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Sample records for intermittent hypoxic exposure

  1. [Effects of intermittent hypoxic exposure on the parameter of erythrocyte and serum hypoxia inducible factor-1 alpha and erythropoietin levels].

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    Zhang, Cheng-yan; Zhang, Ji-xin; Lü, Xiao-tao; Li, Bao-yu

    2009-10-01

    To investigate the effects of intermittent hypoxic exposure and normoxic convalescence on the parameter of erythrocyte and serum hypoxia inducible factor-1 alpha (HIF-1alpha) and erythropoietin (EPO) levels. Rat models of intermittent hypoxic exposure were established, combined with the clinical research on volunteers experiencing the intermittent plateau work. Blood samples for red blood cell (RBC) counts, hemoglobin (Hb) and hematocrit (HCT) were collected, serum HIF-1alpha and EPO levels were measured using enzyme linked immunosorbent assay. RBC counts, Hb concentration and HCT were significantly higher than the normoxic group (P hypoxic exposure can enhance serum hypoxia inducible factor-1 alpha and erythropointin levels and the generation of red blood cells, which leads to an increase in hemoglobin concentration and hematocrit. The results have changed with the hypoxic exposure period prolonged. Normoxic convalescence after intermittent hypoxic exposure can make the related indexes reduced, and contribute to the organism recovery.

  2. Effects of Acutely Intermittent Hypoxic Exposure on Running Economy and Physical Performance in Basketball Players.

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    Kilding, Andrew E; Dobson, Bryan P; Ikeda, Erika

    2016-07-01

    Kilding, AE, Dobson, BP, and Ikeda, E. Effects of acutely intermittent hypoxic exposure on running economy and physical performance in basketball players. J Strength Cond Res 30(7): 2033-2042, 2016-The aim of this study was to determine the effect of short duration intermittent hypoxic exposure (IHE) on physical performance in basketball players. Using a single-blind placebo-controlled group design, 14 trained basketball players were subjected to 15 days of passive short duration IHE (n = 7), or normoxic control (CON, n = 7), using a biofeedback nitrogen dilution device. A range of physiological, performance, and hematological variables were measured at baseline, and 10 days after IHE. After intervention, the IHE group, relative to the CON group, exhibited improvements in the Yo-Yo intermittent recovery level 1 (+4.8 ± 1.6%; effect size [ES]: 1.0 ± 0.4) and repeated high-intensity exercise test performance (-3.5 ± 1.6%; ES: -0.4 ± 0.2). Changes in hematological parameters were minimal, although soluble transferrin receptor increased after IHE (+9.2 ± 10.1%; ES: 0.3 ± 0.3). Running economy at 11 km·h (-9.0 ± 9.7%; ES: -0.7 ± 0.7) and 13 km·h was improved (-8.2 ± 6.9%; ES: -0.7 ± 0.5), but changes to V[Combining Dot Above]O2peak, HRpeak, and lactate were unclear. In summary, acutely IHE resulted in worthwhile changes in physical performance tests among competitive basketball players. However, physiological measures explaining the performance enhancement were in most part unclear.

  3. COMPARISON OF LIVE HIGH: TRAIN LOW ALTITUDE AND INTERMITTENT HYPOXIC EXPOSURE

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    Clare E. Humberstone-Gough

    2013-09-01

    Full Text Available Live High:Train Low (LHTL altitude training is a popular ergogenic aid amongst athletes. An alternative hypoxia protocol, acute (60-90 min daily Intermittent Hypoxic Exposure (IHE, has shown potential for improving athletic performance. The aim of this study was to compare directly the effects of LHTL and IHE on the running and blood characteristics of elite triathletes. Changes in total haemoglobin mass (Hbmass, maximal oxygen consumption (VO2max, velocity at VO2max (vVO2max, time to exhaustion (TTE, running economy, maximal blood lactate concentration ([La] and 3 mM [La] running speed were compared following 17 days of LHTL (240 h of hypoxia, IHE (10.2 h of hypoxia or Placebo treatment in 24 Australian National Team triathletes (7 female, 17 male. There was a clear 3.2 ± 4.8% (mean ± 90% confidence limits increase in Hbmass following LHTL compared with Placebo, whereas the corresponding change of -1.4 ± 4.5% in IHE was unclear. Following LHTL, running economy was 2.8 ± 4.4% improved compared to IHE and 3mM [La] running speed was 4.4 ± 4.5% improved compared to Placebo. After IHE, there were no beneficial changes in running economy or 3mM [La] running speed compared to Placebo. There were no clear changes in VO2max, vVO2max and TTE following either method of hypoxia. The clear difference in Hbmass response between LHTL and IHE indicated that the dose of hypoxia in IHE was insufficient to induce accelerated erythropoiesis. Improved running economy and 3mM [La] running speed following LHTL suggested that this method of hypoxic exposure may enhance performance at submaximal running speeds. Overall, there was no evidence to support the use of IHE in elite triathletes

  4. Metabolic adaptations may counteract ventilatory adaptations of intermittent hypoxic exposure during submaximal exercise at altitudes up to 4000 m.

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    Martin Faulhaber

    Full Text Available Intermittent hypoxic exposure (IHE has been shown to induce aspects of altitude acclimatization which affect ventilatory, cardiovascular and metabolic responses during exercise in normoxia and hypoxia. However, knowledge on altitude-dependent effects and possible interactions remains scarce. Therefore, we determined the effects of IHE on cardiorespiratory and metabolic responses at different simulated altitudes in the same healthy subjects. Eight healthy male volunteers participated in the study and were tested before and 1 to 2 days after IHE (7 × 1 hour at 4500 m. The participants cycled at 2 submaximal workloads (corresponding to 40% and 60% of peak oxygen uptake at low altitude at simulated altitudes of 2000 m, 3000 m, and 4000 m in a randomized order. Gas analysis was performed and arterial oxygen saturation, blood lactate concentrations, and blood gases were determined during exercise. Additionally baroreflex sensitivity, hypoxic and hypercapnic ventilatory response were determined before and after IHE. Hypoxic ventilatory response was increased after IHE (p<0.05. There were no altitude-dependent changes by IHE in any of the determined parameters. However, blood lactate concentrations and carbon dioxide output were reduced; minute ventilation and arterial oxygen saturation were unchanged, and ventilatory equivalent for carbon dioxide was increased after IHE irrespective of altitude. Changes in hypoxic ventilatory response were associated with changes in blood lactate (r = -0.72, p<0.05. Changes in blood lactate correlated with changes in carbon dioxide output (r = 0.61, p<0.01 and minute ventilation (r = 0.54, p<0.01. Based on the present results it seems that the reductions in blood lactate and carbon dioxide output have counteracted the increased hypoxic ventilatory response. As a result minute ventilation and arterial oxygen saturation did not increase during submaximal exercise at simulated altitudes between 2000 m and 4000 m.

  5. Comparison of an Intermittent Hypoxic Exposure Acclimatization Program to Staging at Moderate Altitude on Endurance Performance at 4300 m

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    2009-10-01

    Endurance Performance at 4300 m 7 - 6 RTO-MP-HFM-181 breakfast volunteers were provided with two commercially available energy bars and fruit juice ...food composition = 510 kcal, 14 gm fat, 65 gm carbohydrate, 32 gm protein) at 1 to 2 hrs prior to the beginning of each of the cycle endurance test...JE, Robinson SR, Skrinar GS, Lewis SF and Sawka MN. Intermittent altitude exposures improve muscular performance at 4,300 m. J Appl Physiol 95

  6. Intermittent Hypoxic Episodes in Preterm Infants: Do They Matter?

    OpenAIRE

    Martin, Richard J.; Wang, Katherine; Köroğlu, Özge; Di Fiore, Juliann; Kc, Prabha

    2011-01-01

    Intermittent hypoxic episodes are typically a consequence of immature respiratory control and remain a troublesome challenge for the neonatologist. Furthermore, their frequency and magnitude are underestimated by clinically employed pulse oximeter settings. In extremely low birth weight infants the incidence of intermittent hypoxia progressively increases over the first 4 weeks of postnatal life, with a subsequent plateau followed by a slow decline beginning at weeks 6–8. Such episodic hypoxi...

  7. Intermittent hypoxic episodes in preterm infants: do they matter?

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    Martin, Richard J; Wang, Katherine; Köroğlu, Ozge; Di Fiore, Juliann; Kc, Prabha

    2011-01-01

    Intermittent hypoxic episodes are typically a consequence of immature respiratory control and remain a troublesome challenge for the neonatologist. Furthermore, their frequency and magnitude are underestimated by clinically employed pulse oximeter settings. In extremely low birth weight infants the incidence of intermittent hypoxia progressively increases over the first 4 weeks of postnatal life, with a subsequent plateau followed by a slow decline beginning at weeks 6-8. Such episodic hypoxia/reoxygenation has the potential to sustain a proinflammatory cascade with resultant multisystem morbidity. This morbidity includes retinopathy of prematurity and impaired growth, as well as possible longer-term cardiorespiratory instability and poor neurodevelopmental outcome. Therapeutic approaches for intermittent hypoxic episodes comprise determination of optimal baseline saturation and careful titration of supplemental inspired oxygen, as well as xanthine therapy to prevent apnea of prematurity. In conclusion, characterization of the pathophysiologic basis for such intermittent hypoxic episodes and their consequences during early life is necessary to provide an evidence-based approach to their management. Copyright © 2011 S. Karger AG, Basel.

  8. Physiologic basis for intermittent hypoxic episodes in preterm infants.

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    Martin, R J; Di Fiore, J M; Macfarlane, P M; Wilson, C G

    2012-01-01

    Intermittent hypoxic episodes are typically a consequence of immature respiratory control and remain a troublesome challenge for the neonatologist. Furthermore, their frequency and magnitude are commonly underestimated by clinically employed pulse oximeter settings. In extremely low birth weight infants the incidence of intermittent hypoxia [IH] progressively increases over the first 4 weeks of postnatal life, with a subsequent plateau followed by a slow decline beginning at weeks six to eight. Over this period of unstable respiratory control, increased oxygen-sensitive peripheral chemoreceptor activity has been associated with a higher incidence of apnea of prematurity. In contrast, infants with bronchopulmonary dysplasia [chronic neonatal lung disease] exhibit decreased peripheral chemosensitivity, although the effect on respiratory stability in this population is unclear. Such episodic hypoxia/reoxygenation in early life has the potential to sustain a proinflammatory cascade with resultant multisystem, including respiratory, morbidity. Therapeutic approaches for intermittent hypoxic episodes comprise careful titration of baseline or supplemental inspired oxygen as well as xanthine therapy to prevent apnea of prematurity. Characterization of the pathophysiologic basis for such intermittent hypoxic episodes and their consequences during early life is necessary to provide an evidence-based approach to their management.

  9. Chronic intermittent hyperoxia alters the development of the hypoxic ventilatory response in neonatal rats.

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    Logan, Sarah; Tobin, Kristina E; Fallon, Sarah C; Deng, Kevin S; McDonough, Amy B; Bavis, Ryan W

    2016-01-01

    Chronic exposure to sustained hyperoxia alters the development of the respiratory control system, but the respiratory effects of chronic intermittent hyperoxia have rarely been investigated. We exposed newborn rats to short, repeated bouts of 30% O2 or 60% O2 (5 bouts h(-1)) for 4-15 days and then assessed their hypoxic ventilatory response (HVR; 10 min at 12% O2) by plethysmography. The HVR tended to be enhanced by intermittent hyperoxia at P4 (early phase of the HVR), but it was significantly reduced at P14-15 (primarily late phase of the HVR) compared to age-matched controls; the HVR recovered when individuals were returned to room air and re-studied as adults. To investigate the role of carotid body function in this plasticity, single-unit carotid chemoafferent activity was recorded in vitro. Intermittent hyperoxia tended to decrease spontaneous action potential frequency under normoxic conditions but, contrary to expectations, hypoxic responses were only reduced at P4 (not at P14) and only in rats exposed to higher O2 levels (i.e., intermittent 60% O2). Rats exposed to intermittent hyperoxia had smaller carotid bodies, and this morphological change may contribute to the blunted HVR. In contrast to rats exposed to intermittent hyperoxia beginning at birth, two weeks of intermittent 60% O2 had no effect on the HVR or carotid body size of rats exposed beginning at P28; therefore, intermittent hyperoxia-induced respiratory plasticity appears to be unique to development. Although both intermittent and sustained hyperoxia alter carotid body development and the HVR of rats, the specific effects and time course of this plasticity differs. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Advancing hypoxic training in team sports: from intermittent hypoxic training to repeated sprint training in hypoxia.

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    Faiss, Raphaël; Girard, Olivier; Millet, Grégoire P

    2013-12-01

    Over the past two decades, intermittent hypoxic training (IHT), that is, a method where athletes live at or near sea level but train under hypoxic conditions, has gained unprecedented popularity. By adding the stress of hypoxia during 'aerobic' or 'anaerobic' interval training, it is believed that IHT would potentiate greater performance improvements compared to similar training at sea level. A thorough analysis of studies including IHT, however, leads to strikingly poor benefits for sea-level performance improvement, compared to the same training method performed in normoxia. Despite the positive molecular adaptations observed after various IHT modalities, the characteristics of optimal training stimulus in hypoxia are still unclear and their functional translation in terms of whole-body performance enhancement is minimal. To overcome some of the inherent limitations of IHT (lower training stimulus due to hypoxia), recent studies have successfully investigated a new training method based on the repetition of short (<30 s) 'all-out' sprints with incomplete recoveries in hypoxia, the so-called repeated sprint training in hypoxia (RSH). The aims of the present review are therefore threefold: first, to summarise the main mechanisms for interval training and repeated sprint training in normoxia. Second, to critically analyse the results of the studies involving high-intensity exercises performed in hypoxia for sea-level performance enhancement by differentiating IHT and RSH. Third, to discuss the potential mechanisms underpinning the effectiveness of those methods, and their inherent limitations, along with the new research avenues surrounding this topic.

  11. Sodium bicarbonate supplementation improves severe-intensity intermittent exercise under moderate acute hypoxic conditions.

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    Deb, Sanjoy K; Gough, Lewis A; Sparks, S Andy; McNaughton, Lars R

    2018-03-01

    Acute moderate hypoxic exposure can substantially impair exercise performance, which occurs with a concurrent exacerbated rise in hydrogen cation (H + ) production. The purpose of this study was therefore, to alleviate this acidic stress through sodium bicarbonate (NaHCO 3 ) supplementation and determine the corresponding effects on severe-intensity intermittent exercise performance. Eleven recreationally active individuals participated in this randomised, double-blind, crossover study performed under acute normobaric hypoxic conditions (FiO 2 % = 14.5%). Pre-experimental trials involved the determination of time to attain peak bicarbonate anion concentrations ([HCO 3 - ]) following NaHCO 3 ingestion. The intermittent exercise tests involved repeated 60-s work in their severe-intensity domain and 30-s recovery at 20 W to exhaustion. Participants ingested either 0.3 g kg bm -1 of NaHCO 3 or a matched placebo of 0.21 g kg bm -1 of sodium chloride prior to exercise. Exercise tolerance (+ 110.9 ± 100.6 s; 95% CI 43.3-178 s; g = 1.0) and work performed in the severe-intensity domain (+ 5.8 ± 6.6 kJ; 95% CI 1.3-9.9 kJ; g = 0.8) were enhanced with NaHCO 3 supplementation. Furthermore, a larger post-exercise blood lactate concentration was reported in the experimental group (+ 4 ± 2.4 mmol l -1 ; 95% CI 2.2-5.9; g = 1.8), while blood [HCO 3 - ] and pH remained elevated in the NaHCO 3 condition throughout experimentation. In conclusion, this study reported a positive effect of NaHCO 3 under acute moderate hypoxic conditions during intermittent exercise and therefore, may offer an ergogenic strategy to mitigate hypoxic induced declines in exercise performance.

  12. Intermittent Hypoxia Impairs Glucose Homeostasis in C57BL6/J Mice: Partial Improvement with Cessation of the Exposure

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    Polak, Jan; Shimoda, Larissa A.; Drager, Luciano F.; Undem, Clark; McHugh, Holly; Polotsky, Vsevolod Y.; Punjabi, Naresh M.

    2013-01-01

    Objectives: Obstructive sleep apnea is associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Although several studies have suggested that intermittent hypoxia in obstructive sleep apnea may induce abnormalities in glucose homeostasis, it remains to be determined whether these abnormalities improve after discontinuation of the exposure. The objective of this study was to delineate the effects of intermittent hypoxia on glucose homeostasis, beta cell function, and liver glucose metabolism and to investigate whether the impairments improve after the hypoxic exposure is discontinued. Interventions: C57BL6/J mice were exposed to 14 days of intermittent hypoxia, 14 days of intermittent air, or 7 days of intermittent hypoxia followed by 7 days of intermittent air (recovery paradigm). Glucose and insulin tolerance tests were performed to estimate whole-body insulin sensitivity and calculate measures of beta cell function. Oxidative stress in pancreatic tissue and glucose output from isolated hepatocytes were also assessed. Results: Intermittent hypoxia increased fasting glucose levels and worsened glucose tolerance by 67% and 27%, respectively. Furthermore, intermittent hypoxia exposure was associated with impairments in insulin sensitivity and beta cell function, an increase in liver glycogen, higher hepatocyte glucose output, and an increase in oxidative stress in the pancreas. While fasting glucose levels and hepatic glucose output normalized after discontinuation of the hypoxic exposure, glucose intolerance, insulin resistance, and impairments in beta cell function persisted. Conclusions: Intermittent hypoxia induces insulin resistance, impairs beta cell function, enhances hepatocyte glucose output, and increases oxidative stress in the pancreas. Cessation of the hypoxic exposure does not fully reverse the observed changes in glucose metabolism. Citation: Polak J; Shimoda LA; Drager LF; Undem C; McHugh H; Polotsky VY; Punjabi NM

  13. Intermittent hypoxia impairs glucose homeostasis in C57BL6/J mice: partial improvement with cessation of the exposure.

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    Polak, Jan; Shimoda, Larissa A; Drager, Luciano F; Undem, Clark; McHugh, Holly; Polotsky, Vsevolod Y; Punjabi, Naresh M

    2013-10-01

    Obstructive sleep apnea is associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Although several studies have suggested that intermittent hypoxia in obstructive sleep apnea may induce abnormalities in glucose homeostasis, it remains to be determined whether these abnormalities improve after discontinuation of the exposure. The objective of this study was to delineate the effects of intermittent hypoxia on glucose homeostasis, beta cell function, and liver glucose metabolism and to investigate whether the impairments improve after the hypoxic exposure is discontinued. C57BL6/J mice were exposed to 14 days of intermittent hypoxia, 14 days of intermittent air, or 7 days of intermittent hypoxia followed by 7 days of intermittent air (recovery paradigm). Glucose and insulin tolerance tests were performed to estimate whole-body insulin sensitivity and calculate measures of beta cell function. Oxidative stress in pancreatic tissue and glucose output from isolated hepatocytes were also assessed. Intermittent hypoxia increased fasting glucose levels and worsened glucose tolerance by 67% and 27%, respectively. Furthermore, intermittent hypoxia exposure was associated with impairments in insulin sensitivity and beta cell function, an increase in liver glycogen, higher hepatocyte glucose output, and an increase in oxidative stress in the pancreas. While fasting glucose levels and hepatic glucose output normalized after discontinuation of the hypoxic exposure, glucose intolerance, insulin resistance, and impairments in beta cell function persisted. Intermittent hypoxia induces insulin resistance, impairs beta cell function, enhances hepatocyte glucose output, and increases oxidative stress in the pancreas. Cessation of the hypoxic exposure does not fully reverse the observed changes in glucose metabolism.

  14. Relationship between human respiratory reactivity and neutrophil metabolism under intermittent hypoxic influences in humans exposed to low-level radiation

    International Nuclear Information System (INIS)

    Serebrovskaya, T.V.; Oberenko, O.A.; Guseva, S.A.

    1996-01-01

    The group of 18 men exposed to radiation during amelioration work in the Chernobyl NPP was examined in the course of adaptation to intermittent hypoxia (rebreathing technique during 10 days of three dayly 5-7 min sessions with 15 min break). The starting level of ventilatory response to hypoxic stimulus (HVR) did not differ from the one in persons living in non-contaminated areas. This hypoxic training (HT) caused the increase of HVR, activity of NADPH-oxidase and cationic protein content in neutrophyls as well as various changes in mieloperoxidase activity. The correlation between respiration reactivity and deviations in neutrophil metabolism under HT was found. 14 refs., 2 figs

  15. Physiological Adaptations to Hypoxic vs. Normoxic Training during Intermittent Living High

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    Stefan De Smet

    2017-05-01

    Full Text Available In the setting of “living high,” it is unclear whether high-intensity interval training (HIIT should be performed “low” or “high” to stimulate muscular and performance adaptations. Therefore, 10 physically active males participated in a 5-week “live high-train low or high” program (TR, whilst eight subjects were not engaged in any altitude or training intervention (CON. Five days per week (~15.5 h per day, TR was exposed to normobaric hypoxia simulating progressively increasing altitude of ~2,000–3,250 m. Three times per week, TR performed HIIT, administered as unilateral knee-extension training, with one leg in normobaric hypoxia (~4,300 m; TRHYP and with the other leg in normoxia (TRNOR. “Living high” elicited a consistent elevation in serum erythropoietin concentrations which adequately predicted the increase in hemoglobin mass (r = 0.78, P < 0.05; TR: +2.6%, P < 0.05; CON: −0.7%, P > 0.05. Muscle oxygenation during training was lower in TRHYP vs. TRNOR (P < 0.05. Muscle homogenate buffering capacity and pH-regulating protein abundance were similar between pretest and posttest. Oscillations in muscle blood volume during repeated sprints, as estimated by oscillations in NIRS-derived tHb, increased from pretest to posttest in TRHYP (~80%, P < 0.01 but not in TRNOR (~50%, P = 0.08. Muscle capillarity (~15% as well as repeated-sprint ability (~8% and 3-min maximal performance (~10–15% increased similarly in both legs (P < 0.05. Maximal isometric strength increased in TRHYP (~8%, P < 0.05 but not in TRNOR (~4%, P > 0.05. In conclusion, muscular and performance adaptations were largely similar following normoxic vs. hypoxic HIIT. However, hypoxic HIIT stimulated adaptations in isometric strength and muscle perfusion during intermittent sprinting.

  16. A case of remission from pre-diabetes following intermittent hypoxic training.

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    Fuller, Nicholas R; Courtney, Rosalba

    2016-01-01

    A female patient (49 years of age) with obesity (body mass index: 35.3kg/m(2)) and diagnosed with pre-diabetes presented to the clinic of one of the authors (RC) with recent weight gain (approximately 10kg) over the preceding 12 months, despite several unsuccessful attempts at weight loss. She reported being short of breath performing light activities and feeling fatigued the majority of the time. Treatment consisted of a run in period of five weeks following the Commonwealth Scientific and Industrial Research Organisation (CSIRO) diet, followed by four weeks of the CSIRO diet plus intermittent hypoxic training (IHT) using the GO2(®) altitude training device. Anthropometric measures, bloods and questionnaires were completed before treatment (week 0), end of diet phase (week 5), and end of diet plus IHT phase (week 9). At the end of week five, the patient had lost some weight and had an improvement in glycaemic control. However, there was a clinically greater improvement in weight loss and glycaemic control from week five to nine following the IHT, resulting in remission from pre-diabetes. This case study shows that incorporation of IHT has benefits existing beyond a standard dietary approach, helping to achieve remission from pre-diabetes back to a normal fasting glucose state. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  17. Impaired hypoxic ventilatory response following neonatal sustained and subsequent chronic intermittent hypoxia in rats.

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    Mayer, C A; Ao, J; Di Fiore, J M; Martin, R J; MacFarlane, P M

    2013-06-15

    Neonatal chronic intermittent hypoxia (CIH) enhances the ventilatory sensitivity to acute hypoxia (acute hypoxic ventilatory response, HVR), whereas sustained hypoxia (SH) can have the opposite effect. Therefore, we investigated whether neonatal rats pre-treated with SH prior to CIH exhibit a modified HVR. Rat pups were exposed to CIH (5% O2/5min, 8h/day) between 6 and 15 days of postnatal age (P6-15) after pre-treatment with either normoxia or SH (11% O2; P1-5). Using whole-body plethysmography, the acute (5min, 10% O2) HVR at P16 (1 day post-CIH) was unchanged following CIH (67.9±6.7% above baseline) and also SH (58.8±10.5%) compared to age-matched normoxic rats (54.7±6.3%). In contrast, the HVR was attenuated (16.5±6.0%) in CIH exposed rats pre-treated with SH. These data suggest that while neonatal SH and CIH alone have little effect on the magnitude of the acute HVR, their combined effects impose a synergistic disturbance to postnatal development of the HVR. These data could provide important insight into the consequences of not maintaining adequate levels of oxygen saturation during the early neonatal period, especially in vulnerable preterm infants susceptible to frequent bouts of hypoxemic events (CIH) that are commonly associated with apnea of prematurity. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. β2-Adrenergic receptor-dependent attenuation of hypoxic pulmonary vasoconstriction prevents progression of pulmonary arterial hypertension in intermittent hypoxic rats.

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    Hisashi Nagai

    Full Text Available In sleep apnea syndrome (SAS, intermittent hypoxia (IH induces repeated episodes of hypoxic pulmonary vasoconstriction (HPV during sleep, which presumably contribute to pulmonary arterial hypertension (PAH. However, the prevalence of PAH was low and severity is mostly mild in SAS patients, and mild or no right ventricular hypertrophy (RVH was reported in IH-exposed animals. The question then arises as to why PAH is not a universal finding in SAS if repeated hypoxia of sufficient duration causes cycling HPV. In the present study, rats underwent IH at a rate of 3 min cycles of 4-21% O2 for 8 h/d for 6 w. Assessment of diameter changes in small pulmonary arteries in response to acute hypoxia and drugs were performed using synchrotron radiation microangiography on anesthetized rats. In IH-rats, neither PAH nor RVH was observed and HPV was strongly reversed. Nadolol (a hydrophilic β(1, 2-blocker augmented the attenuated HPV to almost the same level as that in N-rats, but atenolol (a hydrophilic β1-blocker had no effect on the HPV in IH. These β-blockers had almost no effect on the HPV in N-rats. Chronic administration of nadolol during 6 weeks of IH exposure induced PAH and RVH in IH-rats, but did not in N-rats. Meanwhile, atenolol had no effect on morphometric and hemodynamic changes in N and IH-rats. Protein expression of the β1-adrenergic receptor (AR was down-regulated while that of β2AR was preserved in pulmonary arteries of IH-rats. Phosphorylation of p85 (chief component of phosphoinositide 3-kinase (PI3K, protein kinase B (Akt, and endothelial nitric oxide synthase (eNOS were abrogated by chronic administration of nadolol in the lung tissue of IH-rats. We conclude that IH-derived activation of β2AR in the pulmonary arteries attenuates the HPV, thereby preventing progression of IH-induced PAH. This protective effect may depend on the β2AR-Gi mediated PI3K/Akt/eNOS signaling pathway.

  19. Intermittent hypoxic training improves anaerobic performance in competitive swimmers when implemented into a direct competition mesocycle.

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    Miłosz Czuba

    Full Text Available The main objective of this research was to evaluate the efficacy of intermittent hypoxic training (IHT on anaerobic and aerobic capacity and swimming performance in well-trained swimmers. Sixteen male swimmers were randomly divided into a hypoxia (H group (n = 8, which trained in a normobaric hypoxia environment, and a control (C group (n = 8, which exercised under normoxic conditions. However, one participant left the study without explanation. During the experiment group H trained on land twice per week in simulated hypoxia (FiO2 = 15.5%, corresponding to 2,500 m a.s.l; however, they conducted swim training in normoxic conditions. Group C performed the same training program under normoxic conditions. The training program included four weekly microcyles, followed by three days of recovery. During practice sessions on land, the swimmers performed 30 second sprints on an arm-ergometer, alternating with two minute high intensity intervals on a lower limb cycle ergometer. The results showed that the training on land caused a significant (p<0.05 increase in absolute maximal workload (WRmax by 7.4% in group H and by 3.2% in group C and relative values of VO2max by 6.9% in group H and 3.7% in group C. However, absolute values of VO2max were not significantly changed. Additionally, a significant (p<0.05 increase in mean power (Pmean during the first (11.7% and second (11.9% Wingate tests was only observed in group H. The delta values of lactate concentration (ΔLA after both Wingate tests were significantly (p<0.05 higher in comparison to baseline levels by 28.8% in group H. Opposite changes were observed in delta values of blood pH (ΔpH after both Wingate tests in group H, with a significant decrease in values of ΔpH by 33.3%. The IHT caused a significant (p<0.05 improvement in 100m and 200m swimming performance, by 2.1% and 1.8%, respectively in group H. Training in normoxia (group C, resulted in a significant (p<0.05 improvement of swimming

  20. INTERMITTENT HYPOBARIC HYPOXIC STIMULATION IN TREATMENT OF CHILDREN WITH BRONCHIAL ASTHMA AT THE PERIOD OF REHABILITATION

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    G.D. Alemanova

    2009-01-01

    Full Text Available Bronchial asthma is one of the widespread chronic diseases of lungs. Immune mechanisms of disorder are one of the causes which lead to pathologic changes in lungs. The aim: to determine the clinical and immunologic effectiveness of pressure adaptation to the periodical hypobaric hypoxic stimulation of treatment of children with bronchial asthma of prepubertal and pubertal periods. In the present work there were observed the clinical and immunologic parameters of 129 children with the verified atopic bronchial asthma of different degree at the remission period before and after the course of pressure adaptation to the periodical hypobaric hypoxic stimulation in conditions of the medical hypobaric pressure chamber with many seats «Ural'1». Clinic effectiveness of hypobaric hypoxic stimulation revealed in continuation of remissions and diminishing of total numerical score of asthma degree. The positive dynamic indexes of cytokine profile was observed. It revealed in reduction of IL 1_, IL 4, IL 5, IL 18 levels and stimulated production of IFN - in blood serum. The course of hypobaric hypoxic stimulation has the positive impact on the named indexes of the patients with bronchial asthma and its intensity depends on the degree of disease and of the age of the child' patient. Thus the use of pressure adaptation to the periodical hypobaric hypoxic stimulation in treatment of children's with bronchial asthma led to the immunologic positive dynamics, especially of the children of prepubertal period. Determination of the immunologic indexes and the level of the cytokines can be used as the additional tests for the evaluation of the effectiveness of pressure adaptation to the periodical hypobaric hypoxic stimulation of children.Key words: bronchial asthma, periodical hypobaric hypoxic stimulation, cytokines, children.

  1. Intermittent cold exposure enhances fat accumulation in mice.

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    Hyung Sun Yoo

    Full Text Available Due to its high energy consuming characteristics, brown adipose tissue (BAT has been suggested as a key player in energy metabolism. Cold exposure is a physiological activator of BAT. Intermittent cold exposure (ICE, unlike persistent exposure, is clinically feasible. The main objective of this study was to investigate whether ICE reduces adiposity in C57BL/6 mice. Surprisingly, we found that ICE actually increased adiposity despite enhancing Ucp1 expression in BAT and inducing beige adipocytes in subcutaneous white adipose tissue. ICE did not alter basal systemic insulin sensitivity, but it increased liver triglyceride content and secretion rate as well as blood triglyceride levels. Gene profiling further demonstrated that ICE, despite suppressing lipogenic gene expression in white adipose tissue and liver during cold exposure, enhanced lipogenesis between the exposure periods. Together, our results indicate that despite enhancing BAT recruitment, ICE in mice increases fat accumulation by stimulating de novo lipogenesis.

  2. Noradrenergic Activation of Hypoglossal Nucleus Modulates the Central Regulation of Genioglossus in Chronic Intermittent Hypoxic Rats

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    Wei Wang

    2017-05-01

    Full Text Available Neuromuscular compensation of the genioglossus muscle can be induced by chronic intermittent hypoxia (CIH in obstructive sleep apnea to maintain upper airway stability. Noradrenergic activation of hypoglossal nucleus plays a critical role in the central control of the genioglossus. However, it remains unknown whether norepinephrine takes part in the central regulation of the genioglossus during CIH. Adult male Wistar rats (n = 32 were studied to explore the influence of noradrenergic activation of hypoglossal nucleus on the central control of the genioglossus at different stages of CIH. The rats were divided into four groups: normal control or normoxic (NO group, CIH group, CIH + normal saline (NS group, and CIH + prazosin (PZ, α1-adrenergic antagonist group. PZ (0.2 mM, 60 nl and NS (0.9%, 60 nl were microinjected into the hypoglossal nucleus. The responses of the genioglossus corticomotor area to transcranial magnetic stimulation (TMS were recorded on the 1st, 7th, 14th, and 21st day of CIH. The CIH group showed significantly shorter TMS latencies on days 1, 7, and 14 (3.85 ± 0.37 vs. 4.58 ± 0.42, 3.93 ± 0.17 vs. 4.49 ± 0.55, 3.79 ± 0.38 vs. 4.39 ± 0.30 ms, P < 0.05, and higher TMS amplitudes on day 1 (2.74 ± 0.87 vs. 1.60 ± 0.52 mV, P < 0.05 of CIH than the NO group. Compared to the CIH + NS group, the CIH + PZ group showed decreased TMS responses (longer latencies and lower amplitudes only on the 14th day of CIH (3.99 ± 0.28 vs. 4.61 ± 0.48 ms, 2.51 ± 0.67 vs. 1.18 ± 0.62 mV, P < 0.05. These results indicated that noradrenergic activation of the hypoglossal nucleus played a role in the central compensation of genioglossus through α1-adrenoceptor on the 14th day of CIH.

