Science.gov

Sample records for hypoxia augments chemoreflex

  1. Lipopolysaccharide and Interleukin 1 Augment the Effects of Hypoxia and Inflammation in Human Pulmonary Arterial Tissue

    NASA Astrophysics Data System (ADS)

    Ziesche, Rolf; Petkov, Venzeslav; Williams, John; Zakeri, Schaker M.; Mosgoller, Wilhelm; Knofler, Martin; Block, Lutz H.

    1996-10-01

    The combined effects of hypoxia and interleukin 1, lipopolysaccharide, or tumor necrosis factor α on the expression of genes encoding endothelial constitutive and inducible nitric oxide synthases, endothelin 1, interleukin 6, and interleukin 8 were investigated in human primary pulmonary endothelial cells and whole pulmonary artery organoid cultures. Hypoxia decreased the expression of constitutive endothelial nitric oxide synthase (NOS-3) mRNA and NOS-3 protein as compared with normoxic conditions. The inhibition of expression of NOS-3 corresponded with a reduced production of NO. A combination of hypoxia with bacterial lipopolysaccharide, interleukin 1β , or tumor necrosis factor α augmented both effects. In contrast, the combination of hypoxia and the inflammatory mediators superinduced the expression of endothelin 1, interleukin 6, and interleukin 8. Here, we have shown that inflammatory mediators aggravate the effect of hypoxia on the down-regulation of NOS-3 and increase the expression of proinflammatory cytokines in human pulmonary endothelial cells and whole pulmonary artery organoid cultures.

  2. Carotid body chemoreflex: a driver of autonomic abnormalities in sleep apnoea.

    PubMed

    Prabhakar, Nanduri R

    2016-08-01

    What is the topic of this review? This article presents emerging evidence for heightened carotid body chemoreflex activity as a major driver of sympathetic activation and hypertension in sleep apnoea patients. What advances does it heighlight? This article discusses the recent advances on cellular, molecular and epigenetic mechanisms underlying the exaggerated chemoreflex in experimental models of sleep apnoea. The carotid bodies are the principal peripheral chemoreceptors for detecting changes in arterial blood oxygen concentration, and the resulting chemoreflex is a potent regulator of the sympathetic tone, blood pressure and breathing. Sleep apnoea is a disease of the respiratory system that affects several million adult humans. Apnoeas occur during sleep, often as a result of obstruction of the upper airway (obstructive sleep apnoea) or because of defective respiratory rhythm generation by the CNS (central sleep apnoea). Patients with sleep apnoea exhibit several co-morbidities, with the most notable among them being heightened sympathetic nerve activity and hypertension. Emerging evidence suggests that intermittent hypoxia resulting from periodic apnoea stimulates the carotid body, and the ensuing chemoreflex mediates the increased sympathetic tone and hypertension in sleep apnoea patients. Rodent models of intermittent hypoxia that simulate the O2 saturation profiles encountered during sleep apnoea have provided important insights into the cellular and molecular mechanisms underlying the heightened carotid body chemoreflex. This article describes how intermittent hypoxia affects the carotid body function and discusses the cellular, molecular and epigenetic mechanisms underlying the exaggerated chemoreflex. PMID:27474260

  3. Augmentation of aerobic respiration and mitochondrial biogenesis in skeletal muscle by hypoxia preconditioning with cobalt chloride

    SciTech Connect

    Saxena, Saurabh; Shukla, Dhananjay; Bansal, Anju

    2012-11-01

    High altitude/hypoxia training is known to improve physical performance in athletes. Hypoxia induces hypoxia inducible factor-1 (HIF-1) and its downstream genes that facilitate hypoxia adaptation in muscle to increase physical performance. Cobalt chloride (CoCl{sub 2}), a hypoxia mimetic, stabilizes HIF-1, which otherwise is degraded in normoxic conditions. We studied the effects of hypoxia preconditioning by CoCl{sub 2} supplementation on physical performance, glucose metabolism, and mitochondrial biogenesis using rodent model. The results showed significant increase in physical performance in cobalt supplemented rats without (two times) or with training (3.3 times) as compared to control animals. CoCl{sub 2} supplementation in rats augmented the biological activities of enzymes of TCA cycle, glycolysis and cytochrome c oxidase (COX); and increased the expression of glucose transporter-1 (Glut-1) in muscle showing increased glucose metabolism by aerobic respiration. There was also an increase in mitochondrial biogenesis in skeletal muscle observed by increased mRNA expressions of mitochondrial biogenesis markers which was further confirmed by electron microscopy. Moreover, nitric oxide production increased in skeletal muscle in cobalt supplemented rats, which seems to be the major reason for peroxisome proliferator activated receptor-gamma coactivator-1α (PGC-1α) induction and mitochondrial biogenesis. Thus, in conclusion, we state that hypoxia preconditioning by CoCl{sub 2} supplementation in rats increases mitochondrial biogenesis, glucose uptake and metabolism by aerobic respiration in skeletal muscle, which leads to increased physical performance. The significance of this study lies in understanding the molecular mechanism of hypoxia adaptation and improvement of work performance in normal as well as extreme conditions like hypoxia via hypoxia preconditioning. -- Highlights: ► We supplemented rats with CoCl{sub 2} for 15 days along with training. ► Co

  4. Neonatal Maternal Separation Augments Carotid Body Response to Hypoxia in Adult Males but Not Female Rats

    PubMed Central

    Soliz, Jorge; Tam, Rose; Kinkead, Richard

    2016-01-01

    Perinatal exposure to adverse experiences disrupts brain development, including the brainstem network that regulates breathing. At adulthood, rats previously subjected to stress (in the form of neonatal maternal separation; NMS) display features reported in patients suffering from sleep disordered breathing, including an increased hypoxic ventilatory response and hypertension. This effect is also sex-specific (males only). Based on these observations, we hypothesized that NMS augments the carotid body's O2-chemosensitivity. Using an isolated and perfused ex vivo carotid body preparation from adult rats we compared carotid sinus nerve (CSN) responses to hypoxia and hypercapnia in carotid bodies harvested from adult rats that either experienced control conditions (no experimental manipulation) or were subjected to NMS (3 h/day from postnatal days 3 to 12). In males, the CSN response to hypoxia measured in preparations from NMS males was 1.5 fold higher than controls. In control rats, the female's response was similar to that of males; however, the increase in CSN activity measured in NMS females was 3.0 times lower than controls. The CSN response to hypercapnia was not influenced by stress or sex. We conclude that NMS is sufficient to have persistent and sex-specific effects on the carotid body's response to hypoxia. Because NMS also has sex-specific effects on the neuroendocrine response to stress, we propose that carotid body function is influenced by stress hormones. This, in turn, leads to a predisposition toward cardio-respiratory disorders. PMID:27729873

  5. Peripheral chemoreflex inhibition with low-dose dopamine: new insight into mechanisms of extreme apnea.

    PubMed

    Bain, Anthony R; Dujic, Zeljko; Hoiland, Ryan L; Barak, Otto F; Madden, Dennis; Drvis, Ivan; Stembridge, Mike; MacLeod, David B; MacLeod, Douglas M; Ainslie, Philip N

    2015-11-01

    The purpose of this study was to determine the impact of peripheral chemoreflex inhibition with low-dose dopamine on maximal apnea time, and the related hemodynamic and cerebrovascular responses in elite apnea divers. In a randomized order, participants performed a maximal apnea while receiving either intravenous 2 μg·kg(-1)·min(-1) dopamine or volume-matched saline (placebo). The chemoreflex and hemodynamic response to dopamine was also assessed during hypoxia [arterial O2 tension, (PaO2 ) ∼35 mmHg] and mild hypercapnia [arterial CO2 tension (PaCO2 ) ∼46 mmHg] that mimicked the latter parts of apnea. Outcome measures included apnea duration, arterial blood gases (radial), heart rate (HR, ECG), mean arterial pressure (MAP, intra-arterial), middle (MCAv) and posterior (PCAv) cerebral artery blood velocity (transcranial ultrasound), internal carotid (ICA) and vertebral (VA) artery blood flow (ultrasound), and the chemoreflex responses. Although dopamine depressed the ventilatory response by 27 ± 41% (vs. placebo; P = 0.01), the maximal apnea duration was increased by only 5 ± 8% (P = 0.02). The PaCO2 and PaO2 at apnea breakpoint were similar (P > 0.05). When compared with placebo, dopamine increased HR and decreased MAP during both apnea and chemoreflex test (P all <0.05). At rest, dopamine compared with placebo dilated the ICA (3.0 ± 4.1%, P = 0.05) and VA (6.6 ± 5.0%, P < 0.01). During apnea and chemoreflex test, conductance of the cerebral vessels (ICA, VA, MCAv, PCAv) was increased with dopamine; however, flow (ICA and VA) was similar. At least in elite apnea divers, the small increase in apnea time and similar PaO2 at breakpoint (∼31 mmHg) suggest the apnea breakpoint is more related to PaO2 , rather than peripheral chemoreflex drive to breathe.

  6. Mechanisms of maladaptive responses of peripheral chemoreceptors to intermittent hypoxia in sleep-disordered breathing.

    PubMed

    Fung, Man Lung; Tipoe, George Lim; Leung, Po Sing

    2014-02-25

    Peripheral chemoreceptors in the carotid body play important roles in the transduction of chemical stimuli in the arterial blood to the central for eliciting the chemoreflex, which mediates the ventilatory and circulatory responses to hypoxia. The activity of carotid chemoreceptor is modulated and significantly contributes to the ventilatory acclimatization at high altitude. In addition, the carotid chemoreceptor activity is augmented in patients with sleep-disordered breathing, notably in central or obstructive sleep apnea, and also in experimental animals. Thus, the carotid body functions to maintain the oxygen homeostasis, whereas anomalous carotid chemoreceptor activities could be both adaptive and pathogenic in sleep apnea. This review aims to summarize the cellular and molecular mechanisms that could mediate the augmented chemoreceptor activity induced by intermittent hypoxia. Our recent findings suggest a pathogenic role of inflammation mediated by an upregulation of renin-angiotensin system in the carotid body in the over-activity of the chemoreflex. These locally regulated mechanisms are proposed to be a significant part of the hypoxia-mediated maladaptive changes of the carotid body function, which could play a role in the pathophysiology of sleep apnea.

  7. Prediction of the Chemoreflex Gain by Common Clinical Variables in Heart Failure

    PubMed Central

    Mirizzi, Gianluca; Giannoni, Alberto; Ripoli, Andrea; Iudice, Giovanni; Bramanti, Francesca; Emdin, Michele; Passino, Claudio

    2016-01-01

    Background Peripheral and central chemoreflex sensitivity, assessed by the hypoxic or hypercapnic ventilatory response (HVR and HCVR, respectively), is enhanced in heart failure (HF) patients, is involved in the pathophysiology of the disease, and is under investigation as a potential therapeutic target. Chemoreflex sensitivity assessment is however demanding and, therefore, not easily applicable in the clinical setting. We aimed at evaluating whether common clinical variables, broadly obtained by routine clinical and instrumental evaluation, could predict increased HVR and HCVR. Methods and results 191 patients with systolic HF (left ventricular ejection fraction—LVEF—<50%) underwent chemoreflex assessment by rebreathing technique to assess HVR and HCVR. All patients underwent clinical and neurohormonal evaluation, comprising: echocardiogram, cardiopulmonary exercise test (CPET), daytime cardiorespiratory monitoring for breathing pattern evaluation. Regarding HVR, multivariate penalized logistic regression, Bayesian Model Averaging (BMA) logistic regression and random forest analysis identified, as predictors, the presence of periodic breathing and increased slope of the relation between ventilation and carbon dioxide production (VE/VCO2) during exercise. Again, the above-mentioned statistical tools identified as HCVR predictors plasma levels of N-terminal fragment of proBNP and VE/VCO2 slope. Conclusions In HF patients, the simple assessment of breathing pattern, alongside with ventilatory efficiency during exercise and natriuretic peptides levels identifies a subset of patients presenting with increased chemoreflex sensitivity to either hypoxia or hypercapnia. PMID:27099934

  8. Sympathetic neural outflow and chemoreflex sensitivity are related to spontaneous breathing rate in normal men.

    PubMed

    Narkiewicz, Krzysztof; van de Borne, Philippe; Montano, Nicola; Hering, Dagmara; Kara, Tomas; Somers, Virend K

    2006-01-01

    Respiration contributes importantly to short-term modulation of sympathetic nerve activity. However, the relationship between spontaneous breathing rate, chemoreflex function, and direct measures of sympathetic traffic in healthy humans has not been studied previously. We tested the hypothesis that muscle sympathetic nerve activity and chemoreflex sensitivity are linked independently to respiratory rate in normal subjects. We studied 69 normal male subjects aged 29.6+/-8.1 years. Subjects were subdivided according to the tertiles of respiratory rate distributions. Mean respiration rate was 10.6 breaths/min in the first tertile, 14.8 breaths/min in the second tertile, and 18.0 breaths/min in the third tertile. Subjects from the third tertile (faster respiratory rate) had greater sympathetic activity than subjects from the first tertile (slower respiratory rate; 29+/-3 versus 17+/-2 bursts/min; P<0.001). Stepwise multiple linear regression analysis revealed that only respiratory rate was linked independently to sympathetic activity (r=0.42; P<0.001). In comparison to subjects with slow respiratory rate, subjects with fast respiratory rate had greater increases in minute ventilation during both hypercapnia (7.3+/-0.8 versus 3.2+/-1.0 L/min; P=0.005) and hypoxia (5.7+/-0.8 versus 2.4+/-0.7 L/min; P=0.007). Muscle sympathetic nerve activity and chemoreflex sensitivity are linked to spontaneous respiratory rate in normal humans. Faster respiratory rate is associated with higher levels of sympathetic traffic and potentiated responses to hypoxia and hypercapnia. Spontaneous breathing frequency, central sympathetic outflow, and chemoreflex sensitivity exhibit significant and hitherto unrecognized interactions in the modulation of neural circulatory control.

  9. Interaction between cardiac sympathetic afferent reflex and chemoreflex is mediated by the NTS AT1 receptors in heart failure.

    PubMed

    Wang, Wei-Zhong; Gao, Lie; Wang, Han-Jun; Zucker, Irving H; Wang, Wei

    2008-09-01

    Several sympathoexcitatory reflexes, such as the cardiac sympathetic afferent reflex (CSAR) and arterial chemoreflex, are significantly augmented and contribute to elevated sympathetic outflow in chronic heart failure (CHF). This study was undertaken to investigate the interaction between the CSAR and the chemoreflex in CHF and to further identify the involvement of angiotensin II type 1 receptors (AT1Rs) in the nucleus of the tractus solitarius (NTS) in this interaction. CHF was induced in rats by coronary ligation. Acute experiments were performed in anesthetized rats. The chemoreflex-induced increase in cardiovascular responses was significantly greater in CHF than in sham-operated rats after either chemical or electrical activation of the CSAR. The inhibition of the CSAR by epicardial lidocaine reduced the chemoreflex-induced effects in CHF rats but not in sham-operated rats. Bilateral NTS injection of the AT1R antagonist losartan (10 and 100 pmol) dose-dependently decreased basal sympathetic nerve activity in CHF but not in sham-operated rats. This procedure also abolished the CSAR-induced enhancement of the chemoreflex. The discharge and chemosensitivity of NTS chemosensitive neurons were significantly increased following the stimulation of the CSAR in sham-operated and CHF rats, whereas CSAR inhibition by epicardial lidocaine significantly attenuated chemosensitivity of NTS neurons in CHF but not in sham-operated rats. Finally, the protein expression of AT1R in the NTS was significantly higher in CHF than in sham-operated rats. These results demonstrate that the enhanced cardiac sympathetic afferent input contributes to an excitatory effect of chemoreflex function in CHF, which is mediated by an NTS-AT1R-dependent mechanism.

  10. Prolonged (9 h) poikilocapnic hypoxia (12% O2) augments cutaneous thermal hyperaemia in healthy humans.

    PubMed

    Lawley, Justin S; Oliver, Samuel J; Mullins, Paul G; Macdonald, Jamie H; Moore, Jonathan P

    2014-06-01

    The primary aim of this study was to investigate the effect of systemic poikilocapnic hypoxia on forearm cutaneous thermal hyperaemia. A secondary aim was to examine the relationship between the individual susceptibility to oxygen desaturation and cutaneous vasodilator capacity. Twelve healthy participants (seven male) were exposed to 9 h of normoxia and 12% poikilocapnic hypoxia in a temperature- and humidity-controlled environmental chamber. Skin blood flow was assessed at the ventral forearm using laser Doppler flowmetry combined with rapid local heating. After 6 min at baseline (skin temperature clamped at 33°C), local skin temperature was elevated at a rate of 0.5°C every 5 s up to 42°C to elicit a sensory axon response and then held constant for 30 min to cause a plateau. Skin blood flow was calculated as cutaneous vascular conductance [CVC; in perfusion units/mean arterial blood pressure (APU mmHg(-1))] and expressed in raw format and relative to heating at 44°C in normoxia (%CVC44). During hypoxaemia, vasodilatation was greater during the initial peak (raw, Δ0.35 APU mmHg(-1), P = 0.09; %CVC44, Δ18%, P = 0.05) and the plateau phase (raw, Δ0.55 APU mmHg(-1), P = 0.03; %CVC44, Δ26%, P = 0.02). The rate of rise in cutaneous blood flow during the initial peak was significantly greater during poikilocapnic hypoxia (P < 0.01). We observed a negative relationship between oxygen saturation in poikilocapnic hypoxia and the change in baseline (P = 0.06), initial peak (P = 0.01) and plateau phase of thermal hyperaemia (P = 0.01). Prolonged poikilocapnic hypoxia causes robust increases in CVC during both phases of thermal hyperaemia that are dependent on the oxygen saturation of the individual. PMID:24706191

  11. Prolonged (9 h) poikilocapnic hypoxia (12% O2) augments cutaneous thermal hyperaemia in healthy humans.

    PubMed

    Lawley, Justin S; Oliver, Samuel J; Mullins, Paul G; Macdonald, Jamie H; Moore, Jonathan P

    2014-06-01

    The primary aim of this study was to investigate the effect of systemic poikilocapnic hypoxia on forearm cutaneous thermal hyperaemia. A secondary aim was to examine the relationship between the individual susceptibility to oxygen desaturation and cutaneous vasodilator capacity. Twelve healthy participants (seven male) were exposed to 9 h of normoxia and 12% poikilocapnic hypoxia in a temperature- and humidity-controlled environmental chamber. Skin blood flow was assessed at the ventral forearm using laser Doppler flowmetry combined with rapid local heating. After 6 min at baseline (skin temperature clamped at 33°C), local skin temperature was elevated at a rate of 0.5°C every 5 s up to 42°C to elicit a sensory axon response and then held constant for 30 min to cause a plateau. Skin blood flow was calculated as cutaneous vascular conductance [CVC; in perfusion units/mean arterial blood pressure (APU mmHg(-1))] and expressed in raw format and relative to heating at 44°C in normoxia (%CVC44). During hypoxaemia, vasodilatation was greater during the initial peak (raw, Δ0.35 APU mmHg(-1), P = 0.09; %CVC44, Δ18%, P = 0.05) and the plateau phase (raw, Δ0.55 APU mmHg(-1), P = 0.03; %CVC44, Δ26%, P = 0.02). The rate of rise in cutaneous blood flow during the initial peak was significantly greater during poikilocapnic hypoxia (P < 0.01). We observed a negative relationship between oxygen saturation in poikilocapnic hypoxia and the change in baseline (P = 0.06), initial peak (P = 0.01) and plateau phase of thermal hyperaemia (P = 0.01). Prolonged poikilocapnic hypoxia causes robust increases in CVC during both phases of thermal hyperaemia that are dependent on the oxygen saturation of the individual.

  12. Chemoreflexes, Sleep Apnea, and Sympathetic Dysregulation

    PubMed Central

    Mansukhani, Meghna P.; Kara, Tomas; Caples, Sean; Somers, Virend K.

    2014-01-01

    Obstructive sleep apnea (OSA) and hypertension are closely linked conditions. Disordered breathing events in OSA are characterized by increasing efforts against an occluded airway whilst asleep, resulting in a marked sympathetic response. This is predominantly due to hypoxemia activating the chemoreflexes, resulting in reflex increases in sympathetic neural outflow. In addition, apnea, and the consequent lack of inhibition of the sympathetic system that occurs with lung inflation during normal breathing, potentiates central sympathetic outflow. Sympathetic activation persists into the daytime, and is thought to contribute to hypertension and other adverse cardiovascular outcomes. This review discusses chemoreflex physiology and sympathetic modulation during normal sleep, as well as the sympathetic dysregulation seen in OSA, its extension into wakefulness, and changes after treatment. Evidence supporting the role of the peripheral chemoreflex in the sympathetic dysregulation seen in OSA, including in the context of co-morbid obesity, metabolic syndrome and systemic hypertension is reviewed. Finally, alterations in cardiovascular variability and other potential mechanisms that might play a role in the autonomic imbalance seen in OSA are also discussed. PMID:25097113

  13. Chronic intermittent hypoxia alters ventilatory and metabolic responses to acute hypoxia in rats.

    PubMed

    Morgan, Barbara J; Adrian, Russell; Wang, Zun-Yi; Bates, Melissa L; Dopp, John M

    2016-05-15

    We determined the effects of chronic exposure to intermittent hypoxia (CIH) on chemoreflex control of ventilation in conscious animals. Adult male Sprague-Dawley rats were exposed to CIH [nadir oxygen saturation (SpO2), 75%; 15 events/h; 10 h/day] or normoxia (NORM) for 21 days. We assessed the following responses to acute, graded hypoxia before and after exposures: ventilation (V̇e, via barometric plethysmography), V̇o2 and V̇co2 (analysis of expired air), heart rate (HR), and SpO2 (pulse oximetry via neck collar). We quantified hypoxia-induced chemoreceptor sensitivity by calculating the stimulus-response relationship between SpO2 and the ventilatory equivalent for V̇co2 (linear regression). An additional aim was to determine whether CIH causes proliferation of carotid body glomus cells (using bromodeoxyuridine). CIH exposure increased the slope of the V̇e/V̇co2/SpO2 relationship and caused hyperventilation in normoxia. Bromodeoxyuridine staining was comparable in CIH and NORM. Thus our CIH paradigm augmented hypoxic chemosensitivity without causing glomus cell proliferation. PMID:26917692

  14. Prolonged hypoxia augments l-citrulline transport by System A in the newborn piglet pulmonary circulation

    PubMed Central

    Fike, Candice D.; Sidoryk-Wegrzynowicz, Marta; Aschner, Michael; Summar, Marshall; Prince, Lawrence S.; Cunningham, Gary; Kaplowitz, Mark; Zhang, Yongmei; Aschner, Judy L.

    2012-01-01

    Aims Pulmonary arterial endothelial cells (PAECs) express the enzymes needed for generation of l-arginine from intracellular l-citrulline but do not express the enzymes needed for de novo l-citrulline synthesis. Hence, l-citrulline levels in PAECs are dependent on l-citrulline transport. Once generated, l-arginine can be converted to l-citrulline and nitric oxide (NO) by the enzyme NO synthase. We sought to determine whether hypoxia, a condition aetiologically linked to pulmonary hypertension, alters the transport of l-citrulline and the expression of the sodium-coupled neutral amino acid transporters (SNATs) in PAECs from newborn piglets. Methods and results PAECs isolated from newborn piglets were cultured under normoxic and hypoxic conditions and used to measure SNAT1, 2, 3, and 5 protein expression and 14C-l-citrulline uptake. SNAT1 protein expression was increased, while SNAT2, SNAT3, and SNAT5 expression was unaltered in hypoxic PAECs. 14C-l-citrulline uptake was increased in hypoxic PAECs. Studies with inhibitors of System A (SNAT1/2) and System N (SNAT3/5) revealed that the increased 14C-l-citrulline uptake was largely due to System A-mediated transport. Additional studies were performed to evaluate SNAT protein expression and l-citrulline levels in lungs of piglets with chronic hypoxia-induced pulmonary hypertension and comparable age controls. Lungs from piglets raised in chronic hypoxia exhibited greater SNAT1 expression and higher l-citrulline levels than lungs from controls. Conclusion Increased SNAT1 expression and the concomitant enhanced ability to transport l-citrulline in PAECs could represent an important regulatory mechanism to counteract NO signalling impairments known to occur during the development of chronic hypoxia-induced pulmonary hypertension in newborns. PMID:22673370

  15. Failure of anti tumor-derived endothelial cell immunotherapy depends on augmentation of tumor hypoxia.

    PubMed

    Pezzolo, Annalisa; Marimpietri, Danilo; Raffaghello, Lizzia; Cocco, Claudia; Pistorio, Angela; Gambini, Claudio; Cilli, Michele; Horenstein, Alberto; Malavasi, Fabio; Pistoia, Vito

    2014-11-15

    We have previously demonstrated that Tenascin-C (TNC)(+) human neuroblastoma (NB) cells transdifferentiate into tumor-derived endothelial cells (TDEC), which have been detected both in primary tumors and in tumors formed by human NB cell lines in immunodeficient mice. TDEC are genetically unstable and may favor tumor progression, suggesting that their elimination could reduce tumor growth and dissemination. So far, TDEC have never been targeted by antibody-mediated immunotherapy in any of the tumor models investigated. To address this issue, immunodeficient mice carrying orthotopic NB formed by the HTLA-230 human cell line were treated with TDEC-targeting cytotoxic human (h)CD31, that spares host-derived endothelial cells, or isotype-matched mAbs. hCD31 mAb treatment did not affect survival of NB-bearing mice, but increased significantly hypoxia in tumor microenvironment, where apoptotic and proliferating TDEC coexisted, indicating the occurrence of vascular remodeling. Tumor cells from hCD31 mAb treated mice showed i) up-regulation of epithelial-mesenchymal transition (EMT)-related and vascular mimicry (VM)-related gene expression, ii) expression of endothelial (i.e. CD31 and VE-cadherin) and EMT-associated (i.e. Twist-1, N-cadherin and TNC) immunophenotypic markers, and iii) up-regulation of high mobility group box-1 (HMGB-1) expression. In vitro experiments with two NB cell lines showed that hypoxia was the common driver of all the above phenomena and that human recombinant HMGB-1 amplified EMT and TDEC trans-differentiation. In conclusion, TDEC targeting with hCD31 mAb increases tumor hypoxia, setting the stage for the occurrence of EMT and of new waves of TDEC trans-differentiation. These adaptive responses to the changes induced by immunotherapy in the tumor microenvironment allow tumor cells to escape from the effects of hCD31 mAb.

  16. Daily intermittent hypoxia augments spinal BDNF levels, ERK phosphorylation and respiratory long-term facilitation

    PubMed Central

    Wilkerson, Julia E.R.; Mitchell, Gordon S.

    2009-01-01

    Acute intermittent hypoxia (AIH) elicits a form of respiratory plasticity known as long-term facilitation (LTF). We hypothesized that: 1) daily AIH (dAIH) preconditioning enhances phrenic and hypoglossal (XII) LTF in a rat strain with low constitutive LTF expression; 2) dAIH induces brain-derived neurotrophic factor (BDNF), a critical protein for phrenic LTF (pLTF) in the cervical spinal cord; and 3) dAIH increases post-AIH extracellular regulated kinase (ERK) activation. Phrenic and XII motor output were monitored in anesthetized dAIH- or sham-treated Brown Norway rats with and without acute AIH. pLTF was observed in both sham (18 ± 9% baseline; 60 min post-hypoxia; p < 0.05; n = 18) and dAIH treated rats (37 ± 8%; p < 0.05; n = 14), but these values were not significantly different (p = 0.13). XII LTF was not observed in sham-treated rats (4 ± 5%), but was revealed in dAIH pretreated rats (48 ± 18%; p < 0.05). dAIH preconditioning increased basal ventral cervical BDNF protein levels (24 ± 8%; p < 0.05), but had no significant effect on ERK phosphorylation. AIH increased BDNF in sham (25 ± 8%; p < 0.05), but not dAIH-pretreated rats (−7 ± 4%), and had complex effects on ERK phosphorylation (ERK2 increased in shams whereas ERK1 increased in dAIH-treated rats). Thus, dAIH elicits metaplasticity in LTF, revealing XII LTF in a rat strain with no constitutive XII LTF expression. Increased BDNF synthesis may no longer be necessary for phrenic LTF following dAIH preconditioning since BDNF concentration is already elevated. PMID:19416672

  17. Peripheral chemoreception and arterial pressure responses to intermittent hypoxia.

    PubMed

    Prabhakar, Nanduri R; Peng, Ying-Jie; Kumar, Ganesh K; Nanduri, Jayasri

    2015-04-01

    Carotid bodies are the principal peripheral chemoreceptors for detecting changes in arterial blood oxygen levels, and the resulting chemoreflex is a potent regulator of blood pressure. Recurrent apnea with intermittent hypoxia (IH) is a major clinical problem in adult humans and infants born preterm. Adult patients with recurrent apnea exhibit heightened sympathetic nerve activity and hypertension. Adults born preterm are predisposed to early onset of hypertension. Available evidence suggests that carotid body chemoreflex contributes to hypertension caused by IH in both adults and neonates. Experimental models of IH provided important insights into cellular and molecular mechanisms underlying carotid body chemoreflex-mediated hypertension. This article provides a comprehensive appraisal of how IH affects carotid body function, underlying cellular, molecular, and epigenetic mechanisms, and the contribution of chemoreflex to the hypertension.

  18. Peripheral Chemoreception and Arterial Pressure Responses to Intermittent Hypoxia

    PubMed Central

    Prabhakar, Nanduri R.; Peng, Ying-Jie; Kumar, Ganesh K.; Nanduri, Jayasri

    2015-01-01

    Carotid bodies are the principal peripheral chemoreceptors for detecting changes in arterial blood oxygen levels, and the resulting chemoreflex is a potent regulator of blood pressure. Recurrent apnea with intermittent hypoxia (IH) is a major clinical problem in adult humans and infants born preterm. Adult patients with recurrent apnea exhibit heightened sympathetic nerve activity and hypertension. Adults born preterm are predisposed to early onset of hypertension. Available evidence suggests that carotid body chemoreflex contributes to hypertension caused by IH in both adults and neonates. Experimental models of IH provided important insights into cellular and molecular mechanisms underlying carotid body chemoreflex-mediated hypertension. This article provides a comprehensive appraisal of how IH affects carotid body function, underlying cellular, molecular, and epigenetic mechanisms, and the contribution of chemoreflex to the hypertension. PMID:25880505

  19. Molecular Mechanisms of Chronic Intermittent Hypoxia and Hypertension

    PubMed Central

    Sunderram, J.; Androulakis, I.P.

    2013-01-01

    Obstructive sleep apnea (OSA) is characterized by episodes of repeated airway obstruction resulting in cessation (apnea) or reduction (hypopnea) in airflow during sleep. These events lead to intermittent hypoxia and hypercapnia, sleep fragmentation, and changes in intrathoracic pressure, and are associated with a marked surge in sympathetic activity and an abrupt increase in blood pressure. Blood pressure remains elevated during wakefulness despite the absence of obstructive events resulting in a high prevalence of hypertension in patients with OSA. There is substantial evidence that suggests that chronic intermittent hypoxia (CIH) leads to sustained sympathoexcitation during the day and changes in vasculature resulting in hypertension in patients with OSA. Mechanisms of sympathoexcitation include augmentation of peripheral chemoreflex sensitivity and a direct effect on central sites of sympathetic regulation. Interestingly, the vascular changes that occur with CIH have been ascribed to the same molecules that have been implicated in the augmented sympathetic tone in CIH. This review will discuss the hypothesized molecular mechanisms involved in the development of hypertension with CIH, will build a conceptual model for the development of hypertension following CIH, and will propose a systems biology approach in further elucidating the relationship between CIH and the development of hypertension. PMID:23140119

  20. Exercise training attenuates chemoreflex-mediated reductions of renal blood flow in heart failure.

    PubMed

    Marcus, Noah J; Pügge, Carolin; Mediratta, Jai; Schiller, Alicia M; Del Rio, Rodrigo; Zucker, Irving H; Schultz, Harold D

    2015-07-15

    In chronic heart failure (CHF), carotid body chemoreceptor (CBC) activity is increased and contributes to increased tonic and hypoxia-evoked elevation in renal sympathetic nerve activity (RSNA). Elevated RSNA and reduced renal perfusion may contribute to development of the cardio-renal syndrome in CHF. Exercise training (EXT) has been shown to abrogate CBC-mediated increases in RSNA in experimental heart failure; however, the effect of EXT on CBC control of renal blood flow (RBF) is undetermined. We hypothesized that CBCs contribute to tonic reductions in RBF in CHF, that stimulation of the CBC with hypoxia would result in exaggerated reductions in RBF, and that these responses would be attenuated with EXT. RBF was measured in CHF-sedentary (SED), CHF-EXT, CHF-carotid body denervation (CBD), and CHF-renal denervation (RDNX) groups. We measured RBF at rest and in response to hypoxia (FiO2 10%). All animals exhibited similar reductions in ejection fraction and fractional shortening as well as increases in ventricular systolic and diastolic volumes. Resting RBF was lower in CHF-SED (29 ± 2 ml/min) than in CHF-EXT animals (46 ± 2 ml/min, P < 0.05) or in CHF-CBD animals (42 ± 6 ml/min, P < 0.05). In CHF-SED, RBF decreased during hypoxia, and this was prevented in CHF-EXT animals. Both CBD and RDNX abolished the RBF response to hypoxia in CHF. Mean arterial pressure increased in response to hypoxia in CHF-SED, but was prevented by EXT, CBD, and RDNX. EXT is effective in attenuating chemoreflex-mediated tonic and hypoxia-evoked reductions in RBF in CHF.

  1. CaV3.2 T-type Ca2+ channels mediate the augmented calcium influx in carotid body glomus cells by chronic intermittent hypoxia.

    PubMed

    Makarenko, Vladislav V; Ahmmed, Gias U; Peng, Ying-Jie; Khan, Shakil A; Nanduri, Jayasri; Kumar, Ganesh K; Fox, Aaron P; Prabhakar, Nanduri R

    2016-01-01

    Chronic intermittent hypoxia (CIH) is a hallmark manifestation of sleep apnea. A heightened carotid body activity and the resulting chemosensory reflex mediate increased sympathetic nerve activity by CIH. However, the mechanisms underlying heightened carotid body activity by CIH are not known. An elevation of intracellular calcium ion concentration ([Ca(2+)]i) in glomus cells, the primary oxygen-sensing cells, is an essential step for carotid body activation by hypoxia. In the present study, we examined the effects of CIH on the glomus cell [Ca(2+)]i response to hypoxia and assessed the underlying mechanisms. Glomus cells were harvested from adult rats or wild-type mice treated with 10 days of either room air (control) or CIH (alternating cycles of 15 s of hypoxia and 5 min of room air; 9 episodes/h; 8 h/day). CIH-treated glomus cells exhibited an enhanced [Ca(2+)]i response to hypoxia, and this effect was absent in the presence of 2-(4-cyclopropylphenyl)-N-((1R)-1-[5-[(2,2,2-trifluoroethyl)oxo]-pyridin-2-yl]ethyl)acetamide (TTA-A2), a specific inhibitor of T-type Ca(2+) channels, and in voltage-gated calcium channel, type 3.2 (CaV3.2), null glomus cells. CaV3.2 knockout mice exhibited an absence of CIH-induced hypersensitivity of the carotid body. CIH increased reactive oxygen species (ROS) levels in glomus cells. A ROS scavenger prevented the exaggerated TTA-A2-sensitive [Ca(2+)]i response to hypoxia. CIH had no effect on CaV3.2 mRNA levels. CIH augmented Ca(2+) currents and increased CaV3.2 protein in plasma membrane fractions of human embryonic kidney-293 cells stably expressing CaV3.2, and either a ROS scavenger or brefeldin-A, an inhibitor of protein trafficking, prevented these effects. These findings suggest that CIH leads to an augmented Ca(2+) influx via ROS-dependent facilitation of CaV3.2 protein trafficking to the plasma membrane.

  2. A computerized integrated system for the assessment of central and peripheral chemoreflex sensitivity.

    PubMed

    Maestri, Roberto; Bruschi, Claudio; Pinna, Gian Domenico

    2013-04-01

    The assessment of chemoreflex sensitivity (CRS) is of major importance in studies investigating the adaptation of ventilation to the needs of human body. Increased sensitivity of chemoreceptors to both hypoxia and hypercapnia has recently been shown to be a powerful and independent prognosticator in heart failure (HF) patients, thus highlighting the importance of the assessment of CRS also in the clinical setting. In spite of this, the measurement of CRS is currently limited to the research setting. One possible reason might be the lack of suitable commercial equipments. On the basis of these considerations, we designed a system to carry out a comprehensive assessment of CRS, including both central and peripheral chemoreceptors. The system is based on the integration of different commercial devices and is entirely managed by a custom software written in Matlab language. The main features of our system are: (1) the implementation of standard methods (the Read's rebreathing test, the CO2 single breath test and the transient hypoxia test) suitable for both pathological and healthy subjects, (2) data quality assurance and reduction of subjective judgment in the analysis through advanced analysis procedures and statistical outliers rejection, and (3) full interactive control of every step of the recording and analysis procedures. The system is currently used in our Institution in the assessment of CRS in HF patients, chronic obstructive pulmonary disease patients and healthy subjects. It has proven to be very effective and easy to use even by clinical personnel without a specific background in respiratory function assessment.

  3. Contribution of the retrotrapezoid nucleus/parafacial respiratory region to the expiratory-sympathetic coupling in response to peripheral chemoreflex in rats.

    PubMed

    Moraes, Davi J A; Dias, Mirela B; Cavalcanti-Kwiatkoski, Roberta; Machado, Benedito H; Zoccal, Daniel B

    2012-08-01

    Central mechanisms of coupling between respiratory and sympathetic systems are essential for the entrainment between the enhanced respiratory drive and sympathoexcitation in response to hypoxia. However, the brainstem nuclei and neuronal network involved in these respiratory-sympathetic interactions remain unclear. Here, we evaluated whether the increase in expiratory activity and expiratory-modulated sympathoexcitation produced by the peripheral chemoreflex activation involves the retrotrapezoid nucleus/parafacial respiratory region (RTN/pFRG). Using decerebrated arterially perfused in situ rat preparations (60-80 g), we recorded the activities of thoracic sympathetic (tSN), phrenic (PN), and abdominal nerves (AbN) as well as the extracellular activity of RTN/pFRG expiratory neurons, and reflex responses to chemoreflex activation were evaluated before and after inactivation of the RTN/pFRG region with muscimol (1 mM). In the RTN/pFRG, we identified late-expiratory (late-E) neurons (n = 5) that were silent at resting but fired coincidently with the emergence of late-E bursts in AbN after peripheral chemoreceptor activation. Bilateral muscimol microinjections into the RTN/pFRG region (n = 6) significantly reduced basal PN frequency, mean AbN activity, and the amplitude of respiratory modulation of tSN (P < 0.05). With respect to peripheral chemoreflex responses, muscimol microinjections in the RTN/pFRG enhanced the PN inspiratory response, abolished the evoked late-E activity of AbN, but did not alter either the magnitude or pattern of the tSN reflex response. These findings indicate that the RTN/pFRG region is critically involved in the processing of the active expiratory response but not of the expiratory-modulated sympathetic response to peripheral chemoreflex activation of rat in situ preparations.

  4. Combined suppression of the intrarenal and circulating vasoconstrictor renin-ACE-ANG II axis and augmentation of the vasodilator ACE2-ANG 1-7-Mas axis attenuates the systemic hypertension in Ren-2 transgenic rats exposed to chronic hypoxia.

    PubMed

    Červenka, L; Bíbová, J; Husková, Z; Vaňourková, Z; Kramer, H J; Herget, J; Jíchová, Š; Sadowski, J; Hampl, V

    2015-01-01

    The aim of the present study was to test the hypothesis that chronic hypoxia would aggravate hypertension in Ren-2 transgenic rats (TGR), a well-defined monogenetic model of hypertension with increased activity of endogenous renin-angiotensin system (RAS). Systolic blood pressure (SBP) in conscious rats and mean arterial pressure (MAP) in anesthetized TGR and normotensive Hannover Sprague-Dawley (HanSD) rats were determined under normoxia that was either continuous or interrupted by two weeks´ hypoxia. Expression, activities and concentrations of individual components of RAS were studied in plasma and kidney of TGR and HanSD rats under normoxic conditions and after exposure to chronic hypoxia. In HanSD rats two weeks´ exposure to chronic hypoxia did not alter SBP and MAP. Surprisingly, in TGR it decreased markedly SBP and MAP; this was associated with substantial reduction in plasma and kidney renin activities and also of angiotensin II (ANG II) levels, without altering angiotensin-converting enzyme (ACE) activities. Simultaneously, in TGR the exposure to hypoxia increased kidney ACE type 2 (ACE2) activity and angiotensin 1-7 (ANG 1-7) concentrations as compared with TGR under continuous normoxia. Based on these results, we propose that suppression of the hypertensiogenic ACE-ANG II axis in the circulation and kidney tissue, combined with augmentation of the intrarenal vasodilator ACE2-ANG 1-7 axis, is the main mechanism responsible for the blood pressure-lowering effects of chronic hypoxia in TGR. PMID:25194129

  5. Cardiovascular responses to peripheral chemoreflex activation and comparison of different methods to evaluate baroreflex gain in conscious mice using telemetry.

    PubMed

    Braga, Valdir A; Burmeister, Melissa A; Sharma, Ram V; Davisson, Robin L

    2008-10-01

    Peripheral chemoreceptors located in the carotid bodies are the primary sensors of systemic hypoxia. Although the pattern of responses elicited by peripheral chemoreceptor activation is well established in rats, lambs, and rabbits, the cardiovascular responses to peripheral chemoreflex activation in conscious mice have not been delineated. Here we report that stimulation of peripheral chemoreceptors by potassium cyanide (KCN) in conscious mice elicits a unique biphasic response in blood pressure that is characterized by an initial and robust rise followed by a decrease in blood pressure, which is accompanied by a marked reduction in heart rate. The depressor and bradycardic responses to KCN were abolished by muscarinic receptor blockade with atropine, and the pressor response was abolished by alpha-adrenergic receptor blockade with prazosin, suggesting that vagal and sympathetic drive to the heart and sympathetic drive to the vasculature mediate these cardiovascular responses. These studies characterized the chemoreflex in conscious mice and established the reliability of using them for studying hypoxia-related diseases such as obstructive sleep apnea. In another series of experiments, two methods for analyzing baroreflex sensitivity were compared: the classical pharmacological approach using phenylephrine and sodium nitroprusside (i.e., the Oxford technique) or the sequence method for analyzing spontaneous baroreflex activity. Our findings indicate that both methods are reliable, and the sequence method certainly has its benefits as a predictive tool in the context of long-term noninvasive studies using telemetry. However, for absolute determination of baroreflex function, analysis of spontaneous baroreflex activity should be complemented by the classical pharmacological method. PMID:18667715

  6. [Recent knowledges on chemosensitivity to hypoxia and hypercapnia in cardiovascular disease].

    PubMed

    Passino, Claudio; Giannoni, Alberto; Milli, Massimo; Polettii, Roberta; Emdin, Michele

    2010-01-01

    The pathophysiologic role of enhanced chemosensitivity to carbon dioxide and/or hypoxia has been underscored in several cardiovascular diseases, including heart failure. In the early stages of this syndrome, the chemoreflex acts as a compensatory mechanism. Later on, however, it contributes to sustain the sympathetic activation, with detrimental effects on cardiovascular function and prognosis.

  7. Respiratory and sympathetic chemoreflex regulation by Kölliker-Fuse neurons in rats.

    PubMed

    Damasceno, Rosélia S; Takakura, Ana C; Moreira, Thiago S

    2015-02-01

    Chemoreceptor activation increases phrenic nerve activity (PNA) and sympathetic nerve activity (SNA). The dorsolateral pontine neurons, including the parabrachial nucleus and the Kölliker-Fuse (KF) region project to several brainstem areas involved in autonomic and respiratory regulation. Here the objective was to further test the hypothesis that the KF region could contribute to central and peripheral sympathetic chemoreflex activation. In urethane-anesthetized sino-aortic denervated or intact and vagotomized male Wistar rats (N = 7-8/group), hypercapnia (end-expiratory CO2 from 5 to 10 %) or KCN increased mean arterial pressure (MAP), splanchnic SNA, and PNA frequency and amplitude. Bilateral injection of muscimol (GABA-A agonist; 2 mM-50 nl) into the KF region increased resting PNA amplitude and reduced resting PNA frequency, without significant changes in resting MAP and SNA. Bilateral blockade of the KF region reduced the rise in MAP, sSNA, and PNA frequency and amplitude produced by hypercapnia or hypoxia. Our data suggest that the KF neurons could integrate and modulate breathing and sympathetic outflow during chemoreceptor activation.

  8. Menstrual cycle and sex effects on sympathetic responses to acute chemoreflex stress.

    PubMed

    Usselman, Charlotte W; Gimon, Tamara I; Nielson, Chantelle A; Luchyshyn, Torri A; Coverdale, Nicole S; Van Uum, Stan H M; Shoemaker, J Kevin

    2015-03-15

    This study aimed to examine the effects of sex (males vs. females) and sex hormones (menstrual cycle phases in women) on sympathetic responsiveness to severe chemoreflex activation in young, healthy individuals. Muscle sympathetic nerve activity (MSNA) was measured at baseline and during rebreathing followed by a maximal end-inspiratory apnea. In women, baseline MSNA was greater in the midluteal (ML) than early-follicular (EF) phase of the menstrual cycle. Baseline MSNA burst incidence was greater in men than women, while burst frequency and total MSNA were similar between men and women only in the ML phase. Chemoreflex activation evoked graded increases in MSNA burst frequency, amplitude, and total activity in all participants. In women, this sympathoexcitation was greater in the EF than ML phase. The sympathoexcitatory response to chemoreflex stimulation of the EF phase in women was also greater than in men. Nonetheless, changes in total peripheral resistance were similar between sexes and menstrual cycle phases. This indicates that neurovascular transduction was attenuated during the EF phase during chemoreflex activation, thereby offsetting the exaggerated sympathoexcitation. Chemoreflex-induced increases in mean arterial pressure were similar across sexes and menstrual cycle phases. During acute chemoreflex stimulation, reduced neurovascular transduction could provide a mechanism by which apnea-associated morbidity might be attenuated in women relative to men. PMID:25527774

  9. Cerebral Hypoxia

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Cerebral Hypoxia Information Page Synonym(s): Hypoxia, Anoxia Table of Contents ( ... Trials Organizations Publicaciones en Español What is Cerebral Hypoxia? Cerebral hypoxia refers to a condition in which ...

  10. Interactive effect of hypoxia and otolith organ engagement on cardiovascular regulation in humans

    NASA Technical Reports Server (NTRS)

    Monahan, Kevin D.; Ray, Chester A.

    2002-01-01

    We determined the interaction between the vestibulosympathetic reflex and the arterial chemoreflex in 12 healthy subjects. Subjects performed three trials in which continuous recordings of muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP), heart rate (HR), and arterial oxygen saturation were obtained. First, in prone subjects the otolith organs were engaged by use of head-down rotation (HDR). Second, the arterial chemoreflex was activated by inspiration of hypoxic gas (10% O2 and 90% N2) for 7 min with HDR being performed during minute 6. Third, hypoxia was repeated (15 min) with HDR being performed during minute 14. HDR [means +/- SE; increase (Delta)7 +/- 1 bursts/min and Delta50 +/- 11% for burst frequency and total MSNA, respectively; P < 0.05] and hypoxia (Delta6 +/- 2 bursts/min and Delta62 +/- 29%; P < 0.05) increased MSNA. Additionally, MSNA increased when HDR was performed during hypoxia (Delta11 +/- 2 bursts/min and Delta127 +/- 57% change from normoxia; P < 0.05). These increases in MSNA were similar to the algebraic sum of the individual increase in MSNA elicited by HDR and hypoxia (Delta13 +/- 1 bursts/min and Delta115 +/- 36%). Increases in MAP (Delta3 +/- 1 mmHg) and HR (Delta19 +/- 1 beats/min) during combined HDR and hypoxia generally were smaller (P < 0.05) than the algebraic sum of the individual responses (Delta5 +/- 1 mmHg and Delta24 +/- 2 beats/min for MAP and HR, respectively; P < 0.05). These findings indicate an additive interaction between the vestibulosympathetic reflex and arterial chemoreflex for MSNA. Therefore, it appears that MSNA outputs between the vestibulosympathetic reflex and arterial chemoreflex are independent of one another in humans.

  11. Interactions between CO2 chemoreflexes and arterial baroreflexes

    NASA Technical Reports Server (NTRS)

    Henry, R. A.; Lu, I. L.; Beightol, L. A.; Eckberg, D. L.

    1998-01-01

    We studied interactions between CO2 chemoreflexes and arterial baroreflexes in 10 supine healthy young men and women. We measured vagal carotid baroreceptor-cardiac reflexes and steady-state fast Fourier transform R-R interval and photoplethysmographic arterial pressure power spectra at three arterial pressure levels (nitroprusside, saline, and phenylephrine infusions) and three end-tidal CO2 levels (3, 4, and 5%, fixed-frequency, large-tidal-volume breathing, CO2 plus O2). Our study supports three principal conclusions. First, although low levels of CO2 chemoreceptor stimulation reduce R-R intervals and R-R interval variability, statistical modeling suggests that this effect is indirect rather than direct and is mediated by reductions of arterial pressure. Second, reductions of R-R intervals during hypocapnia reflect simple shifting of vagally mediated carotid baroreflex responses on the R-R interval axis rather than changes of baroreflex gain, range, or operational point. Third, the influence of CO2 chemoreceptor stimulation on arterial pressure (and, derivatively, on R-R intervals and R-R interval variability) depends critically on baseline arterial pressure levels: chemoreceptor effects are smaller when pressure is low and larger when arterial pressure is high.

  12. Mechanisms of carotid body chemoreflex dysfunction during heart failure

    PubMed Central

    Schultz, Harold D.; Marcus, Noah J.; Del Rio, Rodrigo

    2015-01-01

    Recent advances have drawn interest in the potential for carotid body (CB) ablation or desensitization as an effective strategy for clinical treatment and management of cardio-respiratory diseases including hypertension, heart failure, diabetes mellitus, metabolic syndrome, and renal failure. These disease states have in common sympathetic overactivity, which plays an important role in the development and progression of the disease and is often associated with breathing dysregulation, which in turn likely mediates or aggravates the autonomic imbalance. Evidence from both chronic heart failure (CHF) patients and animal models indicates that the CB chemoreflex is enhanced in CHF and contributes to the tonic elevation in sympathetic activity and the development of periodic breathing associated with the disease. Although this maladaptive change likely derives from altered function at all levels of the reflex arc, a tonic increase in afferent activity from CB glomus cells is likely to be a main driving force. This report will focus on our understanding of mechanisms that alter CB function in CHF and their potential translational impact on treatment of CHF. PMID:25398713

  13. Interaction of the carotid baroreflex, the muscle chemoreflex and the cardiopulmonary baroreflex in man during exercise

    NASA Technical Reports Server (NTRS)

    Eiken, O.; Convertino, V. A.; Doerr, D. F.; Dudley, G. A.; Morariu, G.; Mekjavic, I. B.

    1991-01-01

    The interaction of the muscle chemoreflex and the cardiopulmonary baroreflex with the carotid baroreflex in humans performing exercise was investigated in healthy subjects using specially designed exercise regimen and apparatus. Stimulation of the muscle chemoreflex was achieved by restricting blood flow in the exercising muscles by means of applying a pressure of 50 mm Hg, whereas cardiopulmonary baroreceptors were unloaded by employing LBNP of -20 mm Hg. The carotid baroreceptors were unloaded and stimulated by neck-pressure maneuvers (Sprenkle et al., 1986). Results showed that the cardiodecelerating capacity of the carotid baroreflex remains active during exercise, and may even be sensitized by the chemoreflex-induced increase in arterial pressure; but it is not affected by the cardiopulmonary baroreceptor activity.

  14. Fos expression in the NTS in response to peripheral chemoreflex activation in awake rats.

    PubMed

    Cruz, Josiane de Campos; Bonagamba, Leni G H; Stern, Javier E; Machado, Benedito H

    2010-01-15

    Chemoreflex afferent fibers terminate in the nucleus tractus solitarii (NTS), but the specific location of the NTS neurons excited by peripheral chemoreflex activation remains to be characterized. Here, the topographic distribution of chemoreflex sensitive cells at the commissural NTS was evaluated. To reach this goal, Fos-immunoreactive neurons (Fos-ir) were accounted in rostro-caudal levels of the intermediate and caudal commissural NTS, after intermittent chemoreflex activation with intravenous injection of potassium cyanide [KCN (80microg/kg) or saline (0.9%, vehicle), one injection every 3min during 30min]. In response to intermittent intravenous injections of KCN, a significant increase in the number of Fos-ir neurons was observed specifically in the lateral intermediate commissural NTS [(LI)NTS (82+/-9 vs. 174+/-16, cell number mean per section)] and lateral caudal commissural NTS [(LC)NTS (71+/-9 vs. 199+/-18, cell number mean per section)]. To evaluate the influence of baroreceptor-mediated inputs following the increase in blood pressure during intermittent chemoreflex activation, we performed an intermittent activation of the arterial baroreflex by intravenous injection of phenylephrine [1.5microg/kg iv (one injection every 3min during 30min)]. This procedure induced no change in Fos-ir in (LI)NTS (64+/-6 vs. 62+/-12, cell number mean per section) or (LC)NTS (56+/-15 vs. 77+/-12, cell number mean per section). These data support the involvement of the commissural NTS in the processing of peripheral chemoreflex, and provide a detailed characterization of the topographical distribution of activated neurons within this brain region.

  15. Hypoxia in Diabetic Kidneys

    PubMed Central

    Takiyama, Yumi; Haneda, Masakazu

    2014-01-01

    Diabetic nephropathy (DN) is now a leading cause of end-stage renal disease. In addition, DN accounts for the increased mortality in type 1 and type 2 diabetes, and then patients without DN achieve long-term survival compatible with general population. Hypoxia represents an early event in the development and progression of DN, and hypoxia-inducible factor- (HIF-) 1 mediates the metabolic responses to renal hypoxia. Diabetes induces the “fraternal twins” of hypoxia, that is, pseudohypoxia and hypoxia. The kidneys are susceptible to hyperoxia because they accept 20% of the cardiac output. Therefore, the kidneys have specific vasculature to avoid hyperoxia, that is, AV oxygen shunting. The NAD-dependent histone deacetylases (HDACs) sirtuins are seven mammalian proteins, SIRTs 1–7, which are known to modulate longevity and metabolism. Recent studies demonstrated that some isoforms of sirtuins inhibit the activation of HIF by deacetylation or noncatalyzing effects. The kidneys, which have a vascular system that protects them against hyperoxia, unfortunately experience extraordinary hypernutrition today. Then, an unexpected overload of glucose augments the oxygen consumption, which ironically results in hypoxia. This review highlights the primary role of HIF in diabetic kidneys for the metabolic adaptation to diabetes-induced hypoxia. PMID:25054148

  16. Spinal cord injury is associated with enhanced peripheral chemoreflex sensitivity.

    PubMed

    Bascom, Amy T; Sankari, Abdulghani; Badr, M Safwan

    2016-09-01

    Sleep-disordered breathing (SDB) is prevalent in individuals with chronic spinal cord injury (SCI), but the exact mechanism is unknown. The aim of this study was to investigate whether peripheral chemoreceptors activity is enhanced in individuals with chronic SCI compared to abled-bodied control subjects using CO2 and O2 chemical tests. In protocol (1) 30 subjects (8 cervical [cSCI], 7 thoracic [tSCI] and 15 able-bodied [AB]) were studied to determine the ventilatory response to hyperoxia during wakefulness in the supine position. In protocol (2) 24 subjects (6 cSCI, 6 tSCI, and 12 AB subjects) were studied to determine the ventilatory response to a single breath of CO2 (SBCO2). The chemoreflex response to SBCO2 was calculated as ∆VE/∆CO2 (L/min/mmHg). The ventilatory response to hyperoxia was defined as the % change in VT following acute hyperoxia compared to preceding baseline. During hyperoxia SCI subjects had a significant decrease in VT and VE (63.4 ± 21.7% and 63.1 ± 23.0% baseline, respectively, P < 0.05) compared to AB (VT: 87.1 ± 14.3% and VE: 91.38 ± 15.1% baseline, respectively, P < 0.05). There was no significant difference between cSCI and tSCI in the VT or VE during hyperoxia (P = NS). There was no significant correlation between AHI and VE% baseline (r = -0.28) in SCI and AB (n = 30). SCI participants had a greater ventilatory response to an SBCO2 than AB (0.78 ± 0.42 L/min/mmHg vs. 0.26 ± 0.10 L/min/mmHg, respectively, P < 0.05). Peripheral ventilatory chemoresponsiveness is elevated in individuals with chronic SCI compared to able-bodied individuals. PMID:27597767

  17. Dopamine microinjected into brainstem of awake rats affects baseline arterial pressure but not chemoreflex responses.

    PubMed

    Oliva, Waldyr M; Granjeiro, Erica M; Bongamba, Leni G H; Mendes, Ricardo A; Machado, Benedito H

    2010-06-24

    Dopamine (DA) is a neuromodulator in the brainstem involved with the generation and modulation of the autonomic and respiratory activities. Here we evaluated the effect of microinjection of DA intracisterna magna (icm) or into the caudal nucleus tractus solitarii (cNTS) on the baseline cardiovascular and respiratory parameters and on the cardiovascular and respiratory responses to chemoreflex activation in awake rats. Guide cannulas were implanted in cisterna magna or cNTS and femoral artery and vein were catheterized. Respiratory frequency (f(R)) was measured by whole-body plethysmography. Chemoreflex was activated with KCN (iv) before and after microinjection of DA icm or into the cNTS bilaterally while mean arterial pressure (MAP), heart rate (HR) and f(R) were recorded. Microinjection of DA icm (n=13), but not into the cNTS (n=8) produced a significant decrease in baseline MAP (-15+/-1 vs 1+/-1mmHg) and HR (-55+/-11 vs -11+/-17bpm) in relation to control (saline with ascorbic acid, n=9) but no significant changes in baseline f(R). Microinjection of DA icm or into the cNTS produced no significant changes in the pressor, bradycardic and tachypneic responses to chemoreflex activation. These data show that a) DA icm affects baseline cardiovascular regulation, but not baseline f(R) and autonomic and respiratory components of chemoreflex and b) DA into the cNTS does not affect either the autonomic activity to the cardiovascular system or the autonomic and respiratory responses of chemoreflex activation.

  18. HypoxiaDB: a database of hypoxia-regulated proteins.

    PubMed

    Khurana, Pankaj; Sugadev, Ragumani; Jain, Jaspreet; Singh, Shashi Bala

    2013-01-01

    There has been intense interest in the cellular response to hypoxia, and a large number of differentially expressed proteins have been identified through various high-throughput experiments. These valuable data are scattered, and there have been no systematic attempts to document the various proteins regulated by hypoxia. Compilation, curation and annotation of these data are important in deciphering their role in hypoxia and hypoxia-related disorders. Therefore, we have compiled HypoxiaDB, a database of hypoxia-regulated proteins. It is a comprehensive, manually-curated, non-redundant catalog of proteins whose expressions are shown experimentally to be altered at different levels and durations of hypoxia. The database currently contains 72 000 manually curated entries taken on 3500 proteins extracted from 73 peer-reviewed publications selected from PubMed. HypoxiaDB is distinctive from other generalized databases: (i) it compiles tissue-specific protein expression changes under different levels and duration of hypoxia. Also, it provides manually curated literature references to support the inclusion of the protein in the database and establish its association with hypoxia. (ii) For each protein, HypoxiaDB integrates data on gene ontology, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway, protein-protein interactions, protein family (Pfam), OMIM (Online Mendelian Inheritance in Man), PDB (Protein Data Bank) structures and homology to other sequenced genomes. (iii) It also provides pre-compiled information on hypoxia-proteins, which otherwise requires tedious computational analysis. This includes information like chromosomal location, identifiers like Entrez, HGNC, Unigene, Uniprot, Ensembl, Vega, GI numbers and Genbank accession numbers associated with the protein. These are further cross-linked to respective public databases augmenting HypoxiaDB to the external repositories. (iv) In addition, HypoxiaDB provides an online sequence-similarity search tool for

  19. Cerebral hypoxia

    MedlinePlus

    ... death. Treatment depends on the cause of the hypoxia. Basic life support is most important. Treatment involves: Breathing ... Complications of cerebral hypoxia include a prolonged vegetative ... sleep-wake cycle, and eye opening, but the person is not alert ...

  20. Autonomic and cardiovascular responses to chemoreflex stress in apnoea divers.

    PubMed

    Steinback, Craig D; Breskovic, Toni; Banic, Ivana; Dujic, Zeljko; Shoemaker, J Kevin

    2010-08-25

    Sleep apnoea, with repeated periods of hypoxia, results in cardiovascular morbidity and concomitant autonomic dysregulation. Trained apnoea divers also perform prolonged apnoeas accompanied by large lung volumes, large reductions in cardiac output and severe hypoxia and hypercapnia. We tested the hypothesis that apnoea training would be associated with decreased cardiovagal and sympathetic baroreflex gains and reduced respiratory modulation of muscle sympathetic nerve activity (MSNA; microneurography). Six trained divers and six controls were studied at rest and during asphyxic rebreathing. Despite an elevated resting heart rate (70+/-14 vs. 56+/-10 bpm; p=0.038), divers had a similar cardiovagal baroreflex gain (-1.22+/-0.47 beats/mmHg) as controls (-1.29+/-0.61; NS). Similarly, though MSNA burst frequency was slightly higher in divers at rest (16+/-4 bursts/min vs. 10+/-5 bursts/min, p=0.03) there was no difference in baseline burst incidence, sympathetic baroreflex gain (-3.8+/-2.1%/mmHg vs. -4.7+/-1.7%/mmHg) or respiratory modulation of MSNA between groups. Resting total peripheral resistance (11.9+/-2.6 vs. 12.3+/-2.2 mmHg/L/min) and pulse wave velocity (5.82+/-0.55 vs. 6.10+/-0.51 m/s) also were similar between divers and controls, respectively. Further, the sympathetic response to asphyxic rebreathing was not different between controls and divers (-1.70+/-1.07 vs. -1.74+/-0.84 a.u./% desaturation). Thus, these data suggest that, unlike patients with sleep apnoea, apnoea training in otherwise healthy individuals does not produce detectable autonomic dysregulation or maladaption.

  1. Noradrenergic inhibitory modulation in the caudal commissural NTS of the pressor response to chemoreflex activation in awake rats.

    PubMed

    Silva de Oliveira, Luciana C; Bonagamba, Leni G H; Machado, Benedito H

    2007-10-30

    In the present study we evaluated the possible modulatory role of noradrenaline on the neurotransmission of the peripheral chemoreflex afferents in the caudal commissural NTS of awake rats. To reach this goal we performed a dose-response curve to microinjection of increasing dose of noradrenaline into the caudal commissural NTS of awake rats and then the threshold dose, which produces minor changes in the baseline mean arterial pressure, was selected to be used in the chemoreflex experiment. The peripheral chemoreflex was activated with KCN before and after bilateral microinjections of noradrenaline (5 nMol/50 nL, threshold dose) into the NTS. The data show that microinjection of noradrenaline into the caudal NTS produced a significant reduction in the pressor response to the chemoreflex 30 s after the injection when compared to the control response (30+/-6 vs. 49+/-3 mm Hg) but no significant changes in the bradycardic response. The data indicate that noradrenaline in the caudal commissural NTS of awake rats may play an important inhibitory neuromodulatory role on the processing of the pressor/sympathoexcitatory component of the chemoreflex.

  2. Do peripheral and/or central chemoreflexes influence skin blood flow in humans?

    PubMed Central

    Heffernan, Matthew J.; Muller, Matthew D.

    2014-01-01

    Abstract Voluntary apnea activates the central and peripheral chemoreceptors, leading to a rise in sympathetic nerve activity and limb vasoconstriction (i.e., brachial blood flow velocity and forearm cutaneous vascular conductance decrease to a similar extent). Whether peripheral and/or central chemoreceptors contribute to the cutaneous vasoconstrictor response remains unknown. We performed three separate experiments in healthy young men to test the following three hypotheses. First, inhibition of peripheral chemoreceptors with brief hyperoxia inhalation (100% O2) would attenuate the cutaneous vasoconstrictor response to voluntary apnea. Second, activation of the peripheral chemoreceptors with 5 min of hypoxia (10% O2, 90% N2) would augment the cutaneous vasoconstrictor response to voluntary apnea. Third, activation of the central chemoreceptors with 5 min of hypercapnia (7% CO2, 30% O2, 63% N2) would have no influence on cutaneous responses to voluntary apnea. Studies were performed in the supine posture with skin temperature maintained at thermoneutral levels. Beat‐by‐beat blood pressure, heart rate, brachial blood flow velocity, and cutaneous vascular conductance were measured and changes from baseline were compared between treatments. Relative to room air, hyperoxia attenuated the vasoconstrictor response to voluntary apnea in both muscle (−16 ± 10 vs. −40 ± 12%, P = 0.023) and skin (−14 ± 6 vs. −24 ± 5%, P = 0.033). Neither hypoxia nor hypercapnia had significant effects on cutaneous responses to apnea. These data indicate that skin blood flow is controlled by the peripheral chemoreceptors but not the central chemoreceptors. PMID:25344478

  3. The myths and physiology surrounding intrapartum decelerations: the critical role of the peripheral chemoreflex.

    PubMed

    Lear, Christopher A; Galinsky, Robert; Wassink, Guido; Yamaguchi, Kyohei; Davidson, Joanne O; Westgate, Jenny A; Bennet, Laura; Gunn, Alistair J

    2016-09-01

    A distinctive pattern of recurrent rapid falls in fetal heart rate, called decelerations, are commonly associated with uterine contractions during labour. These brief decelerations are mediated by vagal activation. The reflex triggering this vagal response has been variably attributed to a mechanoreceptor response to fetal head compression, to baroreflex activation following increased blood pressure during umbilical cord compression, and/or a Bezold-Jarisch reflex response to reduced venous return from the placenta. Although these complex explanations are still widespread today, there is no consistent evidence that they are common during labour. Instead, the only mechanism that has been systematically investigated, proven to be reliably active during labour and, crucially, capable of producing rapid decelerations is the peripheral chemoreflex. The peripheral chemoreflex is triggered by transient periods of asphyxia that are a normal phenomenon associated with all uterine contractions. This should not cause concern as the healthy fetus has a remarkable ability to adapt to these repeated but short periods of asphyxia. This means that the healthy fetus is typically not at risk of hypotension and injury during uncomplicated labour even during repeated brief decelerations. The physiologically incorrect theories surrounding decelerations that ignore the natural occurrence of repeated asphyxia probably gained widespread support to help explain why many babies are born healthy despite repeated decelerations during labour. We propose that a unified and physiological understanding of intrapartum decelerations that accepts the true nature of labour is critical to improve interpretation of intrapartum fetal heart rate patterns. PMID:27328617

  4. Exercise training attenuates the pressor response evoked by peripheral chemoreflex in rats with heart failure.

    PubMed

    Calegari, Leonardo; Mozzaquattro, Bruna B; Rossato, Douglas D; Quagliotto, Edson; Ferreira, Janaina B; Rasia-Filho, Alberto; Dal Lago, Pedro

    2016-09-01

    The effects of exercise training (ExT) on the pressor response elicited by potassium cyanide (KCN) in the rat model of ischemia-induced heart failure (HF) are unknown. We evaluated the effects of ExT on chemoreflex sensitivity and its interaction with baroreflex in rats with HF. Wistar rats were divided into four groups: trained HF (Tr-HF), sedentary HF (Sed-HF), trained sham (Tr-Sham), and sedentary sham (Sed-Sham). Trained animals underwent to a treadmill running protocol for 8 weeks (60 m/day, 5 days/week, 16 m/min). After ExT, arterial pressure (AP), baroreflex sensitivity (BRS), peripheral chemoreflex (KCN: 100 μg/kg body mass), and cardiac function were evaluated. The results demonstrate that ExT induces an improvement in BRS and attenuates the pressor response to KCN relative to the Sed-HF group (P < 0.05). The improvement in BRS was associated with a reduction in the pressor response following ExT in HF rats (P < 0.05). Moreover, ExT induced a reduction in left ventricular end-diastolic pressure and pulmonary congestion compared with the Sed-HF group (P < 0.05). The pressor response to KCN in the hypotensive state is decreased in sedentary HF rats. These results suggest that ExT improves cardiac function and BRS and attenuates the pressor response evoked by KCN in HF rats. PMID:27295522

  5. Acrolein Causes TRPA1-Mediated Sensory Irritation and Indirect Potentiation of TRPV1-Mediated Pulmonary Chemoreflex Response

    EPA Science Inventory

    We previously demonstrated that acute exposure to acrolein causes immediate sensory irritation, with rapid decrease in heart rate (HR) and increase in inspiratory time (Ti), and potentiation of pulmonary chemoreflex response 24hrs later; of these effects only the latter is mediat...

  6. Hypoxia silences retrotrapezoid nucleus respiratory chemoreceptors via alkalosis.

    PubMed

    Basting, Tyler M; Burke, Peter G R; Kanbar, Roy; Viar, Kenneth E; Stornetta, Daniel S; Stornetta, Ruth L; Guyenet, Patrice G

    2015-01-14

    In conscious mammals, hypoxia or hypercapnia stimulates breathing while theoretically exerting opposite effects on central respiratory chemoreceptors (CRCs). We tested this theory by examining how hypoxia and hypercapnia change the activity of the retrotrapezoid nucleus (RTN), a putative CRC and chemoreflex integrator. Archaerhodopsin-(Arch)-transduced RTN neurons were reversibly silenced by light in anesthetized rats. We bilaterally transduced RTN and nearby C1 neurons with Arch (PRSx8-ArchT-EYFP-LVV) and measured the cardiorespiratory consequences of Arch activation (10 s) in conscious rats during normoxia, hypoxia, or hyperoxia. RTN photoinhibition reduced breathing equally during non-REM sleep and quiet wake. Compared with normoxia, the breathing frequency reduction (Δf(R)) was larger in hyperoxia (65% FiO2), smaller in 15% FiO2, and absent in 12% FiO2. Tidal volume changes (ΔV(T)) followed the same trend. The effect of hypoxia on Δf(R) was not arousal-dependent but was reversed by reacidifying the blood (acetazolamide; 3% FiCO2). Δf(R) was highly correlated with arterial pH up to arterial pH (pHa) 7.5 with no frequency inhibition occurring above pHa 7.53. Blood pressure was minimally reduced suggesting that C1 neurons were very modestly inhibited. In conclusion, RTN neurons regulate eupneic breathing about equally during both sleep and wake. RTN neurons are the first putative CRCs demonstrably silenced by hypocapnic hypoxia in conscious mammals. RTN neurons are silent above pHa 7.5 and increasingly active below this value. During hyperoxia, RTN activation maintains breathing despite the inactivity of the carotid bodies. Finally, during hypocapnic hypoxia, carotid body stimulation increases breathing frequency via pathways that bypass RTN.

  7. Sympathetic neural recruitment strategies: responses to severe chemoreflex and baroreflex stress.

    PubMed

    Badrov, Mark B; Usselman, Charlotte W; Shoemaker, J Kevin

    2015-07-15

    This study tested the hypothesis that neural coding patterns exist within the autonomic nervous system. We investigated sympathetic axonal recruitment strategies in humans during chemoreflex- and baroreflex-mediated sympathoexcitation using a novel action potential (AP) analysis technique. Muscle sympathetic nerve activity (microneurography) was collected in 11 young individuals (6 females) during baseline and two subsequent protocols: 1) severe chemoreflex stimulation (maximal end-inspiratory apnea following rebreathe), and 2) severe baroreceptor unloading (-80 mmHg lower body negative pressure; LBNP). When compared with each respective baseline, apnea and LBNP increased AP frequency and mean AP content per sympathetic burst (all P < 0.01). When APs were binned according to peak-to-peak amplitude (i.e., into "clusters"), total clusters detected increased during both apnea (Δ7 ± 5; P = 0.0009) and LBNP (Δ11 ± 8; P = 0.0012) compared with baseline. This was concomitant to an increased number of active clusters per burst during apnea (Δ3 ± 1; P < 0.0001) and LBNP (Δ3 ± 3; P = 0.0076). At baseline and during apnea (R(2) = 0.98; P < 0.0001) and LBNP (R(2) = 0.95; P < 0.0001), a pattern emerged whereby AP cluster latency decreased as cluster size increased. Furthermore, the AP cluster latency profile was shifted downward during apnea (∼53 ms) and upward during LBNP (∼31 ms). The data indicate that variations in synaptic delays and latent subpopulations of larger axons exist as recruitment strategies for sympathetic outflow. The synaptic delay component appears to express reflex specificity, whereas latent subpopulation recruitment demonstrates sensitivity to stress severity.

  8. Effects of simulated reflux laryngitis on laryngeal chemoreflexes in newborn lambs.

    PubMed

    Carreau, Anne-Marie; Patural, Hugues; Samson, Nathalie; Doueik, Alexandre A; Hamon, Julie; Fortier, Pierre-Hugues; Praud, Jean-Paul

    2011-08-01

    It has been suggested that reflux laryngitis (RL) is involved in apneas-bradycardias of the newborn. The aim of the present study was to develop a unique RL model in newborn lambs to test the hypothesis that RL enhances the cardiorespiratory components of the laryngeal chemoreflexes (LCR) in the neonatal period. Gastric juice surrogate (2 ml of normal saline solution with HCl pH 2 + pepsin 300 U/ml) (RL group, n = 6) or normal saline (control group, n = 6) was repeatedly injected onto the posterior aspect of the larynx, 3 times a day for 6 consecutive days, via a retrograde catheter introduced into the cervical esophagus. Lambs instilled with gastric juice surrogate presented clinical signs of RL, as well as moderate laryngitis on histological observation. Laryngeal chemoreflexes were thereafter induced during sleep by injection of 0.5 ml of HCl (pH 2), ewe's milk, distilled water or saline into the laryngeal vestibule via a chronic, transcutaneous supraglottal catheter. Overall, RL led to a significantly greater respiratory inhibition compared with the control group during LCR, including longer apnea duration (P = 0.01), lower minimal respiratory rate (P = 0.002), and a more prominent decrease in arterial hemoglobin saturation (SpO(2)) (P = 0.03). No effects were observed on cardiac variables. In conclusion, 1) our unique neonatal ovine model presents clinical and histological characteristics of RL; and 2) the presence of RL in newborn lambs increases the respiratory inhibition observed with LCR, at times leading to severe apneas and desaturations.

  9. Sympathetic neural recruitment strategies: responses to severe chemoreflex and baroreflex stress

    PubMed Central

    Badrov, Mark B.; Usselman, Charlotte W.

    2015-01-01

    This study tested the hypothesis that neural coding patterns exist within the autonomic nervous system. We investigated sympathetic axonal recruitment strategies in humans during chemoreflex- and baroreflex-mediated sympathoexcitation using a novel action potential (AP) analysis technique. Muscle sympathetic nerve activity (microneurography) was collected in 11 young individuals (6 females) during baseline and two subsequent protocols: 1) severe chemoreflex stimulation (maximal end-inspiratory apnea following rebreathe), and 2) severe baroreceptor unloading (−80 mmHg lower body negative pressure; LBNP). When compared with each respective baseline, apnea and LBNP increased AP frequency and mean AP content per sympathetic burst (all P < 0.01). When APs were binned according to peak-to-peak amplitude (i.e., into “clusters”), total clusters detected increased during both apnea (Δ7 ± 5; P = 0.0009) and LBNP (Δ11 ± 8; P = 0.0012) compared with baseline. This was concomitant to an increased number of active clusters per burst during apnea (Δ3 ± 1; P < 0.0001) and LBNP (Δ3 ± 3; P = 0.0076). At baseline and during apnea (R2 = 0.98; P < 0.0001) and LBNP (R2 = 0.95; P < 0.0001), a pattern emerged whereby AP cluster latency decreased as cluster size increased. Furthermore, the AP cluster latency profile was shifted downward during apnea (∼53 ms) and upward during LBNP (∼31 ms). The data indicate that variations in synaptic delays and latent subpopulations of larger axons exist as recruitment strategies for sympathetic outflow. The synaptic delay component appears to express reflex specificity, whereas latent subpopulation recruitment demonstrates sensitivity to stress severity. PMID:25947171

  10. Enhanced Firing in NTS Induced by Short-Term Sustained Hypoxia Is Modulated by Glia-Neuron Interaction.

    PubMed

    Accorsi-Mendonça, Daniela; Almado, Carlos E L; Bonagamba, Leni G H; Castania, Jaci A; Moraes, Davi J A; Machado, Benedito H

    2015-04-29

    Humans ascending to high altitudes are submitted to sustained hypoxia (SH), activating peripheral chemoreflex with several autonomic and respiratory responses. Here we analyzed the effect of short-term SH (24 h, FIO210%) on the processing of cardiovascular and respiratory reflexes using an in situ preparation of rats. SH increased both the sympatho-inhibitory and bradycardiac components of baroreflex and the sympathetic and respiratory responses of peripheral chemoreflex. Electrophysiological properties and synaptic transmission in the nucleus tractus solitarius (NTS) neurons, the first synaptic station of afferents of baroreflexes and chemoreflexes, were evaluated using brainstem slices and whole-cell patch-clamp. The second-order NTS neurons were identified by previous application of fluorescent tracer onto carotid body for chemoreceptor afferents or onto aortic depressor nerve for baroreceptor afferents. SH increased the intrinsic excitability of NTS neurons. Delayed excitation, caused by A-type potassium current (IKA), was observed in most of NTS neurons from control rats. The IKA amplitude was higher in identified second-order NTS neurons from control than in SH rats. SH also blunted the astrocytic inhibition of IKA in NTS neurons and increased the synaptic transmission in response to afferent fibers stimulation. The frequency of spontaneous excitatory currents was also increased in neurons from SH rats, indicating that SH increased the neurotransmission by presynaptic mechanisms. Therefore, short-term SH changed the glia-neuron interaction, increasing the excitability and excitatory transmission of NTS neurons, which may contribute to the observed increase in the reflex sensitivity of baroreflex and chemoreflex in in situ preparation.

  11. Distinct physiological strategies are used to cope with constant hypoxia and intermittent hypoxia in killifish (Fundulus heteroclitus).

