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Find video protocols related to scientific articles indexed in Pubmed.
Improving Brush Polymer Infrared 1-D Photonic Crystals via Linear Polymer Additives.
J. Am. Chem. Soc.
PUBLISHED: 11-06-2014
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Brush block copolymers (BBCPs) enable the rapid fabrication of self-assembled 1D photonic crystals with photonic band gaps that are tunable in the UV-Vis-IR, where the peak wavelength of reflection scales with the molecular weight of the BBCPs. As a consequence of the difficulty in synthesizing very large BBCPs, the fidelity of the assembled lamellar nanostructures drastically erodes as the domains become large enough to reflect infrared (IR) light, which severely limits their performance as optical filters. To overcome this challenge, short linear homopolymers are used to swell the arrays to up to ~180% of the initial domain spacing, allowing for photonic band gaps up to ~1410 nm without significant opacity in the visible, demonstrating improved ordering of the arrays. Additionally, the blending of BBCPs with random copolymers enables functional groups to be incorporated into the BBCP array without the need to attach them directly to the BBCPs. The addition of short, linear polymers to the brush block copolymer arrays therefore allows for a facile means of both improving the self-assembly and optical properties of these materials, as well as adding a route to achieving films with a greater amount of functionality and tailorability, without the need to develop or optimize the processing conditions for each new brush polymer synthesized.
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Immature teratoma of the maxillary sinus: a rare pediatric tumor.
JAMA Otolaryngol Head Neck Surg
PUBLISHED: 08-22-2014
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Noncongenital immature teratomas in the head and neck are extremely rare, and to our knowledge have not previously been reported in the maxillary sinus of a pediatric patient.
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Interplay between brain stem angiotensins and monocyte chemoattractant protein-1 as a novel mechanism for pressor response after ischemic stroke.
Neurobiol. Dis.
PUBLISHED: 08-12-2014
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Pressor response after stroke commonly leads to early death or susceptibility to stroke recurrence, and detailed mechanisms are still lacking. We assessed the hypothesis that the renin-angiotensin system contributes to pressor response after stroke by differential modulation of the pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) in the rostral ventrolateral medulla (RVLM), a key brain stem site that maintains blood pressure. We also investigated the beneficial effects of a novel renin inhibitor, aliskiren, against stroke-elicited pressor response. Experiments were performed in male adult Sprague-Dawley rats. Stroke induced by middle cerebral artery occlusion elicited significant pressor response, accompanied by activation of angiotensin II (Ang II)/type I receptor (AT1R) and AT2R signaling, depression of Ang-(1-7)/MasR and Ang IV/AT4R cascade, alongside augmentation of MCP-1/C-C chemokine receptor 2 (CCR2) signaling and neuroinflammation in the RVLM. Stroke-elicited pressor response was significantly blunted by antagonism of AT1R, AT2R or MCP-1/CCR2 signaling, and eliminated by applying Ang-(1-7) or Ang IV into the RVLM. Furthermore, stroke-activated MCP-1/CCR2 signaling was enhanced by AT1R and AT2R activation, and depressed by Ang-(1-7)/MasR and Ang IV/AT4R cascade. Aliskiren inhibited stroke-elicited pressor response via downregulating MCP-1/CCR2 activity and reduced neuroinflammation in the RVLM; these effects were potentiated by Ang-(1-7) or Ang IV. We conclude that whereas Ang II/AT1R or Ang II/AT2R signaling in the brain stem enhances, Ang-(1-7)/MasR or Ang IV/AT4R antagonizes pressor response after stroke by differential modulations of MCP-1 in the RVLM. Furthermore, combined administration of aliskiren and Ang-(1-7) or Ang IV into the brain stem provides more effective amelioration of stroked-induced pressor response.
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Prognostic impact of renin-angiotensin system blockade in esophageal squamous cell carcinoma.
J Renin Angiotensin Aldosterone Syst
PUBLISHED: 06-24-2014
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The aim of this study is to evaluate whether the administration of renin-angiotensin system (RAS) inhibitors, angiotensin-I converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), is associated with treatment outcome in patients with esophageal squamous cell carcinoma.
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Simvastatin treatment exerts antidepressant-like effect in rats exposed to chronic mild stress.
Pharmacol. Biochem. Behav.
PUBLISHED: 05-09-2014
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Hyperlipidemia is associated with increased risk of coronary artery disease and stroke, both of which, in turn, are risk factors of old-age depression. Statins are extensively used for decreasing cholesterol levels. Clinical investigations revealed that long-term use of statins appeared to be associated with a lower risk of anxiety and depression. However, the antidepressant property of statins has not been well examined. This study aimed at examining the antidepressant-like effects of statins in rats exposed to chronic mild stress (CMS). We found that animals exposed to CMS for 4 weeks developed depressive-like state, shown by forced swim test and sucrose preference test. However, these CMS-induced behavioral changes were reversed by simvastatin (5 or 10mg/kg/day) for 14 days, comparable to imipramine (10mg/kg/day) treatment. Locomotor activity and anxiety-like behaviors were not altered by CMS or these treatments. These results demonstrated antidepressant-like effects of statin in CMS model of rats and suggested the potential that statins could be used to facilitate antidepressant treatment in clinical setting.
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Abiraterone acetate to lower androgens in women with classic 21-hydroxylase deficiency.
J. Clin. Endocrinol. Metab.
PUBLISHED: 04-29-2014
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Chronic supraphysiological glucocorticoid therapy controls the androgen excess of 21-hydroxylase deficiency (21OHD) but contributes to the high prevalence of obesity, glucose intolerance, and reduced bone mass in these patients. Abiraterone acetate (AA) is a prodrug for abiraterone, a potent CYP17A1 inhibitor used to suppress androgens in the treatment of prostate cancer.
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Predictive modeling of gingivitis severity and susceptibility via oral microbiota.
ISME J
PUBLISHED: 01-29-2014
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Predictive modeling of human disease based on the microbiota holds great potential yet remains challenging. Here, 50 adults underwent controlled transitions from naturally occurring gingivitis, to healthy gingivae (baseline), and to experimental gingivitis (EG). In diseased plaque microbiota, 27 bacterial genera changed in relative abundance and functional genes including 33 flagellar biosynthesis-related groups were enriched. Plaque microbiota structure exhibited a continuous gradient along the first principal component, reflecting transition from healthy to diseased states, which correlated with Mazza Gingival Index. We identified two host types with distinct gingivitis sensitivity. Our proposed microbial indices of gingivitis classified host types with 74% reliability, and, when tested on another 41-member cohort, distinguished healthy from diseased individuals with 95% accuracy. Furthermore, the state of the microbiota in naturally occurring gingivitis predicted the microbiota state and severity of subsequent EG (but not the state of the microbiota during the healthy baseline period). Because the effect of disease is greater than interpersonal variation in plaque, in contrast to the gut, plaque microbiota may provide advantages in predictive modeling of oral diseases.
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Activation of PI3K/Akt signaling in rostral ventrolateral medulla impairs brain stem cardiovascular regulation that underpins circulatory depression during mevinphos intoxication.
Biochem. Pharmacol.