  3. Introduction to altitude/hypoxic training symposium.

    Science.gov (United States)

    Wilber, Randall L

    2007-09-01

    Altitude/hypoxic training has traditionally been an intriguing and controversial area of research and sport performance. This controversial aspect was evident recently in the form of scholarly debates in highly regarded professional journals, as well as the World Anti-Doping Agency's (WADA) consideration of placing "artificially-induced hypoxic conditions" on the 2007 Prohibited List of Substances/Methods. In light of the ongoing controversy surrounding altitude/hypoxic training, this symposium was organized with the following objectives in mind: 1) to examine the primary physiological responses and underlying mechanisms associated with altitude/hypoxic training, including the influence of genetic predisposition; 2) to present evidence supporting the effect of altitude/hypoxic acclimatization on both hematological and nonhematological markers, including erythrocyte volume, skeletal muscle-buffering capacity, hypoxic ventilatory response, and physiological efficiency/economy; 3) to evaluate the efficacy of several contemporary simulated altitude modalities and training strategies, including hypoxic tents, nitrogen apartments, and intermittent hypoxic exposure (IHE) or training, and to address the legal and ethical issues associated with the use of simulated altitude; and 4) to describe different altitude/hypoxic training strategies used by elite-level athletes, including Olympians and military special forces. In addressing these objectives, papers will be presented on the topics of: 1) effect of hypoxic "dose" on physiological responses and sea-level performance (Drs. Benjamin Levine and James Stray-Gundersen), 2) nonhematological mechanisms of improved performance after hypoxic exposure (Dr. Christopher Gore), 3) application of altitude/hypoxic training by elite athletes (Dr. Randall Wilber), and 4) military applications of hypoxic training (Dr. Stephen Muza).

  4. Radiobiologic effect of intermittent radiation exposure in murine tumors

    International Nuclear Information System (INIS)

    Sugie, Chikao; Shibamoto, Yuta; Ito, Masato; Ogino, Hiroyuki; Miyamoto, Akihiko; Fukaya, Nobuyuki; Niimi, Hiroshige; Hashizume, Takuya

    2006-01-01

    Purpose: In stereotactic irradiation using a linear accelerator, the effect of radiation may be reduced during intermittent exposures owing to recovery from sublethal damage in tumor cells. After our previous in vitro study suggesting this phenomenon, we investigated the issue in murine tumors. Methods and Materials: We used EMT6 and SCCVII tumors approximately 1 cm in diameter growing in the hind legs of syngeneic mice. Three schedules of intermittent radiation were investigated. First, 2 fractions of 10 Gy were given at an interval of 15-360 min to investigate the pattern of recovery from sublethal damage. Second, 5 fractions of 4 Gy were given with interfraction intervals of 2.5-15 min each. Third, 10 fractions of 2 Gy were given with interfraction intervals of 1-7 min each. Doses of 15-20 Gy were also given without interruption to estimate the dose-modifying factors. Tumors were excised 20 h later, and tumor cell survival was determined by an in vivo-in vitro assay. Results: In the 2-fraction experiment, the increase in cell survival with elongation of the interval was much less than that observed in our previous in vitro study. In the 5- and 10-fraction experiments, no significant increase in cell survival was observed after the intermittent exposures. Moreover, cell survival decreased at most points of the 5-fraction experiments by interruption of radiation in both EMT6 and SCCVII tumors. In the 10-fraction experiment, cell survival also decreased when the interruption was 3 or 7 min in EMT6 tumors. Conclusion: The results of the present in vivo studies were different from those of our in vitro studies in which cell survival increased significantly when a few minutes or longer intervals were posed between fractions. This suggests that recovery from sublethal damage in vivo may be counterbalanced by other phenomena such as reoxygenation that sensitizes tumor cells to subsequent irradiation

  5. Early Life Exposure to Chronic Intermittent Hypoxia Primes Increased Susceptibility to Hypoxia-Induced Weakness in Rat Sternohyoid Muscle During Adulthood

    Directory of Open Access Journals (Sweden)

    Fiona B Mcdonald

    2016-03-01

    Full Text Available Intermittent hypoxia is a feature of apnea of prematurity, chronic lung disease and sleep apnea. Despite the clinical relevance, the long-term effects of hypoxic exposure in early life on respiratory control are not well defined. We recently reported that exposure to chronic intermittent hypoxia (CIH during postnatal development (pCIH causes upper airway muscle weakness in both sexes, which persists for several weeks. We sought to examine if there are persistent sex-dependent effects of pCIH on respiratory muscle function into adulthood and/or increased susceptibility to re-exposure to CIH in adulthood in animals previously exposed to CIH during postnatal development. We hypothesized that pCIH would cause long-lasting muscle impairment and increased susceptibility to subsequent hypoxia. Within 24 hours of delivery, pups and their respective dams were exposed to CIH: 90s of hypoxia reaching 5% O2 at nadir; once every 5 min, 8 hrs per day for 3 weeks. Sham groups were exposed to normoxia in parallel. Three groups were studied: sham; pCIH; and pCIH combined with adult CIH (p+aCIH, where a subset of the pCIH-exposed pups were re-exposed to the same CIH paradigm beginning at 13 weeks. Following gas exposures, sternohyoid and diaphragm muscle isometric contractile and endurance properties were examined ex vivo. There was no apparent lasting effect of pCIH on respiratory muscle function in adults. However, in both males and females, re-exposure to CIH in adulthood in pCIH-exposed animals caused sternohyoid (but not diaphragm weakness. Exposure to this paradigm of CIH in adulthood alone had no effect on muscle function. Persistent susceptibility in pCIH-exposed airway dilator muscle to subsequent hypoxic insult may have implications for the control of airway patency in adult humans exposed to intermittent hypoxic stress during early life.

  6. Early life exposure to chronic intermittent Hypoxia Primes Increased Susceptibility to Hypoxia-Induced Weakness in Rat Sternohyoid Muscle during adulthood.

    LENUS (Irish Health Repository)

    McDonald, Fiona B

    2016-03-01

    Intermittent hypoxia is a feature of apnea of prematurity (AOP), chronic lung disease, and sleep apnea. Despite the clinical relevance, the long-term effects of hypoxic exposure in early life on respiratory control are not well defined. We recently reported that exposure to chronic intermittent hypoxia (CIH) during postnatal development (pCIH) causes upper airway muscle weakness in both sexes, which persists for several weeks. We sought to examine if there are persistent sex-dependent effects of pCIH on respiratory muscle function into adulthood and\\/or increased susceptibility to re-exposure to CIH in adulthood in animals previously exposed to CIH during postnatal development. We hypothesized that pCIH would cause long-lasting muscle impairment and increased susceptibility to subsequent hypoxia. Within 24 h of delivery, pups and their respective dams were exposed to CIH: 90 s of hypoxia reaching 5% O2 at nadir; once every 5 min, 8 h per day for 3 weeks. Sham groups were exposed to normoxia in parallel. Three groups were studied: sham; pCIH; and pCIH combined with adult CIH (p+aCIH), where a subset of the pCIH-exposed pups were re-exposed to the same CIH paradigm beginning at 13 weeks. Following gas exposures, sternohyoid and diaphragm muscle isometric contractile and endurance properties were examined ex vivo. There was no apparent lasting effect of pCIH on respiratory muscle function in adults. However, in both males and females, re-exposure to CIH in adulthood in pCIH-exposed animals caused sternohyoid (but not diaphragm) weakness. Exposure to this paradigm of CIH in adulthood alone had no effect on muscle function. Persistent susceptibility in pCIH-exposed airway dilator muscle to subsequent hypoxic insult may have implications for the control of airway patency in adult humans exposed to intermittent hypoxic stress during early life.

  7. The impact of intermittent exercise in a hypoxic environment on redox status and cardiac troponin release in the serum of well-trained marathon runners.

    Science.gov (United States)

    Li, Feifei; Nie, Jinlei; Lu, Yifan; Tong, Tom Kwok Keung; Yi, Longyan; Yan, Huiping; Fu, Frank Hoo Kin; Ma, Shengxia

    2016-10-01

    To investigate the effects of hypoxic training on redox status and cardiac troponin (cTn) release after intermittent exercise. Nine well-trained male marathon runners (age, 21.7 ± 2.3 year; body mass, 64.7 ± 4.8 kg; height, 177.9 ± 3.8 cm; and VO2max, 64.3 ± 6.7 ml kg(-1) min(-1)) completed intermittent exercise under normoxic [trial N; fraction of inspiration oxygen (FIO2), 21.0 %] and hypoxic (trial H; FIO2, 14.4 %) conditions in random order. Each bout of intermittent exercise included hard run (16.2 ± 0.8 km h(-1)) at 90 % VO2max for 2 min followed by easy run (9.0 ± 0.4 km h(-1)) at 50 % VO2max for 2 min and 23 bouts in 92 min totally. Malondialdehyde, reduced glutathione (GSH), superoxide dismutase, an estimate of total antioxidant capacity (T-AOC), high-sensitivity cardiac troponin T (hs-cTnT), and cardiac troponin I (cTnI) were measured before, immediately after (0 h), and 2, 4, and 24 h after the completion of trials N and H. GSH was increased immediately after trial N. T-AOC was lower 4 h after trial H than trial N. Hs-cTnT was elevated from 0 to 4 h and returned to baseline 24 h after both trials. CTnI was increased after trial H; peaked at 2-4 h and returned to below the detection by 24 h. The overall redox status was balanced under normoxic conditions, and exercise-induced cTn release did not deviate. However, the protective effects of antioxidant were weaker in the hypoxic state than normoxic, and the stress on the myocardium induced by intermittent exercise was transiently aggravated.

  8. Effect of Intermittent Hypercapnia on Respiratory Control in Rat Pups

    Science.gov (United States)

    Steggerda, Justin A.; Mayer, Catherine A.; Martin, Richard J.; Wilson, Christopher G.

    2010-01-01

    Preterm infants are subject to fluctuations in blood gas status associated with immature respiratory control. Intermittent hypoxia during early postnatal life has been shown to increase chemoreceptor sensitivity and destabilize the breathing pattern; however, intermittent hypercapnia remains poorly studied. Therefore, to test the hypothesis that intermittent hypercapnia results in altered respiratory control, we examined the effects of daily exposure to intermittent hypercapnia on the ventilatory response to subsequent hypercapnic and hypoxic exposure in neonatal rat pups. Exposure cycles consisted of 5 min of intermittent hypercapnia (5% CO2, 21% O2, balance N2) followed by 10 min of normoxia. Rat pups were exposed to 18 exposure cycles each day for 1 week, from postnatal day 7 to 14. We analyzed diaphragm electromyograms (EMGs) from pups exposed to subsequent acute hypercapnic (5% CO2) and hypoxic (12% O2) challenges. In response to a subsequent hypercapnia challenge, there was no significant difference in the ventilatory response between control and intermittent hypercapnia-exposed groups. In contrast, intermittent hypercapnia-exposed rat pups showed an enhanced ventilatory response to hypoxic challenge with an increase in minute EMG to 118 ± 14% of baseline versus 107 ± 13% for control pups (p < 0.05). We speculate that prior hypercapnic exposure may increase peripheral chemoreceptor response to subsequent hypoxic exposures and result in perturbed neonatal respiratory control. PMID:19752577

  9. Impact of repeated daily exposure to intermittent hypoxia and mild sustained hypercapnia on apnea severity.

    Science.gov (United States)

    Yokhana, Sanar S; Gerst, David G; Lee, Dorothy S; Badr, M Safwan; Qureshi, Tabarak; Mateika, Jason H

    2012-02-01

    We examined whether exposure to intermittent hypoxia (IH) during wakefulness impacted on the apnea/hypopnea index (AHI) during sleep in individuals with sleep apnea. Participants were exposed to twelve 4-min episodes of hypoxia in the presence of sustained mild hypercapnia each day for 10 days. A control group was exposed to sustained mild hypercapnia for a similar duration. The intermittent hypoxia protocol was completed in the evening on day 1 and 10 and was followed by a sleep study. During all sleep studies, the change in esophageal pressure (ΔPes) from the beginning to the end of an apnea and the tidal volume immediately following apneic events were used to measure respiratory drive. Following exposure to IH on day 1 and 10, the AHI increased above baseline measures (day 1: 1.95 ± 0.42 fraction of baseline, P ≤ 0.01, vs. day 10: 1.53 ± 0.24 fraction of baseline, P < 0.06). The indexes were correlated to the hypoxic ventilatory response (HVR) measured during the IH protocol but were not correlated to the magnitude of ventilatory long-term facilitation (vLTF). Likewise, ΔPes and tidal volume measures were greater on day 1 and 10 compared with baseline (ΔPes: -8.37 ± 0.84 vs. -5.90 ± 1.30 cmH(2)0, P ≤ 0.04; tidal volume: 1,193.36 ± 101.85 vs. 1,015.14 ± 119.83 ml, P ≤ 0.01). This was not the case in the control group. Interestingly, the AHI on day 10 (0.78 ± 0.13 fraction of baseline, P ≤ 0.01) was significantly less than measures obtained during baseline and day 1 in the mild hypercapnia control group. We conclude that enhancement of the HVR initiated by exposure to IH may lead to increases in the AHI during sleep and that initiation of vLTF did not appear to impact on breathing stability. Lastly, our results suggest that repeated daily exposure to mild sustained hypercapnia may lead to a decrease in breathing events.

  10. Living and Training at 825 m for 8 Weeks Supplemented With Intermittent Hypoxic Training at 3,000 m Improves Blood Parameters and Running Performance.

    Science.gov (United States)

    Wonnabussapawich, Preetiwat; Hamlin, Michael J; Lizamore, Catherine A; Manimmanakorn, Nuttaset; Leelayuwat, Naruemon; Tunkamnerdthai, Orathai; Thuwakum, Worrawut; Manimmanakorn, Apiwan

    2017-12-01

    Wonnabussapawich, P, Hamlin, MJ, Lizamore, CA, Manimmanakorn, N, Leelayuwat, N, Tunkamnerdthai, O, Thuwakum, W, and Manimmanakorn, A. Living and training at 825 m for 8 weeks supplemented with intermittent hypoxic training at 3,000 m improves blood parameters and running performance. J Strength Cond Res 31(12): 3287-3294, 2017-We aimed to investigate the effect of an 8-week low-altitude training block supplemented with intermittent hypoxic training, on blood and performance parameters in soccer players. Forty university-level male soccer players were separated into altitude (n = 20, 825 m) or sea-level (n = 20, 125 m) groups. Before (1-2 days ago) and after (1 and 14 days later) training, players were asked to give a resting venous blood sample and complete a series of performance tests. Compared with sea level, the altitude group increased erythropoietin, red blood cell (RBC) count, and hematocrit 1 day after training (42.6 ± 24.0%, 1.8 ± 1.3%, 1.4 ± 1.1%, mean ± 95% confidence limits (CL), respectively). By 14 days after training, only RBC count and hemoglobin were substantially higher in the altitude compared with the sea-level group (3.2 ± 1.8%, 2.9 ± 2.1% respectively). Compared with sea level, the altitude group 1-2 days after training improved their 50-m (-2.9 ± 1.4%) and 2,800-m (-2.9 ± 4.4%) run times and demonstrated a higher maximal aerobic speed (4.7 ± 7.4%). These performance changes remained at 14 days after training with the addition of a likely higher estimated V[Combining Dot Above]O2max in the altitude compared with the sea-level group (3.2 ± 3.0%). Eight weeks of low-altitude training, supplemented with regular bouts of intermittent hypoxic training at higher altitude, produced beneficial performance improvements in team-sport athletes, which may increase the viability of such training to coaches and players that cannot access more traditional high altitude venues.

  11. Bed Rest and Hypoxic Exposure Affect Sleep Architecture and Breathing Stability

    Directory of Open Access Journals (Sweden)

    Shawnda A. Morrison

    2017-06-01

    Full Text Available Objective: Despite over 50 years of research on the physiological effects of sustained bed rest, data characterizing its effects on sleep macrostructure and breathing stability in humans are scarce. This study was conducted to determine the effects of continuous exposure to hypoxia and sustained best rest, both individually and combined, on nocturnal sleep and breathing stability.Methods: Eleven participants completed three randomized, counter-balanced, 21-days trials of: (1 normoxic bed rest (NBR, PIO2 = 133.1 ± 0.3, (2 hypoxic ambulatory confinement (HAMB, PIO2 = 90.0 ± 0.4 and (3 hypoxic bed rest (HBR, PIO2 = 90.0 ± 0.4; ~4,000 m equivalent altitude. Full objective polysomnography was performed at baseline, on Night 1 and Night 21 in each condition.Results: In NBR Night 1, more time was spent in light sleep (10 ± 2% compared to baseline (8 ± 2%; p = 0.028; Slow-wave sleep (SWS was reduced from baseline in the hypoxic-only trial by 18% (HAMB Night 21, p = 0.028 and further reduced by 33% (HBR Night 1, p = 0.010, and 36% (HBR Night 21, p = 0.008 when combined with bed rest. The apnea-hypopnea index doubled from Night 1 to Night 21 in HBR (32–62 events·h−1 and HAMB (31–59 events·h−1; p = 0.002. Those who experienced greatest breathing instability from Night 1 to Night 21 (NBR were correlated to unchanged or higher (+1% night SpO2 concentrations (R2 = 0.471, p = 0.020.Conclusion: Bed rest negatively affects sleep macrostructure, increases the apnea-hypopnea index, and worsens breathing stability, each independently exacerbated by continuous exposure to hypoxia.

  12. Bed Rest and Hypoxic Exposure Affect Sleep Architecture and Breathing Stability

    Science.gov (United States)

    Morrison, Shawnda A.; Mirnik, Dani; Korsic, Spela; Eiken, Ola; Mekjavic, Igor B.; Dolenc-Groselj, Leja

    2017-01-01

    Objective: Despite over 50 years of research on the physiological effects of sustained bed rest, data characterizing its effects on sleep macrostructure and breathing stability in humans are scarce. This study was conducted to determine the effects of continuous exposure to hypoxia and sustained best rest, both individually and combined, on nocturnal sleep and breathing stability. Methods: Eleven participants completed three randomized, counter-balanced, 21-days trials of: (1) normoxic bed rest (NBR, PIO2 = 133.1 ± 0.3), (2) hypoxic ambulatory confinement (HAMB, PIO2 = 90.0 ± 0.4) and (3) hypoxic bed rest (HBR, PIO2 = 90.0 ± 0.4; ~4,000 m equivalent altitude). Full objective polysomnography was performed at baseline, on Night 1 and Night 21 in each condition. Results: In NBR Night 1, more time was spent in light sleep (10 ± 2%) compared to baseline (8 ± 2%; p = 0.028); Slow-wave sleep (SWS) was reduced from baseline in the hypoxic-only trial by 18% (HAMB Night 21, p = 0.028) and further reduced by 33% (HBR Night 1, p = 0.010), and 36% (HBR Night 21, p = 0.008) when combined with bed rest. The apnea-hypopnea index doubled from Night 1 to Night 21 in HBR (32–62 events·h−1) and HAMB (31–59 events·h−1; p = 0.002). Those who experienced greatest breathing instability from Night 1 to Night 21 (NBR) were correlated to unchanged or higher (+1%) night SpO2 concentrations (R2 = 0.471, p = 0.020). Conclusion: Bed rest negatively affects sleep macrostructure, increases the apnea-hypopnea index, and worsens breathing stability, each independently exacerbated by continuous exposure to hypoxia. PMID:28676764

  13. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER FLASH OR PATTERN REVERSAL EVOKED POTENTIALS IN RATS.

    Science.gov (United States)

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Visual disturbances are often reported following exposure to xenobiotics, and cholinesterase-inhibiting compounds have been reported to alter visual functi...

  14. Enhanced phosphorylation of cyclic AMP response element binding protein in Brain of mice following repetitive hypoxic exposure

    International Nuclear Information System (INIS)

    Gao Yanan; Gao Ge; Long Caixia; Han Song; Zu Pengyu; Fang Li; Li Junfa

    2006-01-01

    Cerebral ischemic/hypoxic preconditioning (I/HPC) is a phenomenon of endogenous protection that renders Brain tolerant to sustained ischemia/hypoxia. This profound protection induced by I/HPC makes it an attractive target for developing potential clinical therapeutic approaches. However, the molecular mechanism of I/HPC is unclear. Cyclic AMP (cAMP) response element binding protein (CREB), a selective nuclear transcriptional factor, plays a key role in the neuronal functions. Phosphorylation of CREB on Ser-133 may facilitate its transcriptional activity in response to various stresses. In the current study, we observed the changes in CREB phosphorylation (Ser-133) and protein expression in Brain of auto-hypoxia-induced HPC mice by using Western blot analysis. We found that the levels of phosphorylated CREB (Ser-133), but not protein expression of CREB, increased significantly (p < 0.05) in the hippocampus and the frontal cortex of mice after repetitive hypoxic exposure (H2-H4, n = 6 for each group), when compared to that of the normoxic (H0, n = 6) or hypoxic exposure once group (H1, n = 6). In addition, a significant enhancement (p < 0.05) of CREB phosphorylation (Ser-133) could also be found in the nuclear extracts from the whole hippocampus of hypoxic preconditioned mice (H2-H4, n = 6 for each group). These results suggest that the phosphorylation of CREB might be involved in the development of cerebral hypoxic preconditioning

  15. The Acute Effects of Intermittent Light Exposure in the Evening on Alertness and Subsequent Sleep Architecture.

    Science.gov (United States)

    Yang, Minqi; Ma, Ning; Zhu, Yingying; Su, Ying-Chu; Chen, Qingwei; Hsiao, Fan-Chi; Ji, Yanran; Yang, Chien-Ming; Zhou, Guofu

    2018-03-15

    Exposure to bright light is typically intermittent in our daily life. However, the acute effects of intermittent light on alertness and sleep have seldom been explored. To investigate this issue, we employed within-subject design and compared the effects of three light conditions: intermittent bright light (30-min pulse of blue-enriched bright light (~1000 lux, ~6000 K) alternating with 30-min dim normal light (~5 lux, ~3600 K) three times); continuous bright light; and continuous dim light on subjective and objective alertness and subsequent sleep structure. Each light exposure was conducted during the three hours before bedtime. Fifteen healthy volunteers (20 ± 3.4 years; seven males) were scheduled to stay in the sleep laboratory for four separated nights (one for adaptation and the others for the light exposures) with a period of at least one week between nights. The results showed that when compared with dim light, both intermittent light and continuous bright light significantly increased subjective alertness and decreased sleep efficiency (SE) and total sleep time (TST). Intermittent light significantly increased objective alertness than dim light did during the second half of the light-exposure period. Our results suggested that intermittent light was as effective as continuous bright light in their acute effects in enhancing subjective and objective alertness and in negatively impacting subsequent sleep.

  16. The Acute Effects of Intermittent Light Exposure in the Evening on Alertness and Subsequent Sleep Architecture

    Directory of Open Access Journals (Sweden)

    Minqi Yang

    2018-03-01

    Full Text Available Exposure to bright light is typically intermittent in our daily life. However, the acute effects of intermittent light on alertness and sleep have seldom been explored. To investigate this issue, we employed within-subject design and compared the effects of three light conditions: intermittent bright light (30-min pulse of blue-enriched bright light (~1000 lux, ~6000 K alternating with 30-min dim normal light (~5 lux, ~3600 K three times; continuous bright light; and continuous dim light on subjective and objective alertness and subsequent sleep structure. Each light exposure was conducted during the three hours before bedtime. Fifteen healthy volunteers (20 ± 3.4 years; seven males were scheduled to stay in the sleep laboratory for four separated nights (one for adaptation and the others for the light exposures with a period of at least one week between nights. The results showed that when compared with dim light, both intermittent light and continuous bright light significantly increased subjective alertness and decreased sleep efficiency (SE and total sleep time (TST. Intermittent light significantly increased objective alertness than dim light did during the second half of the light-exposure period. Our results suggested that intermittent light was as effective as continuous bright light in their acute effects in enhancing subjective and objective alertness and in negatively impacting subsequent sleep.

  17. LONGITUDINAL STUDY OF SEMEN QUALITY AFTER INTERMITTENT EXPOSURE TO AIR POLLUTION

    Science.gov (United States)

    LONGITUDINAL STUDY OF SEMEN QUALITY AFTER INTERMITTENT EXPOSURE TO AIR POLLUTION. J. Rubes*, D. Zudova*, Veterinary Research Institute, Brno, CR, S.G. Selevan*, US EPA/ORD/NCEA, Washington, DC, D.P. Evenson, South Dakota State University, Brookings, SD, and S.D. Perreault, US ...

  18. Effects of Intermittent Altitude Exposures on Acclimatization of 4,300 M

    National Research Council Canada - National Science Library

    Beidleman, Beth

    2001-01-01

    This study examined the effects of 3 wk of intermittent exposures (4 h/d, 5 d/wk) to 4,300 m altitude-equivalent, in combination with either passive sitting or exercise training, on the process of altitude acclimatization...

  19. Exposure to intermittent hypoxia and sustained hypercapnia reduces therapeutic CPAP in participants with obstructive sleep apnea.

    Science.gov (United States)

    El-Chami, Mohamad; Sudan, Sukhesh; Lin, Ho-Sheng; Mateika, Jason H

    2017-10-01

    Our purpose was to determine whether exposure to mild intermittent hypoxia leads to a reduction in the therapeutic continuous positive airway pressure required to eliminate breathing events. Ten male participants were treated with twelve 2-min episodes of hypoxia ([Formula: see text] ≈50 mmHg) separated by 2-min intervals of normoxia in the presence of [Formula: see text] that was sustained 3 mmHg above baseline. During recovery from the last episode, the positive airway pressure was reduced in a stepwise fashion until flow limitation was evident. The participants also completed a sham protocol under normocapnic conditions, which mimicked the time frame of the intermittent hypoxia protocol. After exposure to intermittent hypoxia, the therapeutic pressure was significantly reduced (i.e., 5 cmH 2 O) without evidence of flow limitation (103.4 ± 6.3% of baseline, P = 0.5) or increases in upper airway resistance (95.6 ± 15.0% of baseline, P = 0.6). In contrast, a similar decrease in pressure was accompanied by flow limitation (77.0 ± 1.8% of baseline, P = 0.001) and an increase in upper airway resistance (167.2 ± 17.5% of baseline, P = 0.01) after the sham protocol. Consistent with the initiation of long-term facilitation of upper airway muscle activity, exposure to intermittent hypoxia reduced the therapeutic pressure required to eliminate apneic events that could improve treatment compliance. This possibility, coupled with the potentially beneficial effects of intermittent hypoxia on comorbidities linked to sleep apnea, suggests that mild intermittent hypoxia may have a multipronged therapeutic effect on sleep apnea. NEW & NOTEWORTHY Our new finding is that exposure to mild intermittent hypoxia reduced the therapeutic pressure required to treat sleep apnea. These findings are consistent with previous results, which have shown that long-term facilitation of upper muscle activity can be initiated following exposure to intermittent hypoxia in humans.

  20. Effects of flow intermittency and pharmaceutical exposure on the structure and metabolism of stream biofilms.

    Science.gov (United States)

    Corcoll, Natàlia; Casellas, Maria; Huerta, Belinda; Guasch, Helena; Acuña, Vicenç; Rodríguez-Mozaz, Sara; Serra-Compte, Albert; Barceló, Damià; Sabater, Sergi

    2015-01-15

    Increasing concentrations of pharmaceutical compounds occur in many rivers, but their environmental risk remains poorly studied in stream biofilms. Flow intermittency shapes the structure and functions of ecosystems, and may enhance their sensitivity to toxicants. This study evaluates the effects of a long-term exposure of biofilm communities to a mixture of pharmaceutical compounds at environmental concentrations on biofilm bioaccumulation capacity, the structure and metabolic processes of algae and bacteria communities, and how their potential effects were enhanced or not by the occurrence of flow intermittency. To assess the interaction between those two stressors, an experiment with artificial streams was performed. Stream biofilms were exposed to a mixture of pharmaceuticals, as well as to a short period of flow intermittency. Results indicate that biofilms were negatively affected by pharmaceuticals. The algal biomass and taxa richness decreased and unicellular green algae relatively increased. The structure of the bacterial (based on denaturing gradient gel electrophoresis of amplified 16S rRNA genes) changed and showed a reduction of the operational taxonomic units (OTUs) richness. Exposed biofilms showed higher rates of metabolic processes, such as primary production and community respiration, attributed to pharmaceuticals stimulated an increase of green algae and heterotrophs, respectively. Flow intermittency modulated the effects of chemicals on natural communities. The algal community became more sensitive to short-term exposure of pharmaceuticals (lower EC50 value) when exposed to water intermittency, indicating cumulative effects between the two assessed stressors. In contrast to algae, the bacterial community became less sensitive to short-term exposure of pharmaceuticals (higher EC50) when exposed to water intermittency, indicating co-tolerance phenomena. According to the observed effects, the environmental risk of pharmaceuticals in nature is high

  1. Molecular and biochemical responses of hypoxia exposure in Atlantic croaker collected from hypoxic regions in the northern Gulf of Mexico.

    Science.gov (United States)

    Rahman, Md Saydur; Thomas, Peter

    2017-01-01

    A major impact of global climate change has been the marked increase worldwide in the incidence of coastal hypoxia (dissolved oxygen, DOhypoxic waters as well as their molecular and physiological responses to environmental hypoxia exposure are largely unknown. A suite of potential hypoxia exposure biomarkers was evaluated in Atlantic croaker collected from hypoxic and normoxic regions in the northern Gulf of Mexico (nGOM), and in croaker after laboratory exposure to hypoxia (DO: 1.7 mg l-1). Expression of hypoxia-inducible factor-α, hif-α; neuronal nitric oxide synthase, nNOS; and insulin-like growth factor binding protein, igfbp mRNAs and protein carbonyl (PC, an oxidative stress indicator) content were elevated several-fold in brain and liver tissues of croaker collected from nGOM hypoxic sites. All of these molecular and biochemical biomarkers were also upregulated ~3-10-fold in croaker brain and liver tissues within 1-2 days of hypoxia exposure in controlled laboratory experiments. These results suggest that hif-αs, nNOS and igfbp-1 transcripts and PC contents are useful biomarkers of environmental hypoxia exposure and some of its physiological effects, making them important components for improved assessments of long-term impacts of environmental hypoxia on fish populations.

  2. Changes in resting-state brain function of pilots after hypoxic exposure based on methods for fALFF and ReHo analysis

    Directory of Open Access Journals (Sweden)

    Jie LIU

    2015-07-01

    Full Text Available Objective The objective of this study was to evaluate the basic changes in brain activity of pilots after hypoxic exposure with the use of resting-state functional magnetic resonance imaging (rs-fMRI and regional homogeneity (ReHo method. Methods Thirty healthy male pilots were successively subjected to normal and hypoxic exposure (with an oxygen concentration of 14.5%. Both the fALFF and ReHo methods were adopted to analyze the resting-state functional MRI data before and after hypoxic exposure of the subjects, the areas of the brain with fALFF and ReHo changes after hypoxic exposure were observed. Results  After hypoxic exposure, the pulse was 64.0±10.6 beats/min, and the oxygen saturation was 92.4%±3.9% in these 30 pilots, and it was lower than those before exposure (71.4±10.9 beats/min, 96.3%±1.3%, P<0.05. Compared with the condition before hypoxic exposure, the fALFF value was decreased in superior temporal gyri on both sides and the right superior frontal gyrus, and increase in the left precuneus, while the value of ReHo was decreased in the right superior frontal gyrus (P<0.05. No brain area with an increase in ReHo value was found. Conclusions Hypoxic exposure could significantly affect the brain functions of pilots, which may contribute to change in their cognitive ability. DOI: 10.11855/j.issn.0577-7402.2015.06.18

  3. Hypoxic conditioning as a new therapeutic modality

    Directory of Open Access Journals (Sweden)

    Samuel eVerges

    2015-06-01

    Full Text Available Preconditioning refers to a procedure by which a single noxious stimulus below the threshold of damage is applied to the tissue in order to increase resistance to the same or even different noxious stimuli given above the threshold of damage. Hypoxic preconditioning relies on complex and active defenses that organisms have developed to counter the adverse consequences of oxygen deprivation. The protection it confers against ischemic attack for instance as well as the underlying biological mechanisms have been extensively investigated in animal models. Based on these data, hypoxic conditioning (consisting in recurrent exposure to hypoxia has been suggested a potential non-pharmacological therapeutic intervention to enhance some physiological functions in individuals in whom acute or chronic pathological events are anticipated or existing. In addition to healthy subjects, some benefits have been reported in patients with cardiovascular and pulmonary diseases as well as in overweight and obese individuals. Hypoxic conditioning consisting in sessions of intermittent exposure to moderate hypoxia repeated over several weeks may induce hematological, vascular, metabolic and neurological effects. This review addresses the existing evidence regarding the use of hypoxic conditioning as a potential therapeutic modality and emphasizes on many remaining issues to clarify and future researches to be performed in the field.