    PubMed

    Borowiec, Brittney G; Darcy, Kimberly L; Gillette, Danielle M; Scott, Graham R

    2015-04-15

    Many fish encounter hypoxia on a daily cycle, but the physiological effects of intermittent hypoxia are poorly understood. We investigated whether acclimation to constant (sustained) hypoxia or to intermittent diel cycles of nocturnal hypoxia (12 h normoxia:12 h hypoxia) had distinct effects on hypoxia tolerance or on several determinants of O2 transport and O2 utilization in estuarine killifish. Adult killifish were acclimated to normoxia, constant hypoxia, or intermittent hypoxia for 7 or 28 days in brackish water (4 ppt). Acclimation to both hypoxia patterns led to comparable reductions in critical O2 tension and resting O2 consumption rate, but only constant hypoxia reduced the O2 tension at loss of equilibrium. Constant (but not intermittent) hypoxia decreased filament length and the proportion of seawater-type mitochondrion-rich cells in the gills (which may reduce ion loss and the associated costs of active ion uptake), increased blood haemoglobin content, and reduced the abundance of oxidative fibres in the swimming muscle. In contrast, only intermittent hypoxia augmented the oxidative and gluconeogenic enzyme activities in the liver and increased the capillarity of glycolytic muscle, each of which should facilitate recovery between hypoxia bouts. Neither exposure pattern affected muscle myoglobin content or the activities of metabolic enzymes in the brain or heart, but intermittent hypoxia increased brain mass. We conclude that the pattern of hypoxia exposure has an important influence on the mechanisms of acclimation, and that the optimal strategies used to cope with intermittent hypoxia may be distinct from those for coping with constant hypoxia.

  12. Sympathoexcitation and arterial hypertension associated with obstructive sleep apnea and cyclic intermittent hypoxia.

    PubMed

    Weiss, J Woodrow; Tamisier, Renaud; Liu, Yuzhen

    2015-12-15

    Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway obstruction during sleep. These obstructive episodes are characterized by cyclic intermittent hypoxia (CIH), by sleep fragmentation, and by hemodynamic instability, and they result in sustained sympathoexcitation and elevated arterial pressure that persist during waking, after restoration of normoxia. Early studies established that 1) CIH, rather than sleep disruption, accounts for the increase in arterial pressure; 2) the increase in arterial pressure is a consequence of the sympathoactivation; and 3) arterial hypertension after CIH exposure requires an intact peripheral chemoreflex. More recently, however, evidence has accumulated that sympathoactivation and hypertension after CIH are also dependent on altered central sympathoregulation. Furthermore, although many molecular pathways are activated in both the carotid chemoreceptor and in the central nervous system by CIH exposure, two specific neuromodulators-endothelin-1 and angiotensin II-appear to play crucial roles in mediating the sympathetic and hemodynamic response to intermittent hypoxia.

  13. Serotonin in the solitary tract nucleus shortens the laryngeal chemoreflex in anaesthetized neonatal rats.

    PubMed

    Donnelly, William T; Bartlett, Donald; Leiter, J C

    2016-07-01

    What is the central question of this study? Failure to terminate apnoea and arouse is likely to contribute to sudden infant death syndrome (SIDS). Serotonin is deficient in the brainstems of babies who died of SIDS. Therefore, we tested the hypothesis that serotonin in the nucleus of the solitary tract (NTS) would shorten reflex apnoea. What is the main finding and its importance? Serotonin microinjected into the NTS shortened the apnoea and respiratory inhibition associated with the laryngeal chemoreflex. Moreover, this effect was achieved through a 5-HT3 receptor. This is a new insight that is likely to be relevant to the pathogenesis of SIDS. The laryngeal chemoreflex (LCR), an airway-protective reflex that causes apnoea and bradycardia, has long been suspected as an initiating event in the sudden infant death syndrome. Serotonin (5-HT) and 5-HT receptors may be deficient in the brainstems of babies who die of sudden infant death syndrome, and 5-HT seems to be important in terminating apnoeas directly or in causing arousals or as part of the process of autoresuscitation. We hypothesized that 5-HT in the brainstem would limit the duration of the LCR. We studied anaesthetized rat pups between 7 and 21 days of age and made microinjections into the cisterna magna or into the nucleus of the solitary tract (NTS). Focal, bilateral microinjections of 5-HT into the caudal NTS significantly shortened the LCR. The 5-HT1a receptor antagonist, WAY 100635, did not affect the LCR consistently, nor did a 5-HT2 receptor antagonist, ketanserin, alter the duration of the LCR. The 5-HT3 specific agonist, 1-(3-chlorophenyl)-biguanide, microinjected bilaterally into the caudal NTS significantly shortened the LCR. Thus, endogenous 5-HT released within the NTS may curtail the respiratory depression that is part of the LCR, and serotonergic shortening of the LCR may be attributed to activation of 5-HT3 receptors within the NTS. 5-HT3 receptors are expressed presynaptically on C

  14. Activation of NTS A(1) adenosine receptors inhibits regional sympathetic responses evoked by activation of cardiopulmonary chemoreflex.

    PubMed

    Ichinose, Tomoko K; Minic, Zeljka; Li, Cailian; O'Leary, Donal S; Scislo, Tadeusz J

    2012-09-01

    Previously we have shown that adenosine operating via the A(1) receptor subtype may inhibit glutamatergic transmission in the baroreflex arc within the nucleus of the solitary tract (NTS) and differentially increase renal (RSNA), preganglionic adrenal (pre-ASNA), and lumbar (LSNA) sympathetic nerve activity (ASNA>RSNA≥LSNA). Since the cardiopulmonary chemoreflex and the arterial baroreflex are mediated via similar medullary pathways, and glutamate is a primary transmitter in both pathways, it is likely that adenosine operating via A(1) receptors in the NTS may differentially inhibit regional sympathetic responses evoked by activation of cardiopulmonary chemoreceptors. Therefore, in urethane-chloralose-anesthetized rats (n = 37) we compared regional sympathoinhibition evoked by the cardiopulmonary chemoreflex (activated with right atrial injections of serotonin 5HT(3) receptor agonist phenylbiguanide, PBG, 1-8 μg/kg) before and after selective stimulation of NTS A(1) adenosine receptors [microinjections of N(6)-cyclopentyl adenosine (CPA), 0.033-330 pmol/50 nl]. Activation of cardiopulmonary chemoreceptors evoked differential, dose-dependent sympathoinhibition (RSNA>ASNA>LSNA), and decreases in arterial pressure and heart rate. These differential sympathetic responses were uniformly attenuated in dose-dependent manner by microinjections of CPA into the NTS. Volume control (n = 11) and blockade of adenosine receptor subtypes in the NTS via 8-(p-sulfophenyl)theophylline (8-SPT, 1 nmol in 100 nl) (n = 9) did not affect the reflex responses. We conclude that activation of NTS A(1) adenosine receptors uniformly inhibits neural and cardiovascular cardiopulmonary chemoreflex responses. A(1) adenosine receptors have no tonic modulatory effect on this reflex under normal conditions. However, when adenosine is released into the NTS (i.e., during stress or severe hypotension/ischemia), it may serve as negative feedback regulator for depressor and sympathoinhibitory reflexes

  15. Neural Control of Blood Pressure in Chronic Intermittent Hypoxia

    PubMed Central

    Shell, Brent; Faulk, Katelynn; Cunningham, J. Thomas

    2016-01-01

    Sleep apnea (SA) is increasing in prevalence and is commonly comorbid with hypertension. Chronic intermittent hypoxia is used to model the arterial hypoxemia seen in SA, and through this paradigm, the mechanisms that underlie SA-induced hypertension are becoming clear. Cyclic hypoxic exposure during sleep chronically stimulates the carotid chemoreflexes, inducing sensory long-term facilitation, and drives sympathetic outflow from the hindbrain. The elevated sympathetic tone drives hypertension and renal sympathetic activity to the kidneys resulting in increased plasma renin activity and eventually angiotensin II (Ang II) peripherally. Upon waking, when respiration is normalized, the sympathetic activity does not diminish. This is partially because of adaptations leading to overactivation of the hindbrain regions controlling sympathetic outflow such as the nucleus tractus solitarius (NTS), and rostral ventrolateral medulla (RVLM). The sustained sympathetic activity is also due to enhanced synaptic signaling from the forebrain through the paraventricular nucleus (PVN). During the waking hours, when the chemoreceptors are not exposed to hypoxia, the forebrain circumventricular organs (CVOs) are stimulated by peripherally circulating Ang II from the elevated plasma renin activity. The CVOs and median preoptic nucleus chronically activate the PVN due to the Ang II signaling. All together, this leads to elevated nocturnal mean arterial pressure (MAP) as a response to hypoxemia, as well as inappropriately elevated diurnal MAP in response to maladaptations. PMID:26838032

  16. Effects of caffeine and/or nasal CPAP treatment on laryngeal chemoreflexes in preterm lambs.

    PubMed

    Boudaa, Nadia; Samson, Nathalie; Carrière, Vincent; Germim, Pamela Samanta; Pasquier, Jean-Charles; Bairam, Aida; Praud, Jean-Paul

    2013-03-01

    Current knowledge suggests that laryngeal chemoreflexes (LCR) are involved in the occurrence of certain neonatal apneas/bradycardias, especially in the preterm newborn. While caffeine and/or nasal continuous positive airway pressure (nCPAP) are the most frequent options used for treating apneas in preterm newborns, their effects on LCR-related apneas/bradycardias are virtually unknown. The aim of the present study was to test the hypothesis that caffeine and/or nCPAP decreases LCR-related cardiorespiratory inhibition in a preterm ovine model. Seven preterm lambs were born vaginally on gestational day 133 (normal gestation: 147 days) after intramuscular injections of betamethasone and mifepristone. Five days after birth, a chronic surgical instrumentation was performed to record states of alertness, electrocardiogram, systemic arterial pressure, and electromyographic activity of a laryngeal constrictor muscle, as well as to insert a transcutaneous supraglottal catheter. LCR were induced in quiet sleep under four conditions: 1) control (without caffeine or nCPAP); 2) nCPAP (5 cmH2O, without caffeine); 3) caffeine (10 mg/kg infused intravenously for 30 min, without nCPAP); and 4) nCPAP + caffeine. Our results showed that nCPAP consistently blunted LCR-related cardiorespiratory inhibition vs. control condition, contrary to caffeine whose overall effect was nonsignificant. In addition, nCPAP condition was characterized by a more consistent and rapid arousal after HCl injection. No significant differences were observed between all tested conditions with regard to swallowing and cough. It is concluded that nCPAP should be further assessed for its usefulness in treating neonatal apneas linked to LCR.

  17. Severe hemorrhage attenuates cardiopulmonary chemoreflex control of regional sympathetic outputs via NTS adenosine receptors.

    PubMed

    Minic, Zeljka; Li, Cailian; O'Leary, Donal S; Scislo, Tadeusz J

    2014-09-15

    Selective stimulation of inhibitory A1 and facilitatory A2a adenosine receptor subtypes located in the nucleus of the solitary tract (NTS) powerfully inhibits cardiopulmonary chemoreflex (CCR) control of regional sympathetic outputs via different mechanisms: direct inhibition of glutamate release and facilitation of an inhibitory neurotransmitter release, respectively. However, it remains unknown whether adenosine naturally released into the NTS has similar inhibitory effects on the CCR as the exogenous agonists do. Our previous study showed that adenosine is released into the NTS during severe hemorrhage and contributes to reciprocal changes of renal (decreases) and adrenal (increases) sympathetic nerve activity observed in this setting. Both A1 and A2a adenosine receptors are involved. Therefore, we tested the hypothesis that, during severe hemorrhage, CCR control of the two sympathetic outputs is attenuated by adenosine naturally released into the NTS. We compared renal and adrenal sympathoinhibitory responses evoked by right atrial injections of 5HT3 receptor agonist phenylbiguanide (2-8 μg/kg) under control conditions, during hemorrhage, and during hemorrhage preceded by blockade of NTS adenosine receptors with bilateral microinjections of 8-(p-sulfophenyl) theophylline (1 nmol/100 nl) in urethane/chloralose anesthetized rats. CCR-mediated inhibition of renal and adrenal sympathetic activity was significantly attenuated during severe hemorrhage despite reciprocal changes in the baseline activity levels, and this attenuation was removed by bilateral blockade of adenosine receptors in the caudal NTS. This confirmed that adenosine endogenously released into the NTS has a similar modulatory effect on integration of cardiovascular reflexes as stimulation of NTS adenosine receptors with exogenous agonists.

  18. Nucleus tractus solitarii A(2a) adenosine receptors inhibit cardiopulmonary chemoreflex control of sympathetic outputs.

    PubMed

    Minic, Zeljka; O'Leary, Donal S; Scislo, Tadeusz J

    2014-02-01

    Previously we have shown that stimulation of inhibitory A1 adenosine receptors located in the nucleus tractus solitarii (NTS) attenuates cardiopulmonary chemoreflex (CCR) evoked inhibition of renal, adrenal and lumbar sympathetic nerve activity and reflex decreases in arterial pressure and heart rate. Activation of facilitatory A2a adenosine receptors, which dominate over A1 receptors in the NTS, contrastingly alters baseline activity of regional sympathetic outputs: it decreases renal, increases adrenal and does not change lumbar nerve activity. Considering that NTS A2a receptors may facilitate release of inhibitory transmitters we hypothesized that A2a receptors will act in concert with A1 receptors differentially inhibiting regional sympathetic CCR responses (adrenal>lumbar>renal). In urethane/chloralose anesthetized rats (n=38) we compared regional sympathetic responses evoked by stimulation of the CCR with right atrial injections of serotonin 5HT3 receptor agonist, phenylbiguanide, (1-8μg/kg) before and after selective stimulation, blockade or combined blockade and stimulation of NTS A2a adenosine receptors (microinjections into the NTS of CGS-21680 0.2-20pmol/50nl, ZM-241385 40pmol/100nl or ZM-241385+CGS-21680, respectively). We found that stimulation of A2a adenosine receptors uniformly inhibited the regional sympathetic and hemodynamic reflex responses and this effect was abolished by the selective blockade of NTS A2a receptors. This indicates that A2a receptor triggered inhibition of CCR responses and the contrasting shifts in baseline sympathetic activity are mediated via different mechanisms. These data implicate that stimulation of NTS A2a receptors triggers unknown inhibitory mechanism(s) which in turn inhibit transmission in the CCR pathway when adenosine is released into the NTS during severe hypotension. PMID:24216055

  19. Severe hemorrhage attenuates cardiopulmonary chemoreflex control of regional sympathetic outputs via NTS adenosine receptors.

    PubMed

    Minic, Zeljka; Li, Cailian; O'Leary, Donal S; Scislo, Tadeusz J

    2014-09-15

    Selective stimulation of inhibitory A1 and facilitatory A2a adenosine receptor subtypes located in the nucleus of the solitary tract (NTS) powerfully inhibits cardiopulmonary chemoreflex (CCR) control of regional sympathetic outputs via different mechanisms: direct inhibition of glutamate release and facilitation of an inhibitory neurotransmitter release, respectively. However, it remains unknown whether adenosine naturally released into the NTS has similar inhibitory effects on the CCR as the exogenous agonists do. Our previous study showed that adenosine is released into the NTS during severe hemorrhage and contributes to reciprocal changes of renal (decreases) and adrenal (increases) sympathetic nerve activity observed in this setting. Both A1 and A2a adenosine receptors are involved. Therefore, we tested the hypothesis that, during severe hemorrhage, CCR control of the two sympathetic outputs is attenuated by adenosine naturally released into the NTS. We compared renal and adrenal sympathoinhibitory responses evoked by right atrial injections of 5HT3 receptor agonist phenylbiguanide (2-8 μg/kg) under control conditions, during hemorrhage, and during hemorrhage preceded by blockade of NTS adenosine receptors with bilateral microinjections of 8-(p-sulfophenyl) theophylline (1 nmol/100 nl) in urethane/chloralose anesthetized rats. CCR-mediated inhibition of renal and adrenal sympathetic activity was significantly attenuated during severe hemorrhage despite reciprocal changes in the baseline activity levels, and this attenuation was removed by bilateral blockade of adenosine receptors in the caudal NTS. This confirmed that adenosine endogenously released into the NTS has a similar modulatory effect on integration of cardiovascular reflexes as stimulation of NTS adenosine receptors with exogenous agonists. PMID:25063794

  20. Lip augmentation.

    PubMed

    Byrne, Patrick J; Hilger, Peter A

    2004-02-01

    Lip augmentation has become increasingly popular in recent years as a reflection of cultural trends emphasizing youth and beauty. Techniques to enhance the appearance of the lips have evolved with advances in biotechnology. An understanding of lip anatomy and aesthetics forms the basis for successful results. We outline the pertinent anatomy and aesthetics of the preoperative evaluation. A summary of various filler materials available is provided. Augmentation options include both injectable and open surgical techniques. The procedures and materials currently favored by the authors are described in greater detail.

  1. Hypoxia-induced autophagy mediates cisplatin resistance in lung cancer cells

    PubMed Central

    Wu, Hui-Mei; Jiang, Zi-Feng; Ding, Pei-Shan; Shao, Li-Jie; Liu, Rong-Yu

    2015-01-01

    Hypoxia which commonly exists in solid tumors, leads to cancer cells chemoresistance via provoking adaptive responses including autophagy. Therefore, we sought to evaluate the role of autophagy and hypoxia as well as the underlying mechanism in the cisplatin resistance of lung cancer cells. Our study demonstrated that hypoxia significantly protected A549 and SPC-A1 cells from cisplatin-induced cell death in a Hif-1α- and Hif-2α- dependent manner. Moreover, compared with normoxia, cisplatin-induced apoptosis under hypoxia was markedly reduced. However, when autophagy was inhibited by 3-MA or siRNA targeted ATG5, this reduction was effectively attenuated, which means autophagy mediates cisplatin resisitance under hypoxia. In parallel, we showed that hypoxia robustly augmented cisplatin-induced autophagy activation, accompanying by suppressing cisplatin-induced BNIP3 death pathways, which was due to the more efficient autophagic process under hypoxia. Consequently, we proposed that autophagy was a protective mechanism after cisplatin incubation under both normoxia and hypoxia. However, under normoxia, autophagy activation ‘was unable to counteract the stress induced by cisplatin, therefore resulting in cell death, whereas under hypoxia, autophagy induction was augmented that solved the cisplatin-induced stress, allowing the cells to survival. In conclusion, augmented induction of autophagy by hypoxia decreased lung cancer cells susceptibility to cisplatin-induced apoptosis. PMID:26201611

  2. Vascular effects of intermittent hypoxia.

    PubMed

    Kanagy, Nancy L

    2009-01-01

    Obstructive sleep apnea is characterized by repeated upper airway obstruction during sleep and affects between 5% and 20% of the population. Epidemiological studies reveal that sleep apnea and associated intermittent hypoxemia increase the risk for hypertension and vascular disease but the mechanisms underlying these effects are incompletely understood. This review reports the results of rodent models of intermittent hypoxia (IH) and relates them to the observed hemodynamic and vascular consequences of sleep apnea. These animal studies have demonstrated that IH exposure in the absence of any other comorbidity causes hypertension, endothelial dysfunction, and augmented constrictor sensitivity, all due at least in part to increased vascular oxidative stress. Animal studies have used a variety of exposure paradigms to study intermittent hypoxia and these different exposure protocols can cause hypocapnia or hypercapnia-or maintain eucapnia-with accompanying alterations in plasma pH. It appears that these different profiles of arterial blood gases can lead to divergent results but the impact of these differences is still being investigated. Overall, the studies in rodents have clearly demonstrated that the vascular and hemodynamic impact of intermittent hypoxia provides a strong rationale for treating clinical sleep apnea to prevent the resulting cardiovascular morbidity and mortality.

  3. Augmentation cheiloplasty.

    PubMed

    Ho, L C

    1994-06-01

    A technique of augmentation cheiloplasty with prior correction of a thin vermillion is described. Preserving and accentuating the natural contours of the lips is emphasised in vermillion correction and volume expansion with fat cell grafts. Thin vermillion correction, lip volume expansion and the state of fat cell grafts are reviewed.

  4. Antagonism of glutamate receptors in the intermediate and caudal NTS of awake rats produced no changes in the hypertensive response to chemoreflex activation.

    PubMed

    Machado, Benedito H; Bonagamba, Leni G H

    2005-01-15

    The role of excitatory amino acid (EAA) receptors in the neurotransmission of the sympathoexcitatory component of the chemoreflex (pressor response) in the intermediate and caudal aspects of the commissural nucleus tractus solitarii (NTS) of awake rats was evaluated. Microinjection of kynurenic acid, a non-selective antagonist of EAA receptors, into the intermediate and caudal commissural NTS produced a large increase in the baseline mean arterial pressure (MAP), which may reduce the magnitude of the pressor response to chemoreflex activation. To avoid this problem sodium nitroprusside (SNP) was infused (i.v.) after microinjections of kynurenic acid (2 nmol/50 nl) into the NTS, in order to normalize the MAP and then the chemoreflex was activated and the magnitude of the pressor response evaluated. Microinjection of kynurenic acid into the intermediate (bilaterally) and caudal (midline) commissural NTS (n=6) produced a significant increase in baseline MAP (103+/-5 vs. 137+/-6 mm Hg) normalized by SNP infusion (107+/-4 mm Hg) and under this experimental condition the pressor response to chemoreflex activation was not statistically different in relation to the control (37+/-7 vs. 44+/-6 mm Hg). Bilateral microinjections of kynurenic acid into the caudal NTS (n=8) also produced a significant increase in baseline MAP (109+/-4 vs. 145+/-6 mm Hg) normalized by SNP infusion (109+/-6 mm Hg). After normalization of MAP, the pressor response to chemoreflex activation at 3 (34+/-6 mm Hg) and 10 min (37+/-6 mm Hg) was also not different in relation to the control (46+/-5 mm Hg). These data indicate that the antagonism of EAA receptors simultaneously in the intermediate (bilateral) and caudal (midline) commissural NTS or only in the caudal commissural NTS (bilateral) of awake rats had no effect on the hypertensive response to chemoreflex activation. We suggest that neurotransmitter other than l-glutamate may take part in the neurotransmission of the sympathoexcitatory component

  5. Chin augmentation.

    PubMed

    Choe, K S; Stucki-McCormick, S U

    2000-01-01

    The primary goal of facial aesthetic surgery is to restore, enhance, and rejuvenate the aging face to a more youthful appearance, achieving balance and harmony. The mental area must be addressed in order to have a complete synthesis of the face. The concept of augmenting the mental area with implants has evolved so significantly that it now stands by itself as an important procedure. Various autogenous implants for chin augmentation have been in use for over 100 years but have complications. The advent of synthetic materials has given rise to various types of alloplastic implants: Gore-Tex, Medpor, Supramid, Silastic, and Mersilene. No one implant is perfect for every face. This article overviews several alloplastic implants--their advantages, disadvantages, and complications, in addition to the different techniques of preparing and delivering the implants.

  6. Medullary respiratory neural activity during hypoxia in NREM and REM sleep in the cat.

    PubMed

    Lovering, Andrew T; Fraigne, Jimmy J; Dunin-Barkowski, Witali L; Vidruk, Edward H; Orem, John M

    2006-02-01

    Intact unanesthetized cats hyperventilate in response to hypocapnic hypoxia in both wakefulness and sleep. This hyperventilation is caused by increases in diaphragmatic activity during inspiration and expiration. In this study, we recorded 120 medullary respiratory neurons during sleep in hypoxia. Our goal was to understand how these neurons change their activity to increase breathing efforts and frequency in response to hypoxia. We found that the response of medullary respiratory neurons to hypoxia was variable. While the activity of a small majority of inspiratory (58%) and expiratory (56%) neurons was increased in response to hypoxia, the activity of a small majority of preinspiratory (57%) neurons was decreased. Cells that were more active in hypoxia had discharge rates that averaged 183% (inspiratory decrementing), 154% (inspiratory augmenting), 155% (inspiratory), 230% (expiratory decrementing), 191% (expiratory augmenting), and 136% (expiratory) of the rates in normoxia. The response to hypoxia was similar in non-rapid-eye-movement (NREM) and REM sleep. Additionally, changes in the profile of activity were observed in all cell types examined. These changes included advanced, prolonged, and abbreviated patterns of activity in response to hypoxia; for example, some inspiratory neurons prolonged their discharge into expiration during the postinspiratory period in hypoxia but not in normoxia. Although changes in activity of the inspiratory neurons could account for the increased breathing efforts and activity of the diaphragm observed during hypoxia, the mechanisms responsible for the change in respiratory rate were not revealed by our data.

  7. Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats.

    PubMed

    Del Rio, Rodrigo; Andrade, David C; Lucero, Claudia; Arias, Paulina; Iturriaga, Rodrigo

    2016-08-01

    Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) chemosensory responses to hypoxia and produces autonomic dysfunction, cardiac arrhythmias, and hypertension. We tested whether autonomic alterations, arrhythmogenesis, and the progression of hypertension induced by CIH depend on the enhanced CB chemosensory drive, by ablation of the CB chemoreceptors. Male Sprague-Dawley rats were exposed to control (Sham) conditions for 7 days and then to CIH (5% O2, 12/h 8 h/d) for a total of 28 days. At 21 days of CIH exposure, rats underwent bilateral CB ablation and then exposed to CIH for 7 additional days. Arterial blood pressure and ventilatory chemoreflex response to hypoxia were measured in conscious rats. In addition, cardiac autonomic imbalance, cardiac baroreflex gain, and arrhythmia score were assessed during the length of the experiments. In separate experimental series, we measured extracellular matrix remodeling content in cardiac atrial tissue and systemic oxidative stress. CIH induced hypertension, enhanced ventilatory response to hypoxia, induced autonomic imbalance toward sympathetic preponderance, reduced baroreflex gain, and increased arrhythmias and atrial fibrosis. CB ablation normalized blood pressure, reduced ventilatory response to hypoxia, and restored cardiac autonomic and baroreflex function. In addition, CB ablation reduced the number of arrhythmias, but not extracellular matrix remodeling or systemic oxidative stress, suggesting that reductions in arrhythmia incidence during CIH were related to normalization of cardiac autonomic balance. Present results show that autonomic alterations induced by CIH are critically dependent on the CB and support a main role for the CB in the CIH-induced hypertension. PMID:27381902

  8. The ergogenics of hypoxia training in athletes.

    PubMed

    Loffredo, Brett M; Glazer, James L

    2006-06-01

    Hypoxia elicits hematopoiesis, which ultimately improves oxygen transport to peripheral tissues. In part because of this, altitude training has been used in the conditioning of elite endurance athletes for decades, despite equivocal evidence that such training benefits subsequent sea level performance. Recently, traditional live high-train high athletic conditioning has been implicated in a number of deleterious effects on training intensity, cardiac output, muscle composition, and fluid and metabolite balance--effects that largely offset hematopoietic benefits during sea level performance. Modified live high-train low conditioning regimens appear to capture the beneficial hematopoietic effects of hypoxic training while avoiding many of the deleterious effects of training at altitude. Because of the logistical and financial barriers to living high and training low, various methods to simulate hypoxia have been developed and studied. The data from these studies suggest a threshold requirement for hypoxic exposure to meaningfully augment hematopoiesis, and presumably improve athletic performance.

  9. Intermittent hypoxia and respiratory plasticity in humans and other animals: does exposure to intermittent hypoxia promote or mitigate sleep apnoea?

    PubMed Central

    Mateika, Jason H.; Narwani, Gunjan

    2009-01-01

    This review focuses on two phenomena that are initiated during and after exposure to intermittent hypoxia. The two phenomena are referred to as long-term facilitation and progressive augmentation of respiratory motor output. Both phenomena are forms of respiratory plasticity. Long-term facilitation is characterized by a sustained elevation in respiratory activity after exposure to intermittent hypoxia. Progressive augmentation is characterized by a gradual increase in respiratory activity from the initial to the final hypoxic exposure. There is much speculation that long-term facilitation may have a significant role in individuals with sleep apnoea because this disorder is characterized by periods of upper airway collapse accompanied by intermittent hypoxia, one stimulus known to induce long-term facilitation. It has been suggested that activation of long-term facilitation may serve to mitigate apnoea by facilitating ventilation and, more importantly, upper airway muscle activity. We examine the less discussed but equally plausible situation that exposure to intermittent hypoxia might ultimately lead to the promotion of apnoea. There are at least two scenarios in which apnoea might be promoted following exposure to intermittent hypoxia. In both scenarios, long-term facilitation of upper airway muscle activity is initiated but ultimately rendered ineffective because of other physiological conditions. Thus, one of the primary goals of this review is to discuss, with support from basic and clinical studies, whether various forms of respiratory motor neuronal plasticity have a beneficial and/or a detrimental impact on breathing stability in individuals with sleep apnoea. PMID:19060117

  10. NTS adenosine A2a receptors inhibit the cardiopulmonary chemoreflex control of regional sympathetic outputs via a GABAergic mechanism.

    PubMed

    Minic, Zeljka; O'Leary, Donal S; Scislo, Tadeusz J

    2015-07-01

    Adenosine is a powerful central neuromodulator acting via opposing A1 (inhibitor) and A2a (activator) receptors. However, in the nucleus of the solitary tract (NTS), both adenosine receptor subtypes attenuate cardiopulmonary chemoreflex (CCR) sympathoinhibition of renal, adrenal, and lumbar sympathetic nerve activity and attenuate reflex decreases in arterial pressure and heart rate. Adenosine A1 receptors inhibit glutamatergic transmission in the CCR pathway, whereas adenosine A2a receptors most likely facilitate release of an unknown inhibitory neurotransmitter, which, in turn, inhibits the CCR. We hypothesized that adenosine A2a receptors inhibit the CCR via facilitation of GABA release in the NTS. In urethane-chloralose-anesthetized rats (n = 51), we compared regional sympathetic responses evoked by stimulation of the CCR with right atrial injections of the 5-HT3 receptor agonist phenylbiguanide (1-8 μg/kg) before and after selective stimulation of NTS adenosine A2a receptors [microinjections into the NTS of CGS-21680 (20 pmol/50 nl)] preceded by blockade of GABAA or GABAB receptors in the NTS [bicuculline (10 pmol/100 nl) or SCH-50911 (1 nmol/100 nl)]. Blockade of GABAA receptors virtually abolished adenosine A2a receptor-mediated inhibition of the CCR. GABAB receptors had much weaker but significant effects. These effects were similar for the different sympathetic outputs. We conclude that stimulation of NTS adenosine A2a receptors inhibits CCR-evoked hemodynamic and regional sympathetic reflex responses via a GABA-ergic mechanism.

  11. NTS adenosine A2a receptors inhibit the cardiopulmonary chemoreflex control of regional sympathetic outputs via a GABAergic mechanism.

    PubMed

    Minic, Zeljka; O'Leary, Donal S; Scislo, Tadeusz J

    2015-07-01

    Adenosine is a powerful central neuromodulator acting via opposing A1 (inhibitor) and A2a (activator) receptors. However, in the nucleus of the solitary tract (NTS), both adenosine receptor subtypes attenuate cardiopulmonary chemoreflex (CCR) sympathoinhibition of renal, adrenal, and lumbar sympathetic nerve activity and attenuate reflex decreases in arterial pressure and heart rate. Adenosine A1 receptors inhibit glutamatergic transmission in the CCR pathway, whereas adenosine A2a receptors most likely facilitate release of an unknown inhibitory neurotransmitter, which, in turn, inhibits the CCR. We hypothesized that adenosine A2a receptors inhibit the CCR via facilitation of GABA release in the NTS. In urethane-chloralose-anesthetized rats (n = 51), we compared regional sympathetic responses evoked by stimulation of the CCR with right atrial injections of the 5-HT3 receptor agonist phenylbiguanide (1-8 μg/kg) before and after selective stimulation of NTS adenosine A2a receptors [microinjections into the NTS of CGS-21680 (20 pmol/50 nl)] preceded by blockade of GABAA or GABAB receptors in the NTS [bicuculline (10 pmol/100 nl) or SCH-50911 (1 nmol/100 nl)]. Blockade of GABAA receptors virtually abolished adenosine A2a receptor-mediated inhibition of the CCR. GABAB receptors had much weaker but significant effects. These effects were similar for the different sympathetic outputs. We conclude that stimulation of NTS adenosine A2a receptors inhibits CCR-evoked hemodynamic and regional sympathetic reflex responses via a GABA-ergic mechanism. PMID:25910812

  12. Hypoxia-excited neurons in NTS send axonal projections to Kölliker-Fuse/parabrachial complex in dorsolateral pons.

    PubMed

    Song, G; Xu, H; Wang, H; Macdonald, S M; Poon, C-S

    2011-02-23

    Hypoxic respiratory and cardiovascular responses in mammals are mediated by peripheral chemoreceptor afferents which are relayed centrally via the solitary tract nucleus (NTS) in dorsomedial medulla to other cardiorespiratory-related brainstem regions such as ventrolateral medulla (VLM). Here, we test the hypothesis that peripheral chemoafferents could also be relayed directly to the Kölliker-Fuse/parabrachial complex in dorsolateral pons, an area traditionally thought to subserve pneumotaxic and cardiovascular regulation. Experiments were performed on adult Sprague-Dawley rats. Brainstem neurons with axons projecting to the dorsolateral pons were retrogradely labeled by microinjection with choleras toxin subunit B (CTB). Neurons involved in peripheral chemoreflex were identified by hypoxia-induced c-Fos expression. We found that double-labeled neurons (i.e. immunopositive to both CTB and c-Fos) were localized mostly in the commissural and medial subnuclei of NTS and to a lesser extent in the ventrolateral NTS subnucleus, VLM and ventrolateral pontine A5 region. Extracellular recordings from the commissural and medial NTS subnuclei revealed that some hypoxia-excited NTS neurons could be antidromically activated by electrical stimulations at the dorsolateral pons. These findings demonstrate that hypoxia-activated afferent inputs are relayed to the Kölliker-Fuse/parabrachial complex directly via the commissural and medial NTS and indirectly via the ventrolateral NTS subnucleus, VLM and A5 region. These pontine-projecting peripheral chemoafferent inputs may play an important role in the modulation of cardiorespiratory regulation by dorsolateral pons.

  13. Hypoxia. 4. Hypoxia and ion channel function

    PubMed Central

    Polak, Jan

    2011-01-01

    The ability to sense and respond to oxygen deprivation is required for survival; thus, understanding the mechanisms by which changes in oxygen are linked to cell viability and function is of great importance. Ion channels play a critical role in regulating cell function in a wide variety of biological processes, including neuronal transmission, control of ventilation, cardiac contractility, and control of vasomotor tone. Since the 1988 discovery of oxygen-sensitive potassium channels in chemoreceptors, the effect of hypoxia on an assortment of ion channels has been studied in an array of cell types. In this review, we describe the effects of both acute and sustained hypoxia (continuous and intermittent) on mammalian ion channels in several tissues, the mode of action, and their contribution to diverse cellular processes. PMID:21178108

  14. Imaging hypoxia in gliomas

    PubMed Central

    Mendichovszky, I; Jackson, A

    2011-01-01

    Hypoxia plays a central role in tumour development, angiogenesis, growth and resistance to treatment. Owing to constant developments in medical imaging technology, significant advances have been made towards in vitro and in vivo imaging of hypoxia in a variety of tumours, including gliomas of the central nervous system. The aim of this article is to review the literature on imaging approaches currently available for measuring hypoxia in human gliomas and provide an insight into recent advances and future directions in this field. After a brief overview of hypoxia and its importance in gliomas, several methods of measuring hypoxia will be presented. These range from invasive monitoring by Eppendorf polarographic O2 microelectrodes, positron electron tomography (PET) tracers based on 2-nitroimidazole compounds [18F-labelled fluoro-misonidazole (18F-MISO) or 1-(2-[(18)F]fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole (FRP-170)], 64Cu-ATSM Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) or 99mTc- and 68Ga-labelled metronidazole (MN) agents to advanced MRI methods, such as blood oxygenation level dependent (BOLD) MRI, oxygen-enhanced MRI, diffusion-weighted MRI (DWI-MRI), dynamic contrast-enhanced MRI (DCE-MRI) and 1H-magnetic resonance spectroscopy. PMID:22433825

  15. The efficacy of antihypertensive drugs in chronic intermittent hypoxia conditions

    PubMed Central

    Diogo, Lucilia N.; Monteiro, Emília C.

    2014-01-01

    Sleep apnea/hypopnea disorders include centrally originated diseases and obstructive sleep apnea (OSA). This last condition is renowned as a frequent secondary cause of hypertension (HT). The mechanisms involved in the pathogenesis of HT can be summarized in relation to two main pathways: sympathetic nervous system stimulation mediated mainly by activation of carotid body (CB) chemoreflexes and/or asphyxia, and, by no means the least important, the systemic effects of chronic intermittent hypoxia (CIH). The use of animal models has revealed that CIH is the critical stimulus underlying sympathetic activity and hypertension, and that this effect requires the presence of functional arterial chemoreceptors, which are hyperactive in CIH. These models of CIH mimic the HT observed in humans and allow the study of CIH independently without the mechanical obstruction component. The effect of continuous positive airway pressure (CPAP), the gold standard treatment for OSA patients, to reduce blood pressure seems to be modest and concomitant antihypertensive therapy is still required. We focus this review on the efficacy of pharmacological interventions to revert HT associated with CIH conditions in both animal models and humans. First, we explore the experimental animal models, developed to mimic HT related to CIH, which have been used to investigate the effect of antihypertensive drugs (AHDs). Second, we review what is known about drug efficacy to reverse HT induced by CIH in animals. Moreover, findings in humans with OSA are cited to demonstrate the lack of strong evidence for the establishment of a first-line antihypertensive regimen for these patients. Indeed, specific therapeutic guidelines for the pharmacological treatment of HT in these patients are still lacking. Finally, we discuss the future perspectives concerning the non-pharmacological and pharmacological management of this particular type of HT. PMID:25295010

  16. The efficacy of antihypertensive drugs in chronic intermittent hypoxia conditions.

    PubMed

    Diogo, Lucilia N; Monteiro, Emília C

    2014-01-01

    Sleep apnea/hypopnea disorders include centrally originated diseases and obstructive sleep apnea (OSA). This last condition is renowned as a frequent secondary cause of hypertension (HT). The mechanisms involved in the pathogenesis of HT can be summarized in relation to two main pathways: sympathetic nervous system stimulation mediated mainly by activation of carotid body (CB) chemoreflexes and/or asphyxia, and, by no means the least important, the systemic effects of chronic intermittent hypoxia (CIH). The use of animal models has revealed that CIH is the critical stimulus underlying sympathetic activity and hypertension, and that this effect requires the presence of functional arterial chemoreceptors, which are hyperactive in CIH. These models of CIH mimic the HT observed in humans and allow the study of CIH independently without the mechanical obstruction component. The effect of continuous positive airway pressure (CPAP), the gold standard treatment for OSA patients, to reduce blood pressure seems to be modest and concomitant antihypertensive therapy is still required. We focus this review on the efficacy of pharmacological interventions to revert HT associated with CIH conditions in both animal models and humans. First, we explore the experimental animal models, developed to mimic HT related to CIH, which have been used to investigate the effect of antihypertensive drugs (AHDs). Second, we review what is known about drug efficacy to reverse HT induced by CIH in animals. Moreover, findings in humans with OSA are cited to demonstrate the lack of strong evidence for the establishment of a first-line antihypertensive regimen for these patients. Indeed, specific therapeutic guidelines for the pharmacological treatment of HT in these patients are still lacking. Finally, we discuss the future perspectives concerning the non-pharmacological and pharmacological management of this particular type of HT. PMID:25295010

  17. Inhibitory modulation of chemoreflex bradycardia by stimulation of the nucleus raphe obscurus is mediated by 5-HT3 receptors in the NTS of awake rats.

    PubMed

    Weissheimer, Karin Viana; Machado, Benedito H

    2007-03-30

    Several studies demonstrated the involvement of 5-hydroxytryptamine (5-HT) and its different receptor subtypes in the modulation of neurotransmission of cardiovascular reflexes in the nucleus tractus solitarii (NTS). Moreover, anatomic evidence suggests that nucleus raphe obscurus (ROb) is a source of 5-HT-containing terminals within the NTS. In the present study we investigated the possible changes in the cardiovascular responses to peripheral chemoreceptor activation by potassium cyanide (KCN, i.v.) following ROb stimulation with L-glutamate (10 nmol/50 nL) and also whether 5-HT3 receptors in the caudal commissural NTS are involved in this neuromodulation. The results showed that stimulation of the ROb with L-glutamate in awake rats (n=15) produced a significant reduction in the bradycardic response 30 s after the microinjection (-182+/-19 vs -236+/-10 bpm; Wilcoxon test) but no changes in the pressor response to peripheral chemoreceptor activation (43+/-4 vs 51+/-3 mmHg; two-way ANOVA) in relation to the control. Microinjection of 5--HT3 receptors antagonist granisetron (500 pmol/50 nL), but not the vehicle, into the caudal commissural NTS bilaterally prevented the reduction of chemoreflex bradycardia in response to microinjection of L-glutamate into ROb. These data indicate that 5-HT-containing projections from ROb to the NTS play an inhibitory neuromodulatory role in the chemoreflex evoked bradycardia by releasing 5-HT and activating 5-HT3 receptors in the caudal NTS.

  18. Hypoxia in paradise: widespread hypoxia tolerance in coral reef fishes.

    PubMed Central

    Nilsson, Göran E; Ostlund-Nilsson, Sara

    2004-01-01

    Using respirometry, we examined the hypoxia tolerance of 31 teleost fish species (seven families) inhabiting coral reefs at a 2-5 m depth in the lagoon at Lizard Island (Great Barrier Reef, Australia). All fishes studied maintained their rate of oxygen consumption down to relatively severe hypoxia (20-30% air saturation). Indeed, most fishes appeared unaffected by hypoxia until the oxygen level fell below 10% of air saturation. This, hitherto unrecognized, hypoxia tolerance among coral reef fishes could reflect adaptations to nocturnal hypoxia in tide pools. It may also be needed to enable fishes to reside deep within branching coral at night to avoid predation. Widespread hypoxia tolerance in a habitat with such an extreme biodiversity as coral reefs indicate that there is a wealth of hypoxia related adaptations to be discovered in reef fishes. PMID:15101411

  19. Clinical Biomarkers for Hypoxia Targeting

    PubMed Central

    Le, Quynh-Thu; Courter, Don

    2010-01-01

    Tumor hypoxia or a reduction of the tissue oxygen tension is a key microenvironmental factor for tumor progression and treatment resistance in solid tumors. Because hypoxic tumor cells have been demonstrated to be more resistant to ionizing radiation, hypoxia has been a focus of laboratory and clinical research in radiation therapy for many decades. It is believed that proper detection of hypoxic regions would guide treatment options and ultimately improve tumor response. To date, most clinical efforts in targeting tumor hypoxia have yielded equivocal results due to the lack of appropriate patient selection. However, with improved understanding of the molecular pathways regulated by hypoxia and the discovery of novel hypoxia markers, the prospect of targeting hypoxia has become more tangible. This chapter will focus on the development of clinical biomarkers for hypoxia targeting. PMID:18483785

  20. Imaging hypoxia in tumors.

    PubMed

    Ballinger, J R

    2001-10-01

    For many years, it has been known that hypoxia affects the response to radiotherapy in human cancers. Hypoxic regions can develop as a tumor grows beyond the ability of its blood supply to deliver oxygen to the full extent of the tumor, exacerbated by vascular spasm or compression caused by increased interstitial fluid pressure. However, hypoxia is heterogeneous, and tumors that appear identical by clinical and radiographic criteria can vary greatly in their extent of hypoxia. Several invasive procedures to measure hypoxia in tumors have been developed and are predictive of response to therapy, but none of these is in routine clinical use because of technical complexity, inconvenience, and inability to obtain repeated measures. Noninvasive imaging with a hypoxia-directed radiopharmaceutical could be of great clinical utility. Most such radiopharmaceuticals under development use 2-nitroimidazole as the targeting moiety. 2-Nitroimidazole, which is selectively reduced and bound in hypoxic tissues, has been labeled with F-18, Cu-64/67, I-123, and Tc-99m. Of these, F-18-fluoromisonidazole and I-123-iodoazomycin arabinoside (IAZA) have been most widely studied clinically. Non-nitro-containing bioreductive complexes, such as the Cu-60/62/64 thiosemicarbazone ATSM and Tc-99m butylene amineoxime (BnAO or HL91), have also been evaluated. In particular, 1-123-IAZA and Cu-60-ATSM have shown correlation with response to radiotherapy in preliminary clinical studies. However, more preclinical studies comparing imaging with validated invasive methods and clinical studies with outcome measures are required. Nuclear medicine is poised to play an important role in optimizing the therapy of patients with hypoxic tumors.

  1. Hypoxia promotes Rab5 activation, leading to tumor cell migration, invasion and metastasis.

    PubMed

    Silva, Patricio; Mendoza, Pablo; Rivas, Solange; Díaz, Jorge; Moraga, Carolina; Quest, Andrew F G; Torres, Vicente A

    2016-05-17

    Hypoxia, a common condition of the tumor microenvironment, is associated with poor patient prognosis, tumor cell migration, invasion and metastasis. Recent evidence suggests that hypoxia alters endosome dynamics in tumor cells, leading to augmented cell proliferation and migration and this is particularly relevant, because endosomal components have been shown to be deregulated in cancer. The early endosome protein Rab5 is a small GTPase that promotes integrin trafficking, focal adhesion turnover, Rac1 activation, tumor cell migration and invasion. However, the role of Rab5 and downstream events in hypoxia remain unknown. Here, we identify Rab5 as a critical player in hypoxia-driven tumor cell migration, invasion and metastasis. Exposure of A549 human lung carcinoma, ZR-75, MDA-MB-231 and MCF-7 human breast cancer and B16-F10 mouse melanoma cells to hypoxia increased Rab5 activation, followed by its re-localization to the leading edge and association with focal adhesions. Importantly, Rab5 was required for hypoxia-driven cell migration, FAK phosphorylation and Rac1 activation, as shown by shRNA-targeting and transfection assays with Rab5 mutants. Intriguingly, the effect of hypoxia on both Rab5 activity and migration was substantially higher in metastatic B16-F10 cells than in poorly invasive B16-F0 cells. Furthermore, exogenous expression of Rab5 in B16-F0 cells predisposed to hypoxia-induced migration, whereas expression of the inactive mutant Rab5/S34N prevented the migration of B16-F10 cells induced by hypoxia. Finally, using an in vivo syngenic C57BL/6 mouse model, Rab5 expression was shown to be required for hypoxia-induced metastasis. In summary, these findings identify Rab5 as a key mediator of hypoxia-induced tumor cell migration, invasion and metastasis.

  2. Hypoxia promotes Rab5 activation, leading to tumor cell migration, invasion and metastasis

    PubMed Central

    Silva, Patricio; Mendoza, Pablo; Rivas, Solange; Díaz, Jorge; Moraga, Carolina; Quest, Andrew F.G.; Torres, Vicente A.

    2016-01-01

    Hypoxia, a common condition of the tumor microenvironment, is associated with poor patient prognosis, tumor cell migration, invasion and metastasis. Recent evidence suggests that hypoxia alters endosome dynamics in tumor cells, leading to augmented cell proliferation and migration and this is particularly relevant, because endosomal components have been shown to be deregulated in cancer. The early endosome protein Rab5 is a small GTPase that promotes integrin trafficking, focal adhesion turnover, Rac1 activation, tumor cell migration and invasion. However, the role of Rab5 and downstream events in hypoxia remain unknown. Here, we identify Rab5 as a critical player in hypoxia-driven tumor cell migration, invasion and metastasis. Exposure of A549 human lung carcinoma, ZR-75, MDA-MB-231 and MCF-7 human breast cancer and B16-F10 mouse melanoma cells to hypoxia increased Rab5 activation, followed by its re-localization to the leading edge and association with focal adhesions. Importantly, Rab5 was required for hypoxia-driven cell migration, FAK phosphorylation and Rac1 activation, as shown by shRNA-targeting and transfection assays with Rab5 mutants. Intriguingly, the effect of hypoxia on both Rab5 activity and migration was substantially higher in metastatic B16-F10 cells than in poorly invasive B16-F0 cells. Furthermore, exogenous expression of Rab5 in B16-F0 cells predisposed to hypoxia-induced migration, whereas expression of the inactive mutant Rab5/S34N prevented the migration of B16-F10 cells induced by hypoxia. Finally, using an in vivo syngenic C57BL/6 mouse model, Rab5 expression was shown to be required for hypoxia-induced metastasis. In summary, these findings identify Rab5 as a key mediator of hypoxia-induced tumor cell migration, invasion and metastasis. PMID:27121131

  3. Hypoxia promotes Rab5 activation, leading to tumor cell migration, invasion and metastasis.

    PubMed

    Silva, Patricio; Mendoza, Pablo; Rivas, Solange; Díaz, Jorge; Moraga, Carolina; Quest, Andrew F G; Torres, Vicente A

    2016-05-17

    Hypoxia, a common condition of the tumor microenvironment, is associated with poor patient prognosis, tumor cell migration, invasion and metastasis. Recent evidence suggests that hypoxia alters endosome dynamics in tumor cells, leading to augmented cell proliferation and migration and this is particularly relevant, because endosomal components have been shown to be deregulated in cancer. The early endosome protein Rab5 is a small GTPase that promotes integrin trafficking, focal adhesion turnover, Rac1 activation, tumor cell migration and invasion. However, the role of Rab5 and downstream events in hypoxia remain unknown. Here, we identify Rab5 as a critical player in hypoxia-driven tumor cell migration, invasion and metastasis. Exposure of A549 human lung carcinoma, ZR-75, MDA-MB-231 and MCF-7 human breast cancer and B16-F10 mouse melanoma cells to hypoxia increased Rab5 activation, followed by its re-localization to the leading edge and association with focal adhesions. Importantly, Rab5 was required for hypoxia-driven cell migration, FAK phosphorylation and Rac1 activation, as shown by shRNA-targeting and transfection assays with Rab5 mutants. Intriguingly, the effect of hypoxia on both Rab5 activity and migration was substantially higher in metastatic B16-F10 cells than in poorly invasive B16-F0 cells. Furthermore, exogenous expression of Rab5 in B16-F0 cells predisposed to hypoxia-induced migration, whereas expression of the inactive mutant Rab5/S34N prevented the migration of B16-F10 cells induced by hypoxia. Finally, using an in vivo syngenic C57BL/6 mouse model, Rab5 expression was shown to be required for hypoxia-induced metastasis. In summary, these findings identify Rab5 as a key mediator of hypoxia-induced tumor cell migration, invasion and metastasis. PMID:27121131

  4. Equating of Augmented Subscores

    ERIC Educational Resources Information Center

    Sinharay, Sandip; Haberman, Shelby J.

    2011-01-01

    Recently, there has been an increasing level of interest in subscores for their potential diagnostic value. Haberman (2008b) suggested reporting an augmented subscore that is a linear combination of a subscore and the total score. Sinharay and Haberman (2008) and Sinharay (2010) showed that augmented subscores often lead to more accurate…

  5. Confronting an Augmented Reality

    ERIC Educational Resources Information Center

    Munnerley, Danny; Bacon, Matt; Wilson, Anna; Steele, James; Hedberg, John; Fitzgerald, Robert

    2012-01-01

    How can educators make use of augmented reality technologies and practices to enhance learning and why would we want to embrace such technologies anyway? How can an augmented reality help a learner confront, interpret and ultimately comprehend reality itself ? In this article, we seek to initiate a discussion that focuses on these questions, and…

  6. Malar and submalar augmentation.

    PubMed

    Binder, William J; Azizzadeh, Babak

    2008-02-01

    Over the past four decades, revolutionary improvements in the design and manufacture of facial implants have broadened the application of midface augmentation. The contemporary practice of facial rejuvenation reflects a 20-year culmination of rapid advances made in the understanding and treatment of midface aging. This article highlights the practice of malar and submalar augmentation: when and how it should be used.

  7. Hypoxia and spermatogenesis.

    PubMed

    Jankovic Velickovic, Ljubinka; Stefanovic, Vladisav

    2014-05-01

    This review mainly focuses on our understanding of spermatogenesis in physiological and pathological hypoxic condition. Real hypoxia is closely related to vascular changes and an increase in testicular temperature. Both induce a reduction in sperm count and can be related to the increase in germ cell apoptosis. On the other hand, change in the temperature, and oxygen levels in the microenvironment have influence on spermatogonial stem cell function and differentiation. The initial connection between hypoxia and a factor critical for stem cell maintenance is alteration in Oct-4 expression, and these data may be a useful strategy for modulating stem cell function. Unilateral testicular ischemia-induced cell death can be accompanied by an increase in germ cell apoptosis in the contralateral testis. The injury of contralateral testis following unilateral testicular damage is controversial, and it can contribute to the reduction in fertility. PMID:24265038

  8. Intermittent hypoxia and neurorehabilitation.

    PubMed

    Gonzalez-Rothi, Elisa J; Lee, Kun-Ze; Dale, Erica A; Reier, Paul J; Mitchell, Gordon S; Fuller, David D

    2015-12-15

    In recent years, it has become clear that brief, repeated presentations of hypoxia [i.e., acute intermittent hypoxia (AIH)] can boost the efficacy of more traditional therapeutic strategies in certain cases of neurologic dysfunction. This hypothesis derives from a series of studies in animal models and human subjects performed over the past 35 yr. In 1980, Millhorn et al. (Millhorn DE, Eldridge FL, Waldrop TG. Respir Physiol 41: 87-103, 1980) showed that electrical stimulation of carotid chemoafferent neurons produced a persistent, serotonin-dependent increase in phrenic motor output that outlasts the stimulus for more than 90 min (i.e., a "respiratory memory"). AIH elicits similar phrenic "long-term facilitation" (LTF) by a mechanism that requires cervical spinal serotonin receptor activation and de novo protein synthesis. From 2003 to present, a series of studies demonstrated that AIH can induce neuroplasticity in the injured spinal cord, causing functional recovery of breathing capacity after cervical spinal injury. Subsequently, it was demonstrated that repeated AIH (rAIH) can induce recovery of limb function, and the functional benefits of rAIH are greatest when paired with task-specific training. Since uncontrolled and/or prolonged intermittent hypoxia can elicit pathophysiology, a challenge of intermittent hypoxia research is to ensure that therapeutic protocols are well below the threshold for pathogenesis. This is possible since many low dose rAIH protocols have induced functional benefits without evidence of pathology. We propose that carefully controlled rAIH is a safe and noninvasive modality that can be paired with other neurorehabilitative strategies including traditional activity-based physical therapy or cell-based therapies such as intraspinal transplantation of neural progenitors. PMID:25997947

  9. Hypoxia and fatty liver.

    PubMed

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

    2014-11-01

    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty liver disease, a major cause of chronic liver diseases worldwide, ranging from simple steatosis, through steatohepatitis and hepatic fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in severe liver hypoxia. As master regulators of adaptive responses to hypoxic stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ functions, including erythropoiesis, angiogenesis, metabolic demand, and cell survival, by activating their target genes during fetal development and also in many disease conditions such as cancer, heart failure, and diabetes. In the past decade, it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver formation. This review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease. PMID:25386057

  10. An adenosine A2A agonist injected in the nucleus of the solitary tract prolongs the laryngeal chemoreflex by a GABAergic mechanism in decerebrate piglets

    PubMed Central

    Duy, Philip M.; Xia, Luxi; Bartlett, Donald; Leiter, J.C.

    2010-01-01

    Hyperthermic prolongation of the laryngeal chemoreflex (LCR) in decerebrate piglets is prevented or reversed by gamma-aminobutyric acid A (GABAA) receptor antagonists and adenosine A2A (Ad-A2A) receptor antagonists administered in the nucleus of the solitary tract (NTS). Therefore, we tested the hypothesis that enhanced GABAA activity and administration of the Ad-A2A agonist, CGS-21680, would prolong the LCR under normothermic conditions. We studied 46 decerebrate piglets ranging from 3 to 8 post-natal days of age. Focal injection into the NTS of 100 nl of 0.5 M nipecotic acid, a GABA reuptake inhibitor, significantly (P < 0.05) prolonged the LCR under normothermic conditions in 10 of 11 animals tested. Injecting 100 nl of 5–12.5 microM CGS-21680 unilaterally or bilaterally into the NTS also prolonged the LCR under normothermic conditions (n=15), but the effect was smaller than the effect of unilateral injection of nipecotic acid. Systemic administration of the GABAA receptor antagonist, bicuculline, prevented the CGS-21680-dependent prolongation of the LCR in normothermic animals (n = 11). We conclude that thermal prolongation of the LCR depends on a thermally sensitive process or set of neurons in the NTS, which, when activated by elevated brain temperature, enhance adenosinergic and GABAergic function in the region of the NTS. These results emphasize the importance of a thermally sensitive integrative site in the dorsal medulla that, along with sites in the ventral medulla, determine the response to laryngeal chemoreflex stimulation. PMID:20418346

  11. Hypoxia and fetal heart development.

    PubMed

    Patterson, A J; Zhang, L

    2010-10-01

    Fetal hearts show a remarkable ability to develop under hypoxic conditions. The metabolic flexibility of fetal hearts allows sustained development under low oxygen conditions. In fact, hypoxia is critical for proper myocardial formation. Particularly, hypoxia inducible factor 1 (HIF-1) and vascular endothelial growth factor play central roles in hypoxia-dependent signaling in fetal heart formation, impacting embryonic outflow track remodeling and coronary vessel growth. Although HIF is not the only gene involved in adaptation to hypoxia, its role places it as a central figure in orchestrating events needed for adaptation to hypoxic stress. Although "normal" hypoxia (lower oxygen tension in the fetus as compared with the adult) is essential in heart formation, further abnormal hypoxia in utero adversely affects cardiogenesis. Prenatal hypoxia alters myocardial structure and causes a decline in cardiac performance. Not only are the effects of hypoxia apparent during the perinatal period, but prolonged hypoxia in utero also causes fetal programming of abnormality in the heart's development. The altered expression pattern of cardioprotective genes such as protein kinase c epsilon, heat shock protein 70, and endothelial nitric oxide synthase, likely predispose the developing heart to increased vulnerability to ischemia and reperfusion injury later in life. The events underlying the long-term changes in gene expression are not clear, but likely involve variation in epigenetic regulation.

  12. Augmented reality: a review.

    PubMed

    Berryman, Donna R

    2012-01-01

    Augmented reality is a technology that overlays digital information on objects or places in the real world for the purpose of enhancing the user experience. It is not virtual reality, that is, the technology that creates a totally digital or computer created environment. Augmented reality, with its ability to combine reality and digital information, is being studied and implemented in medicine, marketing, museums, fashion, and numerous other areas. This article presents an overview of augmented reality, discussing what it is, how it works, its current implementations, and its potential impact on libraries.

  13. Augmented reality: a review.

    PubMed

    Berryman, Donna R

    2012-01-01

    Augmented reality is a technology that overlays digital information on objects or places in the real world for the purpose of enhancing the user experience. It is not virtual reality, that is, the technology that creates a totally digital or computer created environment. Augmented reality, with its ability to combine reality and digital information, is being studied and implemented in medicine, marketing, museums, fashion, and numerous other areas. This article presents an overview of augmented reality, discussing what it is, how it works, its current implementations, and its potential impact on libraries. PMID:22559183

  14. Serotoninergic modulation of cortical and respiratory responses to episodic hypoxia

    PubMed Central

    2009-01-01

    Biphasic respiratory response to hypoxia in anesthetized animals is accompanied by changes in the EEG mostly in the low EEG frequency bands. Serotonin is a potent modulator of cortical and respiratory activity through 5-HT2 receptors. Present study investigated whether 5-HT2 receptors might be involved in the EEG and respiratory relationship during normoxic and hypoxic respiration assessed from integrated phrenic (Phr) and hypoglossal (HG) nerve activities. EEG signal recorded from the frontal cortex was subjected to power spectral analysis in delta, theta, alpha, and beta frequency bands. Systemic administration of 5-HT2 agonist DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) enhanced tonic and lowered peak phasic respiratory activity, and increased frequency of bursts of Phr and HG activity. At the same time, EEG activity became desynchronized and arterial blood pressure (ABP) increased. Following DOI pretreatment, 11% hypoxia induced an augmented respiratory response in comparison with the response in the baseline condition. ABP fell less then in the control hypoxia. EEG pattern changed less than in the baseline state. Subsequent administration of ketanserin, a 5-HT2 antagonist increased respiratory activity, elicited a synchronization of EEG activity and hypotension. The respiratory response to hypoxia was attenuated and cortical response was more potent in comparison with that after DOI injection. Arterial blood pressure decreased more then during baseline hypoxic response. The results suggest that modulation of cortical synchronization and desynchronization through 5-HT2 receptor active agents may impact to hypoxic respiratory response. PMID:20156721

  15. RMS active damping augmentation

    NASA Technical Reports Server (NTRS)

    Gilbert, Michael G.; Scott, Michael A.; Demeo, Martha E.

    1992-01-01

    The topics are presented in viewgraph form and include: RMS active damping augmentation; potential space station assembly benefits to CSI; LaRC/JSC bridge program; control law design process; draper RMS simulator; MIMO acceleration control laws improve damping; potential load reduction benefit; DRS modified to model distributed accelerations; accelerometer location; Space Shuttle aft cockpit simulator; simulated shuttle video displays; SES test goals and objectives; and SES modifications to support RMS active damping augmentation.

  16. Hypoxia Inducible Factors and Hypertension: Lessons from Sleep Apnea Syndrome

    PubMed Central

    Nanduri, Jayasri; Peng, Ying-Jie; Yuan, Guoxiang; Kumar, Ganesh K.; Prabhakar, Nanduri R.

    2015-01-01

    Systemic hypertension is one of the most prevalent cardiovascular diseases. Sleep disordered breathing (SDB) with recurrent apnea is a major risk factor for developing essential hypertension. Chronic intermittent hypoxia (CIH) is a hallmark manifestation of recurrent apnea. Rodent models patterned after the O2 profiles seen with SDB patients showed that CIH is the major stimulus for causing systemic hypertension. This article reviews the physiological and molecular basis of CIH-induced hypertension. Physiological studies have identified that augmented carotid body chemosensory reflex and the resulting increase in sympathetic nerve activity is a major contributor to CIH-induced hypertension. Analysis of molecular mechanisms revealed that CIH activates hypoxia-inducible factor (HIF)-1 and suppresses HIF-2- mediated transcription. Dysregulation of HIF-1- and HIF-2- mediated transcription leads to imbalance of pro-oxidant and anti-oxidant enzyme gene expression resulting in increased reactive species (ROS) generation in the chemosensory reflex which is central for developing hypertension. PMID:25772710

  17. The expanding universe of hypoxia.

    PubMed

    Zhang, Huafeng; Semenza, Gregg L

    2008-07-01

    Reduced oxygen availability (hypoxia) is sensed and transduced into changes in the activity or expression of cellular macromolecules. These responses impact on virtually all areas of biology and medicine. In this meeting report, we summarize major developments in the field that were presented at the 2008 Keystone Symposium on Cellular, Physiological, and Pathogenic Responses to Hypoxia.

  18. Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives.

    PubMed

    Brutsaert, Tom D; Parra, Esteban J; Shriver, Mark D; Gamboa, Alfredo; Rivera-Ch, Maria; León-Velarde, Fabiola

    2005-07-01

    Andean high-altitude (HA) natives have a low (blunted) hypoxic ventilatory response (HVR), lower effective alveolar ventilation, and lower ventilation (VE) at rest and during exercise compared with acclimatized newcomers to HA. Despite blunted chemosensitivity and hypoventilation, Andeans maintain comparable arterial O(2) saturation (Sa(O(2))). This study was designed to evaluate the influence of ancestry on these trait differences. At sea level, we measured the HVR in both acute (HVR-A) and sustained (HVR-S) hypoxia in a sample of 32 male Peruvians of mainly Quechua and Spanish origins who were born and raised at sea level. We also measured resting and exercise VE after 10-12 h of exposure to altitude at 4,338 m. Native American ancestry proportion (NAAP) was assessed for each individual using a panel of 80 ancestry-informative molecular markers (AIMs). NAAP was inversely related to HVR-S after 10 min of isocapnic hypoxia (r = -0.36, P = 0.04) but was not associated with HVR-A. In addition, NAAP was inversely related to exercise VE (r = -0.50, P = 0.005) and ventilatory equivalent (VE/Vo(2), r = -0.51, P = 0.004) measured at 4,338 m. Thus Quechua ancestry may partly explain the well-known blunted HVR (10, 35, 36, 57, 62) at least to sustained hypoxia, and the relative exercise hypoventilation at altitude of Andeans compared with European controls. Lower HVR-S and exercise VE could reflect improved gas exchange and/or attenuated chemoreflex sensitivity with increasing NAAP. On the basis of these ancestry associations and on the fact that developmental effects were completely controlled by study design, we suggest both a genetic basis and an evolutionary origin for these traits in Quechua.

  19. Upregulation of NAD(P)H oxidase 1 in hypoxia activates hypoxia-inducible factor 1 via increase in reactive oxygen species.

    PubMed

    Goyal, Parag; Weissmann, Norbert; Grimminger, Friedrich; Hegel, Cornelia; Bader, Lucius; Rose, Frank; Fink, Ludger; Ghofrani, Hossein A; Schermuly, Ralph T; Schmidt, Harald H H W; Seeger, Werner; Hänze, Jörg

    2004-05-15

    Hypoxia sensing and related signaling events, including activation of hypoxia-inducible factor 1 (HIF-1), represent key features in cell physiology and lung function. Using cultured A549 cells, we investigated the role of NAD(P)H oxidase 1 (Nox1), suggested to be a subunit of a low-output NAD(P)H oxidase complex, in hypoxia signaling. Nox1 expression was detected on both the mRNA and protein levels. Upregulation of Nox1 mRNA and protein occurred during hypoxia, accompanied by enhanced reactive oxygen species (ROS) generation. A549 cells, which were transfected with a Nox1 expression vector, revealed an increase in ROS generation accompanied by activation of HIF-1-dependent target gene expression (heme oxygenase 1 mRNA, hypoxia-responsive-element reporter gene activity). In A549 cells stably overexpressing Nox1, accumulation of HIF-1alpha in normoxia and an additional increase in hypoxia were noted. Interference with ROS metabolism by the flavoprotein inhibitor diphenylene iodonium (DPI) and catalase inhibited HIF-1 induction. This suggests that H2O2 links Nox1 and HIF-1 activation. We conclude that hypoxic upregulation of Nox1 and subsequently augmented ROS generation may activate HIF-1-dependent pathways.

  20. Augmenting computer networks

    NASA Technical Reports Server (NTRS)

    Bokhari, S. H.; Raza, A. D.

    1984-01-01

    Three methods of augmenting computer networks by adding at most one link per processor are discussed: (1) A tree of N nodes may be augmented such that the resulting graph has diameter no greater than 4log sub 2((N+2)/3)-2. Thi O(N(3)) algorithm can be applied to any spanning tree of a connected graph to reduce the diameter of that graph to O(log N); (2) Given a binary tree T and a chain C of N nodes each, C may be augmented to produce C so that T is a subgraph of C. This algorithm is O(N) and may be used to produce augmented chains or rings that have diameter no greater than 2log sub 2((N+2)/3) and are planar; (3) Any rectangular two-dimensional 4 (8) nearest neighbor array of size N = 2(k) may be augmented so that it can emulate a single step shuffle-exchange network of size N/2 in 3(t) time steps.

  1. Hypoxia signaling pathways: modulators of oxygen-related organelles

    PubMed Central

    Schönenberger, Miriam J.; Kovacs, Werner J.

    2015-01-01

    Oxygen (O2) is an essential substrate in cellular metabolism, bioenergetics, and signaling and as such linked to the survival and normal function of all metazoans. Low O2 tension (hypoxia) is a fundamental feature of physiological processes as well as pathophysiological conditions such as cancer and ischemic diseases. Central to the molecular mechanisms underlying O2 homeostasis are the hypoxia-inducible factors-1 and -2 alpha (HIF-1α and EPAS1/HIF-2α) that function as master regulators of the adaptive response to hypoxia. HIF-induced genes promote characteristic tumor behaviors, including angiogenesis and metabolic reprogramming. The aim of this review is to critically explore current knowledge of how HIF-α signaling regulates the abundance and function of major O2-consuming organelles. Abundant evidence suggests key roles for HIF-1α in the regulation of mitochondrial homeostasis. An essential adaptation to sustained hypoxia is repression of mitochondrial respiration and induction of glycolysis. HIF-1α activates several genes that trigger mitophagy and represses regulators of mitochondrial biogenesis. Several lines of evidence point to a strong relationship between hypoxia, the accumulation of misfolded proteins in the endoplasmic reticulum, and activation of the unfolded protein response. Surprisingly, although peroxisomes depend highly on molecular O2 for their function, there has been no evidence linking HIF signaling to peroxisomes. We discuss our recent findings that establish HIF-2α as a negative regulator of peroxisome abundance and suggest a mechanism by which cells attune peroxisomal function with O2 availability. HIF-2α activation augments peroxisome turnover by pexophagy and thereby changes lipid composition reminiscent of peroxisomal disorders. We discuss potential mechanisms by which HIF-2α might trigger pexophagy and place special emphasis on the potential pathological implications of HIF-2α-mediated pexophagy for human health. PMID:26258123

  2. Pharmacological approaches in either intermittent or permanent hypoxia: A tale of two exposures.

    PubMed

    Herrera, E A; Farías, J G; Ebensperger, G; Reyes, R V; Llanos, A J; Castillo, R L

    2015-11-01

    Hypoxia induces several responses at cardiovascular, pulmonary and reproductive levels, which may lead to chronic diseases. This is relevant in human populations exposed to high altitude (HA), in either chronic continuous (permanent inhabitants) or intermittent fashion (HA workers, tourists and mountaineers). In Chile, it is estimated that 1.000.000 people live at highlands and more than 55.000 work in HA shifts. Initial responses to hypoxia are compensatory and induce activation of cardioprotective mechanisms, such as those seen under intermittent hypobaric (IH) hypoxia, events that could mediate preconditioning. However, whenever hypoxia is prolonged, the chronic activation of cellular responses induces long-lasting modifications that may result in acclimatization or produce maladaptive changes with increase in cardiovascular risk. HA exposure during pregnancy induces hypoxia and oxidative stress, which in turn may promote cellular responses and epigenetic modifications resulting in severe impairment in growth and development. Sadly, this condition is accompanied with an increased fetal and neonatal morbi-mortality. Further, developmental hypoxia may program cardio-pulmonary circulations later in postnatal life, ending in vascular structural and functional alterations with augmented risk on pulmonary and cardiovascular failure. Additionally, permanent HA inhabitants have augmented risk and prevalence of chronic hypoxic pulmonary hypertension, right ventricular hypertrophy and cardiopulmonary remodeling. Similar responses are seen in adults that are intermittently exposed to chronic hypoxia (CH) such as shift workers in HA areas. The mechanisms involved determining the immediate, short and long-lasting effects are still unclear. For several years, the study of the responses to hypoxic insults and pharmacological targets has been the motivation of our group. This review describes some of the mechanisms underlying hypoxic responses and potential therapeutic

  3. Inflammation and hypoxia linked to renal injury by CCAAT/enhancer-binding protein δ.

    PubMed

    Yamaguchi, Junna; Tanaka, Tetsuhiro; Eto, Nobuaki; Nangaku, Masaomi

    2015-08-01

    Tubulointerstitial hypoxia plays a critical role in the pathogenesis of kidney injury, and hypoxia-inducible factor (HIF)-1 is a master regulator of cellular adaptation to hypoxia. Aside from oxygen molecules, factors that modify HIF-1 expression and functional operation remain obscure. Therefore, we sought to identify novel HIF-1-regulating genes in kidney. A short-hairpin RNA library consisting of 150 hypoxia-inducible genes was derived from a microarray analysis of the rat renal artery stenosis model screened for the effect on HIF-1 response. We report that CCAAT/enhancer-binding protein δ (CEBPD), a transcription factor and inflammatory response gene, is a novel HIF-1 regulator in kidney. CEBPD was induced in the nuclei of tubular epithelial cells in both acute and chronic hypoxic kidneys. In turn, CEBPD induction augmented HIF-1α expression and its transcriptional activity. Mechanistically, CEBPD directly bound to the HIF-1α promoter and enhanced its transcription. Notably, CEBPD was rapidly induced by inflammatory cytokines, such as IL-1β in a nuclear factor-κB-dependent manner, which not only increased HIF-1α expression during hypoxia, but was also indispensable for the non-hypoxic induction of HIF-1α. Thus our study provides novel insight into HIF-1 regulation in tubular epithelial cells and offers a potential hypoxia and inflammation link relevant in both acute and chronic kidney diseases. PMID:25692954

  4. Adrenocortical responses to ACTH in neonatal rats: effect of hypoxia from birth on corticosterone, StAR, and PBR.

    PubMed

    Raff, Hershel; Hong, Julie J; Oaks, Martin K; Widmaier, Eric P

    2003-01-01

    The adrenocortical response to hypoxia may be a critical component of the adaptation to this common neonatal stress. Little is known about adrenal function in vivo in hypoxic neonates. The purpose of this study was to evaluate adrenocortical responses to ACTH in suckling rat pups exposed to hypoxia from birth to 5-7 days of age compared with normoxic controls. We also evaluated potential cellular controllers of steroidogenic function in situ. In 7-day-old pups at 0800, hypoxia from birth resulted in increased basal (12.2 +/- 1.4 ng/ml; n = 12) and ACTH-stimulated (94.0 +/- 9.4 ng/ml; n = 14) corticosterone levels compared with normoxic controls (basal = 8.3 +/- 0.5 ng/ml; n = 11; stimulated = 51.3 +/- 3.8 ng/ml; n = 8). This augmentation occurred despite no significant difference in plasma ACTH levels in normoxic vs. hypoxic pups before (85 +/- 4 vs. 78 +/- 8 pg/ml) or after (481 +/- 73 vs. 498 +/- 52 pg/ml) porcine ACTH injection (20 microg/kg). This effect was similar in the afternoon at 6 days of age and even greater at 5 days of age at 0800. The aldosterone response to ACTH was not augmented by exposure to hypoxia from birth. Adrenocortical hypoxia-inducible factor (HIF)-1alpha mRNA was undetectable by RT-PCR. Steroidogenic acute regulatory (StAR) protein in adrenal subcapsules (zona fasciculata/reticularis) was augmented by exposure to hypoxia; this effect was greatest at 5 days of age. Peripheral-type benzodiazepine receptor (PBR) protein was also increased at 6 and 7 days of age in pups exposed to hypoxia from birth. We conclude that hypoxia from birth results in an augmentation of the corticosterone but not aldosterone response to ACTH. This effect appears to be mediated at least in part by an increase in controllers of mitochondrial cholesterol transport (StAR and PBR) and to occur independently of measurable changes in endogenous plasma ACTH. The augmentation of the corticosterone response to acute increases in ACTH in hypoxic pups is likely to be an

  5. Soft tissue augmentation.

    PubMed

    Hirsch, Ranella J; Cohen, Joel L

    2006-09-01

    Recent additions to the soft tissue augmentation armamentarium have greatly increased the dermatologic surgeon's choices in optimizing facial contouring and the treatment of acne scars. In this article, we review the science of fillers and look at the future of dermal fillers.

  6. Augmented Reality Binoculars.

    PubMed

    Oskiper, Taragay; Sizintsev, Mikhail; Branzoi, Vlad; Samarasekera, Supun; Kumar, Rakesh

    2015-05-01

    In this paper we present an augmented reality binocular system to allow long range high precision augmentation of live telescopic imagery with aerial and terrain based synthetic objects, vehicles, people and effects. The inserted objects must appear stable in the display and must not jitter and drift as the user pans around and examines the scene with the binoculars. The design of the system is based on using two different cameras with wide field of view and narrow field of view lenses enclosed in a binocular shaped shell. Using the wide field of view gives us context and enables us to recover the 3D location and orientation of the binoculars much more robustly, whereas the narrow field of view is used for the actual augmentation as well as to increase precision in tracking. We present our navigation algorithm that uses the two cameras in combination with an inertial measurement unit and global positioning system in an extended Kalman filter and provides jitter free, robust and real-time pose estimation for precise augmentation. We have demonstrated successful use of our system as part of information sharing example as well as a live simulated training system for observer training, in which fixed and rotary wing aircrafts, ground vehicles, and weapon effects are combined with real world scenes. PMID:26357208

  7. Augmentative & Alternative Communication

    ERIC Educational Resources Information Center

    Murphy, Patti

    2007-01-01

    There is no definitive recipe for augmentative and alternative communication (AAC) success, but its universal ingredients can be found at home. The main ones are: (1) Understanding that all children need to express themselves, however outgoing or shy they may be; (2) Willingness to embrace the technology that may help your child regardless of your…

  8. Augmented thermal bus

    NASA Technical Reports Server (NTRS)

    Schrage, Dean S. (Inventor)

    1993-01-01

    The present invention is directed to an augmented thermal bus. In the present design a plurity of thermo-electric heat pumps are used to couple a source plate to a sink plate. Each heat pump is individually controlled by a model based controller. The controller coordinates the heat pump to maintain isothermality in the source.

  9. Augmented Thermal Bus

    NASA Technical Reports Server (NTRS)

    Schrage, Dean S. (Inventor)

    1996-01-01

    The present invention is directed to an augmented thermal bus. In the present design a plurality of thermo-electric heat pumps are used to couple a source plate to a sink plate. Each heat pump is individually controlled by a model based controller. The controller coordinates the heat pumps to maintain isothermality in the source.