PUBLISHED: 01-12-2014
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As the most widely used pesticides in the globe, the organophosphate compounds are understandably linked with the highest incidence of suicidal poisoning. Whereas the elicited toxicity is often associated with circulatory depression, the underlying mechanisms require further delineation. Employing the pesticide mevinphos as our experimental tool, we evaluated the hypothesis that transcriptional upregulation of nitric oxide synthase II (NOS II) by NF-?B on activation of the PI3K/Akt cascade in the rostral ventrolateral medulla (RVLM), the brain stem site that maintains blood pressure and sympathetic vasomotor tone, underpins the circulatory depressive effects of organophosphate poisons. Microinjection of mevinphos (10 nmol) bilaterally into the RVLM of anesthetized Sprague-Dawley rats induced a progressive hypotension that was accompanied sequentially by an increase (Phase I) and a decrease (Phase II) of an experimental index for the baroreflex-mediated sympathetic vasomotor tone. There were also progressive augmentations in PI3K or Akt enzyme activity and phosphorylation of p85 or Akt(Thr308) subunit in the RVLM that were causally related to an increase in NF-?B transcription activity and elevation in NOS II or peroxynitrite expression. Loss-of-function manipulations of PI3K or Akt in the RVLM significantly antagonized the reduced baroreflex-mediated sympathetic vasomotor tone and hypotension during Phase II mevinphos intoxication, and blunted the increase in NF-?B/NOS II/peroxynitrite signaling. We conclude that activation of the PI3K/Akt cascade, leading to upregulation of NF-?B/NOS II/peroxynitrite signaling in the RVLM, elicits impairment of brain stem cardiovascular regulation that underpins circulatory depression during mevinphos intoxication.
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Heat shock protein 70 protects against seizure-induced neuronal cell death in the hippocampus following experimental status epilepticus via inhibition of nuclear factor-?B activation-induced nitric oxide synthase II expression.
Neurobiol. Dis.
PUBLISHED: 07-03-2013
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Status epilepticus induces subcellular changes that may eventually lead to neuronal cell death in the hippocampus. Based on an animal model of status epilepticus, our laboratory showed previously that sustained hippocampal seizure activity activates nuclear factor-?B (NF-?B) and upregulates nitric oxide synthase (NOS) II gene expression, leading to apoptotic neuronal cell death in the hippocampus. The present study examined the potential modulatory role of heat shock protein 70 (HSP70) on NF-?B signaling in the hippocampus following experimental status epilepticus. In Sprague-Dawley rats, kainic acid (KA) was microinjected unilaterally into the hippocampal CA3 subfield to induce prolonged bilateral seizure activity. Expression of HSP70 was elevated as early as 1h after the elicitation of sustained seizure activity, followed by a progressive elevation that peaked at 24h. Pretreatment with an antisense oligonucleotide against hsp70 decreased the HSP70 expression, and significantly augmented I?B kinase (IKK) activity and phosphorylation of I?B?, alongside enhanced nuclear translocation and DNA binding activity of NF-?B in the hippocampal CA3 neurons and glial cells. These cellular events were followed by enhanced upregulation of NOS II and peroxynitrite expression 3h after sustained seizure activity that led to an increase of caspase-3 and DNA fragmentation in the hippocampal CA3 neurons 7days after experimental status epilepticus. We concluded that HSP70 protects against apoptotic cell death induced by NF-?B activation and NOS II-peroxynitrite signaling cascade in the hippocampal CA3 and glial cells following experimental status epilepticus via suppression of IKK activity and deactivation of I?B?.
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Transition from oxidative stress to nitrosative stress in rostral ventrolateral medulla underlies fatal intoxication induced by organophosphate mevinphos.
Toxicol. Sci.
PUBLISHED: 07-03-2013
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As the most widely used pesticides in the world, fatal incidence of suicidal poisoning by organophosphate compounds is high and is often associated with cardiovascular toxicity. Using the pesticide mevinphos as our tool, we investigated the roles of oxidative stress and nitrosative stress at the rostral ventrolateral medulla (RVLM), the brain stem site that maintains arterial pressure (AP) and sympathetic vasomotor tone, in the cardiovascular depressive effects of organophosphate poisons. Microinjection of mevinphos (10 nmol) into the RVLM of anesthetized Sprague-Dawley rats induced progressive hypotension that was accompanied by an increase (phase I), followed by a decrease (phase II) of an experimental index of baroreflex-mediated sympathetic vasomotor tone, with a fatality rate of 35%. During phase I, there was a preferential upregulation of angiotensin type I receptor (AT1R) messenger RNA (mRNA) and protein that leads to activation of NADPH oxidase (Nox) and increase in superoxide at the RVLM. Pharmacological antagonism of these signals exacerbated fatality and shorted survival time by eliminating baroreflex-mediated sympathetic vasomotor tone, AP, and heart rate. During phase II, there was a progressive upregulation of angiotensin type II receptor (AT2R) mRNA and protein that leads to increase in peroxynitrite in the RVLM, blockade of both sustained brain stem cardiovascular regulation and improved survival. We further found that AT1R and AT2R cross-interacted at transcriptional and signaling levels in the RVLM. We conclude that a transition from AT1R-mediated oxidative stress to AT2R-mediated nitrosative stress in the RVLM underlies the shift from sustained to impaired brain stem cardiovascular regulation that underpins cardiovascular fatality during mevinphos intoxication.
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Tracheal foreign bodies: are radiographs misleading?
Pediatr Emerg Care
PUBLISHED: 04-06-2013
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This study aimed to highlight the pitfalls of relying on radiographs in identifying potentially life-threatening upper airway foreign bodies in children.
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Development of indole/indazole-aminopyrimidines as inhibitors of c-Jun N-terminal kinase (JNK): optimization for JNK potency and physicochemical properties.
Bioorg. Med. Chem. Lett.
PUBLISHED: 02-19-2013
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A novel series of indole/indazole-aminopyrimidines was designed and synthesized with an aim to achieve optimal potency and selectivity for the c-Jun kinase family or JNKs. Structure guided design was used to optimize the series resulting in a significant potency improvement. The best compound (17) has IC50 of 3 nM for JNK1 and 20 nM for JNK2, with greater than 40-fold selectivity against other kinases with good physicochemical and pharmacokinetic properties.
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Visualizing oxidative stress-induced depression of cardiac vagal baroreflex by MRI/DTI in a mouse neurogenic hypertension model.
Neuroimage
PUBLISHED: 02-14-2013
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A clinical hallmark of hypertension is impairment of the cardiac vagal baroreflex, which maintains stable blood pressure and heart rate under physiological conditions. There is also evidence that oxidative stress in the brain is associated with neurogenic hypertension. We tested the hypothesis that an augmented superoxide level in the nucleus tractus solitarii (NTS), the terminal site of baroreceptor afferents, contributes to the depression of cardiac vagal baroreflex by disrupting the connectivity between the NTS and the nucleus ambiguus (NA), the origin of the vagus nerve, during neurogenic hypertension. An experimental model of neurogenic hypertension that employed intracerebroventricular infusion of angiotensin II in male adult C57BL/6 mice was used. Based on tractographic evaluations using magnetic resonance imaging/diffusion tensor imaging of the medulla oblongata in the brain stem, we found that the connectivity between the NTS and NA was disrupted in neurogenic hypertension, concurrent with impairment of the cardiac vagal baroreflex as detected by radiotelemetry. We further found that the disrupted NTS-NA connectivity was reversible, and was related to oxidative stress induced by augmented levels of NADPH oxidase-generated superoxide in the NTS. We conclude that depression of the cardiac vagal baroreflex induced by oxidative stress in the NTS in the context of neurogenic hypertension may be manifested in the form of dynamic alterations in the connectivity between the NTS and NA.
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Higher natriuretic peptide levels associate with a favorable adipose tissue distribution profile.
J. Am. Coll. Cardiol.
PUBLISHED: 01-08-2013
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The goal of this study was to investigate the association between natriuretic peptides and body fat distribution in a multiethnic cohort.
