Pathogenic roles of the carotid body inflammation in sleep apnea

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The role of local renin-angiotensin system in arterial chemoreceptors in sleep-breathing disorders

This article is part of the Research Topic: Carotid body: a new target for rescuing neural control of cardiorespiratory balance in diseasepublished_or_final_versio

Involvement of NADPH oxidase and renin-angiotensin system in tissue inflammation of the rat adrenal medulla during intermittent hypoxia

The proceedings of this meeting are published in Journal of the Hong Kong College of Cardiology Vol. 19, Number 2, pp. 63-80 (http://www.icsm-hk.org/conferences.php)published_or_final_versio

Melatonin Attenuates Intermittent Hypoxia-Induced Lipid Peroxidation and Local Inflammation in Rat Adrenal Medulla

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Melatonin ameliorates calcium homeostasis in myocardial and ischemia-reperfusion injury in chronically hypoxic rats

Chronic hypoxia (CH) leads to the deterioration of myocardial functions with impaired calcium handling in the sarcoplasmic reticulum (SR), which may be mediated by oxidative stress. We hypothesized that administration of antioxidant melatonin would protect against cardiac and ischemia-reperfusion (I/R) injury by ameliorating SR calcium handling. Adult Sprague-Dawley rats that had received a daily injection of melatonin or vehicle were exposed to 10% oxygen for 4 wk. The heart of each rat was then dissected and perfused using a Langendorff apparatus. The ratio of heart-to-body weight, ventricular hypertrophy and hematocrit were increased in the hypoxic rats compared with the normoxic controls. Malondialdehyde levels were also increased in the heart of hypoxic rats and were lowered by the treatment of melatonin. The hearts were subjected to left coronary artery ischemia (30 min) followed by 120-min reperfusion. Lactate dehydrogenase leakage before ischemia, during I/R and infarct size of the isolated perfused hearts were significantly elevated in the vehicle-treated hypoxic rats but not in the melatonin-treated rats. Spectroflurometric studies showed that resting calcium levels and I/R-induced calcium overload in the cardiomyocytes were more significantly altered in the hypoxic rats than the normoxic controls. Also, the hypoxic group had decreased levels of the SR calcium content and reduced amplitude and decay time of electrically induced calcium transients, indicating impaired contractility and SR calcium re-uptake. Moreover, there were reductions in protein expression of calcium handling proteins, markedly shown at the level of SR-Ca2+ ATPase (SERCA) in the heart of hypoxic rats. Melatonin treatment significantly mitigated the calcium handling in the hypoxic rats by preserving SERCA expression. The results suggest that melatonin is cardioprotective against CH-induced myocardial injury by improving calcium handling in the SR of cardiomyocytes via an antioxidant mechanism. © 2008 The Authors.postprin

Neuroprotective effects of Lycium barbarum polysaccharides against rat hippocampal apoptosis induced by chronic intermittent hypoxia

