IH and CH groups when compared with the normoxic control. The EPO expression was more markedly increased in the CH than that of the IH groups throughout the time course, reaching a peak level at day 14. The positive EPOr immunostaining was increased significantly in the 3-day CH group. By day 14, the EPOr expression elevated considerably at peak levels in both IH and CH rats, whereas the elevation was greater in the CH rats. These results suggest an upregulation of EPO and its receptor expression in the rat CB under IH and CH conditions, presumably mediated by the activation of HIF-1 pathway. The increased EPO binding to its receptor might play a role in the enhancement of CB excitability during the early pathogenesis in patients with sleep-disordered breathing. © Springer Science+Business Media B.V. 2009.postprin

Lutein enhances survival and reduces neuronal damage in cerebral and retinal ischemia/reperfusion injury

Poster session 3: NeuroprotectionConference theme: Translational Neuroscience: From Molecules To ManPurpose Stroke is one of the leading causes of death worldwide. Protective agents that could diminish the injuries induced by cerebral ischemia/reperfusion (I/R) are crucial to alleviate the detrimental outcome of stroke. Retinal I/R also occurs in many ocular diseases and leads to neuronal death and therefore blindness. Lutein, a safe and potent antioxidant, is known to protect the retina in age-related macular degeneration. The aim of this study is to investigate the protective roles of lutein in cerebral and retinal I/R injury. Methods Two-hour cerebral ischemia was induced by unilateral middle cerebral artery occlusion (MCAo) in mice. Either lutein (0.2mg/kg) or vehicle was given to mice intraperitoneally 1hr after MCAo and 1hr after reperfusion. Neurological deficits were evaluated at 22hr after reperfusion while survival rate was assessed daily until 7 days after reperfusion. Flash electroretinogram (flash ERG) was taken to assess retinal function. After sacrifice, mouse brains were cut into 2mm-thick coronal slices and stained with 2% 2,3,5-triphenyltetrazolium chloride to determine the infarct size after MCAo. Eyes were also enucleated. Paraffin-embedded brain and retinal sections were prepared for TUNEL assay and immunohistochemistry. Protein lysate was collected for Western blotting experiments. Lutein's effect on Müller cells was further evaluated using a model of cobalt chloride-induced hypoxia in immortalized rat Müller cells (rMC-1). Results Higher survival rate, better neurological scores, smaller infarct area and smaller infarct volume were noted in the lutein-treated group. Immunohistochemistry data showed a decrease of immunoreactivity of nitrotyrosine, poly(ADP-ribose) and NFkB in the lutein-treated brains. Western blotting data showed decreased levels of Cox-2, pERK, and pIkB, but increased levels of Bcl-2, heat shock protein 70 and pAkt in the lutein-treated brains. In the retina, severe cell loss in retinal ganglion cell (RGC) layer was noted after I/R injury. Increased oxidative stress was observed in the injured retina. Lutein treatment protected RGC as well as decreased oxidative stress in I/R retina. Lutein treatment also minimized the deterioration of b-wave/a-wave ratio and oscillatory potentials in flash ERG as well as inhibited the up-regulation of GFAP in retinal I/R injury. In the cultured Müller cells, lutein treatment reduced level of nuclear NF-kB together with decreased levels of IL-1b and Cox- 2. Conclusions Post-treatment of lutein protected both the brain and retina from I/R injury. The neuroprotective effect of lutein was associated with reduced oxidative stress. Less production of pro-inflammatory factors from Müller cells suggested an anti-inflammatory role of lutein in retinal ischemic/hypoxic injury. Our results suggest that lutein could diminish the deleterious outcomes of cerebral and retinal I/R probably by its antiapoptotic, anti-oxidative and anti-inflammatory properties. Lutein may have a therapeutic role in protecting the brain in stroke and inner retina in eye diseases with acute ischemia.published_or_final_versio

Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome

Background: Dravet syndrome is a severe form of epilepsy. Majority of patients have a mutation in SCN1A gene, which encodes a voltage-gated sodium channel. A recent study has demonstrated that 16% of SCN1A-negative patients have a mutation in PCDH19, the gene encoding protocadherin-19. Mutations in other genes account for only a very small proportion of families. TSPYL4 is a novel candidate gene within the locus 6q16.3-q22.31 identified by linkage study. Objective: The present study examined the mutations in epileptic Chinese children with emphasis on Dravet syndrome. Methods: A hundred children with severe epilepsy were divided into Dravet syndrome and non-Dravet syndrome groups and screened for SCN1A mutations by direct sequencing. SCN1A-negative Dravet syndrome patients and patients with phenotypes resembling Dravet syndrome were checked for PCDH19 and TSPYL4 mutations. Results: Eighteen patients (9 males, 9 females) were diagnosed to have Dravet syndrome. Among them, 83% (15/18) had SCN1A mutations including truncating (7), splice site (2) and missense mutations (6). The truncating/splice site mutations were associated with moderate to severe degree of intellectual disability (p<0.05). During the progression of disease, 73% (11/15) had features fitting into the diagnostic criteria of autism spectrum disorder and 53% (8/15) had history of vaccination-induced seizures. A novel PCDH19 p.D377N mutation was identified in one SCN1A-negative female patient with Dravet syndrome and a known PCDH19 p.N340S mutation in a female non-Dravet syndrome patient. The former also inherited a TSPYL4 p.G60R variant. Conclusion: A high percentage of SCN1A mutations was identified in our Chinese cohort of Dravet syndrome patients but none in the rest of patients. We demonstrated that truncating/splice site mutations were linked to moderate to severe intellectual disability in these patients. A de novo PCDH19 missense mutation together with an inherited TSPYL4 missense variant were identified in a patient with Dravet syndrome. © 2012 Kwong et al.published_or_final_versio

An in vivo trial comparing the use of different types of 532 nm Neodymium: Yttrium-Aluminum-Garnet (Nd-YAG) lasers in the treatment of facial lentigines in oriential patients

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Two-beam photoacoustic phase measurement of the thermal diffusivity of a Gd-doped bulk YBCO superconductor

The two-beam photoacoustic phase measurement was applied to measure quantitatively the thermal diffusivity (s) of a ceramic bulk high-Tc superconductor. Neglecting the effects of thermal dilation, and thermoelastic bending was proved valid in accordance with our composite piston model for the chosen experimental conditions. It was found that s shows different features at the onset and offset temperatures corresponding to the normal–superconducting (NS) transition. A dip was seen at the resistivity transition onset temperature and a cusp at the offset temperature where the electrical resistance disappears. The presence of the cusp at the offset temperature is proposed to be related to weak coupling between superconducting grains. Our studies indicate that the two-beam phase measurement is a very sensitive method for superconductor characterization and NS transition detection. The experimental results also confirm the presence of a large energy gap and strong electron–phonon coupling mechanism in the YBCO superconductor. ©1996 American Institute of Physics.published_or_final_versio

Nitric oxide synthase (NOS) expression and nitric oxide (NO) production in CCL4-induced hepatotoxicity of rats

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Primary hyperaldosteronism among Chinese hypertensive patients: how are we doing in a local district in Hong Kong