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De novo expression of podocyte proteins in parietal epithelial cells in experimental aging nephropathy.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 11-30-2011
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A progressive decrease in podocyte number underlies the development of glomerulosclerosis and reduced kidney function in aging nephropathy. Recent data suggest that under certain disease states, parietal epithelial cells (PECs) begin to express proteins considered specific to podocytes. To determine whether this phenomenon increases in aging kidneys, 4-, 12-, and 20-mo ad libitum-fed and 20-mo calorie-restricted (CR) rats were studied. Single and double immunostaining were performed with antibodies to the PEC protein paired box gene 2 (PAX2) and tight junction protein claudin-1, the podocyte-specific protein Wilms tumor 1 (WT-1), and the proliferating cell protein (Ki-67). ImageJ software measured Bowmans basement membrane (BBM) length and glomerular tuft area in individual glomeruli from each animal to assess glomerular size. The results showed that in aged ad libitum rats, the decrease in number of podocytes/glomerular tuft area was accompanied by an increase in the number of PECs/BBM length at 12 and 20 mo (P < 0.01 vs. 4 mo). The increase in PEC number was due to proliferation (increase in PAX2/Ki-67 double-positive cells). Aging was accompanied by a progressive increase in the number of glomerular cells double staining for PAX2 and WT-1. In contrast, the control 20-mo-old CR rats had no increase in glomerular size, and podocyte and PEC number were not altered. These results suggest that although the number of PECs and PECs expressing podocyte proteins increase in aging nephropathy, they are likely not sufficient to compensate for the decrease in podocyte number.
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Otogenic cerebral abscess: an unusual complication of otitis media.
Ear Nose Throat J
PUBLISHED: 11-24-2011
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Intracranial complications of otitis media are rare in the age of antiobiotics and in the developed world, but they can be life threatening when they occur. We present a case of a 47-year-old woman with no contributory otologic history who developed an otogenic temporal lobe abscess.
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Albumin-induced apoptosis of glomerular parietal epithelial cells is modulated by extracellular signal-regulated kinase 1/2.
Nephrol. Dial. Transplant.
PUBLISHED: 09-05-2011
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The biological role(s) of glomerular parietal epithelial cells (PECs) is not fully understood in health or disease. Given its location, PECs are constantly exposed to low levels of filtered albumin, which is increased in nephrotic states. We tested the hypothesis that PECs internalize albumin and increased uptake results in apoptosis.
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A double-edged sword role for ubiquitin-proteasome system in brain stem cardiovascular regulation during experimental brain death.
PLoS ONE
PUBLISHED: 09-02-2011
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Brain stem cardiovascular regulatory dysfunction during brain death is underpinned by an upregulation of nitric oxide synthase II (NOS II) in rostral ventrolateral medulla (RVLM), the origin of a life-and-death signal detected from blood pressure of comatose patients that disappears before brain death ensues. Furthermore, the ubiquitin-proteasome system (UPS) may be involved in the synthesis and degradation of NOS II. We assessed the hypothesis that the UPS participates in brain stem cardiovascular regulation during brain death by engaging in both synthesis and degradation of NOS II in RVLM.
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Rapid desensitizing efficacy of a stannous-containing sodium fluoride dentifrice.
J Clin Dent
PUBLISHED: 06-28-2011
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To evaluate the efficacy of an experimental stannous-containing sodium fluoride dentifrice (1450 ppm fluoride) in the reduction of dentinal hypersensitivity over a three-day period as compared to a positive control dentifrice containing 8% arginine, calcium carbonate, and 1450 ppm fluoride as sodium monofluorophosphate.
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Label-free, single protein detection on a near-infrared fluorescent single-walled carbon nanotube/protein microarray fabricated by cell-free synthesis.
Nano Lett.
PUBLISHED: 05-31-2011
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Excessive sample volumes continue to be a major limitation in the analysis of protein-protein interactions, motivating the search for label-free detection methods of greater sensitivity. Herein, we report the first chemical approach for selective protein recognition using fluorescent single-walled carbon nanotubes (SWNTs) enabling label-free microarrays capable of single protein detection. Hexahistidine-tagged capture proteins directly expressed by cell-free synthesis on SWNT/chitosan microarray are bound to a Ni(2+) chelated by N?,N?-bis(carboxymethyl)-L-lysine grafted to chitosan surrounding the SWNT. The Ni(2+) acts as a proximity quencher with the Ni(2+)/SWNT distance altered upon docking of analyte proteins. This ability to discern single protein binding events decreases the apparent detection limit from 100 nM, for the ensemble average, to 10 pM for an observation time of 600 s. This first use of cell-free synthesis to functionalize a nanosensor extends this method to a virtually infinite number of capture proteins. To demonstrate this, the SWNT microarrays are used to analyze a network of 1156 protein-protein interactions in the staurosporine-induced apoptosis of SH-SY5Y cells, confirming literature predictions.
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Polycystic ovarian syndrome and subclinical atherosclerosis among women of reproductive age in the Dallas heart study.
Clin. Endocrinol. (Oxf)
PUBLISHED: 04-01-2011
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Polycystic ovarian syndrome (PCOS), the most common endocrinopathy of young women, is characterized by androgen excess and is frequently associated with cardiovascular risk factors. However, it is unclear whether PCOS is a risk factor for atherosclerosis. We sought to determine in a multiethnic population-based sample whether women with PCOS have greater measures of subclinical atherosclerosis than women without PCOS.
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Catheterization of the thoracic spinal subarachnoid space in mice.
J. Neurosci. Methods
PUBLISHED: 03-31-2011
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The availability of genetically manipulated mice offers a golden opportunity for the study of the contribution of the genome to diseases. Because of the technical difficulty in performing spinal subarachnoid catheterization in mice, this opportunity has hitherto been less harnessed in investigations on the role of the spinal cord in the physiological or pathological processes. Even less explored are spinal mechanisms that underlie cardiovascular regulation since subarachnoid catheterization of the mouse thoracic spinal cord, where preganglionic sympathetic neurons governing vasomotor tone are located posts the highest challenge because of the restricted operating area. We report a procedure for subarachnoid catheterization of the thoracic spinal cord in mice that did not require laminectomy or drilling of the lamina proper, and compared the suitability of two candidate catheters, polyethylene PE-5 catheter (0.51mm, OD) and polyurethane PU-10 catheter (0.25mm, OD). Whereas all implanted mice resumed normal feeding one day after surgery and were devoid of bladder dysfunction or self-mutilation, the smaller and softer PU-10 catheter compared favorably because of lower post-operative mortality rate and no unilateral lower limb paresis.
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Cocaine withdrawal impairs metabotropic glutamate receptor-dependent long-term depression in the nucleus accumbens.
J. Neurosci.
PUBLISHED: 03-18-2011
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Neuroadaptation in the nucleus accumbens (NAc), a central component of the mesolimbic dopamine (DA) system, has been implicated in the development of cocaine-induced psychomotor sensitization and relapse to cocaine seeking. However, little is known about the cellular and synaptic mechanisms underlying such adaptation. Using a mouse model of behavioral sensitization, we show that animals withdrawn from repeated cocaine exposure have a selective deficit in the ability to elicit metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) in the shell of the NAc in response to bath application of the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG). Experiments conducted in the presence of the selective mGluR1 antagonists 7-(hydroxyimino)cyclopropachromen-carboxylate ethyl ester and (S)-(+)-?-amino-4-carboxy-2-methylbenzeneacetic acid, or the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine, demonstrated that the impaired DHPG-LTD is likely attributable to a loss of mGluR5 function. Quantitative real-time reverse transcriptase-PCR and Western blot analysis revealed significant downregulation of mGluR5, but not mGluR1, mRNA and protein levels in the NAc shell. The inhibitory effect of repeated cocaine exposure on DHPG-LTD was selectively prevented when cocaine was coadministered with the selective D(1)-like DA receptor antagonist (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine. Furthermore, the levels of brain-derived neurotrophic factor (BDNF) protein in the NAc shell increased progressively after cocaine withdrawal, and the impairment of DHPG-LTD in the NAc shell was not found in slices from BDNF-knock-out mice after cocaine withdrawal. These results suggest that withdrawal from repeated cocaine exposure may result in increased BDNF levels in the NAc shell, which leads to a selective downregulation of mGluR5 and thereby impairs the induction of mGluR-dependent LTD.