  10. Hypoxia and Hypoxia-Inducible Factors in Leukemias

    PubMed Central

    Deynoux, Margaux; Sunter, Nicola; Hérault, Olivier; Mazurier, Frédéric

    2016-01-01

    Despite huge improvements in the treatment of leukemia, the percentage of patients suffering relapse still remains significant. Relapse most often results from a small number of leukemic stem cells (LSCs) within the bone marrow, which are able to self-renew, and therefore reestablish the full tumor. The marrow microenvironment contributes considerably in supporting the protection and development of leukemic cells. LSCs share specific niches with normal hematopoietic stem cells with the niche itself being composed of a variety of cell types, including mesenchymal stem/stromal cells, bone cells, immune cells, neuronal cells, and vascular cells. A hallmark of the hematopoietic niche is low oxygen partial pressure, indeed this hypoxia is necessary for the long-term maintenance of hematopoietic stem/progenitor cells. Hypoxia is a strong signal, principally maintained by members of the hypoxia-inducible factor (HIF) family. In solid tumors, it has been well established that hypoxia triggers intrinsic metabolic changes and microenvironmental modifications, such as the stimulation of angiogenesis, through activation of HIFs. As leukemia is not considered a “solid” tumor, the role of oxygen in the disease was presumed to be inconsequential and remained long overlooked. This view has now been revised since hypoxia has been shown to influence leukemic cell proliferation, differentiation, and resistance to chemotherapy. However, the role of HIF proteins remains controversial with HIFs being considered as either oncogenes or tumor suppressor genes, depending on the study and model. The purpose of this review is to highlight our knowledge of hypoxia and HIFs in leukemic development and therapeutic resistance and to discuss the recent hypoxia-based strategies proposed to eradicate leukemias. PMID:26955619

  11. Influence of Hypoxia on Cerebral Blood Flow Regulation in Humans.

    PubMed

    Steinback, Craig D; Poulin, Marc J

    2016-01-01

    The brain is a vital organ that relies on a constant and adequate supply of blood to match oxygen and glucose delivery with the local metabolic demands of active neurones. It is well established that cerebral blood flow is altered in response to both neural activity and humoral stimuli. Thus, augmented neural activation (e.g. visual stimulation) leads to locally increased cerebral blood flow via functional hyperaemia, whereas humoral stimuli (i.e. alterations in arterial PO2 and PCO2) produce global increases in cerebral blood flow. Perhaps not surprisingly, cerebrovascular responses to neural activity and humoral stimuli may not be highly correlated because they reflect different physiological mechanisms for vasodilation. Exquisite regulation of cerebral blood flow is particularly important under hypoxic conditions when cerebral PO2 can be reduced substantially. Indeed, cerebrovascular reactivity to hypoxia determines the capacity of cerebral vessels to respond and compensate for a reduced oxygen supply. This reactivity is dynamic, changing with prolonged exposure to hypoxic environments, and in patients and healthy individuals exposed to chronic intermittent periods of hypoxia. More recently, a number of animal studies have provided evidence that glial cells (i.e. astrocytes) play an important role in regulating cerebral blood flow under normoxic and hypoxic conditions. This review aims to summarize our current understanding of cerebral blood flow control during hypoxia in humans and put into context the underlying neurovascular mechanisms that may contribute to this regulation. PMID:27343093

  12. Imaging Tumor Hypoxia to Advance Radiation Oncology

    PubMed Central

    Lee, Chen-Ting; Boss, Mary-Keara

    2014-01-01

    Abstract Significance: Most solid tumors contain regions of low oxygenation or hypoxia. Tumor hypoxia has been associated with a poor clinical outcome and plays a critical role in tumor radioresistance. Recent Advances: Two main types of hypoxia exist in the tumor microenvironment: chronic and cycling hypoxia. Chronic hypoxia results from the limited diffusion distance of oxygen, and cycling hypoxia primarily results from the variation in microvessel red blood cell flux and temporary disturbances in perfusion. Chronic hypoxia may cause either tumor progression or regressive effects depending on the tumor model. However, there is a general trend toward the development of a more aggressive phenotype after cycling hypoxia. With advanced hypoxia imaging techniques, spatiotemporal characteristics of tumor hypoxia and the changes to the tumor microenvironment can be analyzed. Critical Issues: In this review, we focus on the biological and clinical consequences of chronic and cycling hypoxia on radiation treatment. We also discuss the advanced non-invasive imaging techniques that have been developed to detect and monitor tumor hypoxia in preclinical and clinical studies. Future Directions: A better understanding of the mechanisms of tumor hypoxia with non-invasive imaging will provide a basis for improved radiation therapeutic practices. Antioxid. Redox Signal. 21, 313–337. PMID:24329000

  13. Simple Implant Augmentation Rhinoplasty.

    PubMed

    Nguyen, Anh H; Bartlett, Erica L; Kania, Katarzyna; Bae, Sang Mo

    2015-11-01

    Augmentation rhinoplasty among Asian patients is often performed to improve the height of the nasal dorsum. As the use of autogenous tissues poses certain limitations, alloplastic materials are a viable alternative with a long history of use in Asia. The superiority of one implant prosthesis over another for augmentation rhinoplasty is a matter of debate, with each material representing varying strengths and weaknesses, indications for use, and precautions to consider in nasal implant placement. An implant prosthesis should be used on a case-by-case basis. Augmentation rhinoplasty requires the consideration of specific anatomical preoperative factors, including the external nose, nasal length, nasofrontal angle, humps, and facial proportions. It is equally important to consider several operative guidelines to appropriately shape implants to minimize the occurrence of adverse effects and postoperative complications. The most common postoperative complications include infection, nasal height change, movement of implant prosthesis, and silicone implant protrusion. In addition, the surgeon should consider the current standards of Asian beauty aesthetics to better understand the patient's desired outcome. PMID:26648804

  14. Hypoxia and Hypoxia Inducible Factors: Diverse Roles in Liver Diseases

    PubMed Central

    Nath, Bharath; Szabo, Gyongyi

    2011-01-01

    Hypoxia has been shown to have a role in the pathogenesis of several forms of liver disease. The Hypoxia Inducible Factors (HIFs) are a family of evolutionarily conserved transcriptional regulators that affect a homeostatic response to low oxygen tension and have been identified as key mediators of angiogenesis, inflammation, and metabolism. In this review, we summarize the evidence for a role of HIFs across a range of hepatic pathophysiology. We describe regulation of the hypoxia inducible factors and review investigations that demonstrate a role for HIFs in the development of liver fibrosis, activation of innate immune pathways, hepatocellular carcinoma, as well as other liver diseases in both human disease as well as murine models. PMID:22120903

  15. Lung oxidative damage by hypoxia.

    PubMed

    Araneda, O F; Tuesta, M

    2012-01-01

    One of the most important functions of lungs is to maintain an adequate oxygenation in the organism. This organ can be affected by hypoxia facing both physiological and pathological situations. Exposure to this condition favors the increase of reactive oxygen species from mitochondria, as from NADPH oxidase, xanthine oxidase/reductase, and nitric oxide synthase enzymes, as well as establishing an inflammatory process. In lungs, hypoxia also modifies the levels of antioxidant substances causing pulmonary oxidative damage. Imbalance of redox state in lungs induced by hypoxia has been suggested as a participant in the changes observed in lung function in the hypoxic context, such as hypoxic vasoconstriction and pulmonary edema, in addition to vascular remodeling and chronic pulmonary hypertension. In this work, experimental evidence that shows the implied mechanisms in pulmonary redox state by hypoxia is reviewed. Herein, studies of cultures of different lung cells and complete isolated lung and tests conducted in vivo in the different forms of hypoxia, conducted in both animal models and humans, are described. PMID:22966417

  16. Physiological effects of intermittent hypoxia.

    PubMed

    Powell, F L; Garcia, N

    2000-01-01

    Intermittent hypoxia (IH), or periodic exposure to hypoxia interrupted by return to normoxia or less hypoxic conditions, occurs in many circumstances. In high altitude mountaineering, IH is used to optimize acclimatization although laboratory studies have not generally revealed physiologically significant benefits. IH enhances athletic performance at sea level if blood oxygen capacity increases and the usual level of training is not decreased significantly. IH for high altitude workers who commute from low altitude homes is of considerable practical interest and the ideal commuting schedule for physical and mental performance is being studied. The effect of oxygen enrichment at altitude (i.e., intermittent normoxia on a background of chronic hypoxia) on human performance is under study also. Physiological mechanisms of IH, and specifically the differences between effects of IH and acute or chronic continuous hypoxia remains to be determined. Biomedical researchers are defining the molecular and cellular mechanisms for effects of hypoxia on the body in health and disease. A comparative approach may provide additional insight about the biological significance of these effects.

  17. Lung Oxidative Damage by Hypoxia

    PubMed Central

    Araneda, O. F.; Tuesta, M.

    2012-01-01

    One of the most important functions of lungs is to maintain an adequate oxygenation in the organism. This organ can be affected by hypoxia facing both physiological and pathological situations. Exposure to this condition favors the increase of reactive oxygen species from mitochondria, as from NADPH oxidase, xanthine oxidase/reductase, and nitric oxide synthase enzymes, as well as establishing an inflammatory process. In lungs, hypoxia also modifies the levels of antioxidant substances causing pulmonary oxidative damage. Imbalance of redox state in lungs induced by hypoxia has been suggested as a participant in the changes observed in lung function in the hypoxic context, such as hypoxic vasoconstriction and pulmonary edema, in addition to vascular remodeling and chronic pulmonary hypertension. In this work, experimental evidence that shows the implied mechanisms in pulmonary redox state by hypoxia is reviewed. Herein, studies of cultures of different lung cells and complete isolated lung and tests conducted in vivo in the different forms of hypoxia, conducted in both animal models and humans, are described. PMID:22966417

  18. Lung oxidative damage by hypoxia.

    PubMed

    Araneda, O F; Tuesta, M

    2012-01-01

    One of the most important functions of lungs is to maintain an adequate oxygenation in the organism. This organ can be affected by hypoxia facing both physiological and pathological situations. Exposure to this condition favors the increase of reactive oxygen species from mitochondria, as from NADPH oxidase, xanthine oxidase/reductase, and nitric oxide synthase enzymes, as well as establishing an inflammatory process. In lungs, hypoxia also modifies the levels of antioxidant substances causing pulmonary oxidative damage. Imbalance of redox state in lungs induced by hypoxia has been suggested as a participant in the changes observed in lung function in the hypoxic context, such as hypoxic vasoconstriction and pulmonary edema, in addition to vascular remodeling and chronic pulmonary hypertension. In this work, experimental evidence that shows the implied mechanisms in pulmonary redox state by hypoxia is reviewed. Herein, studies of cultures of different lung cells and complete isolated lung and tests conducted in vivo in the different forms of hypoxia, conducted in both animal models and humans, are described.

  19. In utero cannabinoid exposure alters breathing and the response to hypoxia in newborn mice.

    PubMed

    Tree, Keda C; Scotto di Perretolo, Maud; Peyronnet, Julie; Cayetanot, Florence

    2014-07-01

    Cannabis is one of the most commonly used recreational drugs at ages highly correlated with potential pregnancy. Endocannabinoid signalling regulates important stages of neuronal development. When cannabinoid receptors, which are widely distributed through the nervous system, are activated by exogenous cannabinoids, breathing in adult rats is depressed. Here, we show that, in newborn mice, endocannabinoids, through the activation of cannabinoid receptor type 1 (CB1 R), participate in the modulation of respiration and its control. Blocking CB1 Rs at birth suppressed the brake exerted by endocannabinoids on ventilation in basal and in hypoxic conditions. The number of apnoeas and their duration were also minimized by activation of CB1 Rs in normoxic and in hypoxic conditions. However, prenatal cannabis intoxication, caused by a daily injection of WIN55,212-2, in pregnant mice durably modified respiration of the offspring, as shown by hyperventilation in basal conditions, an altered chemoreflex in response to hypoxia, and longer apnoeas. When CB1 Rs were blocked in WIN55,212-2 treated newborns, persistent hyperventilation was still observed, which could partly be explained by a perturbation of the central respiratory network. In fact, in vitro medullary preparations from WIN55,212-2 treated pups, free of peripheral or of supramedullary structures, showed an altered fictive breathing frequency. In conclusion, the endocannabinoid pathway at birth seems to modulate breathing and protect the newborn against apnoeas. However, when exposed prenatally to an excess of cannabinoid, the breathing neuronal network in development seems to be modified, probably rendering the newborn more vulnerable in the face of an unstable environment. PMID:24717006

  20. Distribution of Fos-Like Immunoreactivity, Catecholaminergic and Serotoninergic Neurons Activated by the Laryngeal Chemoreflex in the Medulla Oblongata of Rats.

    PubMed

    Wang, Xiaolu; Guo, Ruichen; Zhao, Wenjing

    2015-01-01

    The laryngeal chemoreflex (LCR) induces apnea, glottis closure, bradycardia and hypertension in young and maturing mammals. We examined the distribution of medullary nuclei that are activated by the LCR and used immunofluorescent detection of Fos protein as a cellular marker for neuronal activation to establish that the medullary catecholaminergic and serotoninergic neurons participate in the modulation of the LCR. The LCR was elicited by the infusion of KCl-HCl solution into the laryngeal lumen of adult rats in the experimental group, whereas the control group received the same surgery but no infusion. In comparison, the number of regions of Fos-like immunoreactivity (FLI) that were activated by the LCR significantly increased in the nucleus of the solitary tract (NTS), the vestibular nuclear complex (VNC), the loose formation of the nucleus ambiguus (AmbL), the rostral ventral respiratory group (RVRG), the ventrolateral reticular complex (VLR), the pre-Bötzinger complex (PrBöt), the Bötzinger complex (Böt), the spinal trigeminal nucleus (SP5), and the raphe obscurus nucleus (ROb) bilaterally from the medulla oblongata. Furthermore, 12.71% of neurons with FLI in the dorsolateral part of the nucleus of the solitary tract (SolDL) showed tyrosine hydroxylase-immunoreactivity (TH-ir, catecholaminergic), and 70.87% of neurons with FLI in the ROb were serotoninergic. Our data demonstrated the distribution of medullary nuclei that were activated by the LCR, and further demonstrated that catecholaminergic neurons of the SolDL and serotoninergic neurons of the ROb were activated by the LCR, indicating the potential central pathway of the LCR. PMID:26087133

  1. Mutually Augmented Cognition

    NASA Astrophysics Data System (ADS)

    Friesdorf, Florian; Pangercic, Dejan; Bubb, Heiner; Beetz, Michael

    In mac, an ergonomic dialog-system and algorithms will be developed that enable human experts and companions to be integrated into knowledge gathering and decision making processes of highly complex cognitive systems (e.g. Assistive Household as manifested further in the paper). In this event we propose to join algorithms and methodologies coming from Ergonomics and Artificial Intelligence that: a) make cognitive systems more congenial for non-expert humans, b) facilitate their comprehension by utilizing a high-level expandable control code for human experts and c) augment representation of such cognitive system into “deep representation” obtained through an interaction with human companions.

  2. Hypoxia and the Lung: Beyond Hypoxic Vasoconstriction

    PubMed Central

    Nicolls, Mark R.; Voelkel, Norbert F.

    2011-01-01

    This article extends the influence and effects of hypoxia on the lung beyond vasoconstriction and regional blood flow control. Clearly, hypoxia, via the transcription factor hypoxia-inducible factor (HIF)-1α, induces a large number of genes encoding proteins, which control cellular metabolism and growth and also participate in inflammation. Hypoxia, likely via vascular endothelial growth factor (VEGF), recruits bone marrow precursor cells to the lung and affects the behavior of immune cells. How hypoxia shapes immune responses through VEGF and its receptors on mast cells, eosinophils, and dendritic cells and through lung endothelial cell/lymphocyte interactions will be a productive area for future research. PMID:17511589

  3. Pilot-optimal augmentation synthesis

    NASA Technical Reports Server (NTRS)

    Schmidt, D. K.

    1978-01-01

    An augmentation synthesis method usable in the absence of quantitative handling qualities specifications, and yet explicitly including design objectives based on pilot-rating concepts, is presented. The algorithm involves the unique approach of simultaneously solving for the stability augmentation system (SAS) gains, pilot equalization and pilot rating prediction via optimal control techniques. Simultaneous solution is required in this case since the pilot model (gains, etc.) depends upon the augmented plant dynamics, and the augmentation is obviously not a priori known. Another special feature is the use of the pilot's objective function (from which the pilot model evolves) to design the SAS.

  4. Augmented reality system

    NASA Astrophysics Data System (ADS)

    Lin, Chien-Liang; Su, Yu-Zheng; Hung, Min-Wei; Huang, Kuo-Cheng

    2010-08-01

    In recent years, Augmented Reality (AR)[1][2][3] is very popular in universities and research organizations. The AR technology has been widely used in Virtual Reality (VR) fields, such as sophisticated weapons, flight vehicle development, data model visualization, virtual training, entertainment and arts. AR has characteristics to enhance the display output as a real environment with specific user interactive functions or specific object recognitions. It can be use in medical treatment, anatomy training, precision instrument casting, warplane guidance, engineering and distance robot control. AR has a lot of vantages than VR. This system developed combines sensors, software and imaging algorithms to make users feel real, actual and existing. Imaging algorithms include gray level method, image binarization method, and white balance method in order to make accurate image recognition and overcome the effects of light.

  5. NASA Communications Augmentation network

    NASA Astrophysics Data System (ADS)

    Omidyar, Guy C.; Butler, Thomas E.; Laios, Straton C.

    1990-09-01

    The NASA Communications (Nascom) Division of the Mission Operations and Data Systems Directorate (MO&DSD) is to undertake a major initiative to develop the Nascom Augmentation (NAUG) network to achieve its long-range service objectives for operational data transport to support the Space Station Freedom Program, the Earth Observing System (EOS), and other projects. The NAUG is the Nascom ground communications network being developed to accommodate the operational traffic of the mid-1990s and beyond. The NAUG network development will be based on the Open Systems Interconnection Reference Model (OSI-RM). This paper describes the NAUG network architecture, subsystems, topology, and services; addresses issues of internetworking the Nascom network with other elements of the Space Station Information System (SSIS); discusses the operations environment. This paper also notes the areas of related research and presents the current conception of how the network will provide broadband services in 1998.

  6. Magnetohydrodynamic Augmented Propulsion Experiment

    NASA Technical Reports Server (NTRS)

    Litchford, Ron J.

    2008-01-01

    Over the past several years, efforts have been under way to design and develop an operationally flexible research facility for investigating the use of cross-field MHD accelerators as a potential thrust augmentation device for thermal propulsion systems. The baseline configuration for this high-power experimental facility utilizes a 1.5-MWe multi-gas arc-heater as a thermal driver for a 2-MWe MHD accelerator, which resides in a large-bore 2-tesla electromagnet. A preliminary design study using NaK seeded nitrogen as the working fluid led to an externally diagonalized segmented MHD channel configuration based on an expendable heat-sink design concept. The current status report includes a review of engineering/design work and performance optimization analyses and summarizes component hardware fabrication and development efforts, preliminary testing results, and recent progress toward full-up assembly and testing

  7. NAESA Augmentation Pilot Project

    NASA Technical Reports Server (NTRS)

    Hoover, John J.

    1998-01-01

    This project was one project within the Native American Earth and Space Academy (NAESA). NAESA is a national initiative comprised of several organizations that support programs which focus on 1) enhancing the technological, scientific and pedagogical skills of K-14 teachers who instruct Native Americans, 2) enhancing the understanding and applications of science, technology, and engineering of college-bound Native Americans and teaching them general college "survival skills" (e.g., test taking, time management, study habits), 3) enhancing the scientific and pedagogical skills of the faculty of tribally-controllcd colleges and community colleges with large Native American enrollments, and 4) strengthening the critical relationships between students, their parents, tribal elders, and their communities. This Augmentation Pilot Project focused on the areas of community-school alliances and intemet technology use in teaching and learning and daily living addressing five major objectives.

  8. Augmented kinematic feedback system

    NASA Astrophysics Data System (ADS)

    Andert, Ed P., Jr.; Archipley-Smith, Donna K.

    1994-07-01

    This paper discusses a real-time augmented kinematic feedback system which can be used as a diagnosis tool for individuals with motor disabilities. The system captures and analyzes movement via color targets attached to an individual and then feeds back information about movement kinematics. This target tracking approach has a high potential for achieving a real- time kinematic assessment capability. The approach recognizes distinct moving colored targets using video data. Multiple colored targets are attached to an individual at strategic locations and then target movement is tracked using a video data acquisition system. The ability to track and assess movement in real-time allows researchers and practitioners to better study and potentially treat various motor disabilities. Recent research has suggested that kinematic feedback can enhance motor recovery of disabled individuals. This approach addresses the need for a real-time measure of human movement and discusses using kinematic feedback to enhance disability recovery.

  9. Augmented Virtual Reality Laboratory

    NASA Technical Reports Server (NTRS)

    Tully-Hanson, Benjamin

    2015-01-01

    Real time motion tracking hardware has for the most part been cost prohibitive for research to regularly take place until recently. With the release of the Microsoft Kinect in November 2010, researchers now have access to a device that for a few hundred dollars is capable of providing redgreenblue (RGB), depth, and skeleton data. It is also capable of tracking multiple people in real time. For its original intended purposes, i.e. gaming, being used with the Xbox 360 and eventually Xbox One, it performs quite well. However, researchers soon found that although the sensor is versatile, it has limitations in real world applications. I was brought aboard this summer by William Little in the Augmented Virtual Reality (AVR) Lab at Kennedy Space Center to find solutions to these limitations.

  10. Hypoxia and the antipredator behaviours of fishes.

    PubMed

    Domenici, P; Lefrançois, C; Shingles, A

    2007-11-29

    Hypoxia is a phenomenon occurring in marine coastal areas with increasing frequency. While hypoxia has been documented to affect fish activity and metabolism, recent evidence shows that hypoxia can also have a detrimental effect on various antipredator behaviours. Here, we review such evidence with a focus on the effect of hypoxia on fish escape responses, its modulation by aquatic surface respiration (ASR) and schooling behaviour. The main effect of hypoxia on escape behaviour was found in responsiveness and directionality. Locomotor performance in escapes was expected to be relatively independent of hypoxia, since escape responses are fuelled anaerobically. However, hypoxia decreased locomotor performance in some species (Mugilidae) although only in the absence of ASR in severe hypoxia. ASR allows fish to show higher escape performance than fish staying in the water column where hypoxia occurs. This situation provides a trade-off whereby fish may perform ASR in order to avoid the detrimental effects of hypoxia, although they would be subjected to higher exposure to aerial predation. As a result of this trade-off, fishes appear to minimize surfacing behaviour in the presence of aerial predators and to surface near shelters, where possible. For many fish species, schooling can be an effective antipredator behaviour. Severe hypoxia may lead to the disruption of the school unit. At moderate levels, hypoxia can increase school volume and can change the shuffling behaviour of individuals. By altering school structure and dynamics, hypoxia may affect the well functioning of schooling in terms of synchronization and execution of antipredator manoeuvres. School structure and volume appear to be the results of numerous trade-offs, where school shape may be dictated by the presence of predators, the need for energy saving via hydrodynamic advantages and oxygen level. The effects of hypoxia on aquatic organisms can be taxon specific. While hypoxia may not necessarily

  11. FDG uptake, a surrogate of tumour hypoxia?

    PubMed Central

    Van de Wiele, Christophe

    2008-01-01

    Introduction Tumour hyperglycolysis is driven by activation of hypoxia-inducible factor-1 (HIF-1) through tumour hypoxia. Accordingly, the degree of 2-fluro-2-deoxy-d-glucose (FDG) uptake by tumours might indirectly reflect the level of hypoxia, obviating the need for more specific radiopharmaceuticals for hypoxia imaging. Discussion In this paper, available data on the relationship between hypoxia and FDG uptake by tumour tissue in vitro and in vivo are reviewed. In pre-clinical in vitro studies, acute hypoxia was consistently shown to increase FDG uptake by normal and tumour cells within a couple of hours after onset with mobilisation or modification of glucose transporters optimising glucose uptake, followed by a delayed response with increased rates of transcription of GLUT mRNA. In pre-clinical imaging studies on chronic hypoxia that compared FDG uptake by tumours grown in rat or mice to uptake by FMISO, the pattern of normoxic and hypoxic regions within the human tumour xenografts, as imaged by FMISO, largely correlated with glucose metabolism although minor locoregional differences could not be excluded. In the clinical setting, data are limited and discordant. Conclusion Further evaluation of FDG uptake by various tumour types in relation to intrinsic and bioreductive markers of hypoxia and response to radiotherapy or hypoxia-dependent drugs is needed to fully assess its application as a marker of hypoxia in the clinical setting. PMID:18509637

  12. Hypoxia drives apoptosis independently of p53 and metallothionein transcript levels in hemocytes of the whiteleg shrimp Litopenaeus vannamei.

    PubMed

    Felix-Portillo, Monserrath; Martínez-Quintana, José A; Arenas-Padilla, Marina; Mata-Haro, Verónica; Gómez-Jiménez, Silvia; Yepiz-Plascencia, Gloria

    2016-10-01

    The cellular mechanisms used by the shrimp Litopenaeus vannamei to respond to hypoxia have been studied from the energetic metabolism and antioxidant angles. We herein investigated the participation of p53 and metallothionein (MT) in the apoptotic process in response to hypoxia in shrimp hemocytes. The Lvp53 or LvMT genes were efficiently silenced by injection of double stranded RNA for p53 or MT. The effects of silencing on apoptosis were measured as caspase-3 activity and flow cytometry in hemocytes after 24 and 48 h of hypoxia (1.5 mg DO L(-1)). Hemocytes from unsilenced animals had significantly higher apoptosis levels upon both times of hypoxia. The apoptotic levels were diminished but not suppressed in dsp53-silenced but not dsMT-silenced hemocytes after 24 h of hypoxia, indicating a contribution of Lvp53 to apoptosis. Apoptosis in normoxia was significantly higher in dsp53-and dsMT-silenced animals compared to the unsilenced controls, pointing to a possible cytoprotective role of LvMT and Lvp53 during the basal apoptotic program in normoxia. Overall, these results indicate that hypoxia augments apoptosis in shrimp hemocytes and high mRNA levels of Lvp53 and LvMT are not necessary for this response.

  13. Hypoxia drives apoptosis independently of p53 and metallothionein transcript levels in hemocytes of the whiteleg shrimp Litopenaeus vannamei.

    PubMed

    Felix-Portillo, Monserrath; Martínez-Quintana, José A; Arenas-Padilla, Marina; Mata-Haro, Verónica; Gómez-Jiménez, Silvia; Yepiz-Plascencia, Gloria

    2016-10-01

    The cellular mechanisms used by the shrimp Litopenaeus vannamei to respond to hypoxia have been studied from the energetic metabolism and antioxidant angles. We herein investigated the participation of p53 and metallothionein (MT) in the apoptotic process in response to hypoxia in shrimp hemocytes. The Lvp53 or LvMT genes were efficiently silenced by injection of double stranded RNA for p53 or MT. The effects of silencing on apoptosis were measured as caspase-3 activity and flow cytometry in hemocytes after 24 and 48 h of hypoxia (1.5 mg DO L(-1)). Hemocytes from unsilenced animals had significantly higher apoptosis levels upon both times of hypoxia. The apoptotic levels were diminished but not suppressed in dsp53-silenced but not dsMT-silenced hemocytes after 24 h of hypoxia, indicating a contribution of Lvp53 to apoptosis. Apoptosis in normoxia was significantly higher in dsp53-and dsMT-silenced animals compared to the unsilenced controls, pointing to a possible cytoprotective role of LvMT and Lvp53 during the basal apoptotic program in normoxia. Overall, these results indicate that hypoxia augments apoptosis in shrimp hemocytes and high mRNA levels of Lvp53 and LvMT are not necessary for this response. PMID:27459156

  14. Inhaled 45-50% argon augments hypothermic brain protection in a piglet model of perinatal asphyxia.

    PubMed

    Broad, Kevin D; Fierens, Igor; Fleiss, Bobbi; Rocha-Ferreira, Eridan; Ezzati, Mojgan; Hassell, Jane; Alonso-Alconada, Daniel; Bainbridge, Alan; Kawano, Go; Ma, Daqing; Tachtsidis, Ilias; Gressens, Pierre; Golay, Xavier; Sanders, Robert D; Robertson, Nicola J

    2016-03-01

    Cooling to 33.5°C in babies with neonatal encephalopathy significantly reduces death and disability, however additional therapies are needed to maximize brain protection. Following hypoxia-ischemia we assessed whether inhaled 45-50% Argon from 2-26h augmented hypothermia neuroprotection in a neonatal piglet model, using MRS and aEEG, which predict outcome in babies with neonatal encephalopathy, and immunohistochemistry. Following cerebral hypoxia-ischemia, 20 Newborn male Large White piglets<40h were randomized to: (i) Cooling (33°C) from 2-26h (n=10); or (ii) Cooling and inhaled 45-50% Argon (Cooling+Argon) from 2-26h (n=8). Whole-brain phosphorus-31 and regional proton MRS were acquired at baseline, 24 and 48h after hypoxia-ischemia. EEG was monitored. At 48h after hypoxia-ischemia, cell death (TUNEL) was evaluated over 7 brain regions. There were no differences in body weight, duration of hypoxia-ischemia or insult severity; throughout the study there were no differences in heart rate, arterial blood pressure, blood biochemistry and inotrope support. Two piglets in the Cooling+Argon group were excluded. Comparing Cooling+Argon with Cooling there was preservation of whole-brain MRS ATP and PCr/Pi at 48h after hypoxia-ischemia (p<0.001 for both) and lower (1)H MRS lactate/N acetyl aspartate in white (p=0.03 and 0.04) but not gray matter at 24 and 48h. EEG background recovery was faster (p<0.01) with Cooling+Argon. An overall difference between average cell-death of Cooling versus Cooling+Argon was observed (p<0.01); estimated cells per mm(2) were 23.9 points lower (95% C.I. 7.3-40.5) for the Cooling+Argon versus Cooling. Inhaled 45-50% Argon from 2-26h augmented hypothermic protection at 48h after hypoxia-ischemia shown by improved brain energy metabolism on MRS, faster EEG recovery and reduced cell death on TUNEL. Argon may provide a cheap and practical therapy to augment cooling for neonatal encephalopathy.

  15. Augmented Reality Comes to Physics

    ERIC Educational Resources Information Center

    Buesing, Mark; Cook, Michael

    2013-01-01

    Augmented reality (AR) is a technology used on computing devices where processor-generated graphics are rendered over real objects to enhance the sensory experience in real time. In other words, what you are really seeing is augmented by the computer. Many AR games already exist for systems such as Kinect and Nintendo 3DS and mobile apps, such as…

  16. The Feyrter cell in hypoxia

    PubMed Central

    Moosavi, Homeira; Smith, Paul; Heath, Donald

    1973-01-01

    Moosavi, H., Smith, P., and Heath, D. (1973).Thorax,28, 729-741. The Feyrter cell in hypoxia. It is clear that the bronchial tree has functions beyond the mere conduction of air into the alveolar spaces. In addition to the familiar ciliated respiratory epithelial cells the bronchus is lined by non-ciliated Clara and Feyrter cells. In the present study we investigated the histological and ultrastructural features of the bronchial argyrophilic (Feyrter) cell of the neonatal rat. On electron microscopy this cell has all the features of an APUD cell which is associated with the secretion of polypeptide hormones. It bears a close ultrastructural resemblance to the chief cell of the carotid body and shows the same changes in its membrane-bound bodies on exposure to chronic hypoxia. These are strong grounds for believing that the bronchi and bronchioles have either a chemoreceptor or an endocrine function in the neonatal period. Images PMID:4787985

  17. Magnetohydrodynamic Augmented Propulsion Experiment

    NASA Technical Reports Server (NTRS)

    Litchford, Ron J.; Cole, John; Lineberry, John; Chapman, Jim; Schmidt, Harold; Cook, Stephen (Technical Monitor)

    2002-01-01

    A fundamental obstacle to routine space access is the specific energy limitations associated with chemical fuels. In the case of vertical take-off, the high thrust needed for vertical liftoff and acceleration to orbit translates into power levels in the 10 GW range. Furthermore, useful payload mass fractions are possible only if the exhaust particle energy (i.e., exhaust velocity) is much greater than that available with traditional chemical propulsion. The electronic binding energy released by the best chemical reactions (e.g., LOX/LH2 for example, is less than 2 eV per product molecule (approx. 1.8 eV per H2O molecule), which translates into particle velocities less than 5 km/s. Useful payload fractions, however, will require exhaust velocities exceeding 15 km/s (i.e., particle energies greater than 20 eV). As an added challenge, the envisioned hypothetical RLV (reusable launch vehicle) should accomplish these amazing performance feats while providing relatively low acceleration levels to orbit (2-3g maximum). From such fundamental considerations, it is painfully obvious that planned and current RLV solutions based on chemical fuels alone represent only a temporary solution and can only result in minor gains, at best. What is truly needed is a revolutionary approach that will dramatically reduce the amount of fuel and size of the launch vehicle. This implies the need for new compact high-power energy sources as well as advanced accelerator technologies for increasing engine exhaust velocity. Electromagnetic acceleration techniques are of immense interest since they can be used to circumvent the thermal limits associated with conventional propulsion systems. This paper describes the Magnetohydrodynamic Augmented Propulsion Experiment (MAPX) being undertaken at NASA Marshall Space Flight Center (MSFC). In this experiment, a 1-MW arc heater is being used as a feeder for a 1-MW magnetohydrodynamic (MHD) accelerator. The purpose of the experiment is to demonstrate

  18. Effect of Hypoxia and Bedrest on Peripheral Vasoconstriction

    NASA Astrophysics Data System (ADS)

    McDonnell, Adam C.; Mekjavic, Igor B.; Dolenc-Groselj, Leja; Jaki Mekjavic, Polona; Eiken, Ola

    2013-02-01

    Future planetary habitats may expose astronauts to both microgravity and hypobaric hypoxia, both inducing a reduction in peripheral perfusion. Peripheral temperature changes have been linked to sleep onset and quality [5]. However, it is still unknown what effect combining hypoxia and bedrest has on this relationship. Eleven male participants underwent three 10-day campaigns in a randomized manner: 1) normobaric hypoxic ambulatory confinement (HAmb); 2) normobaric hypoxic bed rest (HBR); 3) normobaric normoxic bed rest (NBR). There was no change in skin temperature gradient between the calf and toes, an index of peripheral perfusion (Δ Tc-t), over the 10-d period in the HAmb trial. However, there was a significant increase (p< 0.001) in daytime (9am-9pm) Δ Tc-t on day 10 of the inactivity/unloading periods (HBR and NBR trials). This reduction in the perfusion of the toes during the daytime was augmented during the HBR trial compared to NBR (p< 0.001). Before and on day 10 of the interventions we conducted polysomnographic assessment, which revealed no changes in sleep onset and/or architecture. These data support the theory that circadian changes in temperature are functionally linked to sleepiness [1].

  19. [Hypoxia and oxygen content during dialysis].

    PubMed

    Tulli, G; Vignali, G; Guadagnucci, A; Mondello, V; Pacciani, S; Pappagallo, S

    1992-03-01

    In a study of 72 patients treated with acetate and bicarbonate dialysis, the Authors verified if hypoxic hypoxia caused by dialysis depends on a deficit in oxygen content with an inherent risk of tissue hypoxia. PO2uv (uncompensated venous oxygen partial pressure) and CQ (cardiac compensation factor) derived from the oxygen absorption curve were studied by a new Ole Siggard-Andersen algorithm. The results do not show a risk of tissue hypoxia in the postdialytic period. PMID:1589077

  20. Role of HIF-1 on phosphofructokinase and fructose 1, 6-bisphosphatase expression during hypoxia in the white shrimp Litopenaeus vannamei.

    PubMed

    Cota-Ruiz, Keni; Leyva-Carrillo, Lilia; Peregrino-Uriarte, Alma B; Valenzuela-Soto, Elisa M; Gollas-Galván, Teresa; Gómez-Jiménez, Silvia; Hernández, Jesús; Yepiz-Plascencia, Gloria

    2016-08-01

    HIF-1 is a transcription factor that controls a widespread range of genes in metazoan organisms in response to hypoxia and is composed of α and β subunits. In shrimp, phosphofructokinase (PFK) and fructose bisphosphatase (FBP) are up-regulated in hypoxia. We hypothesized that HIF-1 is involved in the regulation of PFK and FBP genes in shrimp hepatopancreas under hypoxia. Long double stranded RNA (dsRNA) intramuscular injection was utilized to silence simultaneously both HIF-1 subunits, and then, we measured the relative expression of PFK and FBP, as well as their corresponding enzymatic activities in hypoxic shrimp hepatopancreas. The results indicated that HIF-1 participates in the up-regulation of PFK transcripts under short-term hypoxia since the induction caused by hypoxia (~1.6 and ~4.2-fold after 3 and 48h, respectively) is significantly reduced in the dsRNA animals treated. Moreover, PFK activity was significantly ~2.8-fold augmented after 3h in hypoxia alongside to an ~1.9-fold increment in lactate. However, when animals were dsRNA treated, both were significantly reduced. On the other hand, FBP transcripts were ~5.3-fold up-regulated in long-term hypoxic conditions (48h). HIF-1 is involved in this process since FBP transcripts were not induced by hypoxia when HIF-1 was silenced. Conversely, the FBP activity was not affected by hypoxia, which suggests its possible regulation at post-translational level. Taken together, these results position HIF-1 as a prime transcription factor in coordinating glucose metabolism through the PFK and FBP genes among others, in shrimp under low oxygen environments.

  1. Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes

    SciTech Connect

    Chen Baoying; Lam, Karen S.L.; Wang Yu; Wu Donghai; Lam, Michael C.; Shen Jiangang; Wong Laiching; Hoo, Ruby L.C.; Zhang Jialiang; Xu Aimin . E-mail: amxu@hkucc.hku.hk

    2006-03-10

    Low plasma levels of adiponectin (hypoadiponectinemia) and elevated circulating concentrations of plasminogen activator inhibitor (PAI)-1 are causally associated with obesity-related insulin resistance and cardiovascular disease. However, the mechanism that mediates the aberrant production of these two adipokines in obesity remains poorly understood. In this study, we investigated the effects of hypoxia and reactive oxygen species (ROS) on production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Quantitative PCR and immunoassays showed that ambient hypoxia markedly suppressed adiponectin mRNA expression and its protein secretion, and increased PAI-1 production in mature adipocytes. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1{alpha} (HIF-1{alpha}), mimicked the hypoxia-mediated modulations of these two adipokines. Hypoxia caused a modest elevation of ROS in adipocytes. However, ablation of intracellular ROS by antioxidants failed to alleviate hypoxia-induced aberrant production of adiponectin and PAI-1. On the other hand, the antioxidants could reverse hydrogen peroxide (H{sub 2}O{sub 2})-induced dysregulation of adiponectin and PAI-1 production. H{sub 2}O{sub 2} treatment decreased the expression levels of peroxisome proliferator-activated receptor gamma (PPAR{gamma}) and CCAAT/enhancer binding protein (C/EBP{alpha}), but had no effect on HIF-1{alpha}, whereas hypoxia stabilized HIF-1{alpha} and decreased expression of C/EBP{alpha}, but not PPAR{gamma}. Taken together, these data suggest that hypoxia and ROS decrease adiponectin production and augment PAI-1 expression in adipocytes via distinct signaling pathways. These effects may contribute to hypoadiponectinemia and elevated PAI-1 levels in obesity, type 2 diabetes, and cardiovascular diseases.

  2. Augmented Likelihood Image Reconstruction.

    PubMed

    Stille, Maik; Kleine, Matthias; Hägele, Julian; Barkhausen, Jörg; Buzug, Thorsten M

    2016-01-01

    The presence of high-density objects remains an open problem in medical CT imaging. Data of projections passing through objects of high density, such as metal implants, are dominated by noise and are highly affected by beam hardening and scatter. Reconstructed images become less diagnostically conclusive because of pronounced artifacts that manifest as dark and bright streaks. A new reconstruction algorithm is proposed with the aim to reduce these artifacts by incorporating information about shape and known attenuation coefficients of a metal implant. Image reconstruction is considered as a variational optimization problem. The afore-mentioned prior knowledge is introduced in terms of equality constraints. An augmented Lagrangian approach is adapted in order to minimize the associated log-likelihood function for transmission CT. During iterations, temporally appearing artifacts are reduced with a bilateral filter and new projection values are calculated, which are used later on for the reconstruction. A detailed evaluation in cooperation with radiologists is performed on software and hardware phantoms, as well as on clinically relevant patient data of subjects with various metal implants. Results show that the proposed reconstruction algorithm is able to outperform contemporary metal artifact reduction methods such as normalized metal artifact reduction.

  3. Control Augmented Structural Synthesis

    NASA Technical Reports Server (NTRS)

    Lust, Robert V.; Schmit, Lucien A.

    1988-01-01

    A methodology for control augmented structural synthesis is proposed for a class of structures which can be modeled as an assemblage of frame and/or truss elements. It is assumed that both the plant (structure) and the active control system dynamics can be adequately represented with a linear model. The structural sizing variables, active control system feedback gains and nonstructural lumped masses are treated simultaneously as independent design variables. Design constraints are imposed on static and dynamic displacements, static stresses, actuator forces and natural frequencies to ensure acceptable system behavior. Multiple static and dynamic loading conditions are considered. Side constraints imposed on the design variables protect against the generation of unrealizable designs. While the proposed approach is fundamentally more general, here the methodology is developed and demonstrated for the case where: (1) the dynamic loading is harmonic and thus the steady state response is of primary interest; (2) direct output feedback is used for the control system model; and (3) the actuators and sensors are collocated.

  4. Hypoxia upregulates Malat1 expression through a CaMKK/AMPK/HIF-1α axis.

    PubMed

    Sallé-Lefort, Sandrine; Miard, Stéphanie; Nolin, Marc-André; Boivin, Louise; Paré, Marie-Ève; Debigaré, Richard; Picard, Frédéric

    2016-10-01

    Increased expression levels of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) have been associated with enhanced proliferation and metastasis of several cancer cell types. Hypoxia, a hallmark characteristic of solid tumors, has been linked to an increase in the activity of the ATP-generating AMPK protein. Since Malat1 was recently shown to be upregulated during hypoxia, the objective of this study was to determine the contribution of AMPK in the mechanistic pathways regulating Malat1 expression in low oxygen conditions. Compared to those cultured in 21% O2 conditions, HeLa cells incubated in 1.5% O2 expressed more Malat1 transcripts. This observation was mimicked in HEK293T cells using a synthetic reporter construct containing 5.6 kb of the human Malat1 promoter, suggesting that hypoxia directly impacted Malat1 gene transcription. Interestingly, pharmacological stimulation of AMPK increased Malat1 promoter transactivation in 21% O2 conditions, whereas inhibition of either AMPK or its upstream activator CaMKK completely abolished the augmentation of Malat1 under hypoxia. Pharmacological modulation of LKB1, another major regulator of AMPK, had no impact on Malat1 promoter transactivation, suggesting that calcium inputs are important in the control of Malat1 expression by AMPK. Overexpression of hypoxia-inducible factor-1α (HIF-1α) increased Malat1 expression in 21% O2 conditions, whereas pharmacological inhibition of HIF-1α blocked the impact of hypoxia on the Malat1 promoter. Taken together, these findings strongly suggest that Malat1 expression is regulated in hypoxic conditions by a CaMKK/AMPK/HIF-1α axis. More research is needed in physiological settings to test the clinical relevance of this pathway.

  5. Hypoxia upregulates Malat1 expression through a CaMKK/AMPK/HIF-1α axis.

    PubMed

    Sallé-Lefort, Sandrine; Miard, Stéphanie; Nolin, Marc-André; Boivin, Louise; Paré, Marie-Ève; Debigaré, Richard; Picard, Frédéric

    2016-10-01

    Increased expression levels of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) have been associated with enhanced proliferation and metastasis of several cancer cell types. Hypoxia, a hallmark characteristic of solid tumors, has been linked to an increase in the activity of the ATP-generating AMPK protein. Since Malat1 was recently shown to be upregulated during hypoxia, the objective of this study was to determine the contribution of AMPK in the mechanistic pathways regulating Malat1 expression in low oxygen conditions. Compared to those cultured in 21% O2 conditions, HeLa cells incubated in 1.5% O2 expressed more Malat1 transcripts. This observation was mimicked in HEK293T cells using a synthetic reporter construct containing 5.6 kb of the human Malat1 promoter, suggesting that hypoxia directly impacted Malat1 gene transcription. Interestingly, pharmacological stimulation of AMPK increased Malat1 promoter transactivation in 21% O2 conditions, whereas inhibition of either AMPK or its upstream activator CaMKK completely abolished the augmentation of Malat1 under hypoxia. Pharmacological modulation of LKB1, another major regulator of AMPK, had no impact on Malat1 promoter transactivation, suggesting that calcium inputs are important in the control of Malat1 expression by AMPK. Overexpression of hypoxia-inducible factor-1α (HIF-1α) increased Malat1 expression in 21% O2 conditions, whereas pharmacological inhibition of HIF-1α blocked the impact of hypoxia on the Malat1 promoter. Taken together, these findings strongly suggest that Malat1 expression is regulated in hypoxic conditions by a CaMKK/AMPK/HIF-1α axis. More research is needed in physiological settings to test the clinical relevance of this pathway. PMID:27499160

  6. Selective depletion of vascular EC-SOD augments chronic hypoxic pulmonary hypertension.

    PubMed

    Nozik-Grayck, Eva; Woods, Crystal; Taylor, Joann M; Benninger, Richard K P; Johnson, Richard D; Villegas, Leah R; Stenmark, Kurt R; Harrison, David G; Majka, Susan M; Irwin, David; Farrow, Kathryn N

    2014-12-01

    Excess superoxide has been implicated in pulmonary hypertension (PH). We previously found lung overexpression of the antioxidant extracellular superoxide dismutase (EC-SOD) attenuates PH and pulmonary artery (PA) remodeling. Although comprising a small fraction of total SOD activity in most tissues, EC-SOD is abundant in arteries. We hypothesize that the selective loss of vascular EC-SOD promotes hypoxia-induced PH through redox-sensitive signaling pathways. EC-SOD(loxp/loxp) × Tg(cre/SMMHC) mice (SMC EC-SOD KO) received tamoxifen to conditionally deplete smooth muscle cell (SMC)-derived EC-SOD. Mice were exposed to hypobaric hypoxia for 35 days, and PH was assessed by right ventricular systolic pressure measurements and right ventricle hypertrophy. Vascular remodeling was evaluated by morphometric analysis and two-photon microscopy for collagen. We examined cGMP content and soluble guanylate cyclase expression and activity in lung, lung phosphodiesterase 5 (PDE5) expression and activity, and expression of endothelial nitric oxide synthase and GTP cyclohydrolase-1 (GTPCH-1), the rate-limiting enzyme in tetrahydrobiopterin synthesis. Knockout of SMC EC-SOD selectively decreased PA EC-SOD without altering total lung EC-SOD. PH and vascular remodeling induced by chronic hypoxia was augmented in SMC EC-SOD KO. Depletion of SMC EC-SOD did not impact content or activity of lung soluble guanylate cyclase or PDE5, yet it blunted the hypoxia-induced increase in cGMP. Although total eNOS was not altered, active eNOS and GTPCH-1 decreased with hypoxia only in SMC EC-SOD KO. We conclude that the localized loss of PA EC-SOD augments chronic hypoxic PH. In addition to oxidative inactivation of NO, deletion of EC-SOD seems to reduce eNOS activity, further compromising pulmonary vascular function. PMID:25326578

  7. Structural consequences of railgun augmentation

    SciTech Connect

    Wellman, G.W.; Schuler, K.W.

    1988-01-01

    An augmented railgun can provide the same driving force on a projectile at a lower plasma arc current and thus less potential erosion and barrel damage as an unaugmented railgun. However, there are structural consequences to railgun augmentation which must be overcome before the advantages of lower plasma arc currents can be realized. To investigate these consequences, a bolted V-block supporting structure is considered with two cores; unaugmented (a single pair of conducting rails), and augmented (conducting rails augmented by a second tandem set of conductors). The mechanical load on the cores consist of the static bolt preload, the plasma pressure behind the projectile, and the magnetic pressure induced by currents flowing in the rails or augmenting conductors. Assuming no current diffusion into the conductors, the magnetic pressure distribution on the conductors is determined by solving the two-dimensional magnetostatic field equations using an analogy with heat transfer. These loads are then used in a dynamic finite element structural model. The maximum rail current is found at which the unaugmented railgun can be repetitively fired without detrimental gaps forming at the bore. For the augmented railgun, at the same projectile acceleration, large permanent deformations can occur. Thus successful implementation of rail gun augmentation will require improvement of the supporting structure.

  8. Structural consequences of railgun augmentation

    SciTech Connect

    Wellman, G.W.; Schuler, K.W. . Applied Mechanics Div. III)

    1989-01-01

    An augmented railgun can provide the same driving force on a projectile at a lower plasma arc current and thus less potential erosion and barrel damage as an unaugmented railgun. However, there are structural consequences to railgun augmentation which must be overcome before the advantages of lower plasma arc currents can be realized. To investigate these consequences, a bolted V-block supporting structure is considered with two cores; unaugmented (a single pair of conducting rails), and augmented (conducting rails augmented by a second tandem set of conductors). The mechanical load on the cores consist of the static bolt preload, the plasma pressure behind the projectile, and the magnetic pressure induced by currents flowing in the rails or augmenting conductors. Assuming no current diffusion into the conductors, the magnetic pressure distribution on the conductors is determined by solving the two dimensional magnetostatic field equations using an analogy with heat transfer. These loads are then used in a dynamic finite element structural model. The maximum rail current is found at which the unaugmented railgun can be repetitively fired without detrimental gaps forming at the bore. For the augmented railgun, at the same projectile acceleration, large permanent deformations can occur. Thus successful implementation of rail gun augmentation will require improvement of the supporting structure.

  9. Regulation of gene expression by hypoxia.

    PubMed

    Kenneth, Niall Steven; Rocha, Sonia

    2008-08-15

    Hypoxia induces profound changes in the cellular gene expression profile. The discovery of a major transcription factor family activated by hypoxia, HIF (hypoxia-inducible factor), and the factors that contribute to HIF regulation have greatly enhanced our knowledge of the molecular aspects of the hypoxic response. However, in addition to HIF, other transcription factors and cellular pathways are activated by exposure to reduced oxygen. In the present review, we summarize the current knowledge of how additional hypoxia-responsive transcription factors integrate with HIF and how other cellular pathways such as chromatin remodelling, translation regulation and microRNA induction, contribute to the co-ordinated cellular response observed following hypoxic stress.

  10. Augmentation cystoplasty in neurogenic bladder

    PubMed Central

    Kocjancic, Ervin; Demirdağ, Çetin

    2016-01-01

    The aim of this review is to update the indications, contraindications, technique, complications, and the tissue engineering approaches of augmentation cystoplasty (AC) in patients with neurogenic bladder. PubMed/MEDLINE was searched for the keywords "augmentation cystoplasty," "neurogenic bladder," and "bladder augmentation." Additional relevant literature was determined by examining the reference lists of articles identified through the search. The update review of of the indications, contraindications, technique, outcome, complications, and tissue engineering approaches of AC in patients with neurogenic bladder is presented. Although some important progress has been made in tissue engineering AC, conventional AC still has an important role in the surgical treatment of refractory neurogenic lower urinary tract dysfunction.

  11. Augmented Reality Comes to Physics

    NASA Astrophysics Data System (ADS)

    Buesing, Mark; Cook, Michael

    2013-04-01

    Augmented reality (AR) is a technology used on computing devices where processor-generated graphics are rendered over real objects to enhance the sensory experience in real time. In other words, what you are really seeing is augmented by the computer. Many AR games already exist for systems such as Kinect and Nintendo 3DS and mobile apps, such as Tagwhat and Star Chart (a must for astronomy class). The yellow line marking first downs in a televised football game2 and the enhanced puck that makes televised hockey easier to follow3 both use augmented reality to do the job.

  12. Bacopa monniera leaf extract ameliorates hypobaric hypoxia induced spatial memory impairment.

    PubMed

    Hota, Sunil Kumar; Barhwal, Kalpana; Baitharu, Iswar; Prasad, Dipti; Singh, Shashi Bala; Ilavazhagan, Govindasamy

    2009-04-01

    Hypobaric hypoxia induced memory impairment has been attributed to several factors including increased oxidative stress, depleted mitochondrial bioenergetics, altered neurotransmission and apoptosis. This multifactorial response of the brain to hypobaric hypoxia limits the use of therapeutic agents that target individual pathways for ameliorating hypobaric hypoxia induced memory impairment. The present study aimed at exploring the therapeutic potential of a bacoside rich leaf extract of Bacopa monniera in improving the memory functions in hypobaric conditions. The learning ability was evaluated in male Sprague Dawley rats along with memory retrieval following exposure to hypobaric conditions simulating an altitude of 25,000 ft for different durations. The effect of bacoside administration on apoptosis, cytochrome c oxidase activity, ATP levels, and oxidative stress markers and on plasma corticosterone levels was investigated. Expression of NR1 subunit of N-methyl-d-aspartate receptors, neuronal cell adhesion molecules and was also studied along with CREB phosphorylation to elucidate the molecular mechanisms of bacoside action. Bacoside administration was seen to enhance learning ability in rats along with augmentation in memory retrieval and prevention of dendritic atrophy following hypoxic exposure. In addition, it decreased oxidative stress, plasma corticosterone levels and neuronal degeneration. Bacoside administration also increased cytochrome c oxidase activity along with a concomitant increase in ATP levels. Hence, administration of bacosides could be a useful therapeutic strategy in ameliorating hypobaric hypoxia induced cognitive dysfunctions and other related neurological disorders.

  13. Approximate Simulation of Acute Hypobaric Hypoxia with Normobaric Hypoxia

    NASA Technical Reports Server (NTRS)

    Conkin, J.; Wessel, J. H., III

    2011-01-01

    INTRODUCTION. Some manufacturers of reduced oxygen (O2) breathing devices claim a comparable hypobaric hypoxia (HH) training experience by providing F(sub I) O2 < 0.209 at or near sea level pressure to match the ambient O2 partial pressure (iso-pO2) of the target altitude. METHODS. Literature from investigators and manufacturers indicate that these devices may not properly account for the 47 mmHg of water vapor partial pressure that reduces the inspired partial pressure of O2 (P(sub I) O2). Nor do they account for the complex reality of alveolar gas composition as defined by the Alveolar Gas Equation. In essence, by providing iso-pO2 conditions for normobaric hypoxia (NH) as for HH exposures the devices ignore P(sub A)O2 and P(sub A)CO2 as more direct agents to induce signs and symptoms of hypoxia during acute training exposures. RESULTS. There is not a sufficient integrated physiological understanding of the determinants of P(sub A)O2 and P(sub A)CO2 under acute NH and HH given the same hypoxic pO2 to claim a device that provides isohypoxia. Isohypoxia is defined as the same distribution of hypoxia signs and symptoms under any circumstances of equivalent hypoxic dose, and hypoxic pO2 is an incomplete hypoxic dose. Some devices that claim an equivalent HH experience under NH conditions significantly overestimate the HH condition, especially when simulating altitudes above 10,000 feet (3,048 m). CONCLUSIONS. At best, the claim should be that the devices provide an approximate HH experience since they only duplicate the ambient pO2 at sea level as at altitude (iso-pO2 machines). An approach to reduce the overestimation is to at least provide machines that create the same P(sub I)O2 (iso-P(sub I)O2 machines) conditions at sea level as at the target altitude, a simple software upgrade.

  14. Soft tissue augmentation using Restylane.

    PubMed

    Biesman, Brian

    2004-05-01

    Soft tissue augmentation plays an important role in facial rejuvenation. To accomplish this goal, numerous materials have been used. Hyaluronic acids represent the latest family of products to become available in the United States. This article provides an introduction to the proper use of Restylane, the first hyaluronic acid product to be approved by the United States Food and Drug Administration for soft tissue augmentation.

  15. Hypoxia signaling--license to metastasize.

    PubMed

    Vanharanta, Sakari; Massagué, Joan

    2013-10-01

    Hypoxia-inducible factors (HIF) have long been linked to malignant tumor phenotypes in various cancer types, and several downstream mediators of HIF action are deregulated in metastatic carcinomas. A new study links hypoxia-induced collagen remodeling to sarcoma progression, providing evidence for unifying mechanisms of carcinoma and sarcoma metastasis. PMID:24124230

  16. The Clinical Importance of Assessing Tumor Hypoxia: Relationship of Tumor Hypoxia to Prognosis and Therapeutic Opportunities

    PubMed Central

    Walsh, Joseph C.; Lebedev, Artem; Aten, Edward; Madsen, Kathleen; Marciano, Liane

    2014-01-01

    I. Introduction II. The Clinical Importance of Tumor Hypoxia A. Pathophysiology of hypoxia B. Hypoxia's negative impact on the effectiveness of curative treatment 1. Hypoxic tumors accumulate and propagate cancer stem cells 2. Hypoxia reduces the effectiveness of radiotherapy 3. Hypoxia increases metastasis risk and reduces the effectiveness of surgery 4. Hypoxic tumors are resistant to the effects of chemotherapy and chemoradiation C. Hypoxia is prognostic for poor patient outcomes III. Diagnosis of Tumor Hypoxia A. Direct methods 1. Oxygen electrode—direct pO2 measurement most used in cancer research 2. Phosphorescence quenching—alternative direct pO2 measurement 3. Electron paramagnetic resonance 4. 19F-magnetic resonance spectroscopy 5. Overhauser-enhanced MRI B. Endogenous markers of hypoxia 1. Hypoxia-inducible factor-1α 2. Carbonic anhydrase IX 3. Glucose transporter 1 4. Osteopontin 5. A combined IHC panel of protein markers for hypoxia 6. Comet assay C. Physiologic methods 1. Near-infrared spectroscopy/tomography—widely used for pulse oximetry 2. Photoacoustic tomography 3. Contrast-enhanced color duplex sonography 4. MRI-based measurements 5. Blood oxygen level-dependent MRI 6. Pimonidazole 7. EF5 (pentafluorinated etanidazole) 8. Hypoxia PET imaging—physiologic hypoxia measurement providing tomographic information a. 18F-fluoromisonidazole b. 18F-fluoroazomycinarabinofuranoside c. 18F-EF5 (pentafluorinated etanidazole) d. 18F-flortanidazole e. Copper (II) (diacetyl-bis (N4-methylthiosemicarbazone)) f. 18F-FDG imaging of hypoxia IV. Modifying Hypoxia to Improve Therapeutic Outcomes A. Use of hypoxia information in radiation therapy planning B. Use of hypoxia assessment for selection of patients responsive to nimorazole C. Use of hypoxia assessment for selection of patients responsive to tirapazamine D. Use of hypoxia assessment for selection of patients

  17. Changes in carotid body and nTS neuronal excitability following neonatal sustained and chronic intermittent hypoxia exposure.

    PubMed

    Mayer, C A; Wilson, C G; MacFarlane, P M

    2015-01-01

    We investigated whether pre-treatment with neonatal sustained hypoxia (SH) prior to chronic intermittent hypoxia (SH+CIH) would modify in vitro carotid body (CB) chemoreceptor activity and the excitability of neurons in the caudal nucleus of the solitary tract (nTS). Sustained hypoxia followed by CIH exposure simulates an oxygen paradigm experienced by extremely premature infants who developed persistent apnea. Rat pups were treated with 5 days of SH (11% O2) from postnatal age 1 (P1) followed by 10 days of subsequent chronic intermittent hypoxia (CIH, 5% O2/5 min, 8 h/day, between P6 and P15) as described previously (Mayer et al., Respir. Physiol. Neurobiol. 187(2): 167-75, 2013). At the end of SH+CIH exposure (P16), basal firing frequency was enhanced, and the hypoxic sensory response of single unit CB chemoafferents was attenuated. Further, basal firing frequency and the amplitude of evoked excitatory post-synaptic currents (ESPC's) of nTS neurons was augmented compared to age-matched rats raised in normoxia. These effects were unique to SH+CIH exposure as neither SH or CIH alone elicited any comparable effect on chemoafferent activity or nTS function. These data indicated that pre-treatment with neonatal SH prior to CIH exposure uniquely modified mechanisms of peripheral (CB) and central (nTS) neural function in a way that would be expected to disturb the ventilatory response to acute hypoxia.

  18. Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK–PKC–CBP signaling cascade

    PubMed Central

    Arya, Aditya; Gangwar, Anamika; Singh, Sushil Kumar; Roy, Manas; Das, Mainak; Sethy, Niroj Kumar; Bhargava, Kalpana

    2016-01-01

    Structural and functional integrity of the brain is adversely affected by reduced oxygen saturation, especially during chronic hypoxia exposure and often encountered by altitude travelers or dwellers. Hypoxia-induced generation of reactive nitrogen and oxygen species reportedly affects the cortex and hippocampus regions of the brain, promoting memory impairment and cognitive dysfunction. Cerium oxide nanoparticles (CNPs), also known as nanoceria, switch between +3 and +4 oxidation states and reportedly scavenge superoxide anions, hydrogen peroxide, and peroxynitrite in vivo. In the present study, we evaluated the neuroprotective as well as the cognition-enhancing activities of nanoceria during hypobaric hypoxia. Using polyethylene glycol-coated 3 nm nanoceria (PEG-CNPs), we have demonstrated efficient localization of PEG-CNPs in rodent brain. This resulted in significant reduction of oxidative stress and associated damage during hypoxia exposure. Morris water maze-based memory function tests revealed that PEG-CNPs ameliorated hypoxia-induced memory impairment. Using microscopic, flow cytometric, and histological studies, we also provide evidences that PEG-CNPs augmented hippocampus neuronal survival and promoted neurogenesis. Molecular studies revealed that PEG-CNPs promoted neurogenesis through the 5′-adenine monophosphate-activated protein kinase–protein kinase C–cyclic adenosine monophosphate response element-binding protein binding (AMPK-PKC-CBP) protein pathway. Our present study results suggest that nanoceria can be translated as promising therapeutic molecules for neurodegenerative diseases. PMID:27069362

  19. Low-dose radiation augments vasculogenesis signaling through HIF-1-dependent and -independent SDF-1 induction.

    PubMed

    Lerman, Oren Z; Greives, Matthew R; Singh, Sunil P; Thanik, Vishal D; Chang, Christopher C; Seiser, Natalie; Brown, Daniel J; Knobel, Denis; Schneider, Robert J; Formenti, Silvia C; Saadeh, Pierre B; Levine, Jamie P

    2010-11-01

    The inflammatory response to ionizing radiation (IR) includes a proangiogenic effect that could be counterproductive in cancer but can be exploited for treating impaired wound healing. We demonstrate for the first time that IR stimulates hypoxia-inducible factor-1α (HIF-1α) up-regulation in endothelial cells (ECs), a HIF-1α-independent up-regulation of stromal cell-derived factor-1 (SDF-1), as well as endothelial migration, all of which are essential for angiogenesis. 5 Gray IR-induced EC HIF-1α and SDF-1 expression was greater when combined with hypoxia suggesting an additive effect. While small interfering RNA silencing of HIF-1α mRNA and abolition of HIF-1α protein induction down-regulated SDF-1 induction by hypoxia alone, it had little effect on SDF-1 induction by IR, demonstrating an independent pathway. SDF-1-mediated EC migration in hypoxic and/or radiation-treated media showed IR induced strong SDF-1-dependent migration of ECs, augmented by hypoxia. IR activates a novel pathway stimulating EC migration directly through the expression of SDF-1 independent of HIF-1α induction. These observations might be exploited for stimulation of wound healing or controlling tumor angiogenesis. PMID:20631377

  20. Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia.

    PubMed

    Lumbroso, Delphine; Joseph, Vincent

    2009-08-01

    We tested the hypothesis that neonatal exposure to hypoxia alters acclimatization to chronic hypoxia later in life. Rat pups were exposed to normobaric hypoxia (12% O(2); nHx group) in a sealed chamber, or to normoxia (21% O(2); nNx group) from the day before birth to postnatal day 10. The animals were then raised in normal conditions until reaching 12 wk of age. At this age, we assessed ventilatory and hematological acclimatization to chronic hypoxia by exposing male and female nHx and nNx rats for 2 wk to 10% O(2). Minute ventilation, metabolic rate, hypoxic ventilatory response, hematocrit, and hemoglobin levels were measured both before and after acclimatization. We also quantified right ventricular hypertrophy as an index of pulmonary hypertension both before and after acclimatization. There was a significant effect of neonatal hypoxia that decreases ventilatory response (relative to metabolic rate, VE/VCO(2)) to acute hypoxia before acclimatization in males but not in females. nHx rats had an impaired acclimatization to chronic hypoxia characterized by altered respiratory pattern and elevated hematocrit and hemoglobin levels after acclimatization, in both males and females. Right ventricular hypertrophy was present before and after acclimatization in nHx rats, indicating that neonatal hypoxia results in pulmonary hypertension in adults. We conclude that neonatal hypoxia impairs acclimatization to chronic hypoxia in adults and may be a factor contributing to the establishment of chronic mountain sickness in humans living at high altitude.

  1. Bayesian Alternation during Tactile Augmentation

    PubMed Central

    Goeke, Caspar M.; Planera, Serena; Finger, Holger; König, Peter

    2016-01-01

    A large number of studies suggest that the integration of multisensory signals by humans is well-described by Bayesian principles. However, there are very few reports about cue combination between a native and an augmented sense. In particular, we asked the question whether adult participants are able to integrate an augmented sensory cue with existing native sensory information. Hence for the purpose of this study, we build a tactile augmentation device. Consequently, we compared different hypotheses of how untrained adult participants combine information from a native and an augmented sense. In a two-interval forced choice (2 IFC) task, while subjects were blindfolded and seated on a rotating platform, our sensory augmentation device translated information on whole body yaw rotation to tactile stimulation. Three conditions were realized: tactile stimulation only (augmented condition), rotation only (native condition), and both augmented and native information (bimodal condition). Participants had to choose one out of two consecutive rotations with higher angular rotation. For the analysis, we fitted the participants' responses with a probit model and calculated the just notable difference (JND). Then, we compared several models for predicting bimodal from unimodal responses. An objective Bayesian alternation model yielded a better prediction (χred2 = 1.67) than the Bayesian integration model (χred2 = 4.34). Slightly higher accuracy showed a non-Bayesian winner takes all (WTA) model (χred2 = 1.64), which either used only native or only augmented values per subject for prediction. However, the performance of the Bayesian alternation model could be substantially improved (χred2 = 1.09) utilizing subjective weights obtained by a questionnaire. As a result, the subjective Bayesian alternation model predicted bimodal performance most accurately among all tested models. These results suggest that information from augmented and existing sensory modalities in

  2. SUSCEPTIBILITY OF A NORTHEASTERN GULF OF MEXICO ESTUARY TO HYPOXIA

    EPA Science Inventory

    Bottom water hypoxia is a common adverse consequence of nutrient enrichment in estuaries and coastal waters. To protect against hypoxia, it is helpful to know which waters are most susceptible to hypoxia. Hypoxia has been observed regularly in Pensacola Bay, a northeastern Gulf o...

  3. Hypoxia and metabolic adaptation of cancer cells

    PubMed Central

    Eales, K L; Hollinshead, K E R; Tennant, D A

    2016-01-01

    Low oxygen tension (hypoxia) is a pervasive physiological and pathophysiological stimulus that metazoan organisms have contended with since they evolved from their single-celled ancestors. The effect of hypoxia on a tissue can be either positive or negative, depending on the severity, duration and context. Over the long-term, hypoxia is not usually consistent with normal function and so multicellular organisms have had to evolve both systemic and cellular responses to hypoxia. Our reliance on oxygen for efficient adenosine triphosphate (ATP) generation has meant that the cellular metabolic network is particularly sensitive to alterations in oxygen tension. Metabolic changes in response to hypoxia are elicited through both direct mechanisms, such as the reduction in ATP generation by oxidative phosphorylation or inhibition of fatty-acid desaturation, and indirect mechanisms including changes in isozyme expression through hypoxia-responsive transcription factor activity. Significant regions of cancers often grow in hypoxic conditions owing to the lack of a functional vasculature. As hypoxic tumour areas contain some of the most malignant cells, it is important that we understand the role metabolism has in keeping these cells alive. This review will outline our current understanding of many of the hypoxia-induced changes in cancer cell metabolism, how they are affected by other genetic defects often present in cancers, and how these metabolic alterations support the malignant hypoxic phenotype. PMID:26807645

  4. Hypoxia-targeted siRNA delivery.

    PubMed

    Perche, F; Biswas, S; Wang, T; Zhu, L; Torchilin, V P

    2014-03-24

    Altered vasculature and the resultant chaotic tumor blood flow lead to the appearance in fast-growing tumors of regions with gradients of oxygen tension and acute hypoxia (less than 1.4% oxygen). Due to its roles in tumorigenesis and resistance to therapy, hypoxia represents a problem in cancer therapy. Insufficient delivery of therapeutic agents to the hypoxic regions in solid tumors is recognized as one of the causes of resistance to therapy. This led to the development of hypoxia imaging agents, and the use of hypoxia-activated anticancer prodrugs. Here we show the first example of the hypoxia-induced siRNA uptake and silencing using a nanocarrier consisting of polyethyleneglycol 2000, azobenzene, polyethyleneimine (PEI)(1.8 kDa), and 1,2-dioleyl-sn-glycero-3-phosphoethanolamine (DOPE) units (the nanocarrier is referred to as PAPD), where azobenzene imparts hypoxia sensitivity and specificity. We report hypoxia-activated green fluorescent protein (GFP) silencing in vitro and its downregulation in GFP-expressing tumors after intravenous administration. The proposed nanoformulation represents a novel tumor-environment-responsive modality for cancer targeting and siRNA delivery. PMID:24554550

  5. Augmentation cystoplasty in neurogenic bladder.

    PubMed

    Çetinel, Bülent; Kocjancic, Ervin; Demirdağ, Çetin

    2016-09-01

    The aim of this review is to update the indications, contraindications, technique, complications, and the tissue engineering approaches of augmentation cystoplasty (AC) in patients with neurogenic bladder. PubMed/MEDLINE was searched for the keywords "augmentation cystoplasty," "neurogenic bladder," and "bladder augmentation." Additional relevant literature was determined by examining the reference lists of articles identified through the search. The update review of of the indications, contraindications, technique, outcome, complications, and tissue engineering approaches of AC in patients with neurogenic bladder is presented. Although some important progress has been made in tissue engineering AC, conventional AC still has an important role in the surgical treatment of refractory neurogenic lower urinary tract dysfunction. PMID:27617312

  6. Augmentation cystoplasty in neurogenic bladder

    PubMed Central

    Kocjancic, Ervin; Demirdağ, Çetin

    2016-01-01

    The aim of this review is to update the indications, contraindications, technique, complications, and the tissue engineering approaches of augmentation cystoplasty (AC) in patients with neurogenic bladder. PubMed/MEDLINE was searched for the keywords "augmentation cystoplasty," "neurogenic bladder," and "bladder augmentation." Additional relevant literature was determined by examining the reference lists of articles identified through the search. The update review of of the indications, contraindications, technique, outcome, complications, and tissue engineering approaches of AC in patients with neurogenic bladder is presented. Although some important progress has been made in tissue engineering AC, conventional AC still has an important role in the surgical treatment of refractory neurogenic lower urinary tract dysfunction. PMID:27617312

  7. Augmented Reality Tower Technology Assessment

    NASA Technical Reports Server (NTRS)

    Reisman, Ronald J.; Brown, David M.

    2009-01-01

    Augmented Reality technology may help improve Air Traffic Control Tower efficiency and safety during low-visibility conditions. This paper presents the assessments of five off-duty controllers who shadow-controlled' with an augmented reality prototype in their own facility. Initial studies indicated unanimous agreement that this technology is potentially beneficial, though the prototype used in the study was not adequate for operational use. Some controllers agreed that augmented reality technology improved situational awareness, had potential to benefit clearance, control, and coordination tasks and duties and could be very useful for acquiring aircraft and weather information, particularly aircraft location, heading, and identification. The strongest objections to the prototype used in this study were directed at aircraft registration errors, unacceptable optical transparency, insufficient display performance in sunlight, inadequate representation of the static environment and insufficient symbology.

  8. Hypoxia activates the cyclooxygenase-2–prostaglandin E synthase axis

    PubMed Central

    Lee, James J.; Natsuizaka, Mitsuteru; Ohashi, Shinya; Wong, Gabrielle S.; Takaoka, Munenori; Michaylira, Carmen Z.; Budo, Daniela; Tobias, John W.; Kanai, Michiyuki; Shirakawa, Yasuhiro; Naomoto, Yoshio; Klein-Szanto, Andres J.P.; Haase, Volker H.; Nakagawa, Hiroshi

    2010-01-01

    Hypoxia-inducible factors (HIFs), in particular HIF-1α, have been implicated in tumor biology. However, HIF target genes in the esophageal tumor microenvironment remain elusive. Gene expression profiling was performed upon hypoxia-exposed non-transformed immortalized human esophageal epithelial cells, EPC2-hTERT, and comparing with a gene signature of esophageal squamous cell carcinoma (ESCC). In addition to known HIF-1α target genes such as carbonic anhydrase 9, insulin-like growth factor binding protein-3 (IGFBP3) and cyclooxygenase (COX)-2, prostaglandin E synthase (PTGES) was identified as a novel target gene among the commonly upregulated genes in ESCC as well as the cells exposed to hypoxia. The PTGES induction was augmented upon stabilization of HIF-1α by hypoxia or cobalt chloride under normoxic conditions and suppressed by dominant-negative HIF-1α. Whereas PTGES messenger RNA (mRNA) was negatively regulated by normoxia, PTGES protein remained stable upon reoxygenation. Prostaglandin E2 (PGE2) biosynthesis was documented in transformed human esophageal cells by ectopic expression of PTGES as well as RNA interference directed against PTGES. Moreover, hypoxia stimulated PGE2 production in a HIF-1α-dependent manner. In ESCC, PTGES was overexpressed frequently at the mRNA and protein levels. Finally, COX-2 and PTGES were colocalized in primary tumors along with HIF-1α and IGFBP3. Activation of the COX-2–PTGES axis in primary tumors was further corroborated by concomitant upregulation of interleukin-1β and downregulation of hydroxylprostaglandin dehydrogenase. Thus, PTGES is a novel HIF-1α target gene, involved in prostaglandin E biosynthesis in the esophageal tumor hypoxic microenvironment, and this has implications in diverse tumors types, especially of squamous origin. PMID:20042640

  9. Mitochondrial respiratory function induces endogenous hypoxia.

    PubMed

    Prior, Sara; Kim, Ara; Yoshihara, Toshitada; Tobita, Seiji; Takeuchi, Toshiyuki; Higuchi, Masahiro

    2014-01-01

    Hypoxia influences many key biological functions. In cancer, it is generally believed that hypoxic condition is generated deep inside the tumor because of the lack of oxygen supply. However, consumption of oxygen by cancer should be one of the key means of regulating oxygen concentration to induce hypoxia but has not been well studied. Here, we provide direct evidence of the mitochondrial role in the induction of intracellular hypoxia. We used Acetylacetonatobis [2-(2'-benzothienyl) pyridinato-kN, kC3'] iridium (III) (BTP), a novel oxygen sensor, to detect intracellular hypoxia in living cells via microscopy. The well-differentiated cancer cell lines, LNCaP and MCF-7, showed intracellular hypoxia without exogenous hypoxia in an open environment. This may be caused by high oxygen consumption, low oxygen diffusion in water, and low oxygen incorporation to the cells. In contrast, the poorly-differentiated cancer cell lines: PC-3 and MDAMB231 exhibited intracellular normoxia by low oxygen consumption. The specific complex I inhibitor, rotenone, and the reduction of mitochondrial DNA (mtDNA) content reduced intracellular hypoxia, indicating that intracellular oxygen concentration is regulated by the consumption of oxygen by mitochondria. HIF-1α was activated in endogenously hypoxic LNCaP and the activation was dependent on mitochondrial respiratory function. Intracellular hypoxic status is regulated by glucose by parabolic dose response. The low concentration of glucose (0.045 mg/ml) induced strongest intracellular hypoxia possibly because of the Crabtree effect. Addition of FCS to the media induced intracellular hypoxia in LNCaP, and this effect was partially mimicked by an androgen analog, R1881, and inhibited by the anti-androgen, flutamide. These results indicate that mitochondrial respiratory function determines intracellular hypoxic status and may regulate oxygen-dependent biological functions. PMID:24586439

  10. Augmentation-related brain plasticity.

    PubMed

    Di Pino, Giovanni; Maravita, Angelo; Zollo, Loredana; Guglielmelli, Eugenio; Di Lazzaro, Vincenzo

    2014-01-01

    Today, the anthropomorphism of the tools and the development of neural interfaces require reconsidering the concept of human-tools interaction in the framework of human augmentation. This review analyses the plastic process that the brain undergoes when it comes into contact with augmenting artificial sensors and effectors and, on the other hand, the changes that the use of external augmenting devices produces in the brain. Hitherto, few studies investigated the neural correlates of augmentation, but clues on it can be borrowed from logically-related paradigms: sensorimotor training, cognitive enhancement, cross-modal plasticity, sensorimotor functional substitution, use and embodiment of tools. Augmentation modifies function and structure of a number of areas, i.e., primary sensory cortices shape their receptive fields to become sensitive to novel inputs. Motor areas adapt the neuroprosthesis representation firing-rate to refine kinematics. As for normal motor outputs, the learning process recruits motor and premotor cortices and the acquisition of proficiency decreases attentional recruitment, focuses the activity on sensorimotor areas and increases the basal ganglia drive on the cortex. Augmentation deeply relies on the frontoparietal network. In particular, premotor cortex is involved in learning the control of an external effector and owns the tool motor representation, while the intraparietal sulcus extracts its visual features. In these areas, multisensory integration neurons enlarge their receptive fields to embody supernumerary limbs. For operating an anthropomorphic neuroprosthesis, the mirror system is required to understand the meaning of the action, the cerebellum for the formation of its internal model and the insula for its interoception. In conclusion, anthropomorphic sensorized devices can provide the critical sensory afferences to evolve the exploitation of tools through their embodiment, reshaping the body representation and the sense of the self

  11. Augmentation-related brain plasticity

    PubMed Central

    Di Pino, Giovanni; Maravita, Angelo; Zollo, Loredana; Guglielmelli, Eugenio; Di Lazzaro, Vincenzo

    2014-01-01

    Today, the anthropomorphism of the tools and the development of neural interfaces require reconsidering the concept of human-tools interaction in the framework of human augmentation. This review analyses the plastic process that the brain undergoes when it comes into contact with augmenting artificial sensors and effectors and, on the other hand, the changes that the use of external augmenting devices produces in the brain. Hitherto, few studies investigated the neural correlates of augmentation, but clues on it can be borrowed from logically-related paradigms: sensorimotor training, cognitive enhancement, cross-modal plasticity, sensorimotor functional substitution, use and embodiment of tools. Augmentation modifies function and structure of a number of areas, i.e., primary sensory cortices shape their receptive fields to become sensitive to novel inputs. Motor areas adapt the neuroprosthesis representation firing-rate to refine kinematics. As for normal motor outputs, the learning process recruits motor and premotor cortices and the acquisition of proficiency decreases attentional recruitment, focuses the activity on sensorimotor areas and increases the basal ganglia drive on the cortex. Augmentation deeply relies on the frontoparietal network. In particular, premotor cortex is involved in learning the control of an external effector and owns the tool motor representation, while the intraparietal sulcus extracts its visual features. In these areas, multisensory integration neurons enlarge their receptive fields to embody supernumerary limbs. For operating an anthropomorphic neuroprosthesis, the mirror system is required to understand the meaning of the action, the cerebellum for the formation of its internal model and the insula for its interoception. In conclusion, anthropomorphic sensorized devices can provide the critical sensory afferences to evolve the exploitation of tools through their embodiment, reshaping the body representation and the sense of the self

  12. Augmentation-related brain plasticity.

    PubMed

    Di Pino, Giovanni; Maravita, Angelo; Zollo, Loredana; Guglielmelli, Eugenio; Di Lazzaro, Vincenzo

    2014-01-01

    Today, the anthropomorphism of the tools and the development of neural interfaces require reconsidering the concept of human-tools interaction in the framework of human augmentation. This review analyses the plastic process that the brain undergoes when it comes into contact with augmenting artificial sensors and effectors and, on the other hand, the changes that the use of external augmenting devices produces in the brain. Hitherto, few studies investigated the neural correlates of augmentation, but clues on it can be borrowed from logically-related paradigms: sensorimotor training, cognitive enhancement, cross-modal plasticity, sensorimotor functional substitution, use and embodiment of tools. Augmentation modifies function and structure of a number of areas, i.e., primary sensory cortices shape their receptive fields to become sensitive to novel inputs. Motor areas adapt the neuroprosthesis representation firing-rate to refine kinematics. As for normal motor outputs, the learning process recruits motor and premotor cortices and the acquisition of proficiency decreases attentional recruitment, focuses the activity on sensorimotor areas and increases the basal ganglia drive on the cortex. Augmentation deeply relies on the frontoparietal network. In particular, premotor cortex is involved in learning the control of an external effector and owns the tool motor representation, while the intraparietal sulcus extracts its visual features. In these areas, multisensory integration neurons enlarge their receptive fields to embody supernumerary limbs. For operating an anthropomorphic neuroprosthesis, the mirror system is required to understand the meaning of the action, the cerebellum for the formation of its internal model and the insula for its interoception. In conclusion, anthropomorphic sensorized devices can provide the critical sensory afferences to evolve the exploitation of tools through their embodiment, reshaping the body representation and the sense of the self.