  4. Intermittent Access to Ethanol Drinking Facilitates the Transition to Excessive Drinking After Chronic Intermittent Ethanol Vapor Exposure.

    Science.gov (United States)

    Kimbrough, Adam; Kim, Sarah; Cole, Maury; Brennan, Molly; George, Olivier

    2017-08-01

    Alcohol binge drinking in humans is thought to increase the risk for alcohol use disorder (AUD). Unclear is whether drinking patterns (e.g., bingelike or stable drinking) differentially affect the transition to compulsive-like drinking in dependent individuals. We examined whether chronic bingelike drinking facilitates the transition to compulsive-like drinking in rats. Male Wistar rats were given 5 months of intermittent access to ethanol (EtOH) (IAE) or continuous access to EtOH (CAE) in a 2-bottle choice paradigm. Then, rats were given chronic intermittent EtOH (CIE) vapor exposure. Escalation of EtOH intake and compulsive-like responding for EtOH, using a progressive-ratio schedule of reinforcement and quinine-adulterated EtOH, were measured. IAE rats escalated EtOH drinking after 2 weeks of 2-bottle choice, whereas CAE rats exhibited stable EtOH drinking for 5 months. After 8 weeks of CIE, both IAE + CIE and CAE + CIE rats escalated their EtOH intake. However, IAE rats escalated their EtOH intake weeks sooner than CAE rats and exhibited greater EtOH intake. No differences in compulsive-like responding were found between IAE + CIE and CAE + CIE rats. However, both IAE + CIE and CAE + CIE rats showed strong compulsive-like responding compared with rats without prior IAE or CAE. Chronic EtOH drinking at stable or escalated levels for several months is associated with more compulsive-like responding for EtOH in rats that are exposed to CIE compared with rats without a prior history of EtOH drinking. Moreover, IAE facilitated the transition to compulsive-like responding for EtOH after CIE exposure, reflected by the escalation of EtOH intake. These results suggest that IAE may facilitate the transition to AUD. This study indicates that despite a moderate level of EtOH drinking, the IAE animal model is highly relevant to early stages of alcohol abuse and suggests that it may be associated with neuroadaptations that produce a faster transition to

  5. Effect of intermittent cold exposure on brown fat activation, obesity, and energy homeostasis in mice.

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    Yann Ravussin

    Full Text Available Homeotherms have specific mechanisms to maintain a constant core body temperature despite changes in thermal environment, food supply, and metabolic demand. Brown adipose tissue, the principal thermogenic organ, quickly and efficiently increases heat production by dissipating the mitochondrial proton motive force. It has been suggested that activation of brown fat, via either environmental (i.e. cold exposure or pharmacologic means, could be used to increase metabolic rate and thus reduce body weight. Here we assess the effects of intermittent cold exposure (4°C for one to eight hours three times a week on C57BL/6J mice fed a high fat diet. Cold exposure increased metabolic rate approximately two-fold during the challenge and activated brown fat. In response, food intake increased to compensate fully for the increased energy expenditure; thus, the mice showed no reduction in body weight or adiposity. Despite the unchanged adiposity, the cold-treated mice showed transient improvements in glucose homeostasis. Administration of the cannabinoid receptor-1 inverse agonist AM251 caused weight loss and improvements in glucose homeostasis, but showed no further improvements when combined with cold exposure. These data suggest that intermittent cold exposure causes transient, meaningful improvements in glucose homeostasis, but without synergy when combined with AM251. Since energy expenditure is significantly increased during cold exposure, a drug that dissociates food intake from metabolic demand during cold exposure may achieve weight loss and further metabolic improvements.

  6. Simulating sleep apnea by exposure to intermittent hypoxia induces inflammation in the lung and liver.

    Science.gov (United States)

    da Rosa, Darlan Pase; Forgiarini, Luiz Felipe; Baronio, Diego; Feijó, Cristiano Andrade; Martinez, Dênis; Marroni, Norma Possa

    2012-01-01

    Sleep apnea is a breathing disorder that results from momentary and cyclic collapse of the upper airway, leading to intermittent hypoxia (IH). IH can lead to the formation of free radicals that increase oxidative stress, and this mechanism may explain the association between central sleep apnea and nonalcoholic steatohepatitis. We assessed the level of inflammation in the lung and liver tissue from animals subjected to intermittent hypoxia and simulated sleep apnea. A total of 12 C57BL/6 mice were divided into two groups and then exposed to IH (n = 6) or a simulated IH (SIH) (n = 6) for 35 days. We observed an increase in oxidative damage and other changes to endogenous antioxidant enzymes in mice exposed to IH. Specifically, the expression of multiple transcription factors, including hypoxia inducible factor (HIF-1α), nuclear factor kappa B (NF-κB), and tumor necrosis factor (TNF-α), inducible NO synthase (iNOS), vascular endothelial growth factor (VEGF), and cleaved caspase 3 were shown to be increased in the IH group. Overall, we found that exposure to intermittent hypoxia for 35 days by simulating sleep apnea leads to oxidative stress, inflammation, and increased activity of caspase 3 in the liver and lung.

  7. Simulating Sleep Apnea by Exposure to Intermittent Hypoxia Induces Inflammation in the Lung and Liver

    Directory of Open Access Journals (Sweden)

    Darlan Pase da Rosa

    2012-01-01

    Full Text Available Sleep apnea is a breathing disorder that results from momentary and cyclic collapse of the upper airway, leading to intermittent hypoxia (IH. IH can lead to the formation of free radicals that increase oxidative stress, and this mechanism may explain the association between central sleep apnea and nonalcoholic steatohepatitis. We assessed the level of inflammation in the lung and liver tissue from animals subjected to intermittent hypoxia and simulated sleep apnea. A total of 12 C57BL/6 mice were divided into two groups and then exposed to IH (n=6 or a simulated IH (SIH (n=6 for 35 days. We observed an increase in oxidative damage and other changes to endogenous antioxidant enzymes in mice exposed to IH. Specifically, the expression of multiple transcription factors, including hypoxia inducible factor (HIF-1α, nuclear factor kappa B (NF-κB, and tumor necrosis factor (TNF-α, inducible NO synthase (iNOS, vascular endothelial growth factor (VEGF, and cleaved caspase 3 were shown to be increased in the IH group. Overall, we found that exposure to intermittent hypoxia for 35 days by simulating sleep apnea leads to oxidative stress, inflammation, and increased activity of caspase 3 in the liver and lung.

  8. Chronic intermittent ethanol exposure during adolescence: effects on social behavior and ethanol sensitivity in adulthood.

    Science.gov (United States)

    Varlinskaya, Elena I; Truxell, Eric; Spear, Linda P

    2014-08-01

    This study assessed long-lasting consequences of repeated ethanol exposure during two different periods of adolescence on 1) baseline levels of social investigation, play fighting, and social preference and 2) sensitivity to the social consequences of acute ethanol challenge. Adult male and female Sprague-Dawley rats were tested 25 days after repeated exposure to ethanol (3.5 g/kg intragastrically [i.g.], every other day for a total of 11 exposures) in a modified social interaction test. Early-mid adolescent intermittent exposure (e-AIE) occurred between postnatal days (P) 25 and 45, whereas late adolescent intermittent exposure (l-AIE) was conducted between P45 and P65. Significant decreases in social investigation and social preference were evident in adult male rats, but not their female counterparts following e-AIE, whereas neither males nor females demonstrated these alterations following l-AIE. In contrast, both e-AIE and l-AIE produced alterations in sensitivity to acute ethanol challenge in males tested 25 days after adolescent exposure. Ethanol-induced facilitation of social investigation and play fighting, reminiscent of that normally seen during adolescence, was evident in adult males after e-AIE, whereas control males showed an age-typical inhibition of social behavior. Males after l-AIE were found to be insensitive to the socially suppressing effects of acute ethanol challenge, suggesting the development of chronic tolerance in these animals. In contrast, females showed little evidence for alterations in sensitivity to acute ethanol challenge following either early or late AIE. The results of the present study demonstrate a particular vulnerability of young adolescent males to long-lasting detrimental effects of repeated ethanol. Retention of adolescent-typical sensitivity to the socially facilitating effects of ethanol could potentially make ethanol especially appealing to these males, therefore promoting relatively high levels of ethanol intake later

  9. Epigenetic regulation of hypoxic sensing disrupts cardiorespiratory homeostasis.

    Science.gov (United States)

    Nanduri, Jayasri; Makarenko, Vladislav; Reddy, Vaddi Damodara; Yuan, Guoxiang; Pawar, Anita; Wang, Ning; Khan, Shakil A; Zhang, Xin; Kinsman, Brian; Peng, Ying-Jie; Kumar, Ganesh K; Fox, Aaron P; Godley, Lucy A; Semenza, Gregg L; Prabhakar, Nanduri R

    2012-02-14

    Recurrent apnea with intermittent hypoxia is a major clinical problem in preterm infants. Recent studies, although limited, showed that adults who were born preterm exhibit increased incidence of sleep-disordered breathing and hypertension, suggesting that apnea of prematurity predisposes to autonomic dysfunction in adulthood. Here, we demonstrate that adult rats that were exposed to intermittent hypoxia as neonates exhibit exaggerated responses to hypoxia by the carotid body and adrenal chromaffin cells, which regulate cardio-respiratory function, resulting in irregular breathing with apneas and hypertension. The enhanced hypoxic sensitivity was associated with elevated oxidative stress, decreased expression of genes encoding antioxidant enzymes, and increased expression of pro-oxidant enzymes. Decreased expression of the Sod2 gene, which encodes the antioxidant enzyme superoxide dismutase 2, was associated with DNA hypermethylation of a single CpG dinucleotide close to the transcription start site. Treating neonatal rats with decitabine, an inhibitor of DNA methylation, during intermittent hypoxia exposure prevented oxidative stress, enhanced hypoxic sensitivity, and autonomic dysfunction. These findings implicate a hitherto uncharacterized role for DNA methylation in mediating neonatal programming of hypoxic sensitivity and the ensuing autonomic dysfunction in adulthood.

  10. EXPOSURE TO INTERMITTENT AIR POLLUTION AND CHANGES IN SEMEN QUALITY: EVIDENCE FOR AN ASSOCIATION AND IMPLICATIONS FOR REPRODUCTIVE RISK ASSESSMENT

    Science.gov (United States)

    Exposure to Intermittent Air Pollution and Changes in Semen Quality:Evidence for an Association and Implications for Reproductive Risk Assessment. S. D. Perreault1, S.G. Selevan2, J. Rubes3, D. Zudova3, and D.P. Evenson4 1US EPA, ORD/NHEERL, Research Triangle Pa...

  11. Overnight hypoxic exposure and glucagon-like peptide-1 and leptin levels in humans

    DEFF Research Database (Denmark)

    Snyder, Eric M; Carr, Richard D; Deacon, Carolyn F

    2008-01-01

    increases with hypoxia; however, the influence of hypoxia on GLP-1 has not been studied in animals or humans to date. We sought to determine the influence of normobaric hypoxia on plasma leptin and GLP-1 levels in 25 healthy humans. Subjects ingested a control meal during normoxia and after 17 h of exposure...

  12. Novel Models to Study Effect of High-Altitude Hypoxic Exposure and Placental Insufficency on Fetal Oxygen Metabolism and Congenital Heart Defects

    Science.gov (United States)

    2016-10-01

    maternal decidua is required for recruitment of uNK and TB cells into the decidua for the purpose of remodeling of the spiral arteries. When this fails , as...AWARD NUMBER: W81XWH-15-1-0238 TITLE: Novel Models to Study Effect of High-Altitude Hypoxic Exposure and Placental Insufficency on Fetal...that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it

  13. HYPOXIC EFFECT ON GROWTH OF PALEOMENETES VULGARIS LARVAE AND OTHER SPECIES: USING CONSTANT EXPOSURE DATA TO PREDICT CYCLIC EXPOSURE RESPONSE

    Science.gov (United States)

    First stage larval marsh grass shrimp, Palaemonetes vulgaris, were exposed to patterns of diurnal, semidiurnal, and constant hypoxia to evaluate effects on growth and to determine if there was a consistent relationship between exposures. A comparison of growth with cyclic exposur...

  14. Intermittent exposure to ethanol vapor affects osteoblast behaviour more severely than estrogen deficiency does

    International Nuclear Information System (INIS)

    Torricelli, Paola; Fini, Milena; Giavaresi, Gianluca; Borsari, Veronica; Rimondini, Lia; Rimondini, Roberto; Carrassi, Antonio; Giardino, Roberto

    2007-01-01

    With rising rates of alcohol consumption acute and chronic damage from alcohol is expected to increase all over the world. Habitual excessive alcohol consumption is associated with pathological effects on bone. The aim of the present in vitro study was to investigate comparatively the proliferation and synthetic activity of osteoblasts (OB) isolated from the trabecular bone of rats previously exposed to 7-week intermittent exposure to ethanol vapor, sham-aged rats and long-term estrogen deficient rats. Cell proliferation (WST1) and synthesis of alkaline phosphatase (ALP), osteocalcin (OC), collagen I (CICP), transforming growth factor beta1 (TGF-β1), interleukin-6 (IL-6), tumor necrosis factor alfa (TNFα) were measured at 3, 7 and 14 days of culture. Osteoblast proliferation rate and TGF-β1, IL-6 and TNFα syntheses were significantly affected by alcohol exposure. Estrogen deficiency and alcohol consumption share many common pathophysiological mechanisms of damage to bone, but alcohol affects OB proliferation and TNFα synthesis significantly more than menopause does. Therefore, these in vitro data suggest that alcohol has even more deleterious effects on bone than estrogen deficiency does

  15. Preacclimatization in hypoxic chambers for high altitude sojourns.

    Science.gov (United States)

    Küpper, Thomas E A H; Schöffl, Volker

    2010-09-01

    Since hypoxic chambers are more and more available, they are used for preacclimatization to prepare for sojourns at high altitude. Since there are different protocols and the data differ, there is no general consensus about the standard how to perform preacclimatization by simulated altitude. The paper reviews the different types of exposure and focuses on the target groups which may benefit from preacclimatization. Since data about intermittent hypoxia for some hours per day to reduce the incidence of acute mountain sickness differ, it is suggested to perform preacclimatization by sleeping some nights at a simulated altitude which follows the altitude profile of the "gold standard" for high altitude acclimatization.

  16. Periodicity during hypercapnic and hypoxic stimulus is crucial in distinct aspects of phrenic nerve plasticity.

    Science.gov (United States)

    Stipica, I; Pavlinac Dodig, I; Pecotic, R; Dogas, Z; Valic, Z; Valic, M

    2016-01-01

    This study was undertaken to determine pattern sensitivity of phrenic nerve plasticity in respect to different respiratory challenges. We compared long-term effects of intermittent and continuous hypercapnic and hypoxic stimuli, and combined intermittent hypercapnia and hypoxia on phrenic nerve plasticity. Adult, male, urethane-anesthetized, vagotomized, paralyzed, mechanically ventilated Sprague-Dawley rats were exposed to: acute intermittent hypercapnia (AIHc or AIHc(O2)), acute intermittent hypoxia (AIH), combined intermittent hypercapnia and hypoxia (AIHcH), continuous hypercapnia (CHc), or continuous hypoxia (CH). Peak phrenic nerve activity (pPNA) and burst frequency were analyzed during baseline (T0), hypercapnia or hypoxia exposures, at 15, 30, and 60 min (T60) after the end of the stimulus. Exposure to acute intermittent hypercapnia elicited decrease of phrenic nerve frequency from 44.25+/-4.06 at T0 to 35.29+/-5.21 at T60, (P=0.038, AIHc) and from 45.5+/-2.62 to 37.17+/-3.68 breaths/min (P=0.049, AIHc(O2)), i.e. frequency phrenic long term depression was induced. Exposure to AIH elicited increase of pPNA at T60 by 141.0+/-28.2 % compared to baseline (P=0.015), i.e. phrenic long-term facilitation was induced. Exposure to AIHcH, CHc, or CH protocols failed to induce long-term plasticity of the phrenic nerve. Thus, we conclude that intermittency of the hypercapnic or hypoxic stimuli is needed to evoke phrenic nerve plasticity.

  17. The effects of continuous and intermittent ethanol exposure in adolesence on the aversive properties of ethanol during adulthood.

    Science.gov (United States)

    Diaz-Granados, Jaime L; Graham, Danielle L

    2007-12-01

    Alcohol abuse among adolescents is prevalent. Epidemiological studies suggest that alcohol abuse during the adolescent developmental period may result in long-term changes such as an increased susceptibility to alcohol-related problems in adulthood. Laboratory findings suggest that alcohol exposure during the adolescent developmental period, as compared with adulthood, may differentially impact subsequent neurobehavioral responses to alcohol. The present study was designed to examine whether ethanol exposure, continuous versus intermittent, during the adolescent developmental period would alter the aversive properties of ethanol in adult C3H mice. Periadolescent (PD28) male C3H mice were exposed to 64 hours of continuous or intermittent ethanol vapor. As a comparison, adult (PD70) C3H mice were also exposed to 64 hours of continuous or intermittent ethanol vapor. Six weeks after ethanol exposure, taste aversion conditioning was carried out on both ethanol pre-exposed and ethanol-naive animals using a 1-trial, 1-flavor taste-conditioning procedure. Ethanol exposure during the periadolescent period significantly attenuated a subsequent ethanol-induced conditioned taste aversion, as compared with control animals. Adult animals exposed to chronic ethanol vapor during adolescence showed less of an aversion to an ethanol-paired flavor than ethanol-naive adults. Intermittent exposure to ethanol vapor during periadolescence produced a greater attenuation. It is suggested that ethanol exposure during the periadolescent period results in long-term neurobehavioral changes, which lessen a conditioned aversion to ethanol in adulthood. It is suggested that this age-related effect may underlie the increased susceptibility to alcohol-related problems which is negatively correlated with the age of onset for alcohol abuse.

  18. Understanding Adherence to Daily and Intermittent Regimens of Oral HIV Pre-exposure Prophylaxis Among Men Who Have Sex with Men in Kenya

    OpenAIRE

    Mugo, Peter Mwangi; Sanders, Eduard J.; Mutua, Gaudensia; van der Elst, Elisabeth; Anzala, Omu; Barin, Burc; Bangsberg, David R.; Priddy, Frances H.; Haberer, Jessica E.

    2014-01-01

    A qualitative assessment of Kenyan men who have sex with men taking daily and intermittent oral HIV pre-exposure prophylaxis (PrEP) found stigma, sex work, mobility, and alcohol impacted adherence. We analyzed quantitative data from the same cohort to explore different definitions of intermittent adherence. Volunteers were randomized to daily emtricitabine/tenofovir or placebo, or intermittent (prescription: Mondays/Fridays/after sex, maximum 1 dose/day) emtricitabine/tenofovir or placebo (2:...

  19. Changes in the Adult GluN2B Associated Proteome following Adolescent Intermittent Ethanol Exposure.

    Directory of Open Access Journals (Sweden)

    H Scott Swartzwelder

    Full Text Available Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment. Given the pattern of changes in hippocampal structure and function, one potential target for these effects is the ethanol sensitive GluN2B subunit of the NMDA receptor, which is known to be involved in synaptic plasticity and dendritic morphology. Thus we sought to determine if there were persistent changes in hippocampal GluN2B signaling cascades following AIE. We employed a previously validated GluN2B-targeted proteomic strategy that was used to identify novel signaling mechanisms altered by chronic ethanol exposure in the adult hippocampus. We collected adult hippocampal tissue (P70 from rats that had been given 2 weeks of AIE from P30-45. Tissue extracts were fractionated into synaptic and non-synaptic pools, immuno-precipitated for GluN2B, and then analyzed using proteomic methods. We detected a large number of proteins associated with GluN2B. AIE produced significant changes in the association of many proteins with GluN2B in both synaptic and non-synaptic fractions. Intriguingly the number of proteins changed in the non-synaptic fraction was double that found in the synaptic fraction. Some of these proteins include those involved in glutamate signaling cytoskeleton rearrangement, calcium signaling, and plasticity. Disruptions in these pathways may contribute to the persistent cellular and behavioral changes found in the adult hippocampus following AIE. Further

  20. Variable effects of chronic intermittent ethanol exposure on ethanol drinking in a genetically diverse mouse cohort.

    Science.gov (United States)

    Lopez, Marcelo F; Miles, Michael F; Williams, Robert W; Becker, Howard C

    2017-02-01

    The BXD family of mice were generated by crossing and inbreeding ethanol-preferring C57BL/6J and ethanol-avoiding DBA/2J strains that differ greatly in genome sequence and other behaviors. This study evaluated variations in the level of voluntary ethanol intake in a cohort of 42 BXD strains and both progenitor strains using a model of alcohol dependence and relapse drinking. A total of 119 BXDs (85 males, 34 females) (n ∼ 4 per genotype; 1/genotype/sex/group) were evaluated along with males from both progenitor strains (n = 14-15/genotype). Mice were evaluated for intake using limited access (2 h/day) 2-bottle (15% v/v ethanol vs. water) model for 6 weeks (baseline intake). Each animal received 4 weekly cycles of chronic intermittent ethanol (CIE) vapor exposure (CIE group) or air control exposure (CTL group) (16 h/day × 4 days) interleaved by 5-day drinking test cycles. Blood ethanol concentrations (BEC) ranged from 150 to 300 mg/dl across genotypes. Baseline intake varied greatly among cases-from ∼0.8 to ∼2.9 g/kg. As expected, CIE exposure induced a significant increase in ethanol drinking in C57BL/6J relative to baseline as well as air controls that remained relatively stable over the four test cycles. In contrast, DBA/2J cases did not show a significant increase in consumption. Heritability of variation in baseline consumption, calculated from C57BL/6J and DBA/2J strains is about 54% but this increases following treatment to 60-80%. As expected from the marked difference between progenitors, ethanol intake and level of escalation varied greatly among BXDs after exposure (∼-1.3 to 2.6 g/kg). Interestingly, the magnitude and direction of changes in ethanol intake did not relate to BEC values of the preceding CIE exposure cycle. Overall, these data indicate significant variation in consumption and even escalation, much of it under genetic control, following repeated CIE treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Intermittent hypoxia hypobaric exposure minimized oxidative stress and antioxidants in brain cells of Sprague Dawleymice

    Directory of Open Access Journals (Sweden)

    Wardaya Wardaya

    2013-05-01

    antioxidants in Sprague Dawley male mice.Methods: The experimental study was in February-April 2010 consisted of one control group and four exposed groups of male mice Sprague Dawley. Each groups consisted of 5 mice. The control group did not have IHH. The exposed groups (with an interval of one week had once, twice, three, or four times IHH using a chamber flight. All exposed groups were treated hypobaric equivalent to: 35,000 ft altitude (1 minutes, 25,000 ft (5 minutes, and 18,000 ft (25 minutes. All of their brains had 8-OHdG and SOD measured.Results: The 8-OHdG level among three time IHH exposures had already returned to the control value (P = 0.843. The SOD level increased progressively among two, three, and four times IHH. However after the second exposure, it was found that the SOD level was similar to the control value, 0.231 ± 0.042 (P = 0.191.Conclusion: In conclusion, three times of IHH may improve the effect of hypoxia hypobaric on oxidative stress and specific activity of antioxidants in Sprague Dawley male mice. The SOD level was increased at an earlier exposure, which was after one IHH exposure.Keywords: intermittent hypoxia hypobaric, oxidative stress, antioxidants

  2. Adolescent Intermittent Alcohol Exposure: Deficits in Object Recognition Memory and Forebrain Cholinergic Markers.

    Directory of Open Access Journals (Sweden)

    H Scott Swartzwelder

    Full Text Available The long-term effects of intermittent ethanol exposure during adolescence (AIE are of intensive interest and investigation. The effects of AIE on learning and memory and the neural functions that drive them are of particular interest as clinical findings suggest enduring deficits in those cognitive domains in humans after ethanol abuse during adolescence. Although studies of such deficits after AIE hold much promise for identifying mechanisms and therapeutic interventions, the findings are sparse and inconclusive. The present results identify a specific deficit in memory function after AIE and establish a possible neural mechanism of that deficit that may be of translational significance. Male rats (starting at PND-30 received exposure to AIE (5g/kg, i.g. or vehicle and were allowed to mature into adulthood. At PND-71, one group of animals was assessed using the spatial-temporal object recognition (stOR test to evaluate memory function. A separate group of animals was used to assess the density of cholinergic neurons in forebrain areas Ch1-4 using immunohistochemistry. AIE exposed animals manifested deficits in the temporal component of the stOR task relative to controls, and a significant decrease in the number of ChAT labeled neurons in forebrain areas Ch1-4. These findings add to the growing literature indicating long-lasting neural and behavioral effects of AIE that persist into adulthood and indicate that memory-related deficits after AIE depend upon the tasks employed, and possibly their degree of complexity. Finally, the parallel finding of diminished cholinergic neuron density suggests a possible mechanism underlying the effects of AIE on memory and hippocampal function as well as possible therapeutic or preventive strategies for AIE.

  3. Long-Term Intermittent Exposure to High Altitude Elevates Asymmetric Dimethylarginine in First Exposed Young Adults.

    Science.gov (United States)

    Lüneburg, Nicole; Siques, Patricia; Brito, Julio; De La Cruz, Juan José; León-Velarde, Fabiola; Hannemann, Juliane; Ibanez, Cristian; Böger, Rainer H

    2017-09-01

    Lüneburg, Nicole, Patricia Siques, Julio Brito, Juan José De La Cruz, Fabiola León-Velarde, Juliane Hannemann, Cristian Ibanez, and Rainer Böger. Long-term intermittent exposure to high altitude elevates asymmetric dimethylarginine in first exposed young adults. High Alt Med Biol. 18:226-233, 2017.-Hypoxia-induced dysregulation of pulmonary and cerebral circulation may be related to an impaired nitric oxide (NO) pathway. We investigated the effect of chronic intermittent hypobaric hypoxia (CIH) on metabolites of the NO pathway. We measured asymmetric and symmetric dimethylarginine (ADMA and SDMA) and monomethyl-L-arginine (L-NMMA) and assessed their associations with acclimatization in male draftees (n = 72) undergoing CIH shifts at altitude (3550 m) during 3 months. Sixteen Andean natives living at altitude (3675 m) (chronic hypobaric hypoxia [CH]) were included for comparison. In CIH, ADMA and L-NMMA plasma concentrations increased from 1.14 ± 0.04 to 1.95 ± 0.09 μmol/L (mean ± SE) and from 0.22 ± 0.07 to 0.39 ± 0.03 μmol/L, respectively, (p < 0.001 for both) after 3 months, whereas SDMA did not change. The concentrations of ADMA and L-NMMA were higher in CH (3.48 ± 0.07, 0.53 ± 0.08 μmol/L; p < 0.001) as compared with CIH. In both CIH and CH, ADMA correlated with hematocrit (r 2  = 0.07, p < 0.05; r 2  = 0.26; p < 0.01). In CIH, an association of ADMA levels with poor acclimatization status was observed. We conclude that the endogenous NO synthase inhibitors, ADMA and L-NMMA, are elevated in hypoxia. This may contribute to impaired NO production at altitude and may also be predictive of altitude-associated health impairment.

  4. Prenatal Opioid Exposure and Intermittent Hypoxemia in Preterm Infants: A Retrospective Assessment

    Directory of Open Access Journals (Sweden)

    Elie G. Abu Jawdeh

    2017-12-01

    Full Text Available IntroductionIntermittent hypoxemia (IH is defined as episodic drops in oxygen saturation (SpO2. Preterm infants are at increased risk for IH due to their immature respiratory control/apnea of prematurity. The clinical relevance of IH is a relatively new observation with rising evidence linking IH to neonatal morbidities and long-term impairment. Hence, assessing factors that influence IH in preterm infants is imperative. Given the epidemic of opioid misuse in the USA, there is an urgent need to understand the impact of prenatal opioid exposure on neonatal outcomes. Hence, we wanted to assess the relationship between isolated prenatal opioid exposure and IH in preterm infants.MethodsIn order to accurately calculate IH, SpO2 data were prospectively collected using high-resolution pulse oximeters during the first 8 weeks of life in preterm infants less than 30 weeks gestational age. Data related to prenatal opioid misuse were retrospectively collected from medical charts. Infants with tobacco or poly-drug exposure were excluded. The primary outcome measure is percent time spent with SpO2 below 80% (%time-SpO2 < 80. The secondary outcome measure is the number of severe IH events/week with SpO2 less than 80% (IH-SpO2 < 80.ResultsA total of 82 infants with isolated opioid exposure (n = 14 or who were unexposed (n = 68 were included. There were no significant differences in baseline characteristics between opioid exposed and unexposed groups. There was a statistically significant increase of 0.23 (95% CI: 0.03, 0.43, p = 0.03 in mean of the square root of %time-SpO2 < 80. The number of IH-SpO2 < 80 events was higher in the opioid exposed group (mean difference = 2.95, 95% CI: −0.35, 6.25, p-value = 0.08, although statistical significance was not quite attained.ConclusionThis study shows that preterm infants prenatally exposed to opioids have increased IH measures compared to unexposed infants. Interestingly

  5. Prenatal Opioid Exposure and Intermittent Hypoxemia in Preterm Infants: A Retrospective Assessment.

    Science.gov (United States)

    Abu Jawdeh, Elie G; Westgate, Philip M; Pant, Amrita; Stacy, Audra L; Mamilla, Divya; Gabrani, Aayush; Patwardhan, Abhijit; Bada, Henrietta S; Giannone, Peter

    2017-01-01

    Intermittent hypoxemia (IH) is defined as episodic drops in oxygen saturation (SpO 2 ). Preterm infants are at increased risk for IH due to their immature respiratory control/apnea of prematurity. The clinical relevance of IH is a relatively new observation with rising evidence linking IH to neonatal morbidities and long-term impairment. Hence, assessing factors that influence IH in preterm infants is imperative. Given the epidemic of opioid misuse in the USA, there is an urgent need to understand the impact of prenatal opioid exposure on neonatal outcomes. Hence, we wanted to assess the relationship between isolated prenatal opioid exposure and IH in preterm infants. In order to accurately calculate IH, SpO 2 data were prospectively collected using high-resolution pulse oximeters during the first 8 weeks of life in preterm infants less than 30 weeks gestational age. Data related to prenatal opioid misuse were retrospectively collected from medical charts. Infants with tobacco or poly-drug exposure were excluded. The primary outcome measure is percent time spent with SpO 2 below 80% (%time-SpO 2  < 80). The secondary outcome measure is the number of severe IH events/week with SpO 2 less than 80% (IH-SpO 2  < 80). A total of 82 infants with isolated opioid exposure ( n  = 14) or who were unexposed ( n  = 68) were included. There were no significant differences in baseline characteristics between opioid exposed and unexposed groups. There was a statistically significant increase of 0.23 (95% CI: 0.03, 0.43, p  = 0.03) in mean of the square root of %time-SpO 2  < 80. The number of IH-SpO 2  < 80 events was higher in the opioid exposed group (mean difference = 2.95, 95% CI: -0.35, 6.25, p -value = 0.08), although statistical significance was not quite attained. This study shows that preterm infants prenatally exposed to opioids have increased IH measures compared to unexposed infants. Interestingly, the increased IH in the opioid

  6. Differential patterns of injury to the proximal tubule of renal cortical slices following in vitro exposure to mercuric chloride, potassium dichromate, or hypoxic conditions.

    Science.gov (United States)

    Ruegg, C E; Gandolfi, A J; Nagle, R B; Brendel, K

    1987-09-15

    The innate susceptibility of renal cell types to these agents was investigated using precision-cut rabbit renal cortical slices made perpendicular to the cortical-papillary axis. Slices were incubated in DME/F12 medium containing 10 microM, 100 microM, or 1 mM concentrations of either metal for 12 hr or in Krebs-Hepes buffer gassed with nitrogen (100%) for 0.75 to 5 hr of hypoxic exposure. To simulate postischemic reperfusion, some slices were transferred to vessels gassed with oxygen after an initial hypoxic period. Mercuric chloride (100 microM) exposure resulted in damage to the straight regions of proximal tubules by 12 hr leaving convoluted regions unaffected. Hypoxia (2.25 hr) and potassium dichromate (100 microM for 12 hr) both caused injury to the convoluted proximal tubules without affecting straight proximal tubular regions. Mercury concentrations of 10 microM and 1 mM had no effect or injured all cell types within the slice, respectively. Similar results were observed for hypoxic periods less than 1.5 hr or greater than 3 hr of exposure. Potassium dichromate had no measurable affect at 10 microM, but at 1 mM focal lesions were observed after 4 hr of exposure, and by 12 hr all cell types within the slice were affected. Intracellular potassium content normalized to DNA correlated well, but always preceded the pathological lesions observed. These results demonstrate that injury to specific regions of the proximal tubule by these agents relates to an innate susceptibility of the intoxicated cell type independent of physiologic feedback or blood delivery patterns proposed as mechanisms of selective injury from in vivo studies.