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Sumoylation of hypoxia-inducible factor-1? ameliorates failure of brain stem cardiovascular regulation in experimental brain death.
PLoS ONE
PUBLISHED: 02-01-2011
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One aspect of brain death is cardiovascular deregulation because asystole invariably occurs shortly after its diagnosis. A suitable neural substrate for mechanistic delineation of this aspect of brain death resides in the rostral ventrolateral medulla (RVLM). RVLM is the origin of a life-and-death signal that our laboratory detected from blood pressure of comatose patients that disappears before brain death ensues. At the same time, transcriptional upregulation of heme oxygenase-1 in RVLM by hypoxia-inducible factor-1? (HIF-1?) plays a pro-life role in experimental brain death, and HIF-1? is subject to sumoylation activated by transient cerebral ischemia. It follows that sumoylation of HIF-1? in RVLM in response to hypoxia may play a modulatory role on brain stem cardiovascular regulation during experimental brain death.
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Clinical characteristics, vascular function, and inflammation in women with angina in the absence of coronary atherosclerosis: the Dallas Heart Study.
JACC Cardiovasc Imaging
PUBLISHED: 01-15-2011
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we sought to evaluate the relationship between angina and coronary artery calcium (CAC) in women, and among women without CAC, the associations between angina and clinical, vascular, and inflammatory factors.
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The potential role of mitochondrial dysfunction in seizure-associated cell death in the hippocampus and epileptogenesis.
J. Bioenerg. Biomembr.
PUBLISHED: 12-15-2010
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Epilepsy is considered one of the most common neurological disorders worldwide. The burst firing neurons associated with prolonged epileptic discharges could lead to a large number of changes with events of cascades at the cellular level. From its role as the cellular powerhouse, mitochondria also play a crucial role in the mechanisms of cell death. Emerging evidence has shown that prolonged seizures may result in mitochondrial dysfunction and increase of oxidative and nitrosative stress in the hippocampus that precede neuronal cell death and cause subsequent epileptogenesis. The selective dysfunction of mitochondrial respiratory chain Complex I has been suggested to be a biochemical hallmark of seizure-induced neuronal cell death and epileptogenesis. Therefore, protection of mitochondria from bioenergetic failure and oxidative stress in the hippocampus may open a new vista to the development of effective neuroprotective strategies against seizure-induced brain damage and to the design of novel treatment perspectives against therapy-resistant forms of epilepsy.
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Transcriptional upregulation of brain-derived neurotrophic factor in rostral ventrolateral medulla by angiotensin II: significance in superoxide homeostasis and neural regulation of arterial pressure.
Circ. Res.
PUBLISHED: 09-02-2010
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Oxidative stress in rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons for the maintenance of neurogenic vasomotor tone are located, contributes to neural mechanisms of hypertension. Emerging evidence suggests that brain-derived neurotrophic factor (BDNF) manifests "nontrophic" actions.
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Heme oxygenase-1 plays a pro-life role in experimental brain stem death via nitric oxide synthase I/protein kinase G signaling at rostral ventrolateral medulla.
J. Biomed. Sci.
PUBLISHED: 07-27-2010
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Despite its clinical importance, a dearth of information exists on the cellular and molecular mechanisms that underpin brain stem death. A suitable neural substrate for mechanistic delineation on brain stem death resides in the rostral ventrolateral medulla (RVLM) because it is the origin of a life-and-death signal that sequentially increases (pro-life) and decreases (pro-death) to reflect the advancing central cardiovascular regulatory dysfunction during the progression towards brain stem death in critically ill patients. The present study evaluated the hypothesis that heme oxygnase-1 (HO-1) may play a pro-life role as an interposing signal between hypoxia-inducible factor-1 (HIF-1) and nitric oxide synthase I (NOS I)/protein kinase G (PKG) cascade in RVLM, which sustains central cardiovascular regulatory functions during brain stem death.
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Proteomic investigation of a neural substrate intimately related to brain death.
Proteomics
PUBLISHED: 07-15-2010
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Our current understanding on brain death remains limited despite its clinical importance. This study evaluated whether the proteome expressed in the rat rostral ventrolateral medulla (RVLM), a neural substrate that our laboratory identified previously to be intimately related to brain death, is uniquely different from other brain areas, using the cerebral cortex, which is defunct under persistent vegetative state for comparison. We found that a group of antioxidant proteins, including members of the peroxiredoxin (Prx) family (Prx-1, Prx-2, Prx-5, Prx-6), thioredoxin and mitochondrial manganese superoxide dismutase, exhibited significantly higher protein and mRNA expression levels in RVLM when compared to cerebral cortex. Tissue oxygen, ATP contents and ATP synthase subunits ? and ? in RVLM were also significantly elevated. On the other hand, protein and mRNA levels of members of the ubiquitin-proteasome system, including proteasome subunit ? type-1, ubiquitin, uniquitin-conjugating enzyme E2 N, ubiquitin carboxyl-terminal hydrolase isozyme L1 and L3, were comparable in both brain regions. We conclude that a significantly elevated level of antioxidant proteins and mRNA in RVLM is consistent with the exhibition of higher tissue oxygen tension and metabolic energy production in this neural substrate, which together constitute a safeguard mechanism against brain death.
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46,XX DSD: the masculinised female.
Best Pract. Res. Clin. Endocrinol. Metab.
PUBLISHED: 06-15-2010
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The 46,XX disorders of sex development (DSDs) cause virilisation or masculinisation of the female foetus. The final common pathway of all 46,XX DSDs is excess dihydrotestosterone (DHT) or potent foreign androgen in the genital tissue during the critical period of sexual differentiation. Whereas the foetal testis is source of androgen in the male, it is the foetal adrenal that produces the DHT precursors in the female. By understanding the principles of human steroid biosynthesis, the pathogenesis of each disorder may be logically deduced, and treatment strategies are rationally constructed. In practice, however, therapies for many of these diseases are fraught with complications and caveats, and current approaches leave much room for improvement. This review discusses these diseases, their pathogenesis and approaches to therapy. We emphasise areas where improved treatments are sorely needed.
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Photoelectrochemical complexes for solar energy conversion that chemically and autonomously regenerate.
Nat Chem
PUBLISHED: 04-15-2010
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Naturally occurring photosynthetic systems use elaborate pathways of self-repair to limit the impact of photo-damage. Here, we demonstrate a complex consisting of two recombinant proteins, phospholipids and a carbon nanotube that mimics this process. The components self-assemble into a configuration in which an array of lipid bilayers aggregate on the surface of the carbon nanotube, creating a platform for the attachment of light-converting proteins. The system can disassemble upon the addition of a surfactant and reassemble upon its removal over an indefinite number of cycles. The assembly is thermodynamically metastable and can only transition reversibly if the rate of surfactant removal exceeds a threshold value. Only in the assembled state do the complexes exhibit photoelectrochemical activity. We demonstrate a regeneration cycle that uses surfactant to switch between assembled and disassembled states, resulting in an increased photoconversion efficiency of more than 300% over 168 hours and an indefinite extension of the system lifetime.
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Measurement of coronary flow response to cold pressor stress in asymptomatic women with cardiovascular risk factors using spiral velocity-encoded cine MRI at 3 Tesla.