  13. Superconducting augmented rail gun (SARG)

    SciTech Connect

    Homan, C.G.; Cummings, C.E.; Fowler, C.M.

    1986-11-01

    Superconducting augmentation consists of a superconducting coil operating in the persistent mode closely coupled magnetically with a normally conducting rail gun. A theoretical investigation of the effect of this system on a rail gun has shown that two benefits occur. Projectile velocities and launch efficiencies increase significantly depending on the magnetic coupling between the rail and augmentation circuits. Previous work evaluated an idealized system by neglecting energy dissipation effects. In this paper, the authors extend the analysis to include the neglected terms and show improved actual launch efficiencies for the SARG configuration. In this paper, the authors discuss details of projectile design in depth and present preliminary results of rail gun performance.

  14. Metabolic consequences of intermittent hypoxia.

    PubMed

    O'Donnell, Christopher P

    2007-01-01

    Insulin resistance is being recognized increasingly as the basis for the constellation of metabolic abnormalities that make up the metabolic syndrome, or Syndrome X. Insulin resistance is also the primary risk factor for the development of type 2 diabetes mellitus, which is currently reaching epidemic proportions by affecting more than 170 million people worldwide. A combination of environmental and genetic factors have led to a dramatic rise in visceral adiposity, the predominant factor causing insulin resistance and type 2 diabetes. Visceral adiposity is also the major risk factor for the development of Sleep Apnea (SA)--an association that has fueled interest in the co-morbidity of SA and the metabolic syndrome, but hampered attempts to ascribe an independent causative role for Sleep Apnea in the development of insulin resistance and type 2 diabetes. Numerous population and clinic-based epidemiologic studies have shown associations, often independent of obesity, between SA (or surrogates such as snoring) and measures of glucose dysregulation or type 2 diabetes. However, treatment of SA with continuous positive airway pressure (CPAP) has not been conclusive in demonstrating improvements in insulin resistance, perhaps due to the overwhelming effects of obesity. Here we show that in lean, otherwise healthy mice that exposure to intermittent hypoxia produced whole-body insulin resistance as determined by the hyperinsulinemic euglycemic clamp and reduced glucose utilization in oxidative muscle fibers, but did not cause a change in hepatic glucose output. Furthermore, the increase in insulin resistance was not affected by blockade of the autonomic nervous system. We conclude that intermittent hypoxia can cause acute insulin resistance in otherwise lean healthy animals, and the response occurs independent of activation of the autonomic nervous system. PMID:18269187

  15. Carotid body denervation prevents fasting hyperglycemia during chronic intermittent hypoxia.

    PubMed

    Shin, Mi-Kyung; Yao, Qiaoling; Jun, Jonathan C; Bevans-Fonti, Shannon; Yoo, Doo-Young; Han, Woobum; Mesarwi, Omar; Richardson, Ria; Fu, Ya-Yuan; Pasricha, Pankaj J; Schwartz, Alan R; Shirahata, Machiko; Polotsky, Vsevolod Y

    2014-10-01

    Obstructive sleep apnea causes chronic intermittent hypoxia (IH) and is associated with impaired glucose metabolism, but mechanisms are unknown. Carotid bodies orchestrate physiological responses to hypoxemia by activating the sympathetic nervous system. Therefore, we hypothesized that carotid body denervation would abolish glucose intolerance and insulin resistance induced by chronic IH. Male C57BL/6J mice underwent carotid sinus nerve dissection (CSND) or sham surgery and then were exposed to IH or intermittent air (IA) for 4 or 6 wk. Hypoxia was administered by decreasing a fraction of inspired oxygen from 20.9% to 6.5% once per minute, during the 12-h light phase (9 a.m.-9 p.m.). As expected, denervated mice exhibited blunted hypoxic ventilatory responses. In sham-operated mice, IH increased fasting blood glucose, baseline hepatic glucose output (HGO), and expression of a rate-liming hepatic enzyme of gluconeogenesis phosphoenolpyruvate carboxykinase (PEPCK), whereas the whole body glucose flux during hyperinsulinemic euglycemic clamp was not changed. IH did not affect glucose tolerance after adjustment for fasting hyperglycemia in the intraperitoneal glucose tolerance test. CSND prevented IH-induced fasting hyperglycemia and increases in baseline HGO and liver PEPCK expression. CSND trended to augment the insulin-stimulated glucose flux and enhanced liver Akt phosphorylation at both hypoxic and normoxic conditions. IH increased serum epinephrine levels and liver sympathetic innervation, and both increases were abolished by CSND. We conclude that chronic IH induces fasting hyperglycemia increasing baseline HGO via the CSN sympathetic output from carotid body chemoreceptors, but does not significantly impair whole body insulin sensitivity. PMID:25103977

  16. Hypoxia and its implications in rheumatoid arthritis.

    PubMed

    Quiñonez-Flores, Celia María; González-Chávez, Susana Aideé; Pacheco-Tena, César

    2016-08-22

    Alterations in tissue oxygen pressure contribute to a number of diseases, including rheumatoid arthritis (RA). Low partial pressure of oxygen, a condition known as hypoxia, is a relevant feature in RA since it is involved in angiogenesis, inflammation, apoptosis, cartilage degradation, energy metabolism, and oxidative damage. Therefore, alterations in hypoxia-related signaling pathways are considered potential mechanisms of disease pathogenesis. The objective of this review is to highlight and update our current knowledge of the role of hypoxia in the pathogenesis of RA. We describe the experimental evidence that RA synovial tissue exists in a hypoxic state, as well as the origin and involvement of synovial hypoxia in different aspects of the pathogenic process.

  17. Hypoxia and its implications in rheumatoid arthritis.

    PubMed

    Quiñonez-Flores, Celia María; González-Chávez, Susana Aideé; Pacheco-Tena, César

    2016-01-01

    Alterations in tissue oxygen pressure contribute to a number of diseases, including rheumatoid arthritis (RA). Low partial pressure of oxygen, a condition known as hypoxia, is a relevant feature in RA since it is involved in angiogenesis, inflammation, apoptosis, cartilage degradation, energy metabolism, and oxidative damage. Therefore, alterations in hypoxia-related signaling pathways are considered potential mechanisms of disease pathogenesis. The objective of this review is to highlight and update our current knowledge of the role of hypoxia in the pathogenesis of RA. We describe the experimental evidence that RA synovial tissue exists in a hypoxic state, as well as the origin and involvement of synovial hypoxia in different aspects of the pathogenic process. PMID:27549205

  18. Evaluation of Hypoxia with Cu-ATSM

    PubMed Central

    Lapi, Suzanne E.; Lewis, Jason S.; Dehdashti, Farrokh

    2015-01-01

    Imaging of hypoxia is important in many diseases states in oncology, cardiology and neurology. The radiopharmaceutical, copper labelled diacetyl-bis(N-methylthiosemicarbazone) (Cu-ATSM), has been used to assess hypoxia in many studies. In particular, Cu-ATSM has been used in oncologic settings to investigate tumor hypoxia and the role of this parameter in response to therapy and outcome. Other groups have conducted imaging studies assessing the role of hypoxia in cardiovascular disease and neurological disorders. Additionally, several groups have made significant progress into understanding the mechanism by which this compound accumulates in cells. Multiple preclinical and clinical studies have been conducted, shedding light on the important of careful image analysis when using this tracer. This review article focusses on the recent preclinical and clinical studies with this tracer. PMID:25704389

  19. Hypoxia: from molecular responses to ecosystem responses.

    PubMed

    Wu, Rudolf S S

    2002-01-01

    Hypoxia affects thousands of km2 of marine waters all over the world, and has caused mass mortality of marine animals, benthic defaunation and decline in fisheries production in many places. The severity, frequency occurrence and spatial scale of hypoxia have increased in the last few decades. Due to rapid human population growth and global warming, the problem of hypoxia is likely to become worse in the coming years. Molecular responses of marine animals to hypoxia are poorly known. In many animals, a haem protein probably serves as the cellular sensor for oxygen, and reactive oxygen species are generated as signaling molecules. In mammal and fish, a heterodimeric transcription factor, hypoxia-inducible factor 1 (HIF-1) has been identified. HIF-1 receives signals from the molecular oxygen senor through redox reactions and/or phosphorylation, and in turn, regulates the transcription of a number of hypoxia-inducible genes, including genes involved in erythropoiesis, angiogenesis and glycolysis. These molecular responses then cascade into a series of biochemical and physiological adjustments, enabling the animal to survive better under hypoxic conditions. Marine animals respond to hypoxia by first attempting to maintain oxygen delivery (e.g. increases in respiration rate, number of red blood cells, or oxygen binding capacity of hemoglobin), then by conserving energy (e.g. metabolic depression, down regulation of protein synthesis and down regulation/modification of certain regulatory enzymes). Upon exposure to prolonged hypoxia, animals must eventually resort to anaerobic respiration. Hypoxia reduces growth and feeding, which may eventually affect individual fitness. Effects of hypoxia on reproduction and development of marine animals, albeit important in affecting species survival, remain almost unknown. Many fish and marine organisms can detect, and actively avoid hypoxia. Some benthos may leave their burrows and move to sediment surface during hypoxia. These

  20. Acid-sensing ion channels under hypoxia

    PubMed Central

    Yingjun, Guo; Xun, Qu

    2013-01-01

    Hypoxia represents the lack of oxygen below the basic level, and the range of known channels related to hypoxia is continually increasing. Since abnormal hypoxia initiates pathological processes in numerous diseases via, to a great degree, producing acidic microenvironment, the significance of these channels in this environment has, until now, remained completely unknown. However, recent discovery of acid-sensing ion channels (ASICs) have enhanced our understanding of the hypoxic channelome. They belong to the degenerin/epithelial Na+ channel family and function once extracellular pH decreases to a certain level. So does the ratiocination emerge that ASICs participate in many hypoxia-induced pathological processes, including pain, apoptosis, malignancy, which all appear to involve them. Since evidence suggests that activity of ASICs is altered under pathological hypoxia, future studies are needed to deeply explore the relationship between ASICs and hypoxia, which may provide a progressive understanding of hypoxic effects in cancer, arthritis, intervertebral disc degeneration, ischemic brain injury and so on. PMID:23764948

  1. Immunohistochemical Detection of Changes in Tumor Hypoxia

    SciTech Connect

    Russell, James Carlin, Sean; Burke, Sean A.; Wen Bixiu; Yang, Kwang Mo; Ling, C. Clifton

    2009-03-15

    Purpose: Although hypoxia is a known prognostic factor, its effect will be modified by the rate of reoxygenation and the extent to which the cells are acutely hypoxic. We tested the ability of exogenous and endogenous markers to detect reoxygenation in a xenograft model. Our technique might be applicable to stored patient samples. Methods and Materials: The human colorectal carcinoma line, HT29, was grown in nude mice. Changes in tumor hypoxia were examined by injection of pimonidazole, followed 24 hours later by EF5. Cryosections were stained for these markers and for carbonic anhydrase IX (CAIX) and hypoxia-inducible factor 1{alpha} (HIF1{alpha}). Tumor hypoxia was artificially manipulated by carbogen exposure. Results: In unstressed tumors, all four markers showed very similar spatial distributions. After carbogen treatment, pimonidazole and EF5 could detect decreased hypoxia. HIF1{alpha} staining was also decreased relative to CAIX, although the effect was less pronounced than for EF5. Control tumors displayed small regions that had undergone spontaneous changes in tumor hypoxia, as judged by pimonidazole relative to EF5; most of these changes were reflected by CAIX and HIF1{alpha}. Conclusion: HIF1{alpha} can be compared with either CAIX or a previously administered nitroimidazole to provide an estimate of reoxygenation.

  2. Sensing and surviving hypoxia in vertebrates.

    PubMed

    Jonz, Michael G; Buck, Leslie T; Perry, Steve F; Schwerte, Thorsten; Zaccone, Giacomo

    2016-02-01

    Surviving hypoxia is one of the most critical challenges faced by vertebrates. Most species have adapted to changing levels of oxygen in their environment with specialized organs that sense hypoxia, while only few have been uniquely adapted to survive prolonged periods of anoxia. The goal of this review is to present the most recent research on oxygen sensing, adaptation to hypoxia, and mechanisms of anoxia tolerance in nonmammalian vertebrates. We discuss the respiratory structures in fish, including the skin, gills, and air-breathing organs, and recent evidence for chemosensory neuroepithelial cells (NECs) in these tissues that initiate reflex responses to hypoxia. The use of the zebrafish as a genetic and developmental model has allowed observation of the ontogenesis of respiratory and chemosensory systems, demonstration of a putative intracellular O2 sensor in chemoreceptors that may initiate transduction of the hypoxia signal, and investigation into the effects of extreme hypoxia on cardiorespiratory development. Other organisms, such as goldfish and freshwater turtles, display a high degree of anoxia tolerance, and these models are revealing important adaptations at the cellular level, such as the regulation of glutamatergic and GABAergic neurotransmission in defense of homeostasis in central neurons.

  3. The influence of chronic hypoxia upon chemoreception

    PubMed Central

    Powell, Frank L.

    2007-01-01

    Carotid body chemoreceptors are essential for time-dependent changes in ventilatory control during chronic hypoxia. Early theories of ventilatory acclimatization to hypoxia focused on time-dependent changes in known ventilatory stimuli, such as small changes in arterial pH that may play a significant role in some species. However, plasticity in the cellular and molecular mechanisms of carotid body chemoreception play a major role in ventilatory acclimatization to hypoxia in all species studied. Chronic hypoxia causes changes in (a) ion channels (potassium, sodium, calcium) to increase glomus cell excitability, and (b) neurotransmitters (dopamine, acetylcholine, ATP) and neuromodulators (endothelin-1) to increase carotid body afferent activity for a given PO2 and optimize O2-sensitivity. O2-sensing heme-containing molecules in the carotid body have not been studied in chronic hypoxia. Plasticity in medullary respiratory centers processing carotid body afferent input also contributes to ventilatory acclimatization to hypoxia. It is not known if the same mechanisms occur in patients with chronic hypoxemia from lung disease or high altitude natives. PMID:17291837

  4. Augmented assessment as a means to augmented reality.

    PubMed

    Bergeron, Bryan

    2006-01-01

    Rigorous scientific assessment of educational technologies typically lags behind the availability of the technologies by years because of the lack of validated instruments and benchmarks. Even when the appropriate assessment instruments are available, they may not be applied because of time and monetary constraints. Work in augmented reality, instrumented mannequins, serious gaming, and similar promising educational technologies that haven't undergone timely, rigorous evaluation, highlights the need for assessment methodologies that address the limitations of traditional approaches. The most promising augmented assessment solutions incorporate elements of rapid prototyping used in the software industry, simulation-based assessment techniques modeled after methods used in bioinformatics, and object-oriented analysis methods borrowed from object oriented programming. PMID:16404012

  5. Effects of cigarette smoke and chronic hypoxia on airways remodeling and resistance. Clinical significance.

    PubMed

    Olea, Elena; Ferrer, Elisabet; Prieto-Lloret, Jesus; Gonzalez-Martin, Carmen; Vega-Agapito, Victoria; Gonzalez-Obeso, Elvira; Agapito, Teresa; Peinado, Victor; Obeso, Ana; Barbera, Joan Albert; Gonzalez, Constancio

    2011-12-15

    Previously we have reported that association of cigarette smoke (CS) and chronic hypoxia (CH) interact positively to physiopathologically remodel pulmonary circulation. In present study we have exposed guinea pigs to CS smoke (four cigarettes/day; 3 months; CS) and to chronic hypoxia (12% O(2), 15 days; CH) alone or in combination (CSCH animals) and evaluated airways remodeling and resistance assessed as Penh (enhance pause). We measured Penh while animals breathe air, 10% O(2) and 5% CO(2) and found that CS and CH animals have higher Penh than controls; Penh was even larger in CSCH animals. A rough parallelism between Penh and thickness of bronchiolar wall and muscular layer and Goblet cell number was noticed. We conclude that CS and CH association accelerates CS-induced respiratory system damage, evidenced by augmented airway resistance, bronchial wall thickness and muscularization and Goblet cell number. Our findings would suggest that appearance of hypoxia would aggravate any preexisting pulmonary pathology by increasing airways resistance and reactivity. PMID:22000990

  6. Potassium Channels and Uterine Vascular Adaptation to Pregnancy and Chronic Hypoxia

    PubMed Central

    Zhu, Ronghui; Xiao, DaLiao; Zhang, Lubo

    2014-01-01

    During a normal course of pregnancy, uterine vascular tone is significantly decreased resulting in a striking increase in uterine blood flow, which is essential for fetal development and fetal growth. Chronic hypoxia during gestation may adversely affect the normal adaptation of uterine vascular tone and increase the risk of preeclampsia and fetal intrauterine growth restriction. In this review, we present evidence that the regulation of K+ channels is an important mechanism in the adaptation of uterine vascular tone to pregnancy and hypoxia. There are four types of K+ channels identified in arterial smooth muscle cells: 1) voltage-dependent K+ (Kv) channels, 2) Ca2+-activated K+ (KCa) channels, 3) inward rectifier K+ (KIR) channels, and 4) ATP-sensitive K+ (KATP) channels. Pregnancy differentially augments the expression and activity of K+ channels via downregulation of protein kinase C signaling in uterine and other vascular beds, leading to decreased uterine vascular tone and increased uterine blood flow. Sex steroid hormones play an important role in the pregnancy-mediated alteration of K+ channels in the uterine vasculature. In addition, chronic hypoxia alters uterine vascular K+ channels expression and activities via modulation of steroid hormones/receptors-mediated signaling, resulting in increased uterine vascular tone during pregnancy. PMID:24063385

  7. Hypoxia in the Northern Gulf of Mexico

    SciTech Connect

    Dale, Virginia H

    2010-01-01

    Since 1985, scientists have been documenting a hypoxic zone in the Gulf of Mexico each year. The hypoxic zone, an area of low dissolved oxygen that cannot support marine life, generally manifests itself in the spring. Since marine species either die or flee the hypoxic zone, the spread of hypoxia reduces the available habitat for marine species, which are important for the ecosystem as well as commercial and recreational fishing in the Gulf. Since 2001, the hypoxic zone has averaged 16,500 km{sup 2} during its peak summer months, an area slightly larger than the state of Connecticut, and ranged from a low of 8,500 km{sup 2} to a high of 22,000 km{sup 2}. To address the hypoxia problem, the Mississippi River/Gulf of Mexico Watershed Nutrient Task Force (or Task Force) was formed to bring together representatives from federal agencies, states, and tribes to consider options for responding to hypoxia. The Task Force asked the White House Office of Science and Technology Policy to conduct a scientific assessment of the causes and consequences of Gulf hypoxia through its Committee on Environment and Natural Resources (CENR). In 2000 the CENR completed An Integrated Assessment: Hypoxia in the Northern Gulf of Mexico (or Integrated Assessment), which formed the scientific basis for the Task Force's Action Plan for Reducing, Mitigating, and Controlling Hypoxia in the Northern Gulf of Mexico (Action Plan, 2001). In its Action Plan, the Task Force pledged to implement ten management actions and to assess progress every 5 years. This reassessment would address the nutrient load reductions achieved, the responses of the hypoxic zone and associated water quality and habitat conditions, and economic and social effects. The Task Force began its reassessment in 2005. In 2006 as part of the reassessment, USEPA's Office of Water, on behalf of the Task Force, requested that the U.S. Environmental Protection Agency (USEPA) Science Advisory Board (SAB) convene an independent panel to

  8. Optimizing Hypoxia Detection and Treatment Strategies

    PubMed Central

    Koch, Cameron J.; Evans, Sydney M.

    2015-01-01

    Clinical studies using Eppendorf® needle sensors have invariably documented the resistance of hypoxic human tumors to therapy. These studies first documented the need for individual patient measurement of hypoxia, since hypoxia varied from tumor-to-tumor. Furthermore, hypoxia in sarcomas & cervical cancer leads to distant metastasis or local/regional spread, respectively. For various reasons, the field has moved away from direct needle-sensor oxygen measurements to indirect assays (HIF-related changes; bioreductive metabolism) and the latter can be imaged non-invasively. Many of hypoxia’s detrimental therapeutic effects are reversible in mice but little treatment-improvement in hypoxic human tumors has been seen. The question is why? What factors cause human tumors to be refractory to anti-hypoxia strategies? We suggest the primary cause to be the complexity of hypoxia formation and its characteristics. Three basic types of hypoxia exist, encompassing various diffusional (distance from perfused vessel), temporal (on/off cycling) and perfusional (blood-flow efficiency) limitations. Surprisingly, there is no current information on their relative prevalence in human tumors and even animal models. This is important because different hypoxia sub-types are predicted to require different diagnostic and therapeutic approaches, but the implications of this remain unknown. Even more challenging, no agreement exists for the best way to measure hypoxia. Some results even suggest that hypoxia is unlikely to be targetable therapeutically. In this review, the authors will revisit various critical aspects of this field that are sometimes forgotten or misrepresented in the recent literature. Since most current non-invasive imaging studies involve PET-isotope-labelled 2-nitroimidazoles, we will emphasize key findings made in our studies using EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide] and F18-labelled EF5. These will show the importance of

  9. Heterogeneous Role of the Glutathione Antioxidant System in Modulating the Response of ESFT to Fenretinide in Normoxia and Hypoxia

    PubMed Central

    Magwere, Tapiwanashe; Burchill, Susan A.

    2011-01-01

    Glutathione (GSH) is implicated in drug resistance mechanisms of several cancers and is a key regulator of cell death pathways within cells. We studied Ewing's sarcoma family of tumours (ESFT) cell lines and three mechanistically distinct anticancer agents (fenretinide, doxorubicin, and vincristine) to investigate whether the GSH antioxidant system is involved in the reduced sensitivity to these chemotherapeutic agents in hypoxia. Cell viability and death were assessed by the trypan blue exclusion assay and annexin V-PI staining, respectively. Hypoxia significantly decreased the sensitivity of all ESFT cell lines to fenretinide-induced death, whereas the effect of doxorubicin or vincristine was marginal and cell-line-specific. The response of the GSH antioxidant system in ESFT cell lines to hypoxia was variable and also cell-line-specific, although the level of GSH appeared to be most dependent on de novo biosynthesis rather than recycling. RNAi-mediated knockdown of key GSH regulatory enzymes γ-glutamylcysteine synthetase or glutathione disulfide reductase partially reversed the hypoxia-induced resistance to fenretinide, and increasing GSH levels using N-acetylcysteine augmented the hypoxia-induced resistance in a cell line-specific manner. These observations are consistent with the conclusion that the role of the GSH antioxidant system in modulating the sensitivity of ESFT cells to fenretinide is heterogeneous depending on environment and cell type. This is likely to limit the value of targeting GSH as a therapeutic strategy to overcome hypoxia-induced drug resistance in ESFT. Whether targeting the GSH antioxidant system in conjunction with other therapeutics may benefit some patients with ESFT remains to be seen. PMID:22174837

  10. Tumor Hypoxia: Causative Mechanisms, Microregional Heterogeneities, and the Role of Tissue-Based Hypoxia Markers.

    PubMed

    Vaupel, Peter; Mayer, Arnulf

    2016-01-01

    Tumor hypoxia is a hallmark of solid malignant tumor growth, profoundly influences malignant progression and contributes to the development of therapeutic resistance. Pathogenesis of tumor hypoxia is multifactorial, with contributions from both acute and chronic factors. Spatial distribution of hypoxia within tumors is markedly heterogeneous and often changes over time, e.g., during a course of radiotherapy. Substantial changes in the oxygenation status can occur within the distance of a few cell layers, explaining the inability of currently used molecular imaging techniques to adequately assess this crucial trait. Due to the possible importance of tumor hypoxia for clinical decision-making, there is a great demand for molecular tools which may provide the necessary resolution down to the single cell level. Exogenous and endogenous markers of tumor hypoxia have been investigated for this purpose. Their potential use may be greatly enhanced by multiparametric in situ methods in experimental and human tumor tissue. PMID:27526128

  11. Complications of soft tissue augmentation.

    PubMed

    Hirsch, Ranella J; Stier, Meghan

    2008-09-01

    The wide variety of dermal fillers presently available has revolutionized treatment options for patients seeking a refreshed appearance. Soft tissue fillers include both bovine and human collagens, the hyaluronans, calcium hydroxyapatite, poly-L-lactic acid, and synthetic polymers. However, soft tissue augmentation is never risk-free, and as these procedures have increased in prevalence, complications have been more frequently reported. This article describes a range of complications resulting from dermal filler injections, reviews key case studies, and discusses possible treatment options for adverse effects. While biodegradable fillers offer the least risk for the patient, location, allergic reactions, granulomas, necrosis, and infection are all serious complications that must be considered before performing soft tissue augmentation with any approved dermal filler.

  12. Effective Augmentation of Complex Networks

    PubMed Central

    Wang, Jinjian; Yu, Xinghuo; Stone, Lewi

    2016-01-01

    Networks science plays an enormous role in many aspects of modern society from distributing electrical power across nations to spreading information and social networking amongst global populations. While modern networks constantly change in size, few studies have sought methods for the difficult task of optimising this growth. Here we study theoretical requirements for augmenting networks by adding source or sink nodes, without requiring additional driver-nodes to accommodate the change i.e., conserving structural controllability. Our “effective augmentation” algorithm takes advantage of clusters intrinsic to the network topology, and permits rapidly and efficient augmentation of a large number of nodes in one time-step. “Effective augmentation” is shown to work successfully on a wide range of model and real networks. The method has numerous applications (e.g. study of biological, social, power and technological networks) and potentially of significant practical and economic value. PMID:27165120

  13. Effective Augmentation of Complex Networks

    NASA Astrophysics Data System (ADS)

    Wang, Jinjian; Yu, Xinghuo; Stone, Lewi

    2016-05-01

    Networks science plays an enormous role in many aspects of modern society from distributing electrical power across nations to spreading information and social networking amongst global populations. While modern networks constantly change in size, few studies have sought methods for the difficult task of optimising this growth. Here we study theoretical requirements for augmenting networks by adding source or sink nodes, without requiring additional driver-nodes to accommodate the change i.e., conserving structural controllability. Our “effective augmentation” algorithm takes advantage of clusters intrinsic to the network topology, and permits rapidly and efficient augmentation of a large number of nodes in one time-step. “Effective augmentation” is shown to work successfully on a wide range of model and real networks. The method has numerous applications (e.g. study of biological, social, power and technological networks) and potentially of significant practical and economic value.

  14. Augmented reality building operations tool

    SciTech Connect

    Brackney, Larry J.

    2014-09-09

    A method (700) for providing an augmented reality operations tool to a mobile client (642) positioned in a building (604). The method (700) includes, with a server (660), receiving (720) from the client (642) an augmented reality request for building system equipment (612) managed by an energy management system (EMS) (620). The method (700) includes transmitting (740) a data request for the equipment (612) to the EMS (620) and receiving (750) building management data (634) for the equipment (612). The method (700) includes generating (760) an overlay (656) with an object created based on the building management data (634), which may be sensor data, diagnostic procedures, or the like. The overlay (656) is configured for concurrent display on a display screen (652) of the client (642) with a real-time image of the building equipment (612). The method (700) includes transmitting (770) the overlay (656) to the client (642).

  15. Energy Flux, Lactate Shuttling, Mitochondrial Dynamics, and Hypoxia.

    PubMed

    Brooks, George A

    2016-01-01

    Our understanding of what happens in working muscle and at the whole-body level at sea level and at high altitude is different from that a few years ago. If dietary CHO and nutrition are adequate, at sea level metabolism shifts from a mix of lipid and CHO-derived fuels toward carbohydrate (glycogen, glucose, and lactate) oxidation at moderate and greater exercise intensities. As given by the Crossover Concept, a percentage to total energy expenditure, lipid oxidation is greatest at exercise power outputs eliciting 45-50 % of VO2max with greater intensities requiring relatively more CHO and lesser lipid oxidation. At altitude, a given exercise power output is achieved at a greater relative intensity expressed as % VO2max. Hence, exercise under conditions of hypoxia requires greater glycolytic flux, and lactate production than does the same effort at sea level, normoxic conditions. Glycolytic flux is further augmented at altitude by the effect of hypoxemia on sympathetic nervous system activity. Hence, augmented lactate production during exercise is adaptive. Over the short term, accelerated lactate flux provides ATP supporting muscle contraction and balances cytosolic redox. As well, lactate provides and energy substrate and gluconeogenic precursor. Over a longer term, via redox and ROS-generating mechanisms, lactate may affect adaptations in mitochondrial biogenesis and solute (glucose and lactate) transport. While important, the energy substrate, gluconeogenic, and signaling qualities of lactate production and disposal at altitude need to be considered within the context of overall dietary energy intake and expenditure during exercise at sea level and high altitude. PMID:27343113

  16. TDRSS Augmentation System for Satellites

    NASA Technical Reports Server (NTRS)

    Heckler, Gregory W.; Gramling, Cheryl; Valdez, Jennifer; Baldwin, Philip

    2016-01-01

    In 2015, NASA Goddard Space Flight Center (GSFC) reinvigorated the development of the TDRSS Augmentation Service for Satellites (TASS). TASS is a global, space-based, communications and navigation service for users of Global Navigation Satellite Systems(GNSS) and the Tracking and Data Relay Satellite System (TDRSS). TASS leverages the existing TDRSS to provide an S-band beacon radio navigation and messaging source to users at orbital altitudes 1400 km and below.

  17. Media-Augmented Exercise Machines

    NASA Astrophysics Data System (ADS)

    Krueger, T.

    2002-01-01

    Cardio-vascular exercise has been used to mitigate the muscle and cardiac atrophy associated with adaptation to micro-gravity environments. Several hours per day may be required. In confined spaces and long duration missions this kind of exercise is inevitably repetitive and rapidly becomes uninteresting. At the same time, there are pressures to accomplish as much as possible given the cost- per-hour for humans occupying orbiting or interplanetary. Media augmentation provides a the means to overlap activities in time by supplementing the exercise with social, recreational, training or collaborative activities and thereby reducing time pressures. In addition, the machine functions as an interface to a wide range of digital environments allowing for spatial variety in an otherwise confined environment. We hypothesize that the adoption of media augmented exercise machines will have a positive effect on psycho-social well-being on long duration missions. By organizing and supplementing exercise machines, data acquisition hardware, computers and displays into an interacting system this proposal increases functionality with limited additional mass. This paper reviews preliminary work on a project to augment exercise equipment in a manner that addresses these issues and at the same time opens possibilities for additional benefits. A testbed augmented exercise machine uses a specialty built cycle trainer as both input to a virtual environment and as an output device from it using spatialized sound, and visual displays, vibration transducers and variable resistance. The resulting interactivity increases a sense of engagement in the exercise, provides a rich experience of the digital environments. Activities in the virtual environment and accompanying physiological and psychological indicators may be correlated to track and evaluate the health of the crew.

  18. Augment railgun and sequential discharge

    NASA Astrophysics Data System (ADS)

    Kobayashi, K.

    1993-01-01

    Proprietary R&D efforts toward the creation of tactical weapon systems-applicable railguns are presented. Attention is given to measures taken for projectile velocity maximization and sequential-discharge operation, and to an augmenting railgun which has demonstrated a 66-percent efficiency improvement over the two-rail baseline railgun system. This device is characterized by strong interaction between capacitor bank submodules during sequential discharge.

  19. Measuring patient outcomes in breast augmentation: introducing the BREAST-Q Augmentation module.

    PubMed

    Pusic, Andrea L; Reavey, Patrick L; Klassen, Anne F; Scott, Amie; McCarthy, Colleen; Cano, Stefan J

    2009-01-01

    The Breast-Q Augmentation module is a new and unique questionnaire for measuring patient-reported outcomes following breast augmentation. It has undergone a rigorous development and validation process and is currently the only questionnaire for breast augmentation that meets international and federal standards for questionnaire development. The Breast-Q Augmentation module covers a comprehensive set of concerns of breast augmentation patients, including satisfaction with breasts and impact on quality of life. With its excellent psychometric properties, the Breast-Q Augmentation module can provide clinicians and researchers with a wealth of essential data to improve the field of breast augmentation from the perspectives of both surgeons and patients.

  20. Functional genomics approach to hypoxia signaling.

    PubMed

    Seta, Karen A; Millhorn, David E

    2004-02-01

    Mammalian cells require a constant supply of oxygen to maintain energy balance, and sustained hypoxia can result in cell death. It is therefore not surprising that sophisticated adaptive mechanisms have evolved that enhance cell survival during hypoxia. During the past few years, there have been a growing number of reports on hypoxia-induced transcription of specific genes. In this review, we describe a unique experimental approach that utilizes focused cDNA libraries coupled to microarray analyses to identify hypoxia-responsive signal transduction pathways and genes that confer the hypoxia-tolerant phenotype. We have used the subtractive suppression hybridization (SSH) method to create a cDNA library enriched in hypoxia-regulated genes in oxygen-sensing pheochromocytoma cells and have used this library to create microarrays that allow us to examine hundreds of genes at a time. This library contains over 300 genes and expressed sequence tags upregulated by hypoxia, including tyrosine hydroxylase, vascular endothelial growth factor, and junB. Hypoxic regulation of these and other genes in the library has been confirmed by microarray, Northern blot, and real-time PCR analyses. Coupling focused SSH libraries with microarray analyses allows one to specifically study genes relevant to a phenotype of interest while reducing much of the biological noise associated with these types of studies. When used in conjunction with high-throughput, dye-based assays for cell survival and apoptosis, this approach offers a rapid method for discovering validated therapeutic targets for the treatment of cardiovascular disease, stroke, and tumors. PMID:14715686

  1. Erythropoietin Synthesis in Renal Myofibroblasts Is Restored by Activation of Hypoxia Signaling.

    PubMed

    Souma, Tomokazu; Nezu, Masahiro; Nakano, Daisuke; Yamazaki, Shun; Hirano, Ikuo; Sekine, Hiroki; Dan, Takashi; Takeda, Kotaro; Fong, Guo-Hua; Nishiyama, Akira; Ito, Sadayoshi; Miyata, Toshio; Yamamoto, Masayuki; Suzuki, Norio

    2016-02-01

    Erythropoietin (Epo) is produced by renal Epo-producing cells (REPs) in a hypoxia-inducible manner. The conversion of REPs into myofibroblasts and coincident loss of Epo-producing ability are the major cause of renal fibrosis and anemia. However, the hypoxic response of these transformed myofibroblasts remains unclear. Here, we used complementary in vivo transgenic and live imaging approaches to better understand the importance of hypoxia signaling in Epo production. Live imaging of REPs in transgenic mice expressing green fluorescent protein from a modified Epo-gene locus revealed that healthy REPs tightly associated with endothelium by wrapping processes around capillaries. However, this association was hampered in states of renal injury-induced inflammation previously shown to correlate with the transition to myofibroblast-transformed renal Epo-producing cells (MF-REPs). Furthermore, activation of hypoxia-inducible factors (HIFs) by genetic inactivation of HIF-prolyl hydroxylases (PHD1, PHD2, and PHD3) selectively in Epo-producing cells reactivated Epo production in MF-REPs. Loss of PHD2 in REPs restored Epo-gene expression in injured kidneys but caused polycythemia. Notably, combined deletions of PHD1 and PHD3 prevented loss of Epo expression without provoking polycythemia. Mice with PHD-deficient REPs also showed resistance to LPS-induced Epo repression in kidneys, suggesting that augmented HIF signaling counterbalances inflammatory stimuli in regulation of Epo production. Thus, augmentation of HIF signaling may be an attractive therapeutic strategy for treating renal anemia by reactivating Epo synthesis in MF-REPs.

  2. Erythropoietin Synthesis in Renal Myofibroblasts Is Restored by Activation of Hypoxia Signaling.

    PubMed

    Souma, Tomokazu; Nezu, Masahiro; Nakano, Daisuke; Yamazaki, Shun; Hirano, Ikuo; Sekine, Hiroki; Dan, Takashi; Takeda, Kotaro; Fong, Guo-Hua; Nishiyama, Akira; Ito, Sadayoshi; Miyata, Toshio; Yamamoto, Masayuki; Suzuki, Norio

    2016-02-01

    Erythropoietin (Epo) is produced by renal Epo-producing cells (REPs) in a hypoxia-inducible manner. The conversion of REPs into myofibroblasts and coincident loss of Epo-producing ability are the major cause of renal fibrosis and anemia. However, the hypoxic response of these transformed myofibroblasts remains unclear. Here, we used complementary in vivo transgenic and live imaging approaches to better understand the importance of hypoxia signaling in Epo production. Live imaging of REPs in transgenic mice expressing green fluorescent protein from a modified Epo-gene locus revealed that healthy REPs tightly associated with endothelium by wrapping processes around capillaries. However, this association was hampered in states of renal injury-induced inflammation previously shown to correlate with the transition to myofibroblast-transformed renal Epo-producing cells (MF-REPs). Furthermore, activation of hypoxia-inducible factors (HIFs) by genetic inactivation of HIF-prolyl hydroxylases (PHD1, PHD2, and PHD3) selectively in Epo-producing cells reactivated Epo production in MF-REPs. Loss of PHD2 in REPs restored Epo-gene expression in injured kidneys but caused polycythemia. Notably, combined deletions of PHD1 and PHD3 prevented loss of Epo expression without provoking polycythemia. Mice with PHD-deficient REPs also showed resistance to LPS-induced Epo repression in kidneys, suggesting that augmented HIF signaling counterbalances inflammatory stimuli in regulation of Epo production. Thus, augmentation of HIF signaling may be an attractive therapeutic strategy for treating renal anemia by reactivating Epo synthesis in MF-REPs. PMID:26054543

  3. Oxygen deprivation and the cellular response to hypoxia in adipocytes - perspectives on white and brown adipose tissues in obesity.

    PubMed

    Trayhurn, Paul; Alomar, Suliman Yousef

    2015-01-01

    Relative hypoxia has been shown to develop in white adipose tissue depots of different types of obese mouse (genetic, dietary), and this leads to substantial changes in white adipocyte function. These changes include increased production of inflammation-related adipokines (such as IL-6, leptin, Angptl4, and VEGF), an increase in glucose utilization and lactate production, and the induction of fibrosis and insulin resistance. Whether hypoxia also occurs in brown adipose tissue depots in obesity has been little considered. However, a recent study has reported low pO2 in brown fat of obese mice, this involving mitochondrial loss and dysfunction. We suggest that obesity-linked hypoxia may lead to similar alterations in brown adipocytes as in white fat cells - particularly changes in adipokine production, increased glucose uptake and lactate release, and insulin resistance. This would be expected to compromise thermogenic activity and the role of brown fat in glucose homeostasis and triglyceride clearance, underpinning the development of the metabolic syndrome. Hypoxia-induced augmentation of lactate production may also stimulate the "browning" of white fat depots through recruitment of UCP1 and the development of brite adipocytes.

  4. Oxygen Deprivation and the Cellular Response to Hypoxia in Adipocytes – Perspectives on White and Brown Adipose Tissues in Obesity

    PubMed Central

    Trayhurn, Paul; Alomar, Suliman Yousef

    2015-01-01

    Relative hypoxia has been shown to develop in white adipose tissue depots of different types of obese mouse (genetic, dietary), and this leads to substantial changes in white adipocyte function. These changes include increased production of inflammation-related adipokines (such as IL-6, leptin, Angptl4, and VEGF), an increase in glucose utilization and lactate production, and the induction of fibrosis and insulin resistance. Whether hypoxia also occurs in brown adipose tissue depots in obesity has been little considered. However, a recent study has reported low pO2 in brown fat of obese mice, this involving mitochondrial loss and dysfunction. We suggest that obesity-linked hypoxia may lead to similar alterations in brown adipocytes as in white fat cells – particularly changes in adipokine production, increased glucose uptake and lactate release, and insulin resistance. This would be expected to compromise thermogenic activity and the role of brown fat in glucose homeostasis and triglyceride clearance, underpinning the development of the metabolic syndrome. Hypoxia-induced augmentation of lactate production may also stimulate the “browning” of white fat depots through recruitment of UCP1 and the development of brite adipocytes. PMID:25745415

  5. Effects of hypoxia on vertebrate blood vessels.

    PubMed

    Russell, Michael J; Dombkowski, Ryan A; Olson, Kenneth R

    2008-03-01

    Hypoxia contracts mammalian respiratory vessels and increases vascular resistance in respiratory tissues of many vertebrates. In systemic vessels these responses vary, hypoxia relaxes mammalian vessels and contracts systemic arteries from cyclostomes. It has been proposed that hypoxic vasoconstriction in cyclostome systemic arteries is the antecedent to mammalian hypoxic pulmonary vasoconstriction, however, phylogenetic characterization of hypoxic responses is lacking. In this study, we characterized the hypoxic response of isolated systemic and respiratory vessels from a variety of vertebrates using standard myography. Pre-gill/respiratory (ventral aorta, afferent branchial artery, pulmonary artery) and post-gill/systemic (dorsal and thoracic aortas, efferent branchial artery) from lamprey (Petromyzon marinus), sandbar shark (Carcharhinus plumbeus), yellowfin tuna (Thunnus albacares), American bullfrog (Rana catesbeiana), American alligator (Alligator mississippiensis), Pekin duck (Anas platyrhynchos domesticus), chicken (Gallus domesticus) and rat (Rattus norvegicus) were exposed to hypoxia at rest or during pre-stimulation (elevated extracellular potassium, epinephrine or norepinephrine). Hypoxia produced a relaxation or transient contraction followed by relaxation in all pre-gill vessels, except for contraction in lamprey, and vasoconstriction or tri-phasic constriction-dilation-constriction in all pulmonary vessels. Hypoxia contracted systemic vessels from all animals except shark and rat and in pre-contracted rat aortas it produced a transient contraction followed by relaxation. These results show that while the classic "systemic hypoxic vasodilation and pulmonary hypoxic vasoconstriction" may occur in the microcirculation, the hypoxic response of the vertebrate macrocirculation is quite variable. These findings also suggest that hypoxic vasoconstriction is a phylogenetically ancient response. PMID:18214862

  6. Imaging tumor hypoxia by magnetic resonance methods.

    PubMed

    Pacheco-Torres, Jesús; López-Larrubia, Pilar; Ballesteros, Paloma; Cerdán, Sebastián

    2011-01-01

    Tumor hypoxia results from the negative balance between the oxygen demands of the tissue and the capacity of the neovasculature to deliver sufficient oxygen. The resulting oxygen deficit has important consequences with regard to the aggressiveness and malignancy of tumors, as well as their resistance to therapy, endowing the imaging of hypoxia with vital repercussions in tumor prognosis and therapy design. The molecular and cellular events underlying hypoxia are mediated mainly through hypoxia-inducible factor, a transcription factor with pleiotropic effects over a variety of cellular processes, including oncologic transformation, invasion and metastasis. However, few methodologies have been able to monitor noninvasively the oxygen tensions in vivo. MRI and MRS are often used for this purpose. Most MRI approaches are based on the effects of the local oxygen tension on: (i) the relaxation times of (19)F or (1)H indicators, such as perfluorocarbons or their (1)H analogs; (ii) the hemodynamics and magnetic susceptibility effects of oxy- and deoxyhemoglobin; and (iii) the effects of paramagnetic oxygen on the relaxation times of tissue water. (19)F MRS approaches monitor tumor hypoxia through the selective accumulation of reduced nitroimidazole derivatives in hypoxic zones, whereas electron spin resonance methods determine the oxygen level through its influence on the linewidths of appropriate paramagnetic probes in vivo. Finally, Overhauser-enhanced MRI combines the sensitivity of EPR methodology with the resolution of MRI, providing a window into the future use of hyperpolarized oxygen probes.

  7. Hypoxia imaging agents labeled with positron emitters.

    PubMed

    Hoigebazar, Lathika; Jeong, Jae Min

    2013-01-01

    Imaging hypoxia using positron emission tomography (PET) is of great importance for therapy of cancer. [(18)F]Fluoromisonidazole (FMISO) was the first PET agent for hypoxia imaging, and various radiolabeled nitroimidazole derivatives such as [(18)F]fluoroerythronitroimidazole (FETNIM), [(18)F]1-α-D: -(2-deoxy-2-fluoroarabinofuranosyl)-2-nitroimidazole (FAZA), [(18)F]2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide (EF-5), and [(18)F]fluoroetanidazole (FETA) have been developed successively. To overcome the high cost of cyclotron installation, (68)Ga-labeled nitroimidazole derivatives also have been developed. Another important hypoxia imaging agent is (64)Cu-diacetyl-bis(N (4)-methylthiosemicarbazone) ((64)Cu-ATSM), which can distribute in cancer tissue rapidly due to high lipophilicity. However, its application is limited due to high cost of radionuclide production. Although various hypoxia imaging agents have been reported and tested, hypoxia PET images still have to be improved, because of the low blood flow in hypoxic tissues and resulting low uptake of the agents.

  8. Analysis of hypoxia-induced metabolic reprogramming.

    PubMed

    Yang, Chendong; Jiang, Lei; Zhang, Huafeng; Shimoda, Larissa A; DeBerardinis, Ralph J; Semenza, Gregg L

    2014-01-01

    Hypoxia is a common finding in advanced human tumors and is often associated with metastatic dissemination and poor prognosis. Cancer cells adapt to hypoxia by utilizing physiological adaptation pathways that promote a switch from oxidative to glycolytic metabolism. This promotes the conversion of glucose into lactate while limiting its transformation into acetyl coenzyme A (acetyl-CoA). The uptake of glucose and the glycolytic flux are increased under hypoxic conditions, mostly owing to the upregulation of genes encoding glucose transporters and glycolytic enzymes, a process that depends on hypoxia-inducible factor 1 (HIF-1). The reduced delivery of acetyl-CoA to the tricarboxylic acid cycle leads to a switch from glucose to glutamine as the major substrate for fatty acid synthesis in hypoxic cells. In addition, hypoxia induces (1) the HIF-1-dependent expression of BCL2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3) and BNIP3-like (BNIP3L), which trigger mitochondrial autophagy, thereby decreasing the oxidative metabolism of both fatty acids and glucose, and (2) the expression of the sodium-hydrogen exchanger NHE1, which maintains an alkaline intracellular pH. Here, we present a compendium of methods to study hypoxia-induced metabolic alterations.

  9. Hypoxia-Inducible Factor in Thyroid Carcinoma

    PubMed Central

    Burrows, Natalie; Babur, Muhammad; Resch, Julia; Williams, Kaye J.; Brabant, Georg

    2011-01-01

    Intratumoural hypoxia (low oxygen tension) is associated with aggressive disease and poor prognosis. Hypoxia-inducible factor-1 is a transcription factor activated by hypoxia that regulates the expression of genes that promote tumour cell survival, progression, metastasis, and resistance to chemo/radiotherapy. In addition to hypoxia, HIF-1 can be activated by growth factor-signalling pathways such as the mitogen-activated protein kinases- (MAPK-) and phosphatidylinositol-3-OH kinases- (PI3K-) signalling cascades. Mutations in these pathways are common in thyroid carcinoma and lead to enhanced HIF-1 expression and activity. Here, we summarise current data that highlights the potential role of both hypoxia and MAPK/PI3K-induced HIF-1 signalling in thyroid carcinoma progression, metastatic characteristics, and the potential role of HIF-1 in thyroid carcinoma response to radiotherapy. Direct or indirect targeting of HIF-1 using an MAPK or PI3K inhibitor in combination with radiotherapy may be a new potential therapeutic target to improve the therapeutic response of thyroid carcinoma to radiotherapy and reduce metastatic burden. PMID:21765994

  10. REST is a hypoxia-responsive transcriptional repressor.

    PubMed

    Cavadas, Miguel A S; Mesnieres, Marion; Crifo, Bianca; Manresa, Mario C; Selfridge, Andrew C; Keogh, Ciara E; Fabian, Zsolt; Scholz, Carsten C; Nolan, Karen A; Rocha, Liliane M A; Tambuwala, Murtaza M; Brown, Stuart; Wdowicz, Anita; Corbett, Danielle; Murphy, Keith J; Godson, Catherine; Cummins, Eoin P; Taylor, Cormac T; Cheong, Alex

    2016-08-17

    Cellular exposure to hypoxia results in altered gene expression in a range of physiologic and pathophysiologic states. Discrete cohorts of genes can be either up- or down-regulated in response to hypoxia. While the Hypoxia-Inducible Factor (HIF) is the primary driver of hypoxia-induced adaptive gene expression, less is known about the signalling mechanisms regulating hypoxia-dependent gene repression. Using RNA-seq, we demonstrate that equivalent numbers of genes are induced and repressed in human embryonic kidney (HEK293) cells. We demonstrate that nuclear localization of the Repressor Element 1-Silencing Transcription factor (REST) is induced in hypoxia and that REST is responsible for regulating approximately 20% of the hypoxia-repressed genes. Using chromatin immunoprecipitation assays we demonstrate that REST-dependent gene repression is at least in part mediated by direct binding to the promoters of target genes. Based on these data, we propose that REST is a key mediator of gene repression in hypoxia.

  11. Withanolide A Prevents Neurodegeneration by Modulating Hippocampal Glutathione Biosynthesis during Hypoxia

    PubMed Central

    Baitharu, Iswar; Jain, Vishal; Deep, Satya Narayan; Shroff, Sabita; Sahu, Jayanta Kumar; Naik, Pradeep Kumar; Ilavazhagan, Govindasamy

    2014-01-01

    Withania somnifera root extract has been used traditionally in ayurvedic system of medicine as a memory enhancer. Present study explores the ameliorative effect of withanolide A, a major component of withania root extract and its molecular mechanism against hypoxia induced memory impairment. Withanolide A was administered to male Sprague Dawley rats before a period of 21 days pre-exposure and during 07 days of exposure to a simulated altitude of 25,000 ft. Glutathione level and glutathione dependent free radicals scavenging enzyme system, ATP, NADPH level, γ-glutamylcysteinyl ligase (GCLC) activity and oxidative stress markers were assessed in the hippocampus. Expression of apoptotic marker caspase 3 in hippocampus was investigated by immunohistochemistry. Transcriptional alteration and expression of GCLC and Nuclear factor (erythroid-derived 2)–related factor 2 (Nrf2) were investigated by real time PCR and immunoblotting respectively. Exposure to hypobaric hypoxia decreased reduced glutathione (GSH) level and impaired reduced gluatathione dependent free radical scavenging system in hippocampus resulting in elevated oxidative stress. Supplementation of withanolide A during hypoxic exposure increased GSH level, augmented GSH dependent free radicals scavenging system and decreased the number of caspase and hoescht positive cells in hippocampus. While withanolide A reversed hypoxia mediated neurodegeneration, administration of buthionine sulfoximine along with withanolide A blunted its neuroprotective effects. Exogenous administration of corticosterone suppressed Nrf2 and GCLC expression whereas inhibition of corticosterone synthesis upregulated Nrf2 as well as GCLC. Thus present study infers that withanolide A reduces neurodegeneration by restoring hypoxia induced glutathione depletion in hippocampus. Further, Withanolide A increases glutathione biosynthesis in neuronal cells by upregulating GCLC level through Nrf2 pathway in a corticosterone dependenet manner

  12. Rat reaction to hypokinesia after prior adaptation to hypoxia

    NASA Technical Reports Server (NTRS)

    Barashova, Z. I.; Tarakanova, O. I.

    1980-01-01

    The effect of prior hypoxia adaptation on body tolerance to hypokinesia was investigated. Rats trained to a 50 day period of hypokinesia and hypoxia with a preliminary month of adaptation to hypoxia showed less weight loss, higher indices for red blood content, heightened reactivity of the overall organism and the central nervous system to acute hypoxia, and decreased modification of the skeletal muscles compared to rats subjected to hypokinesia alone.

  13. Hypoxia: a window into Mycobacterium tuberculosis latency.

    PubMed

    Rustad, Tige R; Sherrid, Ashley M; Minch, Kyle J; Sherman, David R

    2009-08-01

    Tuberculosis is a massive public health problem on a global scale and the success of Mycobacterium tuberculosis is linked to its ability to persist within humans for long periods without causing any overt disease symptoms. Hypoxia is predicted to be a key host-induced stress limiting growth of the pathogen in vivo. However, multiple studies in vitro and in vivo indicate that M. tuberculosis adapts to oxygen limitation by entering into a metabolically altered state, while awaiting the opportunity to reactivate. Molecular signatures of bacteria adapted to hypoxia in vitro are accumulating, although correlations to human disease are only now being established. Similarly, defining the mechanisms that control this adaptation is an active area of research. In this review we discuss the historical precedents linking hypoxia and latency, and the gathering knowledge of M. tuberculosis hypoxic responses. We also examine the role of these responses in tuberculosis latency, and identify promising avenues for future studies.

  14. The blood-brain barrier in hypoxia.

    PubMed

    Lataste, X

    1992-10-01

    The concept of blood-brain barrier has moved over the past years from a passive and relatively immutable structure to a more dynamic interface between blood and brain tissue. The transport mechanisms regulating this adaptative interface might be considered as the most sensitive elements to change such as hypoxia. Among various carrier mediated transports existing at the blood-brain barrier, glucose transport seems to play a predominant role. In severe hypoxia, progressive changes in glucose transport are occurring. These modifications associated with hypoxia can lead to deleterious events when reaching critical threshold. In addition the appearance of vasogenic edema due to changes in cerebral-blood flow, can possibly be prevented by some pharmacological interaction such as the use of selective brain calcium channel blockers.

  15. Hypoxia as a therapy for mitochondrial disease.

    PubMed

    Jain, Isha H; Zazzeron, Luca; Goli, Rahul; Alexa, Kristen; Schatzman-Bone, Stephanie; Dhillon, Harveen; Goldberger, Olga; Peng, Jun; Shalem, Ophir; Sanjana, Neville E; Zhang, Feng; Goessling, Wolfram; Zapol, Warren M; Mootha, Vamsi K

    2016-04-01

    Defects in the mitochondrial respiratory chain (RC) underlie a spectrum of human conditions, ranging from devastating inborn errors of metabolism to aging. We performed a genome-wide Cas9-mediated screen to identify factors that are protective during RC inhibition. Our results highlight the hypoxia response, an endogenous program evolved to adapt to limited oxygen availability. Genetic or small-molecule activation of the hypoxia response is protective against mitochondrial toxicity in cultured cells and zebrafish models. Chronic hypoxia leads to a marked improvement in survival, body weight, body temperature, behavior, neuropathology, and disease biomarkers in a genetic mouse model of Leigh syndrome, the most common pediatric manifestation of mitochondrial disease. Further preclinical studies are required to assess whether hypoxic exposure can be developed into a safe and effective treatment for human diseases associated with mitochondrial dysfunction.

  16. Frequently asked questions in hypoxia research

    PubMed Central

    Wenger, Roland H; Kurtcuoglu, Vartan; Scholz, Carsten C; Marti, Hugo H; Hoogewijs, David

    2015-01-01

    “What is the O2 concentration in a normoxic cell culture incubator?” This and other frequently asked questions in hypoxia research will be answered in this review. Our intention is to give a simple introduction to the physics of gases that would be helpful for newcomers to the field of hypoxia research. We will provide background knowledge about questions often asked, but without straightforward answers. What is O2 concentration, and what is O2 partial pressure? What is normoxia, and what is hypoxia? How much O2 is experienced by a cell residing in a culture dish in vitro vs in a tissue in vivo? By the way, the O2 concentration in a normoxic incubator is 18.6%, rather than 20.9% or 20%, as commonly stated in research publications. And this is strictly only valid for incubators at sea level. PMID:27774480

  17. Kinetic modeling in PET imaging of hypoxia

    PubMed Central

    Li, Fan; Joergensen, Jesper T; Hansen, Anders E; Kjaer, Andreas

    2014-01-01

    Tumor hypoxia is associated with increased therapeutic resistance leading to poor treatment outcome. Therefore the ability to detect and quantify intratumoral oxygenation could play an important role in future individual personalized treatment strategies. Positron Emission Tomography (PET) can be used for non-invasive mapping of tissue oxygenation in vivo and several hypoxia specific PET tracers have been developed. Evaluation of PET data in the clinic is commonly based on visual assessment together with semiquantitative measurements e.g. standard uptake value (SUV). However, dynamic PET contains additional valuable information on the temporal changes in tracer distribution. Kinetic modeling can be used to extract relevant pharmacokinetic parameters of tracer behavior in vivo that reflects relevant physiological processes. In this paper, we review the potential contribution of kinetic analysis for PET imaging of hypoxia. PMID:25250200

  18. Hypoxia as a Therapy for Mitochondrial Disease

    PubMed Central

    Jain, Isha H.; Zazzeron, Luca; Goli, Rahul; Alexa, Kristen; Schatzman-Bone, Stephanie; Dhillon, Harveen; Goldberger, Olga; Peng, Jun; Shalem, Ophir; Sanjana, Neville E.; Zhang, Feng; Goessling, Wolfram; Zapol, Warren M.; Mootha, Vamsi K.

    2016-01-01

    Defects in the mitochondrial respiratory chain (RC) underlie a spectrum of human conditions, ranging from devastating inborn errors of metabolism to aging. We performed a genome-wide, Cas9-mediated screen to identify factors that are protective during RC inhibition. Our results highlight the hypoxia response, an endogenous program evolved to adapt to limiting oxygen availability. Genetic or small molecule activation of the hypoxia response is protective against mitochondrial toxicity in cultured cells and zebrafish models. Chronic hypoxia leads to a marked improvement in survival, body weight, body temperature, behavior, neuropathology and disease biomarkers in a genetic mouse model of Leigh syndrome, the most common pediatric manifestation of mitochondrial disease. Further preclinical studies are required to assess whether hypoxic exposure can be developed into a safe and effective treatment for human diseases associated with mitochondrial dysfunction. PMID:26917594

  19. In Brief: Report finds hypoxia increasing

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2010-09-01

    The occurrence of hypoxia is increasing in coastal waters worldwide and represents a significant threat to the health and economy of U.S. coasts and the Great Lakes, according to a 3 September report issued by the U.S. Interagency Working Group on Harmful Algal Blooms, Hypoxia, and Human Health. The report found that the incidence of hypoxia—low dissolved oxygen that can negatively affect fish and other aquatic species—has increased tenfold globally in the past 50 years and almost thirtyfold in the United States since 1960. Noting that federal research programs are addressing many aspects of eutrophication, enrichment, and hypoxia, the report indicates, “Despite decades of research, however, management efforts to reduce nutrients—particularly from nonpoint sources—and their adverse impacts on coastal ecosystems have not made significant headway, in part due to increased development and population in coastal watersheds.”

  20. Temperature regulation in lizards: effects of hypoxia.

    PubMed

    Hicks, J W; Wood, S C

    1985-05-01

    Temperature regulation during external (lowered lung PO2) and internal hypoxia (anemia) was examined in four species of lizards. Exposure to a hypoxic gas mixture in a thermogradient resulted in the animals lowering their selected (preferred) body temperature. A 50% reduction in the O2 carrying capacity of the blood also reduced the selected body temperature. Lizards "shuttle" when forced to select a temperature either above or below their normal selected temperature. Exposure to hypoxia decreases the upper and lower exit temperatures during shuttling. Furthermore, a decrease in the inspired O2 causes the rate of heating to no longer exceed the rate of cooling as is normal. The behavioral reduction of body temperature and the altered neural and physiological aspects of temperature regulation appear to be generalized responses to impaired O2 transport and not PO2 per se. The reduced body temperature, by lowering metabolic demand, provides an effective, even life-saving, adaptation to hypoxia.

  1. Individual variation in whole-animal hypoxia tolerance is associated with cardiac hypoxia tolerance in a marine teleost

    PubMed Central

    Joyce, William; Ozolina, Karlina; Mauduit, Florian; Ollivier, Hélène; Claireaux, Guy

    2016-01-01

    Hypoxia is a pervasive problem in coastal environments and is predicted to have enduring impacts on aquatic ecosystems. Intraspecific variation in hypoxia tolerance is well documented in fish; however, the factors underlying this variation remain unknown. Here, we investigate the role of the heart in individual hypoxia tolerance of the European sea bass (Dicentrarchus labrax). We found individual whole-animal hypoxia tolerance is a stable trait in sea bass for more than 18 months (duration of study). We next examined in vitro cardiac performance and found myocardial muscle from hypoxia-tolerant individuals generated greater force, with higher rates of contraction and relaxation, than hypoxic-sensitive individuals during hypoxic exposure. Thus, whole-animal hypoxia tolerance is associated with cardiac hypoxia tolerance. As the occurrence of aquatic hypoxia is expected to increase in marine ecosystems, our experimental data suggest that cardiac performance may influence fish survival and distribution. PMID:26740561

  2. Webizing mobile augmented reality content

    NASA Astrophysics Data System (ADS)

    Ahn, Sangchul; Ko, Heedong; Yoo, Byounghyun

    2014-01-01

    This paper presents a content structure for building mobile augmented reality (AR) applications in HTML5 to achieve a clean separation of the mobile AR content and the application logic for scaling as on the Web. We propose that the content structure contains the physical world as well as virtual assets for mobile AR applications as document object model (DOM) elements and that their behaviour and user interactions are controlled through DOM events by representing objects and places with a uniform resource identifier. Our content structure enables mobile AR applications to be seamlessly developed as normal HTML documents under the current Web eco-system.

  3. Augmented reality in medical education?

    PubMed

    Kamphuis, Carolien; Barsom, Esther; Schijven, Marlies; Christoph, Noor

    2014-09-01

    Learning in the medical domain is to a large extent workplace learning and involves mastery of complex skills that require performance up to professional standards in the work environment. Since training in this real-life context is not always possible for reasons of safety, costs, or didactics, alternative ways are needed to achieve clinical excellence. Educational technology and more specifically augmented reality (AR) has the potential to offer a highly realistic situated learning experience supportive of complex medical learning and transfer. AR is a technology that adds virtual content to the physical real world, thereby augmenting the perception of reality. Three examples of dedicated AR learning environments for the medical domain are described. Five types of research questions are identified that may guide empirical research into the effects of these learning environments. Up to now, empirical research mainly appears to focus on the development, usability and initial implementation of AR for learning. Limited review results reflect the motivational value of AR, its potential for training psychomotor skills and the capacity to visualize the invisible, possibly leading to enhanced conceptual understanding of complex causality.

  4. Augmented reality in medical education?

    PubMed

    Kamphuis, Carolien; Barsom, Esther; Schijven, Marlies; Christoph, Noor

    2014-09-01

    Learning in the medical domain is to a large extent workplace learning and involves mastery of complex skills that require performance up to professional standards in the work environment. Since training in this real-life context is not always possible for reasons of safety, costs, or didactics, alternative ways are needed to achieve clinical excellence. Educational technology and more specifically augmented reality (AR) has the potential to offer a highly realistic situated learning experience supportive of complex medical learning and transfer. AR is a technology that adds virtual content to the physical real world, thereby augmenting the perception of reality. Three examples of dedicated AR learning environments for the medical domain are described. Five types of research questions are identified that may guide empirical research into the effects of these learning environments. Up to now, empirical research mainly appears to focus on the development, usability and initial implementation of AR for learning. Limited review results reflect the motivational value of AR, its potential for training psychomotor skills and the capacity to visualize the invisible, possibly leading to enhanced conceptual understanding of complex causality. PMID:24464832

  5. PRP Augmentation for ACL Reconstruction.

    PubMed

    Andriolo, Luca; Di Matteo, Berardo; Kon, Elizaveta; Filardo, Giuseppe; Venieri, Giulia; Marcacci, Maurilio

    2015-01-01

    Current research is investigating new methods to enhance tissue healing to speed up recovery time and decrease the risk of failure in Anterior Cruciate Ligament (ACL) reconstructive surgery. Biological augmentation is one of the most exploited strategies, in particular the application of Platelet Rich Plasma (PRP). Aim of the present paper is to systematically review all the preclinical and clinical papers dealing with the application of PRP as a biological enhancer during ACL reconstructive surgery. Thirty-two studies were included in the present review. The analysis of the preclinical evidence revealed that PRP was able to improve the healing potential of the tendinous graft both in terms of histological and biomechanical performance. Looking at the available clinical evidence, results were not univocal. PRP administration proved to be a safe procedure and there were some evidences that it could favor the donor site healing in case of ACL reconstruction with patellar tendon graft and positively contribute to graft maturation over time, whereas the majority of the papers did not show beneficial effects in terms of bony tunnels/graft area integration. Furthermore, PRP augmentation did not provide superior functional results at short term evaluation. PMID:26064903

  6. Hypoxia inducible factor pathway inhibitors as anticancer therapeutics

    PubMed Central

    Burroughs, Sarah K; Kaluz, Stefan; Wang, Danzhu; Wang, Ke

    2013-01-01

    Hypoxia is a significant feature of solid tumor cancers. Hypoxia leads to a more malignant phenotype that is resistant to chemotherapy and radiation, is more invasive and has greater metastatic potential. Hypoxia activates the hypoxia inducible factor (HIF) pathway, which mediates the biological effects of hypoxia in tissues. The HIF complex acts as a transcription factor for many genes that increase tumor survival and proliferation. To date, many HIF pathway inhibitors indirectly affect HIF but there have been no clinically approved direct HIF inhibitors. This can be attributed to the complexity of the HIF pathway, as well as to the challenges of inhibiting protein–protein interactions. PMID:23573973

  7. Effect of hypobaric hypoxia on immune function in albino rats

    NASA Astrophysics Data System (ADS)

    SaiRam, M.; Sharma, S. K.; Dipti, P.; Pauline, T.; Kain, A. K.; Mongia, S. S.; Bansal, Anju; Patra, B. D.; Ilavazhagan, G.; Devendra, K.; Selvamurthy, W.

    The effect of exposure to hypoxia on macrophage activity, lymphocyte function and oxidative stress was investigated. Hypoxia enhanced peritoneal macrophage activity as revealed by enhanced phagocytosis and free radical production. There was no significant change in antibody titres to sheep red blood cells in either serum or spleen during hypoxia. However, there was a considerable reduction in the delayed-type hypersensitivity response to sheep red blood cells, indicating the impairment of T-cell activity. Hypoxia decreased the blood glutathione (reduced) level and increased plasma malondialdehyde by a factor of about 2. It is therefore speculated that hypoxia imposes an oxidative stress leading to decreased T-cell acivity.

  8. Transcriptomic Changes Triggered by Hypoxia: Evidence for HIF-1α -Independent, [Na+]i/[K+]i-Mediated, Excitation-Transcription Coupling

    PubMed Central

    Koltsova, Svetlana V.; Shilov, Boris; Birulina, Julia G.; Akimova, Olga A.; Haloui, Mounsif; Kapilevich, Leonid V.; Gusakova, Svetlana V.; Tremblay, Johanne; Hamet, Pavel; Orlov, Sergei N.

    2014-01-01

    This study examines the relative impact of canonical hypoxia-inducible factor-1alpha- (HIF-1α and Na+i/K+i-mediated signaling on transcriptomic changes evoked by hypoxia and glucose deprivation. Incubation of RASMC in ischemic conditions resulted in ∼3-fold elevation of [Na+]i and 2-fold reduction of [K+]i. Using global gene expression profiling we found that Na+,K+-ATPase inhibition by ouabain or K+-free medium in rat aortic vascular smooth muscle cells (RASMC) led to the differential expression of dozens of genes whose altered expression was previously detected in cells subjected to hypoxia and ischemia/reperfusion. For further investigations, we selected Cyp1a1, Fos, Atf3, Klf10, Ptgs2, Nr4a1, Per2 and Hes1, i.e. genes possessing the highest increments of expression under sustained Na+,K+-ATPase inhibition and whose implication in the pathogenesis of hypoxia was proved in previous studies. In ouabain-treated RASMC, low-Na+, high-K+ medium abolished amplification of the [Na+]i/[K+]i ratio as well as the increased expression of all tested genes. In cells subjected to hypoxia and glucose deprivation, dissipation of the transmembrane gradient of Na+ and K+ completely eliminated increment of Fos, Atf3, Ptgs2 and Per2 mRNAs and sharply diminished augmentation expression of Klf10, Edn1, Nr4a1 and Hes1. In contrast to low-Na+, high-K+ medium, RASMC transfection with Hif-1a siRNA attenuated increments of Vegfa, Edn1, Klf10 and Nr4a1 mRNAs triggered by hypoxia but did not impact Fos, Atf3, Ptgs2 and Per2 expression. Thus, our investigation demonstrates, for the first time, that Na+i/K+i-mediated, Hif-1α- -independent excitation-transcription coupling contributes to transcriptomic changes evoked in RASMC by hypoxia and glucose deprivation. PMID:25375852

  9. SWI/SNF regulates the cellular response to hypoxia.

    PubMed

    Kenneth, Niall S; Mudie, Sharon; van Uden, Patrick; Rocha, Sonia

    2009-02-13

    Hypoxia induces a variety of cellular responses such as cell cycle arrest, apoptosis, and autophagy. Most of these responses are mediated by the hypoxia-inducible factor-1alpha. To induce target genes, hypoxia-inducible factor-1alpha requires a chromatin environment conducive to allow binding to specific sequences. Here, we have studied the role of the chromatin-remodeling complex SWI/SNF in the cellular response to hypoxia. We find that SWI/SNF is required for several of the cellular responses induced by hypoxia. Surprisingly, hypoxia-inducible factor-1alpha is a direct target of the SWI/SNF chromatin-remodeling complex. SWI/SNF components are found associated with the hypoxia-inducible factor-1alpha promoter and modulation of SWI/SNF levels results in pronounced changes in hypoxia-inducible factor-1alpha expression and its ability to transactivate target genes. Furthermore, impairment of SWI/SNF function renders cells resistant to hypoxia-induced cell cycle arrest. These results reveal a previously uncharacterized dependence of hypoxia signaling on the SWI/SNF complex and demonstrate a new level of control over the hypoxia-inducible factor-1alpha system.

  10. Pre- and Perinatal Ischemia-Hypoxia, the Ischemia-Hypoxia Response Pathway, and ADHD Risk.

    PubMed

    Smith, Taylor F; Schmidt-Kastner, Rainald; McGeary, John E; Kaczorowski, Jessica A; Knopik, Valerie S

    2016-05-01

    This review focuses on how measured pre- and perinatal environmental and (epi)genetic risk factors are interrelated and potentially influence one, of many, common developmental pathway towards ADHD. Consistent with the Developmental Origins of Health and Disease hypothesis, lower birth weight is associated with increased ADHD risk. Prenatal ischemia-hypoxia (insufficient blood and oxygen supply in utero) is a primary pathway to lower birth weight and produces neurodevelopmental risk for ADHD. To promote tissue survival in the context of ischemia-hypoxia, ischemia-hypoxia response (IHR) pathway gene expression is altered in the developing brain and peripheral tissues. Although altered IHR gene expression is adaptive in the context of ischemia-hypoxia, lasting IHR epigenetic modifications may lead to increased ADHD risk. Taken together, IHR genetic vulnerability to ischemia-hypoxia and IHR epigenetic alterations following prenatal ischemia-hypoxia may result in neurodevelopmental vulnerability for ADHD. Limitations of the extant literature and future directions for genetically-informed research are discussed. PMID:26920003

  11. The hypoxia signaling pathway and hypoxic adaptation in fishes.

    PubMed

    Xiao, Wuhan

    2015-02-01

    The hypoxia signaling pathway is an evolutionarily conserved cellular signaling pathway present in animals ranging from Caenorhabditis elegans to mammals. The pathway is crucial for oxygen homeostasis maintenance. Hypoxia-inducible factors (HIF-1α and HIF-2α) are master regulators in the hypoxia signaling pathway. Oxygen concentrations vary a lot in the aquatic environment. To deal with this, fishes have adapted and developed varying strategies for living in hypoxic conditions. Investigations into the strategies and mechanisms of hypoxia adaptation in fishes will allow us to understand fish speciation and breed hypoxia-tolerant fish species/strains. This review summarizes the process of the hypoxia signaling pathway and its regulation, as well as the mechanism of hypoxia adaptation in fishes.

  12. Multimodality imaging of hypoxia in preclinical settings

    PubMed Central

    Mason, Ralph P.; Zhao, Dawen; Pacheco-Torres, Jesús; Cui, Weina; Kodibagkar, Vikram D.; Gulaka, Praveen K.; Hao, Guiyang; Thorpe, Philip; Hahn, Eric W.; Peschke, Peter

    2011-01-01

    Hypoxia has long been recognized to influence solid tumor response to therapy. Increasingly, hypoxia has also been implicated in tumor aggressiveness, including growth, development and metastatic potential. Thus, there is a fundamental, as well as a clinical interest, in assessing in situ tumor hypoxia. This review will examine diverse approaches focusing on the pre-clinical setting, particularly, in rodents. The strategies are inevitably a compromise in terms of sensitivity, precision, temporal and spatial resolution, as well as cost, feasibility, ease and robustness of implementation. We will review capabilities of multiple modalities and examine what makes them particularly suitable for investigating specific aspects of tumor pathophysiology. Current approaches range from nuclear imaging to magnetic resonance and optical, with varying degrees of invasiveness and ability to examine spatial heterogeneity, as well as dynamic response to interventions. Ideally, measurements would be non-invasive, exploiting endogenous reporters to reveal quantitatively local oxygen tension dynamics. A primary focus of this review is magnetic resonance imaging (MRI) based techniques, such as 19F MRI oximetry, which reveals not only hypoxia in vivo, but more significantly, spatial distribution of pO2 quantitatively, with a precision relevant to radiobiology. It should be noted that pre-clinical methods may have very different criteria for acceptance, as compared with potential investigations for prognostic radiology or predictive biomarkers suitable for use in patients. PMID:20639813

  13. GULF OF MEXICO HYPOXIA MONITORING AND MODELING

    EPA Science Inventory

    Greene, Richard M. and Russell G. Kreis. In press. Gulf of Mexico Hypoxia Monitoring and Modeling (Abstract). To be presented at the EPA Science Forum: Healthy Communities and Ecosystems, 1-3 June 2004, Washington, DC. 1 p. (ERL,GB R990).

    Oxygen-depleted or hypoxic bottom...

  14. Acridine-intercalator based hypoxia selective cytotoxins

    DOEpatents

    Papadopoulou-Rosenzweig, M.; Bloomer, W.D.

    1994-03-15

    Hypoxia selective cytotoxins of the general formula STR1 wherein n is from 1 to 5, and NO[sub 2] is in at least one of the 2, 4 or 5-positions of the imidazole are developed. Such compounds have utility as radiosensitizers and chemosensitizers. 9 figs.

  15. Acridine-intercalator based hypoxia selective cytotoxins

    DOEpatents

    Papadopoulou-Rosenzweig, Maria; Bloomer, William D.; Bloomer, William D.

    1994-01-01

    Hypoxia selective cytotoxins of the general formula ##STR1## wherein n is from 1 to 5, and NO.sub.2 is in at least one of the 2, 4 or 5-positions of the imidazole. Such compounds have utility as radiosensitizers and chemosensitizers.

  16. Bioremediation: When is augmentation needed?

    SciTech Connect

    Forsyth, J.V.; Tsao, Y.M.; Bleam, R.D.

    1995-12-31

    Each contaminated site exhibits different characteristics and requires a site-specific remediation plan. The decontamination of a hazardous materials site is a complex procedure involving systematic, step-by-step problem solving. Assessing the conditions necessary to optimize the efficiency of microbial systems in degrading environmental pollutants and the economics required is essential in selecting and implementing cost-effective biotreatment. This assessment requires a good understanding of the microorganisms themselves. A firm grasp of the conditions under which the appropriate mixed culture system can be established and maintained to achieve the desired biodegradation tasks is necessary. The final component, and perhaps the most critical, is the translation of the scientific data into cost-effective full-scale cleanup processes. Augmentation with proven contaminant-degrading microorganisms leads to a higher degree of confidence in remediation success, and for certain sites has been shown to save time and money over alternative approaches.

  17. LOFT Augmented Operator Capability Program

    SciTech Connect

    Hollenbeck, D.A.; Krantz, E.A.; Hunt, G.L.; Meyer, O.R.

    1980-01-01

    The outline of the LOFT Augmented Operator Capability Program is presented. This program utilizes the LOFT (Loss-of-Fluid Test) reactor facility which is located at the Idaho National Engineering Laboratory and the LOFT operational transient experiment series as a test bed for methods of enhancing the reactor operator's capability for safer operation. The design of an Operational Diagnotics and Display System is presented which was backfit to the existing data acquisition computers. Basic color-graphic displays of the process schematic and trend type are presented. In addition, displays were developed and are presented which represent safety state vector information. A task analysis method was applied to LOFT reactor operating procedures to test its usefulness in defining the operator's information needs and workload.

  18. Sensory Augmentation for the Blind

    PubMed Central

    Kärcher, Silke M.; Fenzlaff, Sandra; Hartmann, Daniela; Nagel, Saskia K.; König, Peter

    2012-01-01

    Common navigational aids used by blind travelers during large-scale navigation divert attention away from important cues of the immediate environment (i.e., approaching vehicles). Sensory augmentation devices, relying on principles similar to those at work in sensory substitution, can potentially bypass the bottleneck of attention through sub-cognitive implementation of a set of rules coupling motor actions with sensory stimulation. We provide a late blind subject with a vibrotactile belt that continually signals the direction of magnetic north. The subject completed a set of behavioral tests before and after an extended training period. The tests were complemented by questionnaires and interviews. This newly supplied information improved performance on different time scales. In a pointing task we demonstrate an instant improvement of performance based on the signal provided by the device. Furthermore, the signal was helpful in relevant daily tasks, often complicated for the blind, such as keeping a direction over longer distances or taking shortcuts in familiar environments. A homing task with an additional attentional load demonstrated a significant improvement after training. The subject found the directional information highly expedient for the adjustment of his inner maps of familiar environments and describes an increase in his feeling of security when exploring unfamiliar environments with the belt. The results give evidence for a firm integration of the newly supplied signals into the behavior of this late blind subject with better navigational performance and more courageous behavior in unfamiliar environments. Most importantly, the complementary information provided by the belt lead to a positive emotional impact with enhanced feeling of security. The present experimental approach demonstrates the positive potential of sensory augmentation devices for the help of handicapped people. PMID:22403535

  19. Augmented Reality for Close Quarters Combat

    ScienceCinema

    None

    2016-07-12

    Sandia National Laboratories has developed a state-of-the-art augmented reality training system for close-quarters combat (CQB). This system uses a wearable augmented reality system to place the user in a real environment while engaging enemy combatants in virtual space (Boston Dynamics DI-Guy). Umbra modeling and simulation environment is used to integrate and control the AR system.

  20. Status report of RMS active damping augmentation

    NASA Technical Reports Server (NTRS)

    Gilbert, Mike; Demeo, Martha E.

    1993-01-01

    A status report of Remote Manipulator System (RMS) active damping augmentation is presented. Topics covered include: active damping augmentation; benefits of RMS ADA; simulated payload definition; sensor and actuator definition; ADA control law design; Shuttle Engineering Simulator (SES) real-time simulation; and astronaut evaluation.