  7. 1H magnetic resonance spectroscopy metabolite profiles of neonatal rat hippocampus and brainstem regions following early postnatal exposure to intermittent hypoxia

    Science.gov (United States)

    Darnall, Robert A.; Chen, Xi; Nemani, Krishnamurthy V.; Sirieix, Chrystelle M.; Gimi, Barjor

    2017-03-01

    Most premature infants born at less than 30 weeks gestation are exposed to periods of mild intermittent hypoxia (IH) associated with apnea of prematurity and periodic breathing. In adults, IH associated with sleep apnea causes neurochemical and structural alterations in the brain. However, it is unknown whether IH in the premature infant leads to neurodevelopmental impairment. Quantification of biochemical markers that can precisely identify infants at risk of adverse neurodevelopmental outcome is essential. In vivo 1H magnetic resonance spectroscopy (1H MRS) facilitates the quantification of metabolites from distinct regions of the developing brain. We report the changes in metabolite profiles in the brainstem and hippocampal regions of developing rat brains, resulting from exposure to IH. Rat pups were chosen for study because there is rapid postnatal hippocampal development that occurs during the first 4 weeks in the developing rat brain, which corresponds to the first 2-3 postnatal years of development in humans. The brainstem was examined because of our interest in respiratory control disorders in the newborn and because of brainstem gliosis described in infants who succumb to Sudden Infant Death Syndrome (SIDS). Metabolite profiles were compared between hypoxia treated rat pups (n = 9) and normoxic controls (n = 6). Metabolite profiles were acquired using the Point-RESolved spectroscopy (PRESS) MRS sequence and were quantified using the TARQUIN software. There was a significant difference in the concentrations of creatine (p = 0.031), total creatine (creatine + phosphocreatine) (p = 0.028), and total choline (p = 0.001) in the brainstem, and glycine (p = 0.031) in the hippocampal region. The changes are consistent with altered cellular bioenergetics and metabolism associated with hypoxic insult.

  8. The influence of intermittent fasting on the circadian pattern of melatonin while controlling for caloric intake, energy expenditure, light exposure, and sleep schedules: A preliminary report

    Directory of Open Access Journals (Sweden)

    Aljohara S Almeneessier

    2017-01-01

    Conclusions: In this preliminary report, under controlled conditions of light exposure, meal composition, energy expenditure, and sleep-wake schedules, intermittent fasting has no significant influence on the circadian pattern of melatonin.

  9. Simulating Sleep Apnea by Exposure to Intermittent Hypoxia Induces Inflammation in the Lung and Liver

    OpenAIRE

    da Rosa, Darlan Pase; Forgiarini, Luiz Felipe; Baronio, Diego; Feijó, Cristiano Andrade; Martinez, Dênis; Marroni, Norma Possa

    2012-01-01

    Sleep apnea is a breathing disorder that results from momentary and cyclic collapse of the upper airway, leading to intermittent hypoxia (IH). IH can lead to the formation of free radicals that increase oxidative stress, and this mechanism may explain the association between central sleep apnea and nonalcoholic steatohepatitis. We assessed the level of inflammation in the lung and liver tissue from animals subjected to intermittent hypoxia and simulated sleep apnea. A total of 12 C57BL/6 mice...

  10. Long-Term Effects of Intermittent Adolescent Alcohol Exposure in Male and Female Rats

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    Eva M. Marco

    2017-11-01

    Full Text Available Alcohol is a serious public health concern that has a differential impact on individuals depending upon age and sex. Patterns of alcohol consumption have recently changed: heavy episodic drinking—known as binge-drinking—has become most popular among the youth. Herein, we aimed to investigate the consequences of intermittent adolescent alcohol consumption in male and female animals. Thus, Wistar rats were given free access to ethanol (20% in drinking water or tap water for 2-h sessions during 3 days, and for an additional 4-h session on the 4th day; every week during adolescence, from postnatal day (pnd 28–52. During this period, animals consumed a moderate amount of alcohol despite blood ethanol concentration (BEC did not achieve binge-drinking levels. No withdrawal signs were observed: no changes were observed regarding anxiety-like responses in the elevated plus-maze or plasma corticosterone levels (pnd 53–54. In the novel object recognition (NOR test (pnd 63, a significant deficit in recognition memory was observed in both male and female rats. Western Blot analyses resulted in an increase in the expression of synaptophysin in the frontal cortex (FC of male and female animals, together with a decrease in the expression of the CB2R in the same brain region. In addition, adolescent alcohol induced, exclusively among females, a decrease in several markers of dopaminergic and serotonergic neurotransmission, in which epigenetic mechanisms, i.e., histone acetylation, might be involved. Taken together, further research is still needed to specifically correlate sex-specific brain and behavioral consequences of adolescent alcohol exposure.

  11. Effects of exposure to intermittent versus continuous red light on human circadian rhythms, melatonin suppression, and pupillary constriction.

    Science.gov (United States)

    Ho Mien, Ivan; Chua, Eric Chern-Pin; Lau, Pauline; Tan, Luuan-Chin; Lee, Ivan Tian-Guang; Yeo, Sing-Chen; Tan, Sara Shuhui; Gooley, Joshua J

    2014-01-01

    Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21-28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm(-2) s(-1)), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n = 8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light.

  12. Effects of exposure to intermittent versus continuous red light on human circadian rhythms, melatonin suppression, and pupillary constriction.

    Directory of Open Access Journals (Sweden)

    Ivan Ho Mien

    Full Text Available Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21-28 yr lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm(-2 s(-1, intermittent red light (1 min on/off, or bright white light (2,500 lux near the onset of nocturnal melatonin secretion (n = 8 in each group. Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69, with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light.

  13. Chronic intermittent but not constant hypoxia decreases NAA/Cr ratios in neonatal mouse hippocampus and thalamus.

    Science.gov (United States)

    Douglas, Robert M; Miyasaka, Naoyuki; Takahashi, Kan; Latuszek-Barrantes, Adrianna; Haddad, Gabriel G; Hetherington, Hoby P

    2007-03-01

    Chronic constant hypoxia (CCH) and chronic intermittent hypoxia (CIH) are known to have deleterious effects on the central nervous system. Because of the difference in the pattern of hypoxic exposure, it is possible that the pathological outcome would vary. The N-acetyl aspartate/creatine (NAA/Cr) ratio is a reliable marker of neuronal integrity, and this can be noninvasively measured by proton nuclear magnetic resonance spectroscopy. P2 CD1 mouse pups with their dams were exposed to either CCH, where the Fi(O(2)) was maintained at 11% continuously or to CIH, where the Fi(O(2)) was varied between 21 and 11% every 4 min. P30 mice exposed to intermittent hypoxia for 4 wk demonstrated a significant decrease in the NAA/Cr ratio in the hippocampus and thalamus, which was reversed by a subsequent exposure to 4 wk of normoxia. Meanwhile, mice exposed to 4 wk of constant hypoxia did not demonstrate any differences in their NAA/Cr ratios from controls in these brain regions. These results indicate that an intermittent pattern of hypoxic exposure may have a more adverse effect on neuronal function and integrity than a continuous one. The reversal of NAA/Cr levels to baseline during the return to normoxia indicates that therapeutic strategies targeted at alleviating the intermittent hypoxic stress in diseases, such as obstructive sleep apnea, have the potential for inducing significant neurocognitive recovery in these patients.

  14. Physiological Responses to Two Hypoxic Conditioning Strategies in Healthy Subjects.

    Science.gov (United States)

    Chacaroun, Samarmar; Borowik, Anna; Morrison, Shawnda A; Baillieul, Sébastien; Flore, Patrice; Doutreleau, Stéphane; Verges, Samuel

    2016-01-01

    Objective: Hypoxic exposure can be used as a therapeutic tool by inducing various cardiovascular, neuromuscular, and metabolic adaptations. Hypoxic conditioning strategies have been evaluated in patients with chronic diseases using either sustained (SH) or intermittent (IH) hypoxic sessions. Whether hypoxic conditioning via SH or IH may induce different physiological responses remains to be elucidated. Methods: Fourteen healthy active subjects (7 females, age 25 ± 8 years, body mass index 21.5 ± 2.5 kg·m -2 ) performed two interventions in a single blind, randomized cross-over design, starting with either 3 x SH (48 h apart), or 3 x IH (48 h apart), separated by a 2 week washout period. SH sessions consisted of breathing a gas mixture with reduced inspiratory oxygen fraction (FiO 2 ), continuously adjusted to reach arterial oxygen saturations (SpO 2 ) of 70-80% for 1 h. IH sessions consisted of 5 min with reduced FiO 2 (SpO 2 = 70-80%), followed by 3-min normoxia, repeated seven times. During the first (S1) and third (S3) sessions of each hypoxic intervention, cardiorespiratory parameters, and muscle and pre-frontal cortex oxygenation (near infrared spectroscopy) were assessed continuously. Results : Minute ventilation increased significantly during IH sessions (+2 ± 2 L·min -1 ) while heart rate increased during both SH (+11 ± 4 bpm) and IH (+13 ± 5 bpm) sessions. Arterial blood pressure increased during all hypoxic sessions, although baseline normoxic systolic blood pressure was reduced from S1 to S3 in IH only (-8 ± 11 mmHg). Muscle oxygenation decreased significantly during S3 but not S1, for both hypoxic interventions (S3: SH -6 ± 5%, IH -3 ± 4%); pre-frontal oxygenation decreased in S1 and S3, and to a greater extent in SH vs. IH (-13 ± 3% vs. -6 ± 6%). Heart rate variability indices indicated a significantly larger increase in sympathetic activity in SH vs. IH (lower SDNN, PNN50, and RMSSD values in SH). From S1 to S3, further reduction in heart

  15. Changes of body fluid and hematology in toad and their rehabilitation following intermittent exposure to simulated high altitude

    Science.gov (United States)

    Biswas, H. M.; Boral, M. C.

    1986-06-01

    Three groups of adult male toads were exposed intermittently in a decompression chamber for a daily period of 4 and 8 hours at a time for 6 consecutive days to an “altitude” of 12,000; 18,000 and 24,000 feet (3658; 5486; 7315 m) respectively. Most of the exposed animals were sacrificed immediately after the last exposure, but only a few animals experiencing 8 hours of exposure were sacrificed after a further 16 hours of exposure at normal atmospheric pressure. Eight hours of daily exposure for 6 days causes a decrease of body fluids and an increase of hematological parameters in all the altitude exposed animals compared with to the changes noted in the animals having 4 hours of daily exposure for 6 days at the same altitude levels. The animals that were exposed to pressures equivalent to altitudes of 12,000 and 18,000 feet daily for 8 hours were found to return nearly to their normal body fluids and hematological balance after 16 hours of exposure to normal atmospheric pressure, whereas the animals exposed for a similar period at an equivalent 24,000 feet failed to get back their normal balance of body fluids and hematology after 16 hours of exposure at normal atmospheric pressure. The present experiment shows that the body weight loss and changes of body fluid and hematological parameters in the toad after exposure to simulated high altitude are due not only to dehydration, but suggest that hypoxia may also have a role.

  16. Framework for human health risk assessment of non-cancer effects resulting from short-duration and intermittent exposures to chemicals.

    Science.gov (United States)

    Haber, Lynne T; Sandhu, Reena; Li-Muller, Angela; Mohapatra, Asish; Petrovic, Sanya; Meek, M E Bette

    2016-09-01

    Durations of exposure to chemicals, whether for single, repeated or intermittent periods, may vary from those upon which most guidance values are normally based. Because it is presently not feasible to conduct toxicity studies or develop toxicity reference values (TRVs) specific to each scenario of interest, methods are needed to address these various durations, drawing as much as possible on existing TRVs. A working framework was developed to address the potential for non-cancer effects resulting from continuous short-duration and intermittent exposures to chemicals. The framework presents an integrated, tiered approach that assists the user in identifying when existing TRVs can be applied directly, and the adaptations needed to assess the acceptability of short-duration or intermittent exposure scenarios. Descriptions of when and how toxicokinetic and toxicodynamic aspects need to be taken into consideration are also presented. The framework incorporates the use of TRVs based on exposure periods as similar as possible to the "actual" exposure periods and application of dose averaging under limited, specified conditions. This framework has been developed to aid in improving the scientific basis for the evaluation of short-duration and intermittent exposures in a variety of settings. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Hypoxic Episodes in Bronchopulmonary Dysplasia.

    Science.gov (United States)

    Martin, Richard J; Di Fiore, Juliann M; Walsh, Michele C

    2015-12-01

    Hypoxic episodes are troublesome components of bronchopulmonary dysplasia (BPD) in preterm infants. Immature respiratory control seems to be the major contributor, superimposed on abnormal respiratory function. Relatively short respiratory pauses may precipitate desaturation and bradycardia. This population is predisposed to pulmonary hypertension; it is likely that pulmonary vasoconstriction also plays a role. The natural history has been well-characterized in the preterm population at risk for BPD; however, the consequences are less clear. Proposed associations of intermittent hypoxia include retinopathy of prematurity, sleep disordered breathing, and neurodevelopmental delay. Future study should address whether these associations are causal relationships. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Intermittent PTHrP(1–34) Exposure Augments Chondrogenesis and Reduces Hypertrophy of Mesenchymal Stromal Cells

    Science.gov (United States)

    Fischer, Jennifer; Aulmann, Antje; Dexheimer, Verena; Grossner, Tobias

    2014-01-01

    Phenotype instability and premature hypertrophy prevent the use of human mesenchymal stromal cells (MSCs) for cartilage regeneration. Aim of this study was to investigate whether intermittent supplementation of parathyroid hormone-related protein (PTHrP), as opposed to constant treatment, can beneficially influence MSC chondrogenesis and to explore molecular mechanisms below catabolic and anabolic responses. Human MSCs subjected to chondrogenic induction in high-density culture received PTHrP(1–34), forskolin, dbcAMP, or PTHrP(7–34) either constantly or via 6-h pulses (three times weekly), before proteoglycan, collagen type II, and X deposition; gene expression; and alkaline phosphatase (ALP) activity were assessed. While constant application of PTHrP(1–34) suppressed chondrogenesis of MSCs, pulsed application significantly increased collagen type 2 (COL2A1) gene expression and the collagen type II, proteoglycan, and DNA content of pellets after 6 weeks. Collagen type 10 (COL10A1) gene expression was little affected but Indian hedgehog (IHH) expression and ALP activity were significantly downregulated by pulsed PTHrP. A faster response to PTHrP exposure was recorded for ALP activity over COL2A1 regulation, suggesting that signal duration is critical for catabolic versus anabolic reactions. Stimulation of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling by forskolin reproduced major effects of both treatment modes, whereas application of PTHrP(7–34) capable of protein kinase C (PKC) signaling was ineffective. Pulsed PTHrP exposure of MSCs stimulated chondrogenesis and reduced endochondral differentiation apparently uncoupling chondrogenic matrix deposition from hypertrophic marker expression. cAMP/PKA was the major signaling pathway triggering the opposing effects of both treatment modes. Intermittent application of PTHrP represents an important novel means to improve chondrogenesis of MSCs and may be considered as a supporting clinical

  19. Chronic intermittent ethanol exposure and withdrawal leads to adaptations in nucleus accumbens core postsynaptic density proteome and dendritic spines.

    Science.gov (United States)

    Uys, Joachim D; McGuier, Natalie S; Gass, Justin T; Griffin, William C; Ball, Lauren E; Mulholland, Patrick J

    2016-05-01

    Alcohol use disorder is a chronic relapsing brain disease characterized by the loss of ability to control alcohol (ethanol) intake despite knowledge of detrimental health or personal consequences. Clinical and pre-clinical models provide strong evidence for chronic ethanol-associated alterations in glutamatergic signaling and impaired synaptic plasticity in the nucleus accumbens (NAc). However, the neural mechanisms that contribute to aberrant glutamatergic signaling in ethanol-dependent individuals in this critical brain structure remain unknown. Using an unbiased proteomic approach, we investigated the effects of chronic intermittent ethanol (CIE) exposure on neuroadaptations in postsynaptic density (PSD)-enriched proteins in the NAc of ethanol-dependent mice. Compared with controls, CIE exposure significantly changed expression levels of 50 proteins in the PSD-enriched fraction. Systems biology and functional annotation analyses demonstrated that the dysregulated proteins are expressed at tetrapartite synapses and critically regulate cellular morphology. To confirm this latter finding, the density and morphology of dendritic spines were examined in the NAc core of ethanol-dependent mice. We found that CIE exposure and withdrawal differentially altered dendrite diameter and dendritic spine density and morphology. Through the use of quantitative proteomics and functional annotation, these series of experiments demonstrate that ethanol dependence produces neuroadaptations in proteins that modify dendritic spine morphology. In addition, these studies identified novel PSD-related proteins that contribute to the neurobiological mechanisms of ethanol dependence that drive maladaptive structural plasticity of NAc neurons. © 2015 Society for the Study of Addiction.

  20. Intermittent Exposure to Social Defeat and Open-field Test in Rats : Acute and Long-term Effects on ECG, Body Temperature and Physical Activity

    NARCIS (Netherlands)

    Sgoifo, Andrea; Pozzato, Chiara; Meerlo, Peter; Costoli, Tania; Manghi, Massimo; Stilli, Donatella; Olivetti, Giorgio; Musso, Ezio

    2002-01-01

    This study investigated the effects of exposure to an intermittent homotypic stressor on: (i) habituation of acute autonomic responsivity (i.e. cardiac sympathovagal balance and susceptibility to arrhythmias), and (ii) circadian rhythmicity of heart rate, body temperature, and physical activity.

  1. Motives of Dutch men who have sex with men for daily and intermittent HIV pre-exposure prophylaxis usage and preferences for implementation: A qualitative study

    NARCIS (Netherlands)

    Bil, Janneke P.; van der Veldt, Wendy M.; Prins, Maria; Stolte, Ineke G.; Davidovich, Udi

    2016-01-01

    Although PrEP is not yet registered in Europe, including the Netherlands, its approval and implementation are expected in the near future. To inform future pre-exposure prophylaxis (PrEP) implementation, this study aimed to gain insight into motives and preferences for daily or intermittent PrEP use

  2. Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

    Science.gov (United States)

    Pamenter, Matthew E.; Powell, Frank L.

    2016-01-01

    Ventilatory responses to hypoxia vary widely depending on the pattern and length of hypoxic exposure. Acute, prolonged, or intermittent hypoxic episodes can increase or decrease breathing for seconds to years, both during the hypoxic stimulus, and also after its removal. These myriad effects are the result of a complicated web of molecular interactions that underlie plasticity in the respiratory control reflex circuits and ultimately control the physiology of breathing in hypoxia. Since the time domains of the physiological hypoxic ventilatory response (HVR) were identified, considerable research effort has gone toward elucidating the underlying molecular mechanisms that mediate these varied responses. This research has begun to describe complicated and plastic interactions in the relay circuits between the peripheral chemoreceptors and the ventilatory control circuits within the central nervous system. Intriguingly, many of these molecular pathways seem to share key components between the different time domains, suggesting that varied physiological HVRs are the result of specific modifications to overlapping pathways. This review highlights what has been discovered regarding the cell and molecular level control of the time domains of the HVR, and highlights key areas where further research is required. Understanding the molecular control of ventilation in hypoxia has important implications for basic physiology and is emerging as an important component of several clinical fields. PMID:27347896

  3. Neuroprotective Role of Intermittent Hypobaric Hypoxia in Unpredictable Chronic Mild Stress Induced Depression in Rats

    Science.gov (United States)

    Deep, Satayanarayan; Prasad, Dipti; Singh, Shashi Bala; Khan, Nilofar

    2016-01-01

    Hypoxic exposure results in several pathophysiological conditions associated with nervous system, these include acute and chronic mountain sickness, loss of memory, and high altitude cerebral edema. Previous reports have also suggested the role of hypoxia in pathogenesis of depression and related psychological conditions. On the other hand, sub lethal intermittent hypoxic exposure induces protection against future lethal hypoxia and may have beneficial effect. Therefore, the present study was designed to explore the neuroprotective role of intermittent hypobaric hypoxia (IHH) in Unpredictable Chronic Mild Stress (UCMS) induced depression like behaviour in rats. The IHH refers to the periodic exposures to hypoxic conditions interrupted by the normoxic or lesser hypoxic conditions. The current study examines the effect of IHH against UCMS induced depression, using elevated plus maze (EPM), open field test (OFT), force swim test (FST), as behavioural paradigm and related histological and molecular approaches. The data indicated the UCMS induced depression like behaviour as evident from decreased exploration activity in OFT with increased anxiety levels in EPM, and increased immobility time in the FST; whereas on providing the IHH (5000m altitude, 4hrs/day for two weeks) these behavioural changes were ameliorated. The morphological and molecular studies also validated the neuroprotective effect of IHH against UCMS induced neuronal loss and decreased neurogenesis. Here, we also explored the role of Brain-Derived Neurotrophic Factor (BDNF) in anticipatory action of IHH against detrimental effect of UCMS as upon blocking of BDNF-TrkB signalling the beneficial effect of IHH was nullified. Taken together, the findings of our study demonstrate that the intermittent hypoxia has a therapeutic potential similar to an antidepressant in animal model of depression and could be developed as a preventive therapeutic option against this pathophysiological state. PMID:26901349

  4. Neuroprotective Role of Intermittent Hypobaric Hypoxia in Unpredictable Chronic Mild Stress Induced Depression in Rats.

    Directory of Open Access Journals (Sweden)

    Neetu Kushwah

    Full Text Available Hypoxic exposure results in several pathophysiological conditions associated with nervous system, these include acute and chronic mountain sickness, loss of memory, and high altitude cerebral edema. Previous reports have also suggested the role of hypoxia in pathogenesis of depression and related psychological conditions. On the other hand, sub lethal intermittent hypoxic exposure induces protection against future lethal hypoxia and may have beneficial effect. Therefore, the present study was designed to explore the neuroprotective role of intermittent hypobaric hypoxia (IHH in Unpredictable Chronic Mild Stress (UCMS induced depression like behaviour in rats. The IHH refers to the periodic exposures to hypoxic conditions interrupted by the normoxic or lesser hypoxic conditions. The current study examines the effect of IHH against UCMS induced depression, using elevated plus maze (EPM, open field test (OFT, force swim test (FST, as behavioural paradigm and related histological and molecular approaches. The data indicated the UCMS induced depression like behaviour as evident from decreased exploration activity in OFT with increased anxiety levels in EPM, and increased immobility time in the FST; whereas on providing the IHH (5000m altitude, 4hrs/day for two weeks these behavioural changes were ameliorated. The morphological and molecular studies also validated the neuroprotective effect of IHH against UCMS induced neuronal loss and decreased neurogenesis. Here, we also explored the role of Brain-Derived Neurotrophic Factor (BDNF in anticipatory action of IHH against detrimental effect of UCMS as upon blocking of BDNF-TrkB signalling the beneficial effect of IHH was nullified. Taken together, the findings of our study demonstrate that the intermittent hypoxia has a therapeutic potential similar to an antidepressant in animal model of depression and could be developed as a preventive therapeutic option against this pathophysiological state.

  5. A Novel Chip for Cyclic Stretch and Intermittent Hypoxia Cell Exposures Mimicking Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Noelia Campillo

    2016-07-01

    Full Text Available Intermittent hypoxia (IH, a hallmark of obstructive sleep apnea (OSA, plays a critical role in the pathogenesis of OSA-associated morbidities, especially in the cardiovascular and respiratory systems. Oxidative stress and inflammation induced by IH are suggested as main contributors of end-organ dysfunction in OSA patients and animal models. Since the molecular mechanisms underlying these in vivo pathological responses remain poorly understood, implementation of experimental in vitro cell-based systems capable of inducing high-frequency IH would be highly desirable. Here, we describe the design, fabrication and validation of a versatile chip for subjecting cultured cells to fast changes in gas partial pressure and to cyclic stretch. The chip is fabricated with polydimethylsiloxane (PDMS and consists of a cylindrical well covered by a thin membrane. Cells cultured on top of the membrane can be subjected to fast changes in oxygen concentration (equilibrium time 6 s. Moreover, cells can be subjected to cyclic stretch at cardiac or respiratory frequencies independently or simultaneously. Rat bone marrow-derived mesenchymal stem cells (MSCs exposed to IH mimicking OSA and cyclic stretch at cardiac frequencies revealed that hypoxia-inducible factor 1α (HIF-1α expression was increased in response to both stimuli. Thus, the chip provides a versatile tool for the study of cellular responses to cyclical hypoxia and stretch.

  6. Oxidative stress in erythrocytes: a study on the effect of antioxidant mixtures during intermittent exposures to high altitude

    Science.gov (United States)

    Vani, R.; Shiva Shankar Reddy, C. S.; Asha Devi, S.

    2010-09-01

    The aim of our study was to compare and assess the effectiveness of antioxidant mixtures on the erythrocytes (RBC) of adult male albino rats (Wister) subjected to simulated intermittent high altitudes—5,100 m (AL1) and 6,700 m (AL2)—to induce oxidative stress (OS). To achieve our objective, we pre-supplemented four sets of animals with different antioxidant mixtures [vitamin E (vit.E; 50 IU/kg BW), vitamin C (vit.C; 400 mg/kg) and l-carnitine (400 mg/kg)] in different combinations [M1 (vit.E+vit.C), M2 (vit.C+carnitine), M3 (vit.E+carnitine) and M4 (vit.C+vit.E+carnitine)] for 30 days prior to as well during exposure to intermittent hypobaric hypoxia (IHH). Membrane instability, in terms of osmotic fragility and hemolysis, decreased in RBCs of supplemented animals. There was a significant increase in the activity of glutathione peroxidase in the RBCs of supplemented animals. We confirmed OS imposed by IHH with assays relating to lipid [thiobarbituric acid reactive substances (TBARS) and lipofuscin (LF)] and protein (carbonyl, PrC) oxidation, and found a positive correlation between PrC and hemolysis, with a decrease in both upon supplementation with M3 and M4 mixtures. Fluorescence microscopic observation showed a maximum decrease in the LF content in rats administered M4 and M1 compared to those on M2 and M3 mixtures at both altitudes. We suggest that multiple antioxidant fortifications are effective in overcoming increased OS experienced by RBCs at high altitudes.

  7. Hearing effects from intermittent and continuous noise exposure in a study of Korean factory workers and firefighters

    Directory of Open Access Journals (Sweden)

    Chung In-Sung

    2012-01-01

    Full Text Available Abstract Background South Korea and surrounding countries in East Asia are believed to have the highest proportion in the world of high frequency hearing loss due to occupational noise exposure, yet there has been limited information published in international journals, and limited information for control of noise in local workplaces beyond strategies from western countries. We exploit medical surveillance information from two worker groups to enhance local knowledge about noise-induced hearing loss and explore the possible importance of shift work to risk. Methods Four-years of hearing data were evaluated for 81 male farm machine factory workers and 371 male firefighters who had successfully completed a health examination and questionnaires for the duration of the study period. The averages of hearing thresholds at 2, 3, and 4 kHz were used as the primary end-point for comparison. Repeat measure analysis adjusted for age, exposure duration and smoking status was used to measure the difference in hearing threshold between the two groups. Results Noise levels were measured in the factory at a mean of 82 dBA, with a range of 66-97. No concurrent measurements were taken for the firefighters, but historic comparison values showed a wider range but a similar mean of 76-79 dBA. Although losses during follow-up were negligible, the factory workers had significantly (P 25 dB loss. Firefighters also showed increased losses associated with longer exposure duration, but these were significantly less marked. Losses at lower frequencies ( Conclusions Korean work environments with continuous noise exposure in the measured range should consider implementation of a hearing conservation program. Further evaluation of hearing loss in workers exposed to irregular or intermittent high noise levels, such as firefighters, is also warranted.

  8. Early postnatal exposure to intermittent hypoxia in rodents is proinflammatory, impairs white matter integrity, and alters brain metabolism.

    Science.gov (United States)

    Darnall, Robert A; Chen, Xi; Nemani, Krishnamurthy V; Sirieix, Chrystelle M; Gimi, Barjor; Knoblach, Susan; McEntire, Betty L; Hunt, Carl E

    2017-07-01

    BackgroundPreterm infants are frequently exposed to intermittent hypoxia (IH) associated with apnea and periodic breathing that may result in inflammation and brain injury that later manifests as cognitive and executive function deficits. We used a rodent model to determine whether early postnatal exposure to IH would result in inflammation and brain injury.MethodsRat pups were exposed to IH from P2 to P12. Control animals were exposed to room air. Cytokines were analyzed in plasma and brain tissue at P13 and P18. At P20-P22, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) were performed.ResultsPups exposed to IH had increased plasma Gro/CXCL1 and cerebellar IFN-γ and IL-1β at P13, and brainstem enolase at P18. DTI showed a decrease in FA and AD in the corpus callosum (CC) and cingulate gyrus, and an increase in RD in the CC. MRS revealed decreases in NAA/Cho, Cr, Tau/Cr, and Gly/Cr; increases in TCho and GPC in the brainstem; and decreases in NAA/Cho in the hippocampus.ConclusionsWe conclude that early postnatal exposure to IH, similar in magnitude to that experienced in human preterm infants, is associated with evidence for proinflammatory changes, decreases in white matter integrity, and metabolic changes consistent with hypoxia.

  9. Thermal responses from repeated exposures to severe cold with intermittent warmer temperatures.

    Science.gov (United States)

    Ozaki, H; Enomoto-Koshimizu, H; Tochihara, Y; Nakamura, K

    1998-09-01

    This study was conducted to evaluate physiological reaction and manual performance during exposure to warm (30 degrees C) and cool (10 degrees C) environments after exposure to very low temperatures (-25 degrees C). Furthermore, this experiment was conducted to study whether it is desirable to remove cold-protective jackets in warmer rooms after severe cold exposure. Eight male students remained in an extremely cold room for 20 min, after which they transferred into either the warm room or the cool room for 20 min. This pattern was repeated three times, and the total cold exposure time was 60 min. In the warm and cool rooms, the subjects either removed their cold-protective jackets (Condition A), or wore them continuously (Condition B). Rectal temperature, skin temperatures, manual performance, blood pressure, thermal, comfort and pain sensations were measured during the experiment. The effects of severe cold on almost all measurements in the cool (10 degrees C) environment were greater than those in the warm (30 degrees C) environment under both clothing conditions. The effects of severe cold on all measurements under Condition A except rectal temperature and toe skin temperature were significantly greater than those under Condition B in the cool environment but, not at all differences between Condition A and Condition B in the warm environments were significant. It was recognized that to remove cold-protective jackets in the cool room (10 degrees C) after severe cold exposure promoted the effects of severe cold. When rewarming in the warm resting room (30 degrees C), the physiological and psychological responses and manual performance were not influenced by the presence or absence of cold-protective clothing. These results suggest that it is necessary for workers to make sure to rewarm in the warm room outside of the cold storage and continue to wear cold-protective clothing in the cool room.

  10. Understanding Adherence to Daily and Intermittent Regimens of Oral HIV Pre-exposure Prophylaxis Among Men Who Have Sex with Men in Kenya.

    Science.gov (United States)

    Mugo, Peter Mwangi; Sanders, Eduard J; Mutua, Gaudensia; van der Elst, Elisabeth; Anzala, Omu; Barin, Burc; Bangsberg, David R; Priddy, Frances H; Haberer, Jessica E

    2015-05-01

    A qualitative assessment of Kenyan men who have sex with men taking daily and intermittent oral HIV pre-exposure prophylaxis (PrEP) found stigma, sex work, mobility, and alcohol impacted adherence. We analyzed quantitative data from the same cohort to explore different definitions of intermittent adherence. Volunteers were randomized to daily emtricitabine/tenofovir or placebo, or intermittent (prescription: Mondays/Fridays/after sex, maximum 1 dose/day) emtricitabine/tenofovir or placebo (2:1:2:1), and followed for 4 months. By electronic monitoring, median adherence for daily dosing was 80 %. Median adherence for intermittent dosing was 71 % per a "relaxed" definition (accounting for off-prescription dosing) and 40 % per a "strict" definition (limited to the prescription). Factors associated with lower adherence included travel, transactional sex, and longer follow-up; higher adherence was associated with daily dosing and an income. The definition of intermittent dosing strongly affects interpretation of adherence. These findings suggest interventions should address challenges of mobility, sex work, and long-term PrEP.

  11. Changes in orexinergic immunoreactivity of the piglet hypothalamus and pons after exposure to chronic postnatal nicotine and intermittent hypercapnic hypoxia.