Acta Radiol
PUBLISHED: 03-23-2010
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Background: Coronary sinus (CS) flow in response to a provocative stress has been used as a surrogate measure of coronary flow reserve, and velocity-encoded cine (VEC) magnetic resonance imaging (MRI) is an established technique for measuring CS flow. In this study, the cold pressor test (CPT) was used to measure CS flow response because it elicits an endothelium-dependent coronary vasodilation that may afford greater sensitivity for detecting early changes in coronary endothelial function. Purpose: To investigate the feasibility and reproducibility of CS flow reactivity (CSFR) to CPT using spiral VEC MRI at 3 Tesla in a sample of asymptomatic women with cardiovascular risk factors. Material and Methods: Fourteen asymptomatic women (age 38 years +/- 10) with cardiovascular risk factors were studied using 3D spiral VEC MRI of the CS at 3 T. The CPT was utilized as a provocative stress to measure changes in CS flow. CSFR to CPT was calculated from the ratio of CS flow during peak stress to baseline CS flow. Results: CPT induced a significant hemodynamic response as measured by a 45% increase in rate-pressure product (P<0.01). A significant increase in CS volume flow was also observed (baseline, 116 +/- 26 ml/min; peak stress, 152 +/- 34 ml/min, P=0.01). CSFR to CPT was 1.31 +/- 0.20. Test-retest variability of CS volume flow was 5% at baseline and 6% during peak stress. Conclusion: Spiral CS VEC MRI at 3 T is a feasible and reproducible technique for measuring CS flow in asymptomatic women at risk for cardiovascular disease. Significant changes in CSFR to CPT are detectable, without demanding pharmacologic stress.
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Extracellular signal-regulated kinase 1/2 plays a pro-life role in experimental brain stem death via MAPK signal-interacting kinase at rostral ventrolateral medulla.
J. Biomed. Sci.
PUBLISHED: 02-19-2010
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As the origin of a life-and-death signal detected from systemic arterial pressure, which sequentially increases (pro-life) and decreases (pro-death) to reflect progressive dysfunction of central cardiovascular regulation during the advancement towards brain stem death in critically ill patients, the rostral ventrolateral medulla (RVLM) is a suitable neural substrate for mechanistic delineation of this fatal phenomenon. The present study assessed the hypothesis that extracellular signal-regulated kinase 1/2 (ERK1/2), a member of the mitogen-activated protein kinases (MAPKs) that is important for cell survival and is activated specifically by MAPK kinase 1/2 (MEK1/2), plays a pro-life role in RVLM during brain stem death. We further delineated the participation of MAPK signal-interacting kinase (MNK), a novel substrate of ERK in this process.
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Transcriptional upregulation of nitric oxide synthase II by nuclear factor-kappaB promotes apoptotic neuronal cell death in the hippocampus following experimental status epilepticus.
J. Neurosci. Res.
PUBLISHED: 02-16-2010
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Whereas status epilepticus, or the condition of continuous epileptic seizures, produces a characteristic pattern of preferential neuronal cell loss in the hippocampus, the underlying mechanism is still unsettled. Based on an experimental model of temporal lobe status epilepticus, we demonstrated previously that prolonged seizures prompted an overproduction of nitric oxide (NO) by upregulation of NO synthase II (NOS II) in the hippocampal CA3 subfield, followed by the activation of mitochondrial apoptotic signaling cascade. Using the same animal model, the present study evaluated the hypothesis that transcriptional upregulation of NOS II gene by nuclear factor-kappaB (NF-kappaB) promotes apoptotic neuronal cell death in the hippocampus following status epilepticus. In Sprague-Dawley rats, significantly augmented nucleus-bound translocation of NF-kappaB p50 and p65 subunits and DNA binding activity of NF-kappaB were observed in hippocampal CA3 neurons as early as 30 min after elicitation of sustained seizure activity by microinjection of kainic acid into the CA3 subfield, followed by a progressive elevation that peaked at 90 min. In addition, application bilaterally into the hippocampal CA3 subfield of a selective NF-kappaB inhibitor, pyrrolidine dithiocarbamate or double-stranded kappaB decoy DNA significantly antagonized the activated NOS II-peroxynitrite signaling cascade (3 hr) and the associated manifestations of apoptotic cell death (7 days) in the hippocampus. We conclude that activation of NF-kappaB in hippocampal CA3 neurons upregulates NOS II gene expression following experimental temporal lobe status epilepticus, leading to apoptotic neuronal cell death in the hippocampus.
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ATAC and Mediator coactivators form a stable complex and regulate a set of non-coding RNA genes.
EMBO Rep.
PUBLISHED: 01-14-2010
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The Ada-Two-A-containing (ATAC) histone acetyltransferase and Mediator coactivator complexes regulate independent and distinct steps during transcription initiation and elongation. Here, we report the identification of a new stable molecular assembly formed between the ATAC and Mediator complexes in mouse embryonic stem cells. Moreover, we identify leucine zipper motif-containing protein 1 as a subunit of this meta-coactivator complex (MECO). Finally, we demonstrate that the MECO regulates a subset of RNA polymerase II-transcribed non-coding RNA genes. Our findings establish that transcription coactivator complexes can form stable subcomplexes to facilitate their combined actions on specific target genes.
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The desensitizing efficacy of a novel stannous-containing sodium fluoride dentifrice: an 8-week randomized and controlled clinical trial.
Am J Dent
PUBLISHED: 01-06-2010
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To assess the efficacy of a novel stannous-containing dentifrice in the reduction of dentin hypersensitivity when compared to a marketed positive control dentifrice.
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De novo expression of podocyte proteins in parietal epithelial cells during experimental glomerular disease.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 12-09-2009
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Studies have shown that certain cells of the glomerular tuft begin to express proteins considered unique to other cell types upon injury. Little is known about the response of parietal epithelial cells (PEC) to injury. To determine whether PECs change their phenotype upon injury to also express proteins traditionally considered podocyte specific, the following four models of glomerular disease were studied: the transforming growth factor (TGF)-beta1 transgenic mouse model of global glomerulosclerosis, the adriamycin model of focal segmental glomerulosclerosis (FSGS), the anti-glomerular basement membrane (GBM) model of crescentic glomerulonephritis, and the passive Heymann nephritis model of membranous nephropathy. Double immunostaining was performed with antibodies to podocyte-specific proteins (synaptopodin and Wilms tumor 1) and antibodies to PEC specific proteins (paired box gene 8 and claudin-1). No double staining was detected in normal mice. In contrast, the results showed a statistical increase in the number of cells attached to Bowman basement membrane that were double-positive for both podocyte/PEC proteins in TGF-beta1 transgenic, anti-GBM, and membranous animals. Double-positive cells for both podocyte and PEC proteins were also statistically increased in the glomerular tuft in TGF-beta1 transgenic, anti-GBM, and FSGS mice. These results are consistent with glomerular cells coexpressing podocyte and PEC proteins in experimental glomerular disease, but not under normal circumstances.
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The enigmatic parietal epithelial cell is finally getting noticed: a review.
Kidney Int.
PUBLISHED: 10-21-2009
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Although the normal glomerulus comprises four resident cell types, least is known about the parietal epithelial cells (PECs). This comprehensive review addresses the cellular origin of PECs, discusses the normal structure and protein makeup of PECs, describes PEC function, and defines the responses to injury in disease and how these events lead to clinical events. The data show that PECs have unique properties and that new functions are being recognized such as their role in differentiating into podocytes during disease.
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A new function for parietal epithelial cells: a second glomerular barrier.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 09-30-2009
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The functional role of glomerular parietal epithelial cells (PECs) remains poorly understood. To test the hypothesis that PECs form an impermeable barrier to filtered protein through the formation of tight junctions (TJ), studies were performed in normal animals and in the anti-glomerular basement membrane (GBM) model of crescentic nephritis. Electron microscopy showed well-defined TJ between PECs in normal mice, which no longer could be identified when these cells became extensively damaged or detached from their underlying Bowmans basement membrane. The TJ proteins claudin-1, zonula occludens-1, and occludin stained positive in PECs; however, staining decreased in anti-GBM disease. To show that these events were associated with increased permeability across the PEC-Bowmans basement membrane barrier, control and diseased animals were injected intravenously with either Texas red-conjugated dextran (3 kDa) or ovalbumin (45 kDa) tracers. As expected, both tracers were readily filtered across the glomerular filtration barrier and taken up by proximal tubular cells. However, when the glomerular filtration barrier was injured in anti-GBM disease, tracers were taken up by podocytes and PECs. Moreover, tracers were also detected between PECs and the underlying Bowmans basement membrane, and in many instances were detected in the extraglomerular space. We propose that together with its underlying Bowmans basement membrane, the TJ of PECs serve as a second barrier to protein. When disturbed following PEC injury, the increase in permeability of this layer to filtered protein is a mechanism underlying periglomerular inflammation characteristic of anti-GBM disease.