  1. From Augmentation Media to Meme Media.

    ERIC Educational Resources Information Center

    Tanaka, Yuzuru

    Computers as meta media are now evolving from augmentation media vehicles to meme media vehicles. While an augmentation media system provides a seamlessly integrated environment of various tools and documents, meme media system provides further functions to edit and distribute tools and documents. Documents and tools on meme media can easily…

  2. Enhancing Education through Mobile Augmented Reality

    ERIC Educational Resources Information Center

    Joan, D. R. Robert

    2015-01-01

    In this article, the author has discussed about the Mobile Augmented Reality and enhancing education through it. The aim of the present study was to give some general information about mobile augmented reality which helps to boost education. Purpose of the current study reveals the mobile networks which are used in the institution campus as well…

  3. Embedding Augmentative Communication within Early Childhood Classrooms.

    ERIC Educational Resources Information Center

    DiCarlo, Cynthia; Banajee, Meher; Stricklin, Sarintha Buras

    2000-01-01

    This article first describes various augmentative communication systems including sign language, picture symbols, and voice output communication devices. It then explains ways to embed augmentative communication within four types of early childhood classroom activities: (1) special or planned activities, (2) meal time, (3) circle time, and (4)…

  4. Age grouping to optimize augmentation success.

    PubMed

    Gordon, Robert W

    2010-05-01

    This article has described the different age groups that present for noninvasive injectable lip and perioral augmentation, as well as the breakdown of 3 subgroups that present within the 4 general age groups. With the fundamental understanding of these presenting groups and subgroups, the practicing augmenter will be able to better treatment plan and educate the patient on realistic and optimal aesthetic outcomes.

  5. Nonsteady-Flow Thrust Augmenting Ejectors

    NASA Technical Reports Server (NTRS)

    Foa, J. V.

    1979-01-01

    Ejector augmenters in which the transfer of mechanical energy from the primary to the secondary flow takes place through the work of interface pressure forces are investigated. Nonsteady flow processes are analyzed from the standpoint of energy transfer efficiency and a comparison of a rotary jet augmenter to an ejector is presented.

  6. Augmented Reality for Close Quarters Combat

    SciTech Connect

    2013-09-20

    Sandia National Laboratories has developed a state-of-the-art augmented reality training system for close-quarters combat (CQB). This system uses a wearable augmented reality system to place the user in a real environment while engaging enemy combatants in virtual space (Boston Dynamics DI-Guy). Umbra modeling and simulation environment is used to integrate and control the AR system.

  7. Irradiated homologous costal cartilage for augmentation rhinoplasty

    SciTech Connect

    Lefkovits, G. )

    1990-10-01

    Although the ideal reconstructive material for augmentation rhinoplasty continues to challenge plastic surgeons, there exists no report in the literature that confines the use of irradiated homologous costal cartilage, first reported by Dingman and Grabb in 1961, to dorsal nasal augmentation. The purpose of this paper is to present a retrospective analysis of the author's experience using irradiated homologous costal cartilage in augmentation rhinoplasty. Twenty-seven dorsal nasal augmentations were performed in 24 patients between 16 and 49 years of age with a follow-up ranging from 1 to 27 months. Good-to-excellent results were achieved in 83.3% (20 of 24). Poor results requiring revision were found in 16.7% (4 of 24). Complication rates included 7.4% infection (2 of 27) and 14.8% warping (4 of 27). The resorption rate was zero. These results compare favorably with other forms of nasal augmentation. Advantages and disadvantages of irradiated homologous costal cartilage are discussed.

  8. Performance of a self-augmented railgun

    NASA Astrophysics Data System (ADS)

    Burton, Rodney L.; Witherspoon, F. D.; Goldstein, Shyke A.

    1991-10-01

    The accelerating force of a railgun can be increased by augmenting the self-induced magnetic field created by the armature current. Augmentation fields can be produced by external current coils or, as is done here, by shorting the railgun muzzle, and using the gun rails as the augmentation coil. Experimental results are presented for a 3.6-m railgun operated in this self-augmented mode, and effective inductance gradients are achieved which are as much as 9.3 times that of the unaugmented gun. A circuit model is presented which explains features of the measured shunt current and voltage. It is concluded that self-augmentation is an effective way to reduce ohmic heating in the armature of a railgun.

  9. HIF-1α Promotes A Hypoxia-Independent Cell Migration.

    PubMed

    Li, Liyuan; Madu, Chikezie O; Lu, Andrew; Lu, Yi

    2010-01-01

    Hypoxia-inducible factor-1α (HIF-1α) is known as a transactivator for VEGF gene promoter. It can be induced by hypoxia. However, no study has been done so far to dissect HIF-1α-mediated effects from hypoxia or VEGF-mediated effects. By using a HIF-1α knockout (HIF-1α KO) cell system in mouse embryonic fibroblast (MEF) cells, this study analyzes cell migration and HIF-1α, hypoxia and VEGF activation. A hypoxia-mediated HIF-1α induction and VEGF transactivation were observed: both HIF-1α WT lines had significantly increased VEGF transactivation, as an indicator for HIF-1α induction, in hypoxia compared to normoxia; in contrast, HIF-1α KO line had no increased VEGF transactivation under hypoxia. HIF-1α promotes cell migration: HIF-1α-KO cells had a significantly reduced migration compared to that of the HIF-1α WT cells under both normoxia and hypoxia. The significantly reduced cell migration in HIF-1α KO cells can be partially rescued by the restoration of WT HIF-1α expression mediated by adenoviral-mediated gene transfer. Interestingly, hypoxia has no effect on cell migration: the cells had a similar cell migration rate under hypoxic and normoxic conditions for both HIF-1α WT and HIF-1α KO lines, respectively. Collectively, these data suggest that HIF-1α plays a role in MEF cell migration that is independent from hypoxia-mediated effects.

  10. HIF-1α Promotes A Hypoxia-Independent Cell Migration

    PubMed Central

    Li, Liyuan; Madu, Chikezie O.; Lu, Andrew; Lu, Yi

    2010-01-01

    Hypoxia-inducible factor-1α (HIF-1α) is known as a transactivator for VEGF gene promoter. It can be induced by hypoxia. However, no study has been done so far to dissect HIF-1α-mediated effects from hypoxia or VEGF-mediated effects. By using a HIF-1α knockout (HIF-1α KO) cell system in mouse embryonic fibroblast (MEF) cells, this study analyzes cell migration and HIF-1α, hypoxia and VEGF activation. A hypoxia-mediated HIF-1α induction and VEGF transactivation were observed: both HIF-1α WT lines had significantly increased VEGF transactivation, as an indicator for HIF-1α induction, in hypoxia compared to normoxia; in contrast, HIF-1α KO line had no increased VEGF transactivation under hypoxia. HIF-1α promotes cell migration: HIF-1α-KO cells had a significantly reduced migration compared to that of the HIF-1α WT cells under both normoxia and hypoxia. The significantly reduced cell migration in HIF-1α KO cells can be partially rescued by the restoration of WT HIF-1α expression mediated by adenoviral-mediated gene transfer. Interestingly, hypoxia has no effect on cell migration: the cells had a similar cell migration rate under hypoxic and normoxic conditions for both HIF-1α WT and HIF-1α KO lines, respectively. Collectively, these data suggest that HIF-1α plays a role in MEF cell migration that is independent from hypoxia-mediated effects. PMID:20882121

  11. Hypoxia induces adipogenic differentitation of myoblastic cell lines

    SciTech Connect

    Itoigawa, Yoshiaki; Kishimoto, Koshi N.; Okuno, Hiroshi; Sano, Hirotaka; Kaneko, Kazuo; Itoi, Eiji

    2010-09-03

    Research highlights: {yields} C2C12 and G8 myogenic cell lines treated by hypoxia differentiate into adipocytes. {yields} The expression of C/EBP{beta}, {alpha} and PPAR{gamma} were increased under hypoxia. {yields} Myogenic differentiation of C2C12 was inhibited under hypoxia. -- Abstract: Muscle atrophy usually accompanies fat accumulation in the muscle. In such atrophic conditions as back muscles of kyphotic spine and the rotator cuff muscles with torn tendons, blood flow might be diminished. It is known that hypoxia causes trans-differentiation of mesenchymal stem cells derived from bone marrow into adipocytes. However, it has not been elucidated yet if hypoxia turned myoblasts into adipocytes. We investigated adipogenesis in C2C12 and G8 murine myogenic cell line treated by hypoxia. Cells were also treated with the cocktail of insulin, dexamethasone and IBMX (MDI), which has been known to inhibit Wnt signaling and promote adipogenesis. Adipogenic differentiation was seen in both hypoxia and MDI. Adipogenic marker gene expression was assessed in C2C12. CCAAT/enhancer-binding protein (C/EBP) {beta}, {alpha} and peroxisome proliferator activating receptor (PPAR) {gamma} were increased by both hypoxia and MDI. The expression profile of Wnt10b was different between hypoxia and MDI. The mechanism for adipogenesis of myoblasts in hypoxia might be regulated by different mechanism than the modification of Wnt signaling.

  12. Transcriptional up-regulation of inhibitory PAS domain protein gene expression by hypoxia-inducible factor 1 (HIF-1): a negative feedback regulatory circuit in HIF-1-mediated signaling in hypoxic cells.

    PubMed

    Makino, Yuichi; Uenishi, Rie; Okamoto, Kensaku; Isoe, Tsubasa; Hosono, Osamu; Tanaka, Hirotoshi; Kanopka, Arvydas; Poellinger, Lorenz; Haneda, Masakazu; Morimoto, Chikao

    2007-05-11

    The inhibitory PAS (Per/Arnt/Sim) domain protein (IPAS), a dominant negative regulator of hypoxia-inducible transcription factors (HIFs), is potentially implicated in negative regulation of angiogenesis in such tissues as the avascular cornea of the eye. We have previously shown IPAS mRNA expression is up-regulated in hypoxic tissues, which at least in part involves hypoxia-dependent alternative splicing of the transcripts from the IPAS/HIF-3alpha locus. In the present study, we demonstrate that a hypoxia-driven transcriptional mechanism also plays a role in augmentation of IPAS gene expression. Isolation and analyses of the promoter region flanking to the first exon of IPAS gene revealed a functional hypoxia response element at position -834 to -799, whereas the sequence upstream of the HIF-3alpha first exon scarcely responded to hypoxic stimuli. A transient transfection experiment demonstrated that HIF-1alpha mediates IPAS promoter activation via the functional hypoxia response element under hypoxic conditions and that a constitutively active form of HIF-1alpha is sufficient for induction of the promoter in normoxic cells. Moreover, chromatin immunoprecipitation and electrophoretic mobility shift assays showed binding of the HIF-1 complex to the element in a hypoxia-dependent manner. Taken together, HIF-1 directly up-regulates IPAS gene expression through a mechanism distinct from RNA splicing, providing a further level of negative feedback gene regulation in adaptive responses to hypoxic/ischemic conditions. PMID:17355974

  13. Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease.

    PubMed

    Manukhina, Eugenia B; Downey, H Fred; Shi, Xiangrong; Mallet, Robert T

    2016-06-01

    Alzheimer's disease (AD) is a leading cause of death and disability among older adults. Modifiable vascular risk factors for AD (VRF) include obesity, hypertension, type 2 diabetes mellitus, sleep apnea, and metabolic syndrome. Here, interactions between cerebrovascular function and development of AD are reviewed, as are interventions to improve cerebral blood flow and reduce VRF. Atherosclerosis and small vessel cerebral disease impair metabolic regulation of cerebral blood flow and, along with microvascular rarefaction and altered trans-capillary exchange, create conditions favoring AD development. Although currently there are no definitive therapies for treatment or prevention of AD, reduction of VRFs lowers the risk for cognitive decline. There is increasing evidence that brief repeated exposures to moderate hypoxia, i.e. intermittent hypoxic training (IHT), improve cerebral vascular function and reduce VRFs including systemic hypertension, cardiac arrhythmias, and mental stress. In experimental AD, IHT nearly prevented endothelial dysfunction of both cerebral and extra-cerebral blood vessels, rarefaction of the brain vascular network, and the loss of neurons in the brain cortex. Associated with these vasoprotective effects, IHT improved memory and lessened AD pathology. IHT increases endothelial production of nitric oxide (NO), thereby increasing regional cerebral blood flow and augmenting the vaso- and neuroprotective effects of endothelial NO. On the other hand, in AD excessive production of NO in microglia, astrocytes, and cortical neurons generates neurotoxic peroxynitrite. IHT enhances storage of excessive NO in the form of S-nitrosothiols and dinitrosyl iron complexes. Oxidative stress plays a pivotal role in the pathogenesis of AD, and IHT reduces oxidative stress in a number of experimental pathologies. Beneficial effects of IHT in experimental neuropathologies other than AD, including dyscirculatory encephalopathy, ischemic stroke injury, audiogenic

  14. Chronic intermittent hypoxia exposure-induced atherosclerosis: a brief review.

    PubMed

    Song, Dongmei; Fang, Guoqiang; Greenberg, Harly; Liu, Shu Fang

    2015-12-01

    Obstructive sleep apnea (OSA) is highly prevalent in the USA and is recognized as an independent risk factor for atherosclerotic cardiovascular disease. Identification of atherosclerosis risk factor attributable to OSA may provide opportunity to develop preventive measures for cardiovascular risk reduction. Chronic intermittent hypoxia (CIH) is a prominent feature of OSA pathophysiology and may be a major mechanism linking OSA to arteriosclerosis. Animal studies demonstrated that CIH exposure facilitated high-cholesterol diet (HCD)-induced atherosclerosis, accelerated the progression of existing atherosclerosis, and induced atherosclerotic lesions in the absence of other atherosclerosis risk factors, demonstrating that CIH is an independent causal factor of atherosclerosis. Comparative studies revealed major differences between CIH-induced and the classic HCD-induced atherosclerosis. Systemically, CIH was a much weaker inducer of atherosclerosis. CIH and HCD differentially activated inflammatory pathways. Histologically, CIH-induced atherosclerotic plaques had no clear necrotic core, contained a large number of CD31+ endothelial cells, and had mainly elastin deposition, whereas HCD-induced plaques had typical necrotic cores and fibrous caps, contained few endothelial cells, and had mainly collagen deposition. Metabolically, CIH caused mild, but HCD caused more severe dyslipidemia. Mechanistically, CIH did not, but HCD did, cause macrophage foam cell formation. NF-κB p50 gene deletion augmented CIH-induced, but not HCD-induced atherosclerosis. These differences reflect the intrinsic differences between the two types of atherosclerosis in terms of pathological nature and underlying mechanisms and support the notion that CIH-induced atherosclerosis is a new paradigm that differs from the classic HCD-induced atherosclerosis.

  15. Psychomotor skills learning under chronic hypoxia.

    PubMed

    Bouquet, C A; Gardette, B; Gortan, C; Abraini, J H

    1999-09-29

    Psychomotor deficits are a prominent feature in subjects exposed to hypoxia. Eight subjects exposed to chronic hypoxia during a simulated climb to 8848 m (Everest-Comex 97) were investigated using both a simple psychomotor task (Purdue pegboard) and two complex psychomotor tasks including a recognition task of either a color stimulus (high semantic level) or an abstract sign (low semantic level). Exposure to hypoxic stress mainly produced psychomotor skills learning deficits compared to control study, with greater deficits in the complex psychomotor task. The pattern of results suggests disruptions of motor strategic process. Our data further suggest that the relative strength of implicit or automatic memory processes associated with semantic information processing may increase when disturbances occur in brain functions.

  16. Tumor hypoxia as a driving force in genetic instability

    PubMed Central

    2013-01-01

    Sub-regions of hypoxia exist within all tumors and the presence of intratumoral hypoxia has an adverse impact on patient prognosis. Tumor hypoxia can increase metastatic capacity and lead to resistance to chemotherapy and radiotherapy. Hypoxia also leads to altered transcription and translation of a number of DNA damage response and repair genes. This can lead to inhibition of recombination-mediated repair of DNA double-strand breaks. Hypoxia can also increase the rate of mutation. Therefore, tumor cell adaptation to the hypoxic microenvironment can drive genetic instability and malignant progression. In this review, we focus on hypoxia-mediated genetic instability in the context of aberrant DNA damage signaling and DNA repair. Additionally, we discuss potential therapeutic approaches to specifically target repair-deficient hypoxic tumor cells. PMID:24152759

  17. Hypoxia Responsive Drug Delivery Systems in Tumor Therapy.

    PubMed

    Alimoradi, Houman; Matikonda, Siddharth S; Gamble, Allan B; Giles, Gregory I; Greish, Khaled

    2016-01-01

    Hypoxia is a common characteristic of solid tumors. It is mainly determined by low levels of oxygen resulting from imperfect vascular networks supplying most tumors. In an attempt to improve the present chemotherapeutic treatment and reduce associated side effects, several prodrug strategies have been introduced to achieve hypoxia-specific delivery of cytotoxic anticancer agents. With the advances in nanotechnology, novel delivery systems activated by the consequent outcomes of hypoxia have been developed. However, developing hypoxia responsive drug delivery systems (which only depend on low oxygen levels) is currently naïve. This review discusses four main hypoxia responsive delivery systems: polymeric based drug delivery systems, oxygen delivery systems combined with radiotherapy and chemotherapy, anaerobic bacteria which are used for delivery of genes to express anticancer proteins such as tumor necrosis alpha (TNF-α) and hypoxia-inducible transcription factors 1 alpha (HIF1α) responsive gene delivery systems.

  18. Chondrogenic potential and anti-senescence effect of hypoxia on canine adipose mesenchymal stem cells.

    PubMed

    Lee, Jienny; Byeon, Jeong Su; Lee, Keum Sil; Gu, Na-Yeon; Lee, Gyeong Been; Kim, Hee-Ryang; Cho, In-Soo; Cha, Sang-Ho

    2016-03-01

    Mesenchymal stem cells (MSCs) have the ability to differentiate into multi-lineage cells, which confers great promise for use in regenerative medicine. In this study, canine adipose MSCs (cAD-MSCs) were isolated from canine adipose tissue. These cells clearly represented stemness (Oct4, Sox2, and Nanog) and differentiation potential into the mesoderm (adipocytes, chondrocytes, and osteoblasts) at early passages. The aim of this study was to evaluate the effects of hypoxia on the differentiation potential into mesoderm, and the expression of anti-apoptotic genes associated with cell survival for the optimal culturing of MSCs. We observed that the proliferation of the cAD-MSCs meaningfully increased when cultured under hypoxic condition than in normoxic condition, during 7 consecutive passages. Also, we found that hypoxia strongly expressed anti-senescence related genes such as HDAC1 (histone deacetylase 1), DNMT1 (DNA (cytosine-5)-methyltransferase 1), Bcl-2 (inhibitor of apoptosis), TERT (telomerase reverse transcriptase), LDHA (lactate dehydrogenase A), SLC2A1 (glucose transporter), and DKC1 (telomere holoenzyme complex) and differentiation potential of cAD-MSCs into chondrocytes, than seen under the normoxic culture conditions. We also examined the multipotency of hypoxic conditioned MSCs using quantitative real-time RT-PCR. We found that the expression levels of stemness genes such as Oct-4, Nanog, and Sox-2 were increased in hypoxic condition when compared to the normoxic condition. Collectively, these results suggest that hypoxic conditions have the ability to induce proliferation of MSCs and augment their chondrogenic potential. This study suggests that cell proliferation of cAD-MSC under hypoxia could be beneficial, when considering these cells for cell therapies of canine bone diseases.

  19. Roles of microRNA-1 in hypoxia-induced apoptotic insults to neuronal cells.

    PubMed

    Chang, Chia-Yu; Lui, Tai-Ngar; Lin, Jia-Wei; Lin, Yi-Ling; Hsing, Chung-Hsi; Wang, Jhi-Joung; Chen, Ruei-Ming

    2016-01-01

    Hypoxia is a common occurrence in brain tumors and traumatic brain injury. microRNA (miR)-1 participates in the regulation of brain development and neuronal function. Interestingly, miR-1 can mediate ischemia-induced injury to cardiomyocytes. This study was designed to evaluate the roles of miR-1 in hypoxia-induced insults to neurons and the possible mechanisms. Exposure of neuro-2a cells to oxygen/glucose deprivation (OGD) or cobalt chloride decreased cell viability and induced cell apoptosis in time-dependent manners. In parallel, OGD caused augmentation of cellular Bax and cytochrome c levels, a reduction in the mitochondrial membrane potential (MMP), activation of caspase-3, and fragmentation of DNA. miR-1 was induced in neuro-2a cells by OGD. Knocking down miR-1 expression using specific antisense inhibitors significantly alleviated OGD-induced neuronal death. Administration of OGD to neuro-2a cells induced heat-shock protein (HSP)-70 messenger (m)RNA and protein expressions. A bioinformatic search revealed that miR-1-specific binding elements exist in the 3'-untranslated region of HSP-70 mRNA. Overexpression of miR-1 simultaneously attenuated OGD-induced HSP-70 mRNA and protein expressions. In comparison, knocking down miR-1 expression synergistically enhanced OGD-induced HSP-70 mRNA. As to the mechanism, reducing miR-1 expression lowered OGD-induced alterations in the MMP, caspase-3 activation, DNA fragmentation, and cell apoptosis. Taken together, this study shows that miR-1 can target HSP-70 expression and consequently mediate hypoxia-induced apoptotic insults to neuro-2a cells via an intrinsic Bax-mitochondrion-caspase protease pathway. PMID:25238743

  20. Wireless Augmented Reality Prototype (WARP)

    NASA Technical Reports Server (NTRS)

    Devereaux, A. S.

    1999-01-01

    Initiated in January, 1997, under NASA's Office of Life and Microgravity Sciences and Applications, the Wireless Augmented Reality Prototype (WARP) is a means to leverage recent advances in communications, displays, imaging sensors, biosensors, voice recognition and microelectronics to develop a hands-free, tetherless system capable of real-time personal display and control of computer system resources. Using WARP, an astronaut may efficiently operate and monitor any computer-controllable activity inside or outside the vehicle or station. The WARP concept is a lightweight, unobtrusive heads-up display with a wireless wearable control unit. Connectivity to the external system is achieved through a high-rate radio link from the WARP personal unit to a base station unit installed into any system PC. The radio link has been specially engineered to operate within the high- interference, high-multipath environment of a space shuttle or space station module. Through this virtual terminal, the astronaut will be able to view and manipulate imagery, text or video, using voice commands to control the terminal operations. WARP's hands-free access to computer-based instruction texts, diagrams and checklists replaces juggling manuals and clipboards, and tetherless computer system access allows free motion throughout a cabin while monitoring and operating equipment.

  1. Augmented reality: past, present, future

    NASA Astrophysics Data System (ADS)

    Inzerillo, Laura

    2013-03-01

    A great opportunity has permitted to carry out a cultural, historical, architectural and social research with great impact factor on the international cultural interest. We are talking about the realization of a museum whose the main theme is the visit and the discovery of a monument of great prestige: the monumental building the "Steri" in Palermo. The museum is divided into sub themes including the one above all, that has aroused the international interest so much that it has been presented the instance to include the museum in the cultural heritage of UNESCO. It is the realization of a museum path that regards the cells of the Inquisition, which are located just inside of some buildings of the monumental building. The project, as a whole, is faced, in a total view, between the various competences implicated: historic, chemic, architectonic, topographic, drawing, representation, virtual communication, informatics. The birth of the museum will be a sum of the results of all these disciplines involved. Methodology, implementation, fruition, virtual museum, goals, 2D graphic restitution, effects on the cultural heritage and landscape environmental, augmented reality, Surveying 2D and 3D, hi-touch screen, Photogrammetric survey, Photographic survey, representation, drawing 3D and more than this has been dealt with this research.

  2. Augmented reality in surgical procedures

    NASA Astrophysics Data System (ADS)

    Samset, E.; Schmalstieg, D.; Vander Sloten, J.; Freudenthal, A.; Declerck, J.; Casciaro, S.; Rideng, Ø.; Gersak, B.

    2008-02-01

    Minimally invasive therapy (MIT) is one of the most important trends in modern medicine. It includes a wide range of therapies in videoscopic surgery and interventional radiology and is performed through small incisions. It reduces hospital stay-time by allowing faster recovery and offers substantially improved cost-effectiveness for the hospital and the society. However, the introduction of MIT has also led to new problems. The manipulation of structures within the body through small incisions reduces dexterity and tactile feedback. It requires a different approach than conventional surgical procedures, since eye-hand co-ordination is not based on direct vision, but more predominantly on image guidance via endoscopes or radiological imaging modalities. ARIS*ER is a multidisciplinary consortium developing a new generation of decision support tools for MIT by augmenting visual and sensorial feedback. We will present tools based on novel concepts in visualization, robotics and haptics providing tailored solutions for a range of clinical applications. Examples from radio-frequency ablation of liver-tumors, laparoscopic liver surgery and minimally invasive cardiac surgery will be presented. Demonstrators were developed with the aim to provide a seamless workflow for the clinical user conducting image-guided therapy.

  3. Postauricular fascia in augmentation rhinoplasty.

    PubMed

    Guerra, Aldo Benjamin

    2014-06-01

    Ten rhinoplasty operations performed using postauricular fascia for the purpose of augmenting the radix and dorsum of the nose were analyzed retrospectively. All the operations were performed over a 1-year period, between 2005 and 2006. The fascia of the postauricular area has been used as a source of pliable soft-tissue grafts in primary and revision rhinoplasty. It may be easily accessed using a single sulcus incision that also enables harvesting of ear cartilage grafts. Deficiency in the radix is an overlooked abnormality seen in many patients undergoing primary as well as revision rhinoplasty after aggressive hump removal. Recent trends in rhinoplasty have been to avoid the overly reduced nasal skeleton and to create a more balanced nasal surgery result. This article presents the use of the postauricular fascia as a radix graft that has been found to be simple to carry out, reliable, and long lasting. In addition, the fascia graft is useful in the camouflage of various nasal deformities in the dorsum and sidewalls. The average patient follow-up for the study was 24 months.

  4. Humans In Hypoxia: A Conspiracy Of Maladaptation?!

    PubMed Central

    Morgan, Barbara J.

    2015-01-01

    We address adaptive vs. maladaptive responses to hypoxemia in healthy humans and hypoxic-tolerant species during wakefulness, sleep, and exercise. Types of hypoxemia discussed include short-term and life-long residence at high altitudes, the intermittent hypoxemia attending sleep apnea, or training regimens prescribed for endurance athletes. We propose that hypoxia presents an insult to O2 transport, which is poorly tolerated in most humans because of the physiological cost. PMID:26136544

  5. NASA Gulf of Mexico Initiative Hypoxia Research

    NASA Technical Reports Server (NTRS)

    Armstrong, Curtis D.

    2012-01-01

    The Applied Science & Technology Project Office at Stennis Space Center (SSC) manages NASA's Gulf of Mexico Initiative (GOMI). Addressing short-term crises and long-term issues, GOMI participants seek to understand the environment using remote sensing, in-situ observations, laboratory analyses, field observations and computational models. New capabilities are transferred to end-users to help them make informed decisions. Some GOMI activities of interest to the hypoxia research community are highlighted.

  6. Humans In Hypoxia: A Conspiracy Of Maladaptation?!

    PubMed

    Dempsey, Jerome A; Morgan, Barbara J

    2015-07-01

    We address adaptive vs. maladaptive responses to hypoxemia in healthy humans and hypoxic-tolerant species during wakefulness, sleep, and exercise. Types of hypoxemia discussed include short-term and life-long residence at high altitudes, the intermittent hypoxemia attending sleep apnea, or training regimens prescribed for endurance athletes. We propose that hypoxia presents an insult to O2 transport, which is poorly tolerated in most humans because of the physiological cost. PMID:26136544

  7. Upregulation of hypoxia-inducible factors in normal and psoriatic skin.

    PubMed

    Rosenberger, Christian; Solovan, Caius; Rosenberger, Alina D; Jinping, Li; Treudler, Regina; Frei, Ulrich; Eckardt, Kai-Uwe; Brown, Lawrence F

    2007-10-01

    Angiogenesis induced by vascular endothelial growth factor (VEGF) plays an important role in psoriasis. Hypoxic adaptation is conferred through hypoxia-inducible transcription factors (HIFs). VEGF and its receptor Flt-1 are HIF target genes. Growth factors and inflammatory cytokines activate the phosphoinositol-3 kinase pathway, and via activated protein kinase B (phospho-Akt) augment HIF activity. Here, we demonstrate that the major oxygen-dependent HIF isoforms are strongly upregulated in psoriatic skin: HIF-1alpha mainly in the epidermis, in an expression pattern similar to VEGF mRNA; HIF-2alpha in both the epidermis and in capillary endothelial cells of the dermis. In contrast, normal human skin shows low expression of HIF-alpha proteins, with the exception of hair follicles, and glands, which strongly express HIF-1alpha. In normal human skin, phospho-Akt appeared in the basal epidermal layer, in hair follicles, and in dermal glands. In contrast, in psoriasis, phospho-Akt expression was low in the epidermis, but markedly enhanced in the dermal capillaries and in surrounding interstitial/inflammatory cells. Our data suggest that hypoxia initiates a potentially self-perpetuating cycle involving HIF, VEGF, and Akt activation, which could drive physiologic growth of hair follicles and skin glands. Furthermore, such a cycle may exist in psoriasis in dermal capillaries and contribute to disease progression. PMID:17495954

  8. Hypoxia in the changing marine environment

    NASA Astrophysics Data System (ADS)

    Zhang, J.; Cowie, G.; Naqvi, S. W. A.

    2013-03-01

    The predicted future of the global marine environment, as a combined result of forcing due to climate change (e.g. warming and acidification) and other anthropogenic perturbation (e.g. eutrophication), presents a challenge to the sustainability of ecosystems from tropics to high latitudes. Among the various associated phenomena of ecosystem deterioration, hypoxia can cause serious problems in coastal areas as well as oxygen minimum zones in the open ocean (Diaz and Rosenberg 2008 Science 321 926-9, Stramma et al 2008 Science 320 655-8). The negative impacts of hypoxia include changes in populations of marine organisms, such as large-scale mortality and behavioral responses, as well as variations of species distributions, biodiversity, physiological stress, and other sub-lethal effects (e.g. growth and reproduction). Social and economic activities that are related to services provided by the marine ecosystems, such as tourism and fisheries, can be negatively affected by the aesthetic outcomes as well as perceived or real impacts on seafood quality (STAP 2011 (Washington, DC: Global Environment Facility) p 88). Moreover, low oxygen concentration in marine waters can have considerable feedbacks to other compartments of the Earth system, like the emission of greenhouse gases to the atmosphere, and can affect the global biogeochemical cycles of nutrients and trace elements. It is of critical importance to prediction and adaptation strategies that the key processes of hypoxia in marine environments be precisely determined and understood (cf Zhang et al 2010 Biogeosciences 7 1-24).

  9. Optical imaging of tumor hypoxia dynamics

    PubMed Central

    Palmer, Gregory M.; Fontanella, Andrew N.; Zhang, Guoqing; Hanna, Gabi; Fraser, Cassandra L.; Dewhirst, Mark W.

    2010-01-01

    The influence of the tumor microenvironment and hypoxia plays a significant role in determining cancer progression, treatment response, and treatment resistance. That the tumor microenvironment is highly heterogeneous with significant intratumor and intertumor variability presents a significant challenge in developing effective cancer therapies. Critical to understanding the role of the tumor microenvironment is the ability to dynamically quantify oxygen levels in the vasculature and tissue in order to elucidate the roles of oxygen supply and consumption, spatially and temporally. To this end, we describe the use of hyperspectral imaging to characterize hemoglobin absorption to quantify hemoglobin content and oxygen saturation, as well as dual emissive fluorescent∕phosphorescent boron nanoparticles, which serve as ratiometric indicators of tissue oxygen tension. Applying these techniques to a window-chamber tumor model illustrates the role of fluctuations in hemoglobin saturation in driving changes in tissue oxygenation, the two being significantly correlated (r = 0.77). Finally, a green-fluorescence-protein reporter for hypoxia inducible factor-1 (HIF-1) provides an endpoint for hypoxic stress in the tumor, which is used to demonstrate a significant association between tumor hypoxia dynamics and HIF-1 activity in an in vivo demonstration of the technique. PMID:21198195

  10. Structural integration in hypoxia-inducible factors

    SciTech Connect

    Wu, Dalei; Potluri, Nalini; Lu, Jingping; Kim, Youngchang; Rastinejad, Fraydoon

    2015-08-20

    The hypoxia-inducible factors (HIFs) coordinate cellular adaptations to low oxygen stress by regulating transcriptional programs in erythropoiesis, angiogenesis and metabolism. These programs promote the growth and progression of many tumours, making HIFs attractive anticancer targets. Transcriptionally active HIFs consist of HIF-alpha and ARNT (also called HIF-1 beta) subunits. Here we describe crystal structures for each of mouse HIF-2 alpha-ARNT and HIF-1 alpha-ARNT heterodimers in states that include bound small molecules and their hypoxia response element. A highly integrated quaternary architecture is shared by HIF-2 alpha-ARNT and HIF-1 alpha-ARNT, wherein ARNT spirals around the outside of each HIF-alpha subunit. Five distinct pockets are observed that permit small-molecule binding, including PAS domain encapsulated sites and an interfacial cavity formed through subunit heterodimerization. The DNA-reading head rotates, extends and cooperates with a distal PAS domain to bind hypoxia response elements. HIF-alpha mutations linked to human cancers map to sensitive sites that establish DNA binding and the stability of PAS domains and pockets.

  11. Nutrient Enrichment Drives Gulf of Mexico Hypoxia

    NASA Astrophysics Data System (ADS)

    Boesch, Donald F.; Boynton, Walter R.; Crowder, Larry B.; Diaz, Robert J.; Howarth, Robert W.; Mee, Laurence D.; Nixon, Scott W.; Rabalais, Nancy N.; Rosenberg, Rutger; Sanders, James G.; Scavia, Donald; Turner, R. Eugene

    2009-04-01

    During most summers over the past 30 years, bottom dissolved oxygen across a large area of the Louisiana and upper Texas continental shelf declined to concentrations too low (hypoxia) for most fish and large invertebrate animals to survive. This area is one of the best known “dead zones” proliferating around the world [Diaz and Rosenberg, 2008]. During July 2008, hypoxic bottom waters extended across 20,720 square kilometers (Figure 1), but they were probably even more extensive because winds from Hurricane Dolly mixed the waters off Texas before the survey could be completed. Increased inputs of nutrients (principally nitrogen and phosphorus) from the U.S. agricultural heartland within the Mississippi-Atchafalaya River Basin (MARB) are implicated in the development and spread of hypoxia in the Gulf of Mexico. Consequently, the causes of, and solutions for, hypoxia have been subjects of extensive debate and analysis. An integrated scientific assessment led to a 2001 Action Plan [Mississippi River/Gulf of Mexico Watershed Nutrient Task Force, 2001] with a goal of reducing the area of the hypoxic zone to less than 5000 square kilometers by reducing nitrogen loading [Rabalais et al., 2007].

  12. Optical imaging of tumor hypoxia dynamics

    NASA Astrophysics Data System (ADS)

    Palmer, Gregory M.; Fontanella, Andrew N.; Zhang, Guoqing; Hanna, Gabi; Fraser, Cassandra L.; Dewhirst, Mark W.

    2010-11-01

    The influence of the tumor microenvironment and hypoxia plays a significant role in determining cancer progression, treatment response, and treatment resistance. That the tumor microenvironment is highly heterogeneous with significant intratumor and intertumor variability presents a significant challenge in developing effective cancer therapies. Critical to understanding the role of the tumor microenvironment is the ability to dynamically quantify oxygen levels in the vasculature and tissue in order to elucidate the roles of oxygen supply and consumption, spatially and temporally. To this end, we describe the use of hyperspectral imaging to characterize hemoglobin absorption to quantify hemoglobin content and oxygen saturation, as well as dual emissive fluorescent/phosphorescent boron nanoparticles, which serve as ratiometric indicators of tissue oxygen tension. Applying these techniques to a window-chamber tumor model illustrates the role of fluctuations in hemoglobin saturation in driving changes in tissue oxygenation, the two being significantly correlated (r = 0.77). Finally, a green-fluorescence-protein reporter for hypoxia inducible factor-1 (HIF-1) provides an endpoint for hypoxic stress in the tumor, which is used to demonstrate a significant association between tumor hypoxia dynamics and HIF-1 activity in an in vivo demonstration of the technique.

  13. Regulation of gene expression by hypoxia.

    PubMed

    Millhorn, D E; Czyzyk-Krzeska, M; Bayliss, D A; Lawson, E E

    1993-12-01

    The present study was undertaken to determine if gene expression for tyrosine hydroxylase (TH), the rate limiting enzyme in the biosynthesis of catecholamines, is regulated in the carotid body, sympathetic ganglia and adrenal medulla by hypoxia. We found that a reduction in oxygen tension from 21% to 10% caused a substantial increase (200% at 1 hour and 500% at 6 hours exposure) in the concentration of TH mRNA in carotid body type I cells but not in either the sympathetic ganglia or adrenal gland. In addition, we found that hypercapnia, another natural stimulus of carotid body activity, failed to enhance TH mRNA in type I cells. Removal of the sensory and sympathetic innervation of the carotid body failed to prevent the induction of TH mRNA by hypoxia in type I cells. Our results show that TH gene expression is regulated by hypoxia in the carotid body but not in other peripheral catecholamine synthesizing tissue and that the regulatory mechanism is intrinsic to type I cells. PMID:7909954

  14. Imaging hypoxia using 3D photoacoustic spectroscopy

    NASA Astrophysics Data System (ADS)

    Stantz, Keith M.

    2010-02-01

    Purpose: The objective is to develop a multivariate in vivo hemodynamic model of tissue oxygenation (MiHMO2) based on 3D photoacoustic spectroscopy. Introduction: Low oxygen levels, or hypoxia, deprives cancer cells of oxygen and confers resistance to irradiation, some chemotherapeutic drugs, and oxygen-dependent therapies (phototherapy) leading to treatment failure and poor disease-free and overall survival. For example, clinical studies of patients with breast carcinomas, cervical cancer, and head and neck carcinomas (HNC) are more likely to suffer local reoccurrence and metastasis if their tumors are hypoxic. A novel method to non invasively measure tumor hypoxia, identify its type, and monitor its heterogeneity is devised by measuring tumor hemodynamics, MiHMO2. Material and Methods: Simulations are performed to compare tumor pO2 levels and hypoxia based on physiology - perfusion, fractional plasma volume, fractional cellular volume - and its hemoglobin status - oxygen saturation and hemoglobin concentration - based on in vivo measurements of breast, prostate, and ovarian tumors. Simulations of MiHMO2 are performed to assess the influence of scanner resolutions and different mathematic models of oxygen delivery. Results: Sensitivity of pO2 and hypoxic fraction to photoacoustic scanner resolution and dependencies on model complexity will be presented using hemodynamic parameters for different tumors. Conclusions: Photoacoustic CT spectroscopy provides a unique ability to monitor hemodynamic and cellular physiology in tissue, which can be used to longitudinally monitor tumor oxygenation and its response to anti-angiogenic therapies.

  15. Hypoxia enhances aggressiveness of cholangiocarcinoma cells.

    PubMed

    Seubwai, Wunchana; Kraiklang, Ratthaphol; Wongkham, Chaisiri; Wongkham, Sopit

    2012-01-01

    Hypoxia, a common feature of solid tumors, plays a significant role in determining tumor phenotype and tumor progression. In this study, using an in-house PCR-array, we investigated phenotypic changes and differentially expressed hypoxia related genes in the KKU-M213 CCA cell line, cultured under hypoxic (1% O2) condition. Trefoil factor-1 (TFF1), a disintegrin, and metalloprotease 12 (ADAM12), integrin-alpha 5 (ITGA5) and baculoviral IAP repeat-containing 5 (BIRC5/survivin), proteins involved with cell proliferation, metastasis and apoptosis resistance, were up-regulated whereas uridine 5'-monophosphate synthase (UMPS) and S100 calcium binding protein P (S100P), involved with chemosensitivity and cell adhesion, were down-regulated. Growth arrest, apoptosis resistance to UV-irradiation and chemotherapeutic drugs (5- flourouracil, cisplatin, doxorubicin) as well as cell adhesion were thus significantly enhanced upon exposure to hypoxic condition. These findings emphasize the significance of a hypoxic state in the induction of an aggressive phenotype and suggest the potential of targeting hypoxia regulated genes to enhance the sensitivity of chemotherapeutic drug against CCA.

  16. Effects of hypoxia on sympathetic neural control in humans

    NASA Technical Reports Server (NTRS)

    Smith, M. L.; Muenter, N. K.

    2000-01-01

    This special issue is principally focused on the time domain of the adaptive mechanisms of ventilatory responses to short-term, long-term and intermittent hypoxia. The purpose of this review is to summarize the limited literature on the sympathetic neural responses to sustained or intermittent hypoxia in humans and attempt to discern the time domain of these responses and potential adaptive processes that are evoked during short and long-term exposures to hypoxia.

  17. Augmented reality-assisted skull base surgery.

    PubMed

    Cabrilo, I; Sarrafzadeh, A; Bijlenga, P; Landis, B N; Schaller, K

    2014-12-01

    Neuronavigation is widely considered as a valuable tool during skull base surgery. Advances in neuronavigation technology, with the integration of augmented reality, present advantages over traditional point-based neuronavigation. However, this development has not yet made its way into routine surgical practice, possibly due to a lack of acquaintance with these systems. In this report, we illustrate the usefulness and easy application of augmented reality-based neuronavigation through a case example of a patient with a clivus chordoma. We also demonstrate how augmented reality can help throughout all phases of a skull base procedure, from the verification of neuronavigation accuracy to intraoperative image-guidance.

  18. Prolonged lobar hypoxia in vivo enhances the responsivity of isolated pulmonary veins to hypoxia

    NASA Technical Reports Server (NTRS)

    Sheehan, D. W.; Farhi, L. E.; Russell, J. A.

    1992-01-01

    The hypoxic response of pulmonary vessels isolated from eight sheep whose right apical lobes (RAL) had inspired 100% N2 for 20 h was studied. The RAL of these conscious sheep inspired hypoxic gas and the remainder of the lung inspired air. During hypoxia, RAL perfusion was 33 +/- 3% of its air value, carotid arterial PO2 averaged 86 +/- 3 mm Hg and pulmonary perfusion pressure was not significantly different from the initial control period when the RAL inspired air. At the end of the hypoxic exposure, the sheep were killed, and pulmonary artery and vein rings (0.5 to 2 mm inner diameter) were isolated from both the RAL and the right cardiac lobe, which served as the control lobe (CL). Arteries from the RAL and CL did not contract in response to 6% O2/6% CO2/88% N2 (hypoxia). In contrast, RAL veins did contract vigorously in response to hypoxia, whereas CL veins did not contract or contracted only minimally. Rubbing of the endothelium or prior incubation of RAL veins with catalase (1,200 units/ml), indomethacin (10(-5) M), or the thromboxane A2/prostaglandin H2 (TxA2/PGH2) receptor antagonist, SQ 29,548 (3 X 10(-6) M) each significantly reduced the response to hypoxia. RAL veins were also found to be more reactive than CL veins to the prostaglandin endoperoxide analogue U46619. We conclude that prolonged lobar hypoxia in vivo increases the responsivity of isolated pulmonary veins to hypoxia. These contractions may result from an increase in reactive O2 species, which in turn modify production of, metabolism of, and/or tissue responsivity to TxA2/PGH2.

  19. Glioblastoma multiforme: Effect of hypoxia and hypoxia inducible factors on therapeutic approaches

    PubMed Central

    Huang, Wen-Juan; Chen, Wei-Wei; Zhang, Xia

    2016-01-01

    Central nervous system-based cancers have a much higher mortality rate with the 2016 estimates at 6.4 for incidence and 4.3 for deaths per 100,000 individuals. Grade IV astrocytomas, known as glioblastomas are highly aggressive and show a high proliferation index, diffused infiltration, angiogenesis, microvascular proliferation and pleomorphic vessels, resistance to apoptosis, and pseudopalisading necrosis. Extensive hypoxic regions in glioblastomas contribute to the highly malignant phenotype of these tumors. Hypoxic regions of glioblastoma exacerbate the prognosis and clinical outcomes of the patients as hypoxic tumor cells are resistant to chemo- and radiation therapy and are also protected by the malfunctional vasculature that developed due to hypoxia. Predominantly, hypoxia-inducible factor-1α, vascular endothelial growth factor (VEGF)/VEGF receptor, transforming growth factor-β, epidermal growth factor receptor and PI3 kinase/Akt signaling systems are involved in tumor progression and growth. Glioblastomas are predominantly glycolytic and hypoxia-induced factors are useful in the metabolic reprogramming of these tumors. Abnormal vessel formation is crucial in generating pseudopalisading necrosis regions that protect cancer stem cells residing in that region from therapeutic agents and this facilitates the cancer stem cell niche to expand and contribute to cell proliferation and tumor growth. Therapeutic approaches that target hypoxia-induced factors, such as use of the monoclonal antibody against VEGF, bevacizumab, have been useful only in stabilizing the disease but failed to increase overall survival. Hypoxia-activated TH-302, a nitroimidazole prodrug of cytotoxin bromo-isophosphoramide mustard, appears to be more attractive due to its better beneficial effects in glioblastoma patients. A better understanding of the hypoxia-mediated protection of glioblastoma cells is required for developing more effective therapeutics. PMID:27698790

  20. Glioblastoma multiforme: Effect of hypoxia and hypoxia inducible factors on therapeutic approaches

    PubMed Central

    Huang, Wen-Juan; Chen, Wei-Wei; Zhang, Xia

    2016-01-01

    Central nervous system-based cancers have a much higher mortality rate with the 2016 estimates at 6.4 for incidence and 4.3 for deaths per 100,000 individuals. Grade IV astrocytomas, known as glioblastomas are highly aggressive and show a high proliferation index, diffused infiltration, angiogenesis, microvascular proliferation and pleomorphic vessels, resistance to apoptosis, and pseudopalisading necrosis. Extensive hypoxic regions in glioblastomas contribute to the highly malignant phenotype of these tumors. Hypoxic regions of glioblastoma exacerbate the prognosis and clinical outcomes of the patients as hypoxic tumor cells are resistant to chemo- and radiation therapy and are also protected by the malfunctional vasculature that developed due to hypoxia. Predominantly, hypoxia-inducible factor-1α, vascular endothelial growth factor (VEGF)/VEGF receptor, transforming growth factor-β, epidermal growth factor receptor and PI3 kinase/Akt signaling systems are involved in tumor progression and growth. Glioblastomas are predominantly glycolytic and hypoxia-induced factors are useful in the metabolic reprogramming of these tumors. Abnormal vessel formation is crucial in generating pseudopalisading necrosis regions that protect cancer stem cells residing in that region from therapeutic agents and this facilitates the cancer stem cell niche to expand and contribute to cell proliferation and tumor growth. Therapeutic approaches that target hypoxia-induced factors, such as use of the monoclonal antibody against VEGF, bevacizumab, have been useful only in stabilizing the disease but failed to increase overall survival. Hypoxia-activated TH-302, a nitroimidazole prodrug of cytotoxin bromo-isophosphoramide mustard, appears to be more attractive due to its better beneficial effects in glioblastoma patients. A better understanding of the hypoxia-mediated protection of glioblastoma cells is required for developing more effective therapeutics.

  1. Repeated acute hypoxia temporarily attenuates the ventilatory respiratory response to hypoxia in conscious newborn rats.

    PubMed

    Matsuoka, T; Yoda, T; Ushikubo, S; Matsuzawa, S; Sasano, T; Komiyama, A

    1999-07-01

    We asked whether repeated hypoxic exposures during the early neonatal periods could affect the ventilatory control, such as the lung volume-dependent ventilatory inhibition (HBR), pulmonary ventilation (VE), and CO2 production (VCO2). Within each litter of rats, one group of pups (experimental group H) was exposed to 6% O2 (30-min duration twice a day from postnatal d 1 to 4). The other group (control group C) was exposed to air. At 5 d after birth, the HBR was triggered by lung inflation via negative body surface pressure (10 cm H2O). Measurements of VE and VCO2 were done by plethysmography and the inflow-outflow CO2 difference, respectively. At 2 wk of age, VE and VCO2 measurements were repeated by the barometric technique and the inflow-outflow CO2 difference, respectively. Each conscious pup was breathing normoxia (21% O2) and then hypoxia (10% O2). Results were as follows: 1) during normoxia, HBR was stronger and both VE and VCO2 were higher in H pups than in C pups; 2) during hypoxia, the HBR of C was as in normoxia, whereas that of H was increased above the normoxic value; 3) during hypoxia, C maintained VE, whereas H decreased it; 4) in hypoxia, VCO2 was reduced significantly in both groups; 5) at 2 wk of age, VE and VCO2 did not differ between H and C during normoxia or in response to 10% hypoxia. We conclude that in rat pups, repeated hypoxic episodes can modify the HBR and, at least temporarily, reduce the VE response to hypoxia with a decrease in VCO2. The findings are in agreement with the view that repeated hypoxic exposures in the neonatal period could interfere with the development of respiratory control and could possibly be involved in the mechanisms of neonatal apnea or sudden infant death syndrome. PMID:10400145

  2. Declining threshold for hypoxia in the Gulf of Mexico.

    PubMed

    Stow, Craig A; Qian, Song S; Craig, J Kevin

    2005-02-01

    The northwestern Gulf of Mexico shelf has been nicknamed "The Dead Zone" due to annual summertime (May-September) bottom-water hypoxia (dissolved oxygen < or =2 mg L(-1)) that can be extensive (>20 000 km2) and last for several months. Hypoxia has been attributed to eutrophication caused by increasing nitrogen loads, although directly linking hypoxia to nitrogen is difficult. While the areal extent of hypoxia has been shown to increase with Mississippi River flow, it is unclear whether this increase results from enhanced vertical water-column stratification or from eutrophication caused by river-borne nutrients. Disentangling the relative contributions of eutrophication versus stratification has important management consequences. Our analysis indicates that the top:bottom salinity difference is an important predictor of hypoxia, exhibiting a threshold, where the probability of hypoxia increases rapidly, at approximately 4.1 ppt. Using a Bayesian change-point model, we show that this stratification threshold decreased from 1982 to 2002, indicating the degree of stratification needed to induce hypoxia has gone down. Although this declining threshold does not link hypoxia and nitrogen, it does implicate a long-term factor transcending yearly flow-induced stratification differences. Concurrently, we show that surface temperature increased, while surface dissolved oxygen decreased, suggesting that factors in addition to nitrogen may be influencing the incidence of hypoxia in the bottom water.

  3. Imaging tumor hypoxia by near-infrared fluorescence tomography

    NASA Astrophysics Data System (ADS)

    Biswal, Nrusingh C.; Pavlik, Christopher; Smith, Michael B.; Aguirre, Andres; Xu, Yan; Zanganeh, Saeid; Kuhn, Liisa T.; Claffey, Kevin P.; Zhu, Quing

    2011-06-01

    We have developed a novel nitroimidazole indocyanine dye conjugate for tumor-targeted hypoxia fluorescence tomography. The hypoxia probe has been evaluated in vitro using tumor cell lines and in vivo with tumor targeting in mice. The in vitro cell studies were performed to assess fluorescence labeling differences between hypoxia and normoxia conditions. When treated with the hypoxia probe, a fluorescence emission ratio of 2.5-fold was found between the cells incubated under hypoxia compared to the cells in normoxia condition. Hypoxia specificity was also confirmed by comparing the cells treated with indocyanine dye alone. In vivo tumor targeting in mice showed that the fluorescence signals measured at the tumor site were twice those at the normal site after 150 min post-injection of the hypoxia probe. On the other hand, the fluorescence signals measured after injection of indocyanine dye were the same at tumor and normal sites. In vivo fluorescence tomography images of mice injected with the hypoxia probe showed that the probe remained for more than 5 to 7 h in the tumors, however, the images of mice injected with indocyanine only dye confirmed that the unbound dye washed out in less than 3 h. These findings are supported with fluorescence images of histological sections of tumor samples using a Li-COR scanner and immunohistochemistry technique for tumor hypoxia.

  4. Diffuser for augmenting a wind turbine

    DOEpatents

    Foreman, Kenneth M.; Gilbert, Barry L.

    1984-01-01

    A diffuser for augmenting a wind turbine having means for energizing the boundary layer at several locations along the diffuser walls is improved by the addition of a short collar extending radially outward from the outlet of the diffuser.

  5. Improved diffuser for augmenting a wind turbine

    DOEpatents

    Foreman, K.M.; Gilbert, B.L.

    A diffuser for augmenting a wind turbine having means for energizing the boundary layer at several locations along the diffuser walls is improved by the addition of a short collar extending radially outward from the outlet of the diffuser.

  6. Augmented Reality Simulations on Handheld Computers

    ERIC Educational Resources Information Center

    Squire, Kurt; Klopfer, Eric

    2007-01-01

    Advancements in handheld computing, particularly its portability, social interactivity, context sensitivity, connectivity, and individuality, open new opportunities for immersive learning environments. This article articulates the pedagogical potential of augmented reality simulations in environmental engineering education by immersing students in…

  7. Dermal fillers for facial soft tissue augmentation.

    PubMed

    Dastoor, Sarosh F; Misch, Carl E; Wang, Hom-Lay

    2007-01-01

    Nowadays, patients are demanding not only enhancement to their dental (micro) esthetics, but also their overall facial (macro) esthetics. Soft tissue augmentation via dermal filling agents may be used to correct facial defects such as wrinkles caused by age, gravity, and trauma; thin lips; asymmetrical facial appearances; buccal fold depressions; and others. This article will review the pathogenesis of facial wrinkles, history, techniques, materials, complications, and clinical controversies regarding dermal fillers for soft tissue augmentation.

  8. The HART I augmented electric gun facility

    SciTech Connect

    Fikse, D.A.; Ciesar, J.A.; Wehrli, H.A.; Rimersma, H.; Docherty, E.F.; Pipich, C.W. )

    1991-01-01

    This paper reports on an augmented electric gun system that has been commissioned. This system, called HART I (Hypervelocity Augmented Railgun Test), is built around a double augmented rail arrangement with a 1.27-cm square bore. It is powered by the SUVAC II 5.6-MJ distributed capacitor power supply. This arrangement allows operation in a simple, series augmented, or transaugmented gun system configuration. The objective of this facility is to perform materials research augmentation studies, and armature development in the 10-km/s regime. Armature masses of 2 to 4 g will be accelerated in a 4-m long barrel. Baseline bore materials will begin with conventional G9/GlidCop systems and then move into pyrolytic boron nitride/refractory materials. Hybrids, plasma, and ablation stabilized armature systems are planned. The gun system is instrumented with plasma and rail B-dot probes for inbore velocity measurements. In addition, breech and muzzle voltages, currents, and external velocities are measured. The HART I system is currently performing hypervelocity experiments to verify the augmentation models.

  9. Brainstem PCO2 modulates phrenic responses to specific carotid body hypoxia in an in situ dual perfused rat preparation

    PubMed Central

    Day, Trevor A; Wilson, Richard J A

    2007-01-01

    Inputs from central (brainstem) and peripheral (carotid body) respiratory chemoreceptors are coordinated to protect blood gases against potentially deleterious fluctuations. However, the mathematics of the steady-state interaction between chemoreceptors has been difficult to ascertain. Further, how this interaction affects time-dependent phenomena (in which chemoresponses depend upon previous experience) is largely unknown. To determine how central PCO2 modulates the response to peripheral chemostimulation in the rat, we utilized an in situ arterially perfused, vagotomized, decerebrate preparation, in which central and peripheral chemoreceptors were perfused separately (i.e. dual perfused preparation (DPP)). We carried out two sets of experiments: in Experiment 1, we alternated steady-state brainstem PCO2 between 25 and 50 Torr in each preparation, and applied specific carotid body hypoxia (60 Torr PO2 and 40 Torr PCO2) under both conditions; in Experiment 2, we applied four 5 min bouts (separated by 5 min) of specific carotid body hypoxia (60 Torr PO2 and 40 Torr PCO2) while holding the brainstem at either 30 Torr or 50 Torr PCO2. We demonstrate that the level of brainstem PCO2 modulates (a) the magnitude of the phrenic responses to a single step of specific carotid body hypoxia and (b) the magnitude of time-dependent phenomena. We report that the interaction between chemoreceptors is negative (i.e. hypo-additive), whereby a lower brainstem PCO2 augments phrenic responses resulting from specific carotid body hypoxia. A negative interaction may underlie the pathophysiology of central sleep apnoea in populations that are chronically hypocapnic. PMID:17082232

  10. Augmenting digital displays with computation

    NASA Astrophysics Data System (ADS)

    Liu, Jing

    As we inevitably step deeper and deeper into a world connected via the Internet, more and more information will be exchanged digitally. Displays are the interface between digital information and each individual. Naturally, one fundamental goal of displays is to reproduce information as realistically as possible since humans still care a lot about what happens in the real world. Human eyes are the receiving end of such information exchange; therefore it is impossible to study displays without studying the human visual system. In fact, the design of displays is rather closely coupled with what human eyes are capable of perceiving. For example, we are less interested in building displays that emit light in the invisible spectrum. This dissertation explores how we can augment displays with computation, which takes both display hardware and the human visual system into consideration. Four novel projects on display technologies are included in this dissertation: First, we propose a software-based approach to driving multiview autostereoscopic displays. Our display algorithm can dynamically assign views to hardware display zones based on multiple observers' current head positions, substantially reducing crosstalk and stereo inversion. Second, we present a dense projector array that creates a seamless 3D viewing experience for multiple viewers. We smoothly interpolate the set of viewer heights and distances on a per-vertex basis across the arrays field of view, reducing image distortion, crosstalk, and artifacts from tracking errors. Third, we propose a method for high dynamic range display calibration that takes into account the variation of the chrominance error over luminance. We propose a data structure for enabling efficient representation and querying of the calibration function, which also allows user-guided balancing between memory consumption and the amount of computation. Fourth, we present user studies that demonstrate that the ˜ 60 Hz critical flicker fusion

  11. Effect of temperature on hypoxia tolerance and its underlying biochemical mechanism in two juvenile cyprinids exhibiting distinct hypoxia sensitivities.

    PubMed

    He, Wei; Cao, Zhen-Dong; Fu, Shi-Jian

    2015-09-01

    It is increasingly important to investigate the effect of temperature on hypoxia tolerance in fish species, as worldwide hypoxia worsens with increases in global warming. We selected the hypoxia-tolerant crucian carp (Carassius carassius) and the hypoxia-sensitive Chinese bream (Parabramis pekinensis) as model fish and investigated their hypoxia tolerance based on the critical oxygen tension of the routine metabolic rate (M˙O2rout) (Pcrit), aquatic surface respiration (ASRcrit) and loss of equilibrium (LOEcrit) after two weeks of acclimation at either 10, 20 or 30 °C. We also measured the tissue substrate (glycogen and glucose of muscle and liver) and lactate levels of both normoxia- and hypoxia-treated fish (post-LOE). Crucian carp exhibited significantly lower Pcrit and LOEcrit but not ASRcrit. Crucian carp possessed higher hypoxia tolerance, partially due to a higher tissue glycogen reserve, which provides cellular fuel under severe hypoxia, as well as higher lactate tolerance and clearance ability than Chinese bream. The hypoxia tolerance was maintained in crucian carp but was decreased in Chinese bream as the temperature increased. The difference between the two species is based on the greater recruitment of tissue glycogen, resulting in an increased level of cellular fuel during hypoxia in crucian carp than in Chinese bream. In addition, crucian carp possessed the greater liver lactate clearance capacity, and the smaller increase in the M˙O2rout at higher temperatures compared to Chinese bream. Furthermore, substrate shortage and decreased lactate tolerance at high temperatures in Chinese bream might also contribute to the difference in hypoxia tolerance between the two species. PMID:24853206

  12. Cognitive responses to hypobaric hypoxia: implications for aviation training

    PubMed Central

    Neuhaus, Christopher; Hinkelbein, Jochen

    2014-01-01

    The aim of this narrative review is to provide an overview on cognitive responses to hypobaric hypoxia and to show relevant implications for aviation training. A principal element of hypoxia-awareness training is the intentional evocation of hypoxia symptoms during specific training sessions within a safe and controlled environment. Repetitive training should enable pilots to learn and recognize their personal hypoxia symptoms. A time span of 3–6 years is generally considered suitable to refresh knowledge of the more subtle and early symptoms especially. Currently, there are two different technical approaches available to induce hypoxia during training: hypobaric chamber training and reduced-oxygen breathing devices. Hypoxia training for aircrew is extremely important and effective, and the hypoxia symptoms should be emphasized clearly to aircrews. The use of tight-fitting masks, leak checks, and equipment checks should be taught to all aircrew and reinforced regularly. It is noteworthy that there are major differences in the required quality and quantity of hypoxia training for both military and civilian pilots. PMID:25419162

  13. Regulation of Proliferation-Survival Decisions during Tumor Cell Hypoxia

    PubMed Central

    Schmaltz, Cornelius; Hardenbergh, Patricia Harrigan; Wells, Audrey; Fisher, David E.

    1998-01-01

    Hypoxia may influence tumor biology in paradoxically opposing ways: it is lethal as a direct stress trigger, yet hypoxic zones in solid tumors harbor viable cells which are particularly resistant to treatment and contribute importantly to disease relapse. To examine mechanisms underlying growth-survival decisions during hypoxia, we have compared genetically related transformed and untransformed fibroblast cells in vitro for proliferation, survival, clonogenicity, cell cycle, and p53 expression. Hypoxia induces G0/G1 arrest in primary fibroblasts but triggers apoptosis in oncogene-transformed derivatives. Unexpectedly, the mechanism of apoptosis is seen to require accumulated acidosis and is rescued by enhanced buffering. The direct effect of hypoxia under nonacidotic conditions is unique to transformed cells in that they override the hypoxic G0/G1 arrest of primary cells. Moreover, when uncoupled from acidosis, hypoxia enhances tumor cell viability and clonogenicity relative to normoxia. p53 is correspondingly upregulated in response to hypoxia-induced acidosis but downregulated during hypoxia without acidosis. Hypoxia may thus produce both treatment resistance and a growth advantage. Given strong evidence that hypoxic regions in solid tumors are often nonacidotic (G. Helmlinger, F. Yuan, M. Dellian, and R. K. Jain, Nat. Med. 3:177–182, 1997), this behavior may influence relapse and implicates such cells as potentially important therapeutic targets. PMID:9566903

  14. Blockade of processing/activation of caspase-3 by hypoxia

    SciTech Connect

    Han, Sang Hee; Kim, Moonil; Park, Kyoungsook; Kim, Tae-Hyoung; Seol, Dai-Wu

    2008-10-31

    Tumor hypoxia, which is caused by the rapid proliferation of tumor cells and aberrant vasculature in tumors, results in inadequate supplies of oxygen and nutrients to tumor cells. Paradoxically, these unfavorable growth conditions benefit tumor cell survival, although the mechanism is poorly understood. We have demonstrated for the first time that hypoxia inhibits TRAIL-induced apoptosis by blocking translocation of Bax from cytosol to the mitochondria in tumor cells. However, it is largely unknown how hypoxia-inhibited Bax translocation attenuates TRAIL-induced apoptosis. Here, we demonstrate that despite its inhibitory activity in TRAIL-induced apoptosis, hypoxia does not affect TRAIL-triggered proximal apoptotic signaling events, including caspase-8 activation and Bid cleavage. Instead, hypoxia inhibited processing of caspase-3, leading to incomplete activation of the caspase. Importantly, hypoxia-blocked translocation of Bax to the mitochondria significantly inhibited releasing the mitochondrial factors, such as cytochrome c and Smac/DIABLO, to the cytosol in response to TRAIL. It is well-known that complete processing/activation of caspase-3 requires Smac/DIABLO released from mitochondria. Therefore, our data indicate that an engagement of the apoptotic mitochondrial events leading to caspase-3 activation is blocked by hypoxia. Our data shed new light on understanding of the apoptotic signal transduction and targets regulated by tumor hypoxia.

  15. REST is a hypoxia-responsive transcriptional repressor.

    PubMed

    Cavadas, Miguel A S; Mesnieres, Marion; Crifo, Bianca; Manresa, Mario C; Selfridge, Andrew C; Keogh, Ciara E; Fabian, Zsolt; Scholz, Carsten C; Nolan, Karen A; Rocha, Liliane M A; Tambuwala, Murtaza M; Brown, Stuart; Wdowicz, Anita; Corbett, Danielle; Murphy, Keith J; Godson, Catherine; Cummins, Eoin P; Taylor, Cormac T; Cheong, Alex

    2016-01-01

    Cellular exposure to hypoxia results in altered gene expression in a range of physiologic and pathophysiologic states. Discrete cohorts of genes can be either up- or down-regulated in response to hypoxia. While the Hypoxia-Inducible Factor (HIF) is the primary driver of hypoxia-induced adaptive gene expression, less is known about the signalling mechanisms regulating hypoxia-dependent gene repression. Using RNA-seq, we demonstrate that equivalent numbers of genes are induced and repressed in human embryonic kidney (HEK293) cells. We demonstrate that nuclear localization of the Repressor Element 1-Silencing Transcription factor (REST) is induced in hypoxia and that REST is responsible for regulating approximately 20% of the hypoxia-repressed genes. Using chromatin immunoprecipitation assays we demonstrate that REST-dependent gene repression is at least in part mediated by direct binding to the promoters of target genes. Based on these data, we propose that REST is a key mediator of gene repression in hypoxia. PMID:27531581

  16. NO-dependent mechanisms of adaptation to hypoxia.

    PubMed

    Malyshev, I Y; Zenina, T A; Golubeva, L Y; Saltykova, V A; Manukhina, E B; Mikoyan, V D; Kubrina, L N; Vanin, A F

    1999-01-01

    In studying NO-dependent mechanisms of resistance to hypoxia, it was shown that (1) acute hypoxia induces NO overproduction in brain and leaves unaffected NO production in liver of rats; (2) adaptation to hypoxia decreases NO production in liver and brain; and (3) adaptation to hypoxia prevents NO overproduction in brain and potentiates NO synthesis in liver in acute hypoxia. Dinitrosyl iron complex (DNIC, 200 microg/kg, single dose, iv), a NO donor, decreases the resistance of animals to acute hypoxia by 30%. Nomega-nitro-L-arginine (L-NNA, 50 mg/kg, single dose, ip), a NO synthase inhibitor, and diethyl dithiocarbamate (DETC, 200 mg/kg, single dose, iv), a NO trap, increases this parameter 1.3 and 2 times, respectively. Adaptation to hypoxia developed against a background of accumulation of heat shock protein HSP70 in liver and brain. A course of DNIC reproduced the antihypoxic effect of adaptation. A course of L-NNA during adaptation hampered both accumulation of HSP70 and development of the antihypoxic effect. Therefore, NO and the NO-dependent activation of HSP70 synthesis play important roles in adaptation to hypoxia. PMID:10369180

  17. REST is a hypoxia-responsive transcriptional repressor

    PubMed Central

    Cavadas, Miguel A. S.; Mesnieres, Marion; Crifo, Bianca; Manresa, Mario C.; Selfridge, Andrew C.; Keogh, Ciara E.; Fabian, Zsolt; Scholz, Carsten C.; Nolan, Karen A.; Rocha, Liliane M. A.; Tambuwala, Murtaza M.; Brown, Stuart; Wdowicz, Anita; Corbett, Danielle; Murphy, Keith J.; Godson, Catherine; Cummins, Eoin P.; Taylor, Cormac T.; Cheong, Alex

    2016-01-01

    Cellular exposure to hypoxia results in altered gene expression in a range of physiologic and pathophysiologic states. Discrete cohorts of genes can be either up- or down-regulated in response to hypoxia. While the Hypoxia-Inducible Factor (HIF) is the primary driver of hypoxia-induced adaptive gene expression, less is known about the signalling mechanisms regulating hypoxia-dependent gene repression. Using RNA-seq, we demonstrate that equivalent numbers of genes are induced and repressed in human embryonic kidney (HEK293) cells. We demonstrate that nuclear localization of the Repressor Element 1-Silencing Transcription factor (REST) is induced in hypoxia and that REST is responsible for regulating approximately 20% of the hypoxia-repressed genes. Using chromatin immunoprecipitation assays we demonstrate that REST-dependent gene repression is at least in part mediated by direct binding to the promoters of target genes. Based on these data, we propose that REST is a key mediator of gene repression in hypoxia. PMID:27531581

  18. Efficient utilization of aerobic metabolism helps Tibetan locusts conquer hypoxia

    PubMed Central

    2013-01-01

    Background Responses to hypoxia have been investigated in many species; however, comparative studies between conspecific geographical populations at different altitudes are rare, especially for invertebrates. The migratory locust, Locusta migratoria, is widely distributed around the world, including on the high-altitude Tibetan Plateau (TP) and the low-altitude North China Plain (NP). TP locusts have inhabited Tibetan Plateau for over 34,000 years and thus probably have evolved superior capacity to cope with hypoxia. Results Here we compared the hypoxic responses of TP and NP locusts from morphological, behavioral, and physiological perspectives. We found that TP locusts were more tolerant of extreme hypoxia than NP locusts. To evaluate why TP locusts respond to extreme hypoxia differently from NP locusts, we subjected them to extreme hypoxia and compared their transcriptional responses. We found that the aerobic metabolism was less affected in TP locusts than in NP locusts. RNAi disruption of PDHE1β, an entry gene from glycolysis to TCA cycle, increased the ratio of stupor in TP locusts and decreased the ATP content of TP locusts in hypoxia, confirming that aerobic metabolism is critical for TP locusts to maintain activity in hypoxia. Conclusions Our results indicate that TP and NP locusts have undergone divergence in hypoxia tolerance. These findings also indicate that insects can adapt to hypoxic pressure by modulating basic metabolic processes. PMID:24047108

  19. Mitochondrial Reactive Oxygen Species Trigger Hypoxia-Induced Transcription

    NASA Astrophysics Data System (ADS)

    Chandel, N. S.; Maltepe, E.; Goldwasser, E.; Mathieu, C. E.; Simon, M. C.; Schumacker, P. T.

    1998-09-01

    Transcriptional activation of erythropoietin, glycolytic enzymes, and vascular endothelial growth factor occurs during hypoxia or in response to cobalt chloride (CoCl2) in Hep3B cells. However, neither the mechanism of cellular O2 sensing nor that of cobalt is fully understood. We tested whether mitochondria act as O2 sensors during hypoxia and whether hypoxia and cobalt activate transcription by increasing generation of reactive oxygen species (ROS). Results show (i) wild-type Hep3B cells increase ROS generation during hypoxia (1.5% O2) or CoCl2 incubation, (ii) Hep3B cells depleted of mitochondrial DNA (ρ 0 cells) fail to respire, fail to activate mRNA for erythropoietin, glycolytic enzymes, or vascular endothelial growth factor during hypoxia, and fail to increase ROS generation during hypoxia; (iii) ρ 0 cells increase ROS generation in response to CoCl2 and retain the ability to induce expression of these genes; and (iv) the antioxidants pyrrolidine dithiocarbamate and ebselen abolish transcriptional activation of these genes during hypoxia or CoCl2 in wild-type cells, and abolish the response to CoCl2 in ρ 0 cells. Thus, hypoxia activates transcription via a mitochondria-dependent signaling process involving increased ROS, whereas CoCl2 activates transcription by stimulating ROS generation via a mitochondria-independent mechanism.

  20. Thermoregulatory and metabolic responses of Japanese quail to hypoxia

    PubMed Central

    Atchley, Dylan S.; Foster, Jennifer A.; Bavis, Ryan W.

    2008-01-01

    Common responses to hypoxia include decreased body temperature (Tb) and decreased energy metabolism. In this study, the effects of hypoxia and hypercapnia on Tb and metabolic oxygen consumption (V̇o2) were investigated in Japanese quail (Coturnix japonica). When exposed to hypoxia (15, 13, 11 and 9% O2), Tb decreased only at 11% and 9% O2 compared to normoxia; quail were better able to maintain Tb during acute hypoxia after a one-week acclimation to 10% O2. V̇o2 also decreased during hypoxia, but at 9% O2 this was partially offset by increased anaerobic metabolism. Tb and V̇o2 responses to 9% O2 were exaggerated at lower ambient temperature (Ta), reflecting a decreased lower critical temperature during hypoxia. Conversely, hypoxia had little effect on Tb or V̇o2 at higher Ta (36°C). We conclude that Japanese quail respond to hypoxia in much the same way as mammals, by reducing both Tb and V̇o2. No relationship was found between the magnitudes of decreases in Tb and V̇o2 during 9% O2, however. Since metabolism is the source of heat generation, this suggests that Japanese quail increase thermolysis to reduce Tb. During hypercapnia (3, 6 and 9% CO2), Tb was reduced only at 9% CO2 while V̇o2 was unchanged. PMID:18727957

  1. 20 CFR 725.210 - Duration of augmented benefits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Duration of augmented benefits. 725.210... Entitlement Conditions and Duration of Entitlement: Miner's Dependents (augmented Benefits) § 725.210 Duration of augmented benefits. Augmented benefits payable on behalf of a spouse or divorced spouse, or...

  2. 20 CFR 725.210 - Duration of augmented benefits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Duration of augmented benefits. 725.210... Entitlement Conditions and Duration of Entitlement: Miner's Dependents (augmented Benefits) § 725.210 Duration of augmented benefits. Augmented benefits payable on behalf of a spouse or divorced spouse, or...

  3. WSB1: from homeostasis to hypoxia.

    PubMed

    Haque, Moinul; Kendal, Joseph Keith; MacIsaac, Ryan Matthew; Demetrick, Douglas James

    2016-01-01

    The wsb1 gene has been identified to be important in developmental biology and cancer. A complex transcriptional regulation of wsb1 yields at least three functional transcripts. The major expressed isoform, WSB1 protein, is a substrate recognition protein within an E3 ubiquitin ligase, with the capability to bind diverse targets and mediate ubiquitinylation and proteolytic degradation. Recent data suggests a new role for WSB1 as a component of a neuroprotective pathway which results in modification and aggregation of neurotoxic proteins such as LRRK2 in Parkinson's Disease, via an unusual mode of protein ubiquitinylation.WSB1 is also involved in thyroid hormone homeostasis, immune regulation and cellular metabolism, particularly glucose metabolism and hypoxia. In hypoxia, wsb1 is a HIF-1 target, and is a regulator of the degradation of diverse proteins associated with the cellular response to hypoxia, including HIPK2, RhoGDI2 and VHL. Major roles are to both protect HIF-1 function through degradation of VHL, and decrease apoptosis through degradation of HIPK2. These activities suggest a role for wsb1 in cancer cell proliferation and metastasis. As well, recent work has identified a role for WSB1 in glucose metabolism, and perhaps in mediating the Warburg effect in cancer cells by maintaining the function of HIF1. Furthermore, studies of cancer specimens have identified dysregulation of wsb1 associated with several types of cancer, suggesting a biologically relevant role in cancer development and/or progression.Recent development of an inducible expression system for wsb1 could aid in the further understanding of the varied functions of this protein in the cell, and roles as a potential oncogene and neuroprotective protein. PMID:27542736

  4. Effect of Acute Exposure to Moderate Altitude on Muscle Power: Hypobaric Hypoxia vs. Normobaric Hypoxia

    PubMed Central

    Feriche, Belén; García-Ramos, Amador; Calderón-Soto, Carmen; Drobnic, Franchek; Bonitch- Góngora, Juan G.; Galilea, Pedro A.; Riera, Joan; Padial, Paulino

    2014-01-01

    When ascending to a higher altitude, changes in air density and oxygen levels affect the way in which explosive actions are executed. This study was designed to compare the effects of acute exposure to real or simulated moderate hypoxia on the dynamics of the force-velocity relationship observed in bench press exercise. Twenty-eight combat sports athletes were assigned to two groups and assessed on two separate occasions: G1 (n = 17) in conditions of normoxia (N1) and hypobaric hypoxia (HH) and G2 (n = 11) in conditions of normoxia (N2) and normobaric hypoxia (NH). Individual and complete force-velocity relationships in bench press were determined on each assessment day. For each exercise repetition, we obtained the mean and peak velocity and power shown by the athletes. Maximum power (Pmax) was recorded as the highest Pmean obtained across the complete force-velocity curve. Our findings indicate a significantly higher absolute load linked to Pmax (∼3%) and maximal strength (1RM) (∼6%) in G1 attributable to the climb to altitude (P<0.05). We also observed a stimulating effect of natural hypoxia on Pmean and Ppeak in the middle-high part of the curve (≥60 kg; P<0.01) and a 7.8% mean increase in barbell displacement velocity (P<0.001). No changes in any of the variables examined were observed in G2. According to these data, we can state that acute exposure to natural moderate altitude as opposed to simulated normobaric hypoxia leads to gains in 1RM, movement velocity and power during the execution of a force-velocity curve in bench press. PMID:25474104

  5. Effect of acute exposure to moderate altitude on muscle power: hypobaric hypoxia vs. normobaric hypoxia.

    PubMed

    Feriche, Belén; García-Ramos, Amador; Calderón-Soto, Carmen; Drobnic, Franchek; Bonitch-Góngora, Juan G; Galilea, Pedro A; Riera, Joan; Padial, Paulino

    2014-01-01

    When ascending to a higher altitude, changes in air density and oxygen levels affect the way in which explosive actions are executed. This study was designed to compare the effects of acute exposure to real or simulated moderate hypoxia on the dynamics of the force-velocity relationship observed in bench press exercise. Twenty-eight combat sports athletes were assigned to two groups and assessed on two separate occasions: G1 (n = 17) in conditions of normoxia (N1) and hypobaric hypoxia (HH) and G2 (n = 11) in conditions of normoxia (N2) and normobaric hypoxia (NH). Individual and complete force-velocity relationships in bench press were determined on each assessment day. For each exercise repetition, we obtained the mean and peak velocity and power shown by the athletes. Maximum power (Pmax) was recorded as the highest P(mean) obtained across the complete force-velocity curve. Our findings indicate a significantly higher absolute load linked to P(max) (∼ 3%) and maximal strength (1 RM) (∼ 6%) in G1 attributable to the climb to altitude (P<0.05). We also observed a stimulating effect of natural hypoxia on P(mean) and P(peak) in the middle-high part of the curve (≥ 60 kg; P<0.01) and a 7.8% mean increase in barbell displacement velocity (P<0.001). No changes in any of the variables examined were observed in G2. According to these data, we can state that acute exposure to natural moderate altitude as opposed to simulated normobaric hypoxia leads to gains in 1 RM, movement velocity and power during the execution of a force-velocity curve in bench press.

  6. 2013 Gulf of Mexico Hypoxia Forecast

    USGS Publications Warehouse

    Scavia, Donald; Evans, Mary Anne; Obenour, Dan

    2013-01-01

    The Gulf of Mexico annual summer hypoxia forecasts are based on average May total nitrogen loads from the Mississippi River basin for that year. The load estimate, recently released by USGS, is 7,316 metric tons per day. Based on that estimate, we predict the area of this summer’s hypoxic zone to be 18,900 square kilometers (95% credible interval, 13,400 to 24,200), the 7th largest reported and about the size of New Jersey. Our forecast hypoxic volume is 74.5 km3 (95% credible interval, 51.5 to 97.0), also the 7th largest on record.

  7. 2014 Gulf of Mexico Hypoxia Forecast

    USGS Publications Warehouse

    Scavia, Donald; Evans, Mary Anne; Obenour, Dan

    2014-01-01

    The Gulf of Mexico annual summer hypoxia forecasts are based on average May total nitrogen loads from the Mississippi River basin for that year. The load estimate, recently released by USGS, is 4,761 metric tons per day. Based on that estimate, we predict the area of this summer’s hypoxic zone to be 14,000 square kilometers (95% credible interval, 8,000 to 20,000) – an “average year”. Our forecast hypoxic volume is 50 km3 (95% credible interval, 20 to 77).