    Science.gov (United States)

    Hunt, Nicholas J; Russell, Benjamin; Du, Man K; Waters, Karen A; Machaalani, Rita

    2016-06-01

    We recently showed that orexin expression in sudden infant death syndrome (SIDS) infants was reduced by 21% in the hypothalamus and by 40-50% in the pons as compared with controls. Orexin maintains wakefulness/sleeping states, arousal, and rapid eye movement sleep, abnormalities of which have been reported in SIDS. This study examined the effects of two prominent risk factors for SIDS, intermittent hypercapnic hypoxia (IHH) (prone-sleeping) and chronic nicotine exposure (cigarette-smoking), on orexin A (OxA) and orexin B (OxB) expression in piglets. Piglets were randomly assigned to five groups: saline control (n = 7), air control (n = 7), nicotine [2 mg/kg per day (14 days)] (n = 7), IHH (6 min of 7% O2 /8% CO2 alternating with 6-min periods of breathing air, for four cycles) (n = 7), and the combination of nicotine and IHH (N + IHH) (n = 7). OxA/OxB expression was quantified in the central tuberal hypothalamus [dorsal medial hypothalamus (DMH), perifornical area (PeF), and lateral hypothalamus], and the dorsal raphe, locus coeruleus of the pons. Nicotine and N + IHH exposures significantly increased: (i) orexin expression in the hypothalamus and pons; and (ii) the total number of neurons in the DMH and PeF. IHH decreased orexin expression in the hypothalamus and pons without changing neuronal numbers. Linear relationships existed between the percentage of orexin-positive neurons and the area of pontine orexin immunoreactivity of control and exposure piglets. These results demonstrate that postnatal nicotine exposure increases the proportion of orexin-positive neurons in the hypothalamus and fibre expression in the pons, and that IHH exposure does not prevent the nicotine-induced increase. Thus, although both nicotine and IHH are risk factors for SIDS, it appears they have opposing effects on OxA and OxB expression, with the IHH exposure closely mimicking what we recently found in SIDS. © 2016 Federation of European Neuroscience Societies and John

  12. Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells

    DEFF Research Database (Denmark)

    Dreyer-Andersen, Nanna; Almeida, Ana Sofia; Jensen, Pia

    2018-01-01

    cells constitute an alternative source of cells for transplantation in Parkinson's disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting...... in both protection and generation of reactive oxygen species. The present study investigated the effect of CO produced by a novel CO-releasing molecule on dopaminergic differentiation of human neural stem cells. Short-term exposure to 25 ppm CO at days 0 and 4 significantly increased the relative content...... of β-tubulin III-immunoreactive immature neurons and tyrosine hydroxylase expressing catecholaminergic neurons, as assessed 6 days after differentiation. Also the number of microtubule associated protein 2-positive mature neurons had increased significantly. Moreover, the content of apoptotic cells...

  13. An ontogenic study of the behavioral effects of chronic intermittent exposure to ayahuasca in mice.

    Science.gov (United States)

    Correa-Netto, N F; Masukawa, M Y; Nishide, F; Galfano, G S; Tamura, F; Shimizo, M K; Marcato, M P; Santos, J G; Linardi, A

    2017-06-05

    Ayahuasca is a beverage obtained from decoctions of the Banisteriopsis caapi plus Psychotria viridis. In religious contexts, ayahuasca is used by different age groups. However, little is known of the effects of ayahuasca during ontogenic development, particularly with regard to the functional characteristics of the central nervous system. Animal models are useful for studying the ontogenic effects of ayahuasca because they allow exclusion of the behavioral influence associated with the ritualistic use. We investigated the effects of exposure to ayahuasca (1.5 mL/kg, orally, twice a week) on memory and anxiety in C57BL/6 mice, with the post-natal day (PND) being used as the ontogenic criterion for classification: childhood (PND21 to PND35), adolescence (PND35 to PND63), adulthood (PND90-PND118), childhood-adolescence (PND21 to PND63), childhood-adulthood (PND21 to PND118) and adolescence-adulthood (PND35 to PND118). One day after the last ayahuasca exposure, the mice were subjected to the Morris water maze (MWM), open field and elevated plus maze tasks (EPM). Ayahuasca did not affect locomotion in the open field or open arms exploration in the EPM, but increased the risk assessment behavior in the childhood group. Ayahuasca did not cause any change in acquisition of spatial reference memory in the MWM task, but decreased the time spent on the platform quadrant during the test session in the adolescence group. These results suggest that, in mice, exposure to ayahuasca in childhood and adolescence promoted anxiety and memory impairment, respectively. However, these behavioral changes were not long-lasting since they were not observed in the childhood-adulthood and adolescence-adulthood groups.

  14. An ontogenic study of the behavioral effects of chronic intermittent exposure to ayahuasca in mice

    Directory of Open Access Journals (Sweden)

    N.F. Correa-Netto

    Full Text Available Ayahuasca is a beverage obtained from decoctions of the Banisteriopsis caapi plus Psychotria viridis. In religious contexts, ayahuasca is used by different age groups. However, little is known of the effects of ayahuasca during ontogenic development, particularly with regard to the functional characteristics of the central nervous system. Animal models are useful for studying the ontogenic effects of ayahuasca because they allow exclusion of the behavioral influence associated with the ritualistic use. We investigated the effects of exposure to ayahuasca (1.5 mL/kg, orally, twice a week on memory and anxiety in C57BL/6 mice, with the post-natal day (PND being used as the ontogenic criterion for classification: childhood (PND21 to PND35, adolescence (PND35 to PND63, adulthood (PND90-PND118, childhood-adolescence (PND21 to PND63, childhood-adulthood (PND21 to PND118 and adolescence-adulthood (PND35 to PND118. One day after the last ayahuasca exposure, the mice were subjected to the Morris water maze (MWM, open field and elevated plus maze tasks (EPM. Ayahuasca did not affect locomotion in the open field or open arms exploration in the EPM, but increased the risk assessment behavior in the childhood group. Ayahuasca did not cause any change in acquisition of spatial reference memory in the MWM task, but decreased the time spent on the platform quadrant during the test session in the adolescence group. These results suggest that, in mice, exposure to ayahuasca in childhood and adolescence promoted anxiety and memory impairment, respectively. However, these behavioral changes were not long-lasting since they were not observed in the childhood-adulthood and adolescence-adulthood groups.

  15. Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells

    DEFF Research Database (Denmark)

    Dreyer-Andersen, Nanna; Almeida, Ana Sofia; Jensen, Pia

    2018-01-01

    Exploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson's disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem...... cells constitute an alternative source of cells for transplantation in Parkinson's disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting...... in Parkinson's disease....

  16. Chronic intermittent exposure to ayahuasca during aging does not affect memory in mice

    Directory of Open Access Journals (Sweden)

    N.F. Correa-Netto

    Full Text Available The Quechua term ayahuasca refers to a beverage obtained from decoctions of the liana Banisteriopsis caapi with leaves of Psychotria viridis. The ritualistic use of ayahuasca is becoming a global phenomenon, with some individuals using this beverage throughout life, including in old age. Cognitive impairment is a common manifestation during aging. There are conflicting reports on the ability of some ayahuasca compounds to exert neuroprotective or neurotoxic effects that could improve or impair learning and memory. Animal models provide a relevant and accessible means of investigating the behavioral effects of ayahuasca without the environmental conditions associated with the ritualistic use of the beverage. In this study, we investigated the influence of chronic ayahuasca exposure throughout aging on the spatial reference and habituation memories of mice. Twenty-eight male c57bl/6 mice (6 months old received ayahuasca or water (1.5 mL/kg, orally twice a week for 12 months and were tested in the Morris water maze (MWM, open field and elevated plus maze (EPM tasks before and after treatment. During aging, there was significant impairment in the evocation (but not acquisition of spatial reference memory and in habituation to the open field. There was also a decrease in locomotor activity in the open field and EPM tests, whereas the anxiety parameters were unaltered. Ayahuasca treatment did not alter any of these parameters associated with aging. These findings indicate that chronic exposure to ayahuasca during aging did not affect memory in mice.

  17. Chronic intermittent exposure to ayahuasca during aging does not affect memory in mice.

    Science.gov (United States)

    Correa-Netto, N F; Coelho, L S; Galfano, G S; Nishide, F; Tamura, F; Shimizu, M K; Santos, J G; Linardi, A

    2017-06-05

    The Quechua term ayahuasca refers to a beverage obtained from decoctions of the liana Banisteriopsis caapi with leaves of Psychotria viridis. The ritualistic use of ayahuasca is becoming a global phenomenon, with some individuals using this beverage throughout life, including in old age. Cognitive impairment is a common manifestation during aging. There are conflicting reports on the ability of some ayahuasca compounds to exert neuroprotective or neurotoxic effects that could improve or impair learning and memory. Animal models provide a relevant and accessible means of investigating the behavioral effects of ayahuasca without the environmental conditions associated with the ritualistic use of the beverage. In this study, we investigated the influence of chronic ayahuasca exposure throughout aging on the spatial reference and habituation memories of mice. Twenty-eight male c57bl/6 mice (6 months old) received ayahuasca or water (1.5 mL/kg, orally) twice a week for 12 months and were tested in the Morris water maze (MWM), open field and elevated plus maze (EPM) tasks before and after treatment. During aging, there was significant impairment in the evocation (but not acquisition) of spatial reference memory and in habituation to the open field. There was also a decrease in locomotor activity in the open field and EPM tests, whereas the anxiety parameters were unaltered. Ayahuasca treatment did not alter any of these parameters associated with aging. These findings indicate that chronic exposure to ayahuasca during aging did not affect memory in mice.

  18. In vitro effects of piracetam on the radiosensitivity of hypoxic cells (adaptation of MTT assay to hypoxic conditions)

    International Nuclear Information System (INIS)

    Gheuens, E.E.O.; Bruijn, E.A. de; Van der Heyden, S.; Van Oosterom, A.T.; Lagarde, P.; Pooter, C.M.J. de; Chomy, F.

    1995-01-01

    This paper describes the adaptation of the MTT assay to hypoxic conditions in order to test the in vitro effect of piracetam on hypoxic cells and particularly on the radiosensitivity of hypoxic cells since this drug has shown clinical effect on acute and chronic hypoxia. The V79 cell line was selected by reference to preliminary hypoxic experiments using clonogenic assay and euoxic experiments using clonogenic and MTT assays. Cell growth and survival in our hypoxic conditions were assessed using MTT assay with an enclosure and special 48-well plates both made of glass. Growth curves on glass plates after 1-hour exposure to nitrogen versus air were comparable, so there is no bias effect due to gas composition. Survival curves using MTT versus reference clonogenic assay were comparable after radiation exposure in eu- and hypoxic conditions, and confirm the validity of our original technique for creating hypoxia. The Oxygen Enhancement Ratio was of about 3 for 1-hour hypoxic exposure. Piracetam gave no cytotoxic effect up to 10 mM of piracetam. Growth curves after continuous drug exposure and 1-hour euoxic versus hypoxic exposure gave no cytotoxic effect up to 10 mM of piracetam. Survival curves after continuous drug exposure to 10 mM of piracetam gave no significant effect on the radiosensitivity of hypoxic V79 cells using MTT or clonogenic assay. (author). 32 refs., 6 figs

  19. Using tensor-based morphometry to detect structural brain abnormalities in rats with adolescent intermittent alcohol exposure

    Science.gov (United States)

    Paniagua, Beatriz; Ehlers, Cindy; Crews, Fulton; Budin, Francois; Larson, Garrett; Styner, Martin; Oguz, Ipek

    2011-03-01

    Understanding the effects of adolescent binge drinking that persist into adulthood is a crucial public health issue. Adolescent intermittent ethanol exposure (AIE) is an animal model that can be used to investigate these effects in rodents. In this work, we investigate the application of a particular image analysis technique, tensor-based morphometry, for detecting anatomical differences between AIE and control rats using Diffusion Tensor Imaging (DTI). Deformation field analysis is a popular method for detecting volumetric changes analyzing Jacobian determinants calculated on deformation fields. Recent studies showed that computing deformation field metrics on the full deformation tensor, often referred to as tensor-based morphometry (TBM), increases the sensitivity to anatomical differences. In this paper we conduct a comprehensive TBM study for precisely locating differences between control and AIE rats. Using a DTI RARE sequence designed for minimal geometric distortion, 12-directional images were acquired postmortem for control and AIE rats (n=9). After preprocessing, average images for the two groups were constructed using an unbiased atlas building approach. We non-rigidly register the two atlases using Large Deformation Diffeomorphic Metric Mapping, and analyze the resulting deformation field using TBM. In particular, we evaluate the tensor determinant, geodesic anisotropy, and deformation direction vector (DDV) on the deformation field to detect structural differences. This yields data on the local amount of growth, shrinkage and the directionality of deformation between the groups. We show that TBM can thus be used to measure group morphological differences between rat populations, demonstrating the potential of the proposed framework.

  20. Chronic intermittent ethanol exposure during adolescence: Effects on stress-induced social alterations and social drinking in adulthood.

    Science.gov (United States)

    Varlinskaya, Elena I; Kim, Esther U; Spear, Linda P

    2017-01-01

    We previously observed lasting and sex-specific detrimental consequences of early adolescent intermittent ethanol exposure (AIE), with male, but not female, rats showing social anxiety-like alterations when tested as adults. The present study used Sprague Dawley rats to assess whether social alterations induced by AIE (3.5g/kg, intragastrically, every other day, between postnatal days [P] 25-45) are further exacerbated by stressors later in life. Another aim was to determine whether AIE alone or in combination with stress influenced intake of a sweetened ethanol solution (Experiment 1) or a sweetened solution ("supersac") alone (Experiment 2) under social circumstances. Animals were exposed to restraint on P66-P70 (90min/day) or left nonstressed, with corticosterone (CORT) levels assessed on day 1 and day 5 in Experiment 2. Social anxiety-like behavior emerged after AIE in non-stressed males, but not females, whereas stress-induced social anxiety was evident only in water-exposed males and females. Adult-typical habituation of the CORT response to repeated restraint was not evident in adult animals after AIE, a lack of habituation reminiscent of that normally evident in adolescents. Neither AIE nor stress affected ethanol intake under social circumstances, although AIE and restraint independently increased adolescent-typical play fighting in males during social drinking. Among males, the combination of AIE and restraint suppressed "supersac" intake; this index of depression-like behavior was not seen in females. The results provide experimental evidence associating adolescent alcohol exposure, later stress, anxiety, and depression, with young adolescent males being particularly vulnerable to long-lasting adverse effects of repeated ethanol. This article is part of a Special Issue entitled SI: Adolescent plasticity. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Energy intermittency

    CERN Document Server

    Sorensen, Bent

    2014-01-01

    The first book to consider intermittency as a key point of an energy system, Energy Intermittency describes different levels of variability for traditional and renewable energy sources, presenting detailed solutions for handling energy intermittency through trade, collaboration, demand management, and active energy storage. Addressing energy supply intermittency systematically, this practical text:Analyzes typical time-distributions and intervals between episodes of demand-supply mismatch and explores their dependence on system layouts and energy source characteristicsSimulates scenarios regar

  2. Increased expression of protein kinase A inhibitor alpha (PKI-alpha) and decreased PKA-regulated genes in chronic intermittent alcohol exposure.

    Science.gov (United States)

    Repunte-Canonigo, Vez; Lutjens, Robert; van der Stap, Lena D; Sanna, Pietro Paolo

    2007-03-23

    Intermittent models of alcohol exposure that mimic human patterns of alcohol consumption produce profound physiological and biochemical changes and induce rapid increases in alcohol self-administration. We used high-density oligonucleotide microarrays to investigate gene expression changes during chronic intermittent alcohol exposure in three brain regions that receive mesocorticolimbic dopaminergic projections and that are believed to be involved in alcohol's reinforcing actions: the medial prefrontal cortex, the nucleus accumbens and the amygdala. An independent replication of the experiment was used for RT-PCR validation of the microarray results. The protein kinase A inhibitor alpha (PKI-alpha, Pkia), a member of the endogenous PKI family implicated in reducing nuclear PKA activity, was found to be increased in all three regions tested. Conversely, we observed a downregulation of the expression of several PKA-regulated transcripts in one or more of the brain regions studied, including the activity and neurotransmitter-regulated early gene (Ania) - 1, -3, -7, -8, the transcription factors Egr1 and NGFI-B (Nr4a1) and the neuropeptide NPY. Reduced expression of PKA-regulated genes in mesocorticolimbic projection areas may have motivational significance in the rapid increase in alcohol self-administration induced by intermittent alcohol exposure.

  3. Three hours of intermittent hypoxia increases circulating glucose levels in healthy adults.

    Science.gov (United States)

    Newhouse, Lauren P; Joyner, Michael J; Curry, Timothy B; Laurenti, Marcello C; Man, Chiara Dalla; Cobelli, Claudio; Vella, Adrian; Limberg, Jacqueline K

    2017-01-01

    An independent association exists between sleep apnea and diabetes. Animal models suggest exposure to intermittent hypoxia, a consequence of sleep apnea, results in altered glucose metabolism and fasting hyperglycemia. However, it is unknown if acute exposure to intermittent hypoxia increases glucose concentrations in nondiabetic humans. We hypothesized plasma glucose would be increased from baseline following 3 h of intermittent hypoxia in healthy humans independent of any effect on insulin sensitivity. Eight (7M/1F, 21-34 years) healthy subjects completed two study visits randomized to 3 h of intermittent hypoxia or continuous normoxia, followed by an oral glucose tolerance test. Intermittent hypoxia consisted of 25 hypoxic events per hour where oxygen saturation (SpO 2 ) was significantly reduced (Normoxia: 97 ± 1%, Hypoxia: 90 ± 2%, P  0.05). In contrast, circulating glucose concentrations were increased after 3 h of intermittent hypoxia when compared to baseline (5.0 ± 0.2 vs. 5.3 ± 0.2 mmol/L, P = 0.01). There were no detectable changes in insulin sensitivity following intermittent hypoxia when compared to continuous normoxia, as assessed by the oral glucose tolerance test (P > 0.05). Circulating glucose is increased after 3 h of intermittent hypoxia in healthy humans, independent of any lasting changes in insulin sensitivity. These novel findings could explain, in part, the high prevalence of diabetes in patients with sleep apnea and warrant future studies to identify underlying mechanisms. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  4. The influence of intermittent fasting on the circadian pattern of melatonin while controlling for caloric intake, energy expenditure, light exposure, and sleep schedules: A preliminary report.

    Science.gov (United States)

    Almeneessier, Aljohara S; Bahammam, Ahmed S; Sharif, Munir M; Bahammam, Salman A; Nashwan, Samar Z; Pandi Perumal, Seithikurippu R; Cardinali, Daniel P; Alzoghaibi, Mohammad

    2017-01-01

    We hypothesized that if we control for food composition, caloric intake, light exposure, sleep schedule, and exercise, intermittent fasting would not influence the circadian pattern of melatonin. Therefore, we designed this study to assess the effect of intermittent fasting on the circadian pattern of melatonin. Eight healthy volunteers with a mean age of 26.6 ± 4.9 years and body mass index of 23.7 ± 3.5 kg/m 2 reported to the Sleep Disorders Center (the laboratory) on four occasions: (1) adaptation, (2) 4 weeks before Ramadan while performing Islamic intermittent fasting for 1 week (fasting outside Ramadan [FOR]), (3) 1 week before Ramadan (nonfasting baseline [BL]), and (4) during the 2 nd week of Ramadan while fasting ( Ramadan ). The plasma levels of melatonin were measured using enzyme-linked immunoassays at 22:00, 02:00, 04:00, 06:00, and 11:00 h. The light exposure, meal composition, energy expenditure, and sleep schedules remained the same while the participants stayed at the laboratory. The melatonin levels followed the same circadian pattern during the three monitoring periods (BL, FOR, and Ramadan ). The peak melatonin level was at 02:00 h and the trough level was at 11:00 h in all studied periods. Lower melatonin levels at 22:00 h were found during fasting compared to BL. Cosinor analysis revealed no significant changes in the acrophase of melatonin levels. In this preliminary report, under controlled conditions of light exposure, meal composition, energy expenditure, and sleep-wake schedules, intermittent fasting has no significant influence on the circadian pattern of melatonin.

  5. Effect of intermittent exposure to ethanol and MDMA during adolescence on learning and memory in adult mice

    Directory of Open Access Journals (Sweden)

    Vidal-Infer Antonio

    2012-06-01

    Full Text Available Abstract Background Heavy binge drinking is increasingly frequent among adolescents, and consumption of 3,4-methylenedioxymethamphetamine (MDMA is often combined with ethanol (EtOH. The long-lasting effects of intermittent exposure to EtOH and MDMA during adolescence on learning and memory were evaluated in adult mice using the Hebb-Williams maze. Methods Adolescent OF1 mice were exposed to EtOH (1.25 g/kg on two consecutive days at 48-h intervals over a 14-day period (from PD 29 to 42. MDMA (10 or 20 mg/kg was injected twice daily at 4-h intervals over two consecutive days, and this schedule was repeated six days later (PD 33, 34, 41 and 42, resulting in a total of eight injections. Animals were initiated in the Hebb-Williams maze on PND 64. The concentration of brain monoamines in the striatum and hippocampus was then measured. Results At the doses employed, both EtOH and MDMA, administered alone or together, impaired learning in the Hebb-Williams maze, as treated animals required more time to reach the goal than their saline-treated counterparts. The groups treated during adolescence with EtOH, alone or plus MDMA, also presented longer latency scores and needed more trials to reach the acquisition criterion score. MDMA induced a decrease in striatal DA concentration, an effect that was augmented by the co-administration of EtOH. All the treatment groups displayed an imbalance in the interaction DA/serotonin. Conclusions The present findings indicate that the developing brain is highly vulnerable to the damaging effects of EtOH and/or MDMA, since mice receiving these drugs in a binge pattern during adolescence exhibit impaired learning and memory in adulthood.

  6. Very low frequency oscillations in the power spectra of heart rate variability during dry supine immersion and exposure to non-hypoxic hypobaria.

    Science.gov (United States)

    Tripathi, K K

    2011-06-01

    The origin of very low frequency (VLF) oscillations in the power spectra of heart rate variability (HRV) is controversial with possible mechanisms involving thermoregulation and/or renin-angiotensin-aldosterone system. Recently, a major contribution from vagal influences has been suggested. The present study investigated the behaviour of VLF (0.004-0.040 Hz) components of HRV power spectra in a group of healthy male volunteers during their exposure to (1) dry, supine, immersion in thermo-neutral water for 6 h (n = 7) and (2) non-hypoxic hypobaria (breathing 40-60% oxygen at 15,000' simulated in a decompression chamber) for 5 h (n = 15). The two manoeuvres are established to increase vagal outflow. During both the manoeuvres, all the frequency domain indices of HRV exhibited a significant increase. Increase in HRV was much more than that in the R-R interval. At 6 h of immersion, the R-R interval increased by ∼ 15% but the total power increased ∼ fourfold. Similarly, at 5 h of exposure to hypobaria, total power increased ∼ twofold with a very modest increase in an R-R of ∼ 9%. Increase in spectral power was appreciable even after normalization with mean R-R(2). Increase in VLF during immersion was more than reported during enalaprilat blockade of angiotensin convertase enzyme. Plasma renin activity did not vary during hypobaria. There was a significant increase in pNN50, an established marker of cardiac vagal activity. Centre frequencies of the spectra and slope (β) of the relation between log(PSD) and log(frequency) did not change. Results were supportive of the notion that the parasympathetic system is pre-potent to influence slower (than respiratory) frequency components in HRV spectrum. Additionally, such an effect was without a change in the time constant of effector responses or pacemaker frequencies of VLF and LF periodicities and HRV was not a simple linear surrogate for cardiac vagal effects. An invariance of spectral exponent (β) ruled out

  7. [Effects of intermittent hypoxia on the responses of genioglossus motor cortex to transcranial magnetic stimulation in rats].

    Science.gov (United States)

    Li, Ting; Wang, Wei; Kong, De-lei; Su, Jiao; Kang, Jian

    2012-04-01

    To explore the influence of intermittent hypoxia on the responses of genioglossus motor cortex to transcranial magnetic stimulation. Male Sprague-Dawley rats were randomly divided into a control group and a chronic intermittent hypoxia group. Transcranial magnetic stimulation was applied in genioglossus motor cortex of the 2 groups. The responses of transcranial magnetic stimulation were recorded and analyzed by single factor analysis of variance. The anterolateral area provided an optimal motor evoked potential response to transcranial magnetic stimulation in the genioglossus motor cortex of the rats. Genioglossus motor evoked potential latency and amplitude were significantly modified by intermittent hypoxic exposure, with a significant decrease in latency (F = 3.294, P motor cortex in rats.

  8. Postnatal morphology of hematoencephalic barrier in hypoxic lesion

    Directory of Open Access Journals (Sweden)

    E. V. Kikhtenko

    2012-12-01

    Full Text Available In infants with perinatal hypoxic lesion of the central nervous system swelling and death of the endothelium, thickening of the capillary basement membranes, karyorrhexis and plasmorrhexis of astrocytes are observed. The severity and degree of pathological changes depends on the time of hypoxic exposure (antenatal or intrapartum period and the term of postnatal life.

  9. Effects of different acute hypoxic regimens on tissue oxygen profiles and metabolic outcomes.

    Science.gov (United States)

    Reinke, Christian; Bevans-Fonti, Shannon; Drager, Luciano F; Shin, Mi-Kyung; Polotsky, Vsevolod Y

    2011-09-01

    Obstructive sleep apnea (OSA) causes intermittent hypoxia (IH) during sleep. Both obesity and OSA are associated with insulin resistance and systemic inflammation, which may be attributable to tissue hypoxia. We hypothesized that a pattern of hypoxic exposure determines both oxygen profiles in peripheral tissues and systemic metabolic outcomes, and that obesity has a modifying effect. Lean and obese C57BL6 mice were exposed to 12 h of intermittent hypoxia 60 times/h (IH60) [inspired O₂ fraction (Fi(O₂)) 21-5%, 60/h], IH 12 times/h (Fi(O₂) 5% for 15 s, 12/h), sustained hypoxia (SH; Fi(O₂) 10%), or normoxia while fasting. Tissue oxygen partial pressure (Pti(O₂)) in liver, skeletal muscle and epididymal fat, plasma leptin, adiponectin, insulin, blood glucose, and adipose tumor necrosis factor-α (TNF-α) were measured. In lean mice, IH60 caused oxygen swings in the liver, whereas fluctuations of Pti(O₂) were attenuated in muscle and abolished in fat. In obese mice, baseline liver Pti(O₂) was lower than in lean mice, whereas muscle and fat Pti(O₂) did not differ. During IH, Pti(O₂) was similar in obese and lean mice. All hypoxic regimens caused insulin resistance. In lean mice, hypoxia significantly increased leptin, especially during SH (44-fold); IH60, but not SH, induced a 2.5- to 3-fold increase in TNF-α secretion by fat. Obesity was associated with striking increases in leptin and TNF-α, which overwhelmed effects of hypoxia. In conclusion, IH60 led to oxygen fluctuations in liver and muscle and steady hypoxia in fat. IH and SH induced insulin resistance, but inflammation was increased only by IH60 in lean mice. Obesity caused severe inflammation, which was not augmented by acute hypoxic regimens.

  10. Intermittent hypobaric hypoxia exposure does not cause sustained alterations in autonomic control of blood pressure in young athletes.

    NARCIS (Netherlands)

    Fu, Q.; Townsend, N.E.; Shiller, S.M.; Martini, E.R.; Okazaki, K.; Shibata, S.; Truijens, M.J.; Rodriquez, F.A.; Gore, C.J.; Stray-Gundersen, J.; Levine, B.D.

    2007-01-01

    Intermittent hypoxia (IH), which refers to the discontinuous use of hypoxia to reproduce some key features of altitude acclimatization, is commonly used in athletes to improve their performance. However, variations of IH are also used as a model for sleep apnea, causing sustained sympathoexcitation

  11. Hypoxic ventilatory sensitivity in men is not reduced by prolonged hyperoxia (Predictive Studies V and VI)

    Science.gov (United States)

    Gelfand, R.; Lambertsen, C. J.; Clark, J. M.; Hopkin, E.

    1998-01-01

    Potential adverse effects on the O2-sensing function of the carotid body when its cells are exposed to toxic O2 pressures were assessed during investigations of human organ tolerance to prolonged continuous and intermittent hyperoxia (Predictive Studies V and VI). Isocapnic hypoxic ventilatory responses (HVR) were determined at 1.0 ATA before and after severe hyperoxic exposures: 1) continuous O2 breathing at 1.5, 2.0, and 2.5 ATA for 17.7, 9.0, and 5.7 h and 2) intermittent O2 breathing at 2.0 ATA (30 min O2-30 min normoxia) for 14.3 O2 h within 30-h total time. Postexposure curvature of HVR hyperbolas was not reduced compared with preexposure controls. The hyperbolas were temporarily elevated to higher ventilations than controls due to increments in respiratory frequency that were proportional to O2 exposure time, not O2 pressure. In humans, prolonged hyperoxia does not attenuate the hypoxia-sensing function of the peripheral chemoreceptors, even after exposures that approach limits of human pulmonary and central nervous system O2 tolerance. Current applications of hyperoxia in hyperbaric O2 therapy and in subsea- and aerospace-related operations are guided by and are well within these exposure limits.

  12. Intermittent Testicular Torsion

    African Journals Online (AJOL)

    2017-06-02

    Jun 2, 2017 ... had prior episodes of testicular pain, suggesting that they may have had intermittent torsion before .... None of the patients had antecedent history of sexual exposure, fever, or urinary tract infection .... torsion of the spermatic cord portends an increased risk of acute testicular infarction. J Urol 2008;180 4 ...

  13. Selective alterations of NMDAR function and plasticity in D1 and D2 medium spiny neurons in the nucleus accumbens shell following chronic intermittent ethanol exposure.

    Science.gov (United States)

    Renteria, Rafael; Maier, Esther Y; Buske, Tavanna R; Morrisett, Richard A

    2017-01-01

    A major mouse model widely adopted in recent years to induce pronounced ethanol intake is the ethanol vapor model known as "CIE" or "Chronic Intermittent Ethanol." One critical question concerning this model is whether the rapid induction of high blood ethanol levels for such short time periods is sufficient to induce alterations in N-methyl-d-aspartate receptor (NMDAR) function which may contribute to excessive ethanol intake. In this study, we determined whether such short term intermittent ethanol exposure modulates NMDAR function as well as other prominent electrophysiological properties and the expression of plasticity in both D1 (D1+) and D2 (D1-) dopamine receptor expressing medium spiny neurons (MSNs) in the nucleus accumbens (NAc) shell. To distinguish between the two subtypes of MSNs in the NAc we treated Drd1a-TdTomato transgenic mice with CIE vapor and electrophysiological recordings were conducted 24 h after the last vapor exposure. To investigate CIE induced alterations in plasticity, long-term depression (LTD) was induced by pairing low frequency stimulation (LFS) with post synaptic depolarization. In ethanol naïve mice, LFS induced synaptic depression (LTD) was apparent exclusively in D1+ MSNs. Whereas in slices prepared from CIE treated mice, LFS induced synaptic potentiation (LTP) in D1+ MSNs. Furthermore, following CIE exposure, LFS now produced LTD in D1- MSNs. We found that CIE exposure induced an increase in excitability in D1+ MSNs with no change in D1- MSNs. After CIE, we found a significant increase in spontaneous EPSCs (sEPSCs) frequency in D1+ but not D1- MSNs suggesting alterations in baseline α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) mediated signaling. CIE induced changes in NMDAR function were measured using the NMDA/AMPA ratio and input-output curves of isolated NMDAR currents. We observed a significant increase in NMDAR function in D1+ MSNs and a decrease in D1- MSNs after ethanol vapor exposure. The

  14. The effects of intermittent exposure to low pH and oxygen conditions on survival and growth of juvenile red abalone

    Science.gov (United States)

    Kim, T. W.; Barry, J. P.; Micheli, F.

    2013-02-01

    Exposure of nearshore animals to hypoxic, low pH waters upwelled from below the continental shelf and advected near the coast may be stressful to marine organisms and lead to impaired physiological performance. We mimicked upwelling conditions in the laboratory and tested the effect of fluctuating exposure to water with low pH and/or low oxygen levels on the mortality and growth of juvenile red abalone (Haliotis rufescens, shell length 5-10 mm). Mortality rates of juvenile abalone exposed to low pH (7.5, total scale) and low O2 (40% saturation, 5 mg L-1) conditions for periods of 3 to 6 h every 3-5 days over 2 weeks did not differ from those exposed to control conditions (O2: 100% saturation, 12 mg L-1; pH 8.0). However, when exposure was extended to 24 h repeated twice over a 15 day period, juveniles experienced higher mortality in the low oxygen treatments compared to control conditions, regardless of pH levels (pH 7.5 vs. 8.0). Growth rates were reduced significantly when juveniles were exposed to low pH or low oxygen treatments and the growth was lowest when low pH exposure was combined with low O2. Furthermore, individual variation of growth rate increased when they were exposed to low pH and low O2 conditions. These results indicate that prolonged exposure to low oxygen levels is detrimental for the survival of red abalone, whereas both pH and oxygen is a crucial factor for their growth. However, given the higher individual variation in growth rate, they may have an ability to adapt to extended exposure to upwelling conditions.

  15. Forced swim stress increases ethanol consumption in C57BL/6J mice with a history of chronic intermittent ethanol exposure.