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Transcriptional upregulation of mitochondrial uncoupling protein 2 protects against oxidative stress-associated neurogenic hypertension.
Circ. Res.
PUBLISHED: 09-17-2009
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Mitochondrial uncoupling proteins (UCPs) belong to a superfamily of mitochondrial anion transporters that uncouple ATP synthesis from oxidative phosphorylation and mitigates mitochondrial reactive oxygen species production.
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Physical and biological aspects of renal vitrification.
Organogenesis
PUBLISHED: 07-15-2009
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Cryopreservation would potentially very much facilitate the inventory control and distribution of laboratory-produced organs and tissues. Although simple freezing methods are effective for many simple tissues, bioartificial organs and complex tissue constructs may be unacceptably altered by ice formation and dissolution. Vitrification, in which the liquids in a living system are converted into the glassy state at low temperatures, provides a potential alternative to freezing that can in principle avoid ice formation altogether. The present report provides a brief overview of the problem of renal vitrification. We report here the detailed case history of a rabbit kidney that survived vitrification and subsequent transplantation, a case that demonstrates both the fundamental feasibility of complex system vitrification and the obstacles that must still be overcome, of which the chief one in the case of the kidney is adequate distribution of cryoprotectant to the renal medulla. Medullary equilibration can be monitored by monitoring urine concentrations of cryoprotectant, and urine flow rate correlates with vitrification solution viscosity and the speed of equilibration. By taking these factors into account and by using higher perfusion pressures as per the case of the kidney that survived vitrification, it is becoming possible to design protocols for equilibrating kidneys that protect against both devitrification and excessive cryoprotectant toxicity.
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Brain stem death as the vital determinant for resumption of spontaneous circulation after cardiac arrest in rats.
PLoS ONE
PUBLISHED: 07-13-2009
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Spontaneous circulation returns to less than half of adult cardiac arrest victims who received in-hospital resuscitation. One clue for this disheartening outcome arises from the prognosis that asystole invariably takes place, after a time lag, on diagnosis of brain stem death. The designation of brain stem death as the point of no return further suggests that permanent impairment of the brain stem cardiovascular regulatory machinery precedes death. It follows that a crucial determinant for successful revival of an arrested heart is that spontaneous circulation must resume before brain stem death commences. Here, we evaluated the hypothesis that maintained functional integrity of the rostral ventrolateral medulla (RVLM), a neural substrate that is intimately related to brain stem death and central circulatory regulation, holds the key to the vital time-window between cardiac arrest and resumption of spontaneous circulation.
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Characterizing cardiovascular risk in women with polycystic ovary syndrome: more than the sum of its parts?
Semin. Reprod. Med.
PUBLISHED: 06-15-2009
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Polycystic ovary syndrome (PCOS), a condition of irregular menses and androgen excess, is the most common endocrinopathy of young women. Insulin resistance is a well-established feature among many women with PCOS, even in the nonobese. Therefore, it is not surprising that PCOS is frequently associated with cardiovascular risk factors and the metabolic syndrome. However, it is not known whether PCOS is an independent risk factor for atherosclerosis and cardiovascular (CV) events or whether CV risk is attributable to associated risk factors. We review previous studies on CV risk and disease in women with PCOS, describing the pitfalls and challenges in ascribing CV risk to PCOS. Women with PCOS might be partly reassured that their relative risk approximates that of the metabolic syndrome (RR 1.5) and also strongly counseled at the individual level about the greatest potential threat to their CV health, the development of type 2 diabetes.
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Hypoxia-inducible factor 1/heme oxygenase 1 cascade as upstream signals in the prolife role of heat shock protein 70 at rostral ventrolateral medulla during experimental brain stem death.
Shock
PUBLISHED: 04-01-2009
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As the origin of a life-and-death signal that reflects central cardiovascular regulatory failure during brain stem death, the rostral ventrolateral medulla (RVLM) is a suitable neural substrate to delineate the cellular mechanisms of this fateful phenomenon. Based on a clinically relevant animal model that used the organophosphate pesticide mevinphos (Mev) as the experimental insult, we reported previously that heat shock protein 70 (HSP70) in RVLM plays a prolife role by ameliorating circulatory depression during brain stem death. Because Mev also elicits significant hypoxia in RVLM, this study evaluated the hypothesis that the hypoxia-inducible factor 1 (HIF-1)/heme oxygenase 1 (HO-1) cascade acts as upstream signals in the prolife role of HSP70 at RVLM during experimental brain stem death. In Sprague-Dawley rats maintained under propofol anesthesia, transcription activity assay or Western blot analysis revealed an enhancement of nuclear activity of HIF-1alpha or augmentation of HO-1 and HSP70 expression in RVLM preferentially during the prolife phase of Mev intoxication. Loss-of-function manipulations in RVLM using HIF-1alpha, HIF-1beta, or HO-1 antiserum or antisense hif-1alpha or ho-1 oligonucleotide significantly antagonized the preferential upregulation of HSP70, depressed the sustained cardiovascular regulatory machinery during the prolife phase, and exacerbated circulatory depression during the prodeath phase. Immunoneutralization of HIF-1alpha also blunted the preferential increase in HO-1 expression. We conclude that the repertoire of cellular events in RVLM during the prolife phase in our Mev intoxication of brain stem death triggered by hypoxia entails sequential activation of HIF-1, HO-1, and HSP70, leading to neuroprotection by amelioration of cardiovascular depression.
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Cardiovascular risk factors and coronary atherosclerosis in retired National Football League players.
Am. J. Cardiol.
PUBLISHED: 03-19-2009
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A high prevalence of obesity exists in National Football League (NFL) players as determined by body mass index (BMI). It is not established whether increased BMI is associated with a greater prevalence of cardiovascular (CV) risk factors or coronary atherosclerosis in former NFL players than in nonathletes. This study compared CV risk factors and coronary atherosclerosis in retired NFL players to 2 groups of community controls, the population-based Dallas Heart Study and the preventive medicine cohort, the Aerobics Center Longitudinal Study. Retired NFL players (n = 201) were matched for ethnicity, age, and BMI (Aerobics Center Longitudinal Study, age only). CV risk factors were assessed by survey and screening visit. Coronary atherosclerosis was measured by computed tomography as coronary artery calcium (CAC). Compared to population-based controls, retired NFL players had a significantly lower prevalence of diabetes, hypertension, sedentary lifestyle, and metabolic syndrome, yet a higher prevalence of impaired fasting glucose and hyperlipidemia. However, there was no significant difference in the prevalence of detectable CAC (46% vs 48.3%, p = 0.69) or distribution of CAC (0 to 10, 10 to 100, 100 to 400, > or =400, p = 0.11). Comparing retired NFL players to the physically active preventive medicine controls, there was no difference in the amount of CAC. In retired NFL players, age and hyperlipidemia, not body size, were the most significant predictors of CAC. In conclusion, despite their large body size, retired NFL players do not have a greater prevalence of CV risk factors or amount of CAC than community controls.
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Enhancing effects of morphine on methamphetamine-induced reinforcing behavior and its association with dopamine release and metabolism in mice.