  8. TRAIL restores DCA/metformin-mediated cell death in hypoxia.

    PubMed

    Hong, Sung-Eun; Kim, Chang Soon; An, Sungkwan; Kim, Hyun-Ah; Hwang, Sang-Gu; Song, Jie-Young; Lee, Jin Kyung; Hong, Jungil; Kim, Jong-Il; Noh, Woo Chul; Jin, Hyeon-Ok; Park, In-Chul

    2016-09-23

    Previous studies have shown that hypoxia can reverse DCA/metformin-induced cell death in breast cancer cells. Therefore, targeting hypoxia is necessary for therapies targeting cancer metabolism. In the present study, we found that TRAIL can overcome the effect of hypoxia on the cell death induced by treatment of DCA and metformin in breast cancer cells. Unexpectedly, DR5 is upregulated in the cells treated with DCA/metformin, and sustained under hypoxia. Blocking DR5 by siRNA inhibited DCA/metformin/TRAIL-induced cell death, indicating that DR5 upregulation plays an important role in sensitizing cancer cells to TRAIL-induced cell death. Furthermore, we found that activation of JNK and c-Jun is responsible for upregulation of DR5 induced by DCA/metformin. These findings support the potential application of combining TRAIL and metabolism-targeting drugs in the treatment of cancers under hypoxia. PMID:27569287

  9. c-MYC inhibition impairs hypoxia response in glioblastoma multiforme.

    PubMed

    Mongiardi, Maria Patrizia; Savino, Mauro; Falchetti, Maria Laura; Illi, Barbara; Bozzo, Francesca; Valle, Cristiana; Helmer-Citterich, Manuela; Ferrè, Fabrizio; Nasi, Sergio; Levi, Andrea

    2016-05-31

    The c-MYC oncoprotein is a DNA binding transcription factor that enhances the expression of many active genes. c-MYC transcriptional signatures vary according to the transcriptional program defined in each cell type during differentiation. Little is known on the involvement of c-MYC in regulation of gene expression programs that are induced by extracellular cues such as a changing microenvironment. Here we demonstrate that inhibition of c-MYC in glioblastoma multiforme cells blunts hypoxia-dependent glycolytic reprogramming and mitochondria fragmentation in hypoxia. This happens because c-MYC inhibition alters the cell transcriptional response to hypoxia and finely tunes the expression of a subset of Hypoxia Inducible Factor 1-regulated genes. We also show that genes whose expression in hypoxia is affected by c-MYC inhibition are able to distinguish the Proneural subtype of glioblastoma multiforme, thus potentially providing a molecular signature for this class of tumors that are the least tractable among glioblastomas. PMID:27119353

  10. Hypoxia causes transgenerational impairments in reproduction of fish

    PubMed Central

    Wang, Simon Yuan; Lau, Karen; Lai, Keng-Po; Zhang, Jiang-Wen; Tse, Anna Chung-Kwan; Li, Jing-Woei; Tong, Yin; Chan, Ting-Fung; Wong, Chris Kong-Chu; Chiu, Jill Man-Ying; Au, Doris Wai-Ting; Wong, Alice Sze-Tsai; Kong, Richard Yuen-Chong; Wu, Rudolf Shiu-Sun

    2016-01-01

    Hypoxia is amongst the most widespread and pressing problems in aquatic environments. Here we demonstrate that fish (Oryzias melastigma) exposed to hypoxia show reproductive impairments (retarded gonad development, decrease in sperm count and sperm motility) in F1 and F2 generations despite these progenies (and their germ cells) having never been exposed to hypoxia. We further show that the observed transgenerational reproductive impairments are associated with a differential methylation pattern of specific genes in sperm of both F0 and F2 coupled with relevant transcriptomic and proteomic alterations, which may impair spermatogenesis. The discovered transgenerational and epigenetic effects suggest that hypoxia might pose a dramatic and long-lasting threat to the sustainability of fish populations. Because the genes regulating spermatogenesis and epigenetic modifications are highly conserved among vertebrates, these results may also shed light on the potential transgenerational effects of hypoxia on other vertebrates, including humans. PMID:27373813

  11. Hypoxia causes transgenerational impairments in reproduction of fish.

    PubMed

    Wang, Simon Yuan; Lau, Karen; Lai, Keng-Po; Zhang, Jiang-Wen; Tse, Anna Chung-Kwan; Li, Jing-Woei; Tong, Yin; Chan, Ting-Fung; Wong, Chris Kong-Chu; Chiu, Jill Man-Ying; Au, Doris Wai-Ting; Wong, Alice Sze-Tsai; Kong, Richard Yuen-Chong; Wu, Rudolf Shiu-Sun

    2016-01-01

    Hypoxia is amongst the most widespread and pressing problems in aquatic environments. Here we demonstrate that fish (Oryzias melastigma) exposed to hypoxia show reproductive impairments (retarded gonad development, decrease in sperm count and sperm motility) in F1 and F2 generations despite these progenies (and their germ cells) having never been exposed to hypoxia. We further show that the observed transgenerational reproductive impairments are associated with a differential methylation pattern of specific genes in sperm of both F0 and F2 coupled with relevant transcriptomic and proteomic alterations, which may impair spermatogenesis. The discovered transgenerational and epigenetic effects suggest that hypoxia might pose a dramatic and long-lasting threat to the sustainability of fish populations. Because the genes regulating spermatogenesis and epigenetic modifications are highly conserved among vertebrates, these results may also shed light on the potential transgenerational effects of hypoxia on other vertebrates, including humans. PMID:27373813

  12. Hypoxia: developments in basic science, physiology and clinical studies.

    PubMed

    Ward, D S; Karan, S B; Pandit, J J

    2011-12-01

    Airway management is primarily designed to avoid hypoxia, yet hypoxia remains the main ultimate cause of anaesthetic-related death and morbidity. Understanding some of the physiology of hypoxia is therefore essential as part of a 'holistic' approach to airway management. Furthermore, it is strategically important that national specialist societies dedicated to airway management do not only focus upon the technical aspects of airway management, but also embrace some of the relevant scientific questions. There has been a great deal of research into causation of hypoxia and the body's natural protective mechanisms and responses to it. This enables us to think of ways in which we might manipulate the cellular and molecular responses to confer greater protection against hypoxia-induced tissue injury. This article reviews some of those aspects. PMID:22074075

  13. [Influence of hypoxia on the human auditory system].

    PubMed

    Lucertini, M; Urbani, L

    1997-02-01

    The present paper presents a review of the literature on "hypoxia and human auditory mechanisms". It examines and discusses, above all, the results obtained in the various studies using pure tone audiometry and auditory evoked potentials. At the present time, the two areas which appear most sensitive to hypoxia are the cochlea and, above all, the telencephalic auditory cortex (specifically those sectors dedicated to cognitive processing of auditory stimulation). However, many other areas which are sensitive to hypoxia, but to a lesser extent, have also been identified, even in other sectors of the auditory pathway. Particularly worthy of note is the effectiveness of the metabolic compensatory mechanisms which come into play upon hypoxic stress. These mechanisms include vasodilation and the presence of metabolic reservoirs. Nevertheless, there are still a number of open questions regarding how the auditory pathway functions in the case of hypoxia; thus the experimental study of hypoxic hypoxia is still an interesting, fruitful research field in audiology.

  14. Augmented Reality for the Improvement of Remote Laboratories: An Augmented Remote Laboratory

    ERIC Educational Resources Information Center

    Andujar, J. M.; Mejias, A.; Marquez, M. A.

    2011-01-01

    Augmented reality (AR) provides huge opportunities for online teaching in science and engineering, as these disciplines place emphasis on practical training and unsuited to completely nonclassroom training. This paper proposes a new concept in virtual and remote laboratories: the augmented remote laboratory (ARL). ARL is being tested in the first…

  15. ARSC: Augmented Reality Student Card--An Augmented Reality Solution for the Education Field

    ERIC Educational Resources Information Center

    El Sayed, Neven A. M.; Zayed, Hala H.; Sharawy, Mohamed I.

    2011-01-01

    Augmented Reality (AR) is the technology of adding virtual objects to real scenes through enabling the addition of missing information in real life. As the lack of resources is a problem that can be solved through AR, this paper presents and explains the usage of AR technology we introduce Augmented Reality Student Card (ARSC) as an application of…

  16. Hypoxia-inducible factor-1α and erythropoietin expression in the hippocampus of neonatal rats following hypoxia-ischemia.

    PubMed

    Lu, Junjie; Jiang, Li; Zhu, Huan; Zhang, Long; Wang, Ting

    2014-08-01

    In some regions of the hippocampus, neurogenesis persists throughout life and is upregulated following hypoxia/ischemia. The mechanisms underlying the upregulation of neurogenesis, however, are not known. Here we examined the expression of two factors thought to be involved in hypoxia-related neurogenesis, hypoxia-inducible factor-1α (HIF-1α) and brain-derived erythropoietin (EPO), in the hippocampus of neonatal rats following hypoxia-ischemia. Sprague-Dawley rat pups were exposed to hypoxia-ischemia conditions or hypoxia conditions only. For the hypoxia-ischemia experiment, the left common carotid artery of Sprague-Dawley rat pups was ligated on postnatal day 7. The pups were exposed to hypoxic conditions and then returned to normoxia for re-oxygenation. Immunohistochemical staining was performed to evaluate EPO and HIF-1α expression at various time points after re-oxygenation (1 h, 6 h, 16 h, 1 d, 3 d, and 7 d). EPO expression in the hippocampus was verified using Western blot studies. For the hypoxia-only experiment, postnatal day 7 rat pups were continuously exposed to hypoxic conditions for different durations (0.5 h, 1 h, 2 h, 3 h, and 5 h). HIF-1α expression in the hippocampus was evaluated by immunohistochemical staining. In the hypoxia-ischemia group, EPO expression was significantly altered. The EPO expression increased during re-oxygenation, peaked at 16 h, and decreased thereafter. In the hypoxia-only group, the EPO protein was not detectable. When the rat pups were returned to normoxia for re-oxygenation, there was no HIF-1α expression. HIF-1α immunoreactivity was present in the hypoxia-only group and peaked in rats exposed to continuous hypoxic conditions for 3 h. In addition, endogenous EPO increased in the neonatal rats after the hypoxia-ischemia event. Furthermore, HIF-1α was induced as a result of hypoxia. We postulate that disruption of homeostasis triggers and enhances hippocampal neurogenesis. Thus, HIF-1α/EPO hypoxic signal

  17. The transareolar incision for breast augmentation revisited.

    PubMed

    Kompatscher, Peter; Schuler, Christine; Beer, Gertrude M

    2004-01-01

    Of the various possible incisions for breast augmentation, the transareolar access has gained only limited popularity. The potential side effects of this incision are said to be altered nipple sensation, impaired lactation, an increased rate of infections with capsular fibrosis, well visible scar formation with hypopigmentation, and the need for an additional access in case a breast ptosis correction should prove necessary at a later date. The purpose of this retrospective study was to judge advantages and limitations of transareolar breast augmentation, and to verify whether the reluctant attitude toward this surgical approach is justified. A sample of 18 patients with a transareolar, retropectoral breast augmentation was selected for a retrospective evaluation. The suitability of the technique in general was examined together with early postoperative complications, sensory changes, and late complications on the basis of an evaluation system for cosmetic surgical results. The study showed that only women with an areolar diameter of 3.5 cm or more without pronounced breast ptosis were suitable for the transareolar access. No early infections were noted. The rate of capsular fibrosis was 11%. Two years after breast augmentation, 16 women (89%) judged their breast sensation to be normal, but objective assessment showed that mean pressure and vibration sensation were moderately compromised in all parts of the breast. The scars were of good quality, with very little hypopigmentation. With appropriate patient selection, respecting the advantages and limitations, the transareolar incision has its definite place among the different incisions for breast augmentation. PMID:15164231

  18. News about VDAC1 in Hypoxia

    PubMed Central

    Mazure, N. M.

    2016-01-01

    The voltage-dependent anion channel (VDAC) is the main interface between the cytosol and mitochondria of cells. It plays a crucial role in both mitochondrial metabolism and cell death. The main basic function of this channel is to mediate and gate the flux of small ions, metabolites, and adenosine triphosphate. Changes in its structure, and thus conformation, are expected to affect its activity and modulate the ability of cancer cells to expand. In this review, we describe a novel mechanism by which mitochondria of cells in hypoxia, a low level of oxygen, protects from apoptosis. In hypoxia, some mitochondria become enlarged due to hyperfusion. These mitochondria possess a truncated form of VDAC1 (VDAC1-ΔC), which is linked to the higher metabolic capacity and the greater resistance to cell death of hypoxic cells. However, not all of the VDAC1 protein is truncated, but the amount of the full-length form is diminished compared to the amount in normoxic cells. First, we describe how such a decrease effects cell proliferation, respiration, glycolysis, and other processes. Second, we report on a novel mitochondrial-endolysosomal crosstalk that leads to VDAC1 truncation. By pharmacological targeting of VDAC1-ΔC, the production of energy could be turned off and the sensitivity to cell death restored. This could counteract the favorable microenvironment that gives cancer cells a growth advantage and thereby disrupts the balance between life and death, which is controlled by VDAC1. PMID:27625993

  19. News about VDAC1 in Hypoxia

    PubMed Central

    Mazure, N. M.

    2016-01-01

    The voltage-dependent anion channel (VDAC) is the main interface between the cytosol and mitochondria of cells. It plays a crucial role in both mitochondrial metabolism and cell death. The main basic function of this channel is to mediate and gate the flux of small ions, metabolites, and adenosine triphosphate. Changes in its structure, and thus conformation, are expected to affect its activity and modulate the ability of cancer cells to expand. In this review, we describe a novel mechanism by which mitochondria of cells in hypoxia, a low level of oxygen, protects from apoptosis. In hypoxia, some mitochondria become enlarged due to hyperfusion. These mitochondria possess a truncated form of VDAC1 (VDAC1-ΔC), which is linked to the higher metabolic capacity and the greater resistance to cell death of hypoxic cells. However, not all of the VDAC1 protein is truncated, but the amount of the full-length form is diminished compared to the amount in normoxic cells. First, we describe how such a decrease effects cell proliferation, respiration, glycolysis, and other processes. Second, we report on a novel mitochondrial-endolysosomal crosstalk that leads to VDAC1 truncation. By pharmacological targeting of VDAC1-ΔC, the production of energy could be turned off and the sensitivity to cell death restored. This could counteract the favorable microenvironment that gives cancer cells a growth advantage and thereby disrupts the balance between life and death, which is controlled by VDAC1.

  20. News about VDAC1 in Hypoxia.

    PubMed

    Mazure, N M

    2016-01-01

    The voltage-dependent anion channel (VDAC) is the main interface between the cytosol and mitochondria of cells. It plays a crucial role in both mitochondrial metabolism and cell death. The main basic function of this channel is to mediate and gate the flux of small ions, metabolites, and adenosine triphosphate. Changes in its structure, and thus conformation, are expected to affect its activity and modulate the ability of cancer cells to expand. In this review, we describe a novel mechanism by which mitochondria of cells in hypoxia, a low level of oxygen, protects from apoptosis. In hypoxia, some mitochondria become enlarged due to hyperfusion. These mitochondria possess a truncated form of VDAC1 (VDAC1-ΔC), which is linked to the higher metabolic capacity and the greater resistance to cell death of hypoxic cells. However, not all of the VDAC1 protein is truncated, but the amount of the full-length form is diminished compared to the amount in normoxic cells. First, we describe how such a decrease effects cell proliferation, respiration, glycolysis, and other processes. Second, we report on a novel mitochondrial-endolysosomal crosstalk that leads to VDAC1 truncation. By pharmacological targeting of VDAC1-ΔC, the production of energy could be turned off and the sensitivity to cell death restored. This could counteract the favorable microenvironment that gives cancer cells a growth advantage and thereby disrupts the balance between life and death, which is controlled by VDAC1. PMID:27625993

  1. Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) contains hypoxia response elements: relevance to lytic induction by hypoxia.

    PubMed

    Haque, Muzammel; Davis, David A; Wang, Victoria; Widmer, Isabelle; Yarchoan, Robert

    2003-06-01

    Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), also known as human herpesvirus 8, is an etiologic agent of KS, primary effusion lymphoma (PEL), and multicentric Castleman's disease. We recently demonstrated that hypoxia can induce lytic replication of KSHV in PEL cell lines. Hypoxia induces the accumulation of hypoxia-inducible factors (HIF), and we hypothesized that the KSHV genome may respond to hypoxia through functional hypoxia response elements (HREs). Here, we demonstrate the presence of at least two promoters within the KSHV genome that are activated by hypoxia or hypoxia mimics. One is in the promoter region of the gene for Rta, the main lytic switch gene, and the other is within the promoter region of ORF34, a lytic gene of unknown function. The ORF34 promoter contains three putative consensus HREs oriented in the direction of the gene. Dissection and site-directed mutagenesis studies confirmed that one of the HREs of the ORF34 promoter is functional. Under conditions of hypoxia, the ORF34 promoter was strongly upregulated by HIF-1 alpha and HIF-2 alpha. By contrast, the promoter of the gene for Rta appeared to be preferentially upregulated by HIF-2 alpha. Reverse transcription-PCR analysis revealed that specific messages for ORF34 and ORF50 are upregulated in BCBL-1 cells exposed to hypoxia. An HIF-1 binding and competition assay demonstrated that the HRE sequence from the ORF34 promoter can compete for HIF-1 alpha binding to an erythropoietin HRE oligonucleotide while a mutant sequence cannot. Thus, we demonstrated that a viral gene can be activated by hypoxia through activation of a functional viral HRE. To our knowledge, this is the first example of a functional HRE in a viral promoter. PMID:12767996

  2. Orthobiologics in the augmentation of osteoporotic fractures.

    PubMed

    Watson, J Tracy; Nicolaou, Daemeon A

    2015-02-01

    Many orthobiologic adjuvants are available and widely utilized for general skeletal restoration. Their use for the specific task of osteoporotic fracture augmentation is less well recognized. Common conductive materials are reviewed for their value in this patient population including the large group of allograft adjuvants categorically known as the demineralized bone matrices (DBMs). Another large group of alloplastic materials is also examined-the calcium phosphate and sulfate ceramics. Both of these materials, when used for the proper indications, demonstrate efficacy for these patients. The inductive properties of bone morphogenic proteins (BMPs) and platelet concentrates show no clear advantages for this group of patients. Systemic agents including bisphosphonates, receptor activator of nuclear factor κβ ligand (RANKL) inhibitors, and parathyroid hormone augmentation all demonstrate positive effects with this fracture cohort. Newer modalities, such as trace ion bioceramic augmentation, are also reviewed for their positive effects on osteoporotic fracture healing. PMID:25431160

  3. Augmented repair of acute Achilles tendon ruptures.

    PubMed

    Zell, R A; Santoro, V M

    2000-06-01

    Twenty-five patients who had an acute Achilles tendon rupture were managed with an augmented repair using the gastrocnemius-soleus fascia. All patients healed their repair and there were no re-ruptures. There was one infection. Augmented repair allowed early functional recovery as evidenced by full ankle motion by four to eight weeks, full unassisted weight bearing by three weeks, cessation of braces by four weeks, and return to work by one to six weeks post-operatively. Augmentation adds a sufficient amount of collagen to allow early range of motion and weight bearing without re-rupture. Disadvantages included a long incision, soft tissue prominence, one infection, and sural nerve injury.

  4. Flap-augmented shrouds for aerogenerators

    NASA Technical Reports Server (NTRS)

    Seginer, A.

    1976-01-01

    Axisymmetrical shrouds for windmills are augmented by ring-shaped 'flaps' and their performance is studied experimentally. The concept of the shroud as an annular 'wing' is justified, leading to the conclusion that high-lift techniques should be used in shroud design, and that high-lift devices, such as flaps, would increase the power output of the windmill. It is shown experimentally that the ideal power output of a flap-augmented shrouded turbine can be more than 4 times the power of unshrouded turbines of the same diameter.

  5. Minimal inframammary incision for breast augmentation

    PubMed Central

    Fanous, Nabil; Tawilé, Caroline; Brousseau, Valérie J

    2008-01-01

    The inframammary approach in breast augmentation, still the most popular technique among plastic surgeons, has always been hampered by the undesirable appearance of its scar. The present paper describes a modified approach to inframammary augmentation with saline-filled prostheses. This approach uses a very short incision, thus resulting in a much less noticeable scar. The surgical technique is easy to learn, simple to execute, does not necessitate any special equipment and gives consistent results. Decreasing the scar length to an absolute minimum ensures higher patient and surgeon satisfaction. PMID:19554159

  6. Hypoxia inhibits Moloney murine leukemia virus expression in activated macrophages.

    PubMed

    Puppo, Maura; Bosco, Maria Carla; Federico, Maurizio; Pastorino, Sandra; Varesio, Luigi

    2007-02-01

    Hypoxia, a local decrease in oxygen tension, occurring in many pathological processes, modifies macrophage (Mphi) gene expression and function. Here, we provide the first evidence that hypoxia inhibits transgene expression driven by the Moloney murine leukemia virus-long terminal repeats (MoMLV-LTR) in IFN-gamma-activated Mphi. Hypoxia silenced the expression of several MoMLV-LTR-driven genes, including v-myc, enhanced green fluorescence protein, and env, and was effective in different mouse Mphi cell lines and on distinct MoMLV backbone-based viruses. Down-regulation of MoMLV mRNA occurred at the transcriptional level and was associated with decreased retrovirus production, as determined by titration experiments, suggesting that hypoxia may control MoMLV retroviral spread through the suppression of LTR activity. In contrast, genes driven by the CMV or the SV40 promoter were up-regulated or unchanged by hypoxia, indicating a selective inhibitory activity on the MoMLV promoter. It is interesting that hypoxia was ineffective in suppressing MoMLV-LTR-controlled gene expression in T or fibroblast cell lines, suggesting a Mphi lineage-selective action. Finally, we found that MoMLV-mediated gene expression in Mphi was also inhibited by picolinic acid, a tryptophan catabolite with hypoxia-like activity and Mphi-activating properties, suggesting a pathophysiological role of this molecule in viral resistance and its possible use as an antiviral agent.

  7. Molecular probes for imaging of hypoxia in the retina.

    PubMed

    Evans, Stephanie M; Kim, Kwangho; Moore, Chauca E; Uddin, Md Imam; Capozzi, Megan E; Craft, Jason R; Sulikowski, Gary A; Jayagopal, Ashwath

    2014-11-19

    Hypoxia has been associated with retinal diseases which lead the causes of irreversible vision loss, including diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration. Therefore, technologies for imaging hypoxia in the retina are needed for early disease detection, monitoring of disease progression, and assessment of therapeutic responses in the patient. Toward this goal, we developed two hypoxia-sensitive imaging agents based on nitroimidazoles which are capable of accumulating in hypoxic cells in vivo. 2-nitroimidazole or Pimonidazole was conjugated to fluorescent dyes to yield the imaging agents HYPOX-1 and HYPOX-2. Imaging agents were characterized in cell culture and animal models of retinal vascular diseases which exhibit hypoxia. Both HYPOX-1 and -2 were capable of detecting hypoxia in cell culture models with >10:1 signal-to-noise ratios without acute toxicity. Furthermore, intraocular administration of contrast agents in mouse models of retinal hypoxia enabled ex vivo detection of hypoxic tissue. These imaging agents are a promising step toward translation of hypoxia-sensitive molecular imaging agents in preclinical animal models and patients.

  8. Resveratrol attenuates hypoxia-induced neurotoxicity through inhibiting microglial activation.

    PubMed

    Zhang, Qun; Yuan, Lin; Zhang, Qingrui; Gao, Yan; Liu, Guangheng; Xiu, Meng; Wei, Xiang; Wang, Zhen; Liu, Dexiang

    2015-09-01

    Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has been found to afford neuroprotective effects against neuroinflammation in the brain. Activated microglia can secrete various pro-inflammatory cytokines and neurotoxic mediators, which may contribute to hypoxic brain injuries. The aim of this study is to investigate the potential role of resveratrol in attenuating hypoxia-induced neurotoxicity via its anti-inflammatory actions through in vitro models of the BV-2 microglial cell line and primary microglia. We found that resveratrol significantly inhibited hypoxia-induced microglial activation and reduced subsequent release of pro-inflammatory factors. In addition, resveratrol inhibited the hypoxia-induced degradation of IκB-alpha and phosphorylation of p65 NF-κB protein. Hypoxia-induced ERK1/2 and JNK phosphorylation was also strongly inhibited by resveratrol, whereas resveratrol had no effect on hypoxia-stimulated p38 MAPK phosphorylation. Importantly, treating primary cortical neurons with conditioned medium (CM) from hypoxia-stimulated microglia induced neuronal apoptosis, which was reversed by CM co-treated with resveratrol. Taken together, resveratrol exerts neuroprotection against hypoxia-induced neurotoxicity through its anti-inflammatory effects in microglia. These effects were mediated, at least in part, by suppressing the activation of NF-ĸB, ERK and JNK MAPK signaling pathways. PMID:26225925

  9. Acute hypoxia produces a superoxide burst in cells.

    PubMed

    Hernansanz-Agustín, Pablo; Izquierdo-Álvarez, Alicia; Sánchez-Gómez, Francisco J; Ramos, Elena; Villa-Piña, Tamara; Lamas, Santiago; Bogdanova, Anna; Martínez-Ruiz, Antonio

    2014-06-01

    Oxygen is a key molecule for cell metabolism. Eukaryotic cells sense the reduction in oxygen availability (hypoxia) and trigger a series of cellular and systemic responses to adapt to hypoxia, including the optimization of oxygen consumption. Many of these responses are mediated by a genetic program induced by the hypoxia-inducible transcription factors (HIFs), regulated by a family of prolyl hydroxylases (PHD or EGLN) that use oxygen as a substrate producing HIF hydroxylation. In parallel to these oxygen sensors modulating gene expression within hours, acute modulation of protein function in response to hypoxia is known to occur within minutes. Free radicals acting as second messengers, and oxidative posttranslational modifications, have been implied in both groups of responses. Localization and speciation of the paradoxical increase in reactive oxygen species production in hypoxia remain debatable. We have observed that several cell types respond to acute hypoxia with a transient increase in superoxide production for about 10 min, probably originating in the mitochondria. This may explain in part the apparently divergent results found by various groups that have not taken into account the time frame of hypoxic ROS production. We propose that this acute and transient hypoxia-induced superoxide burst may be translated into oxidative signals contributing to hypoxic adaptation and preconditioning.

  10. Evolutionary Genetics of Hypoxia Tolerance in Cetaceans during Diving

    PubMed Central

    Tian, Ran; Wang, Zhengfei; Niu, Xu; Zhou, Kaiya; Xu, Shixia; Yang, Guang

    2016-01-01

    Hypoxia was a major challenge faced by cetaceans during the course of secondary aquatic adaptation. Although physiological traits of hypoxia tolerance in cetaceans have been well characterized, the underlying molecular mechanisms remain unknown. We investigated the sequences of 17 hypoxia-tolerance-related genes in representative cetaceans to provide a comprehensive insight into the genetic basis of hypoxia tolerance in these animals. Genes involved in carrying and transporting oxygen in the blood and muscle (hemoglobin-α and β, myoglobin), and genes involved in the regulation of vasoconstriction (endothelin-1, -2, and -3; endothelin receptor type A and B; adrenergic receptor α-1D; and arginine vasopressin) appear to have undergone adaptive evolution, evidence for positive selection on their particular sites, and radical physiochemical property changes of selected condons. Interestingly, “long-diving” cetaceans had relatively higher ω (dN/dS) values than “short-diving” cetaceans for the hemoglobin β gene, indicating divergent selective pressure presented in cetacean lineages with different diving abilities. Additionally, parallel positive selection or amino acid changes (ADRA1D: P50A, A53G, AVPR1B: I/V270T) among animals exposed to different hypoxia habitats reflect functional convergence or similar genetic mechanisms of hypoxia tolerance. In summary, positive selection, divergent selective pressures, and parallel evolution at the molecular level provided some new insights into the genetic adaptation of hypoxia tolerance. PMID:26912402

  11. Role of nitric oxide in cardiovascular adaptation to intermittent hypoxia.

    PubMed

    Manukhina, Eugenia B; Downey, H Fred; Mallet, Robert T

    2006-04-01

    Hypoxia is one of the most frequently encountered stresses in health and disease. The duration, frequency, and severity of hypoxic episodes are critical factors determining whether hypoxia is beneficial or harmful. Adaptation to intermittent hypoxia has been demonstrated to confer cardiovascular protection against more severe and sustained hypoxia, and, moreover, to protect against other stresses, including ischemia. Thus, the direct and cross protective effects of adaptation to intermittent hypoxia have been used for treatment and prevention of a variety of diseases and to increase efficiency of exercise training. Evidence is mounting that nitric oxide (NO) plays a central role in these adaptive mechanisms. NO-dependent protective mechanisms activated by intermittent hypoxia include stimulation of NO synthesis as well as restriction of NO overproduction. In addition, alternative, nonenzymic sources of NO and negative feedback of NO synthesis are important factors in optimizing NO concentrations. The adaptive enhancement of NO synthesis and/or availability activates or increases expression of other protective factors, including heat shock proteins, antioxidants and prostaglandins, making the protection more robust and sustained. Understanding the role of NO in mechanisms of adaptation to hypoxia will support development of therapies to prevent and treat hypoxic or ischemic damage to organs and cells and to increase adaptive capabilities of the organism. PMID:16565431

  12. Ventilatory adaptation to hypoxia occurs in serotonin-depleted rats.

    PubMed

    Olson, E B

    1987-08-01

    To test the hypothesis that serotonin mediated respiratory activity is involved in ventilatory adaptation to hypoxia, rats were treated with parachlorophenylalanine (PCPA), a potent, long-acting inhibitor of tryptophan hydroxylase, the rate-limiting enzyme in the biosynthesis of serotonin. In normoxia, a single, intraperitoneal injection of 300 mg PCPA/kg body weight decreased the Paco2 from a control level at 39.1 +/- 0.6 Torr (mean +/- 95% confidence limits) to 34.0 +/- 0.6 Torr measured during a period from 1 to 48 h following PCPA treatment. This PCPA-produced hyperventilation corresponds to an increase of 3.7 +/- 0.5 in the VA (BTPS)/Vco2 (STPD) ratio. Hyperventilation during ventilatory adaptation to hypoxia (PIO2 approximately equal to 90 Torr) was superimposed in an additive fashion on the underlying hyperventilation due to PCPA pretreatment. Specifically, PCPA pretreatment caused an average 3.5 +/- 1.2 increase in the VA/VCO2 ratio determined in acute (1 h) hypoxia, chronic (24 h) hypoxia and acute return to normoxia following chronic hypoxia. Since ventilatory adaptation to hypoxia occurred in rats treated with PCPA, the prolonged, serotonin mediated respiratory activity described by Millhorn et al. (1980b) is probably not important in ventilatory acclimatization to - or deacclimatization from - hypoxia. PMID:2957766

  13. Regulation of CREB by moderate hypoxia in PC12 cells.

    PubMed

    Beitner-Johnson, D; Rust, R T; Hsieh, T; Millhorn, D E

    2000-01-01

    The mechanisms by which excitable cells adapt and respond to changes in O2 levels remain largely unknown. We have investigated the effect of hypoxia on the cyclic AMP response element binding protein (CREB) transcription factor. PC12 cells were exposed to moderate levels of hypoxia (5% O2) for various times between 20 min and 6 hr. We found that hypoxia rapidly and persistently induced ser133 phosphorylation of CREB. This effect was more robust than that produced by exposing PC12 cells to either forskolin, KCl, or NGF. This effect was not due to activation of any of the previously known CREB kinases, including PKA, CaMK, PKC, p70s6k, or MAPKAP kinase-2. Thus, hypoxia may induce activation of a novel CREB kinase. To test whether phosphorylation of CREB was associated with an activation of CRE-dependent gene expression, cells were transfected with wild type and mutated regions of the 5'-flanking region of the tyrosine hydroxylase (TH) gene fused to a CAT reporter gene. Mutation of the CRE element in a TH reporter gene reduced, but did not abolish, the effects of hypoxia on TH gene expression. However, hypoxia did not induce transactivation of a GAL4-luciferase reporter by a GAL4-CREB fusion protein. Thus, the mechanism by which hypoxia regulates CREB is distinct, and more complex, than that induced by forskolin, depolarization, or nerve growth factor. PMID:10849656

  14. Melatonin modulates the fetal cardiovascular defense response to acute hypoxia.

    PubMed

    Thakor, Avnesh S; Allison, Beth J; Niu, Youguo; Botting, Kimberley J; Serón-Ferré, Maria; Herrera, Emilio A; Giussani, Dino A

    2015-08-01

    Experimental studies in animal models supporting protective effects on the fetus of melatonin in adverse pregnancy have prompted clinical trials in human pregnancy complicated by fetal growth restriction. However, the effects of melatonin on the fetal defense to acute hypoxia, such as that which may occur during labor, remain unknown. This translational study tested the hypothesis, in vivo, that melatonin modulates the fetal cardiometabolic defense responses to acute hypoxia in chronically instrumented late gestation fetal sheep via alterations in fetal nitric oxide (NO) bioavailability. Under anesthesia, 6 fetal sheep at 0.85 gestation were instrumented with vascular catheters and a Transonic flow probe around a femoral artery. Five days later, fetuses were exposed to acute hypoxia with or without melatonin treatment. Fetal blood was taken to determine blood gas and metabolic status and plasma catecholamine concentrations. Hypoxia during melatonin treatment was repeated during in vivo NO blockade with the NO clamp. This technique permits blockade of de novo synthesis of NO while compensating for the tonic production of the gas, thereby maintaining basal cardiovascular function. Melatonin suppressed the redistribution of blood flow away from peripheral circulations and the glycemic and plasma catecholamine responses to acute hypoxia. These are important components of the fetal brain sparing response to acute hypoxia. The effects of melatonin involved NO-dependent mechanisms as the responses were reverted by fetal treatment with the NO clamp. Melatonin modulates the in vivo fetal cardiometabolic responses to acute hypoxia by increasing NO bioavailability.

  15. Myocardial metabolism during hypoxia: Maintained lactate oxidation during increased glycolysis

    SciTech Connect

    Mazer, C.D.; Stanley, W.C.; Hickey, R.F.; Neese, R.A.; Cason, B.A.; Demas, K.A.; Wisneski, J.A.; Gertz, E.W. )

    1990-09-01

    In the intact animal, myocardial lactate utilization and oxidation during hypoxia are not well understood. Nine dogs were chronically instrumented with flow probes on the left anterior descending coronary artery and with a coronary sinus sampling catheter. ({sup 14}C)lactate and ({sup 13}C)glucose tracers, or ({sup 13}C)lactate and ({sup 14}C)glucose were administered to quantitate lactate and glucose oxidation, lactate conversion to glucose, and simultaneous lactate extraction and release. The animals were anesthetized and exposed to 90 minutes of severe hypoxia (PO2 = 25 +/- 4 torr). Hypoxia resulted in significant increases in heart rate, cardiac output and myocardial blood flow, but no significant change in myocardial oxygen consumption. The arterial/coronary sinus differences for glucose and lactate did not change from normoxia to hypoxia; however, the rate of glucose uptake increased significantly due to the increase in myocardial blood flow. Tracer-measured lactate extraction did not decrease with hypoxia, despite a 250% increase in lactate release. During hypoxia, 90% +/- 4% of the extracted {sup 14}C-lactate was accounted for by the appearance of {sup 14}CO{sub 2} in the coronary sinus, compared with 88% +/- 4% during normoxia. Thus, in addition to the expected increase in glucose uptake and lactate production, we observed an increase in lactate oxidation during hypoxia.

  16. Hypoxia-related processes in the Baltic Sea.

    PubMed

    Conley, Daniel J; Björck, Svante; Bonsdorff, Erik; Carstensen, Jacob; Destouni, Georgia; Gustafsson, Bo G; Hietanen, Susanna; Kortekaas, Marloes; Kuosa, Harri; Meier, H E Markus; Müller-Karulis, Baerbel; Nordberg, Kjell; Norkko, Alf; Nürnberg, Gertrud; Pitkänen, Heikki; Rabalais, Nancy N; Rosenberg, Rutger; Savchuk, Oleg P; Slomp, Caroline P; Voss, Maren; Wulff, Fredrik; Zillén, Lovisa

    2009-05-15

    Hypoxia, a growing worldwide problem, has been intermittently present in the modern Baltic Sea since its formation ca. 8000 cal. yr BP. However, both the spatial extent and intensity of hypoxia have increased with anthropogenic eutrophication due to nutrient inputs. Physical processes, which control stratification and the renewal of oxygen in bottom waters, are important constraints on the formation and maintenance of hypoxia. Climate controlled inflows of saline water from the North Sea through the Danish Straits is a critical controlling factor governing the spatial extent and duration of hypoxia. Hypoxia regulates the biogeochemical cycles of both phosphorus (P) and nitrogen (N) in the water column and sediments. Significant amounts of P are currently released from sediments, an order of magnitude larger than anthropogenic inputs. The Baltic Sea is unique for coastal marine ecosystems experiencing N losses in hypoxic waters below the halocline. Although benthic communities in the Baltic Sea are naturally constrained by salinity gradients, hypoxia has resulted in habitat loss over vast areas and the elimination of benthic fauna, and has severely disrupted benthic food webs. Nutrient load reductions are needed to reduce the extent, severity, and effects of hypoxia. PMID:19544833

  17. Glycolysis determines dichotomous regulation of T cell subsets in hypoxia

    PubMed Central

    Xu, Yang; Zhang, Ming; Savoldo, Barbara; Metelitsa, Leonid S.; Rodgers, John; Yustein, Jason T.; Neilson, Joel R.

    2016-01-01

    Hypoxia occurs in many pathological conditions, including chronic inflammation and tumors, and is considered to be an inhibitor of T cell function. However, robust T cell responses occur at many hypoxic inflammatory sites, suggesting that functions of some subsets are stimulated under low oxygen conditions. Here, we investigated how hypoxic conditions influence human T cell functions and found that, in contrast to naive and central memory T cells (TN and TCM), hypoxia enhances the proliferation, viability, and cytotoxic action of effector memory T cells (TEM). Enhanced TEM expansion in hypoxia corresponded to high hypoxia-inducible factor 1α (HIF1α) expression and glycolytic activity compared with that observed in TN and TCM. We determined that the glycolytic enzyme GAPDH negatively regulates HIF1A expression by binding to adenylate-uridylate–rich elements in the 3′-UTR region of HIF1A mRNA in glycolytically inactive TN and TCM. Conversely, active glycolysis with decreased GAPDH availability in TEM resulted in elevated HIF1α expression. Furthermore, GAPDH overexpression reduced HIF1α expression and impaired proliferation and survival of T cells in hypoxia, indicating that high glycolytic metabolism drives increases in HIF1α to enhance TEM function during hypoxia. This work demonstrates that glycolytic metabolism regulates the translation of HIF1A to determine T cell responses to hypoxia and implicates GAPDH as a potential mechanism for controlling T cell function in peripheral tissue. PMID:27294526

  18. Regulation of wound healing and fibrosis by hypoxia and hypoxia-inducible factor-1.

    PubMed

    Ruthenborg, Robin J; Ban, Jae-Jun; Wazir, Anum; Takeda, Norihiko; Kim, Jung-Whan

    2014-09-01

    Wound healing is a complex multi-step process that requires spatial and temporal orchestration of cellular and non-cellular components. Hypoxia is one of the prominent microenvironmental factors in tissue injury and wound healing. Hypoxic responses, mainly mediated by a master transcription factor of oxygen homeostasis, hypoxia-inducible factor-1 (HIF-1), have been shown to be critically involved in virtually all processes of wound healing and remodeling. Yet, mechanisms underlying hypoxic regulation of wound healing are still poorly understood. Better understanding of how the wound healing process is regulated by the hypoxic microenvironment and HIF-1 signaling pathway will provide insight into the development of a novel therapeutic strategy for impaired wound healing conditions such as diabetic wound and fibrosis. In this review, we will discuss recent studies illuminating the roles of HIF-1 in physiologic and pathologic wound repair and further, the therapeutic potentials of HIF-1 stabilization or inhibition.

  19. Hypoxia in human colorectal adenocarcinoma: Comparison between extrinsic and potential intrinsic hypoxia markers

    SciTech Connect

    Goethals, Laurence; Debucquoy, Annelies; Perneel, Christiaan; Geboes, Karel; Ectors, Nadine; De Schutter, Harlinde; Penninckx, Freddy; McBride, William H.; Begg, Adrian C.; Haustermans, Karin M. . E-mail: karin.haustermans@uzleuven.be

    2006-05-01

    Purpose: To detect and quantify hypoxia in colorectal adenocarcinomas by use of pimonidazole and iododeoxyuridine (IdUrd) as extrinsic markers and carbonic anhydrase IX (CA IX), microvessel density (MVD), epidermal growth-factor receptor (EGFR), and vascular endothelial growth factor (VEGF) as intrinsic markers of hypoxia. Methods and Material: Twenty patients with an adenocarcinoma of the left colon and rectum treated by primary surgery were injected with pimonidazole and IdUrd. Serial sections of tumor biopsies were single stained for VEGF, EGFR, Ki67, and double stained for blood vessels in combination with either pimonidazole, IdUrd, or CA IX. Percentage of expression was scored as well as colocalization of pimonidazole with CA IX. Results: The median percentage of hypoxia, as judged by pimonidazole staining, was 16.7% (range, 0-52.4%). The expression of pimonidazole correlated inversely with the total MVD and endothelial cord MVD (R = -0.55, p = 0.01; R = -0.47, p = 0.04). Good colocalization was found between pimonidazole and CA IX in only 30% of tumors, with no correlation overall between pimonidazole and CA IX, VEGF, or EGFR or between the different intrinsic markers. Cells around some vessels (0.08-11%) were negative for IdUrd but positive for Ki 67, which indicated their lack of perfusion at the time of injection. Conclusion: Chronic and acute hypoxic regions are present in colorectal tumors, as shown by pimonidazole and IdUrd staining. Only in a minority of tumors did an association exist between the areas stained by pimonidazole and those positive for CA IX. Pimonidazole also did not correlate with expression of other putative intrinsic hypoxia markers (VEGF, EGFR)

  20. Role of catalase on the hypoxia/reoxygenation stress in the hypoxia-tolerant Nile tilapia.

    PubMed

    Welker, Alexis F; Campos, Elida G; Cardoso, Luciano A; Hermes-Lima, Marcelo

    2012-05-01

    The specific contribution of each antioxidant enzyme to protection against the reoxygenation-associated oxidative stress after periods of hypoxia is not well understood. We assessed the physiological role of catalase during posthypoxic reoxygenation by the combination of two approaches. First, catalase activity of Nile tilapias (Oreochromis niloticus) was 90% suppressed by intraperitoneal injection of 3-amino-1,2,4-triazole (ATZ, 1g/kg). In ATZ-injected fish, liver GSH levels, oxidative stress markers, and activities of other antioxidant enzymes remained unchanged. Second, animals with depleted catalase activity (or those saline-injected) were subjected to a cycle of severe hypoxia (dissolved O(2) = 0.28 mg/l for 3 h) followed by reoxygenation (0.5 to 24 h). Hypoxia did not induce changes in the above-mentioned parameters, either in saline- or in ATZ-injected animals. Reoxygenation increased superoxide dismutase activity in saline-injected fish, whose levels were similar to ATZ-injected animals. The activities of glutathione S-transferase, selenium-dependent glutathione peroxidase, and total-GPX and the levels of GSH-eq, GSSG, and thiobarbituric acid reactive substances remained unchanged during reoxygenation in both saline- and ATZ-injected fish. The GSSG/GSH-eq ratio in ATZ-injected fish increased at 30 min of reoxygenation compared with saline-injected ones. Reoxygenation also increased carbonyl protein levels in saline-injected fish, whose levels were similar to the ATZ-injected group. Our work shows that inhibition of liver tilapia catalase causes a redox imbalance during reoxygenation, which is insufficient to induce further oxidative stress. This indicates the relevance of hepatic catalase for hypoxia/reoxygenation stress in tilapia fish. PMID:22378777

  1. Investigation of the combined effects of bedrest and mild hypoxia

    NASA Technical Reports Server (NTRS)

    Waligora, J. M.; Horrigan, D. J., Jr.; Bungo, M. W.; Conkin, J.

    1982-01-01

    Subjects were exposed to an 8-h mild hypoxia exposure (8000 ft. equivalent, 2438 m) with and without a 28-h period of 6 deg headdown bedrest. Anticipated responses to the bedrest and the hypoxia were observed. There was no indication that bedrest affected the arterial oxygenation or the oxygen gradient across the lungs of the subjects undergoing mild hypoxia. It is concluded that there is no evidence that would preclude an alveolar O2 pressure as low as 69 torr during contingency spacecraft operation.

  2. Hypoxia inducible factor-1 alpha and multiple myeloma

    PubMed Central

    Tiwary, Bhupendra Nath

    2016-01-01

    Rapid tumor growth creates a state of hypoxia in the tumor microenvironment and results in release of hypoxia inducible factor-1 alpha (HiF-1α) in the local milieu. Hypoxia inducible factor activity is deregulated in many human cancers, especially those that are highly hypoxic. In multiple myeloma (MM) in initial stages of disease establishment, the hypoxic bone marrow microenvironment supports the initial survival and growth of the myeloma cells. Hypoxic tumour cells are usually resistant to radiotherapy and most conventional chemotherapeutic agents, rendering them highly aggressive and metastatic. Therefore, HIF is an attractive, although challenging, therapeutic target in MM directly or indirectly in recent years. PMID:26900575

  3. Modulation of human sinus node function by systemic hypoxia

    NASA Technical Reports Server (NTRS)

    Eckberg, D. L.; Bastow, H., III; Scruby, A. E.

    1982-01-01

    The present study was conducted to determine whether bradycardia develops during systemic hypoxia in supine conscious human volunteers when respiratory frequency and tidal volume are maintained at constant levels. The obtained results suggest that mild hypoxia provokes cardioacceleration in humans, independent of changes of ventilation or baroreflex responsiveness. The earliest cardioacceleration is more prominent in the inspiratory than in the expiratory phase of respiration, and occurs with very small reductions of arterial oxygen saturation. Moderate systemic hypoxia dampens fluctuations of heart rate during the respiratory cycle.

  4. Developing vascular and hypoxia based theranostics in solid tumors

    NASA Astrophysics Data System (ADS)

    Koonce, Nathan A.

    Tissue hypoxia was recognized for its biological attenuating effects on ionizing radiation over a century ago and is a characteristic feature of many solid tumors. Clinical and experimental evidence indicates tumor hypoxia plays diverse and key roles in tumor progression, angiogenesis, and resistance to chemotherapy/radiotherapy. Hypoxia has known effects on progression and resistance to several standard treatment approaches and the significant history of study might suggest diagnostic imaging and therapeutic interventions would be routine in oncological practice. Curiously, this is not the case and the research results involved in this report will attempt to better understand and contribute to why this gap in knowledge exists and a rationale for harnessing the potential of detecting and targeting hypoxia. Despite the addition of oxygen and reversal of hypoxia being known as the best radiosensitizer, hypoxia remains unexploited in clinical cancer therapy. The studies reported herein detail development of a novel imaging technique to detect a subtype of tumor hypoxia, vascular hypoxia or hypoxemia, with a 17-fold increase (p<0.05) in uptake of pimonidazole targeted microbubbles observed compared to controls. This technique creates the potential to study the role of hypoxemia in progression and therapeutic response. Additionally, description of a nanoparticle-based therapy that targets tumor areas associated with tumor hypoxia and the tumor microenvironment in general is reported. TNF-loaded nanoparticles combined with radiotherapy resulted in a 5.25-fold growth delay that was found to be synergistic (p<0.05) and suggests clinical evaluation is warranted. An additional study to evaluate an approach to use thermal ablation of intratumoral hypoxia by an image-guided technique developed in our group is described along with a sequence dependence of radiation preceding ablation. A final study on the use of galectin-1 antagonist to significantly decrease (p<0.05) hypoxia

  5. Correlating hypoxia with insulin secretion using a fluorescent hypoxia detection system.

    PubMed

    Skiles, Matthew L; Fancy, Romone; Topiwala, Pritesh; Sahai, Suchit; Blanchette, James O

    2011-04-01

    A common obstacle to the survival of encapsulated tissue is oxygen insufficiency. This appears particularly true of encapsulated pancreatic β-cells. Our work investigates a fluorescent hypoxia detection system for early recognition of hypoxic stress in encapsulated pancreatic tissue. Murine insulinoma (MIN6) cells were engineered to produce a red fluorescent protein under the control of hypoxia-inducible-factor-1. Aggregates of these cells were encapsulated in poly(ethylene glycol) hydrogels at densities of 200,000, 600,000, and 1 million cells per capsule then incubated in either a 1% or 20% oxygen environment. Cell function was evaluated by daily measurement of glucose-stimulated insulin secretion. Encapsulated cells were also fluorescently imaged periodically over 72 h for expression of the marker signal. Results indicate that oxygen insufficiency severely impacts insulin release from MIN6 cells, and that large aggregates are especially vulnerable to oxygen limitations. Our marker was found to be successfully indicative of hypoxia and could be used as a predictor of subsequent insulin release. Further work will be required to fully characterize signal dynamics and to evaluate in vivo efficacy. The method presented here represents a unique and valuable approach to detecting hypoxic stress in living tissues which may prove useful to a variety of fields of biological research.

  6. Mitochondrial physiology and reactive oxygen species production are altered by hypoxia acclimation in killifish (Fundulus heteroclitus).

    PubMed

    Du, Sherry N N; Mahalingam, Sajeni; Borowiec, Brittney G; Scott, Graham R

    2016-04-15

    Many fish encounter hypoxia in their native environment, but the role of mitochondrial physiology in hypoxia acclimation and hypoxia tolerance is poorly understood. We investigated the effects of hypoxia acclimation on mitochondrial respiration, O2kinetics, emission of reactive oxygen species (ROS), and antioxidant capacity in the estuarine killifish ( ITALIC! Fundulus heteroclitus). Killifish were acclimated to normoxia, constant hypoxia (5 kPa O2) or intermittent diel cycles of nocturnal hypoxia (12 h:12 h normoxia:hypoxia) for 28-33 days and mitochondria were isolated from liver. Neither pattern of hypoxia acclimation affected the respiratory capacities for oxidative phosphorylation or electron transport, leak respiration, coupling control or phosphorylation efficiency. Hypoxia acclimation also had no effect on mitochondrial O2kinetics, but ITALIC! P50(the O2tension at which hypoxia inhibits respiration by 50%) was lower in the leak state than during maximal respiration, and killifish mitochondria endured anoxia-reoxygenation without any impact on mitochondrial respiration. However, both patterns of hypoxia acclimation reduced the rate of ROS emission from mitochondria when compared at a common O2tension. Hypoxia acclimation also increased the levels of protein carbonyls and the activities of superoxide dismutase and catalase in liver tissue (the latter only occurred in constant hypoxia). Our results suggest that hypoxia acclimation is associated with changes in mitochondrial physiology that decrease ROS production and may help improve hypoxia tolerance. PMID:26896545

  7. Intelligent Augmented Reality Training for Motherboard Assembly

    ERIC Educational Resources Information Center

    Westerfield, Giles; Mitrovic, Antonija; Billinghurst, Mark

    2015-01-01

    We investigate the combination of Augmented Reality (AR) with Intelligent Tutoring Systems (ITS) to assist with training for manual assembly tasks. Our approach combines AR graphics with adaptive guidance from the ITS to provide a more effective learning experience. We have developed a modular software framework for intelligent AR training…

  8. An Asynchronous Augmentation to Traditional Course Delivery.

    ERIC Educational Resources Information Center

    Wolverton, Marvin L.; Wolverton, Mimi

    Asynchronous augmentation facilitates distributed learning, which relies heavily on technology and self-learning. This paper reports the results of delivering a real estate principles course using an asynchronous course delivery format. It highlights one of many ways to enhance learning using technology, and it provides information concerning how…

  9. Personalized augmented reality for anatomy education.

    PubMed

    Ma, Meng; Fallavollita, Pascal; Seelbach, Ina; Von Der Heide, Anna Maria; Euler, Ekkehard; Waschke, Jens; Navab, Nassir

    2016-05-01

    Anatomy education is a challenging but vital element in forming future medical professionals. In this work, a personalized and interactive augmented reality system is developed to facilitate education. This system behaves as a "magic mirror" which allows personalized in-situ visualization of anatomy on the user's body. Real-time volume visualization of a CT dataset creates the illusion that the user can look inside their body. The system comprises a RGB-D sensor as a real-time tracking device to detect the user moving in front of a display. In addition, the magic mirror system shows text information, medical images, and 3D models of organs that the user can interact with. Through the participation of 7 clinicians and 72 students, two user studies were designed to respectively assess the precision and acceptability of the magic mirror system for education. The results of the first study demonstrated that the average precision of the augmented reality overlay on the user body was 0.96 cm, while the results of the second study indicate 86.1% approval for the educational value of the magic mirror, and 91.7% approval for the augmented reality capability of displaying organs in three dimensions. The usefulness of this unique type of personalized augmented reality technology has been demonstrated in this paper.

  10. CARE: Creating Augmented Reality in Education

    ERIC Educational Resources Information Center

    Latif, Farzana

    2012-01-01

    This paper explores how Augmented Reality using mobile phones can enhance teaching and learning in education. It specifically examines its application in two cases, where it is identified that the agility of mobile devices and the ability to overlay context specific resources offers opportunities to enhance learning that would not otherwise exist.…

  11. Get Real: Augmented Reality for the Classroom

    ERIC Educational Resources Information Center

    Mitchell, Rebecca; DeBay, Dennis

    2012-01-01

    Kids love augmented reality (AR) simulations because they are like real-life video games. AR simulations allow students to learn content while collaborating face to face and interacting with a multimedia-enhanced version of the world around them. Although the technology may seem advanced, AR software makes it easy to develop content-based…

  12. Location-Based Learning through Augmented Reality

    ERIC Educational Resources Information Center

    Chou, Te-Lien; Chanlin, Lih-Juan

    2014-01-01

    A context-aware and mixed-reality exploring tool cannot only effectively provide an information-rich environment to users, but also allows them to quickly utilize useful resources and enhance environment awareness. This study integrates Augmented Reality (AR) technology into smartphones to create a stimulating learning experience at a university…

  13. Design Principles for Augmented Reality Learning

    ERIC Educational Resources Information Center

    Dunleavy, Matt

    2014-01-01

    Augmented reality is an emerging technology that utilizes mobile, context-aware devices (e.g., smartphones, tablets) that enable participants to interact with digital information embedded within the physical environment. This overview of design principles focuses on specific strategies that instructional designers can use to develop AR learning…

  14. A Universal Logging Format for Augmentative Communication.

    ERIC Educational Resources Information Center

    Lesher, Gregory W.; Moulton, Bryan J.; Rinkus, Gerard; Higginbotham, D. Jeffery

    This report discusses how technical and technological advances in alternative and augmentative communication (AAC) have outstripped the ability to assess their impact on actual communication and argues that this is due in part to the lack of a consistent and reliable method to measure long-term communicative efficacy. The report proposes a…

  15. Introduction to augmented and virtual reality

    NASA Astrophysics Data System (ADS)

    Caudell, Thomas P.

    1995-12-01

    This paper introduces the field of augmented reality as a prolog to the body of papers in the remainder of this session. I describe the use of head-mounted display technologies to improve the efficiency and quality of human workers in their performance of engineering design, manufacturing, construction, testing, and maintenance activities. This technology is used to `augment' the visual field of the wearer with information necessary in the performance of the current task. The enabling technology is head-up (see-through) display head sets (HUDsets) combined with head position sensing, real world registration systems, and database access software. A primary difference between virtual reality (VR) and `augmented reality' (AR) is in the complexity of the perceived graphical objects. In AR systems, only simple wire frames, template outlines, designators, and text is displayed. An immediate result of this difference is that augmented reality systems can be driven by standard and inexpensive microprocessors. Many research issues must be addressed before this technology can be widely used, including tracking and registration, human 3D perception and reasoning, and human task performance issues.

  16. Antidepressant augmentation with anti-inflammatory agents.

    PubMed

    Andrade, Chittaranjan

    2014-09-01

    Antidepressant augmentation strategies are commonly employed to treat depressed patients who do not respond to antidepressant monotherapy. Neuroinflammatory mechanisms have been implicated in depression, and nonsteroidal anti-inflammatory drugs (NSAIDs) have been found effective in animal models of depression both in monotherapy and when used to augment antidepressant drugs. However, results with NSAIDs have been mixed in human observational studies, with both better and worse depression outcomes reported. Four small (pooled N = 160) randomized controlled trials suggest that celecoxib (200-400 mg/d) augmentation of antidepressant medication improves 4-6 week outcomes in major depressive disorder. There are no data, however, to support the use of celecoxib or other NSAIDs in antidepressant-resistant depression. There are also concerns about adverse events associated with NSAID treatment, and about pharmacodynamic drug interactions between these drugs and serotonin reuptake inhibitors. A reasonable conclusion for the present is that NSAID augmentation of antidepressants is, at best, a tentative approach in nonrefractory major depression.

  17. Augmenting the ADDIE Paradigm for Instructional Design

    ERIC Educational Resources Information Center

    Ni, Xiaopeng; Branch, Robert Maribe

    2008-01-01

    The authors discuss topics appropriate for augmenting the ADDIE paradigm for instructional design. The topics selected are based on data from a study of working professionals who successfully completed an instructional design and technology certificate program and who identified related topics that they regarded as beneficial. The participants…

  18. Expanded polytetrafluoroethylene augmentation of the lower face.

    PubMed

    Sherris, D A; Larrabee, W F

    1996-05-01

    Most options for rejuvenation of the lower face use soft-tissue fillers that augment the appropriate sites. Each of these options has associated risks and benefits. The U.S. Food and Drug Administration recently approved the use of expanded polytetrafluoroethylene (E-PTFE) as a soft-tissue filler in the face. From January 1991 through December 1993, the authors used E-PTFE soft-tissue patches for lower facial augmentation in 41 patients at 115 implant sites. Postsurgical follow-up has ranged from 2.5 to 4.5 years; during this time, complications have occurred in 4 patients. One implant had to be removed because of a seroma (1 patient), 4 implants required further secondary augmentation (2 patients), and 1 implant required revision because of malposition (1 patient). There have been no cases of implant infection, extrusion, long-term inflammation, or capsule formation. In this article, the authors review the technical aspects of E-PTFE use and discuss issues relating to the long-term efficacy of this new option for soft-tissue augmentation. The technique is also compared with other options for rejuvenation of the lower face. PMID:8628100

  19. Placental hypoxia: the lesions of maternal malperfusion.

    PubMed

    Parks, W Tony

    2015-02-01

    The placental lesions classically ascribed to placental hypoxia, here denoted maternal malperfusion (MMP), are among the more significant that a placental pathologist may encounter. Yet the appearance of these lesions may be subtle, and the clinical implication of their diagnosis is frequently unclear. The aim of this review is to provide a more nuanced perspective on the clinical utility of placental pathology for the detection of MMP. The review will first detail MMP lesions in the placenta and discuss their associations with pregnancy complications. The review will then delve into the diagnostic and interpretive difficulties of these lesions. Finally, recent research findings that may aid in the development of better diagnostic tools will be briefly discussed.

  20. Heart Rhythm Genomic Fabric in Hypoxia

    PubMed Central

    Iacobas, Dumitru A; Iacobas, Sanda; Haddad, Gabriel G

    2010-01-01

    The molecular mechanisms by which chronic hypoxia, whether constant (CCH) or intermittent (CIH), alters the heart rhythm are still under debate. Expression level, control, maturational profile and intercoordination of 54 genes encoding heart rhythm determinants (HRDs) were analyzed in 36 mice subjected for one, two or four weeks of their early life to normal atmospheric conditions or to CCH or CIH. Our analysis revealed a complex network of genes encoding various heart rate, inotropy and development controllers, receptors, ion channels and transporters, ankyrins, epigenetic modulators and intercalated disc components (adherens, cadherins, catenins, desmosomal, gap and tight junction proteins). The network is remodeled during maturation and substantially and differently altered by CIH and CCH. Gene Prominence Analysis that ranks the genes according to their expression stability and networking within functional gene webs, confirmed the HRD status of certain epigenetic modulators and components of the intercalated discs not yet associated with arrhythmia. PMID:20044980

  1. Plasma from human volunteers subjected to remote ischemic preconditioning protects human endothelial cells from hypoxia-induced cell damage.

    PubMed

    Weber, Nina C; Riedemann, Isabelle; Smit, Kirsten F; Zitta, Karina; van de Vondervoort, Djai; Zuurbier, Coert J; Hollmann, Markus W; Preckel, Benedikt; Albrecht, Martin

    2015-03-01

    Short repeated cycles of peripheral ischemia/reperfusion (I/R) can protect distant organs from subsequent prolonged I/R injury; a phenomenon known as remote ischemic preconditioning (RIPC). A RIPC-mediated release of humoral factors might play a key role in this protection and vascular endothelial cells are potential targets for these secreted factors. In the present study, RIPC-plasma obtained from healthy male volunteers was tested for its ability to protect human umbilical endothelial cells (HUVEC) from hypoxia-induced cell damage. 10 healthy male volunteers were subjected to a RIPC-protocol consisting of 4 × 5 min inflation/deflation of a blood pressure cuff located at the upper arm. Plasma was collected before (T0; control), directly after (T1) and 1 h after (T2) the RIPC procedure. HUVEC were subjected to 24 h hypoxia damage and simultaneously incubated with 5% of the respective RIPC-plasma. Cell damage was evaluated by lactate dehydrogenase (LDH)-measurements. Western blot experiments of hypoxia inducible factor 1 alpha (HIF1alpha), phosphorylated signal transducer and activator of transcription 5 (STAT5), protein kinase B (AKT) and extracellular signal-related kinase 1/2 (ERK-1/2) were performed. Furthermore, the concentrations of hVEGF were evaluated in the RIPC-plasma by sandwich ELISA. Hypoxia-induced cell damage was significantly reduced by plasma T1 (p = 0.02 vs T0). The protective effect of plasma T1 was accompanied by an augmentation of the intracellular HIF1alpha (p = 0.01 vs T0) and increased phosphorylation of ERK-1/2 (p = 0.03 vs T0). Phosphorylation of AKT and STAT5 remained unchanged. Analysis of the protective RIPC-plasma T1 showed significantly reduced levels of hVEGF (p = 0.01 vs T0). RIPC plasma protects endothelial cells from hypoxia-induced cell damage and humoral mediators as well as intracellular HIF1alpha may be involved.

  2. The Effect of Prenatal Hypoxia on Brain Development: Short- and Long-Term Consequences Demonstrated in Rodent Models

    ERIC Educational Resources Information Center

    Golan, Hava; Huleihel, Mahmoud

    2006-01-01

    Hypoxia (H) and hypoxia-ischemia (HI) are major causes of foetal brain damage with long-lasting behavioral implications. The effect of hypoxia has been widely studied in human and a variety of animal models. In the present review, we summarize the latest studies testing the behavioral outcomes following prenatal hypoxia/hypoxia-ischemia in rodent…

  3. Hypoxia-Responsive Copolymer for siRNA Delivery.

    PubMed

    Perche, Federico; Biswas, Swati; Patel, Niravkumar R; Torchilin, Vladimir P

    2016-01-01

    A wide variety of nanomedicine has been designed for cancer therapy. Herein, we describe the synthesis and evaluation of a hypoxia-responsive copolymer for siRNA delivery (Perche et al., Angew Chem Int Ed Engl 53:3362-3366, 2014). The synthesis is achieved using established coupling chemistry and accessible purification procedures. A polyelectrolyte-lipid conjugate (polyethyleneimine 1.8 kDa-dioleyl-phosphatidylinositol, PEI-PE) and polyethylene glycol 2000 (PEG) were assembled via the hypoxia-sensitive azobenzene (Azo) unit to obtain the PEG-Azo-PEI-DOPE copolymer. This copolymer can condense siRNA and shows hypoxia-induced cellular internalization and reporter gene downregulation in vitro and tumor accumulation in vivo after parenteral administration (Perche et al., Angew Chem Int Ed Engl 53:3362-3366, 2014). We also detail procedures to evaluate hypoxia-targeted polymers both in monolayer cultures, cancer cell spheroids and in tumor xenografts murine models. PMID:26530922

  4. DUBs, New Members in the Hypoxia Signaling clUb

    PubMed Central

    Schober, Amelie S.; Berra, Edurne

    2016-01-01

    Cellular protein homeostasis is tightly regulated by ubiquitination. Responsible for target protein ubiquitination is a class of enzymes, the so-called ubiquitin E3 ligases. They are opposed to a second class of enzymes, called deubiquitinating enzymes (DUBs), which can remove polyubiquitin chains from their specific target proteins. The coaction of the two sets of enzymes allows the cell to adapt its overall protein content and the abundance of particular proteins to a variety of cellular and environmental stresses, including hypoxia. In recent years, DUBs have been highlighted to play major roles in many diseases, including cancer, both as tumor suppressors and oncogenes. Therefore, DUBs are emerging as promising targets for cancer-cell specific treatment. Here, we will review the current understanding of DUBs implicated in the control of hypoxia-inducible factor, the regulation of DUBs by hypoxia, and the use of DUB-specific drugs to target tumor hypoxia-signaling. PMID:27014628

  5. Rearing of silkworm under hypobaric and hypoxia conditions

    NASA Astrophysics Data System (ADS)

    Hashimoto, Hirofumi; Nakayama, Shin; Yamashita, Masamichi; Space Agriculture Task Force, J.

    In order to investigate of a possibility of utilizing silkworm for the space agriculture, rearing of silkworms was examined under hypobaric and hypoxia conditions. In terms of structural mechanics, the lower inner pressure of Martian greenhouse has advantage to reduce requirements on physical properties of mechanical member of the pressurized structure. The main objective of this study is to know the influence of lower total pressure and hypoxia condition on silkworm. Silkworms are reared under following four hypobaric and hypoxia conditions, 10kPa pure oxygen, 20kPa pure oxygen, 10kPa oxygen and 10kPa nitrogen, and 10kPa oxygen and 90kPa nitrogen. After rearing them to pupa stage, growth of silkworms was found poor under all hypobaric hypoxia conditions compared to those grown under the normal atmospheric condition; the control group. The growth under total pressure of 20kPa is slightly fast.

  6. A New Device to Mimic Intermittent Hypoxia in Mice

    PubMed Central

    Vanhamme, Luc; Van Antwerpen, Pierre; Kerkhofs, Myriam; Legros, J. L.; Vanhaeverbeek, Michel; Van Meerhaeghe, Alain; Coussement, Gregory; Boudjeltia, Karim Zouaoui; Legrand, Alexandre

    2013-01-01

    Intermittent hypoxia (hypoxia-reoxygenation) is often associated with cardiovascular morbidity and mortality. We describe a new device which can be used to submit cohorts of mice to controlled and standardised hypoxia-normoxia cycles at an individual level. Mice were placed in individual compartments to which similar gas flow parameters were provided using an open loop strategy. Evaluations made using computational fluid dynamics were confirmed by studying changes in haemoglobin oxygen saturation in vivo. We also modified the parameters of the system and demonstrated its ability to generate different severities of cyclic hypoxemia very precisely, even with very high frequency cycles of hypoxia-reoxygenation. The importance of the parameters on reoxygenation was shown. This device will allow investigators to assess the effects of hypoxia–reoxygenation on different pathological conditions, such as obstructive sleep apnoea or chronic obstructive pulmonary disease. PMID:23565179

  7. Implications of Hypoxia in Breast Cancer Metastasis to Bone

    PubMed Central

    Gilkes, Daniele M.

    2016-01-01

    Most solid tumors contain regions of hypoxia in which increased cell proliferation promotes increased oxygen consumption and the condition is further exacerbated as cancer cells become localized far from a functional blood vessel, further decreasing the oxygen supply. An important mechanism that promotes cell adaptation to hypoxic conditions is the expression of hypoxia-inducible factors (HIFs). Hypoxia-inducible factors transcriptionally regulate many genes involved in the invasion and metastasis of breast cancer cells. Patients, whose primary tumor biopsies show high HIF expression levels, have a greater risk of metastasis. The current review will highlight the potential role of hypoxia in breast cancer metastasis to the bone by considering the regulation of many steps in the metastatic process that include invasion, migration, margination and extravasation, as well as homing signals and regulation of the bone microenvironment. PMID:27706047

  8. Role of posterior hypothalamus in hypobaric hypoxia induced pulmonary edema.

    PubMed

    Sharma, R K; Choudhary, R C; Reddy, M K; Ray, A; Ravi, K

    2015-01-01

    To investigate the role of posterior hypothalamus and central neurotransmitters in the pulmonary edema due to hypobaric hypoxia, rats were placed in a high altitude simulation chamber (barometric pressure-294.4 mmHg) for 24 h. Exposure to hypobaric hypoxia resulted in increases in mean arterial blood pressure, renal sympathetic nerve activity, right ventricular systolic pressure, lung wet to dry weight ratio and Evans blue dye leakage. There was a significant attenuation in these responses to hypobaric hypoxia (a) after lesioning posterior hypothalamus and (b) after chronic infusion of GABAA receptor agonist muscimol into posterior hypothalamus. No such attenuation was evident with the chronic infusion of the nitric oxide donor SNAP into the posterior hypothalamus. It is concluded that in hypobaric hypoxia, there is over-activity of posterior hypothalamic neurons probably due to a local decrease in GABA-ergic inhibition which increases the sympathetic drive causing pulmonary hypertension and edema. PMID:25448396

  9. Distribution of hypoxia and pycnocline off the Changjiang Estuary, China

    NASA Astrophysics Data System (ADS)

    Zhu, Jianrong; Zhu, Zhuoyi; Lin, Jun; Wu, Hui; Zhang, Jing

    2016-02-01

    The distributions of hypoxia and the pycnocline off the Changjiang Estuary were investigated by making several field observations from June 2 to 11, from July 18 to 23, from August 20 to 30, from October 3 to 13, 2006, and from August 27 to September 3, 2009. The observations from July 18 to 23, 2006, mainly focused on analyzing the relationship between hypoxia and the extension of the river plume and vertical stratification. In July, the Changjiang diluted water (CDW) was influenced by the easterly typhoon winds, causing it to extend northward rather than northeastward. By using the maximum vertical density gradient as a stratification intensity index, we found that the area of low (< 3 mg/L) dissolved oxygen (DO) was similar to the area of the pycnocline (> 2.0 kg/m4), which indicated that the summer pycnocline can effectively block vertical DO exchange and maintain hypoxia near the bottom. The observed hypoxic area was 500 km2, which was much smaller than the hypoxic areas observed in previous studies, and occurred because of the enhanced mixing that resulted from Typhoon Bill. During the observation period of August 20-30, 2006, the maximum density gradient was weaker due to distinct low river discharge. No hypoxia was observed in the eastern and southeastern sea off the Changjiang Estuary where hypoxia often occurs. However, hypoxia occurred over a large area of 15,400 km2 in the northern observation domain where hypoxia rarely occurs. During June 2-11 and October 3-13, 2006, the maximum density gradient was weaker, and the area with low DO was smaller than in July 2006. This finding resulted from relatively low river discharge and weaker solar heating. Consequently, no hypoxia occurred in the bottom layer. The area of low DO was similar to that of the maximum vertical density gradient. From August 27 to September 3, 2009, high river discharge and strong solar heating produced a larger and more intense pycnocline. The hypoxic area reached 3735 km2 and was very

  10. International hypoxia symposium XVIII: 26 February–02 March 2013

    PubMed Central

    2013-01-01

    The 18th International Hypoxia Symposia, Lake Louise, Alberta, Canada, February 26–March 02, 2013, covered molecular basis of hypoxic responses (e.g., hypoxia inducible factor, nitrite, nitrate, and hemoglobin) and integrative physiology (e.g., exercise physiology, cerebral blood flow responses, live-high train-low, and population genetics). Free communications and poster sessions covered scientific areas from controlled lab settings to field settings of high altitudes (Andes to Himalayas). PMID:24229461

  11. Circulatory responses to hypoxia in experimental myocardial infarction.

    NASA Technical Reports Server (NTRS)

    Schroll, M.; Robison, S. C.; Harrison, D. C.

    1971-01-01

    Three levels of decreased arterial oxygen saturation elicited a graded circulatory response in dogs, manifested by stepwise increases in cardiac output, left ventricular dp/dt, and stroke volume, and decreases in systemic vascular resistance. Responses to similar hypoxia challenges after experimental myocardial infarction were qualitatively similar but quantitatively less. Although the circulatory compensation for hypoxia was less effective after myocardial infarction, no further deterioration of the haemodynamics was noted.

  12. Upregulated Copper Transporters in Hypoxia-Induced Pulmonary Hypertension

    PubMed Central

    Zimnicka, Adriana M.; Tang, Haiyang; Guo, Qiang; Kuhr, Frank K.; Oh, Myung-Jin; Wan, Jun; Chen, Jiwang; Smith, Kimberly A.; Fraidenburg, Dustin R.; Choudhury, Moumita S. R.; Levitan, Irena; Machado, Roberto F.; Kaplan, Jack H.; Yuan, Jason X.-J.

    2014-01-01

    Pulmonary vascular remodeling and increased arterial wall stiffness are two major causes for the elevated pulmonary vascular resistance and pulmonary arterial pressure in patients and animals with pulmonary hypertension. Cellular copper (Cu) plays an important role in angiogenesis and extracellular matrix remodeling; increased Cu in vascular smooth muscle cells has been demonstrated to be associated with atherosclerosis and hypertension in animal experiments. In this study, we show that the Cu-uptake transporter 1, CTR1, and the Cu-efflux pump, ATP7A, were both upregulated in the lung tissues and pulmonary arteries of mice with hypoxia-induced pulmonary hypertension. Hypoxia also significantly increased expression and activity of lysyl oxidase (LOX), a Cu-dependent enzyme that causes crosslinks of collagen and elastin in the extracellular matrix. In vitro experiments show that exposure to hypoxia or treatment with cobalt (CoCl2) also increased protein expression of CTR1, ATP7A, and LOX in pulmonary arterial smooth muscle cells (PASMC). In PASMC exposed to hypoxia or treated with CoCl2, we also confirmed that the Cu transport is increased using 64Cu uptake assays. Furthermore, hypoxia increased both cell migration and proliferation in a Cu-dependent manner. Downregulation of hypoxia-inducible factor 1α (HIF-1α) with siRNA significantly attenuated hypoxia-mediated upregulation of CTR1 mRNA. In summary, the data from this study indicate that increased Cu transportation due to upregulated CTR1 and ATP7A in pulmonary arteries and PASMC contributes to the development of hypoxia-induced pulmonary hypertension. The increased Cu uptake and elevated ATP7A also facilitate the increase in LOX activity and thus the increase in crosslink of extracellular matrix, and eventually leading to the increase in pulmonary arterial stiffness. PMID:24614111

  13. Influence of sustained hypoxia on the sensation of dyspnea.

    PubMed

    Chonan, T; Okabe, S; Hida, W; Satoh, M; Kikuchi, Y; Takishima, T; Shirato, K

    1998-08-01

    We assessed the effect of sustained isocapnic hypoxia (PCO2 = 40 Torr, SaO2 = 80%) on the sensation of dyspnea in 16 normal healthy males. Subjects rated the sensation of dyspnea (c) on 15 cm visual analog scales during 20 min of sustained hypoxia. Following this hypoxic period, 8 subjects undertook mild exercise (10-50 W on a bicycle ergometer for 3 min) under the continuation of hypoxia. During sustained hypoxia, psi increased initially with ventilation from 0.6 +/- 0.2 (n = 16, mean +/- SE) to 2.9 +/- 0.6 at peak ventilation, but it decreased with ventilatory depression to 1.6 +/- 0.4. Dyspnea intensity during hypoxic exercise was significantly smaller than that at peak ventilation in the resting hypoxic period (2.3 +/- 0.7 vs. 3.9 +/- 1.0), although the ventilation was greater during exercise (24.0 +/- 3.0 vs. 19.7 +/- 1.4 l/min). These results indicate that sustained hypoxia has a biphasic, i.e., initial stimulatory and delayed depressant, effect on dyspnea and on ventilation. It is suggested that the dyspnea sensing mechanism is suppressed during mild exercise under sustained hypoxia.

  14. Carotid body oxygen sensing and adaptation to hypoxia.

    PubMed

    López-Barneo, José; Macías, David; Platero-Luengo, Aida; Ortega-Sáenz, Patricia; Pardal, Ricardo

    2016-01-01

    The carotid body (CB) is the principal arterial chemoreceptor that mediates the hyperventilatory response to hypoxia. Our understanding of CB function and its role in disease mechanisms has progressed considerably in the last decades, particularly in recent years. The sensory elements of the CB are the neuron-like glomus cells, which contain numerous transmitters and form synapses with afferent sensory fibers. The activation of glomus cells under hypoxia mainly depends on the modulation of O2-sensitive K(+) channels which leads to cell depolarization and the opening of Ca(2+) channels. This model of sensory transduction operates in all mammalian species studied thus far, including man. However, the molecular mechanisms underlying the modulation of ion channel function by changes in the O2 level are as yet unknown. The CB plays a fundamental role in acclimatization to sustained hypoxia. Mice with CB atrophy or patients who have undergone CB resection due to surgical treatments show a marked intolerance to even mild hypoxia. CB growth under hypoxia is supported by the existence of a resident population of neural crest-derived stem cells of glia-like phenotype. These stem cells are not highly affected by exposure to low O2 tension; however, there are abundant synapse-like contacts between the glomus cells and stem cells (chemoproliferative synapses), which may be needed to trigger progenitor cell proliferation and differentiation under hypoxia. CB hypo- or hyper-activation may also contribute to the pathogenesis of several prevalent human diseases.