    Science.gov (United States)

    Anderson, Rachel I; Lopez, Marcelo F; Becker, Howard C

    2016-06-01

    Stress exposure has been identified as one risk factor for alcohol abuse that may facilitate the transition from social or regulated alcohol use to the development of alcohol dependence. Additionally, stress is a common trigger for relapse and subsequent loss of control of drinking in alcohol-dependent individuals. The present study was designed to characterize effects of repeated forced swim stress (FSS) on ethanol consumption in three rodent drinking models that engender high levels of ethanol consumption. Adult male C57BL/6J mice were exposed to 10-min FSS 4 h prior to each drinking session in three different models of high ethanol consumption: chronic intermittent ethanol (CIE) drinking (a model of dependence-like drinking), drinking-in-the-dark (DID; a model of binge-like drinking), and intermittent vs. continuous access (a model of escalated drinking). In the CIE drinking paradigm, daily FSS facilitated the escalation of ethanol intake that is typically seen in CIE-exposed mice without altering ethanol consumption in control mice exposed to FSS. FSS prior to drinking sessions did not alter ethanol consumption in the DID or intermittent access paradigms, whereas stressed mice in the continuous access procedure consumed less ethanol than their nonstressed counterparts. The CIE drinking paradigm may provide a helpful preclinical model of stress-induced transition to ethanol dependence that can be used to (1) identify underlying neural mechanisms that facilitate this transition and (2) evaluate the therapeutic potential of various pharmacological agents hypothesized to alleviate stress-induced drinking.

  16. The effects of intermittent exposure to low-pH and low-oxygen conditions on survival and growth of juvenile red abalone

    Science.gov (United States)

    Kim, T. W.; Barry, J. P.; Micheli, F.

    2013-11-01

    Exposure of nearshore animals to hypoxic, low-pH waters upwelled from below the continental shelf and advected near the coast may be stressful to marine organisms and lead to impaired physiological performance. We mimicked upwelling conditions in the laboratory and tested the effect of fluctuating exposure to water with low-pH and/or low-oxygen levels on the mortality and growth of juvenile red abalone (Haliotis rufescens, shell length 5-10 mm). Mortality rates of juvenile abalone exposed to low-pH (7.5, total scale) and low-O2 (40% saturation, mg L-1) conditions for periods of 3 to 6 h every 3-5 days over 2 weeks did not differ from those exposed to control conditions (O2: 100% saturation, 12 mg L-1; pH 8.0). However, when exposure was extended to 24 h, twice over a 15-day period, juveniles experienced 5-20% higher mortality in the low-oxygen treatments compared to control conditions. Growth rates were reduced significantly when juveniles were exposed to low-oxygen and low-pH treatments. Furthermore, individual variation of growth rate increased when juveniles were exposed simultaneously to low-pH and low-O2 conditions. These results indicate that prolonged exposure to low-oxygen levels is detrimental for the survival of red abalone, whereas pH is a crucial factor for their growth. However, the high individual variation in growth rate under low levels of both pH and oxygen suggests that cryptic phenotypic plasticity may promote resistance to prolonged upwelling conditions by a portion of the population.

  17. Motives of Dutch men who have sex with men for daily and intermittent HIV pre-exposure prophylaxis usage and preferences for implementation: A qualitative study.

    Science.gov (United States)

    Bil, Janneke P; van der Veldt, Wendy M; Prins, Maria; Stolte, Ineke G; Davidovich, Udi

    2016-09-01

    Although PrEP is not yet registered in Europe, including the Netherlands, its approval and implementation are expected in the near future. To inform future pre-exposure prophylaxis (PrEP) implementation, this study aimed to gain insight into motives and preferences for daily or intermittent PrEP use among Dutch HIV-negative men having sex with men (MSM).Between February and December 2013, semistructured interviews were conducted until data saturation was reached (N = 20). Interviews were analyzed using the Grounded Theory approach.Motives for (not) using daily PrEP were based on beliefs about PrEP efficacy and side effects, preferences for other prevention strategies, self-perceived HIV risk, self-perceived efficacy of PrEP adherence, beliefs about possible benefits (e.g., anxiety reduction, sex life improvement), and barriers of PrEP use (e.g., costs, monitoring procedures). The perceived benefits of intermittent versus daily PrEP use were the lower costs and side effects and the lower threshold to decision to start using intermittent PrEP. Barriers of intermittent PrEP versus daily PrEP use were the perceived need to plan their sex life and adhere to multiple prevention strategies. Although some perceived PrEP as a condom substitute, others were likely to combine PrEP and condoms for sexually transmitted infections (STI) prevention and increased HIV protection. Participants preferred PrEP service locations to have specialized knowledge of HIV, antiretroviral therapy, sexual behavior, STIs, patients' medical background, be easily approachable, be able to perform PrEP follow-up monitoring, and provide support.To maximize the public health impact of PrEP, ensuring high uptake among MSM at highest risk is important. Therefore, targeted information about PrEP efficacy and side effects need to be developed, barriers for accessing PrEP services should be minimized, and perceived self-efficacy to use PrEP should be addressed and improved. To prevent increases in STIs

  18. Motives of Dutch men who have sex with men for daily and intermittent HIV pre-exposure prophylaxis usage and preferences for implementation

    Science.gov (United States)

    Bil, Janneke P.; van der Veldt, Wendy M.; Prins, Maria; Stolte, Ineke G.; Davidovich, Udi

    2016-01-01

    Abstract Although PrEP is not yet registered in Europe, including the Netherlands, its approval and implementation are expected in the near future. To inform future pre-exposure prophylaxis (PrEP) implementation, this study aimed to gain insight into motives and preferences for daily or intermittent PrEP use among Dutch HIV-negative men having sex with men (MSM). Between February and December 2013, semistructured interviews were conducted until data saturation was reached (N = 20). Interviews were analyzed using the Grounded Theory approach. Motives for (not) using daily PrEP were based on beliefs about PrEP efficacy and side effects, preferences for other prevention strategies, self-perceived HIV risk, self-perceived efficacy of PrEP adherence, beliefs about possible benefits (e.g., anxiety reduction, sex life improvement), and barriers of PrEP use (e.g., costs, monitoring procedures). The perceived benefits of intermittent versus daily PrEP use were the lower costs and side effects and the lower threshold to decision to start using intermittent PrEP. Barriers of intermittent PrEP versus daily PrEP use were the perceived need to plan their sex life and adhere to multiple prevention strategies. Although some perceived PrEP as a condom substitute, others were likely to combine PrEP and condoms for sexually transmitted infections (STI) prevention and increased HIV protection. Participants preferred PrEP service locations to have specialized knowledge of HIV, antiretroviral therapy, sexual behavior, STIs, patients’ medical background, be easily approachable, be able to perform PrEP follow-up monitoring, and provide support. To maximize the public health impact of PrEP, ensuring high uptake among MSM at highest risk is important. Therefore, targeted information about PrEP efficacy and side effects need to be developed, barriers for accessing PrEP services should be minimized, and perceived self-efficacy to use PrEP should be addressed and improved. To prevent

  19. Intermittent hydronephrosis

    International Nuclear Information System (INIS)

    Knop, J.; Vogel, H.; Hupe, W.

    1981-01-01

    An intermittent hydronephrosis was observed in a 40-year old patient. This disease pattern is due to an incongruity between the formation of urine and the transport capacity in the ureteropelvic junction. The latent impediment of flow becomes manifest with increased urine secretion. Irreversible renal damage can be the result of the repeatedly occurring hydronephrotic crises. (orig.) [de

  20. Effects of Adolescent Intermittent Alcohol Exposure on the Expression of Endocannabinoid Signaling-Related Proteins in the Spleen of Young Adult Rats

    Science.gov (United States)

    Vázquez, Mariam; Sánchez, Laura; Rivera, Patricia; Gavito, Ana; Mela, Virginia; Alén, Francisco; Decara, Juan; Suárez, Juan; Giné, Elena; López-Moreno, José Antonio; Chowen, Julie; Rodríguez-de-Fonseca, Fernando; Serrano, Antonia; Viveros, María Paz

    2016-01-01

    Intermittent alcohol exposure is a common pattern of alcohol consumption among adolescents and alcohol is known to modulate the expression of the endocannabinoid system (ECS), which is involved in metabolism and inflammation. However, it is unknown whether this pattern may have short-term consequences on the ECS in the spleen. To address this question, we examined the plasma concentrations of metabolic and inflammatory signals and the splenic ECS in early adult rats exposed to alcohol during adolescence. A 4-day drinking in the dark (DID) procedure for 4 weeks was used as a model of intermittent forced-alcohol administration (20%, v/v) in female and male Wistar rats, which were sacrificed 2 weeks after the last DID session. First, there was no liver damage or alterations in plasma metabolic parameters. However, certain plasma inflammatory signals were altered according to sex and alcohol exposition. Whereas fractalkine [chemokine (C-X3-C motif) ligand 1] was only affected by sex with lower concentration in male rats, there was an interaction between sex and alcohol exposure in the TNF-α and interleukin-6 concentrations and only female rats displayed changes. Regarding the mRNA and protein expression of the ECS, the receptors and endocannabinoid-synthesizing enzymes were found to be altered with area-specific expression patterns in the spleen. Overall, whereas the expression of the cannabinoid receptor CB1 and the nuclear peroxisome proliferator-activated receptor PPARα were lower in alcohol-exposed rats compared to control rats, the CB2 expression was higher. Additionally, the N-acyl-phosphatidylethanolamine-specific phospholipase D expression was high in female alcohol-exposed rats and low in male alcohol-exposed rats. In conclusion, intermittent alcohol consumption during adolescence may be sufficient to induce short-term changes in the expression of splenic endocannabinoid signaling-related proteins and plasma pro-inflammatory cytokines in young adult rats

  1. Effects of Adolescent Intermittent Alcohol Exposure on the Expression of Endocannabinoid Signaling-Related Proteins in the Spleen of Young Adult Rats.

    Directory of Open Access Journals (Sweden)

    Francisco Javier Pavón

    Full Text Available Intermittent alcohol exposure is a common pattern of alcohol consumption among adolescents and alcohol is known to modulate the expression of the endocannabinoid system (ECS, which is involved in metabolism and inflammation. However, it is unknown whether this pattern may have short-term consequences on the ECS in the spleen. To address this question, we examined the plasma concentrations of metabolic and inflammatory signals and the splenic ECS in early adult rats exposed to alcohol during adolescence. A 4-day drinking in the dark (DID procedure for 4 weeks was used as a model of intermittent forced-alcohol administration (20%, v/v in female and male Wistar rats, which were sacrificed 2 weeks after the last DID session. First, there was no liver damage or alterations in plasma metabolic parameters. However, certain plasma inflammatory signals were altered according to sex and alcohol exposition. Whereas fractalkine [chemokine (C-X3-C motif ligand 1] was only affected by sex with lower concentration in male rats, there was an interaction between sex and alcohol exposure in the TNF-α and interleukin-6 concentrations and only female rats displayed changes. Regarding the mRNA and protein expression of the ECS, the receptors and endocannabinoid-synthesizing enzymes were found to be altered with area-specific expression patterns in the spleen. Overall, whereas the expression of the cannabinoid receptor CB1 and the nuclear peroxisome proliferator-activated receptor PPARα were lower in alcohol-exposed rats compared to control rats, the CB2 expression was higher. Additionally, the N-acyl-phosphatidylethanolamine-specific phospholipase D expression was high in female alcohol-exposed rats and low in male alcohol-exposed rats. In conclusion, intermittent alcohol consumption during adolescence may be sufficient to induce short-term changes in the expression of splenic endocannabinoid signaling-related proteins and plasma pro-inflammatory cytokines in

  2. Hypoxic radiosensitization: adored and ignored

    DEFF Research Database (Denmark)

    Overgaard, Jens

    2007-01-01

    resistance can be eliminated or modified by normobaric or hyperbaric oxygen or by the use of nitroimidazoles as hypoxic radiation sensitizers. More recently, attention has been given to hypoxic cytotoxins, a group of drugs that selectively or preferably destroys cells in a hypoxic environment. An updated......Since observations from the beginning of the last century, it has become well established that solid tumors may contain oxygen-deficient hypoxic areas and that cells in such areas may cause tumors to become radioresistant. Identifying hypoxic cells in human tumors has improved by the help of new...

  3. Chronic intermittent ethanol exposure in early adolescent and adult male rats: effects on tolerance, social behavior, and ethanol intake.

    Science.gov (United States)

    Broadwater, Margaret; Varlinskaya, Elena I; Spear, Linda P

    2011-08-01

    Given the prevalence of alcohol use in adolescence, it is important to understand the consequences of chronic ethanol exposure during this critical period in development. The purpose of this study was to assess possible age-related differences in susceptibility to tolerance development to ethanol-induced sedation and withdrawal-related anxiety, as well as voluntary ethanol intake after chronic exposure to relatively high doses of ethanol during adolescence or adulthood. Juvenile/adolescent and adult male Sprague-Dawley rats were assigned to one of five 10-day exposure conditions: chronic ethanol (4 g/kg every 48 hours), chronic saline (equivalent volume every 24 hours), chronic saline/acutely challenged with ethanol (4 g/kg on day 10), nonmanipulated/acutely challenged with ethanol (4 g/kg on day 10), or nonmanipulated. For assessment of tolerance development, duration of the loss of righting reflex (LORR) and blood ethanol concentrations (BECs) upon regaining of righting reflex (RORR) were tested on the first and last ethanol exposure days in the chronic ethanol group, with both saline and nonmanipulated animals likewise challenged on the last exposure day. Withdrawal-induced anxiety was indexed in a social interaction test 24 hours after the last ethanol exposure, with ethanol-naïve chronic saline and nonmanipulated animals serving as controls. Voluntary intake was assessed 48 hours after the chronic exposure period in chronic ethanol, chronic saline and nonmanipulated animals using an 8-day 2 bottle choice, limited-access ethanol intake procedure. In general, adolescent animals showed shorter durations of LORR and higher BECs upon RORR than adults on the first and last ethanol exposure days, regardless of chronic exposure condition. Adults, but not adolescents, developed chronic tolerance to the sedative effects of ethanol, tolerance that appeared to be metabolic in nature. Social deficits were observed after chronic ethanol in both adolescents and adults

  4. Intermittency '93

    International Nuclear Information System (INIS)

    Bialas, A.

    1993-01-01

    The existing data definitely indicate the existence of intermittency, i.e. of self similar structures in the systems of particles created in high-energy collisions. The effect seems universal: it was found in most of the processes investigated and its measures parameters depend only weakly (if at all) on the process in question. Strong HBT effect was found, suggesting that intermittency is related to space-time structure of the pion source rather than to detailed momentum structure of the production amplitudes. There are indications that this space time structure may be fractal, but more data is needed to establish this. The theoretical explanation remains obscure: it seems that both parton cascade and hadronization play an important role. Their interrelation, however, remains a mystery. 5 figs., 19 refs

  5. The lifetime of hypoxic human tumor cells

    International Nuclear Information System (INIS)

    Durand, Ralph E.; Sham, Edward

    1998-01-01

    Purpose: For hypoxic and anoxic cells in solid tumors to be a therapeutic problem, they must live long enough to be therapeutically relevant, or else be rapidly recruited into the proliferating compartment during therapy. We have, therefore, estimated lifetime and recruitment rate of hypoxic human tumor cells in multicell spheroids in vitro, or in xenografted tumors in SCID mice. Materials and Methods: Cell turnover was followed by flow cytometry techniques, using antibodies directed at incorporated halogenated pyrimidines. The disappearance of labeled cells was quantified, and verified to be cell loss rather than label dilution. Repopulation was studied in SiHa tumor xenografts during twice-daily 2.5-Gy radiation exposures. Results: The longevity of hypoxic human tumor cells in spheroids or xenografts exceeded that of rodent cell lines, and cell turnover was slower in xenografts than under static growth as spheroids. Human tumor cells remained viable in the hypoxic regions of xenografts for 4-10 days, compared to 3-5 days in spheroids, and 1-3 days for most rodent cells in spheroids. Repopulation was observed within the first few radiation treatments for the SiHa xenografts and, with accumulated doses of more than 10 Gy, virtually all recovered cells had progressed through at least one S-phase. Conclusion: Our results suggest an important difference in the ability of human vs. rodent tumor cells to withstand hypoxia, and raise questions concerning the increased longevity seen in vivo relative to the steady-state spheroid system

  6. Glucoregulatory consequences and cardiorespiratory parameters in rats exposed to chronic-intermittent hypoxia: Effects of the duration of exposure and losartan

    Directory of Open Access Journals (Sweden)

    Victor B Fenik

    2012-04-01

    Full Text Available Background: Obstructive sleep apnea (OSA is associated with glucose intolerance. Both chronic sleep disruption and recurrent blood oxygen desaturations (chronic-intermittent hypoxia – CIH may cause, or exacerbate, metabolic derangements. Methods: To assess the impact of CIH alone, without accompanying upper airway obstructions, on the counter-regulatory response to glucose load and cardiorespiratory parameters, we exposed adult male Sprague-Dawley rats to CIH or sham room air exchanges for 10 h/day for 7, 21 or 35 days and then, one day after conclusion of CIH exposure, conducted intravenous glucose tolerance tests (ivgtt under urethane anesthesia. Additional rats underwent 35 days of CIH followed by 35 days of regular housing, or had 35 day-long CIH exposure combined with daily administration of the type 1 angiotensin II receptor antagonist, losartan (15 mg/kg, p.o., and then were also subjected to ivgtt. Results: Compared with the corresponding control groups, CIH rats had progressively reduced glucose-stimulated insulin release and impaired glucose clearance, only mildly elevated heart rate and/or arterial blood pressure and slightly reduced respiratory rate. The differences in insulin release between the CIH and sham-treated rats disappeared in the rats normally housed for 35 days after 35 days of CIH/sham exposure. The losartan-treated rats had improved insulin sensitivity, with no evidence of suppressed insulin release in the CIH group. Conclusions: In adult rats, the glucose-stimulated insulin release is gradually suppressed with the duration of exposure to CIH, but the effect is reversible. Elimination of the detrimental effect of CIH on insulin release by losartan suggests that CIH disrupts glucoregulation through angiotensin/catecholaminergic pathways. Accordingly, treatment with continuous positive airway pressure may ameliorate pre-diabetic conditions in OSA patients, in part, by reducing sympathoexcitatory effects of recurrent

  7. Hypoxic sensitizers (A review)

    International Nuclear Information System (INIS)

    Ohno, Tadao; Shikita, Mikio

    1976-01-01

    Since the early works of Bridges (1960) and Adams (1963), electron-affinic compounds have long been the subject of a number of studies in the search for a drug which sensitizes radio-resistant hypoxic tumor cells for improvement of radiotherapy of cancer. However, clinical application of this kind of drugs has been hampered by the fact that most of the compounds which exhibited radiosensitizing action in vitro exerted no such action against hypoxic tumor cells in vivo, because of rapid metabolical decomposition or because of great toxicity in vivo. Low solubility of these compounds in aqueous solution was another problem which made it difficult to use the compounds in proper concentrations. The authors have found that furylfuramide (AF-2), possesses a typical radiosensitizing potency. The radiosensitizing action of AF-2 was demonstrated in hypoxic yeasts as well as in mouse leukemic cells (L-5178 Y). Injection of 4.7 μg of AF-2 into a mouse mammary carcinoma 5 min before a single dose (3500 rad) of x-irradiation reduced regrowth of the tumors to a greater extent than irradiation alone, giving an enhancing ratio of 1.6. The effect of AF-2 was insignificant when radiation was given in divided doses (800 rad for 5 times) with the drug injected each time prior to irradiation. (auth.)

  8. Radioresistance and hypoxic cells

    International Nuclear Information System (INIS)

    Ando, Koichi

    1989-01-01

    Current progress to explore further understanding of tumor hypoxia was reviewed. At subcellular level, hypoxia induces specific proteins, inhibits DNA synthesis as well as initiation of DNA replicon. Radioresistant characteristics of hypoxic cells is questioned in condition where irradiated cells were kept hypoxia during colony formation. Chronically hypoxic cells recovered from the inner layer of V79 multicellular spheroids are more sensitive to radiation than those from the oxic, outer layer. A novel sandwich culture method, which enables to reoxygenate chronic hypoxia, implies that chronically hypoxic cells are less sensitive to radiation after reoxygenation than oxic cells. For in vivo tumor, two types of tumor hypoxia are reported: diffusion-limited, chronic hypoxia and perfusion-limited, acute hypoxia. Evidence supporting the existence of perfusion-limited hypoxia is provided by an elegant method using vital staining and cell sorter. Data of our own laboratory also implies 2 types of tumor hypoxia; fractional hypoxia and incomplete hypoxia. Fractional hypoxia corresponds to a radioresistant tail on a biphasic tumor cell survival curves while tumors with incomplete hypoxia demonstrate only single component with radioresistant characteristics, instead. (author)

  9. Hypoxic-cell sensitizers

    International Nuclear Information System (INIS)

    Dische, S.

    1983-01-01

    There is now 6 years of clinical experience with misonidazole as a hypoxic-cell sensitizer. Neurotoxicity limits the total dose which may be given, and so relatively low concentrations of radiosensitizing drugs are likely to be achieved in hypoxic cells in man as compared with those in animal tumors. It is likely that benefit will only be shown in those situations where radioresistant hypoxic cells strongly dominate as a cause of radiation failure. Many clinical trials are underway, and thus far some show no benefit while in others there is a definite advantage to the patients given the drug. These trials must be continued to their conclusion, but misonidazole must be regarded as the first of a series of radiosensitizers to reach the clinic for trial. There is a promise of more effective drugs becoming available within the next few years. Those showing a lower lipophilicity than misonidazole have been found to have a shorter half-life and a lower uptake in neural tissue in animal studies. One such drug, desmethylmisonidazole, is presently undergoing clinical trial

  10. Distinct Effects of Nalmefene on Dopamine Uptake Rates and Kappa Opioid Receptor Activity in the Nucleus Accumbens Following Chronic Intermittent Ethanol Exposure

    Directory of Open Access Journals (Sweden)

    Jamie H. Rose

    2016-07-01

    Full Text Available The development of pharmacotherapeutics that reduce relapse to alcohol drinking in patients with alcohol dependence is of considerable research interest. Preclinical data support a role for nucleus accumbens (NAc κ opioid receptors (KOR in chronic intermittent ethanol (CIE exposure-induced increases in ethanol intake. Nalmefene, a high-affinity KOR partial agonist, reduces drinking in at-risk patients and relapse drinking in rodents, potentially due to its effects on NAc KORs. However, the effects of nalmefene on accumbal dopamine transmission and KOR function are poorly understood. We investigated the effects of nalmefene on dopamine transmission and KORs using fast scan cyclic voltammetry in NAc brain slices from male C57BL/6J mice following five weeks of CIE or air exposure. Nalmefene concentration-dependently reduced dopamine release similarly in air and CIE groups, suggesting that dynorphin tone may not be present in brain slices. Further, nalmefene attenuated dopamine uptake rates to a greater extent in brain slices from CIE-exposed mice, suggesting that dopamine transporter-KOR interactions may be fundamentally altered following CIE. Additionally, nalmefene reversed the dopamine-decreasing effects of a maximal concentration of a KOR agonist selectively in brain slices of CIE-exposed mice. It is possible that nalmefene may attenuate withdrawal-induced increases in ethanol consumption by modulation of dopamine transmission through KORs.

  11. Distinct Effects of Nalmefene on Dopamine Uptake Rates and Kappa Opioid Receptor Activity in the Nucleus Accumbens Following Chronic Intermittent Ethanol Exposure

    Science.gov (United States)

    Rose, Jamie H.; Karkhanis, Anushree N.; Steiniger-Brach, Björn; Jones, Sara R.

    2016-01-01

    The development of pharmacotherapeutics that reduce relapse to alcohol drinking in patients with alcohol dependence is of considerable research interest. Preclinical data support a role for nucleus accumbens (NAc) κ opioid receptors (KOR) in chronic intermittent ethanol (CIE) exposure-induced increases in ethanol intake. Nalmefene, a high-affinity KOR partial agonist, reduces drinking in at-risk patients and relapse drinking in rodents, potentially due to its effects on NAc KORs. However, the effects of nalmefene on accumbal dopamine transmission and KOR function are poorly understood. We investigated the effects of nalmefene on dopamine transmission and KORs using fast scan cyclic voltammetry in NAc brain slices from male C57BL/6J mice following five weeks of CIE or air exposure. Nalmefene concentration-dependently reduced dopamine release similarly in air and CIE groups, suggesting that dynorphin tone may not be present in brain slices. Further, nalmefene attenuated dopamine uptake rates to a greater extent in brain slices from CIE-exposed mice, suggesting that dopamine transporter-KOR interactions may be fundamentally altered following CIE. Additionally, nalmefene reversed the dopamine-decreasing effects of a maximal concentration of a KOR agonist selectively in brain slices of CIE-exposed mice. It is possible that nalmefene may attenuate withdrawal-induced increases in ethanol consumption by modulation of dopamine transmission through KORs. PMID:27472317

  12. Early post-natal exposure to intermittent hypoxia in rodents is pro-inflammatory, impairs white matter integrity and alters brain metabolism

    Science.gov (United States)

    Darnall, Robert A.; Chen, Xi; Nemani, Krishnamurthy V.; Sirieix, Chrystelle M.; Gimi, Barjor; Knoblach, Susan; McEntire, Betty L.; Hunt, Carl E.

    2017-01-01

    Background Preterm infants are frequently exposed to intermittent hypoxia (IH) associated with apnea and periodic breathing that may result in inflammation and brain injury that later manifests as cognitive and executive function deficits. We used a rodent model to determine whether early postnatal exposure to IH would result in inflammation and brain injury. Methods Rat pups were exposed to IH from P2–P12. Control animals were exposed to room air. Cytokines were analyzed in plasma and brain tissue at P13 and P18. At P20–P22, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) were performed. Results Pups exposed to IH had increased plasma Gro/CXCL1 and cerebellar IFN-γ and IL-1β at P13, and brainstem enolase at P18. DTI showed a decrease in FA and AD in the corpus callosum (CC) and cingulate gyrus and an increase in RD in the CC. MRS revealed decreases in NAA/Cho, Cr, Tau/Cr and Gly/Cr and increases in TCho and GPC in the brainstem and decreases in NAA/Cho in the hippocampus. Conclusions We conclude that early postnatal exposure to IH, similar in magnitude experienced in human preterm infants, is associated with evidence for pro-inflammatory changes, decreases in white matter integrity, and metabolic changes consistent with hypoxia. PMID:28388601

  13. Caffeine reduces apnea frequency and enhances ventilatory long-term facilitation in rat pups raised in chronic intermittent hypoxia.

    Science.gov (United States)

    Julien, Cécile A; Joseph, Vincent; Bairam, Aida

    2010-08-01

    The mechanisms underlying the therapeutic function of caffeine on apneas in preterm neonates are not well determined. To better understand these effects, we exposed rat pups from postnatal d 3-12 to chronic intermittent hypoxia (5% O2/100 s every 10 min; 6 cycles/h followed by 1 h at 21% O2, 24 h/d), a model mimicking hypoxemic exposure in apneic neonates. Then, using whole-body plethysmography, we evaluated minute ventilation, apnea frequency, and duration after i.p injection of caffeine citrate (20 mg/kg) or saline under normoxia and in response to either sustained (FiO2 12%, 20 min) or brief (FiO2 5%, 60 s, total 10 episodes of 8 min each) hypoxia. These tests were used to assess peripheral and central components of hypoxic response. The latter also assessed the ventilatory long-term facilitation during recovery (2 h). Caffeine injection increased minute ventilation under baseline and during recovery. This effect was correlated with a decrease in apnea frequency (not duration). On the contrary, caffeine did not change the ventilatory response to sustained or brief hypoxic exposure. These results suggest that the effects of caffeine on apnea depend on increased central normoxic respiratory drive and enhancement of ventilatory long-term facilitation rather than on higher hypoxic ventilatory response.

  14. The Effect of Natural or Simulated Altitude Training on High-Intensity Intermittent Running Performance in Team-Sport Athletes: A Meta-Analysis.

    Science.gov (United States)

    Hamlin, Michael J; Lizamore, Catherine A; Hopkins, Will G

    2018-02-01

    While adaptation to hypoxia at natural or simulated altitude has long been used with endurance athletes, it has only recently gained popularity for team-sport athletes. To analyse the effect of hypoxic interventions on high-intensity intermittent running performance in team-sport athletes. A systematic literature search of five journal databases was performed. Percent change in performance (distance covered) in the Yo-Yo intermittent recovery test (level 1 and level 2 were used without differentiation) in hypoxic (natural or simulated altitude) and control (sea level or normoxic placebo) groups was meta-analyzed with a mixed model. The modifying effects of study characteristics (type and dose of hypoxic exposure, training duration, post-altitude duration) were estimated with fixed effects, random effects allowed for repeated measurement within studies and residual real differences between studies, and the standard-error weighting factors were derived or imputed via standard deviations of change scores. Effects and their uncertainty were assessed with magnitude-based inference, with a smallest important improvement of 4% estimated via between-athlete standard deviations of performance at baseline. Ten studies qualified for inclusion, but two were excluded owing to small sample size and risk of publication bias. Hypoxic interventions occurred over a period of 7-28 days, and the range of total hypoxic exposure (in effective altitude-hours) was 4.5-33 km h in the intermittent-hypoxia studies and 180-710 km h in the live-high studies. There were 11 control and 15 experimental study-estimates in the final meta-analysis. Training effects were moderate and very likely beneficial in the control groups at 1 week (20 ± 14%, percent estimate, ± 90% confidence limits) and 4-week post-intervention (25 ± 23%). The intermittent and live-high hypoxic groups experienced additional likely beneficial gains at 1 week (13 ± 16%; 13 ± 15%) and 4-week post

  15. Long-term effects of chronic intermittent ethanol exposure in adolescent and adult rats: radial-arm maze performance and operant food reinforced responding.

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    Mary-Louise Risher

    Full Text Available Adolescence is not only a critical period of late-stage neurological development in humans, but is also a period in which ethanol consumption is often at its highest. Given the prevalence of ethanol use during this vulnerable developmental period we assessed the long-term effects of chronic intermittent ethanol (CIE exposure during adolescence, compared to adulthood, on performance in the radial-arm maze (RAM and operant food-reinforced responding in male rats.Male Sprague Dawley rats were exposed to CIE (or saline and then allowed to recover. Animals were then trained in either the RAM task or an operant task using fixed- and progressive- ratio schedules. After baseline testing was completed all animals received an acute ethanol challenge while blood ethanol levels (BECs were monitored in a subset of animals. CIE exposure during adolescence, but not adulthood decreased the amount of time that animals spent in the open portions of the RAM arms (reminiscent of deficits in risk-reward integration and rendered animals more susceptible to the acute effects of an ethanol challenge on working memory tasks. The operant food reinforced task showed that these effects were not due to altered food motivation or to differential sensitivity to the nonspecific performance-disrupting effects of ethanol. However, CIE pre-treated animals had lower BEC levels than controls during the acute ethanol challenges indicating persistent pharmacokinetic tolerance to ethanol after the CIE treatment. There was little evidence of enduring effects of CIE alone on traditional measures of spatial and working memory.These effects indicate that adolescence is a time of selective vulnerability to the long-term effects of repeated ethanol exposure on neurobehavioral function and acute ethanol sensitivity. The positive and negative findings reported here help to further define the nature and extent of the impairments observed after adolescent CIE and provide direction for future

  16. Long-Term Effects of Chronic Intermittent Ethanol Exposure in Adolescent and Adult Rats: Radial-Arm Maze Performance and Operant Food Reinforced Responding

    Science.gov (United States)

    Risher, Mary-Louise; Fleming, Rebekah L.; Boutros, Nathalie; Semenova, Svetlana; Wilson, Wilkie A.; Levin, Edward D.; Markou, Athina; Swartzwelder, H. Scott; Acheson, Shawn K.

    2013-01-01

    Background Adolescence is not only a critical period of late-stage neurological development in humans, but is also a period in which ethanol consumption is often at its highest. Given the prevalence of ethanol use during this vulnerable developmental period we assessed the long-term effects of chronic intermittent ethanol (CIE) exposure during adolescence, compared to adulthood, on performance in the radial-arm maze (RAM) and operant food-reinforced responding in male rats. Methodology/Principal Findings Male Sprague Dawley rats were exposed to CIE (or saline) and then allowed to recover. Animals were then trained in either the RAM task or an operant task using fixed- and progressive- ratio schedules. After baseline testing was completed all animals received an acute ethanol challenge while blood ethanol levels (BECs) were monitored in a subset of animals. CIE exposure during adolescence, but not adulthood decreased the amount of time that animals spent in the open portions of the RAM arms (reminiscent of deficits in risk-reward integration) and rendered animals more susceptible to the acute effects of an ethanol challenge on working memory tasks. The operant food reinforced task showed that these effects were not due to altered food motivation or to differential sensitivity to the nonspecific performance-disrupting effects of ethanol. However, CIE pre-treated animals had lower BEC levels than controls during the acute ethanol challenges indicating persistent pharmacokinetic tolerance to ethanol after the CIE treatment. There was little evidence of enduring effects of CIE alone on traditional measures of spatial and working memory. Conclusions/Significance These effects indicate that adolescence is a time of selective vulnerability to the long-term effects of repeated ethanol exposure on neurobehavioral function and acute ethanol sensitivity. The positive and negative findings reported here help to further define the nature and extent of the impairments observed

  17. Deficits in the extinction of ethanol-seeking behavior following chronic intermittent ethanol exposure are attenuated with positive allosteric modulation of mGlu5.