Poster presentationWe have shown neuronal apoptosis in the hippocampus of rats exposed to chronic intermittent hypoxia mimicking severe conditions of obstructive sleep apnea (OSA) syndrome in patients [1]. Lycium barbarum polysaccharides (LBP), active biological ingredients of traditional Chinese herbal medicine Goji, have been shown to possess cytoprotective properties [2]. The aim of this study was to examine the protective effects of LBP against neuronal apoptosis in the hippocampus in a severe OSA rodent model. We hypothesized that oral administration of LBP ameliorates neuronal apoptosis in the rat hippocampus induced by chronic intermittent hypoxia. Adult SD rats were randomly divided into 4 experimental groups, namely: (i) normoxic control (Nx); (ii) Nx treated with LBP; hypoxic groups treated with either (iii) LBP or (iv) vehicle. The hypoxic groups were kept in a normobaric chamber with inspired oxygen alternating from 21 to 5 ± 0.5% oxygen per minute for 8 hr/day for 7 days, whereas Nx groups was maintained in room air for 7 days. LBP (1mg/kg) were orally fed to the rats 2 hours prior the daily hypoxic treatment. Rats were sacrificed and the hippocampus was harvested for measurements of oxidative marker, malondialdehyde (MDA), apoptotic cell death using TUNEL assay, protein expression levels of antioxidant enzymes, and inflammatory cytokines by Western blot. There were significantly more TUNEL positive –labeling cells in the CA regions and dentate gyrus of the hippocampus in the vehicle-treated hypoxic group than those of the Nx control and LBP-treated groups. In addition, levels of MDA and the protein expressions of cleaved caspase 3 and inflammatory cytokines were increased in the vehicle-treated hypoxic group when compared to the Nx groups and were lowered by the LBP treatment. Intriguingly, there were significantly more PCNA-labeling cells in the dentate gyrus of the hippocampus in the LBP-treated hypoxic groups than those of the other groups. Also, the protein expression of cyclin D1 was increased in the hypoxic groups when compared to the Nx groups. In conclusion, oral administration of LBP significantly ameliorates oxidative stress, inflammation and neuronal apoptosis with enhanced proliferative activities in the hippocampus of rats exposed to chronic intermittent hypoxia. Thus, LBP may be proposed as a health supplement to mitigate neurological deficits in OSA patients, for which awaits future studies to delineate the neuroprotective mechanism of LBP. [Studies supported by research grants (HKU 7510/06M, HKU 766110M) from RGC and funding (201007176007, SFPBR 200911159072) from HKU] [1] Hung, M.W., et al. (2008) J Pineal Res 44: 214-221. [2] Chang, R.C., et al. (2008). Cell Mol Neurobiol 28: 643-652.published_or_final_versio

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

The University of Pittsburgh: a three and three-quarter-year experience with cadaveric renal transplantation under the point system.

Eight hundred and sixty kidney transplants were performed at the University of Pittsburgh over a 3.75-year period between January 1, 1986 and October 19, 1989. Recipient selection was by means of a computerized point system designed to allocate organs equitably. Ninety-three percent 1-year patient survival and 74% 1-year graft survival were obtained in the overall group; 80% 1-year graft survival was obtained in patients receiving immunosuppression with CsA, azathioprine, and prednisone. These data serve as a measure of what can be achieved with an equitably based allocation system and can serve as a basis of comparison with other allocation protocols or new immunosuppressive regimens

Chronic intermittent hypoxia induces oxidative stress and inflammation via Angiotensin II Receptor 1 in rat liver

Poster Presentation: no. P17Chronic intermittent hypoxia (IH) associated with obstructive sleep apnea (OSA) is characterized by repetitive cycles of hypoxia and reoxygenation, leading to excessive production of reactive oxygen species and oxidative stress in tissues and organs. However the mechanistic effects of chronic IH on the liver are not clear at present. We hypothesized that renin-angiotensin system (RAS) plays a role in the IH-induced oxidative stress and tissue inflammation in the rat liver. Adult Sprague-Dawley rats were exposed to air (normoxic (Nx) control) or IH treatment (with inspired oxygen fraction in the normobaric chamber cyclic between 5-21% ± 0.5% per min, 8 hours per day) for 14 days. Rats were fed with an angiotensin II type 1 (AT1) receptors blocker telmisartan (10mg/kg body weight), or vehicle daily before the IH treatment. Hepatic expression levels of pro-inflammatory …postprin

Randomized trial of FK 506/prednisone vs FK 506/azathioprine/prednisone after renal transplantation: preliminary report.

FK 506 was used as a primary immunosuppressive agent in 125 cases of renal transplantation in a randomized trial comparing FK 506/prednisone with FK 506/azathioprine/prednisone. With a mean follow-up of 5.5 +/- 2.5 months, there has been a 6-month actuarial patient survival of 99% and graft survival of 88%. There is no difference thus far between the two-drug and three-drug groups, although there may be less rejection and diabetes in the three-drug group. These results suggest that FK 506 is a useful immunosuppressive agent in kidney transplantation