  15. The Effect of Hypoxia on Mesenchymal Stem Cell Biology

    PubMed Central

    Ejtehadifar, Mostafa; Shamsasenjan, Karim; Movassaghpour, Aliakbar; Akbarzadehlaleh, Parvin; Dehdilani, Nima; Abbasi, Parvaneh; Molaeipour, Zahra; Saleh, Mahshid

    2015-01-01

    Although physiological and pathological role of hypoxia have been appreciated in mammalians for decades however the cellular biology of hypoxia more clarified in the past 20 years. Discovery of the transcription factor hypoxia-inducible factor (HIF)-1, in the 1990s opened a new window to investigate the mechanisms behind hypoxia. In different cellular contexts HIF-1 activation show variable results by impacting various aspects of cell biology such as cell cycle, apoptosis, differentiation and etc. Mesenchymal stem cells (MSC) are unique cells which take important role in tissue regeneration. They are characterized by self-renewal capacity, multilineage potential, and immunosuppressive property. Like so many kind of cells, hypoxia induces different responses in MSCs by HIF- 1 activation. The activation of this molecule changes the growth, multiplication, differentiation and gene expression profile of MSCs in their niche by a complex of signals. This article briefly discusses the most important effects of hypoxia in growth kinetics, signalling pathways, cytokine secretion profile and expression of chemokine receptors in different conditions. PMID:26236651

  16. Hypoxia and adipose tissue function and dysfunction in obesity.

    PubMed

    Trayhurn, Paul

    2013-01-01

    The rise in the incidence of obesity has led to a major interest in the biology of white adipose tissue. The tissue is a major endocrine and signaling organ, with adipocytes, the characteristic cell type, secreting a multiplicity of protein factors, the adipokines. Increases in the secretion of a number of adipokines occur in obesity, underpinning inflammation in white adipose tissue and the development of obesity-associated diseases. There is substantial evidence, particularly from animal studies, that hypoxia develops in adipose tissue as the tissue mass expands, and the reduction in Po(2) is considered to underlie the inflammatory response. Exposure of white adipocytes to hypoxic conditions in culture induces changes in the expression of >1,000 genes. The secretion of a number of inflammation-related adipokines is upregulated by hypoxia, and there is a switch from oxidative metabolism to anaerobic glycolysis. Glucose utilization is increased in hypoxic adipocytes with corresponding increases in lactate production. Importantly, hypoxia induces insulin resistance in fat cells and leads to the development of adipose tissue fibrosis. Many of the responses of adipocytes to hypoxia are initiated at Po(2) levels above the normal physiological range for adipose tissue. The other cell types within the tissue also respond to hypoxia, with the differentiation of preadipocytes to adipocytes being inhibited and preadipocytes being transformed into leptin-secreting cells. Overall, hypoxia has pervasive effects on the function of adipocytes and appears to be a key factor in adipose tissue dysfunction in obesity.

  17. Wnt Pathway Activation Increases Hypoxia Tolerance during Development

    PubMed Central

    Gersten, Merril; Zhou, Dan; Azad, Priti; Haddad, Gabriel G.; Subramaniam, Shankar

    2014-01-01

    Adaptation to hypoxia, defined as a condition of inadequate oxygen supply, has enabled humans to successfully colonize high altitude regions. The mechanisms attempted by organisms to cope with short-term hypoxia include increased ATP production via anaerobic respiration and stabilization of Hypoxia Inducible Factor 1α (HIF-1α). However, less is known about the means through which populations adapt to chronic hypoxia during the process of development within a life time or over generations. Here we show that signaling via the highly conserved Wnt pathway impacts the ability of Drosophila melanogaster to complete its life cycle under hypoxia. We identify this pathway through analyses of genome sequencing and gene expression of a Drosophila melanogaster population adapted over >180 generations to tolerate a concentration of 3.5–4% O2 in air. We then show that genetic activation of the Wnt canonical pathway leads to increased rates of adult eclosion in low O2. Our results indicate that a previously unsuspected major developmental pathway, Wnt, plays a significant role in hypoxia tolerance. PMID:25093834

  18. Mild hypoxia affects synaptic connectivity in cultured neuronal networks.

    PubMed

    Hofmeijer, Jeannette; Mulder, Alex T B; Farinha, Ana C; van Putten, Michel J A M; le Feber, Joost

    2014-04-01

    Eighty percent of patients with chronic mild cerebral ischemia/hypoxia resulting from chronic heart failure or pulmonary disease have cognitive impairment. Overt structural neuronal damage is lacking and the precise cause of neuronal damage is unclear. As almost half of the cerebral energy consumption is used for synaptic transmission, and synaptic failure is the first abrupt consequence of acute complete anoxia, synaptic dysfunction is a candidate mechanism for the cognitive deterioration in chronic mild ischemia/hypoxia. Because measurement of synaptic functioning in patients is problematic, we use cultured networks of cortical neurons from new born rats, grown over a multi-electrode array, as a model system. These were exposed to partial hypoxia (partial oxygen pressure of 150Torr lowered to 40-50Torr) during 3 (n=14) or 6 (n=8) hours. Synaptic functioning was assessed before, during, and after hypoxia by assessment of spontaneous network activity, functional connectivity, and synaptically driven network responses to electrical stimulation. Action potential heights and shapes and non-synaptic stimulus responses were used as measures of individual neuronal integrity. During hypoxia of 3 and 6h, there was a statistically significant decrease of spontaneous network activity, functional connectivity, and synaptically driven network responses, whereas direct responses and action potentials remained unchanged. These changes were largely reversible. Our results indicate that in cultured neuronal networks, partial hypoxia during 3 or 6h causes isolated disturbances of synaptic connectivity.

  19. Babies who die from labour-related intrapartum hypoxia: a confidential enquiry in South African public hospitals.

    PubMed

    Buchmann, E J; Pattinson, R C

    2006-01-01

    Seventeen hospitals, from a range of health-care environments, participated in confidential enquiries of perinatal deaths resulting from labour-related intrapartum hypoxia. There were 102 deaths, including 22 stillbirths and 80 neonatal deaths. The mean birthweight was 3021 g. The active phase of the first stage of labour was prolonged beyond 12 h in six cases, and oxytocin was used for induction or augmentation in 10 women. Fetal heart decelerations were detected in 39 (49%) of the babies that went on to die in the neonatal period, and meconium passage was evident in 50 (63%). There were six breech presentations, and seven cases of cord prolapse. The majority of these deaths occurred in low-risk women with apparently uncomplicated labour. There appears to be a failure to detect or respond to evidence of fetal distress. Intrapartum care for all women in labour requires close attention to detail in monitoring fetal health.

  20. Hypoxia-induced carbonic anhydrase IX facilitates lactate flux in human breast cancer cells by non-catalytic function

    PubMed Central

    Jamali, Somayeh; Klier, Michael; Ames, Samantha; Felipe Barros, L.; McKenna, Robert; Deitmer, Joachim W.; Becker, Holger M.

    2015-01-01

    The most aggressive tumour cells, which often reside in hypoxic environments, rely on glycolysis for energy production. Thereby they release vast amounts of lactate and protons via monocarboxylate transporters (MCTs), which exacerbates extracellular acidification and supports the formation of a hostile environment. We have studied the mechanisms of regulated lactate transport in MCF-7 human breast cancer cells. Under hypoxia, expression of MCT1 and MCT4 remained unchanged, while expression of carbonic anhydrase IX (CAIX) was greatly enhanced. Our results show that CAIX augments MCT1 transport activity by a non-catalytic interaction. Mutation studies in Xenopus oocytes indicate that CAIX, via its intramolecular H+-shuttle His200, functions as a “proton-collecting/distributing antenna” to facilitate rapid lactate flux via MCT1. Knockdown of CAIX significantly reduced proliferation of cancer cells, suggesting that rapid efflux of lactate and H+, as enhanced by CAIX, contributes to cancer cell survival under hypoxic conditions. PMID:26337752

  1. Differential alteration by hypercapnia and hypoxia of the apneustic respiratory pattern in decerebrate cats

    PubMed Central

    John, Walter M. St

    1979-01-01

    1. A combination of bilateral lesions within the nucleus parabrachialis medialis complex (n.p.b.m.) and bilateral vagotomy typically resulted in an apneustic respiratory pattern in decerebrate and paralysed cats. Integrated efferent phrenic nerve activity was recorded as an index of the respiratory rhythm. 2. Changes in components of this apneustic breathing cycle were evaluated in response to steady-state hypercapnia and hypoxia. The components evaluated were (a) the period of phrenic discharge (inspiratory time, TI), (b) the period of no detectable phrenic activity (expiratory time, TE), (c) the total duration of the apneustic respiratory cycle (TTOT, the sum of TI and TE), and (d) the average height of the integrated phrenic nerve activity (apneustic depth). 3. Elevations of PA, CO2 from values below 45 torr to 50-60 torr, under both hyperoxic and normoxic conditions, resulted in significant elevations of TI, TE, TTOT and depth. Further PA, CO2 elevations to approximately 70 torr caused no change, or frequently, a decrease in TI, TE and TTOT; the apneustic depth increased in most animals. 4. Diminutions in PA, O2 from normoxic to hypoxic levels at isocapnia typically caused an increase in apneustic depth and, concomitantly, significant decreases in TI, TE and TTOT. 5. Pharmacological stimulation of the carotid chemoreceptors by intracarotid administration of 1·0-20 μg NaCN produced a premature onset of phrenic nerve activity if delivered during the expiratory period. Such NaCN administrations, delivered during the inspiratory phase, resulted in an augmentation of the integrated phrenic discharge and a premature termination of phrenic activity. Carotid sinus nerve section eliminated the response to NaCN administration. 6. In experimental animals having bilateral carotid sinus nerve section, normoxic hypercapnia caused similar changes in the apneustic breathing pattern to those recorded in cats having intact carotid chemoreceptors. However, isocapnic hypoxia

  2. FemHab: The effects of bed rest and hypoxia on oxidative stress in healthy women.

    PubMed

    Debevec, Tadej; Pialoux, Vincent; Ehrström, Sabine; Ribon, Alexandra; Eiken, Ola; Mekjavic, Igor B; Millet, Grégoire P

    2016-04-15

    Independently, both inactivity and hypoxia augment oxidative stress. This study, part of the FemHab project, investigated the combined effects of bed rest-induced unloading and hypoxic exposure on oxidative stress and antioxidant status. Healthy, eumenorrheic women were randomly assigned to the following three 10-day experimental interventions: normoxic bed rest (NBR;n= 11; PiO2 = 133 mmHg), normobaric hypoxic bed rest (HBR;n= 12; PiO2 = 90 mmHg), and ambulatory hypoxic confinement (HAMB;n= 8: PiO2 = 90 mmHg). Plasma samples, obtained before (Pre), during (D2, D6), immediately after (Post) and 24 h after (Post+1) each intervention, were analyzed for oxidative stress markers [advanced oxidation protein products (AOPP), malondialdehyde (MDA), and nitrotyrosine], antioxidant status [superoxide dismutase (SOD), catalase, ferric-reducing antioxidant power (FRAP), glutathione peroxidase (GPX), and uric acid (UA)], NO metabolism end-products (NOx), and nitrites. Compared with baseline, AOPP increased in NBR and HBR on D2 (+14%; +12%;P< 0.05), D6 (+19%; +15%;P< 0.05), and Post (+22%; +21%;P< 0.05), respectively. MDA increased at Post+1 in NBR (+116%;P< 0.01) and D2 in HBR (+114%;P< 0.01) and HAMB (+95%;P< 0.05). Nitrotyrosine decreased (-45%;P< 0.05) and nitrites increased (+46%;P< 0.05) at Post+1 in HAMB only. Whereas SOD was higher at D6 (+82%) and Post+1 (+67%) in HAMB only, the catalase activity increased on D6 (128%) and Post (146%) in HBR and HAMB, respectively (P< 0.05). GPX was only reduced on D6 (-20%;P< 0.01) and Post (-18%;P< 0.05) in HBR. No differences were observed in FRAP and NOx. UA was higher at Post in HBR compared with HAMB (P< 0.05). These data indicate that exposure to combined inactivity and hypoxia impairs prooxidant/antioxidant balance in healthy women. Moreover, habitual activity levels, as opposed to inactivity, seem to blunt hypoxia-related oxidative stress via antioxidant system upregulation. PMID:26796757

  3. Molecular Imaging of Tumor Hypoxia: Existing Problems and Their Potential Model-Based Solutions.

    PubMed

    Shi, Kuangyu; Ziegler, Sibylle I; Vaupel, Peter

    2016-01-01

    Molecular imaging of tissue hypoxia generates contrast in hypoxic areas by applying hypoxia-specific tracers in organisms. In cancer tissue, the injected tracer needs to be transported over relatively long distances and accumulates slowly in hypoxic regions. Thus, the signal-to-background ratio of hypoxia imaging is very small and a non-specific accumulation may suppress the real hypoxia-specific signals. In addition, the heterogeneous tumor microenvironment makes the assessment of the tissue oxygenation status more challenging. In this study, the diffusion potential of oxygen and of a hypoxia tracer for 4 different hypoxia subtypes: ischemic acute hypoxia, hypoxemic acute hypoxia, diffusion-limited chronic hypoxia and anemic chronic hypoxia are theoretically assessed. In particular, a reaction-diffusion equation is introduced to quantitatively analyze the interstitial diffusion of the hypoxia tracer [(18)F]FMISO. Imaging analysis strategies are explored based on reaction-diffusion simulations. For hypoxia imaging of low signal-to-background ratio, pharmacokinetic modelling has advantages to extract underlying specific binding signals from non-specific background signals and to improve the assessment of tumor oxygenation. Different pharmacokinetic models are evaluated for the analysis of the hypoxia tracer [(18)F]FMISO and optimal analysis model were identified accordingly. The improvements by model-based methods for the estimation of tumor oxygenation are in agreement with experimental data. The computational modelling offers a tool to explore molecular imaging of hypoxia and pharmacokinetic modelling is encouraged to be employed in the corresponding data analysis. PMID:27526129

  4. HYPOXIA IN THE NORTHERN GULF OF MEXICO: DOES THE SCIENCE SUPPORT THE PLAN TO REDUCE, MITIGATE, AND CONTROL HYPOXIA?

    EPA Science Inventory

    We update and reevaluate the scientific information on the distribution, history and causes of continental shelf hypoxia that supports the 2001 "Action Plan for Reducing, Mitigating, and Controlling Hypoxiain the Northern Gulf of Mexico," incorporating data, publications, and res...

  5. TCDD Induces the Hypoxia-Inducible Factor (HIF)-1α Regulatory Pathway in Human Trophoblastic JAR Cells

    PubMed Central

    Liao, Tien-Ling; Chen, Su-Chee; Tzeng, Chii-Reuy; Kao, Shu-Huei

    2014-01-01

    The exposure to dioxin can compromise pregnancy outcomes and increase the risk of preterm births. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been demonstrated to induce placental hypoxia at the end of pregnancy in a rat model, and hypoxia has been suggested to be the cause of abnormal trophoblast differentiation and placental insufficiency syndromes. In this study, we demonstrate that the non-hypoxic stimulation of human trophoblastic cells by TCDD strongly increased hypoxia inducible factor-1 alpha (HIF-1α) stabilization. TCDD exposure induced the generation of reactive oxygen species (ROS) and nitric oxide. TCDD-induced HIF-1α stabilization and Akt phosphorylation was inhibited by pretreatment with wortmannin (a phosphatidylinositol 3-kinase (PI3K) inhibitor) or N-acetylcysteine (a ROS scavenger). The augmented HIF-1α stabilization by TCDD occurred via the ROS-dependent activation of the PI3K/Akt pathway. Additionally, a significant increase in invasion and metallomatrix protease-9 activity was found in TCDD-treated cells. The gene expression of vascular endothelial growth factor and placental growth factor was induced upon TCDD stimulation, whereas the protein levels of peroxisome proliferator-activated receptor γ (PPARγ), PPARγ coactivator-1α, mitochondrial transcription factor, and uncoupling protein 2 were decreased. Our results indicate that an activated HIF-1α pathway, elicited oxidative stress, and induced metabolic stress contribute to TCDD-induced trophoblastic toxicity. These findings may provide molecular insight into the TCDD-induced impairment of trophoblast function and placental development. PMID:25272228

  6. Alterations in left ventricular function during intermittent hypoxia: Possible involvement of O-GlcNAc protein and MAPK signaling.

    PubMed

    Guo, Xueling; Shang, Jin; Deng, Yan; Yuan, Xiao; Zhu, Die; Liu, Huiguo

    2015-07-01

    Obstructive sleep apnea, characterized by recurrent episodes of hypoxia [intermittent hypoxia (IH)], has been identified as a risk factor for cardiovascular diseases. The O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) of proteins has important regulatory implications on the pathophysiology of cardiovascular disorders. In this study, we examined the role of O-GlcNAcylation in cardiac architecture and left ventricular function following IH. Rats were randomly assigned to a normoxia and IH group (2 min 21% O2; 2 min 6-8% O2). Left ventricular function, myocardial morphology and the levels of signaling molecules were then measured. IH induced a significant increase in blood pressure, associated with a gradually abnormal myocardial architecture. The rats exposed to 2 or 3 weeks of IH presented with augmented left ventricular systolic and diastolic function, which declined at week 4. Consistently, the O-GlcNAc protein and O-GlcNAcase (OGA) levels in the left ventricular tissues steadily increased following IH, reaching peak levels at week 3. The O-GlcNAc transferase (OGT), extracellular signal-regulated kinase 1/2 (ERK1/2) and the p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation levels were affected in an opposite manner. The phosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) remained unaltered. In parallel, compared with exposure to normoxia, 4 weeks of IH augmented the O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease in OGA levels and an increase in the levels of myocardial nuclear factor-κB (NF-κB), inflammatory cytokines, caspase-3 and cardiomyocyte apoptosis. Taken together, our suggest a possible involvement of O-GlcNAc protein and MAPK signaling in the alterations of left ventricular function and cardiac injury following IH.

  7. H2S Regulates Hypobaric Hypoxia-Induced Early Glio-Vascular Dysfunction and Neuro-Pathophysiological Effects

    PubMed Central

    Kumar, Gaurav; Chhabra, Aastha; Mishra, Shalini; Kalam, Haroon; Kumar, Dhiraj; Meena, Ramniwas; Ahmad, Yasmin; Bhargava, Kalpana; Prasad, Dipti N.; Sharma, Manish

    2016-01-01

    Hypobaric Hypoxia (HH) is an established risk factor for various neuro-physiological perturbations including cognitive impairment. The origin and mechanistic basis of such responses however remain elusive. We here combined systems level analysis with classical neuro-physiological approaches, in a rat model system, to understand pathological responses of brain to HH. Unbiased ‘statistical co-expression networks’ generated utilizing temporal, differential transcriptome signatures of hippocampus—centrally involved in regulating cognition—implicated perturbation of Glio-Vascular homeostasis during early responses to HH, with concurrent modulation of vasomodulatory, hemostatic and proteolytic processes. Further, multiple lines of experimental evidence from ultra-structural, immuno-histological, substrate-zymography and barrier function studies unambiguously supported this proposition. Interestingly, we show a significant lowering of H2S levels in the brain, under chronic HH conditions. This phenomenon functionally impacted hypoxia-induced modulation of cerebral blood flow (hypoxic autoregulation) besides perturbing the strength of functional hyperemia responses. The augmentation of H2S levels, during HH conditions, remarkably preserved Glio-Vascular homeostasis and key neuro-physiological functions (cerebral blood flow, functional hyperemia and spatial memory) besides curtailing HH-induced neuronal apoptosis in hippocampus. Our data thus revealed causal role of H2S during HH-induced early Glio-Vascular dysfunction and consequent cognitive impairment. PMID:27211559

  8. An Augmented Reality based 3D Catalog

    NASA Astrophysics Data System (ADS)

    Yamada, Ryo; Kishimoto, Katsumi

    This paper presents a 3D catalog system that uses Augmented Reality technology. The use of Web-based catalog systems that present products in 3D form is increasing in various fields, along with the rapid and widespread adoption of Electronic Commerce. However, 3D shapes could previously only be seen in a virtual space, and it was difficult to understand how the products would actually look in the real world. To solve this, we propose a method that combines the virtual and real worlds simply and intuitively. The method applies Augmented Reality technology, and the system developed based on the method enables users to evaluate 3D virtual products in a real environment.

  9. Augmenting Probabilistic Risk Assesment with Malevolent Initiators

    SciTech Connect

    Curtis Smith; David Schwieder

    2011-11-01

    As commonly practiced, the use of probabilistic risk assessment (PRA) in nuclear power plants only considers accident initiators such as natural hazards, equipment failures, and human error. Malevolent initiators are ignored in PRA, but are considered the domain of physical security, which uses vulnerability assessment based on an officially specified threat (design basis threat). This paper explores the implications of augmenting and extending existing PRA models by considering new and modified scenarios resulting from malevolent initiators. Teaming the augmented PRA models with conventional vulnerability assessments can cost-effectively enhance security of a nuclear power plant. This methodology is useful for operating plants, as well as in the design of new plants. For the methodology, we have proposed an approach that builds on and extends the practice of PRA for nuclear power plants for security-related issues. Rather than only considering 'random' failures, we demonstrated a framework that is able to represent and model malevolent initiating events and associated plant impacts.

  10. Detonation wave augmentation of gas turbines

    NASA Technical Reports Server (NTRS)

    Wortman, A.

    1984-01-01

    The results of a feasibility study that examined the effects of using detonation waves to augment the performance of gas turbines are reported. The central ideas were to reduce compressor requirements and to maintain high performance in jet engines. Gasdynamic equations were used to model the flows associated with shock waves generated by the detonation of fuel in detonator tubes. Shock wave attenuation to the level of Mach waves was found possible, thus eliminating interference with the compressor and the necessity of valves and seals. A preliminary parametric study of the performance of a compressor working at a 4:1 ratio in a conceptual design of a detonation wave augmented jet engine in subsonic flight indicated a clear superiority over conventional designs in terms of fuel efficiency and thrust.

  11. Vertebral Augmentation: State of the Art

    PubMed Central

    Nabhane, Linda; Issa El Khoury, Fouad; Kreichati, Gaby; El Rachkidi, Rami

    2016-01-01

    Osteoporotic vertebral compression fractures (OVF) are an increasing public health problem. Cement augmentation (vertebroplasty of kyphoplasty) helps stabilize painful OVF refractory to medical treatment. This stabilization is thought to improve pain and functional outcome. Vertebroplasty consists of injecting cement into a fractured vertebra using a percutaneous transpedicular approach. Balloon kyphoplasty uses an inflatable balloon prior to injecting the cement. Although kyphoplasty is associated with significant improvement of local kyphosis and less cement leakage, this does not result in long-term clinical and functional improvement. Moreover, vertebroplasty is favored by some due to the high cost of kyphoplasty. The injection of cement increases the stiffness of the fracture vertebrae. This can lead, in theory, to adjacent OVF. However, many studies found no increase of subsequent fracture when comparing medical treatment to cement augmentation. Kyphoplasty can have a protective effect due to restoration of sagittal balance. PMID:27114782

  12. Improved approximations for control augmented structural synthesis

    NASA Technical Reports Server (NTRS)

    Thomas, H. L.; Schmit, L. A.

    1990-01-01

    A methodology for control-augmented structural synthesis is presented for structure-control systems which can be modeled as an assemblage of beam, truss, and nonstructural mass elements augmented by a noncollocated direct output feedback control system. Truss areas, beam cross sectional dimensions, nonstructural masses and rotary inertias, and controller position and velocity gains are treated simultaneously as design variables. The structural mass and a control-system performance index can be minimized simultaneously, with design constraints placed on static stresses and displacements, dynamic harmonic displacements and forces, structural frequencies, and closed-loop eigenvalues and damping ratios. Intermediate design-variable and response-quantity concepts are used to generate new approximations for displacements and actuator forces under harmonic dynamic loads and for system complex eigenvalues. This improves the overall efficiency of the procedure by reducing the number of complete analyses required for convergence. Numerical results which illustrate the effectiveness of the method are given.

  13. [Augmentation enterocystoplasty. Apropos of 15 cases].

    PubMed

    Benjelloun, S; Elmrini, M; Bennani, S; Aboutaieb, R

    1995-01-01

    We reviewed the efficacy of augmentation enterocystoplasty about 15 cases, based on technical modalities and intestinal loop used. There were 10 tuberculosis bladders, 2 bilharzial bladders, 2 interstitial cystitis and one neurogenic bladder. We used for bladder augmentation the sigmoid (7 cases), ileum (6 cases) and coeco-ileum (2 cases). Ureteroileoplasty is associated in three cases for large tuberculous ureteral stenosis, and reimplantation of ureter in the neobladder is realised in seven cases. The results with detubularized ileum were excellent. We observed in one patient persistence of dilatation of upper urinary tract after use of detubularized sigmoid. The results with use of ileocoecum are poor. We observed good results by using detubularized ileum, so we prefer this intestinal loop than the others. There was no significative difference between different detubularisation technics. Reimplantation of ureter inneobladder is indicated when there is terminal ureteral lesions. PMID:8554290

  14. Projectile oscillations in augmented rail guns

    SciTech Connect

    Hodgdon, M.L.; Fowler, C.M.; Homan, C.G.

    1986-01-01

    The projectile in an inductive store-powered rail gun, augmented by an external magnetic field, will oscillate under certain conditions. This behavior is easily understood when there is no resistance in the circuit comprising the storage coil, rails and armature. In this case, the flux in the complete circuit is conserved. However, as the projectile moves down the rails, more flux from the augmenting field is picked up. This must be accompanied by a decrease in current in the system to conserve the total flux. At a certain distance down the rails, the current must reverse to conserve the flux, and thus the force on the projectile reverses. This mechanism leads to oscillation of the projectile. An analytic solution is given for the case in which the resistance is zero.

  15. TDRSS Augmentation Service for Satellites (TASS)

    NASA Technical Reports Server (NTRS)

    Heckler, Gregory W.; Gramling, Cheryl; Valdez, Jennifer; Baldwin, Philip

    2016-01-01

    In 2015, NASA Goddard Space Flight Center (GSFC) reinvigorated the development of the TDRSS Augmentation Service for Satellites (TASS). TASS is a global, space-based, communications and navigation service for users of Global Navigation Satellite Systems (GNSS) and the Tracking and Data Relay Satellite System (TDRSS). TASS leverages the existing TDRSS to provide an S-band beacon radio navigation and messaging source to users at orbital altitudes 1400 km and below.

  16. The ligament augmentation device: an historical perspective.

    PubMed

    Kumar, K; Maffulli, N

    1999-05-01

    Anterior cruciate ligament (ACL) injury is the most common ligament injury in the knee, and a significant number of patients may develop progressive instability and disability despite aggressive rehabilitation. Various materials have been used for its reconstruction. These include autografts, allografts, prosthetic ligaments, and synthetic augmentation of the biological tissue. The concept of ligament augmentation device (LAD) arose from the observation that biological grafts undergo a phase of degeneration and loss of strength before being incorporated. The LAD is meant to protect the biological graft during this vulnerable phase. However, it provokes an inflammatory reaction in the knee, and has been found to delay maturation of autogenous graft in humans. In experimental situations, the LAD has been found to share loads in a composite graft. It has also been found to be substantially stronger than the biological graft. However, in clinical situations no significant advantages have been observed with the use of LAD to augment patellar tendon or hamstring reconstruction of the chronic ACL-deficient knee or in the acute setting to augment repair of the torn ACL. There are very few reports of the use of LAD in reconstruction of the posterior cruciate ligament, and again these do not suggest any advantage in its use. Insertion of the LAD implies the introduction of a foreign material into the knee, has been associated with complications such as reactive synovitis and effusions, and may also be associated with an increased risk of infection. At present, there is no evidence that its routine use should be advocated in uncomplicated reconstructions of the ACL using biological grafts.

  17. Primary Breast Augmentation with Fat Grafting.

    PubMed

    Coleman, Sydney R; Saboeiro, Alesia P

    2015-07-01

    The controversy over fat grafting to the breasts has now been settled. In 2009, the American Society of Plastic Surgeons Fat Graft Task Force stated that "Fat grafting may be considered for breast augmentation and correction of defects associated with medical conditions and previous breast surgeries; however, results are dependent on technique and surgeon expertise." This article discusses the history, indications, planning, complications, and present technique of fat grafting to the breast using the Coleman technique.

  18. Augmented reality visualization for thoracoscopic spine surgery

    NASA Astrophysics Data System (ADS)

    Sauer, Frank; Vogt, Sebastian; Khamene, Ali; Heining, Sandro; Euler, Ekkehard; Schneberger, Marc; Zuerl, Konrad; Mutschler, Wolf

    2006-03-01

    We are developing an augmented reality (AR) image guidance system in which information derived from medical images is overlaid onto a video view of the patient. The centerpiece of the system is a head-mounted display custom fitted with two miniature color video cameras that capture the stereo view of the scene. Medical graphics is overlaid onto the video view and appears firmly anchored in the scene, without perceivable time lag or jitter. We have been testing the system for different clinical applications. In this paper we discuss minimally invasive thoracoscopic spine surgery as a promising new orthopedic application. In the standard approach, the thoracoscope - a rigid endoscope - provides visual feedback for the minimally invasive procedure of removing a damaged disc and fusing the two neighboring vertebrae. The navigation challenges are twofold. From a global perspective, the correct vertebrae on the spine have to be located with the inserted instruments. From a local perspective, the actual spine procedure has to be performed precisely. Visual feedback from the thoracoscope provides only limited support for both of these tasks. In the augmented reality approach, we give the surgeon additional anatomical context for the navigation. Before the surgery, we derive a model of the patient's anatomy from a CT scan, and during surgery we track the location of the surgical instruments in relation to patient and model. With this information, we can help the surgeon in both the global and local navigation, providing a global map and 3D information beyond the local 2D view of the thoracoscope. Augmented reality visualization is a particularly intuitive method of displaying this information to the surgeon. To adapt our augmented reality system to this application, we had to add an external optical tracking system, which works now in combination with our head-mounted tracking camera. The surgeon's feedback to the initial phantom experiments is very positive.

  19. The ligament augmentation device: an historical perspective.

    PubMed

    Kumar, K; Maffulli, N

    1999-05-01

    Anterior cruciate ligament (ACL) injury is the most common ligament injury in the knee, and a significant number of patients may develop progressive instability and disability despite aggressive rehabilitation. Various materials have been used for its reconstruction. These include autografts, allografts, prosthetic ligaments, and synthetic augmentation of the biological tissue. The concept of ligament augmentation device (LAD) arose from the observation that biological grafts undergo a phase of degeneration and loss of strength before being incorporated. The LAD is meant to protect the biological graft during this vulnerable phase. However, it provokes an inflammatory reaction in the knee, and has been found to delay maturation of autogenous graft in humans. In experimental situations, the LAD has been found to share loads in a composite graft. It has also been found to be substantially stronger than the biological graft. However, in clinical situations no significant advantages have been observed with the use of LAD to augment patellar tendon or hamstring reconstruction of the chronic ACL-deficient knee or in the acute setting to augment repair of the torn ACL. There are very few reports of the use of LAD in reconstruction of the posterior cruciate ligament, and again these do not suggest any advantage in its use. Insertion of the LAD implies the introduction of a foreign material into the knee, has been associated with complications such as reactive synovitis and effusions, and may also be associated with an increased risk of infection. At present, there is no evidence that its routine use should be advocated in uncomplicated reconstructions of the ACL using biological grafts. PMID:10355719

  20. Augmentation mammaplasty using implants: a review.

    PubMed

    Takayanagi, Susumu

    2012-09-01

    One of the techniques for augmentation mammaplasty is the procedure using implants. Even though this technique has been used for many years, there are still several controversial issues to be discussed and overcome for patient safety. In this review article, capsular contracture, leak or rupture of the implants, possible systemic disease, relation with breast cancer, and recent problems with Poly Implant Prothese implants are described and discussed. PMID:23094237

  1. Augmentation Mammaplasty Using Implants: A Review

    PubMed Central

    2012-01-01

    One of the techniques for augmentation mammaplasty is the procedure using implants. Even though this technique has been used for many years, there are still several controversial issues to be discussed and overcome for patient safety. In this review article, capsular contracture, leak or rupture of the implants, possible systemic disease, relation with breast cancer, and recent problems with Poly Implant Prothese implants are described and discussed. PMID:23094237

  2. Percutaneous Vertebral Body Augmentation: An Updated Review

    PubMed Central

    Omidi-Kashani, Farzad

    2014-01-01

    There are many medical conditions like osteoporosis, tumor, or osteonecrosis that weaken the structural strength of the vertebral body and prone it to fracture. Percutaneous vertebral augmentation that is usually applied by polymethylmethacrylate is a relatively safe, effective, and long lasting procedure commonly performed in these situations. In this paper, we updated a review of biomechanics, indications, contraindications, surgical techniques, complications, and overall prognosis of these minimally invasive spinal procedures. PMID:25379561

  3. Synovial tissue hypoxia and inflammation in vivo

    PubMed Central

    Ng, C T; Biniecka, M; Kennedy, A; McCormick, J; FitzGerald, O; Bresnihan, B; Buggy, D; Taylor, C T; O'Sullivan, J; Fearon, U; Veale, D J

    2010-01-01

    Introduction Hypoxia is a microenvironmental feature in the inflamed joint, which promotes survival advantage for cells. The aim of this study was to examine the relationship of partial oxygen pressure in the synovial tissue (tPO2) in patients with inflammatory arthritis with macroscopic/microscopic inflammation and local levels of proinflammatory mediators. Methods Patients with inflammatory arthritis underwent full clinical assessment and video arthroscopy to quantify macroscopic synovitis and measure synovial tPO2 under direct visualisation. Cell specific markers (CD3 (T cells), CD68 (macrophages), Ki67 (cell proliferation) and terminal deoxynucleotidyl transferase dUTP nick end labelling (cell apoptosis)) were quantified by immunohistology. In vitro migration was assessed in primary and normal synoviocytes (synovial fibroblast cells (SFCs)) using a wound repair scratch assay. Levels of tumour necrosis factor α (TNFα), interleukin 1β (IL1β), interferon γ (IFNγ), IL6, macrophage inflammatory protein 3α (MIP3α) and IL8 were quantified, in matched serum and synovial fluid, by multiplex cytokine assay and ELISA. Results The tPO2 was 22.5 (range 3.2–54.1) mm Hg and correlated inversely with macroscopic synovitis (r=−0.421, p=0.02), sublining CD3 cells (−0.611, p<0.01) and sublining CD68 cells (r=−0.615, p<0.001). No relationship with cell proliferation or apoptosis was found. Primary and normal SFCs exposed to 1% and 3% oxygen (reflecting the median tPO2 in vivo) induced cell migration. This was coupled with significantly higher levels of synovial fluid tumour necrosis factor α (TNFα), IL1β, IFNγ and MIP3α in patients with tPO2 <20 mm Hg (all p values <0.05). Conclusions This is the first study to show a direct in vivo correlation between synovial tPO2, inflammation and cell migration, thus it is proposed that hypoxia is a possible primary driver of inflammatory processes in the arthritic joint. PMID:20439288

  4. Augmented Classical Least Squares Multivariate Spectral Analysis

    DOEpatents

    Haaland, David M.; Melgaard, David K.

    2005-01-11

    A method of multivariate spectral analysis, termed augmented classical least squares (ACLS), provides an improved CLS calibration model when unmodeled sources of spectral variation are contained in a calibration sample set. The ACLS methods use information derived from component or spectral residuals during the CLS calibration to provide an improved calibration-augmented CLS model. The ACLS methods are based on CLS so that they retain the qualitative benefits of CLS, yet they have the flexibility of PLS and other hybrid techniques in that they can define a prediction model even with unmodeled sources of spectral variation that are not explicitly included in the calibration model. The unmodeled sources of spectral variation may be unknown constituents, constituents with unknown concentrations, nonlinear responses, non-uniform and correlated errors, or other sources of spectral variation that are present in the calibration sample spectra. Also, since the various ACLS methods are based on CLS, they can incorporate the new prediction-augmented CLS (PACLS) method of updating the prediction model for new sources of spectral variation contained in the prediction sample set without having to return to the calibration process. The ACLS methods can also be applied to alternating least squares models. The ACLS methods can be applied to all types of multivariate data.

  5. Augmented Classical Least Squares Multivariate Spectral Analysis

    DOEpatents

    Haaland, David M.; Melgaard, David K.

    2005-07-26

    A method of multivariate spectral analysis, termed augmented classical least squares (ACLS), provides an improved CLS calibration model when unmodeled sources of spectral variation are contained in a calibration sample set. The ACLS methods use information derived from component or spectral residuals during the CLS calibration to provide an improved calibration-augmented CLS model. The ACLS methods are based on CLS so that they retain the qualitative benefits of CLS, yet they have the flexibility of PLS and other hybrid techniques in that they can define a prediction model even with unmodeled sources of spectral variation that are not explicitly included in the calibration model. The unmodeled sources of spectral variation may be unknown constituents, constituents with unknown concentrations, nonlinear responses, non-uniform and correlated errors, or other sources of spectral variation that are present in the calibration sample spectra. Also, since the various ACLS methods are based on CLS, they can incorporate the new prediction-augmented CLS (PACLS) method of updating the prediction model for new sources of spectral variation contained in the prediction sample set without having to return to the calibration process. The ACLS methods can also be applied to alternating least squares models. The ACLS methods can be applied to all types of multivariate data.

  6. Augmented classical least squares multivariate spectral analysis

    DOEpatents

    Haaland, David M.; Melgaard, David K.

    2004-02-03

    A method of multivariate spectral analysis, termed augmented classical least squares (ACLS), provides an improved CLS calibration model when unmodeled sources of spectral variation are contained in a calibration sample set. The ACLS methods use information derived from component or spectral residuals during the CLS calibration to provide an improved calibration-augmented CLS model. The ACLS methods are based on CLS so that they retain the qualitative benefits of CLS, yet they have the flexibility of PLS and other hybrid techniques in that they can define a prediction model even with unmodeled sources of spectral variation that are not explicitly included in the calibration model. The unmodeled sources of spectral variation may be unknown constituents, constituents with unknown concentrations, nonlinear responses, non-uniform and correlated errors, or other sources of spectral variation that are present in the calibration sample spectra. Also, since the various ACLS methods are based on CLS, they can incorporate the new prediction-augmented CLS (PACLS) method of updating the prediction model for new sources of spectral variation contained in the prediction sample set without having to return to the calibration process. The ACLS methods can also be applied to alternating least squares models. The ACLS methods can be applied to all types of multivariate data.

  7. Augmented amputations of the lower extremity.

    PubMed

    Mohler, D G; Kessler, J I; Earp, B E

    2000-02-01

    Ten patients who had amputations of a lower extremity for high-grade sarcomas underwent bone augmentation with either allograft or autograft between 1988 and 1996. There were eight transfemoral amputations and two transtibial amputations. The transferred segments consisted of one proximal tibia and six distal tibia autografts, two allografts, one autograft talar dome and first metatarsal, and one with a patellar cap of a supracondylar amputation. The average length of followup was 54 months. There were no nonunions of any of the grafts. There were three wound problems requiring additional operations. One autograft resorbed, and one autograft had a late infection. There was one local recurrence. Augmentation to provide length resulted in a 42% increase in bone length in those performed purely for length. All patients were able to use standard prostheses. Functional outcome was appropriate to the amputation level. Half of the patients avoided more proximal levels of amputation because of the ability to augment the osteotomy. The use of nonvascularized structural autografts or allografts is a simple procedure that can produce a superior residual limb in patients undergoing amputation. Its use should be considered in patients for whom traditional amputation techniques will result in poor function, difficulty in fitting a prosthesis, or greater than necessary anatomic loss. PMID:10693566

  8. Service connectivity architecture for mobile augmented reality

    NASA Astrophysics Data System (ADS)

    Turunen, Tuukka; Pyssysalo, Tino; Roening, Juha

    2001-06-01

    Mobile augmented reality can be utilized in a number of different services, and it provides a lot of added value compared to the interfaces used in mobile multimedia today. Intelligent service connectivity architecture is needed for the emerging commercial mobile augmented reality services, to guarantee mobility and interoperability on a global scale. Some of the key responsibilities of this architecture are to find suitable service providers, to manage the connection with and utilization of such providers, and to allow smooth switching between them whenever the user moves out of the service area of the service provider she is currently connected to. We have studied the potential support technologies for such architectures and propose a way to create an intelligent service connectivity architecture based on current and upcoming wireless networks, an Internet backbone, and mechanisms to manage service connectivity in the upper layers of the protocol stack. In this paper, we explain the key issues of service connectivity, describe the properties of our architecture, and analyze the functionality of an example system. Based on these, we consider our proposition a good solution to the quest for global interoperability in mobile augmented reality services.

  9. Adaptive information design for outdoor augmented reality.

    PubMed

    Neuhöfer, Jan A; Govaers, Felix; El Mokni, Hichem; Alexander, Thomas

    2012-01-01

    Augmented Reality focuses on the enrichment of the user's natural field of view by consistent integration of text, symbols and interactive three-dimensional objects in real time. Placing virtual objects directly into the user's view in a natural context empowers highly dynamic applications. On the other hand, this necessitates deliberate choice of information design and density, in particular for deployment in hazardous environments like military combat scenarios. As the amount of information needed is not foreseeable and strongly depends on the individual mission, an appropriate system must offer adequate adaptation capabilities. The paper presents a prototypical, vehicle-mountable Augmented Reality vision system, designed for enhancing situation awareness in stressful urban warfare scenarios. Tracking, as one of the most crucial challenges for outdoor Augmented Reality, is accomplished by means of a Differential-GPS approach while the type of display to attach can be modified, ranging from ocular displays to standard LCD mini-screens. The overall concept also includes envisioning of own troops (blue forces), for which a multi-sensor tracking approach has been chosen. As a main feature, the system allows switching between different information categories, focusing on friendly, hostile, unidentified or neutral data. Results of an empirical study on the superiority of an in-view navigation cue approach conclude the paper.

  10. Magnetohydrodynamic Augmentation of Pulse Detonation Engines

    NASA Astrophysics Data System (ADS)

    Zeineh, Christopher; Cole, Lord; Karagozian, Ann

    2010-11-01

    Pulse detonation engines (PDEs) are the focus of increasing attention due to their potentially superior performance over constant pressure engines. Yet due to its unsteady chamber pressure, the PDE system will either be over- or under-expanded for the majority of the cycle, with energy being used without maximum gain. Magnetohydrodynamic (MHD) augmentation offers the opportunity to extract energy and apply it to a separate stream where the net thrust will be increased. With MHD augmentation, such as in the Pulse Detonation Rocket-Induced MHD Ejector (PDRIME) concept, energy could be extracted from the high speed portion of the system, e.g., through a generator in the nozzle, and then applied directly to another flow or portion of the flow as a body force. The present high resolution numerical simulations explore the flow evolution and potential performance of such propulsion systems. An additional magnetic piston applying energy in the PDE chamber can also act in concert with the PDRIME for separate thrust augmentation. Results show that MHD can indeed influence the flow and pressure fields in a beneficial way in these configurations, with potential performance gains under a variety of flight and operating conditions. There are some challenges associated with achieving these gains, however, suggesting further optimization is required.

  11. Adult Partner-Augmented Communication Input to Youth with Mental Retardation Using the System for Augmenting Language (SAL).

    ERIC Educational Resources Information Center

    Sevcik, Rose A.; And Others

    1995-01-01

    This study examined the frequency and nature of augmented input that adult partners provided to 13 youth with moderate to severe mental retardation as they began to use the System for Augmenting Language. Analyses revealed differences in the frequency and in the manner and style with which home and school partners provided augmented input.…

  12. Distinct regulatory mechanisms of the human ferritin gene by hypoxia and hypoxia mimetic cobalt chloride at the transcriptional and post-transcriptional levels.

    PubMed

    Huang, Bo-Wen; Miyazawa, Masaki; Tsuji, Yoshiaki

    2014-12-01

    Cobalt chloride has been used as a hypoxia mimetic because it stabilizes hypoxia inducible factor-1α (HIF1-α) and activates gene transcription through a hypoxia responsive element (HRE). However, differences between hypoxia and hypoxia mimetic cobalt chloride in gene regulation remain elusive. Expression of ferritin, the major iron storage protein, is regulated at the transcriptional and posttranscriptional levels through DNA and RNA regulatory elements. Here we demonstrate that hypoxia and cobalt chloride regulate ferritin heavy chain (ferritin H) expression by two distinct mechanisms. Both hypoxia and cobalt chloride increased HIF1-α but a putative HRE in the human ferritin H gene was not activated. Instead, cobalt chloride but not hypoxia activated ferritin H transcription through an antioxidant responsive element (ARE), to which Nrf2 was recruited. Intriguingly, cobalt chloride downregulated ferritin H protein expression while it upregulated other ARE-regulated antioxidant genes in K562 cells. Further characterization demonstrated that cobalt chloride increased interaction between iron regulatory proteins (IRP1 and IRP2) and iron responsive element (IRE) in the 5'UTR of ferritin H mRNA, resulting in translational block of the accumulated ferritin H mRNA. In contrast, hypoxia had marginal effect on ferritin H transcription but increased its translation through decreased IRP1-IRE interaction. These results suggest that hypoxia and hypoxia mimetic cobalt chloride employ distinct regulatory mechanisms through the interplay between DNA and mRNA elements at the transcriptional and post-transcriptional levels.

  13. Temporal Onset of Hypoxia and Oxidative Stress After Pulmonary Irradiation

    SciTech Connect

    Fleckenstein, Katharina; Zgonjanin, Larisa; Chen Liguang; Rabbani, Zahid; Jackson, Isabel L.; Thrasher, Bradley; Kirkpatrick, John; Foster, W. Michael; Vujaskovic, Zeljko . E-mail: vujas@radonc.duke.edu

    2007-05-01

    Purpose: To investigate the temporal onset of hypoxia following irradiation, and to show how it relates to pulmonary vascular damage, macrophage accumulation, and the production of reactive oxygen species and cytokines. Our previous studies showed that tissue hypoxia in the lung after irradiation contributed to radiation-induced injury. Methods and Materials: Female Fisher 344 rats were irradiated to the right hemithorax with a single dose of 28 Gy. Serial studies were performed up to 20 weeks following irradiation. Radionuclide lung-perfusion studies were performed to detect changes in pulmonary vasculature. Immunohistochemical studies were conducted to study macrophages, tissue hypoxia (carbonic anhydrase-9 marker), oxidative stress (8-hydroxy-2'-deoxyguanosine), and the expression of profibrogenic (transforming growth factor-{beta} [TGF-{beta}]) and proangiogenic (vascular endothelial growth factor [VEGF]) cytokines. Results: Significant changes in lung perfusion along with tissue hypoxia were observed 3 days after irradiation. Significant oxidative stress was detected 1 week after radiation, whereas macrophages started to accumulate at 4 weeks. A significant increase in TGF-{beta} expression was seen within 1 day after radiation, and for VEGF at 2 weeks after radiation. Levels of hypoxia, oxidative stress, and both cytokines continued to rise with time after irradiation. The steepest increase correlated with vast macrophage accumulation. Conclusions: Early changes in lung perfusion, among other factors initiate, the development of hypoxia and chronic oxidative stress after irradiation. Tissue hypoxia is associated with a significant increase in the activation of macrophages and their continuous production of reactive oxygen species, stimulating the production of fibrogenic and angiogenic cytokines, and maintaining the development of chronic radiation-induced lung injury.

  14. No Detectable Hypoxia in Malignant Salivary Gland Tumors: Preliminary Results

    SciTech Connect

    Wijffels, Karien; Hoogsteen, Ilse J.; Lok, Jasper; Rijken, Paulus F.J.W.; Marres, Henri A.M.; Wilde, Peter C.M. de; Kogel, Albert J. van der; Kaanders, Johannes H.A.M.

    2009-04-01

    Purpose: Hypoxia is detected in most solid tumors and is associated with malignant progression and adverse treatment outcomes. However, the oxygenation status of malignant salivary gland tumors has not been previously studied. The aim of this study was to investigate the potential clinical relevance of hypoxia in this tumor type. Methods and Materials: Twelve patients scheduled for surgical resection of a salivary gland tumor were preoperatively injected with the hypoxia marker pimonidazole and the proliferation marker iododeoxyuridine. Tissue samples of the dissected tumor were immunohistochemically stained for blood vessels, pimonidazole, carbonic anhydrase-IX, glucose transporters-1 and -3 (Glut-1, Glut-3), hypoxia-inducible factor-1{alpha}, iododeoxyuridine, and epidermal growth factor receptor. The tissue sections were quantitatively assessed by computerized image analysis. Results: The tissue material from 8 patients was of sufficient quality for quantitative analysis. All tumors were negative for pimonidazole binding, as well as for carbonic anhydrase-IX, Glut-1, Glut-3, and hypoxia-inducible factor-1{alpha}. The vascular density was high, with a median value of 285 mm{sup -2} (range, 209-546). The iododeoxyuridine-labeling index varied from <0.1% to 12.2% (median, 2.2%). Epidermal growth factor receptor expression levels were mostly moderate to high. In one-half of the cases, nuclear expression of epidermal growth factor receptor was observed. Conclusion: The absence of detectable pimonidazole binding, as well as the lack of expression of hypoxia-associated proteins in all tumors, indicates that malignant salivary gland tumors are generally well oxygenated. It is unlikely that hypoxia is a relevant factor for their clinical behavior and treatment responsiveness.

  15. Is hypoxia training good for muscles and exercise performance?

    PubMed

    Vogt, Michael; Hoppeler, Hans

    2010-01-01

    Altitude training has become very popular among athletes as a means to further increase exercise performance at sea level or to acclimatize to competition at altitude. Several approaches have evolved during the last few decades, with "live high-train low" and "live low-train high" being the most popular. This review focuses on functional, muscular, and practical aspects derived from extensive research on the "live low-train high" approach. According to this, subjects train in hypoxia but remain under normoxia for the rest of the time. It has been reasoned that exercising in hypoxia could increase the training stimulus. Hypoxia training studies published in the past have varied considerably in altitude (2300-5700 m) and training duration (10 days to 8 weeks) and the fitness of the subjects. The evidence from muscle structural, biochemical, and molecular findings point to a specific role of hypoxia in endurance training. However, based on the available performance capacity data such as maximal oxygen uptake (Vo(2)max) and (maximal) power output, hypoxia as a supplement to training is not consistently found to be advantageous for performance at sea level. Stronger evidence exists for benefits of hypoxic training on performance at altitude. "Live low-train high" may thus be considered when altitude acclimatization is not an option. In addition, the complex pattern of gene expression adaptations induced by supplemental training in hypoxia, but not normoxia, suggest that muscle tissue specifically responds to hypoxia. Whether and to what degree these gene expression changes translate into significant changes in protein concentrations that are ultimately responsible for observable structural or functional phenotypes remains open. It is conceivable that the global functional markers such as Vo(2)max and (maximal) power output are too coarse to detect more subtle changes that might still be functionally relevant, at least to high-level athletes.

  16. Quinoxaline 1,4-dioxides: hypoxia-selective therapeutic agents.

    PubMed

    Diab-Assef, Mona; Haddadin, Makhluf J; Yared, Pierre; Assaad, Chafika; Gali-Muhtasib, Hala U

    2002-04-01

    A problem that confronts clinicians in the treatment of cancer is the resistance of hypoxic tumors to chemotherapy and radiation therapy. Thus, the development of new drugs that are toxic to hypoxic cells found in solid tumors is an important objective for effective anticancer chemotherapy. We recently showed that the heterocyclic aromatic N-oxides, quinoxaline 1,4-dioxides (QdNOs), are cytotoxic to tumor cells cultured under hypoxia. In this study, we evaluated the hypoxia-selective toxicity of four diversely substituted QdNOs and determined their effect on the expression of hypoxia inducible factor (HIF) 1alpha in the human colon cancer cell line T-84. The various QdNOs were found to possess a 50- to 100-fold greater cytotoxicity to T-84 cells cultured under hypoxia compared with oxia. Interestingly, the hypoxia cytotoxicity ratio (HCR), the ratio of equitoxic concentrations of the drug under aerobic/anoxic conditions, was highly structure related and depended on the nature of the substituents on the QdNO heterocycle. The most cytotoxic 2-benzoyl-3-phenyl-6,7-dichloro derivative of QdNO (DCQ) was potent at a dose of 1 microM with an HCR of 100 and significantly reduced the levels of HIF-1alpha transcript and protein. The 2-benzoyl-3-phenyl derivative (BPQ) had a hypoxia potency of 20 microM and an HCR of 40. By contrast, the 2-aceto-3-methyl and the 2,3-tetramethylene (TMQ) derivatives of QdNO were much less cytotoxic under hypoxia (HCRs of 8.5 and 6.5, respectively) and reduced the expression of HIF-1alpha mRNA to a much lesser extent. Because the nonchlorinated analogue BPQ did not demonstrate behavior similar to that of DCQ, we hypothesize that the C-6, C-7-chlorine of DCQ might play a significant role in the selective hypoxic cytotoxicity of the drug.

  17. PH2O and simulated hypobaric hypoxia.

    PubMed

    Conkin, Johnny

    2011-12-01

    Some manufacturers of reduced oxygen (O2) breathing devices claim a comparable hypobaric hypoxia (HH) training experience by providing F1O2 < 0.209 at or near sea level pressure to match the ambient oxygen partial pressure (iso-PO2) of the target altitude. I conclude after a review of literature from investigators and manufacturers that these devices may not properly account for the 47 mmHg of water vapor partial pressure that reduces the inspired partial pressure of oxygen (P1O2), which is substantial at higher altitude relative to sea level. Consequently, some devices claiming an equivalent HH experience under normobaric conditions would significantly overestimate the HH condition, especially when simulating altitudes above 10,000 ft (3048 m). At best, the claim should be that the devices provide an approximate HH experience since they only duplicate the ambient PO2 at sea level as at altitude. An approach to reduce the overestimation and standardize the operation is to at least provide machines that create the same P1O2 conditions at sea level as at the target altitude, a simple software upgrade. PMID:22195399

  18. Hypoxia Adjacent to the Mississippi River Plume

    NASA Astrophysics Data System (ADS)

    Rabalais, N. N.; Turner, R. E.

    2005-05-01

    The northern Gulf of Mexico receives the freshwater and constituent flux from the Mississippi River, which integrates 40% of the lower 48 United States. In the last half of the 20th century, the flux of nitrogen tripled, phosphorus concentration appears to have increased, and silicate concentration decreased. These changes result from landscape alterations over two centuries with an intensification of human activities that increased the flux of nitrogen and phosphorus particularly in the 1960s to 1980s. Evidence for eutrophication in the coastal ecosystem includes an increase in algal biomass, carbon accumulation from nutrient-enhanced production, worsening oxygen deficiency in the lower water column, and shifts in food web structure. The extent of the oxygen deficiency reaches 20,000 km2 of the inner continental shelf over long periods in summer with the potential for affecting commercially important fisheries in the Gulf. There is daily, weekly and seasonal variability in currents and stratification on the shelf and, therefore, no simple description of the couplings between nutrient delivery, carbon production in surface waters and delivery to and cycling in bottom waters. There are, however, multiple lines of evidence to implicate changes in riverine nutrient loads with overall primary and secondary production, carbon accumulation at the seabed, and low oxygen conditions on the shelf. The change in nutrient loads and responses of the northern Gulf coastal ecosystem, including widespread, severe seasonal hypoxia, parallel similar conditions in the coastal ocean on a global scale.

  19. The cerebral venous system and hypoxia.

    PubMed

    Wilson, Mark H; Imray, Christopher H E

    2016-01-15

    Most hypobaric hypoxia studies have focused on oxygen delivery and therefore cerebral blood inflow. Few have studied venous outflow. However, the volume of blood entering and leaving the skull (∼700 ml/min) is considerably greater than cerebrospinal fluid production (0.35 ml/min) or edema formation rates and slight imbalances of in- and outflow have considerable effects on intracranial pressure. This dynamic phenomenon is not necessarily appreciated in the currently taught static "Monro-Kellie" doctrine, which forms the basis of the "Tight-Fit" hypothesis thought to underlie high altitude headache, acute mountain sickness, and high altitude cerebral edema. Investigating both sides of the cerebral circulation was an integral part of the 2007 Xtreme Everest Expedition. The results of the relevant studies performed as part of and subsequent to this expedition are reviewed here. The evidence from recent studies suggests a relative venous outflow insufficiency is an early step in the pathogenesis of high altitude headache. Translation of knowledge gained from high altitude studies is important. Many patients in a critical care environment develop hypoxemia akin to that of high altitude exposure. An inability to drain the hypoxemic induced increase in cerebral blood flow could be an underappreciated regulatory mechanism of intracranial pressure.

  20. Exposure to hypobaric hypoxia results in higher oxidative stress compared to normobaric hypoxia.

    PubMed

    Ribon, A; Pialoux, V; Saugy, J J; Rupp, T; Faiss, R; Debevec, T; Millet, G P

    2016-03-01

    Sixteen healthy exercise trained participants underwent the following three, 10-h exposures in a randomized manner: (1) Hypobaric hypoxia (HH; 3450m terrestrial altitude) (2) Normobaric hypoxia (NH; 3450m simulated altitude) and (3) Normobaric normoxia (NN). Plasma oxidative stress (malondialdehyde, MDA; advanced oxidation protein products, AOPP) and antioxidant markers (superoxide dismutase, SOD; glutathione peroxidase, GPX; catalase; ferric reducing antioxidant power, FRAP) were measured before and after each exposure. MDA was significantly higher after HH compared to NN condition (+24%). SOD and GPX activities were increased (vs. before; +29% and +54%) while FRAP was decreased (vs. before; -34%) only after 10h of HH. AOPP significantly increased after 10h for NH (vs. before; +83%), and HH (vs. before; +99%) whereas it remained stable in NN. These results provide evidence that prooxidant/antioxidant balance was impaired to a greater degree following acute exposure to terrestrial (HH) vs. simulated altitude (NH) and that the chamber confinement (NN) did likely not explain these differences. PMID:26732282

  1. Adult partner-augmented communication input to youth with mental retardation using the System for Augmenting Language (SAL).

    PubMed

    Sevcik, R A; Romski, M A; Watkins, R V; Deffebach, K P

    1995-08-01

    The primary purpose of this study was to characterize the frequency and nature of augmented input that adult partners provided to 13 youth with mental retardation as they began to use the System for Augmenting Language (SAL). Analyses of youth-partner interactions revealed differences in the frequency with which home and school partners provided augmented input and in the manner and style of home and school partners' augmented input, particularly in directiveness and position of lexigram symbols within Utterances. Overall, partners naturally provided augmented input in a manner likely to promote youth's learning of the SAL. PMID:7474982

  2. Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen induction by hypoxia and hypoxia-inducible factors.

    PubMed

    Veeranna, Ravindra P; Haque, Muzammel; Davis, David A; Yang, Min; Yarchoan, Robert

    2012-01-01

    Hypoxia and hypoxia-inducible factors (HIFs) play an important role in the Kaposi's sarcoma-associated herpesvirus (KSHV) life cycle. In particular, hypoxia can activate lytic replication of KSHV and specific lytic genes, including the replication and transcription activator (RTA), while KSHV infection in turn can increase the levels and activity of HIFs. In the present study, we show that hypoxia increases the levels of mRNAs encoding KSHV latency-associated nuclear antigen (LANA) in primary effusion lymphoma (PEL) cell lines and also increases the levels of LANA protein. Luciferase reporter assays in Hep3B cells revealed a moderate activation of the LANA promoter region by hypoxia as well as by cotransfection with degradation-resistant HIF-1α or HIF-2α expression plasmids. Computer analysis of a 1.2-kb sequence upstream of the LANA translational start site identified six potential hypoxia-responsive elements (HRE). Sequential deletion studies revealed that much of this activity was mediated by one of these HREs (HRE 4R) oriented in the 3' to 5' direction and located between the constitutive (LTc) and RTA-inducible (LTi) mRNA start sites. Site-directed mutation of this HRE substantially reduced the response to both HIF-1α and HIF-2α in a luciferase reporter assay. Electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) assays demonstrated binding of both HIF-1α and HIF-2α to this region. Also, HIF-1α was found to associate with RTA, and HIFs enhanced the activation of LTi by RTA. These results provide evidence that hypoxia and HIFs upregulate both latent and lytic KSHV replication and play a central role in the life cycle of this virus. PMID:22090111

  3. Ventilatory response to acute hypoxia in transgenic mice over-expressing erythropoietin: effect of acclimation to 3-week hypobaric hypoxia.

    PubMed

    Villafuerte, Francisco C; Cárdenas-Alayza, Rosa; Macarlupú, José Luis; Monge-C, Carlos; León-Velarde, Fabiola

    2007-09-30

    We used transgenic mice constitutively over-expressing erythropoietin ("tg6" mice) and wild-type (wt) mice to investigate whether the high hematocrit (hct), consequence of Epo over-expression affected: (1) the normoxic ventilation (V (E)) and the acute hypoxic ventilatory response (HVR) and decline (HVD), (2) the increase in ventilation observed after chronic exposure to hypobaric hypoxia (430mmHg for 21 days), (3) the respiratory "blunting", and (4) the erythrocythemic response induced by chronic hypoxia exposure. V (E) was found to be similar in tg6 and wt mice in normoxia (FIO2=0.21). Post-acclimation V (E) was significantly elevated in every time point in wt mice at FIO2=0.10 when compared to pre-acclimation values. In contrast, tg6 mice exhibited a non-significant increase in V (E) throughout acute hypoxia exposure. Changes in V (E) are associated with adjustments in tidal volume (V(T)). HVR and HVD were independent of EE in tg6 and wt mice before chornic hypoxia exposure. HVR was significantly greater in wt than in tg6 mice after chronic hypoxia. After acclimation, HVD decreased in tg6 mice. Chronic hypoxia exposure caused hct to increase significantly in wt mice, while only a marginal increase occurred in the tg6 group. Although pre-existent EE does not appear to have an effect on HVR, the observation of alterations on V(T) suggests that it may contribute to time-dependent changes in ventilation and in the acute HVR during exposure to chronic hypoxia. In addition, our results suggest that EE may lead to an early "blunting" of the ventilatory response.

  4. Modelling macrofaunal biomass in relation to hypoxia and nutrient loading

    NASA Astrophysics Data System (ADS)

    Timmermann, Karen; Norkko, Joanna; Janas, Urszula; Norkko, Alf; Gustafsson, Bo G.; Bonsdorff, Erik

    2012-12-01

    Nutrient loading of aquatic ecosystems results in more food for benthic macrofaunal communities but also increases the risk of hypoxia, resulting in a reduction or complete loss of benthic biomass. This study investigates the interaction between eutrophication, hypoxia and benthic biomass with emphasis on the balance between gains and loss of benthic biomass due to changes in nutrient loadings. A physiological fauna model with 5 functional groups was linked to a 3D coupled hydrodynamic-ecological Baltic Sea model. Model results revealed that benthic biomass increased between 0 and 700% after re-oxygenating bottom waters. Nutrient reduction scenarios indicated improved oxygen concentrations in bottom waters and decreased sedimentation of organic matter up to 40% after a nutrient load reduction following the Baltic Sea Action Plan. The lower food supply to benthos reduced the macrofaunal biomass up to 35% especially in areas not currently affected by hypoxia, whereas benthic biomass increased up to 200% in areas affected by eutrophication-induced hypoxia. The expected changes in benthic biomass resulting from nutrient load reductions and subsequent reduced hypoxia may not only increase the food supply for benthivorous fish, but also significantly affect the biogeochemical functioning of the ecosystem.

  5. Hypoxia increases intensity of epidermal papillomatosis in roach Rutilus rutilus.

    PubMed

    Korkea-aho, Tiina L; Partanen, Janne M; Kukkonen, Jussi V K; Taskinen, Jouni

    2008-01-24

    Hypoxia, which occurs frequently in aquatic ecosystems and is mainly due to increasing eutrophication can cause severe environmental stress in fish. We investigated experimentally the hypothesis that hypoxia could be one of the environmental stress factors that can induce papillomatosis in fish. Male roach Rutilus rutilus exposed to periodic oxygen deficiency and accompanied temperature increases (OT group) showed the highest increase in the intensity of papillomatosis, as measured by the number of scales covered by papillomatosis tumors. The second highest increase in disease intensity was among male roach exposed to periodical temperature increases. The incidence of such tumors was lowest in the control group, which was exposed to neither hypoxia nor increased temperature. The mortality of fish during the 17 d experiment was highest and the condition factor was lowest in the OT group, indicating this group experienced a higher level of stress. The apparent interaction of hypoxia and temperature suggests that these environmental stressors are among the multifactorial elements leading to papillomatosis in roach. Furthermore, these results provide experimental evidence to indicate that hypoxia may contribute to tumor development in fish. PMID:18380222

  6. Intermittent hypoxia induces functional recovery following cervical spinal injury

    PubMed Central

    Vinit, Stéphane; Lovett-Barr, Mary Rachael; Mitchell, Gordon S.

    2009-01-01

    Respiratory-related complications are the leading cause of death in spinal cord injury (SCI) patients. Few effective SCI treatments are available after therapeutic interventions are performed in the period shortly after injury (e.g. spine stabilization and prevention of further spinal damage). In this review we explore the capacity to harness endogenous spinal plasticity induced by intermittent hypoxia to optimize function of surviving (spared) neural pathways associated with breathing. Two primary questions are addressed: 1) does intermittent hypoxia induce plasticity in spinal synaptic pathways to respiratory motor neurons following experimental SCI? and 2) can this plasticity improve respiratory function? In normal rats, intermittent hypoxia induces serotonin-dependent plasticity in spinal pathways to respiratory motor neurons. Early experiments suggest that intermittent hypoxia also enhances respiratory motor output in experimental models of cervical SCI, (cervical hemisection) and that the capacity to induce functional recovery is greater with longer durations post-injury. Available evidence suggests that intermittent hypoxia-induced spinal plasticity has considerable therapeutic potential to treat respiratory insufficiency following chronic cervical spinal injury. PMID:19651247

  7. Heart disease link to fetal hypoxia and oxidative stress.

    PubMed

    Giussani, Dino A; Niu, Youguo; Herrera, Emilio A; Richter, Hans G; Camm, Emily J; Thakor, Avnesh S; Kane, Andrew D; Hansell, Jeremy A; Brain, Kirsty L; Skeffington, Katie L; Itani, Nozomi; Wooding, F B Peter; Cross, Christine M; Allison, Beth J

    2014-01-01

    The quality of the intrauterine environment interacts with our genetic makeup to shape the risk of developing disease in later life. Fetal chronic hypoxia is a common complication of pregnancy. This chapter reviews how fetal chronic hypoxia programmes cardiac and endothelial dysfunction in the offspring in adult life and discusses the mechanisms via which this may occur. Using an integrative approach in large and small animal models at the in vivo, isolated organ, cellular and molecular levels, our programmes of work have raised the hypothesis that oxidative stress in the fetal heart and vasculature underlies the mechanism via which prenatal hypoxia programmes cardiovascular dysfunction in later life. Developmental hypoxia independent of changes in maternal nutrition promotes fetal growth restriction and induces changes in the cardiovascular, metabolic and endocrine systems of the adult offspring, which are normally associated with disease states during ageing. Treatment with antioxidants of animal pregnancies complicated with reduced oxygen delivery to the fetus prevents the alterations in fetal growth, and the cardiovascular, metabolic and endocrine dysfunction in the fetal and adult offspring. The work reviewed offers both insight into mechanisms and possible therapeutic targets for clinical intervention against the early origin of cardiometabolic disease in pregnancy complicated by fetal chronic hypoxia.

  8. Could mild hypoxia impair pilot decision making in emergencies?

    PubMed

    Legg, Stephen; Hill, Stephen; Mundel, Toby; Gilbey, Andrew; Schlader, Zac; Raman, Aaron

    2012-01-01

    The decreased pressure in the cabin of a pressurised aircraft (typically equivalent to ~8000 ft) reduces the oxygen level so that the blood oxygen saturation of all occupants falls from >97% (normoxia) at sea-level to below 92% (mild hypoxia). Although exposure to mild hypoxia does not affect well-learned cognitive and motor performance of aircrew, it has been proposed that it can affect the performance of some complex cognitive performance tasks involving multiple demands typical of emergency tasks that may have to be performed by pilots. In order to simulate some of these complex cognitive demands, 25 student volunteers participated in an experiment which assessed performance of complex logical reasoning and and multiple memory tasks before and after 2 hours of exposure to normoxia and mild hypoxia. Performance for the more difficult components of the complex reasoning task, especially involving conflict decisions, were marginally significantly degraded by mild hypoxia. Since the effects were only marginally significant future studies should investigate the effects of mild hypoxia on more subtle complex decision-making tasks. PMID:22316722

  9. Vitamin C supplementation does not improve hypoxia-induced erythropoiesis.

    PubMed

    Martinez-Bello, Vladimir E; Sanchis-Gomar, Fabian; Martinez-Bello, Daniel; Olaso-Gonzalez, Gloria; Gomez-Cabrera, Mari Carmen; Viña, Jose

    2012-12-01

    Hypoxia induces reactive oxygen species production. Supplements with antioxidant mixtures can compensate for the decline in red cell membrane stability following intermittent hypobaric hypoxia by decreasing protein and lipid oxidation. We aimed to determine whether supplementation with vitamin C is implicated in the regulation of erythropoiesis and in the oxygen-carrying capacity of the blood, and also whether antioxidant supplementation prevents the oxidative stress associated to intermittent hypoxia. Twenty-four male Wistar rats were randomly divided into four experimental groups: normoxia control (n=6), normoxia + vitamin C (n=6), hypoxia control (12 h pO(2) 12%/12 h pO(2) 21%) (n=6), and hypoxia + vitamin C (n=6). Animals were supplemented with vitamin C at a dose of 250 mg·kg(-1)·day(-1) for 21 days. Red blood cell count, hemoglobin, hematocrit, reticulocytes, erythropoietin, and oxidative stress parameters such as malondialdehyde and protein oxidation in plasma were analyzed at two different time points: basal sample (day zero) and final sample (day 21). Similar RBC, Hb, Hct, and Epo increments were observed in both hypoxic groups regardless of the vitamin C supplementation. There was no change on MDA levels after intermittent hypoxic exposure in any experimental group. However, we found an increase in plasma protein oxidation in both hypoxic groups. Vitamin C does not affect erythropoiesis and protein oxidation in rats submitted to intermittent hypoxic exposure. PMID:23270444

  10. Circulating factors are involved in hypoxia-induced hepcidin suppression.

    PubMed

    Ravasi, Giulia; Pelucchi, Sara; Greni, Federico; Mariani, Raffaella; Giuliano, Andrea; Parati, Gianfranco; Silvestri, Laura; Piperno, Alberto

    2014-12-01

    Hepcidin transcription is strongly down-regulated under hypoxic conditions, however whether hypoxia inhibits hepcidin directly or indirectly is still unknown. We investigated the time course of hypoxia-mediated hepcidin down-regulation in vivo in healthy volunteers exposed to hypobaric hypoxia at high altitude and, based on the hypothesis that circulating factors are implicated in hepcidin inhibition, we analyzed the effect of sera of these volunteers exposed to normoxia and hypoxia on hepcidin expression in Huh-7 cell lines. Hypoxia led to a significant hepcidin down-regulation in vivo that was almost complete within 72h of exposure and followed erythropoietin induction. This delay in hepcidin down-regulation suggests the existence of soluble factor/s regulating hepcidin production. We then stimulated HuH-7 cells with normoxic and hypoxic sera to analyze the effects of sera on hepcidin regulation. Hypoxic sera had a significant inhibitory effect on hepcidin promoter activity assessed by a luciferase assay, although the amount of such decrease was not as relevant as that observed in vivo. Cellular mRNA analysis showed that a number of volunteers' sera inhibited hepcidin expression, concurrently with ID1 inhibition, suggesting that inhibitory factor(s) may act through the SMAD-pathway. PMID:25065484

  11. Effect of chronic hypoxia on penile erectile function in rats.

    PubMed

    Yu, D P; Liu, X H; Wei, A Y

    2015-09-08

    We examined the relationship between chronic hypoxia and erectile dysfunction in rat and its possible pathogenic mechanism. Forty-eight white male adult Sprague-Dawley rats were randomly divided into a test group and a control group. In accordance with the experimental time (2, 6, and 10 weeks), each group was divided into 3 subgroups, with 8 rats in each subgroup. Rats in the test group were fed in an airtight hypoxia cabin, while rats in the control group were maintained in a normal environment, with other conditions kept the same. At 2, 6, and 10 weeks, the rats in each group were observed for erectile function. Affinity purification was used to detect neural nitric oxide synthase (nNOS)-positive nerve fibers and endothelial nitric oxide synthase (eNOS) expression. After hypoxia, erectile frequency decreased significantly compared to before hypoxia (P < 0.001). Comparison of the test group and control group revealed a significant difference in the quantity of nNOS-positive nerve fiber and eNOS protein expression (P < 0.01). Hypoxia may influence erectile function and nNOS and eNOS expression in rats. The decrease in the quantity of nNOS nerve fibers and expression of eNOS may contribute to erectile dysfunction under hypoxic conditions in rats.

  12. Hypoxia Alters Gene Expression in the Gonads of Zebrafish (Danio Rerio) Oral Presentation

    EPA Science Inventory

    Reproduction is affected by hypoxia via direct modulation of expression of steroidogenic genes, but also via multiple indirect mechanisms involved in responding th hypoxia. The concern over the expansion of hypoxic environments has led to resurfacing of interest in understanding...

  13. Hypoxia Alters Gene Expression in the Gonads of Zebrafish (Danio rerio)

    EPA Science Inventory

    Reproduction is affected by hypoxia via direct modulation of expression of steroidogenic genes, but also via multiple indirect mechanisms involved in responding to hypoxia. The concern over the expansion of hypoxic environments has led to resurfacing of interest in understanding...

  14. Effect of Organic Enrichment and Hypoxia on the Biodiversity of Benthic Communities in Narragansett Bay

    EPA Science Inventory

    Excessive input of nitrogen to coastal waters leads to eutrophication and hypoxia that reduce biodiversity and impair key ecosystem services provided by benthic communities; for example, fish and shellfish production, bioturbation, nutrient cycling, and water filtration. Hypoxia ...

  15. Effects of Hypoxia on Animal Burrow Construction and Consequent Effects on Sediment Redox Profiles

    EPA Science Inventory

    Previous studies investigating the effects of hypoxia on benthic infauna and consequent effects on sediment chemistry provide only correlative results from the field. In order to establish causation and isolate effects of hypoxia on individual species, we conducted a laboratory ...

  16. Alterations in Expression of HIF-1α, HIF-2α and VEGF by Idiopathic Overactive Bladder Urothelial Cells During Stretch Suggest a Role for Hypoxia

    PubMed Central

    Christiaansen, Charlotte E.; Sun, Yan; Hsu, Yu-chao; Chai, Toby C.

    2011-01-01

    Objectives Hypoxia has been theorized to play a role in overactive bladder (OAB) symptoms. This study was designed to test this hypothesis by studying how in vitro stretch of primary cultured bladder urothelial cells (BUC) from OAB subjects and asymptomatic subjects (NB) altered the expression of angiogenic factors: hypoxia-inducible factor 1 alpha subunit (HIF-1α), hypoxia-inducible factor 2 alpha subunit (HIF-2α), and vascular endothelial growth factor (VEGF). Methods HIF-1α, HIF-2α and VEGF mRNA expression were analyzed using real-time quantitative PCR (qPCR). Fluorescence activated cell sorting (FACS) was used to measure protein expression. Release of VEGF in the supernatant of stretched OAB and NB BUC was measured with ELISA. Results Stretching of OAB BUC increased expression of mRNA for HIF-1α, HIF-2α, and VEGF by 1.5 (p<0.01), 1.5 (p<0.01) and 3.5 fold (p<0.001) over unstretched OAB BUC. This augmentation was not detected comparing stretched NB with unstretched NB BUC. Using FACS quantitation, only HIF-2α found to be significantly increased (p<0.01). Measuring VEGF in supernatant revealed that stretched OAB released significantly more VEGF than non-stretched OAB BUC at multiple time points whereas stretched NB BUC did not release VEGF. Conclusions OAB BUC responded to stretch by expressing increased angiogenic markers HIF-1α, HIF-2α and/or VEGF, measured at the transcript and protein levels. This suggested that OAB BUC respond as if they were primed by hypoxia. The knowledge would add to the pathophysiologic understanding of OAB. PMID:21397301

  17. Role of chemoreception in cardiorespiratory acclimatization to, and deacclimatization from, hypoxia.

    PubMed

    Dempsey, Jerome A; Powell, Frank L; Bisgard, Gerald E; Blain, Gregory M; Poulin, Marc J; Smith, Curtis A

    2014-04-01

    During sojourn to high altitudes, progressive time-dependent increases occur in ventilation and in sympathetic nerve activity over several days, and these increases persist upon acute restoration of normoxia. We discuss evidence concerning potential mediators of these changes, including the following: 1) correction of alkalinity in cerebrospinal fluid; 2) increased sensitivity of carotid chemoreceptors; and 3) augmented translation of carotid chemoreceptor input (at the level of the central nervous system) into increased respiratory motor output via sensitization of hypoxic sensitive neurons in the central nervous system and/or an interdependence of central chemoreceptor responsiveness on peripheral chemoreceptor sensory input. The pros and cons of chemoreceptor sensitization and cardiorespiratory acclimatization to hypoxia and intermittent hypoxemia are also discussed in terms of their influences on arterial oxygenation, the work of breathing, sympathoexcitation, systemic blood pressure, and exercise performance. We propose that these adaptive processes may have negative implications for the cardiovascular health of patients with sleep apnea and perhaps even for athletes undergoing regimens of "sleep high-train low"!

  18. Cardiosphere-derived cell sheet primed with hypoxia improves left ventricular function of chronically infarcted heart.

    PubMed

    Hosoyama, Tohru; Samura, Makoto; Kudo, Tomoaki; Nishimoto, Arata; Ueno, Koji; Murata, Tomoaki; Ohama, Takashi; Sato, Koichi; Mikamo, Akihito; Yoshimura, Koichi; Li, Tao-Sheng; Hamano, Kimikazu

    2015-01-01

    Cardiosphere-derived cells (CDCs) isolated from postnatal heart tissue are a convenient and efficientresource for the treatment of myocardial infarction. However, poor retention of CDCs in infarcted hearts often causes less than ideal therapeutic outcomes. Cell sheet technology has been developed as a means of permitting longer retention of graft cells, and this therapeutic strategy has opened new avenues of cell-based therapy for severe ischemic diseases. However, there is still scope for improvement before this treatment can be routinely applied in clinical settings. In this study, we investigated whether hypoxic preconditioning enhances the therapeutic efficacy of CDC monolayer sheets. To induce hypoxia priming, CDC monolayer sheets were placed in an incubator adjusted to 2% oxygen for 24 hours, and then preconditioned mouse CDC sheets were implanted into the infarcted heart of old myocardial infarction mouse models. Hypoxic preconditioning of CDC sheets remarkably increased the expression of vascular endothelial growth factor through the PI3-kinase/Akt signaling pathway. Implantation of preconditioned CDC sheets improved left ventricular function inchronically infarcted hearts and reduced fibrosis. The therapeutic efficacy of preconditioned CDC sheets was higher than the CDC sheets that were cultured under normaxia condition. These results suggest that hypoxic preconditioning augments the therapeutic angiogenic and anti-fibrotic activity of CDC sheets. A combination of cell sheets and hypoxic preconditioning offers an attractive therapeutic protocol for CDC transplantation into chronically infarcted hearts. PMID:26885271

  19. Inhibition of hypoxia inducible factor-1α attenuates abdominal aortic aneurysm progression through the down-regulation of matrix metalloproteinases

    PubMed Central

    Tsai, Shih-Hung; Huang, Po-Hsun; Hsu, Yu-Juei; Peng, Yi-Jen; Lee, Chien-Hsing; Wang, Jen-Chun; Chen, Jaw-Wen; Lin, Shing-Jong

    2016-01-01

    Hypoxia inducible factor-1α (HIF-1α) pathway is associated with many vascular diseases, including atherosclerosis, arterial aneurysms, pulmonary hypertension and chronic venous diseases. Significant HIF-1α expression could be found at the rupture edge at human abdominal aortic aneurysm (AAA) tissues. While our initial in vitro experiments had shown that deferoxamine (DFO) could attenuate angiotensin II (AngII) induced endothelial activations; we unexpectedly found that DFO augmented the severity of AngII-induced AAA, at least partly through increased accumulation of HIF-1α. The findings promoted us to test whether aneurysmal prone factors could up-regulate the expression of MMP-2 and MMP-9 through aberrantly increased HIF-1α and promote AAA development. AngII induced AAA in hyperlipidemic mice model was used. DFO, as a prolyl hydroxylase inhibitor, stabilized HIF-1α and augmented MMPs activities. Aneurysmal-prone factors induced HIF-1α can cause overexpression of MMP-2 and MMP-9 and promote aneurysmal progression. Pharmacological HIF-1α inhibitors, digoxin and 2-ME could ameliorate AngII induced AAA in vivo. HIF-1α is pivotal for the development of AAA. Our study provides a rationale for using HIF-1α inhibitors as an adjunctive medical therapy in addition to current cardiovascular risk-reducing regimens. PMID:27363580

  20. Inhibition of hypoxia inducible factor-1α attenuates abdominal aortic aneurysm progression through the down-regulation of matrix metalloproteinases.