J. Neurochem.
PUBLISHED: 02-20-2009
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Polydrug abuse has become a significant problem worldwide, and the combined use of methamphetamine (MA) and morphine (M) is now highly prevalent among addicts. In the present study, we investigated the neurobehavioral effects of repeated treatment regimens of these drugs (i.p. administration of 0.75 mg/kg/day MA, 5 mg/kg/day M, and their combination for five consecutive days followed by once weekly for five consecutive weeks) in mice. In addition, we used an in vivo microdialysis technique to study the changes in extracellular concentrations of dopamine (DA) and its metabolites in the mouse striatum after challenge administration of these drugs. The results showed that systemic M increased MA-induced conditioned place preference (CPP), as revealed by higher CPP values which were also maintained for a longer duration compared with those induced by an identical dose of MA or M alone. Subsequent to challenge with combined MA and M, mice exhibited an increase in stereotyped behavior, which appeared to be associated with an elevation of extracellular concentration of DA in the striatum. Our findings suggest that M not only produces synergistic effects on MA-induced CPP, but also interacts with MA to induce stereotyped behavioral sensitization which is mediated by an increase in DA outflow in the striatum. These findings provide insight into the behavioral and neurochemical basis responsible for the combined abuse liability of MA and M.
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Oxidative impairment of mitochondrial electron transport chain complexes in rostral ventrolateral medulla contributes to neurogenic hypertension.
Hypertension
PUBLISHED: 02-14-2009
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The role for mitochondrial electron transport chain (ETC) in neurogenic hypertension is unidentified. We evaluated the hypothesis that feedforward depression of mitochondrial ETC functions by superoxide anion (O(2)(.-)) and hydrogen peroxide (H(2)O(2)) in rostral ventrolateral medulla (RVLM), a brain stem site that maintains sympathetic vasomotor tone and contributes to oxidative stress and neural mechanism of hypertension. Compared with normotensive Wistar-Kyoto rats, spontaneously hypertensive rats exhibited mitochondrial ETC dysfunctions in RVLM in the forms of depressed complex I or III activity and reduced electron coupling capacity between complexes I and III or II and III. Microinjection of coenzyme Q(10) into RVLM of spontaneously hypertensive rats reversed the depressed ETC activity and augmented O(2)(.-) production and hypertensive phenotypes. This mobile electron carrier also antagonized the elevated H(2)O(2) in RVLM and vasopressor responses to complex I (rotenone) or III (antimycin A) inhibitor in Wistar-Kyoto or prehypertensive rats. Intracerebroventricular infusion of angiotensin II promoted mitochondrial ETC dysfunctions in Wistar-Kyoto rats, and coenzyme Q(10) or gene knockdown of the p22(phox) subunit of NADPH oxidase antagonized the resultant elevation of H(2)O(2) in RVLM. Overexpression of superoxide dismutase or catalase in RVLM of spontaneously hypertensive rats by gene transfer reversed mitochondrial dysfunctions and blunted the augmented O(2)(.-) and H(2)O(2) in RVLM. We conclude that O(2)(.-)- and H(2)O(2)-dependent feedforward impairment of mitochondrial ETC complexes because of predisposed downregulation of superoxide dismutase or catalase and a cross-talk between NADPH oxidase-derived O(2)(.-) and ETC enzymes contribute to chronic oxidative stress in the RVLM of spontaneously hypertensive rats, leading to augmented sympathetic vasomotor tone and hypertension.
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Contribution of nitric oxide, superoxide anion, and peroxynitrite to activation of mitochondrial apoptotic signaling in hippocampal CA3 subfield following experimental temporal lobe status epilepticus.
Epilepsia
PUBLISHED: 01-31-2009
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One cellular consequence of status epilepticus is apoptosis in the hippocampal CA3 subfield. We evaluated the hypothesis that the repertoire of cellular events that underlie such elicited cell death entails mitochondrial dysfunction induced by an excessive production of nitric oxide synthase II (NOS II)-derived NO, increased superoxide anion (O(2)(-)) production, and peroxynitrite formation.
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Differential protection against oxidative stress and nitric oxide overproduction in cardiovascular and pulmonary systems by propofol during endotoxemia.
J. Biomed. Sci.
PUBLISHED: 01-15-2009
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Both overproduction of nitric oxide (NO) and oxidative injury of cardiovascular and pulmonary systems contribute to fatal cardiovascular depression during endotoxemia. We investigated in the present study the relative contribution of oxidative stress and NO to cardiovascular depression during different stages of endotoxemia, and delineated their roles in cardiovascular protective effects of a commonly used anesthetic propofol during endotoxemia.
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The role of simulation in neurosurgical education: a survey of 99 United States neurosurgery program directors.
World Neurosurg
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With the reduction of resident work hours and the increasing focus on patient safety, it has become evident that simulation has a growing role to play in surgical education. We surveyed the program directors of 99 U.S. Neurosurgery programs in an effort to better understand how simulation can be implemented in Neurosurgery and to gain insight into key issues that are currently being discussed amongst Neurosurgical educators.
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Pro-life role for c-Jun N-terminal kinase and p38 mitogen-activated protein kinase at rostral ventrolateral medulla in experimental brain stem death.
J. Biomed. Sci.
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Based on an experimental brain stem death model, we demonstrated previously that activation of the mitogen-activated protein kinase kinase 1/2 (MEK1/2)/extracellular signal-regulated kinase 1/2 (ERK1/2)/ mitogen-activated protein kinase signal-interacting kinase 1/2 (MNK1/2) cascade plays a pro-life role in the rostral ventrolateral medulla (RVLM), the origin of a life-and-death signal detected from systemic arterial pressure, which sequentially increases (pro-life) and decreases (pro-death) to reflect progressive dysfunction of central cardiovascular regulation during the advancement towards brain stem death in critically ill patients. The present study assessed the hypothesis that, in addition to ERK1/2, c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK), the other two mammalian members of MAPKs that are originally identified as stress-activated protein kinases, are activated specifically by MAPK kinase 4 (MAP2K4) or MAP2K6 and play a pro-life role in RVLM during experimental brain stem death. We further delineated the participation of phosphorylating activating transcriptional factor-2 (ATF-2) and c-Jun, the classical transcription factor activated by JNK or p38MAPK, in this process.
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Discovery of a novel series of 4-quinolone JNK inhibitors.
Bioorg. Med. Chem. Lett.
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A novel series of highly selective JNK inhibitors based on the 4-quinolone scaffold was designed and synthesized. Structure based drug design was utilized to guide the compound design as well as improvements in the physicochemical properties of the series. Compound (13c) has an IC(50) of 62/170 nM for JNK1/2, excellent kinase selectivity and impressive efficacy in a rodent asthma model.
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Effects of video game playing on cerebral blood flow in young adults: a SPECT study.
Psychiatry Res
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To study the impact of video game playing on the human brain, the effects of two video games playing on cerebral blood flow (CBF) in young adults were determined. Thirty healthy subjects comprising 18 males and 12 females who were familiar with video game playing were recruited. Each subject underwent three sessions of single photon emission computed tomography (SPECT) with a bolus injection of 20 mCi (99m)Tc ECD IV to measure their CBF. The first measurement was performed as baseline, the second and third measurements were performed after playing two different video games for 30 min, respectively. Statistic parametric mapping (SPM2) with Matlab 6.5 implemented on a personal computer was used for image analysis. CBF was significantly decreased in the prefrontal cortex and significantly increased in the temporal and occipital cortices after both video games playing. Furthermore, decreased CBF in the anterior cingulate cortex (ACC) which was significantly correlated with the number of killed characters was found after the violent game playing. The major finding of hypo-perfusion in prefrontal regions after video game playing is consistent with a previous study showing reduced or abnormal prefrontal cortex functions after video game playing. The second finding of decreased CBF in the ACC after playing the violent video game provides support for a previous hypothesis that the ACC might play a role in regulating violent behavior.
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Aggression in bipolar II disorder and its relation to the serotonin transporter.