    Science.gov (United States)

    Gass, J T; McGonigal, J T; Chandler, L J

    2017-02-01

    Alcoholism is a chronic relapsing disorder characterized by periods of heavy alcohol consumption and unsuccessful attempts at abstinence. Relapse is one of the most problematic aspects in the treatment of alcoholism and is triggered by ethanol-associated cues. Extinction-based cue exposure therapies have proven ineffective in the treatment of alcoholism. However, positive allosteric modulation of mGlu5 with CDPPB enhances the extinction learning of alcohol-seeking behavior. The current study investigated the impact of chronic alcohol exposure on the extinction of ethanol-seeking behavior. Adult Wistar rats were trained to self-administer alcohol with a light/tone stimulus serving as the alcohol cue. After training, one group of rats was exposed to chronic intermittent ethanol (CIE) daily for a period of 2 weeks to induce ethanol dependence. Control rats were exposed to air for the same period of time. Both groups were then retrained to self-administer ethanol and subsequently tested for changes in extinction learning. CIE exposed rats consumed more ethanol compared to their pre-CIE levels and to control rats. During extinction training, CIE rats responded significantly more on the previously active lever and required more sessions to reach extinction criteria compared to control rats. Treatment with CDPPB facilitated extinction in control rats and attenuated the increased resistance to extinction in CIE-exposed rats. These results demonstrate that chronic ethanol exposure not only alters ethanol intake, but also the extinction of ethanol-seeking behaviors. The ability to attenuate deficits through modulation of mGlu5 provides a potential target for pharmacological manipulation that could ultimately reduce relapse in alcoholics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Key Brainstem Structures Activated during Hypoxic Exposure in One-day-old Mice Highlight Characteristics for Modeling Breathing Network in Premature Infants

    Science.gov (United States)

    Joubert, Fanny; Loiseau, Camille; Perrin-Terrin, Anne-Sophie; Cayetanot, Florence; Frugière, Alain; Voituron, Nicolas; Bodineau, Laurence

    2016-01-01

    We mapped and characterized changes in the activity of brainstem cell groups under hypoxia in one-day-old newborn mice, an animal model in which the central nervous system at birth is particularly immature. The classical biphasic respiratory response characterized by transient hyperventilation, followed by severe ventilation decline, was associated with increased c-FOS immunoreactivity in brainstem cell groups: the nucleus of the solitary tract, ventral reticular nucleus of the medulla, retrotrapezoid/parafacial region, parapyramidal group, raphe magnus nucleus, lateral, and medial parabrachial nucleus, and dorsal subcoeruleus nucleus. In contrast, the hypoglossal nucleus displayed decreased c-FOS immunoreactivity. There were fewer or no activated catecholaminergic cells activated in the medulla oblongata, whereas ~45% of the c-FOS-positive cells in the dorsal subcoeruleus were co-labeled. Approximately 30% of the c-FOS-positive cells in the parapyramidal group were serotoninergic, whereas only a small portion were labeled for serotonin in the raphe magnus nucleus. None of the c-FOS-positive cells in the retrotrapezoid/parafacial region were co-labeled for PHOX2B. Thus, the hypoxia-activated brainstem neuronal network of one-day-old mice is characterized by (i) the activation of catecholaminergic cells of the dorsal subcoeruleus nucleus, a structure implicated in the strong depressive pontine influence previously reported in the fetus but not in newborns, (ii) the weak activation of catecholaminergic cells of the ventral reticular nucleus of the medulla, an area involved in hypoxic hyperventilation, and (iii) the absence of PHOX2B-positive cells activated in the retrotrapezoid/parafacial region. Based on these results, one-day-old mice could highlight characteristics for modeling the breathing network of premature infants. PMID:28018238

  19. Key brainstem structures activated during hypoxic exposure in one-day-old mice highlight characteristics for modelling breathing network in premature infants

    Directory of Open Access Journals (Sweden)

    Fanny JOUBERT

    2016-12-01

    Full Text Available We mapped and characterized changes in the activity of brainstem cell groups under hypoxia in one-day-old newborn mice, an animal model in which the central nervous system at birth is particularly immature. The classical biphasic respiratory response characterized by transient hyperventilation, followed by severe ventilation decline, was associated with increased c-FOS immunoreactivity in brainstem cell groups: the nucleus of the solitary tract, ventral reticular nucleus of the medulla, retrotrapezoid/parafacial region, parapyramidal group, raphe magnus nucleus, lateral and medial parabrachial nucleus, and dorsal subcoeruleus nucleus. In contrast, the hypoglossal nucleus displayed decreased c-FOS immunoreactivity. There were fewer or no activated catecholaminergic cells activated in the medulla oblongata, whereas approximately 45% of the c-FOS-positive cells in the dorsal subcoeruleus were co-labelled. Approximately 30% of the c-FOS-positive cells in the parapyramidal group were serotoninergic, whereas only a small portion were labelled for serotonin in the raphe magnus nucleus. None of the c-FOS-positive cells in the retrotrapezoid/parafacial region were co-labelled for PHOX2B. Thus, the hypoxia-activated brainstem neuronal network of one-day-old mice is characterized by i the activation of catecholaminergic cells of the dorsal subcoeruleus nucleus, a structure implicated in the strong depressive pontine influence previously reported in the fetus but not in newborns, ii the weak activation of catecholaminergic cells of the ventral reticular nucleus of the medulla, an area involved in hypoxic hyperventilation, and iii the absence of PHOX2B-positive cells activated in the retrotrapezoid/parafacial region. Based on these results, one-day-old mice could highlight characteristics for modelling the breathing network of premature infants.

  20. Intermittent hyperthyreosis

    International Nuclear Information System (INIS)

    Sulman, F.G.; Tal, E.; Pfeifer, Y.; Superstine, E.

    1975-01-01

    Intermittent hyperthyreosis occurs under various forms of stress, especially heat stress. The clinician may diagnose such cases as masked or apathetic hyperthyroidism or 'forme fruste' hyperthyreosis or thyroid autonomy. As most routine and standard tests may here yield inconsistent results, it is the patients' anamnesis which may provide the clue. Our Bioclimatology Unit has now seen over 100 cases in which thyroid hypersensitivity towards heat was the most prominent syndrome: 10-15% of weather-sensitive patients are affected. The patients complain before or during heat spells of such contradictory symptoms as insomnia, irritability, tension, tachycardia, palpitations, precordial pain, dyspnoe, flushes with sweating or chills, tremor, abdominal pain or diarrhea, polyuria or pollakisuria, weight loss in spite of ravenous appetite, fatigue, exhaustion, depression, adynamia, lack of concentration and confusion. Determination of urinary neurohormones allows a differential diagnosis, intermittent hyperthyreosis being characterized by three cardinal symptoms: tachycardia - every case with more than 80 pulse beats being suspect (not specific); urinary histamine - every case excreting more than 90 μg/day being suspect. Again the drawback of this test is its lack of specificity, as histamine may also be increased in cases of allergy and spondylitis; urinary thyroxine - every case excreting more than 20 μg/day T-4 being suspect. This is the only specific test. Therapy should make use of lithium carbonate and betablockers. Propyl thiouracil is rarely required. (orig.) [de

  1. Hypoxic enhancement of exosome release by breast cancer cells

    International Nuclear Information System (INIS)

    King, Hamish W; Michael, Michael Z; Gleadle, Jonathan M

    2012-01-01

    Exosomes are nanovesicles secreted by tumour cells which have roles in paracrine signalling during tumour progression, including tumour-stromal interactions, activation of proliferative pathways and bestowing immunosuppression. Hypoxia is an important feature of solid tumours which promotes tumour progression, angiogenesis and metastasis, potentially through exosome-mediated signalling. Breast cancer cell lines were cultured under either moderate (1% O 2 ) or severe (0.1% O 2 ) hypoxia. Exosomes were isolated from conditioned media and quantitated by nanoparticle tracking analysis (NTA) and immunoblotting for the exosomal protein CD63 in order to assess the impact of hypoxia on exosome release. Hypoxic exosome fractions were assayed for miR-210 by real-time reverse transcription polymerase chain reaction and normalised to exogenous and endogenous control genes. Statistical significance was determined using the Student T test with a P value of < 0.05 considered significant. Exposure of three different breast cancer cell lines to moderate (1% O 2 ) and severe (0.1% O 2 ) hypoxia resulted in significant increases in the number of exosomes present in the conditioned media as determined by NTA and CD63 immunoblotting. Activation of hypoxic signalling by dimethyloxalylglycine, a hypoxia-inducible factor (HIF) hydroxylase inhibitor, resulted in significant increase in exosome release. Transfection of cells with HIF-1α siRNA prior to hypoxic exposure prevented the enhancement of exosome release by hypoxia. The hypoxically regulated miR-210 was identified to be present at elevated levels in hypoxic exosome fractions. These data provide evidence that hypoxia promotes the release of exosomes by breast cancer cells, and that this hypoxic response may be mediated by HIF-1α. Given an emerging role for tumour cell-derived exosomes in tumour progression, this has significant implications for understanding the hypoxic tumour phenotype, whereby hypoxic cancer cells may release

  2. Safety, adherence and acceptability of intermittent tenofovir/emtricitabine as HIV pre-exposure prophylaxis (PrEP among HIV-uninfected Ugandan volunteers living in HIV-serodiscordant relationships: a randomized, clinical trial.

    Directory of Open Access Journals (Sweden)

    Freddie M Kibengo

    Full Text Available BACKGROUND: Efficacy of oral pre-exposure prophylaxis (PrEP in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens. DESIGN: Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment. METHODS: Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS and self-report. Sexual activity data were collected via daily short text message (SMS and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT. RESULTS: Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100 for daily PrEP regimen, 91% (IQR: 73-97 for fixed intermittent dosing and 45% (IQR: 20-63 for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen. CONCLUSIONS: Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be

  3. Understanding Hypoxic Drive and the Release of Hypoxic Vasoconstriction.

    Science.gov (United States)

    Inkrott, Jon C

    2016-01-01

    Understanding the hypoxic drive and release of hypoxic vasoconstriction in the chronic obstructive pulmonary disease population can be somewhat confusing and misunderstood. Furthermore, the hypoxic drive theory is one in which there really is no scientific evidence to support and yet continues to prosper in every aspect of care in regard to the chronic lung patient, from prehospital all the way to intensive care unit and home care therapy. This subject review will hopefully enhance some understanding of what exactly goes on with these patients and the importance of providing oxygen when it is desperately needed. Copyright © 2016 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.

  4. In vitro effects of piracetam on the radiosensitivity of hypoxic cells (adaptation of MTT assay to hypoxic conditions); Effets in vitro du piracetam sur la radiosensibilite des cellules hypoxiques (adapatation du test au MTT aux conditions d`hypoxie)

    Energy Technology Data Exchange (ETDEWEB)

    Gheuens, E.E.O.; Bruijn, E.A. de; Van der Heyden, S.; Van Oosterom, A.T. [Universitaire Instelling Antwerpen, Antwerp (Belgium); Lagarde, P. [Universitaire Instelling Antwerpen, Antwerp (Belgium)]|[Institut Bergonie, 33 - Bordeaux (France); Pooter, C.M.J. de [Universitaire Instelling Antwerpen, Antwerp (Belgium)]|[Hopital de Middelheim, Anvers (Belgium); Chomy, F. [Institut Bergonie, 33 - Bordeaux (France)

    1995-12-31

    This paper describes the adaptation of the MTT assay to hypoxic conditions in order to test the in vitro effect of piracetam on hypoxic cells and particularly on the radiosensitivity of hypoxic cells since this drug has shown clinical effect on acute and chronic hypoxia. The V79 cell line was selected by reference to preliminary hypoxic experiments using clonogenic assay and euoxic experiments using clonogenic and MTT assays. Cell growth and survival in our hypoxic conditions were assessed using MTT assay with an enclosure and special 48-well plates both made of glass. Growth curves on glass plates after 1-hour exposure to nitrogen versus air were comparable, so there is no bias effect due to gas composition. Survival curves using MTT versus reference clonogenic assay were comparable after radiation exposure in eu- and hypoxic conditions, and confirm the validity of our original technique for creating hypoxia. The Oxygen Enhancement Ratio was of about 3 for 1-hour hypoxic exposure. Piracetam gave no cytotoxic effect up to 10 mM of piracetam. Growth curves after continuous drug exposure and 1-hour euoxic versus hypoxic exposure gave no cytotoxic effect up to 10 mM of piracetam. Survival curves after continuous drug exposure to 10 mM of piracetam gave no significant effect on the radiosensitivity of hypoxic V79 cells using MTT or clonogenic assay. (author). 32 refs., 6 figs.

  5. Prolonged Exposures to Intermittent Hypoxia Promote Visceral White Adipose Tissue Inflammation in a Murine Model of Severe Sleep Apnea: Effect of Normoxic Recovery.

    Science.gov (United States)

    Gileles-Hillel, Alex; Almendros, Isaac; Khalyfa, Abdelnaby; Nigdelioglu, Recep; Qiao, Zhuanhong; Hamanaka, Robert B; Mutlu, Gökhan M; Akbarpour, Mahzad; Gozal, David

    2017-03-01

    Increased visceral white adipose tissue (vWAT) mass results in infiltration of inflammatory macrophages that drive inflammation and insulin resistance. Patients with obstructive sleep apnea (OSA) suffer from increased prevalence of obesity, insulin resistance, and metabolic syndrome. Murine models of intermittent hypoxia (IH) mimicking moderate-severe OSA manifest insulin resistance following short-term IH. We examined in mice the effect of long-term IH on the inflammatory cellular changes within vWAT and the potential effect of normoxic recovery (IH-R). Male C57BL/6J mice were subjected to IH for 20 weeks, and a subset was allowed to recover in room air (RA) for 6 or 12 weeks (IH-R). Stromal vascular fraction was isolated from epididymal vWAT and mesenteric vWAT depots, and single-cell suspensions were prepared for flow cytometry analyses, reactive oxygen species (ROS), and metabolic assays. IH reduced body weight and vWAT mass and IH-R resulted in catch-up weight and vWAT mass. IH-exposed vWAT exhibited increased macrophage counts (ATMs) that were only partially improved in IH-R. IH also caused a proinflammatory shift in ATMs (increased Ly6c(hi)(+) and CD36(+) ATMs). These changes were accompanied by increased vWAT insulin resistance with only partial improvements in IH-R. In addition, ATMs exhibited increased ROS production, altered metabolism, and changes in electron transport chain, which were only partially improved in IH-R. Prolonged exposures to IH during the sleep period induce pronounced vWAT inflammation and insulin resistance despite concomitant vWAT mass reductions. These changes are only partially reversible after 3 months of normoxic recovery. Thus, long-lasting OSA may preclude complete reversibility of metabolic changes. © Sleep Research Society (SRS) 2016. All rights reserved. For permissions, please email: journals.permissions@oup.com

  6. New strategy of cancer therapy by targeting the hypoxic circumstances

    International Nuclear Information System (INIS)

    Yasui, Hironobu; Yamamori, Tohru; Meike, Shunsuke; Eitaki, Masato; Kuwabara, Mikinori; Inanami, Osamu; Iizuka, Daisuke

    2010-01-01

    Described are studies on the sensitization of tumor cells in hypoxic circumstances (known as radio-resistant cells) by authors' recent molecular targeting to adaptive response as well as by the usual agents like nitro-imidazole compounds, and on the intermittent hypoxia, a new topic in this field. The hypoxia-inducible factor-1 (HIF-1) is a transcriptional factor and has been known to activate its many downstream genes to cause adoptive response of hypoxic cells. Authors have studied the anti-tumor and radiation sensitizing effects of ethynyl-cytidine (EC) which is found to suppress RNA synthesis through cytidine kinase (CK) inhibition, and the compound is of specificity to tumor cells as they have 5-10 times higher CK activity than normal cells. Authors have also found that EC is of the sensitizing efficacy to normoxic and hypoxic cells by enhancing the radiation-induced apoptosis essentially through inhibition of HIF-1 expression. Intermittent hypoxia in the tumor which has characteristic abnormal vascular morphology and function, occurs by the transient reduction of blood flow and occlusion of vessels in the tissue within minute to hour time cycles. Little is known about the regional hypoxic region and its distribution in the tumor due to difficulty of their detection and quantification. For this, authors have measured the temporal changes of oxygen levels in the mouse tumor with triaryl methyl radical, an oxygen-sensitive contrast compound continuously injected, by microwave-pulsed electron spin resonance imaging (EPRI). By superimposing the EPRI and T2-weighted MRI, the oxymetric imaging is possible in the tumor, which reveals the difference of oxygen level variation depending on the cell type and tissue size. Findings in the field are expected to give important information for more effective cancer therapy and its prognostic prediction in future. (T.T.)

  7. Effect of leucine supplementation on fat free mass with prolonged hypoxic exposure during a 13-day trek to Everest Base Camp: a double-blind randomized study.

    Science.gov (United States)

    Wing-Gaia, Stacie L; Gershenoff, Dana C; Drummond, Micah J; Askew, E Wayne

    2014-03-01

    Loss of body weight and fat-free mass (FFM) are commonly noted with prolonged exposure to hypobaric hypoxia. Recent evidence suggests protein supplementation, specifically leucine, may potentially attenuate loss of FFM in subcaloric conditions during normoxia. The purpose of this study was to determine if leucine supplementation would prevent the loss of FFM in subcaloric conditions during prolonged hypoxia. Eighteen physically active male (n = 10) and female (n = 8) trekkers completed a 13-day trek in Nepal to Everest Base Camp with a mean altitude of 4140 m (range 2810-5364 m). In this double-blind study, participants were randomized to ingest either leucine (LEU) (7 g leucine, 93 kcal, 14.5 g whey-based protein) or an isocaloric isonitrogenous control (CON) (0.3 g LEU, 93 kcal, 11.3 g collagen protein) twice daily prior to meals. Body weight, body composition, and circumferences of bicep, thigh, and calf were measured pre- and post-trek. There was a significant time effect for body weight (-2.2% ± 1.7%), FFM (-1.7% ± 1.5%), fat mass (-4.0% ± 6.9%), and circumferences (p FFM (CON -2.1 ± 1.5%; LEU -1.2 ± 1.6%), fat mass (CON -2.9% ± 5.9%; LEU -5.4% ± 8.1%), or circumferences. Although a significant loss of body weight, FFM, and fat mass was noted in 13 days of high altitude exposure, FFM loss was not attenuated by leucine. Future studies are needed to determine if leucine attenuates loss of FFM with longer duration high altitude exposure.

  8. Hypoxic training methods for improving endurance exercise performance

    Directory of Open Access Journals (Sweden)

    Jacob A. Sinex

    2015-12-01

    Full Text Available Endurance athletic performance is highly related to a number of factors that can be altered through altitude and hypoxic training including increases in erythrocyte volume, maximal aerobic exercise capacity, capillary density, and economy. Physiological adaptations in response to acute and chronic exposure to hypoxic environments are well documented and range from short-term detrimental effects to longer-term adaptations that can improve performance at altitude and in sea-level competitions. Many altitude and hypoxic training protocols have been developed, employing various combinations of living and training at sea-level, low, moderate, and high altitudes and utilizing natural and artificial altitudes, with varying degrees of effectiveness. Several factors have been identified that are associated with individual responses to hypoxic training, and techniques for identifying those athletes most likely to benefit from hypoxic training continue to be investigated. Exposure to sufficiently high altitude (2000–3000 m for more than 12 h/day, while training at lower altitudes, for a minimum of 21 days is recommended. Timing of altitude training related to competition remains under debate, although general recommendations can be considered.

  9. Enhancement of Exposure and Reduction of Elimination for Paeoniflorin or Albiflorin via Co-Administration with Total Peony Glucosides and Hypoxic Pharmacokinetics Comparison

    Directory of Open Access Journals (Sweden)

    Weizhe Xu

    2016-07-01

    Full Text Available There is evidence suggesting that herbal extracts demonstrate greater bioactivities than their isolated constituents at an equivalent dose. This phenomenon could be attributed to the absence of interacting substances present in the extracts. By measuring the pharmacokinetic parameters of paeoniflorin (PF and albiflorin (AF after being orally administered to rats in isolated form, in combination with each other and within total peony glucosides (TPG, respectively, the current study aimed to identify positive pharmacokinetic interactions between components of peony radix extracts. Moreover, the pharmacokinetic profiles of PF and AF under normoxia and hypoxia were also investigated and compared. In order to achieve these goals, a highly sensitive and reproducible ultra-peformance liquid chromatography–mass spectrometry (UPLC-MS method was developed and validated for simultaneously quantitation of PF and AF in rat plasma. This study found that compared with that of single component (PF/AF, the exposure of PF in rat plasma after combination administration or TPG administration was significantly increased, meanwhile the elimination of PF/AF was remarkably reduced. It was also noticed that AUC and Cmax of PF in hypoxia rats were significantly decreased compared with that of normaxia rats, suggesting that there was a decreased exposure of PF in rats under hypoxia. The current study, for the first time, revealed the pharmacokinetic interactions between PF/AF and other constitutes in TGP and the pharmacokinetic profiles of PF and AF under hypoxia. In view of the current findings, it could be supposed that the clinical performance of total peony glucosides would be better than that of single constitute (PF/AF. The outcomes of this animal study are expected to serve as a basis for development of clinical guidelines on total peony glucosides usage.

  10. Repeated intermittent alcohol exposure during the third trimester-equivalent increases expression of the GABA(A) receptor δ subunit in cerebellar granule neurons and delays motor development in rats.

    Science.gov (United States)

    Diaz, Marvin R; Vollmer, Cyndel C; Zamudio-Bulcock, Paula A; Vollmer, William; Blomquist, Samantha L; Morton, Russell A; Everett, Julie C; Zurek, Agnieszka A; Yu, Jieying; Orser, Beverley A; Valenzuela, C Fernando

    2014-04-01

    Exposure to ethanol (EtOH) during fetal development can lead to long-lasting alterations, including deficits in fine motor skills and motor learning. Studies suggest that these are, in part, a consequence of cerebellar damage. Cerebellar granule neurons (CGNs) are the gateway of information into the cerebellar cortex. Functionally, CGNs are heavily regulated by phasic and tonic GABAergic inhibition from Golgi cell interneurons; however, the effect of EtOH exposure on the development of GABAergic transmission in immature CGNs has not been investigated. To model EtOH exposure during the 3rd trimester-equivalent of human pregnancy, neonatal pups were exposed intermittently to high levels of vaporized EtOH from postnatal day (P) 2 to P12. This exposure gradually increased pup serum EtOH concentrations (SECs) to ∼60 mM (∼0.28 g/dl) during the 4 h of exposure. EtOH levels gradually decreased to baseline 8 h after the end of exposure. Surprisingly, basal tonic and phasic GABAergic currents in CGNs were not significantly affected by postnatal alcohol exposure (PAE). However, PAE increased δ subunit expression at P28 as detected by immunohistochemical and western blot analyses. Also, electrophysiological studies with an agonist that is highly selective for δ-containing GABA(A) receptors, 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol (THIP), showed an increase in THIP-induced tonic current. Behavioral studies of PAE rats did not reveal any deficits in motor coordination, except for a delay in the acquisition of the mid-air righting reflex that was apparent at P15 to P18. These findings demonstrate that repeated intermittent exposure to high levels of EtOH during the equivalent of the last trimester of human pregnancy has significant but relatively subtle effects on motor coordination and GABAergic transmission in CGNs in rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Safety and adherence to intermittent pre-exposure prophylaxis (PrEP for HIV-1 in African men who have sex with men and female sex workers.

    Directory of Open Access Journals (Sweden)

    Gaudensia Mutua

    Full Text Available Little is known about safety of and adherence to intermittent HIV PrEP regimens, which may be more feasible than daily dosing in some settings. We present safety and adherence data from the first trial of an intermittent PrEP regimen among Kenyan men who have sex with men (MSM and female sex workers (FSW.MSM and FSW were randomized to daily oral FTC/TDF or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day oral FTC/TDF or placebo in a 2:1:2:1 ratio; volunteers were followed monthly for 4 months. Adherence was assessed with the medication event monitoring system (MEMS. Sexual activity data were collected via daily text message (SMS queries and timeline followback interviews with a one-month recall period. Sixty-seven men and 5 women were randomized into the study. Safety was similar among all groups. Median MEMS adherence rates were 83% [IQR: 63-92] for daily dosing and 55% [IQR:28-78] for fixed intermittent dosing (p = 0.003, while adherence to any post-coital doses was 26% [IQR:14-50]. SMS response rates were low, which may have impaired measurement of post-coital dosing adherence. Acceptability of PrEP was high, regardless of dosing regimen.Adherence to intermittent dosing regimens, fixed doses, and in particular coitally-dependent doses, may be more difficult than adherence to daily dosing. However, intermittent dosing may still be appropriate for PrEP if intracellular drug levels, which correlate with prevention of HIV acquisition, can be attained with less than daily dosing and if barriers to adherence can be addressed. Additional drug level data, qualitative data on adherence barriers, and better methods to measure sexual activity are necessary to determine whether adherence to post-coital PrEP could be comparable to more standard regimens.ClinicalTrials.gov NCT00971230.

  12. Safety and adherence to intermittent pre-exposure prophylaxis (PrEP) for HIV-1 in African men who have sex with men and female sex workers.

    Science.gov (United States)

    Mutua, Gaudensia; Sanders, Eduard; Mugo, Peter; Anzala, Omu; Haberer, Jessica E; Bangsberg, David; Barin, Burc; Rooney, James F; Mark, David; Chetty, Paramesh; Fast, Patricia; Priddy, Frances H

    2012-01-01

    Little is known about safety of and adherence to intermittent HIV PrEP regimens, which may be more feasible than daily dosing in some settings. We present safety and adherence data from the first trial of an intermittent PrEP regimen among Kenyan men who have sex with men (MSM) and female sex workers (FSW). MSM and FSW were randomized to daily oral FTC/TDF or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral FTC/TDF or placebo in a 2:1:2:1 ratio; volunteers were followed monthly for 4 months. Adherence was assessed with the medication event monitoring system (MEMS). Sexual activity data were collected via daily text message (SMS) queries and timeline followback interviews with a one-month recall period. Sixty-seven men and 5 women were randomized into the study. Safety was similar among all groups. Median MEMS adherence rates were 83% [IQR: 63-92] for daily dosing and 55% [IQR:28-78] for fixed intermittent dosing (p = 0.003), while adherence to any post-coital doses was 26% [IQR:14-50]. SMS response rates were low, which may have impaired measurement of post-coital dosing adherence. Acceptability of PrEP was high, regardless of dosing regimen. Adherence to intermittent dosing regimens, fixed doses, and in particular coitally-dependent doses, may be more difficult than adherence to daily dosing. However, intermittent dosing may still be appropriate for PrEP if intracellular drug levels, which correlate with prevention of HIV acquisition, can be attained with less than daily dosing and if barriers to adherence can be addressed. Additional drug level data, qualitative data on adherence barriers, and better methods to measure sexual activity are necessary to determine whether adherence to post-coital PrEP could be comparable to more standard regimens. ClinicalTrials.gov NCT00971230.

  13. Losartan reduces the immediate and sustained increases in muscle sympathetic nerve activity after hyperacute intermittent hypoxia.

    Science.gov (United States)

    Jouett, Noah P; Moralez, Gilbert; Raven, Peter B; Smith, Michael L

    2017-04-01

    Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia, which produces elevations in sympathetic nerve activity (SNA) and associated hypertension in experimental models that persist beyond the initial exposure. We tested the hypotheses that angiotensin receptor blockade in humans using losartan attenuates the immediate and immediately persistent increases in 1 ) SNA discharge and 2 ) mean arterial pressure (MAP) after hyperacute intermittent hypoxia training (IHT) using a randomized, placebo-controlled, repeated-measures experimental design. We measured ECG and photoplethysmographic arterial pressure in nine healthy human subjects, while muscle SNA (MSNA) was recorded in seven subjects using microneurography. Subjects were exposed to a series of hypoxic apneas in which they inhaled two to three breaths of nitrogen, followed by a 20-s apnea and 40 s of room air breathing every minute for 20 min. Hyperacute IHT produced substantial and persistent elevations in MSNA burst frequency (baseline: 15.3 ± 1.8, IHT: 24 ± 1.5, post-IHT 20.0 ± 1.3 bursts/min, all P 0.70). This investigation confirms the role of angiotensin II type 1a receptors in the immediate and persistent sympathoexcitatory and pressor responses to IHT. NEW & NOTEWORTHY This study demonstrates for the first time in humans that losartan, an angiotensin receptor blocker (ARB), abrogates the acute and immediately persistent increases in muscle sympathetic nerve activity and arterial pressure in response to acute intermittent hypoxia. This investigation, along with others, provides important beginning translational evidence for using ARBs in treatment of the intermittent hypoxia observed in obstructive sleep apnea patients. Copyright © 2017 the American Physiological Society.

  14. Intermittent hypoxia, respiratory plasticity and sleep apnea in humans: present knowledge and future investigations.

    Science.gov (United States)

    Mateika, Jason H; Syed, Ziauddin

    2013-09-15

    This review examines the role that respiratory plasticity has in the maintenance of breathing stability during sleep in individuals with sleep apnea. The initial portion of the review considers the manner in which repetitive breathing events may be initiated in individuals with sleep apnea. Thereafter, the role that two forms of respiratory plasticity, progressive augmentation of the hypoxic ventilatory response and long-term facilitation of upper airway and respiratory muscle activity, might have in modifying breathing events in humans is examined. In this context, present knowledge regarding the initiation of respiratory plasticity in humans during wakefulness and sleep is addressed. Also, published findings which reveal that exposure to intermittent hypoxia promotes breathing instability, at least in part, because of progressive augmentation of the hypoxic ventilatory response and the absence of long-term facilitation, are considered. Next, future directions are presented and are focused on the manner in which forms of plasticity that stabilize breathing might be promoted while diminishing destabilizing forms, concurrently. These future directions will consider the potential role of circadian rhythms in the promotion of respiratory plasticity and the role of respiratory plasticity in enhancing established treatments for sleep apnea. Published by Elsevier B.V.

  15. Effect of endothelin antagonism on apnea frequency following chronic intermittent hypoxia.

    Science.gov (United States)

    Donovan, Lucas M; Liu, Yuzhen; Weiss, J Woodrow

    2014-04-01

    Chronic hypoxia increases the hypoxic ventilatory response (HVR). Augmented HVR contributes to central apneas seen in heart failure and complex sleep apnea. Endothelin receptor (ETR) antagonism decreases carotid body afferent activity following chronic intermittent hypoxia (CIH). We speculated ETR antagonism would reduce HVR and apneas following CIH. HVR and apneas were measured after exposure to CIH and room air sham (SHAM). ETR blocker Ambrisentan was administered via the chow of CIH-exposed animals from days 1 to 12 of CIH (CIH/AMB). A separate crossover group was exposed to CIH and fed normal chow (placebo) days 1-6, and Ambrisentan days 7-12 (CIH/PLA-AMB). SHAM and CIH/PLA animals were fed placebo days 1-12. The CIH/AMB and CIH/PLA-AMB rats had reduced HVR compared to CIH/PLA, similar HVR compared to sham exposed animals, and reduced apnea frequency compared to CIH/PLA animals. The reduced HVR and post-hypoxic apneas resulting from Ambrisentan administration suggests ETR antagonists may have utility in reducing central apneas following CIH. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Intermittent hypoxia, respiratory plasticity and sleep apnea in humans; present knowledge and future investigations

    Science.gov (United States)

    Mateika, Jason H.; Syed, Ziauddin

    2013-01-01

    This review examines the role that respiratory plasticity has in the maintenance of breathing stability during sleep in individuals with sleep apnea. The initial portion of the review considers the manner in which repetitive breathing events may be initiated in individuals with sleep apnea. Thereafter, the role that two forms of respiratory plasticity, progressive augmentation of the hypoxic ventilatory response and long-term facilitation of upper airway and respiratory muscle activity, might have in modifying breathing events in humans is examined. In this context, present knowledge regarding the initiation of respiratory plasticity in humans during wakefulness and sleep is addressed. Also, published findings which reveal that exposure to intermittent hypoxia promotes breathing instability, at least in part, because of progressive augmentation of the hypoxic ventilatory response and the absence of long-term facilitation, are considered. Next, future directions are presented and are focused on the manner in which forms of plasticity that stabilize breathing might be promoted while diminishing destabilizing forms, concurrently. These future directions will consider the potential role of circadian rhythms in the promotion of respiratory plasticity and the role of respiratory plasticity in enhancing established treatments for sleep apnea. PMID:23587570

  17. Role of Carotid Body in Intermittent Hypoxia-Related Hypertension.

    Science.gov (United States)

    Iturriaga, Rodrigo; Oyarce, María Paz; Dias, Ana Carolina Rodrigues

    2017-05-01

    Obstructive sleep apnea (OSA), a common breathing disorder, is recognized as an independent risk factor for systemic hypertension. Among the alterations induced by OSA, the chronic intermittent hypoxia (CIH) is considered the main factor for the hypertension. Exposure of rodents to CIH is the gold-standard method to study the mechanisms involved in the cardiovascular alterations induced by OSA. Although it is well known that CIH produces hypertension, the underlying mechanisms are not totally elucidated. It is likely that the CIH-induced systemic oxidative stress and inflammation may elicit endothelial dysfunction and increase the arterial blood pressure. In addition, OSA patients and animals exposed to CIH show sympathetic hyperactivity and potentiated cardiorespiratory responses to acute hypoxia, suggesting that CIH enhances the peripheral hypoxic chemoreflex. Recent experimental evidences support the proposal that CIH selectively enhances carotid body (CB) chemosensory reactivity to oxygen, which in turn increases sympathetic outflow leading to neurogenic hypertension. In this review, we will discuss the supporting evidence for a critical role of the CB in the generation and maintenance of the hypertension induced by CIH, also, the contribution of oxidative stress to enhance CB chemosensory drive and the activation of sympathetic-related centers in the brain.