OBJECTIVES: To estimate the point prevalence of primary hyperaldosteronism in a government out-patient setting and to compare associated patient characteristics with those having essential hypertension. DESIGN: Case series with external comparison. SETTING: A single public hospital (Caritas Medical Centre) and all five associated general out-patient clinics in Sham Shui Po district in Hong Kong. PATIENTS: All patients with confirmed primary hyperaldosteronism and randomly selected patients with essential hypertension from a medical specialist clinic and general out-patient clinics, retrieved from a computer database for the period January 2007 to December 2008. MAIN OUTCOME MEASURES: Estimated point prevalence of primary hyperaldosteronism among hypertensive patients treated in the public sector of Sham Shui Po district. Patient age when hypertension was diagnosed, number of antihypertensive drugs used for treatment, and the presence of target organ damage in the patients with primary hyperaldosteronism and those with essential hypertension were compared. RESULTS: Among the 46 012 patients receiving antihypertensive treatment, 49 were confirmed to have primary hyperaldosteronism. The estimated point prevalence of primary hyperaldosteronism among these hypertensive patients was 0.106% only, which was far smaller than figures from other countries. When compared with the 147 patients with essential hypertension by multivariate analysis, those with primary hyperaldosteronism were: (1) associated with longer durations of hypertension (odds ratio=1.14; 95% confidence interval, 1.06-1.24) despite being younger at the time of study, (2) likely to be taking three or more antihypertensive drugs (odds ratio=2.51; 95% confidence interval, 1.59-3.95), and (3) more likely to have left ventricular hypertrophy (odds ratio=5.01; 95% confidence interval, 1.83-13.69). All primary hyperaldosteronism patients studied presented with hypokalaemia. The need for antihypertensive drugs was markedly reduced after adrenalectomy for adrenal adenoma. CONCLUSIONS: Primary hyperaldosteronism, which is potentially a surgically curable cause of hypertension, appeared to be underdiagnosed in our locality. Screening by aldosterone-renin ratio of high-risk individuals may help improve patient outcomes.published_or_final_versio

Towards InAs nanowire double quantum dots for quantum information processing

Currently, a major challenge for solid-state spin qubit systems is achieving one-qubit operations on a timescale shorter than the spin coherence time, T2*, a goal currently two orders of magnitude away. By taking advantage of the quasi-one-dimensional structure of a nanowire and the strong spin-orbit interaction of InAs, it is estimated that π-rotations can be implemented using electric dipole spin resonance on the order of 10 ns. To this end, a procedure for the fabrication of homogeneous InAs nanowire quantum dot devices is presented herein for future investigations of solid state spin qubits as a test bed for quantum computing. Both single and double quantum dot systems are formed using local gating of InAs nanowires. Single quantum dot systems were characterized through electron transport measurements in a dilution refrigerator; in one case, the charging energy was measured to be 5.0 meV and the orbital energy was measured to be 1.5-3.5 meV. The total capacitance of the single quantum dot system was determined to be approximately 30 aF. An estimate of the quantum dot geometry resulting from confinement suggests that the quantum dot is approximately 115 nm long. The coupling energy of the double quantum dot system was measured to be approximately 4.5 meV. The electron temperature achieved with our circuitry in the dilution refrigerator is estimated to be approximately 125 mK

Anti-inflammatory effects of lutein in retinal ischemic injury: in vivo and in vitro studies

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Sequence Effect of Self-Assembling Peptides on the Complexation and In Vitro Delivery of the Hydrophobic Anticancer Drug Ellipticine

A special class of self-assembling peptides has been found to be capable of stabilizing the hydrophobic anticancer agent ellipticine in aqueous solution. Here we study the effect of peptide sequence on the complex formation and its anticancer activity in vitro. Three peptides, EAK16-II, EAK16-IV and EFK16-II, were selected to have either a different charge distribution (EAK16-II vs. EAK16-IV) or a varying hydrophobicity (EAK16-II vs. EFK16-II). Results on their complexation with ellipticine revealed that EAK16-II and EAK16-IV were able to stabilize protonated ellipticine or ellipticine microcrystals depending on the peptide concentration; EFK16-II could stabilize neutral ellipticine molecules and ellipticine microcrystals. These different molecular states of ellipticine were expected to affect ellipticine delivery. The anticancer activity of these complexes was tested against two cancer cell lines: A549 and MCF-7, and related to the cell viability. The viability results showed that the complexes with protonated ellipticine were effective in eradicating both cancer cells (viability <0.05), but their dilutions in water were not stable, leading to a fast decrease in their toxicity. In contrast, the complexes formulated with EFK16-II were relatively stable upon dilution, but their original toxicity was relatively low compared to that with protonated ellipticine. Overall, the charge distribution of the peptides seemed not to affect the complex formation and its therapeutic efficacy in vitro; however, the increase in hydrophobicity of the peptides significantly altered the state of stabilized ellipticine and increased the stability of the complexes. This work provides essential information for peptide sequence design in the development of self-assembling peptide-based delivery of hydrophobic anticancer drugs