    PubMed

    Tsai, Shih-Hung; Huang, Po-Hsun; Hsu, Yu-Juei; Peng, Yi-Jen; Lee, Chien-Hsing; Wang, Jen-Chun; Chen, Jaw-Wen; Lin, Shing-Jong

    2016-01-01

    Hypoxia inducible factor-1α (HIF-1α) pathway is associated with many vascular diseases, including atherosclerosis, arterial aneurysms, pulmonary hypertension and chronic venous diseases. Significant HIF-1α expression could be found at the rupture edge at human abdominal aortic aneurysm (AAA) tissues. While our initial in vitro experiments had shown that deferoxamine (DFO) could attenuate angiotensin II (AngII) induced endothelial activations; we unexpectedly found that DFO augmented the severity of AngII-induced AAA, at least partly through increased accumulation of HIF-1α. The findings promoted us to test whether aneurysmal prone factors could up-regulate the expression of MMP-2 and MMP-9 through aberrantly increased HIF-1α and promote AAA development. AngII induced AAA in hyperlipidemic mice model was used. DFO, as a prolyl hydroxylase inhibitor, stabilized HIF-1α and augmented MMPs activities. Aneurysmal-prone factors induced HIF-1α can cause overexpression of MMP-2 and MMP-9 and promote aneurysmal progression. Pharmacological HIF-1α inhibitors, digoxin and 2-ME could ameliorate AngII induced AAA in vivo. HIF-1α is pivotal for the development of AAA. Our study provides a rationale for using HIF-1α inhibitors as an adjunctive medical therapy in addition to current cardiovascular risk-reducing regimens. PMID:27363580

  1. The effects of diel-cycling hypoxia acclimation on the hypoxia tolerance, swimming capacity and growth performance of southern catfish (Silurus meridionalis).

    PubMed

    Yang, Han; Cao, Zhen-Dong; Fu, Shi-Jian

    2013-06-01

    To investigate the effects of diel-cycling hypoxia acclimation on the hypoxia tolerance, swimming and growth performance of juvenile southern catfish, we initially measured the critical oxygen tension (P(crit)), oxygen thresholds of aquatic surface respiration (ASR) and loss of equilibrium (LOE) of diel-cycling hypoxia-acclimated (15 d, 7:00-21:00, dissolved oxygen level (DO) = 7.0 ± 0.2 mg L(-1); 21:00-7:00, DO = 3.0 ± 0.2 mg L(-1)) and non-acclimated (15 d, DO = 7.0 ± 0.2 mg L(-1)) southern catfish at 25 °C. We then measured the critical swimming speed (U(crit)) and metabolic rate (MR) of hypoxia-acclimated and non-acclimated fish (under both hypoxic and normoxic conditions). The feeding rate (FR), feeding efficiency (FE) and specific growth rate (SGR) of fish in hypoxia-acclimated and non-acclimated groups were also measured. The P(crit), ASR and LOE of hypoxia-acclimated fish were significantly lower than those of non-acclimated fish. Hypoxia acclimation resulted in a significantly higher U(crit) when the individuals swam in hypoxia. The U(crit), maximum metabolic rate (MMR) and metabolic scope (MS) of both the hypoxia-acclimated and non-acclimated fish all decreased with the decrease of DO. However, the U(crit), MMR and MS decreased by 31, 43 and 54%, respectively, in non-acclimated fish, whereas these values decreased by 15, 28 and 29%, respectively, in hypoxia-acclimated fish, which suggests that hypoxia-acclimated fish were less sensitive to the DO decrease. The FR, FE and SGR all decreased by 21, 20 and 45%, respectively, in the hypoxia-acclimated group compared to the non-acclimated group. This result suggests that diel-cycling hypoxia acclimation improved the hypoxia tolerance and aerobic swimming performance of southern catfish, whereas impaired the growth performance. The high hypoxia tolerance and physiological plasticity to hypoxia-acclimated southern catfish may be related to its lower maintenance energy expenditure, sit-and-wait lifestyle and

  2. Resorbable polymer fibers for ligament augmentation.

    PubMed

    Dürselen, L; Dauner, M; Hierlemann, H; Planck, H; Claes, L E; Ignatius, A

    2001-01-01

    Resorbable augmentation devices for cruciate ligament surgery have been developed to temporarily protect healing tendon grafts or sutured ligaments against high tensile loads during the postoperative healing period. Materials available at present [e.g., polydioxanone (PDS)] show a half-life tensile strength of only 4-6 weeks, whereas the process of revitalization and recovering of the transplanted tendon graft can take up to 12 months. Therefore, a device that provides gradually decreasing mechanical properties with a half-time strength of at least 6 months would be desirable. In order to obtain a suitable material, we investigated the degradation kinetics of a variety of different resorbable fibers made of poly(L-lactide) and poly(L-lactide-co-glycolide). The fiber materials differed in processing and treatment parameters like thermal posttreatment, irradiation, and fiber diameter. The fibers were degraded in vitro and were tested for mechanical properties and molecular weight at various time points up to 72 weeks. The half-time strength of the materials ranged between 5 and 64 weeks, depending on their treatment parameters. In contrast, the stiffness did not decrease adequately. However, an augmentation stiffness that does not change much versus time could not provide a gradual increase in graft load, which is important to stimulate the orientation of the collagenous tissue. Therefore, design of an augmentation construct braided out of more than one quickly degrading fiber materials is suggested. After the breakdown of the faster-degrading fiber components the stiffness would automatically decrease by the diminution of the load-carrying fiber volume. PMID:11745519

  3. Hypoxia Alters Progression of the Erythroid Program

    PubMed Central

    Rogers, Heather M.; Yu, Xiaobing; Wen, Jie; Smith, Reginald; Fibach, Eitan; Noguchi, Constance Tom

    2008-01-01

    Hypoxia can induce erythropoiesis through regulated increase of erythropoietin (Epo) production. We investigated the direct influence of oxygen tension (pO2) in the physiologic range (2–8%) on erythroid progenitor cell differentiation using cultures of adult human hematopoietic progenitor cells exposed to decreasing (20 – 2%) pO2 and independent of variation in Epo levels. Decreases in Hb-containing cells were observed at the end of the culture period with decreasing pO2. This is due in part to a reduction in cell growth, and at 2% O2 a marked increase in cell toxicity. Analysis of the kinetics of cell differentiation showed an increase in the proportion of cells with glycophorin A expression and Hb accumulation at physiologic pO2. The cells were characterized by an early induction of γ-globin expression and a delay and reduction in peak levels of β-globin expression. Overall, fetal Hb and γ-globin expression were increased at physiologic pO2 but the increases were reduced at 2% O2 as cultures become cytotoxic. At reduced pO2, induction of EPO-receptor (EPO-R) by Epo was decreased and delayed, analogous to the delay in β-globin induction. The oxygen dependent reduction of EPO-R can account for the associated cytotoxicity at 2% O2. Epo induction of erythroid transcription factors, EKLF, GATA-1 and SCL/Tal-1, was also delayed and decreased at reduced pO2, consistent with lower levels of EPO-R and resultant Epo signaling. These changes in EPO-R and globin gene expression raise the possibility that the early increase of γ-globin is a consequence of reduced Epo signaling and a delay in induction of erythroid transcription factors. PMID:17936496

  4. B-52 stability augmentation system reliability

    NASA Technical Reports Server (NTRS)

    Bowling, T. C.; Key, L. W.

    1976-01-01

    The B-52 SAS (Stability Augmentation System) was developed and retrofitted to nearly 300 aircraft. It actively controls B-52 structural bending, provides improved yaw and pitch damping through sensors and electronic control channels, and puts complete reliance on hydraulic control power for rudder and elevators. The system has experienced over 300,000 flight hours and has exhibited service reliability comparable to the results of the reliability test program. Development experience points out numerous lessons with potential application in the mechanization and development of advanced technology control systems of high reliability.

  5. Intermittent hypoxia and diet-induced obesity: effects on oxidative status, sympathetic tone, plasma glucose and insulin levels, and arterial pressure.

    PubMed

    Olea, Elena; Agapito, Maria Teresa; Gallego-Martin, Teresa; Rocher, Asuncion; Gomez-Niño, Angela; Obeso, Ana; Gonzalez, Constancio; Yubero, Sara

    2014-10-01

    Obstructive sleep apnea (OSA) consists of sleep-related repetitive obstructions of upper airways that generate episodes of recurrent or intermittent hypoxia (IH). OSA commonly generates cardiovascular and metabolic pathologies defining the obstructive sleep apnea syndrome (OSAS). Literature usually links OSA-associated pathologies to IH episodes that would cause an oxidative status and a carotid body-mediated sympathetic hyperactivity. Because cardiovascular and metabolic pathologies in obese patients and those with OSAS are analogous, we used models (24-wk-old Wistar rats) of IH (applied from weeks 22 to 24) and diet-induced obesity (O; animals fed a high-fat diet from weeks 12 to 24) to define the effect of each individual maneuver and their combination on the oxidative status and sympathetic tone of animals, and to quantify cardiovascular and metabolic parameters and their deviation from normality. We found that IH and O cause an oxidative status (increased lipid peroxides and diminished activities of superoxide dismutases), an inflammatory status (augmented C-reactive protein and nuclear factor kappa-B activation), and sympathetic hyperactivity (augmented plasma and renal artery catecholamine levels and synthesis rate); combined treatments worsened those alterations. IH and O augmented liver lipid content and plasma cholesterol, triglycerides, leptin, glycemia, insulin levels, and HOMA index, and caused hypertension; most of these parameters were aggravated when IH and O were combined. IH diminished ventilatory response to hypoxia, and hypercapnia and O created a restrictive ventilatory pattern; a combination of treatments led to restrictive hypoventilation. Data demonstrate that IH and O cause comparable metabolic and cardiovascular pathologies via misregulation of the redox status and sympathetic hyperactivity. PMID:25103975

  6. Progressive multicystic encephalopathy: is there more than hypoxia-ischemia?

    PubMed

    Garten, Lars; Hueseman, Dieter; Stoltenburg-Didinger, Gisela; Felderhoff-Mueser, Ursula; Weizsaecker, Katharina; Scheer, Ianina; Boltshauser, Eugen; Obladen, Michael

    2007-05-01

    Progressive multicystic encephalopathy following prenatal or perinatal hypoxia-ischemia is a well-described phenomenon in the literature. The authors report on a term infant with a devastating encephalopathy and severe neuronal dysfunction immediately after delivery without a known antecedent of prenatal or perinatal hypoxia or distress. Clinical and paraclinical findings in the patient are compared with those described in the literature. The authors focus on the specific results guiding to the final diagnosis of progressive multicystic encephalopathy and the timing of morphologic changes. As in this case, if the criteria of an acute hypoxic event sufficient to cause neonatal encephalopathy are not met, then factors other than hypoxia-ischemia may be leading to progressive multicystic encephalopathy.

  7. Obstructive sleep apnea and cancer: effects of intermittent hypoxia?

    PubMed

    Kukwa, Wojciech; Migacz, Ewa; Druc, Karolina; Grzesiuk, Elzbieta; Czarnecka, Anna M

    2015-01-01

    Obstructive sleep apnea (OSA) is a common disorder characterized by pauses in regular breathing. Apneic episodes lead to recurrent hypoxemia-reoxygenation cycles with concomitant cellular intermittent hypoxia. Studies suggest that intermittent hypoxia in OSA may influence tumorigenesis. This review presents recent articles on the potential role of OSA in cancer development. Relevant research has focused on: molecular pathways mediating the influence of intermittent hypoxia on tumor physiology, animal and epidemiological human studies linking OSA and cancer. Current data relating OSA to risk of neoplastic disease remain scarce, but recent studies reveal the potential for a strong relation. More work is, therefore, needed on the impact of OSA on many cancer-related aspects. Results may offer enlightenment for improved cancer diagnosis and treatment. PMID:26562000

  8. Hypoxia-mediated regulation of gene expression in mammalian cells

    PubMed Central

    Shih, Shu-Ching; Claffey, Kevin P.

    1998-01-01

    The molecular mechanism underlying oxygen sensing in mammalian cells has been extensively investigated in the areas of glucose transport, glycolysis, erythropoiesis, angiogenesis and catecholamine metabolism. Expression of functionally operative representative proteins in these specific areas, such as the glucose transporter 1, glycolytic enzymes, erythropoietin, vascular endothelial growth factor and tyrosine hydroxylase are all induced by hypoxia. Recent studies demonstrated that both transcriptional activation and post-transcriptional mechanisms are important to the hypoxia-mediated regulation of gene expression. In this article, the cis-acting elements and trans-acting factors involved in the transcriptional activation of gene expression will be reviewed. In addition, the mechanisms of post-transcriptional mRNA stabilization will also be addressed. We will discuss whether these two processes of regulation of hypoxia-responsive genes are mechanistically linked and co-operative in nature. PMID:10319016

  9. Calcium-dependent activation of Pyk2 by hypoxia.

    PubMed

    Beitner-Johnson, Dana; Ferguson, Tsuneo; Rust, Randy T; Kobayashi, Shuichi; Millhorn, David E

    2002-02-01

    The Pyk2 tyrosine kinase can be activated by both calcium-dependent and calcium-independent mechanisms. Exposure to moderate hypoxia (5% O(2)) induced a rapid and persistent tyrosine phosphorylation of Pyk2 in pheochromocytoma (PC12) cells. Hypoxia and KCl-depolarization increased the phosphotyrosine content of Pyk2 by twofold and fourfold, respectively. Both of these effects were abolished in the absence of extracellular calcium. There was a modest activation of MAPK in parallel with the onset of Pyk2 phosphorylation. However, there was no detectable activation of either JNK or c-src, two other known downstream targets of Pyk2. Thus, exposure to hypoxia may selectively target specific subsets of Pyk2 signalling pathways. PMID:11781137

  10. Relationships between Cycling Hypoxia, HIF-1, Angiogenesis and Oxidative Stress

    PubMed Central

    Dewhirst, Mark W.

    2009-01-01

    This Failla Lecture focused on the inter-relationships between tumor angiogenesis, HIF-1 expression and radiotherapy responses. A common thread that bonds all of these factors together is microenvironmental stress caused by reactive oxygen and nitrogen species formed during tumor growth and angiogenesis or in response to cytotoxic treatment. In this review we focus on one aspect of the crossroad between oxidative stress and angiogenesis, namely cycling hypoxia. Understanding of the relative importance of this feature of the tumor microenvironment has recently expanded; it influences tumor biology in ways that are separate from chronic hypoxia. Cycling hypoxia can influence angiogenesis, treatment responses and metastatic behavior. It represents an important and relatively less well understood feature of tumor biology that requires additional research. PMID:19929412

  11. Metabolic and locomotor responses of juvenile paddlefish Polyodon spathula to hypoxia and temperature

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hypoxia is an increasing problem in the natural habitats that the paddlefish (Polyodon spathula) has historically inhabited, and a potential problem in managed culture conditions. However, the effects of hypoxia on paddlefish are not well understood. In order to understand the effects of hypoxia on ...

  12. Aging, Tolerance to High Altitude, and Cardiorespiratory Response to Hypoxia.

    PubMed

    Richalet, Jean-Paul; Lhuissier, François J

    2015-06-01

    Richalet, Jean-Paul, and François J. Lhuissier. Aging, tolerance to high altitude, and cardiorespiratory response to hypoxia. High Alt Med Biol. 16:117-124, 2015.--It is generally accepted that aging is rather protective, at least at moderate altitude. Some anecdotal reports even mention successful ascent of peaks over 8000 m and even Everest by elderly people. However, very few studies have explored the influence of aging on tolerance to high altitude and prevalence of acute high altitude related diseases, taking into account all confounding factors such as speed of ascent, altitude reached, sex, training status, and chemo-responsiveness. Changes in physiological responses to hypoxia with aging were assessed through a cross-sectional 20-year study including 4675 subjects (2789 men, 1886 women; 14-85 yrs old) and a longitudinal study including 30 subjects explored at a mean 10.4-year interval. In men, ventilatory response to hypoxia increased, while desaturation was less pronounced with aging. Cardiac response to hypoxia was blunted with aging in both genders. Similar results were found in the longitudinal study, with a decrease in cardiac and an increase in ventilatory response to hypoxia with aging. These adaptive responses were less pronounced or absent in post-menopausal untrained women. In conclusion, in normal healthy and active subjects, aging has no deleterious effect on cardiac and ventilatory responses to hypoxia, at least up to the eighth decade. Aging is not a contraindication for high altitude, as far as no pathological condition interferes and physical fitness is compatible with the intensity of the expected physical demand of one's individual. Physiological evaluation through hypoxic exercise testing before going to high altitude is helpful to detect risk factors of severe high altitude-related diseases.

  13. Ventilation during simulated altitude, normobaric hypoxia and normoxic hypobaria

    NASA Technical Reports Server (NTRS)

    Loeppky, J. A.; Icenogle, M.; Scotto, P.; Robergs, R.; Hinghofer-Szalkay, H.; Roach, R. C.; Leoppky, J. A. (Principal Investigator)

    1997-01-01

    To investigate the possible effect of hypobaria on ventilation (VE) at high altitude, we exposed nine men to three conditions for 10 h in a chamber on separate occasions at least 1 week apart. These three conditions were: altitude (PB = 432, FIO2 = 0.207), normobaric hypoxia (PB = 614, FIO2 = 0.142) and normoxic hypobaria (PB = 434, FIO2 = 0.296). In addition, post-test measurements were made 2 h after returning to ambient conditions at normobaric normoxia (PB = 636, FIO2 = 0.204). In the first hour of exposure VE was increased similarly by altitude and normobaric hypoxia. The was 38% above post-test values and end-tidal CO2 (PET(CO2) was lower by 4 mmHg. After 3, 6 and 9 h, the average VE in normobaric hypoxia was 26% higher than at altitude (p < 0.01), resulting primarily from a decline in VE at altitude. The difference between altitude and normobaric hypoxia was greatest at 3 h (+ 39%). In spite of the higher VE during normobaric hypoxia, the PET(CO2) was higher than at altitude. Changes in VE and PET(CO2) in normoxic hypobaria were minimal relative to normobaric normoxia post-test measurements. One possible explanation for the lower VE at altitude is that CO2 elimination is relatively less at altitude because of a reduction in inspired gas density compared to normobaric hypoxia; this may reduce the work of breathing or alveolar deadspace. The greater VE during the first hour at altitude, relative to subsequent measurements, may be related to the appearance of microbubbles in the pulmonary circulation acting to transiently worsen matching. Results indicate that hypobaria per se effects ventilation under altitude conditions.

  14. Impaired response of mature adipocytes of diabetic mice to hypoxia

    SciTech Connect

    Hong, Seok Jong Jin, Da P.; Buck, Donald W.; Galiano, Robert D.; Mustoe, Thomas A.

    2011-10-01

    Adipose tissue contains various cells such as infiltrated monocytes/macrophages, endothelial cells, preadipocytes, and adipocytes. Adipocytes have an endocrine function by secreting adipokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-{alpha}, leptin, and adiponectin. Dysregulation of adipokines in adipose tissues leads to a chronic low-grade inflammation which could result in atherosclerosis, hypertension, and type 2 diabetes. A sustained inflammatory state, which is characterized by prolonged persistence of macrophages and neutrophils, is found in diabetic wounds. In addition, subcutaneous adipocytes are enormously increased in amount clinically in type 2 diabetes. However, the function of subcutaneous adipocytes, which play an important role in injured tissue subjected to hypoxia, has not been well characterized in vitro due to the difficulty of maintaining mature adipocytes in culture using conventional methods because of their buoyancy. In this study, we established a novel in vitro culture method of mature adipocytes by enclosing them in a hyaluronan (HA) based hydrogel to study their role in response to stress such as hypoxia. BrdU labeling and Ki67 immunostaining experiments showed that hydrogel enclosed mature adipocytes proliferate in vitro. Both mRNA and protein expression analyses for hypoxia regulated genes, such as vascular endothelial growth factor (VEGF) and heme oxygenase 1 (HO1), showed that mature adipocytes of wild type mice respond to hypoxia. In contrast, mature adipocytes of diabetic db/db and TallyHo mice did not efficiently respond to hypoxia. Our studies suggest that mature adipocytes are functionally active cells, and their abnormal function to hypoxia can be one of underlining mechanisms in type 2 diabetes.

  15. Periodic breathing in healthy humans at exercise in hypoxia.

    PubMed

    Hermand, Eric; Pichon, Aurélien; Lhuissier, François J; Richalet, Jean-Paul

    2015-01-01

    Periodic breathing is frequent in heart failure or ventilatory disorders during sleep, and common during sleep at high altitude, but has been rarely studied in wakefulness and during exercise. A retrospective analysis of ventilation from hypoxia exercise tests was realized in 82 healthy subjects separated into two groups with either high or low ventilatory response to hypoxia at exercise (HVRe). A fast Fourier transform spectral analysis of the breath-by-breath ventilation (V̇e) signal, O2 saturation, and end-tidal PCO2 evidenced a periodic pattern with a period of 11.1 to 12.0 s. The peak power of the V̇e spectrum was higher in the high HVRe group (P < 0.001). A prospective study (25 subjects) was performed to evaluate the influence of cardiorespiratory factors on the amplitude and period of oscillations in various conditions of exercise (20 to 40% maximal aerobic power) and hypoxia (0 to 4,000 m altitude). The period of V̇e was shorter at exercise (vs. rest, P < 0.001) and hypoxia (vs. normoxia, P < 0.001), and inversely related with cardiac output and V̇e (P < 0.001). V̇e peak power was higher at exercise (P < 0.001) and hypoxia (P < 0.001), and was positively related with cardiac output and V̇e (P < 0.001). V̇e peak power in hypoxia was positively related with the ventilatory response to CO2 (HCVR). This novel observation suggests that healthy subjects demonstrate a spontaneous periodic breathing, not clearly observable at rest and in normoxia, but triggered by hypoxic exercise. The periodic pattern is enhanced in subjects with high HVRe and high HCVR, suggesting that oxygen and CO2 play synergistic roles in the modulation of these oscillations.

  16. Hypoxia reduces the hypothalamic thermogenic threshold and thermosensitivity.

    PubMed

    Tattersall, Glenn J; Milsom, William K

    2009-11-01

    Hypoxia is well known to reduce the body temperature (T(b)) of mammals, although the neural origins of this response remain uncertain. Short-term hypoxic exposure causes a reduction in the lower critical temperature of the thermal neutral zone and a reduction in whole body thermal conductance of rodents, providing indirect support that hypoxia lowers T(b) in a regulated manner. In this study, we examined directly the potential for changes in central thermosensitivity to evoke the hypoxic metabolic response by heating and cooling the preoptic area of the hypothalamus (the area which integrates thermoreceptor input and regulates thermoeffector outputs) using chronic, indwelling thermodes in ground squirrels during normoxia and hypoxia (7, 10 and 12% O(2)). We found that the threshold hypothalamic temperature for the metabolic response to cooling (T(th)) of approximately 38 degrees C in normoxia was proportionately reduced in hypoxia (down to 28-31 degrees C at 7% O(2)) and that the metabolic thermosensitivity (alpha; the change in metabolic rate for any given change in hypothalamic temperature below the lower critical temperature) was comparatively reduced by 5 to 9 times. This provides strong support for the hypothesis that the fall in temperature that occurs during hypoxia is the result of a reduction in the activation of thermogenic mechanisms. The decrease in the central thermosensitivity in hypoxia, however, appears to be a critical factor in the alteration of mammalian T(b). We suggest, therefore, that an altered central thermosensitivity may provide a proximate explanation of how low oxygen and similar stressors reduce normal fluctuations in T(b) (i.e. circadian), in addition to the depression in regulated T(b).

  17. Evaluation of CT Perfusion Biomarkers of Tumor Hypoxia

    PubMed Central

    Qi, Qi; Yeung, Timothy Pok Chi; Lee, Ting-Yim; Bauman, Glenn; Crukley, Cathie; Morrison, Laura; Hoffman, Lisa; Yartsev, Slav

    2016-01-01

    Background Tumor hypoxia is associated with treatment resistance to cancer therapies. Hypoxia can be investigated by immunohistopathologic methods but such procedure is invasive. A non-invasive method to interrogate tumor hypoxia is an attractive option as such method can provide information before, during, and after treatment for personalized therapies. Our study evaluated the correlations between computed tomography (CT) perfusion parameters and immunohistopathologic measurement of tumor hypoxia. Methods Wistar rats, 18 controls and 19 treated with stereotactic radiosurgery (SRS), implanted with the C6 glioma tumor were imaged using CT perfusion on average every five days to monitor tumor growth. A final CT perfusion scan and the brain were obtained on average 14 days (8–22 days) after tumor implantation. Tumor hypoxia was detected immunohistopathologically with pimonidazole. The tumor, necrotic, and pimonidazole-positive areas on histology samples were measured. Percent necrotic area and percent hypoxic areas were calculated. Tumor volume (TV), blood flow (BF), blood volume (BV), and permeability-surface area product (PS) were obtained from the CT perfusion studies. Correlations between CT perfusion parameters and histological parameters were assessed by Spearman’s ρ correlation. A Bonferroni-corrected P value < 0.05 was considered significant. Results BF and BV showed significant correlations with percent hypoxic area ρ = -0.88, P < 0.001 and ρ = -0.81, P < 0.001, respectively, for control animals and ρ = -0.7, P < 0.001 and ρ = -0.6, P = 0.003, respectively, for all animals, while TV and BV were correlated (ρ = -0.64, P = 0.01 and ρ = -0.43, P = 0.043, respectively) with percent necrotic area. PS was not correlated with either percent necrotic or percent hypoxic areas. Conclusions Percent hypoxic area provided significant correlations with BF and BV, suggesting that CT perfusion parameters are potential non-invasive imaging biomarkers of tumor

  18. Quantifying hypoxia-induced chemoreceptor sensitivity in the awake rodent.

    PubMed

    Morgan, Barbara J; Adrian, Russell; Bates, Melissa L; Dopp, John M; Dempsey, Jerome A

    2014-10-01

    We evaluated several methods for characterizing hypoxic chemosensitivity in the conscious rat. Adult Sprague-Dawley rats (n = 30) were exposed to normobaric hypoxia [inspired oxygen fraction (Fio2) 0.15, 0.12, and 0.09]. We measured ventilation (V̇e; barometric plethysmography), arterial oxygen saturation (SpO2; pulse oximeter), and oxygen consumption and carbon dioxide production (V̇o2 and V̇co2; analysis of expired air). Linear regression analysis was used to define stimulus-response relationships. Testing was performed on 2 days to assess day-to-day reproducibility. Exposure to graded, steady-state hypoxia caused progressive reductions in SpO2 that were, for any given Fio2, quite variable (SpO2 range, 20-30%) among individuals. Hypoxia produced progressive increases in V̇e caused by increases in both tidal volume (VT) and breathing frequency. Hypoxia also increased the VT:inspiratory time (Ti) ratio, an indicator of central respiratory "drive." Hypoxia caused consistent, progressive declines in V̇o2, V̇co2, and core temperature (>20% at the lowest SpO2). We propose that optimal quantification of carotid chemoreceptor hypoxic sensitivity in the unanesthetized rodent should employ SpO2 [a surrogate for arterial Po2 (PaO2 )] as the stimulus variable and the ventilatory equivalent for V̇co2 (V̇e/V̇co2) and/or mean inspiratory flow rate (VT/Ti) normalized for V̇co2 as the response variables. Both metrics take into account not only the important influence of a falling metabolic rate, but also SpO2, which represents the hypoxic stimulus at the carotid body. Because of the somewhat curvilinear nature of these responses, exposure to multiple levels of graded hypoxia provides the most complete characterization of hypoxic chemosensitivity. PMID:25080926

  19. Augmenting Your Own Reality: Student Authoring of Science-Based Augmented Reality Games

    ERIC Educational Resources Information Center

    Klopfer, Eric; Sheldon, Josh

    2010-01-01

    Augmented Reality (AR) simulations superimpose a virtual overlay of data and interactions onto a real-world context. The simulation engine at the heart of this technology is built to afford elements of game play that support explorations and learning in students' natural context--their own community and surroundings. In one of the more recent…

  20. Past Occurrences of Hypoxia in the Baltic Sea

    NASA Astrophysics Data System (ADS)

    Zillen, L.; Conley, D. J.; Bjorck, S.

    2007-12-01

    The hypoxic zone in the Baltic Sea has increased in area by about four times since 1950. Widespread oxygen deficiency below the halocline has severely reduced macro benthic communities in the Baltic Proper and the Gulf of Finland over the past decades and negatively effected food chain dynamics, fish habitats and fisheries in the entire Baltic Sea. In addition, hypoxia alters nutrient biogeochemical cycles. The cause of the increased hypoxia is believed to be enhanced eutrophication through increased anthropogenic input of nutrients, such as phosphorous and nitrogen. Conditions prior to the 1950s are considered as the benchmark and some authors suggest that the earlier Baltic Sea was an oligothrophic, clear-water body with oxygenated deep waters. By contrast, studies of short sediment cores reveal that hypoxia has been present in some of the deepest basins for at least the last 100-200 years. In addition, long sediment cores suggest that hypoxia in the Baltic Sea has occurred intermittently in deep basins over the last c. 8500 years. Thus, the occurrence of present day hypoxia in the deeper basins need not necessarily be attributed to human activity but rather to natural oceanographic, geologic and climate conditions. We present a compilation of previous publications that reported the occurrence of laminated sediments (i.e. a palaeo-proxy for hypoxia) in the Baltic Sea. This review shows that the deeper parts of the Baltic Sea have experienced either intermittent or more regular hypoxia during most of the Holocene and that more continuous laminations started to form c. 7800-8500 cal. yr BP ago, in association with the establishment of a permanent halocline during the transition from the Ancylus Lake to the Littorina Sea. Laminated sediments were more common during the early and late Holocene and coincided with intervals of high organic productivity (high TOC content) and high salinity during the Holocene Thermal Maximum and the Medieval Climate Optimum. This study

  1. [EFFECT OF HYPOXIA ON THE CHARACTERISTICS OF HUMAN AUDITORY PERCEPTION].

    PubMed

    Ogorodnikova, E A; Stolvaroya, E I; Pak, S P; Bogomolova, G M; Korolev, Yu N; Golubev, V N; Lesova, E M

    2015-12-01

    The effect of normobaric hypoxic hypoxia (single and interval training) on the characteristics of human hearing was investigated. The hearing thresholds (tonal audiograms), reaction time of subjects in psychophysical experiments (pause detection, perception of rhythm and target words), and short-term auditory memory were measured before and after hypoxia. The obtained data revealed improvement of the auditory sensitivity and characteristics of working memory, and increasing of response speed. It was demonstrated that interval hypoxic training had positive effect on the processes of auditory perception. PMID:26987233

  2. Virtually-augmented interfaces for tactical aircraft.

    PubMed

    Haas, M W

    1995-05-01

    The term Fusion Interface is defined as a class of interface which integrally incorporates both virtual and non-virtual concepts and devices across the visual, auditory and haptic sensory modalities. A fusion interface is a multi-sensory virtually-augmented synthetic environment. A new facility has been developed within the Human Engineering Division of the Armstrong Laboratory dedicated to exploratory development of fusion-interface concepts. One of the virtual concepts to be investigated in the Fusion Interfaces for Tactical Environments facility (FITE) is the application of EEG and other physiological measures for virtual control of functions within the flight environment. FITE is a specialized flight simulator which allows efficient concept development through the use of rapid prototyping followed by direct experience of new fusion concepts. The FITE facility also supports evaluation of fusion concepts by operational fighter pilots in a high fidelity simulated air combat environment. The facility was utilized by a multi-disciplinary team composed of operational pilots, human-factors engineers, electronics engineers, computer scientists, and experimental psychologists to prototype and evaluate the first multi-sensory, virtually-augmented cockpit. The cockpit employed LCD-based head-down displays, a helmet-mounted display, three-dimensionally localized audio displays, and a haptic display. This paper will endeavor to describe the FITE facility architecture, some of the characteristics of the FITE virtual display and control devices, and the potential application of EEG and other physiological measures within the FITE facility.

  3. HDF Augmentation: Interoperability in the Last Mile

    NASA Astrophysics Data System (ADS)

    Plutchak, J.; Folk, M. J.; Habermann, T.; Knox, L.

    2014-12-01

    Science data files are generally written to serve well-defined purposes for a small science teams. In many cases, the organization of the data and the metadata are designed for custom tools developed and maintained by and for the team. Using these data outside of this context many times involves restructuring, re-documenting, or reformatting the data. This expensive and time-consuming process usually prevents data reuse and thus decreases the total life-cycle value of the data considerably. If the data are unique or critically important to solving a particular problem, they can be modified into a more generally usable form or metadata can be added in order to enable reuse. This augmentation process can be done to enhance data for the intended purpose or for a new purpose, to make the data available to new tools and applications, to make the data more conventional or standard, or to simplify preservation of the data. The HDF Group has addressed augmentation needs in many ways: by adding extra information, by renaming objects or moving them around in the file, by reducing complexity of the organization, and sometimes by hiding data objects that are not understood by specific applications. In some cases these approaches require re-writing the data into new files and in some cases it can be done externally, without affecting the original file. We will describe and compare several examples of each approach.

  4. Vertical Alveolar Ridge Augmentation by Distraction Osteogenesis

    PubMed Central

    Kumar, N. Nanda; Ravindran, C.

    2015-01-01

    Introduction Compromised alveolar ridge in vertical and horizontal dimension is a common finding in patients visiting practitioners for dental prosthesis. Various treatment modalities are available for correction of deficient ridges among which alveolar distraction osteogenesis is one. Aim To study the efficacy of alveolar distraction osteogenesis in augmentation of alveolar ridges deficient in vertical dimension. Materials and Methods Ten patients aged 16 to 46 years with deficient alveolar ridge underwent ridge augmentation in 11 alveolar segments using the distraction osteogenesis method. For each patient a custom made distraction device was fabricated. The device was indigenously manufactured with SS-316 (ISO 3506). Results The vertical bone gain reached more than 10mm without the use of bone transplantation. Certain complications like incorrect vector of distraction, paresthesia, pain and loss of transport segment were encountered during the course of the study. Conclusion Alveolar vertical distraction osteogenesis is a reliable and predictable technique for both hard and soft tissue genesis. Implant placement is feasible with primary stability in neogenerated bone at the level of the distracted areas. PMID:26816991

  5. Preconditioning stimuli that augment chromaffin cell secretion.

    PubMed

    Tapia, Laura; García-Eguiagaray, Josefina; García, Antonio G; Gandía, Luis

    2009-04-01

    We have investigated here whether a preconditioned stimulation of nicotinic and muscarinic receptors augmented the catecholamine release responses elicited by supramaximal 3-s pulses of 100 muM acetylcholine (100ACh) or 100 mM K(+) (100K(+)) applied to fast-perifused bovine adrenal chromaffin cells. Threshold concentrations of nicotine (1-3 muM) that caused only a tiny secretion did, however, augment the responses elicited by 100ACh or 100K(+) by 2- to 3.5-fold. This effect was suppressed by mecamylamine and by Ca(2+) deprivation, was developed with a half-time (t(1/2)) of 1 min, and was reversible. The nicotine effect was mimicked by threshold concentrations of ACh, choline, epibatidine, and oxotremorine-M but not by methacholine. Threshold concentrations of K(+) caused lesser potentiation of secretion compared with that of threshold nicotine. The data are compatible with an hypothesis implying 1) that continuous low-frequency sympathetic discharge places chromaffin cells at the adrenal gland in a permanent "hypersensitive" state; and 2) this allows an explosive secretion of catecholamines by high-frequency sympathetic discharge during stress.

  6. Soft tissue augmentation with ArteFill.

    PubMed

    Hilinski, John M; Cohen, Steven R

    2009-05-01

    ArteFill is a novel, third-generation polymethylmethacrylate (PMMA) injectable filler with unique properties. When compared with predecessor materials, ArteFill demonstrates improved biocompatibility as a result of more uniform PMMA microsphere size and shape. This translates into less adverse events after placement. ArteFill can provide a permanent volume enhancement by stimulation of fibroblasts that encapsulate nonabsorbable microspheres with collagen deposition. Currently, ArteFill is FDA approved for permanent augmentation of moderately deep nasolabial folds. It is also commonly used off-label for augmentation of other skin creases and regional areas of volume deficiency, such as the tear trough-malar and marionette line-prejowl sulcus regions. The key to success with ArteFill is a conservative approach with avoidance of overcorrection. Proper technique includes deep dermal to subcutaneous placement with full correction achieved gradually over several treatments. Complications are mostly limited to nodule formation, which is easily managed in most cases with conservative intervention.

  7. Biological Augmentation of Rotator Cuff Tendon Repair

    PubMed Central

    Kovacevic, David

    2008-01-01

    A histologically normal insertion site does not regenerate following rotator cuff tendon-to-bone repair, which is likely due to abnormal or insufficient gene expression and/or cell differentiation at the repair site. Techniques to manipulate the biologic events following tendon repair may improve healing. We used a sheep infraspinatus repair model to evaluate the effect of osteoinductive growth factors and BMP-12 on tendon-to-bone healing. Magnetic resonance imaging and histology showed increased formation of new bone and fibrocartilage at the healing tendon attachment site in the treated animals, and biomechanical testing showed improved load-to-failure. Other techniques with potential to augment repair site biology include use of platelets isolated from autologous blood to deliver growth factors to a tendon repair site. Modalities that improve local vascularity, such as pulsed ultrasound, have the potential to augment rotator cuff healing. Important information about the biology of tendon healing can also be gained from studies of substances that inhibit healing, such as nicotine and antiinflammatory medications. Future approaches may include the use of stem cells and transcription factors to induce formation of the native tendon-bone insertion site after rotator cuff repair surgery. PMID:18264850

  8. Prospects for Optogenetic Augmentation of Brain Function

    PubMed Central

    Jarvis, Sarah; Schultz, Simon R.

    2015-01-01

    The ability to optically control neural activity opens up possibilities for the restoration of normal function following neurological disorders. The temporal precision, spatial resolution, and neuronal specificity that optogenetics offers is unequalled by other available methods, so will it be suitable for not only restoring but also extending brain function? As the first demonstrations of optically “implanted” novel memories emerge, we examine the suitability of optogenetics as a technique for extending neural function. While optogenetics is an effective tool for altering neural activity, the largest impediment for optogenetics in neural augmentation is our systems level understanding of brain function. Furthermore, a number of clinical limitations currently remain as substantial hurdles for the applications proposed. While neurotechnologies for treating brain disorders and interfacing with prosthetics have advanced rapidly in the past few years, partially addressing some of these critical problems, optogenetics is not yet suitable for use in humans. Instead we conclude that for the immediate future, optogenetics is the neurological equivalent of the 3D printer: its flexibility providing an ideal tool for testing and prototyping solutions for treating brain disorders and augmenting brain function. PMID:26635547

  9. Breast Augmentation With Autologous Fat Injection

    PubMed Central

    Li, Fa-Cheng; Chen, Bing; Cheng, Lin

    2014-01-01

    Introduction Autologous fat transplantation has attracted great interest in breast augmentation for cosmetic purpose. In the present study, we reported our experience in fat grafting in breast in 105 cases, and some detailed procedure concerning efficacy and safety of grafting was evaluated. Methods Fat was harvested using 20-mL syringe attached to a 3-hole blunt cannula in a diameter not beyond 3 mm. After washing with cool normal saline to remove blood, the fat was managed with open method using cotton towel as a platform for concentration fat tissue and separating them from fluids, oil, and debris. A 14-gauge, 1-hole blunt cannula was used to place the fat through 3-mm incision on inframammary fold. The fat was infiltrated into the breast from deep to superficial subcutaneous plane. Results Between July 2002 and August 2010, 105 patients have undergone this procedure. The age distribution of the patients ranged from 18 to 45 years, with a mean of 31.3 years. Grafted fat volume has ranged from 120 to 250 mL (average, 205 mL) per breast per session. All women had a significant improvement in their breast size and shape postoperatively, and the breasts were soft and natural in appearance. Conclusions Liposuction and autologous fat transplantation is a suitable approach for augmentation mammaplasty. PMID:25003461

  10. NADPH Oxidase-Derived ROS Induced by Chronic Intermittent Hypoxia Mediates Hypersensitivity of Lung Vagal C Fibers in Rats.

    PubMed

    Yang, Chang-Huan; Zhuang, Wei-Ling; Shen, Yan-Jhih; Lai, Ching Jung; Kou, Yu Ru

    2016-01-01

    Obstructive sleep apnea (OSA), manifested by exposure to chronic intermittent hypoxia (CIH) and excess production of reactive oxygen species (ROS) in the airways, is associated with hyperreactive airway diseases. ROS, particularly when created by NADPH oxidase, are known to sensitize lung vagal C fibers (LVCFs), which may contribute to airway hypersensitivity pathogenesis. We investigated whether CIH augments the reflex and afferent responses of LVCFs to chemical stimulants and the roles of ROS and NADPH oxidase in such airway hypersensitivity. Rats were exposed to room air (RA) or CIH with/without daily treatment with MnTMPyP (a superoxide anion scavenger), apocynin (an NADPH oxidase inhibitor), or vehicle. At 16 h after their last exposure, intravenous capsaicin, adenosine, or α,β-methylene-ATP evoked an augmented apneic response in anesthetized rats with 14-days CIH exposure, compared to anesthetized rats with 14-days RA exposure. The augmented apneic responses to these LVCF stimulants were abolished by bilateral vagotomy or perivagal capsaicin treatment, which block LVCFs neural conduction and were significantly suppressed by treatment with MnTMPyP or apocynin, but not vehicle. Electrophysiological studies revealed that 14-days CIH exposure potentiated the responses of LVCFs to these stimulants. This effect was inhibited by treatment with MnTMPyP or apocynin treatment and was not seen in rats who received 7-days of CIH exposure. Biochemical analysis indicated that 14-days CIH exposure increased both lung lipid peroxidation, which is indicative of oxidative stress, and expression of the p47(phox) subunit in the membrane fraction of lung tissue, which is an index of NADPH oxidase activation. The former was prevented by treatment with either MnTMPyP or apocynin, while the later was prevented by treatment with apocynin only. These results suggest that 14-days CIH exposure sensitizes LVCFs in rats, leading to an exaggerated reflex and afferent responses to

  11. NADPH Oxidase-Derived ROS Induced by Chronic Intermittent Hypoxia Mediates Hypersensitivity of Lung Vagal C Fibers in Rats

    PubMed Central

    Yang, Chang-Huan; Zhuang, Wei-Ling; Shen, Yan-Jhih; Lai, Ching Jung; Kou, Yu Ru

    2016-01-01

    Obstructive sleep apnea (OSA), manifested by exposure to chronic intermittent hypoxia (CIH) and excess production of reactive oxygen species (ROS) in the airways, is associated with hyperreactive airway diseases. ROS, particularly when created by NADPH oxidase, are known to sensitize lung vagal C fibers (LVCFs), which may contribute to airway hypersensitivity pathogenesis. We investigated whether CIH augments the reflex and afferent responses of LVCFs to chemical stimulants and the roles of ROS and NADPH oxidase in such airway hypersensitivity. Rats were exposed to room air (RA) or CIH with/without daily treatment with MnTMPyP (a superoxide anion scavenger), apocynin (an NADPH oxidase inhibitor), or vehicle. At 16 h after their last exposure, intravenous capsaicin, adenosine, or α,β-methylene-ATP evoked an augmented apneic response in anesthetized rats with 14-days CIH exposure, compared to anesthetized rats with 14-days RA exposure. The augmented apneic responses to these LVCF stimulants were abolished by bilateral vagotomy or perivagal capsaicin treatment, which block LVCFs neural conduction and were significantly suppressed by treatment with MnTMPyP or apocynin, but not vehicle. Electrophysiological studies revealed that 14-days CIH exposure potentiated the responses of LVCFs to these stimulants. This effect was inhibited by treatment with MnTMPyP or apocynin treatment and was not seen in rats who received 7-days of CIH exposure. Biochemical analysis indicated that 14-days CIH exposure increased both lung lipid peroxidation, which is indicative of oxidative stress, and expression of the p47phox subunit in the membrane fraction of lung tissue, which is an index of NADPH oxidase activation. The former was prevented by treatment with either MnTMPyP or apocynin, while the later was prevented by treatment with apocynin only. These results suggest that 14-days CIH exposure sensitizes LVCFs in rats, leading to an exaggerated reflex and afferent responses to

  12. Hypoxia tolerance in elasmobranchs. I. Critical oxygen tension as a measure of blood oxygen transport during hypoxia exposure.

    PubMed

    Speers-Roesch, Ben; Richards, Jeffrey G; Brauner, Colin J; Farrell, Anthony P; Hickey, Anthony J R; Wang, Yuxiang S; Renshaw, Gillian M C

    2012-01-01

    The critical O(2) tension of whole-animal O(2) consumption rate (M(O2)), or P(crit), is the water P(O2) (Pw(O(2))) at which an animal transitions from an oxyregulator to an oxyconformer. Although P(crit) is a popular measure of hypoxia tolerance in fishes because it reflects the capacity for O(2) uptake from the environment at low Pw(O(2)), little is known about the interrelationships between P(crit) and blood O(2) transport characteristics and increased use of anaerobic metabolism during hypoxia exposure in fishes, especially elasmobranchs. We addressed this knowledge gap using progressive hypoxia exposures of two elasmobranch species with differing hypoxia tolerance. The P(crit) of the hypoxia-tolerant epaulette shark (Hemiscyllium ocellatum, 5.10±0.37 kPa) was significantly lower than that of the comparatively hypoxia-sensitive shovelnose ray (Aptychotrema rostrata, 7.23±0.40 kPa). Plasma [lactate] was elevated above normoxic values at around P(crit) in epaulette sharks, but increased relative to normoxic values at Pw(O(2)) below P(crit) in shovelnose rays, providing equivocal support for the hypothesis that P(crit) is associated with increased anaerobic metabolism. The M(O2), arterial P(O2) and arterial blood O(2) content (Ca(O(2))) were similar between the two species under normoxia and decreased in both species with progressive hypoxia, but as Pw(O(2)) declined, epaulette sharks had a consistently higher M(O2) and Ca(O(2)) than shovelnose rays, probably due to their significantly greater in vivo haemoglobin (Hb)-O(2) binding affinity (in vivo Hb-O(2) P(50)=4.27±0.57 kPa for epaulette sharks vs 6.35±0.34 kPa for shovelnose rays). However, at Pw(O(2)) values representing the same percentage of each species' P(crit) (up to ∼175% of P(crit)), Hb-O(2) saturation and Ca(O(2)) were similar between species. These data support the hypothesis that Hb-O(2) P(50) is an important determinant of P(crit) and suggest that P(crit) can predict Hb-O(2) saturation and Ca

  13. A preliminary look at control augmented dynamic response of structures

    NASA Technical Reports Server (NTRS)

    Ryan, R. S.; Jewell, R. E.

    1983-01-01

    The augmentation of structural characteristics, mass, damping, and stiffness through the use of control theory in lieu of structural redesign or augmentation was reported. The standard single-degree-of-freedom system was followed by a treatment of the same system using control augmentation. The system was extended to elastic structures using single and multisensor approaches and concludes with a brief discussion of potential application to large orbiting space structures.

  14. Optimal Constellation Design for Satellite Based Augmentation System

    NASA Astrophysics Data System (ADS)

    Kawano, Isao

    Global Positioning System (GPS) is widely utilized in daily life, for instance car navigation. Wide Area Augmentation System (WAAS) and Local Area Augmentation System (LAAS) are proposed so as to provide GPS better navigation accuracy and integrity capability. Satellite Based Augmentation System (SBAS) is a kind of WAAS and Multi-functional Transportation Satellite (MTSAT) has been developed in Japan. To improve navigation accuracy most efficiently, augmentation satellites should be so placed that minimize Geometric Dilution of Precision (GDOP) of constellation. In this paper the result of optimal constellation design for SBAS is shown.

  15. Recent changes in hypoxia training at the Royal Air Force Centre of Aviation Medicine.

    PubMed

    Wrigley, A

    2015-01-01

    Hypoxia training at the Royal Air Force Centre of Aviation Medicine (RAF CAM) has traditionally involved the use of a hypobaric chamber to induce hypoxia. While giving the student experience of both hypoxia and decompression, hypobaric chamber training is not without risks such as decompression sickness and barotrauma. This article describes the new system for hypoxia training known as Scenario-Based Hypoxia Training (SBHT), which involves the subject sitting in an aircraft simulator and wearing a mask linked by hose to a Reduced Oxygen Breathing Device (ROBD). The occupational requirements to be declared fit for this new training method are also discussed. PMID:26867422

  16. Progress toward overcoming hypoxia-induced resistance to solid tumor therapy

    PubMed Central

    Karakashev, Sergey V; Reginato, Mauricio J

    2015-01-01

    Hypoxic tumors are associated with poor clinical outcome for multiple types of human cancer. This may be due, in part, to hypoxic cancer cells being resistant to anticancer therapy, including radiation therapy, chemotherapy, and targeted therapy. Hypoxia inducible factor 1, a major regulator of cellular response to hypoxia, regulates the expression of genes that are involved in multiple aspects of cancer biology, including cell survival, proliferation, metabolism, invasion, and angiogenesis. Here, we review multiple pathways regulated by hypoxia/hypoxia inducible factor 1 in cancer cells and discuss the latest advancements in overcoming hypoxia-mediated tumor resistance. PMID:26316817

  17. Augmentation of Creatine in the Heart.

    PubMed

    Zervou, Sevasti; Whittington, Hannah J; Russell, Angela J; Lygate, Craig A

    2016-01-01

    Creatine is a principle component of the creatine kinase (CK) phosphagen system common to all vertebrates. It is found in excitable cells, such as cardiomyocytes, where it plays an important role in the buffering and transport of chemical energy to ensure that supply meets the dynamic demands of the heart. Multiple components of the CK system, including intracellular creatine levels, are reduced in heart failure, while ischaemia and hypoxia represent acute crises of energy provision. Elevation of myocardial creatine levels has therefore been suggested as potentially beneficial, however, achieving this goal is not trivial. This mini-review outlines the evidence in support of creatine elevation and critically examines the pharmacological approaches that are currently available. In particular, dietary creatine-supplementation does not sufficiently elevate creatine levels in the heart due to subsequent down-regulation of the plasma membrane creatine transporter (CrT). Attempts to increase passive diffusion and bypass the CrT, e.g. via creatine esters, have yet to be tested in the heart. However, studies in mice with genetic overexpression of the CrT demonstrate proof-of-principle that elevated creatine protects the heart from ischaemia-reperfusion injury. This suggests activation of the CrT as a major unmet pharmacological target. However, translation of this finding to the clinic will require a greater understanding of CrT regulation in health and disease and the development of small molecule activators.

  18. Augmentation of Creatine in the Heart

    PubMed Central

    Zervou, Sevasti; Whittington, Hannah J.; Russell, Angela J.; Lygate, Craig A.

    2016-01-01

    Creatine is a principle component of the creatine kinase (CK) phosphagen system common to all vertebrates. It is found in excitable cells, such as cardiomyocytes, where it plays an important role in the buffering and transport of chemical energy to ensure that supply meets the dynamic demands of the heart. Multiple components of the CK system, including intracellular creatine levels, are reduced in heart failure, while ischaemia and hypoxia represent acute crises of energy provision. Elevation of myocardial creatine levels has therefore been suggested as potentially beneficial, however, achieving this goal is not trivial. This mini-review outlines the evidence in support of creatine elevation and critically examines the pharmacological approaches that are currently available. In particular, dietary creatine-supplementation does not sufficiently elevate creatine levels in the heart due to subsequent down-regulation of the plasma membrane creatine transporter (CrT). Attempts to increase passive diffusion and bypass the CrT, e.g. via creatine esters, have yet to be tested in the heart. However, studies in mice with genetic overexpression of the CrT demonstrate proof-of-principle that elevated creatine protects the heart from ischaemia-reperfusion injury. This suggests activation of the CrT as a major unmet pharmacological target. However, translation of this finding to the clinic will require a greater understanding of CrT regulation in health and disease and the development of small molecule activators. PMID:26202199

  19. Tasting arterial blood: what do the carotid chemoreceptors sense?

    PubMed Central

    Prabhakhar, Nanduri R.; Joyner, Michael J.

    2015-01-01

    The carotid bodies are sensory organs that detect the chemical composition of the arterial blood. The carotid body sensory activity increases in response to arterial hypoxemia and the ensuing chemoreflex regulates vital homeostatic functions. Recent studies suggest that the carotid bodies might also sense arterial blood glucose and circulating insulin levels. This review focuses on how the carotid bodies sense O2, glucose, and insulin and some potential implications of these sensory functions on physiological regulation and in pathophysiological conditions. Emerging evidence suggests that carbon monoxide (CO)-regulated hydrogen sulfide (H2S), stemming from hypoxia, depolarizes type I cells by inhibiting certain K+ channels, facilitates voltage-gated Ca2+ influx leading to sensory excitation of the carotid body. Elevated CO and decreased H2S renders the carotid bodies insensitive to hypoxia resulting in attenuated ventilatory adaptations to high altitude hypoxia, whereas reduced CO and high H2S result in hypersensitivity of the carotid bodies to hypoxia and hypertension. Acute hypoglycemia augments the carotid body responses to hypoxia but that a prolonged lack of glucose in the carotid bodies can lead to a failure to sense hypoxia. Emerging evidence also indicates that carotid bodies might sense insulin directly independent of its effect on glucose, linking the carotid bodies to the pathophysiological consequences of the metabolic syndrome. How glucose and insulin interact with the CO-H2S signaling is an area of ongoing study. PMID:25642193

  20. Tasting arterial blood: what do the carotid chemoreceptors sense?

    PubMed

    Prabhakhar, Nanduri R; Joyner, Michael J

    2014-01-01

    The carotid bodies are sensory organs that detect the chemical composition of the arterial blood. The carotid body sensory activity increases in response to arterial hypoxemia and the ensuing chemoreflex regulates vital homeostatic functions. Recent studies suggest that the carotid bodies might also sense arterial blood glucose and circulating insulin levels. This review focuses on how the carotid bodies sense O2, glucose, and insulin and some potential implications of these sensory functions on physiological regulation and in pathophysiological conditions. Emerging evidence suggests that carbon monoxide (CO)-regulated hydrogen sulfide (H2S), stemming from hypoxia, depolarizes type I cells by inhibiting certain K(+) channels, facilitates voltage-gated Ca(2+) influx leading to sensory excitation of the carotid body. Elevated CO and decreased H2S renders the carotid bodies insensitive to hypoxia resulting in attenuated ventilatory adaptations to high altitude hypoxia, whereas reduced CO and high H2S result in hypersensitivity of the carotid bodies to hypoxia and hypertension. Acute hypoglycemia augments the carotid body responses to hypoxia but that a prolonged lack of glucose in the carotid bodies can lead to a failure to sense hypoxia. Emerging evidence also indicates that carotid bodies might sense insulin directly independent of its effect on glucose, linking the carotid bodies to the pathophysiological consequences of the metabolic syndrome. How glucose and insulin interact with the CO-H2S signaling is an area of ongoing study. PMID:25642193

  1. Assessment of hypoxia-inducible factor-1α mRNA expression in mantis shrimp as a biomarker of environmental hypoxia exposure.

    PubMed

    Kodama, Keita; Rahman, Md Saydur; Horiguchi, Toshihiro; Thomas, Peter

    2012-04-23

    Efforts to assess the ecological impacts of the marked increase in coastal hypoxia worldwide have been hampered by a lack of biomarkers of hypoxia exposure in marine benthic organisms. Here, we show that hypoxia-inducible factor-1α (HIF-1α) transcript levels in the heart and cerebral ganglion of mantis shrimp (Oratosquilla oratoria) collected from hypoxic sites in Tokyo Bay are elevated several-fold over those in shrimp collected from normoxic sites. Upregulation of HIF-1α mRNA levels in the heart after exposure to sub-lethal hypoxia was confirmed in controlled laboratory experiments. HIF-1α transcript levels were increased at approximately threefold after 7 and 14 days of hypoxia exposure and declined to control levels within 24 h of restoration to normoxic conditions. The results provide the first evidence for upregulation of HIF-1α transcript levels in two hypoxia-sensitive organs, heart and cerebral ganglion, in a marine invertebrate exposed to environmental hypoxia. These results suggest that upregulation of HIF-1α transcript levels is an important component in adaptation of mantis shrimp to chronic hypoxia and is a potentially useful biomarker of environmental hypoxia exposure. PMID:22031724

  2. The molecular basis of O2-sensing and hypoxia tolerance in pheochromocytoma cells.

    PubMed

    Conrad, P W; Conforti, L; Kobayashi, S; Beitner-Johnson, D; Rust, R T; Yuan, Y; Kim, H W; Kim, R H; Seta, K; Millhorn, D E

    2001-02-01

    Hypoxia is a common environmental stimulus. However, very little is known about the mechanisms by which cells sense and respond to changes in oxygen. Our laboratory has utilized the PC12 cell line in order to study the biophysical and molecular response to hypoxia. The current review summarizes our results. We demonstrate that the O2-sensitive K(+) channel, Kv1.2, is present in PC12 cells and plays a critical role in the hypoxia-induced depolarization of PC12 cells. Previous studies have shown that PC12 cells secrete a variety of autocrine/paracrine factors, including dopamine, norepinephrine, and adenosine during hypoxia. We investigated the mechanisms by which adenosine modulates cell function and the effect of chronic hypoxia on this modulation. Finally, we present results identifying the mitogen- and stress-activated protein kinases (MAPKs and SAPKs) as hypoxia-regulated protein kinases. Specifically, we show that p38 and an isoform, p38gamma, are activated by hypoxia. In addition, our results demonstrate that the p42/p44 MAPK protein kinases are activated by hypoxia. We further show that p42/p44 MAPK is critical for the hypoxia-induced transactivation of endothelial PAS-domain protein 1 (EPAS1), a hypoxia-inducible transcription factor. Together, these results provide greater insight into the mechanisms by which cells sense and adapt to hypoxia. PMID:11207433

  3. Transcriptomic responses of marine medaka's ovary to hypoxia.

    PubMed

    Lai, Keng Po; Li, Jing Woei; Tse, Anna Chung Kwan; Cheung, Angela; Wang, Simon; Chan, Ting Fung; Kong, Richard Yuen Chong; Wu, Rudolf Shiu Sun

    2016-08-01

    Hypoxia, an endocrine disruptor, is pressing global problem affecting marine organisms in over 400 "Dead Zones" worldwide. There is growing evident demonstrated the disruptive effect of hypoxia on reproductive systems of marine fish through the impairments of steroidogenic gene expression, leading to the alteration of sex hormone production in gonads. But the detailed molecular mechanism underlying the responses of female reproductive systems to hypoxic stress remains largely unknown. In the present report, we used marine medaka Oryzias melastigma as a model, together with high-throughput transcriptome sequencing and bioinformatics analysis, aiming to determine the changes in transcriptional signature in the ovary of marine fish under hypoxic stress. Our result discovered over two hundred differential expressed genes in ovary in response to hypoxia. The bioinformatics analysis together with quantitative RT-PCR validation on the deregulated genes highlighted the dysregulations of a number of female reproductive functions including interruptions of ovarian follicle development, gonad development and steroid metabolic process. Additionally, we revealed that these deregulations are through the modulation of leukemia inhibitory factor (LIF), insulin-like growth factor 1 receptor (IGF1R) and follicle stimulating hormone (FSH). The result of this work complements previous studies and provides additional insights into the underlying molecular mechanism of hypoxia-induced impairment of female reproductive system. PMID:27423118

  4. Hypoxia impacts large adults first: consequences in a warming world.

    PubMed

    Clark, Melody S; Husmann, Gunnar; Thorne, Michael A S; Burns, Gavin; Truebano, Manuela; Peck, Lloyd S; Abele, Doris; Philipp, Eva E R

    2013-07-01

    Future oceans are predicted to contain less oxygen than at present. This is because oxygen is less soluble in warmer water and predicted stratification will reduce mixing. Hypoxia in marine environments is thus likely to become more widespread in marine environments and understanding species-responses is important to predicting future impacts on biodiversity. This study used a tractable model, the Antarctic clam, Laternula elliptica, which can live for 36 years, and has a well-characterized ecology and physiology to understand responses to hypoxia and how the effect varied with age. Younger animals had a higher condition index, higher adenylate energy charge and transcriptional profiling indicated that they were physically active in their response to hypoxia, whereas older animals were more sedentary, with higher levels of oxidative damage and apoptosis in the gills. These effects could be attributed, in part, to age-related tissue scaling; older animals had proportionally less contractile muscle mass and smaller gills and foot compared with younger animals, with consequential effects on the whole-animal physiological response. The data here emphasize the importance of including age effects, as large mature individuals appear to be less able to resist hypoxic conditions and this is the size range that is the major contributor to future generations. Thus, the increased prevalence of hypoxia in future oceans may have marked effects on benthic organisms' abilities to persist and this is especially so for long-lived species when predicting responses to environmental perturbation.

  5. Acetazolamide and chronic hypoxia: effects on haemorheology and pulmonary haemodynamics.

    PubMed

    Pichon, Aurélien; Connes, Philippe; Quidu, Patricia; Marchant, Dominique; Brunet, Julien; Levy, Bernard I; Vilar, José; Safeukui, Innocent; Cymbalista, Florence; Maignan, Maxime; Richalet, Jean-Paul; Favret, Fabrice

    2012-12-01

    We tested the effect of acetazolamide on blood mechanical properties and pulmonary vascular resistance (PVR) during chronic hypoxia. Six groups of rats were either treated or not treated with acetazolamide (curative: treated after 10 days of hypoxic exposure; preventive: treated before hypoxic exposure with 40 mg · kg(-1) · day(-1)) and either exposed or not exposed to 3 weeks of hypoxia (at altitude >5,500 m). They were then used to assess the role of acetazolamide on pulmonary artery pressure, cardiac output, blood volume, haematological and haemorheological parameters. Chronic hypoxia increased haematocrit, blood viscosity and PVR, and decreased cardiac output. Acetazolamide treatment in hypoxic rats decreased haematocrit (curative by -10% and preventive by -11%), PVR (curative by -36% and preventive by -49%) and right ventricular hypertrophy (preventive -20%), and increased cardiac output (curative by +60% and preventive by +115%). Blood viscosity was significantly decreased after curative acetazolamide treatment (-16%) and was correlated with PVR (r=0.87, p<0.05), suggesting that blood viscosity could influence pulmonary haemodynamics. The fall in pulmonary vascular hindrance (curative by -27% and preventive by -45%) after treatment suggests that acetazolamide could decrease pulmonary vessels remodelling under chronic hypoxia. The effect of acetazolamide is multifactorial by acting on erythropoiesis, pulmonary circulation, haemorheological properties and cardiac output, and could represent a pertinent treatment of chronic mountain sickness. PMID:22523353

  6. LETHAL LEVELS OF HYPOXIA FOR GULF COAST ESTUARINE ANIMALS

    EPA Science Inventory

    There is increasing concern about eutrophication and subsequent hypoxia problems in estuaries. The U.S. Environmental Protection Agency has developed Water Quality Criteria (WQC) for dissolved oxygen (DO) in saltwater for Cape Cod, MA to Cape Hatteras, NC but inadequate data exis...

  7. The influence of altitude hypoxia on uroflowmetry parameters in women.

    PubMed

    Verratti, Vittore; Paulesu, Luana; Pietrangelo, Tiziana; Doria, Christian; Di Giulio, Camillo; Aloisi, Anna Maria

    2016-09-01

    There is scientific evidence to suggest a correlation between hypoxia and the physiology of micturition. During a Himalayan Scientific and Mountaineering Expedition, we performed tests to investigate the functional interactions between altitude hypoxia and uroflowmetry parameters in women. The tests were carried out in seven women (36.3 ± 7.1 yr) from normoxic [1,340 meters above sea level (m a.s.l.)] to hypoxic conditions (up to 5,050 m a.s.l.) and during the return descent. The following measures were determined: uroflowmetry parameters and saturation of peripheral oxygen (SpO2 ). As expected, SpO2 decreased from 97.7 to 77.8% with increasing altitude. Micturition flow time, flow volume, and voiding time increased with altitude (P < 0.04 for all), indicating a negative correlation with SpO2 In conclusion, in young adult women, micturition physiological parameters were affected during adaptation to hypoxia; the correlation with SpO2 strongly suggests a role of hypoxia in these changes. These data could help to support the design of new strategies for both prevention and medical treatment. An example of the latter might be hyperbaric oxygen therapy, which in some studies has proved able to reduce the symptoms in patients with hypoxic bladder. PMID:27358054

  8. The problem of hypoxia, hyperoxia and hypercapnia in space physiology

    NASA Technical Reports Server (NTRS)

    Agadzhanyan, N. A.; Gramenitskiy, P. M.; Kovalenko, Y. A.; Dvorzhak, I. I.; Moravek, M.; Palash, L.

    1974-01-01

    The dynamics of basic functional systems and behavioral reactions depend on the oxygen regime of the human body when confined in pressurized compartments during space flight. Permissible concentrations of oxygen, carbon dioxide and other gases to avoid symptoms of hypoxia, hyperoxia and hypercapnia are discussed in relation to numerous human tolerance studies.

  9. Visual Deficits and Improvements in Children after Perinatal Hypoxia.

    ERIC Educational Resources Information Center

    Groenendaal, F.; Van Hof-Van Duin, J.

    1992-01-01

    Study of the visual development of 38 infants, children, and youths who were neurologically impaired following perinatal hypoxia found that all children showed impairments of 1 or more visual functions, though visual development continued and visual improvements were demonstrated up to age 16. (Author/JDD)

  10. Human Skin Hypoxia Modulates Cerebrovascular and Autonomic Functions

    PubMed Central

    Pucci, Olivia; Qualls, Clifford; Battisti-Charbonney, Anne; Balaban, Dahlia Y.; Fisher, Joe A.; Duffin, Jim; Appenzeller, Otto

    2012-01-01

    Because the skin is an oxygen sensor in amphibians and mice, we thought to confirm this function also in humans. The human upright posture, however, introduces additional functional demands for the maintenance of oxygen homeostasis in which cerebral blood flow and autonomic nervous system (ANS) function may also be involved. We examined nine males and three females. While subjects were breathing ambient air, at sea level, we changed gases in a plastic body-bag during two conditions of the experiment such as to induce skin hypoxia (with pure nitrogen) or skin normoxia (with air). The subjects performed a test of hypoxic ventilatory drive during each condition of the experiment. We found no differences in the hypoxic ventilatory drive tests. However, ANS function and cerebral blood flow velocities were modulated by skin hypoxia and the effect was significantly greater on the left than right middle cerebral arteries. We conclude that skin hypoxia modulates ANS function and cerebral blood flow velocities and this might impact life styles and tolerance to ambient hypoxia at altitude. Thus the skin in normal humans, in addition to its numerous other functions, is also an oxygen sensor. PMID:23056597

  11. Antenatal Hypoxia and Pulmonary Vascular Function and Remodeling

    PubMed Central

    Papamatheakis, Demosthenes G.; Blood, Arlin B.; Kim, Joon H.; Wilson, Sean M.

    2015-01-01

    This review provides evidence that antenatal hypoxia, which represents a significant and worldwide problem, causes prenatal programming of the lung. A general overview of lung development is provided along with some background regarding transcriptional and signaling systems of the lung. The review illustrates that antenatal hypoxic stress can induce a continuum of responses depending on the species examined. Fetuses and newborns of certain species and specific human populations are well acclimated to antenatal hypoxia. However, antenatal hypoxia causes pulmonary vascular disease in fetuses and newborns of most mammalian species and humans. Disease can range from mild pulmonary hypertension, to severe vascular remodeling and dangerous elevations in pressure. The timing, length, and magnitude of the intrauterine hypoxic stress are important to disease development, however there is also a genetic-environmental relationship that is not yet completely understood. Determining the origins of pulmonary vascular remodeling and pulmonary hypertension and their associated effects is a challenging task, but is necessary in order to develop targeted therapies for pulmonary hypertension in the newborn due to antenatal hypoxia that can both treat the symptoms and curtail or reverse disease progression. PMID:24063380

  12. Antenatal hypoxia and pulmonary vascular function and remodeling.

    PubMed

    Papamatheakis, Demosthenes G; Blood, Arlin B; Kim, Joon H; Wilson, Sean M

    2013-09-01

    This review provides evidence that antenatal hypoxia, which represents a significant and worldwide problem, causes prenatal programming of the lung. A general overview of lung development is provided along with some background regarding transcriptional and signaling systems of the lung. The review illustrates that antenatal hypoxic stress can induce a continuum of responses depending on the species examined. Fetuses and newborns of certain species and specific human populations are well acclimated to antenatal hypoxia. However, antenatal hypoxia causes pulmonary vascular disease in fetuses and newborns of most mammalian species and humans. Disease can range from mild pulmonary hypertension, to severe vascular remodeling and dangerous elevations in pressure. The timing, length, and magnitude of the intrauterine hypoxic stress are important to disease development, however there is also a genetic-environmental relationship that is not yet completely understood. Determining the origins of pulmonary vascular remodeling and pulmonary hypertension and their associated effects is a challenging task, but is necessary in order to develop targeted therapies for pulmonary hypertension in the newborn due to antenatal hypoxia that can both treat the symptoms and curtail or reverse disease progression.

  13. Hypoxia impairs visual acuity in snapper (Pagrus auratus).

    PubMed

    Robinson, Esme; Jerrett, Alistair; Black, Suzanne; Davison, William

    2013-07-01

    We investigated the effect of environmental hypoxia on vision in snapper (Pagrus auratus). Juvenile snapper inhabit estuarine environments where oxygen conditions fluctuate on a seasonal basis. Optomotor experiments demonstrated that visual acuity is impaired by environmental hypoxia, but not until levels approach the critical oxygen tension (P crit) of this species (around 25% air-saturated seawater). In 100, 80, and 60% air-saturated seawater, a positive optomotor response was present at a minimum separable angle (M SA) of 1°. In 40% air-saturated seawater, vision was partially impaired with positive responses at M SAs of 2° and above. However, in 25% air-saturated seawater, visual acuity was seriously impaired, with positive responses only present at M SAs of 6° and above. Snapper were found to possess a choroid rete, facilitating the maintenance of high ocular oxygen partial pressures (PO2) during normoxia and moderate hypoxia (PO2, between 269 and 290 mmHg). However, at 40 and 25% water oxygen saturation, ocular PO2 was reduced to below 175 mmHg, which is perhaps linked to impairment of visual acuity in these conditions. The ability to preserve visual function during moderate hypoxia is beneficial for the maintenance of a visual lifestyle in the fluctuating oxygen environments of estuaries.

  14. Progressive hypoxia decouples activity and aerobic performance of skate embryos

    PubMed Central

    Di Santo, Valentina; Tran, Anna H.; Svendsen, Jon C.

    2016-01-01

    Although fish population size is strongly affected by survival during embryonic stages, our understanding of physiological responses to environmental stressors is based primarily on studies of post-hatch fishes. Embryonic responses to acute exposure to changes in abiotic conditions, including increase in hypoxia, could be particularly important in species exhibiting long developmental time, as embryos are unable to select a different environment behaviourally. Given that oxygen is key to metabolic processes in fishes and aquatic hypoxia is becoming more severe and frequent worldwide, organisms are expected to reduce their aerobic performance. Here, we examined the metabolic and behavioural responses of embryos of a benthic elasmobranch fish, the little skate (Leucoraja erinacea), to acute progressive hypoxia, by measuring oxygen consumption and movement (tail-beat) rates inside the egg case. Oxygen consumption rates were not significantly affected by ambient oxygen levels until reaching 45% air saturation (critical oxygen saturation, Scrit). Below Scrit, oxygen consumption rates declined rapidly, revealing an oxygen conformity response. Surprisingly, we observed a decoupling of aerobic performance and activity, as tail-beat rates increased, rather than matching the declining metabolic rates, at air saturation levels of 55% and below. These results suggest a significantly divergent response at the physiological and behavioural levels. While skate embryos depressed their metabolic rates in response to progressive hypoxia, they increased water circulation inside the egg case, presumably to restore normoxic conditions, until activity ceased abruptly around 9.8% air saturation. PMID:27293746

  15. Hypoxia-related brain dysfunction in forensic medicine.

    PubMed

    Suslo, R; Trnka, J; Siewiera, J; Drobnik, J

    2015-01-01

    Blood gases levels imbalances belong to important factors triggering central nervous system (CNS) functional disturbances. Hypoxia can be illness-related, like in many COPD patients, or it may be caused by broad range of external or iatrogenic factors - including influence of drugs depressing respiration, failure to keep the patient's prosthesis-supported airways patent, or a mistake in the operation of medical equipment supporting patient's respiration. Hypoxia, especially when it is not accompanied by rapid carbon dioxide retention, can go unnoticed for prolonged times, deepening existing CNS disorders, sometimes rapidly triggering their manifestation, or evoking quite new conditions and symptoms - like anxiety, agitation, aggressive behavior, euphoria, or hallucinations. Those, in turn, often result in situations raising interest in law enforcement institutions which need forensic medicine specialist's assistance and opinion. The possibility of illness or drug-related hypoxia, especially in terminal patients, is used to raise questions about the patients' ability to properly express their will in the way demanded by law - it also must be considered as a factor limiting the patients' responsibility in case they commit crimes. The possibility of hallucinations in hypoxia patients limits their credibility as witnesses or even their ability to report crime or sexual abuse they have been subjected to.

  16. Reactive Oxygen Species and Respiratory Plasticity Following Intermittent Hypoxia

    PubMed Central

    MacFarlane, P.M.; Wilkerson, J.E.R.; Lovett-Barr, M.R.; Mitchell, G.S.

    2008-01-01

    The neural network controlling breathing exhibits plasticity in response to environmental or physiological challenges. For example, while hypoxia initiates rapid and robust increases in respiratory motor output to defend against hypoxemia, it also triggers persistent changes, or plasticity, in chemosensory neurons and integrative pathways that transmit brainstem respiratory activity to respiratory motor neurons. Frequently studied models of hypoxia-induced respiratory plasticity include: 1) carotid chemosensory plasticity and metaplasticity induced by chronic intermittent hypoxia (CIH), and 2) acute intermittent hypoxia (AIH) induced phrenic long-term facilitation (pLTF) in naïve and CIH preconditioned rats. These forms of plasticity share some mechanistic elements, although they differ in anatomical location and the requirement for CIH preconditioning. Both forms of plasticity require serotonin receptor activation and formation of reactive oxygen species (ROS). While the cellular sources and targets of ROS are not well known, recent evidence suggests that ROS modify the balance of protein phosphatase and kinase activities, shifting the balance towards net phosphorylation and favoring cellular reactions that induce and/or maintain plasticity. Here, we review possible sources of ROS, and the impact of ROS on phosphorylation events relevant to respiratory plasticity. PMID:18692605

  17. HIF-1 and ventilatory acclimatization to chronic hypoxia

    PubMed Central

    Powell, Frank L.; Fu, Zhenxing

    2008-01-01

    Ventilatory acclimatization to hypoxia (VAH) is a time-dependent increase in ventilation and ventilatory O2-sensitivity that involves plasticity in carotid body chemoreceptors and CNS respiratory centers. Hypoxia inducible factor-1α (HIF-1α) controls the expression of several genes that increase physiological O2 supply. Studies using transgenic mice show HIF-1α expression in the carotid bodies and CNS with chronic sustained and intermittent hypoxia is important for VAH. Other O2-sensitive transcription factors such as HIF-2α may be important for VAH by reducing metabolic O2 demands also. Specific gene targets of HIF-1α shown to be involved in VAH include erythropoietin, endothelin-1, neuronal nitric oxide synthase and tyrosine hydroxylase. Other HIF-1α targets that may be involved in VAH include vascular endothelial growth factor, heme oxygenase 1 and cytoglobin. Interactions between these multiple pathways and feedback control of HIF-1α expression from some of the targets support a complex and powerful role for HIF-1α in neural plasticity of physiological control circuits with chronic hypoxia. PMID:18708172

  18. Use of Satellite Remote Sensing to Improve Coastal Hypoxia Prediction

    EPA Science Inventory

    We describe the use of Giovanni satellite remote sensing products in the development and testing of a new modeling system that represents the processes leading to hypoxia (defined as water O2 concentration < 63 mmol m-3) on the Louisiana continental shelf (LCS). The modeling ...

  19. Heritable Cancer Syndromes Related to the Hypoxia Pathway

    PubMed Central

    Henegan, John Clark; Gomez, Christian R.

    2016-01-01

    Families of tumor-suppressor genes, such as those involved in homologous recombination or mismatch repair, contain individual genes implicated in hereditary cancer syndromes. Collectively, such groupings establish that inactivating germline changes in genes within pathways related to genomic repair can promote carcinogenesis. The hypoxia pathway, whose activation is associated with aggressive and resistant sporadic tumors, is another pathway in which tumor-suppressor genes have been identified. von Hippel–Lindau disease, some of the hereditary paraganglioma–pheochromocytoma (PGL/PCC) syndromes, and the syndrome of hereditary leiomyomatosis and renal cell carcinoma are heritable conditions associated with genes involved or associated with the hypoxia pathway. This review links these heritable cancer syndromes to the hypoxia pathway while also comparing the relative aggression and treatment resistance of syndrome-associated tumors to similar, sporadic tumors. The reader will become aware of shared phenotypes (e.g., PGL/PCC, renal cell carcinoma) among these three hypoxia-pathway-associated heritable cancer syndromes as well as the known associations of tumor aggressiveness and treatment resistance within these pathways. PMID:27047799

  20. Reconfigurable hardware for an augmented reality application

    NASA Astrophysics Data System (ADS)

    Toledo Moreo, F. Javier; Martinez Alvarez, J. Javier; Garrigos Guerrero, F. Javier; Ferrandez Vicente, J. Manuel

    2005-06-01

    An FPGA-based approach is proposed to build an augmented reality system in order to aid people affected by a visual disorder known as tunnel vision. The aim is to increase the user's knowledge of his environment by superimposing on his own view useful information obtained with image processing. Two different alternatives have been explored to perform the required image processing: a specific purpose algorithm to extract edge detection information, and a cellular neural network with the suitable template. Their implementations in reconfigurable hardware pursue to take advantage of the performance and flexibility that show modern FPGAs. This paper describes the hardware implementation of both the Canny algorithm and the cellular neural network, and the overall system architecture. Results of the implementations and examples of the system functionality are presented.