J Affect Disord
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Aggression is frequently observed in patients diagnosed with bipolar disorder (BD). Previous studies found a negative association between aggression and serotoninergic function in patients with BD, as well as in healthy subjects. The objective of this study was to determine whether there is an association between aggression and the availability of the serotonin transporter (SERT) in euthymic BD II patients.
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Understanding oligonucleotide-templated nanocrystals: growth mechanisms and surface properties.
ACS Nano
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We describe studies of nanoparticle synthesis using oligonucleotides as capping ligands. The oligonucleotides nucleate, grow, and stabilize near-infrared fluorescent, approximately uniform PbS nanocrystals in an aqueous environment. The properties of the resulting particles strongly depend upon the sequences as well as synthesis conditions. Fourier Transform infrared measurements suggest that functional groups on the nucleobases such as carbonyl and amine moieties are responsible for surface passivation, while the phosphate backbone is strained to accommodate nucleobase bonding, preventing irreversible aggregation and thereby stabilizing the colloids. Our theoretical model indicates that oligonucleotide-mediated particle growth relies on the chemical reactivity of the oligonucleotide ligands that saturate dangling bonds of growing clusters, and favorable sequences are those that have the highest surface reactivity with growing particles. The oligonucleotide template approach is facile and versatile, offering a route to produce a range of material compositions for other chalcogenide semiconductor quantum dots and metal oxide nanoparticles.
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Peroxisome proliferator-activated receptors ?/mitochondrial uncoupling protein 2 signaling protects against seizure-induced neuronal cell death in the hippocampus following experimental status epilepticus.
J Neuroinflammation
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Status epilepticus induces subcellular changes that may lead to neuronal cell death in the hippocampus. However, the mechanism of seizure-induced neuronal cell death remains unclear. The mitochondrial uncoupling protein 2 (UCP2) is expressed in selected regions of the brain and is emerged as an endogenous neuroprotective molecule in many neurological disorders. We evaluated the neuroprotective role of UCP2 against seizure-induced hippocampal neuronal cell death under experimental status epilepticus.
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Redox-sensitive oxidation and phosphorylation of PTEN contribute to enhanced activation of PI3K/Akt signaling in rostral ventrolateral medulla and neurogenic hypertension in spontaneously hypertensive rats.
Antioxid. Redox Signal.
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The activity of phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (Akt) is enhanced under hypertension. The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a negative regulator of PI3K signaling, and its activity is redox-sensitive. In the rostral ventrolateral medulla (RVLM), which is responsible for the maintenance of blood pressure, oxidative stress plays a pivotal role in neurogenic hypertension. The present study evaluated the hypothesis that redox-sensitive inactivation of PTEN results in enhanced PI3K/Akt signaling in RVLM, leading to neurogenic hypertension.
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Engagement of ubiquitination and de-ubiquitination at rostral ventrolateral medulla in experimental brain death.
J. Biomed. Sci.
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Whereas brain death is a vitally important clinical phenomenon, our contemporary understanding on its underlying cellular mechanisms remains elusive. This study evaluated whether the ubiquitin-proteasome system (UPS) in the rostral ventrolateral medulla (RVLM), a neural substrate that our laboratory identified previously to be intimately related to brain death, is engaged in this fatal process.
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Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.
PLoS ONE
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Status epilepticus (SE) is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM), a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF) via an antioxidant action.
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Clinical significance of serological biomarkers and neuropsychological performances in patients with temporal lobe epilepsy.
BMC Neurol
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Temporal lobe epilepsy (TLE) is a common form of focal epilepsy. Serum biomarkers to predict cognitive performance in TLE patients without psychiatric comorbidities and the link with gray matter (GM) atrophy have not been fully explored.
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Defunct brain stem cardiovascular regulation underlies cardiovascular collapse associated with methamphetamine intoxication.
J. Biomed. Sci.
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Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism.
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Bioenergetics failure and oxidative stress in brain stem mediates cardiovascular collapse associated with fatal methamphetamine intoxication.
PLoS ONE
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Whereas sudden death, most often associated with cardiovascular collapse, occurs in abusers of the psychostimulant methamphetamine (METH), the underlying mechanism is much less understood. The demonstration that successful resuscitation of an arrested heart depends on maintained functionality of the rostral ventrolateral medulla (RVLM), which is responsible for the maintenance of stable blood pressure, suggests that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse. We tested the hypothesis that cessation of brain stem cardiovascular regulation because of a loss of functionality in RVLM mediated by bioenergetics failure and oxidative stress underlies the cardiovascular collapse elicited by lethal doses of METH.
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Both cyclin I and p35 are required for maximal survival benefit of cyclin-dependent kinase 5 in kidney podocytes.
Am. J. Physiol. Renal Physiol.
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Cyclin-dependent kinase (Cdk)-5 is activated by both cyclin I and the noncyclin activator p35 in terminally differentiated cells such as kidney podocytes and neurons. Cyclin I and p35 are restricted to podocytes in the kidney, and each limit podocyte apoptosis by activating Cdk5. To determine whether both activators are necessary, or whether they serve backup roles, a double cyclin I-p35 null mouse was generated. Experimental glomerular disease characterized by podocyte apoptosis was then induced by administering an anti-podocyte antibody. The results showed that under nonstressed conditions double mutants had normal kidney structure and function and were indistinguishable from wild-type, cyclin I(-/-), or p35(-/-) mice. In contrast, when stressed with disease, podocyte apoptosis increased fourfold compared with diseased cyclin I(-/-) or p35(-/-) mice. This resulted in a more pronounced decrease in podocyte number, proteinuria, and glomerulosclerosis. Under normal states and nephritic states, levels for the prosurvival protein Bcl-2 were lower in double cyclin I(-/-) p35(-/-) mice than the other mice. Similarly, levels of Bcl-xL, another prosurvival member, were lower in normal and nephritic double cyclin I(-/-) p35(-/-) mice but similar to single-cyclin I(-/-) mice. Moreover, levels of ERK1/2 and MEK1/2 activation were lower in nephritic double cyclin I(-/-) p35(-/-) mice but similar to single-cyclin I(-/-) mice. The results demonstrate that the activators of Cdk5, p35, and cyclin I are not required for normal kidney function. However, they play pivotal coordinated roles in maintaining podocyte survival during stress states in disease.
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Biphasic Response of Mitochondrial Biogenesis to Oxidative Stress in Visceral Fat of Diet-Induced Obesity Mice.
Antioxid. Redox Signal.
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Aims Studies in skeletal muscle demonstrate a strong association of mitochondrial dysfunction with insulin resistance (IR). However, there is still a paucity of knowledge regarding the alteration of mitochondria in adipose tissue in the pathogenesis of IR in obesity. We investigated the mitochondrial biogenesis in visceral fat (VF) and subcutaneous fat (SF) in C57BL/6J mice fed a high-fat, high-sucrose diet for 12 months. Results Impairment of glucose tolerance and insulin sensitivity developed after one month of the diet and was associated with a prompt increase of VF. The VF adipocytes were larger than those in the SF and had increased expressions of HIF1? and p-NF?B p65. However, alteration of mitochondrial biogenesis did not occur in the early stage, when increased intracellular reactive oxygen species (ROS), mitochondrial oxygen consumption rate, and mitochondrial ROS emerged at the 1st, 2nd and 2nd month, respectively. Until the 6th month, the VF had markedly increased mitochondrial DNA content and expression of PGC1?, Tfam, ATP5A, and MnSOD. This increase of mitochondrial biogenesis was followed by a generalized decrease at the 12th month and the mitochondrial morphology altered markedly. In the late stage, although mitochondrial ROS decreased, the increased expression of 8-OHdG in VF continued. Innovation and Conclusion These data suggest that IR and ROS production occur before the biphasic changes of mitochondrial biogenesis in adipose tissue and the VF plays a more crucial role.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.