  18. High acceptability of HIV pre-exposure prophylaxis but challenges in adherence and use: qualitative insights from a phase I trial of intermittent and daily PrEP in at-risk populations in Kenya.

    Science.gov (United States)

    Van der Elst, Elisabeth Maria; Mbogua, Judie; Operario, Don; Mutua, Gaudensia; Kuo, Caroline; Mugo, Peter; Kanungi, Jennifer; Singh, Sagri; Haberer, Jessica; Priddy, Frances; Sanders, Eduard Joachim

    2013-07-01

    This paper used qualitative methods to explore experiences of men who have sex with men and female sex workers in Nairobi and Mtwapa, Kenya, who used oral pre-exposure prophylaxis (PrEP) for HIV prevention as part of a four-month trial of safety, acceptability and adherence. Fifty-one of 72 volunteers who took part in a randomized, placebo-controlled, blinded trial that compared daily and intermittent dosage of PrEP underwent qualitative assessments after completing the trial. Analyses identified three themes: (i) acceptability of PrEP was high, i.e. side effects were experienced early in the study but diminished over time, however characteristics of pills could improve comfort and use; (ii) social impacts such as stigma, rumors, and relationship difficulties due to being perceived as HIV positive were prevalent; (iii) adherence was challenged by complexities of daily life, in particular post-coital dosing adherence suffered from alcohol use around time of sex, mobile populations, and transactional sex work. These themes resonated across dosing regimens and gender, and while most participants favored the intermittent dosing schedule, those in the intermittent group noted particular challenges in adhering to the post-coital dose. Culturally appropriate and consistent counseling addressing these issues may be critical for PrEP effectiveness.

  19. Hypoxic pretreatment protects against neuronal damage of the rat hippocampus induced by severe hypoxia.

    Science.gov (United States)

    Gorgias, N; Maidatsi, P; Tsolaki, M; Alvanou, A; Kiriazis, G; Kaidoglou, K; Giala, M

    1996-04-01

    The present study investigates whether under conditions of successive hypoxic exposures pretreatment with mild (15% O(2)) or moderate (10% O(2)) hypoxia, protects hippocampal neurones against damage induced by severe (3% O(2)) hypoxia. The ultrastructural findings were also correlated with regional superoxide dismutase (SOD) activity changes. In unpretreated rats severe hypoxia induced ultrastructural changes consistent with the aspects of delayed neuronal death (DND). However, in preexposed animals hippocampal damage was attenuated in an inversely proportional way with the severity of the hypoxic pretreatment. The ultrastructural hypoxic tolerance findings were also closely related to increased regional SOD activity levels. Thus the activation of the endogenous antioxidant defense by hypoxic preconditioning, protects against hippocampal damage induced by severe hypoxia. The eventual contribution of increased endogenous adenosine and/or reduced excitotoxicity to induce hypoxic tolerance is discussed.

  20. SU-E-I-34: Intermittent Low- and High-Dose Ethanol Exposure Alters Neurochemical Responses in Adult Rat Brain: An Ex Vivo 1H NMR Spectroscopy at 11.7 T

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Do-Wan; Kim, Sang-Young; Song, Kyu-Ho; Choe, Bo-Young [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2014-06-01

    Purpose: The first goal of this study was to determine the influence of the dose-dependent effects of intermittent ethanol intoxication on cerebral neurochemical responses among sham controls and low- and high-dose-ethanol-exposed rats with ex vivo high-resolution spectra. The second goal of this study was to determine the correlations between the metabolite-metabolite levels (pairs-of-metabolite levels) from all of the individual data from the frontal cortex of the intermittent ethanol-intoxicated rats. Methods: Eight-week-old male Wistar rats were divided into 3 groups. Twenty rats in the LDE (n = 10) and the HDE (n = 10) groups received ethanol doses of 1.5 g/kg and 2.5 g/kg, respectively, through oral gavage every 8-h for 4 days. At the end of the 4-day intermittent ethanol exposure, one-dimensional ex vivo 500-MHz proton nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the 3 groups). Results: Normalized total-N-acetylaspartate (tNAA: NAA + NAAG [N-acetylaspartyl-glutamate]), gamma-aminobutyric acid (GABA), and glutathione (GSH) levels were significantly lower in the frontal cortex of the HDE-exposed rats than that of the LDE-exposed rats. Moreover, compared to the CNTL group, the LDE rats exhibited significantly higher normalized GABA levels. The 6 pairs of normalized metabolite levels were positively (+) or negatively (−) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and Aspartate (Asp) (−), myo-Inositol (mIns) and Asp (−), mIns and Alanine (+), mIns and Taurine (+), and mIns and tNAA (−). Conclusion: Our results suggested that repeated intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo 1H high-resolution-magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose

  1. SU-E-I-34: Intermittent Low- and High-Dose Ethanol Exposure Alters Neurochemical Responses in Adult Rat Brain: An Ex Vivo 1H NMR Spectroscopy at 11.7 T

    International Nuclear Information System (INIS)

    Lee, Do-Wan; Kim, Sang-Young; Song, Kyu-Ho; Choe, Bo-Young

    2014-01-01

    Purpose: The first goal of this study was to determine the influence of the dose-dependent effects of intermittent ethanol intoxication on cerebral neurochemical responses among sham controls and low- and high-dose-ethanol-exposed rats with ex vivo high-resolution spectra. The second goal of this study was to determine the correlations between the metabolite-metabolite levels (pairs-of-metabolite levels) from all of the individual data from the frontal cortex of the intermittent ethanol-intoxicated rats. Methods: Eight-week-old male Wistar rats were divided into 3 groups. Twenty rats in the LDE (n = 10) and the HDE (n = 10) groups received ethanol doses of 1.5 g/kg and 2.5 g/kg, respectively, through oral gavage every 8-h for 4 days. At the end of the 4-day intermittent ethanol exposure, one-dimensional ex vivo 500-MHz proton nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the 3 groups). Results: Normalized total-N-acetylaspartate (tNAA: NAA + NAAG [N-acetylaspartyl-glutamate]), gamma-aminobutyric acid (GABA), and glutathione (GSH) levels were significantly lower in the frontal cortex of the HDE-exposed rats than that of the LDE-exposed rats. Moreover, compared to the CNTL group, the LDE rats exhibited significantly higher normalized GABA levels. The 6 pairs of normalized metabolite levels were positively (+) or negatively (−) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and Aspartate (Asp) (−), myo-Inositol (mIns) and Asp (−), mIns and Alanine (+), mIns and Taurine (+), and mIns and tNAA (−). Conclusion: Our results suggested that repeated intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo 1H high-resolution-magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose

  2. Intermittent search strategies

    Science.gov (United States)

    Bénichou, O.; Loverdo, C.; Moreau, M.; Voituriez, R.

    2011-01-01

    This review examines intermittent target search strategies, which combine phases of slow motion, allowing the searcher to detect the target, and phases of fast motion during which targets cannot be detected. It is first shown that intermittent search strategies are actually widely observed at various scales. At the macroscopic scale, this is, for example, the case of animals looking for food; at the microscopic scale, intermittent transport patterns are involved in a reaction pathway of DNA-binding proteins as well as in intracellular transport. Second, generic stochastic models are introduced, which show that intermittent strategies are efficient strategies that enable the minimization of search time. This suggests that the intrinsic efficiency of intermittent search strategies could justify their frequent observation in nature. Last, beyond these modeling aspects, it is proposed that intermittent strategies could also be used in a broader context to design and accelerate search processes.

  3. A Molecular and Whole Body Insight of the Mechanisms Surrounding Glucose Disposal and Insulin Resistance with Hypoxic Treatment in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    R. W. A. Mackenzie

    2016-01-01

    Full Text Available Although the mechanisms are largely unidentified, the chronic or intermittent hypoxic patterns occurring with respiratory diseases, such as chronic pulmonary disease or obstructive sleep apnea (OSA and obesity, are commonly associated with glucose intolerance. Indeed, hypoxia has been widely implicated in the development of insulin resistance either via the direct action on insulin receptor substrate (IRS and protein kinase B (PKB/Akt or indirectly through adipose tissue expansion and systemic inflammation. Yet hypoxia is also known to encourage glucose transport using insulin-dependent mechanisms, largely reliant on the metabolic master switch, 5′ AMP-activated protein kinase (AMPK. In addition, hypoxic exposure has been shown to improve glucose control in type 2 diabetics. The literature surrounding hypoxia-induced changes to glycemic control appears to be confusing and conflicting. How is it that the same stress can seemingly cause insulin resistance while increasing glucose uptake? There is little doubt that acute hypoxia increases glucose metabolism in skeletal muscle and does so using the same pathway as muscle contraction. The purpose of this review paper is to provide an insight into the mechanisms underpinning the observed effects and to open up discussions around the conflicting data surrounding hypoxia and glucose control.

  4. Effects of bleomycin and irradiation on euoxic and hypoxic cells

    International Nuclear Information System (INIS)

    Shrieve, D.C.; Harris, J.W.

    1979-01-01

    EMT6 cells in vitro were exposed to bleomycin (BLM), either alone (under euoxic or hypoxic conditions) or in conjunction with x-radiation. Hypoxic and euoxic cells were equally sensitive to the drug in both of the systems used to induce hypoxia (ampules or chambers). Exposure to BLM immediately before x-irradiation altered the shape of the radiation survival curve decreasing the D 0 by a factor of 1.3. Simultaneous exposure to x-ray and BLM resulted in lower survivals than when radiation was given either before or after drug treatment. Cells recovered quickly from BLM damage if trypsinization was delayed. The results indicate that BLM and x-rays interact to lower cell survival but that cells recover from this effect if trypsinization is delayed

  5. Intermittency in branching models

    International Nuclear Information System (INIS)

    Chiu, C.B.; Texas Univ., Austin; Hwa, R.C.; Oregon Univ., Eugene

    1990-01-01

    The intermittency properties of three branching models have been investigated. The factorial moments show power-law behavior as function of small rapidity width. The slopes and energy dependences reveal different characteristics of the models. The gluon model has the weakest intermittency. (orig.)

  6. New avenues in hypoxic cell sensitization

    International Nuclear Information System (INIS)

    Huilgol, N.G.; Chatterjee, N.A.; Singh, B.B.

    1995-01-01

    Hypoxic cells in tumors represent a population of cells that are resistant to radiotherapy. Bio-reductive agents like RSU 1069, RBU 6145 and EOg and vasoactive drugs in conjunction with hypoxic cell sensitizers are being evaluated as hypoxic cell cytotoxins. Chlorpromazine a membrane active drug and AK-2123- a nitrotriazole with a potential to deplete intracellular thiols induced vasoconstriction and sensitize hypoxic cells have stretched the boundaries of innovation. A preliminary experience with these drugs is discussed. 8 refs., 2 tabs., 2 figs

  7. Intermittent degradation and schizotypy

    Directory of Open Access Journals (Sweden)

    Matthew W. Roché

    2015-06-01

    Full Text Available Intermittent degradation refers to transient detrimental disruptions in task performance. This phenomenon has been repeatedly observed in the performance data of patients with schizophrenia. Whether intermittent degradation is a feature of the liability for schizophrenia (i.e., schizotypy is an open question. Further, the specificity of intermittent degradation to schizotypy has yet to be investigated. To address these questions, 92 undergraduate participants completed a battery of self-report questionnaires assessing schizotypy and psychological state variables (e.g., anxiety, depression, and their reaction times were recorded as they did so. Intermittent degradation was defined as the number of times a subject’s reaction time for questionnaire items met or exceeded three standard deviations from his or her mean reaction time after controlling for each item’s information processing load. Intermittent degradation scores were correlated with questionnaire scores. Our results indicate that intermittent degradation is associated with total scores on measures of positive and disorganized schizotypy, but unrelated to total scores on measures of negative schizotypy and psychological state variables. Intermittent degradation is interpreted as potentially derivative of schizotypy and a candidate endophenotypic marker worthy of continued research.

  8. Hypoxic preconditioning induces neuroprotective stanniocalcin-1 in brain via IL-6 signaling

    DEFF Research Database (Denmark)

    Westberg, Johan A; Serlachius, Martina; Lankila, Petri

    2007-01-01

    BACKGROUND AND PURPOSE: Exposure of animals for a few hours to moderate hypoxia confers relative protection against subsequent ischemic brain damage. This phenomenon, known as hypoxic preconditioning, depends on new RNA and protein synthesis, but its molecular mechanisms are poorly understood...... originally reported expression of mammalian STC-1 in brain neurons and showed that STC-1 guards neurons against hypercalcemic and hypoxic damage. METHODS: We treated neural Paju cells with IL-6 and measured the induction of STC-1 mRNA. In addition, we quantified the effect of hypoxic preconditioning on Stc-1...... mRNA levels in brains of wild-type and IL-6 deficient mice. Furthermore, we monitored the Stc-1 response in brains of wild-type and transgenic mice, overexpressing IL-6 in the astroglia, before and after induced brain injury. RESULTS: Hypoxic preconditioning induced an upregulated expression of Stc...

  9. The effect of dexamethasone on the radiation survival response and misonidazole-induced hypoxic-cell cytotoxicity in Chinese hamster cells V-79-753B in vitro

    International Nuclear Information System (INIS)

    Millar, B.C.; Jinks, S.

    1981-01-01

    Overnight exposure of Chinese hamster cells, V-79-753B, to microgram quantities of the synthetic corticosteroid, dexamethasone, resulted in a decrease in sensitivity towards radiation, both in air and in hypoxia. The effect was dose-modifying and the oxygen enhancement ratio did not change appreciably. Similarly, when dexamethasone-treated hypoxic cells were irradiated in the presence of misonidazole, a hypoxic cell radiosensitizer, there was a decrease in radiation sensitivity compared with untreated hypoxic cells irradiated with misonidazole. (author)

  10. On the use of mobile inflatable hypoxic marquees for sport-specific altitude training in team sports.

    Science.gov (United States)

    Girard, Olivier; Brocherie, Franck; Millet, Grégoire P

    2013-12-01

    With the evolving boundaries of sports science and greater understanding of the driving factors in the human performance physiology, one of the limiting factors has now become the technology. The growing scientific interest on the practical application of hypoxic training for intermittent activities such as team and racket sports legitimises the development of innovative technologies serving athletes in a sport-specific setting. Description of a new mobile inflatable simulated hypoxic equipment. The system comprises two inflatable units-that is, a tunnel and a rectangular design, each with a 215 m(3) volume and a hypoxic trailer generating over 3000 Lpm of hypoxic air with FiO₂ between 0.21 and 0.10 (a simulated altitude up to 5100 m). The inflatable units offer a 45 m running lane (width=1.8 m and height=2.5 m) as well as a 8 m × 10 m dome tent. FiO₂ is stable within a range of 0.1% in normal conditions inside the tunnel. The air supplied is very dry-typically 10-15% relative humidity. This mobile inflatable simulated hypoxic equipment is a promising technological advance within sport sciences. It offers an opportunity for team-sport players to train under hypoxic conditions, both for repeating sprints (tunnel configuration) or small-side games (rectangular configuration).

  11. Intermittent Explosive Disorder

    Directory of Open Access Journals (Sweden)

    Lut Tamam

    2011-09-01

    Full Text Available Intermittent explosive disorder is an impulse control disorder characterized by the occurrence of discrete episodes of failure to resist aggressive impulses that result in violent assault or destruction of property. Though the prevalence intermittent explosive disorder has been reported to be relatively rare in frontier studies on the field, it is now common opinion that intermittent explosive disorder is far more common than previously thought especially in clinical psychiatry settings. Etiological studies displayed the role of both psychosocial factors like childhood traumas and biological factors like dysfunctional neurotransmitter systems and genetics. In differential diagnosis of the disorder, disorders involving agression as a symptom such as alcohol and drug intoxication, antisocial and borderline personality disorders, personality changes due to general medical conditions and behavioral disorder should be considered. A combination of pharmacological and psychotherapeutic approaches are suggested in the treatment of the disorder. This article briefly reviews the historical background, diagnostic criteria, epidemiology, etiology and treatment of intermittent explosive disorder.

  12. Intermittent heating of buildings

    Energy Technology Data Exchange (ETDEWEB)

    Kohonen, K

    1983-02-01

    Conditions for intermittent heating of buildings are considered both theoretically and experimentally. Thermal behaviour of buildings adn rooms in intermittent heating is simulated by a program based on the convective heat balance equation and by simplified RC-models. The preheat times and the heating energy savings compared with continuous heating are presented for typical lightweight, mediumweight and heavyweight classroom and office modules. Formulaes for estimating the oversizing of the radiator network, the maximum heat output of heat exchangers in district heating and the efficiency of heating boilers in intermittent heating are presented. The preheat times and heating energy savings with different heating control systems are determined also experimentally in eight existing buildings. In addition some principles for the planning and application of intermittent heating systems are suggested.

  13. Optimal intermittent search strategies

    International Nuclear Information System (INIS)

    Rojo, F; Budde, C E; Wio, H S

    2009-01-01

    We study the search kinetics of a single fixed target by a set of searchers performing an intermittent random walk, jumping between different internal states. Exploiting concepts of multi-state and continuous-time random walks we have calculated the survival probability of a target up to time t, and have 'optimized' (minimized) it with regard to the transition probability among internal states. Our model shows that intermittent strategies always improve target detection, even for simple diffusion states of motion

  14. Effect of intermittent normobaric hypoxia on aerobic capacity and cognitive function in older people.

    Science.gov (United States)

    Schega, Lutz; Peter, Beate; Brigadski, Tanja; Leßmann, Volkmar; Isermann, Berend; Hamacher, Dennis; Törpel, Alexander

    2016-11-01

    Physical exercise, especially aerobic training, improves physical performance and cognitive function of older people. Furthermore, it has been speculated that age-associated deteriorations in physical performance and cognitive function could be counteracted through exposures to passive intermittent normobaric hypoxia (IH). Thus, the present investigation aimed at investigating the effect of passive IH combined with subsequent aerobic training on hematological parameters and aerobic physical performance (V˙O 2max ) as well as peripheral levels of the neurotrophin brain-derived neurotrophic factor (BDNF) and cognitive function. Randomized controlled trial in a repeated measure design. 34 older participants were randomly assigned to an intervention group (IG) or control group (CG). While IG was supplied with passive IH for 90min, CG breathed ambient air. Subsequently, both groups underwent 30min of aerobic training three times per week for four consecutive weeks. Aerobic physical performance and cognitive function was tested with spiroergometry and the Stroop test. Blood samples were taken to measure hematological parameters and the peripheral serum BDNF-level. We found increases in the values of hematological parameters, the time to exhaustion in the load test and an augmented and sustainable improvement in cognitive function within the IG of the older people only. However, in both groups, the V˙O 2max and serum BDNF-level did not increase. Based on these results, hypoxic training seems to be beneficial to enhance hematological parameters, physical performance and cognitive function in older people. The current hypoxic-dose was not able to enhance the serum BDNF-level or V˙O 2max . Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  15. Exposure to hot and cold environmental conditions does not affect the decision making ability of soccer referees following an intermittent sprint protocol.

    Directory of Open Access Journals (Sweden)

    Lee eTaylor

    2014-05-01

    Full Text Available Soccer referees enforce the laws of the game and the decisions they make can directly affect match results. Fixtures within European competitions take place in climatic conditions that are often challenging (e.g. Moscow ~ -5oC, Madrid ~30oC. Effects of these temperatures on player performance are well documented; however, little is known how this environmental stress may impair cognitive performance of soccer referees and if so, whether exercise exasperates this. The present study aims to investigate the effect of cold (COLD; 5oC, 40% relative humidity (RH, hot (HOT; 30oC, 40% RH and temperate (CONT; 18oC, 40% RH conditions on decision making during soccer specific exercise. On separate occasions within each condition, thirteen physically active males; either semi-professional referees or semi-professional soccer players completed three 90 min intermittent treadmill protocols that simulated match play, interspersed with 4 computer delivered cognitive tests to measure vigilance and dual task capacity. Core and skin temperature, heart rate, rating of perceived exertion and thermal sensation were recorded throughout the protocol. There was no significant difference between conditions for decision making (p > 0.05 despite significant differences in measured physiological variables (skin temperature = HOT 34.5 ± 5.1°C; CONT 31.2 ± 0.1°C and COLD 26.7 ± 0.5°C; p < 0.05. It is hypothesised that the lack of difference observed in decision making ability between conditions was due to the exercise protocol used, as it may not have elicited an appropriate and valid soccer specific internal load to alter cognitive functioning.

  16. Exposure to hot and cold environmental conditions does not affect the decision making ability of soccer referees following an intermittent sprint protocol.

    Science.gov (United States)

    Taylor, Lee; Fitch, Natalie; Castle, Paul; Watkins, Samuel; Aldous, Jeffrey; Sculthorpe, Nicholas; Midgely, Adrian; Brewer, John; Mauger, Alexis

    2014-01-01

    Soccer referees enforce the laws of the game and the decisions they make can directly affect match results. Fixtures within European competitions take place in climatic conditions that are often challenging (e.g., Moscow ~ -5°C, Madrid ~30°C). Effects of these temperatures on player performance are well-documented; however, little is known how this environmental stress may impair cognitive performance of soccer referees and if so, whether exercise exasperates this. The present study aims to investigate the effect of cold [COLD; -5°C, 40% relative humidity (RH)], hot (HOT; 30°C, 40% RH) and temperate (CONT; 18°C, 40% RH) conditions on decision making during soccer specific exercise. On separate occasions within each condition, 13 physically active males; either semi-professional referees or semi-professional soccer players completed three 90 min intermittent treadmill protocols that simulated match play, interspersed with 4 computer delivered cognitive tests to measure vigilance and dual task capacity. Core and skin temperature, heart rate, rating of perceived exertion (RPE) and thermal sensation (TS) were recorded throughout the protocol. There was no significant difference between conditions for decision making in either the dual task (interaction effects: FALSE p = 0.46; MISSED p = 0.72; TRACKING p = 0.22) or vigilance assessments (interaction effects: FALSE p = 0.31; HIT p = 0.15; MISSED p = 0.17) despite significant differences in measured physiological variables (skin temperature: HOT vs. CONT 95% CI = 2.6 to 3.9, p decision making ability between conditions was due to the exercise protocol used, as it may not have elicited an appropriate and valid soccer specific internal load to alter cognitive functioning.

  17. Hypoxic preconditioning protects photoreceptors against light damage independently of hypoxia inducible transcription factors in rods.

    Science.gov (United States)

    Kast, Brigitte; Schori, Christian; Grimm, Christian

    2016-05-01

    Hypoxic preconditioning protects photoreceptors against light-induced degeneration preserving retinal morphology and function. Although hypoxia inducible transcription factors 1 and 2 (HIF1, HIF2) are the main regulators of the hypoxic response, photoreceptor protection does not depend on HIF1 in rods. Here we used rod-specific Hif2a single and Hif1a;Hif2a double knockout mice to investigate the potential involvement of HIF2 in rods for protection after hypoxic preconditioning. To identify potential HIF2 target genes in rods we determined the retinal transcriptome of hypoxic control and rod-specific Hif2a knockouts by RNA sequencing. We show that rods do not need HIF2 for hypoxia-induced increased survival after light exposure. The transcriptomic analysis revealed a number of genes that are potentially regulated by HIF2 in rods; among those were Htra1, Timp3 and Hmox1, candidates that are interesting due to their connection to human degenerative diseases of the retina. We conclude that neither HIF1 nor HIF2 are required in photoreceptors for protection by hypoxic preconditioning. We hypothesize that HIF transcription factors may be needed in other cells to produce protective factors acting in a paracrine fashion on photoreceptor cells. Alternatively, hypoxic preconditioning induces a rod-intrinsic response that is independent of HIF transcription factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Transient hypoxic respiratory failure in a patient with severe hypophosphatemia.

    Science.gov (United States)

    Oud, Lavi

    2009-03-01

    Respiratory failure in severely hypophosphatemic patients has been attributed to respiratory muscle weakness, leading to ventilatory failure. While frequently documenting hypercarbic respiratory failure, previous reports of hypophosphatemia-related respiratory failure in patients otherwise free of pulmonary or airway disease often did not provide sufficient information on gas exchange and pulmonary function, precluding inference on alternative or additional sources of respiratory dysfunction in this population. We report a case of acute hypoxic respiratory failure in a 26 year-old bulimic woman with severe hypophosphatemia. The patient presented with acute onset of dyspnea, paresthesias, limb shaking, and severe hyperventilation. SpO2 was 74%, requiring administration of 100% O2, with normal chest radiograph. Serum phosphate was <0.3 mmol/liter (1.0 mg/dL). Further evaluation did not support pulmonary, vascular, neurogenic or external exposure-related causes of hypoxic respiratory failure, which rapidly resolved with parenteral correction of hypophosphatemia. To date, hypoxic respiratory failure has not been reported in association with hypophosphatemia. Increased awareness and further investigations can help elucidate the mechanisms of hypophosphatemia-associated hypoxemia.

  19. Transcriptome analysis of severe hypoxic stress during development in zebrafish

    Directory of Open Access Journals (Sweden)

    I.G. Woods

    2015-12-01

    Full Text Available Hypoxia causes critical cellular injury both in early human development and in adulthood, leading to cerebral palsy, stroke, and myocardial infarction. Interestingly, a remarkable phenomenon known as hypoxic preconditioning arises when a brief hypoxia exposure protects target organs against subsequent, severe hypoxia. Although hypoxic preconditioning has been demonstrated in several model organisms and tissues including the heart and brain, its molecular mechanisms remain poorly understood. Accordingly, we used embryonic and larval zebrafish to develop a novel vertebrate model for hypoxic preconditioning, and used this model to identify conserved hypoxia-regulated transcripts for further functional study as published in Manchenkov et al. (2015 in G3: Genes|Genomes|Genetics. In this Brief article, we provide extensive annotation for the most strongly hypoxia-regulated genes in zebrafish, including their human orthologs, and describe in detail the methods used to identify, filter, and annotate hypoxia-regulated transcripts for downstream functional and bioinformatic assays using the source data provided in Gene Expression Omnibus Accession GSE68473.

  20. Apoptosis, energy metabolism, and fraction of radiobiologically hypoxic cells: a study of human melanoma multicellular spheroids.

    Science.gov (United States)

    Rofstad, E K; Eide, K; Skøyum, R; Hystad, M E; Lyng, H

    1996-09-01

    The magnitude of the fraction of radiobiologically hypoxic cells in tumours is generally believed to reflect the efficiency of the vascular network. Theoretical studies have suggested that the hypoxic fraction might also be influenced by biological properties of the tumour cells. Quantitative experimental results of cell energy metabolism, hypoxia- induced apoptosis, and radiobiological hypoxia are reported here. Human melanoma multicellular spheroids (BEX-c and WIX-c) were used as tumour models to avoid confounding effects of the vascular network. Radiobiological studies showed that the fractions of hypoxic cells in 1000-microM spheroids were 32 +/- 12% (BEX-c) and 2.5 +/- 1.1% (WIX-c). The spheroid hypoxic volume fractions (28 +/- 6% (BEX-c) and 1.4 +/- 7% (WIX-c)), calculated from the rate of oxygen consumption per cell, the cell packing density, and the thickness of the viable rim, were similar to the fractions of radiobiologically hypoxic cells. Large differences between tumours in fraction of hypoxic cells are therefore not necessarily a result of differences in the efficiency of the vascular network. Studies of monolayer cell cultures, performed to identify the biological properties of the BEX-c and WIX-c cells leading to this large difference in fraction of hypoxic cells, gave the following results: (1) WIX-c showed lower cell surviving fractions after exposure to hypoxia than BEX-c, (2) WIX-c showed higher glucose uptake and lactate release rates than BEX-c both under aerobic and hypoxic conditions, and (3) hypoxia induced apoptosis in WIX-c but not in BEX-c. These observations suggested that the difference between BEX-c and WIX-c spheroids in fraction of hypoxic cells resulted partly from differences in cell energy metabolism and partly from a difference in capacity to retain viability under hypoxic stress. The induction of apoptosis by hypoxia was identified as a phenomenon which has an important influence on the magnitude of the fraction of

  1. Cardiac biomarkers in neonatal hypoxic ischaemia.

    LENUS (Irish Health Repository)

    Sweetman, D

    2012-04-01

    Following a perinatal hypoxic-ischaemic insult, term infants commonly develop cardiovascular dysfunction. Troponin-T, troponin-I and brain natriuretic peptide are sensitive indicators of myocardial compromise. The long-term effects of cardiovascular dysfunction on neurodevelopmental outcome following perinatal hypoxic ischaemia remain controversial. Follow-up studies are warranted to ensure optimal cardiac function in adulthood. CONCLUSION: Cardiac biomarkers may improve the diagnosis of myocardial injury, help guide management, estimate mortality risk and may also aid in longterm neurodevelopmental outcome prediction following neonatal hypoxic-ischaemia.

  2. Early cerebral hemodynamic, metabolic and histological changes in hypoxic-ischemic fetal lambs during postnatal life

    Directory of Open Access Journals (Sweden)

    Carmen eRey-Santano

    2011-09-01

    Full Text Available The hemodynamic, metabolic and biochemical changes produce during transition from fetal to neonatal life could be aggravated if asphyctic event occur during fetal life. The aim of the study was to examine the regional cerebral blood flow (RCBF, histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress for the first hours of postnatal life following severe fetal asphyxia. 18 chronically instrumented fetal lambs were assigned to: hypoxic-ischemic group, following fetal asphyxia animals were delivered and maintained on intermittent-positive-pressure-ventilation for 3 hours, and non-injured animals that were managed similarly to the previous group and used as control group. During hypoxic-ischemic insult, injured group developed acidosis, hypoxia, hypercapnia, latacidaemia and tachycardia in comparison to control group, without hypotension. Intermittent-positive-pressure-ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilation-support, the increased RCBF in inner zones was maintained for hypoxic-ischemic group, but cortical flow did not exhibit differences compared to the control group. Also, the increase of TUNEL positive cells (apoptosis and antioxidant enzymes, and decrease of ATP reserves was significantly higher in the brain regions where the RCBF were not increased.In conclusion, early metabolic, histological and hemodynamic changes involved in brain damage have been intensively investigated and reported in premature asphyctic lambs for the first 3 hours of postnatal life. Those changes have been described in human neonates, so our model could be useful to test the security and the effectiveness of different neuroprotective or ventilatory strategies when are applied in the first hours after fetal hypoxic-ischemic injury.

  3. Optimal intermittent search strategies

    Energy Technology Data Exchange (ETDEWEB)

    Rojo, F; Budde, C E [FaMAF, Universidad Nacional de Cordoba, Ciudad Universitaria, X5000HUA Cordoba (Argentina); Wio, H S [Instituto de Fisica de Cantabria, Universidad de Cantabria and CSIC E-39005 Santander (Spain)

    2009-03-27

    We study the search kinetics of a single fixed target by a set of searchers performing an intermittent random walk, jumping between different internal states. Exploiting concepts of multi-state and continuous-time random walks we have calculated the survival probability of a target up to time t, and have 'optimized' (minimized) it with regard to the transition probability among internal states. Our model shows that intermittent strategies always improve target detection, even for simple diffusion states of motion.

  4. Intermittency and random matrices

    Science.gov (United States)

    Sokoloff, Dmitry; Illarionov, E. A.

    2015-08-01

    A spectacular phenomenon of intermittency, i.e. a progressive growth of higher statistical moments of a physical field excited by an instability in a random medium, attracted the attention of Zeldovich in the last years of his life. At that time, the mathematical aspects underlying the physical description of this phenomenon were still under development and relations between various findings in the field remained obscure. Contemporary results from the theory of the product of independent random matrices (the Furstenberg theory) allowed the elaboration of the phenomenon of intermittency in a systematic way. We consider applications of the Furstenberg theory to some problems in cosmology and dynamo theory.

  5. Response of streptozotocin-induced diabetes in rats under oxidative stress of intermittent radiation exposure to either antioxidant or insulin mimic treatment

    International Nuclear Information System (INIS)

    Noaman, E.; El-Tahawy, N.A.; Hedayat, I.S.; Mansour, S.Z.; Fahmy, Y.N.

    2005-01-01

    Diabetic rats were treated with 0.5% a-lipoic acid, as a diet supplement, or was administered with vanadyl sulphate in drinking water at a dose of 75 mg/kg with or without whole body gamma radiation exposure with repeated dose of 4 Gy/week for 4 weeks. Both treatments significantly improved diabetes-induced increase in glucose concentration. Treating diabetic rats with a-lipoic acid prevented the diabetes-induced increase in thiobarbituric acid reactive substances in plasma and significantly improved liver glutathione levels. On the other hand, treating diabetic rats with vanadyl sulphate not only prevented diabetes-induced changes of either of these oxidative stress markers but also normalized glucose concentration and ameliorated the increase in body weight gain. Diabetes with or without radiation exposure induced increase in liver conjugated diene levels and such elevation was improved by the treatment with either a-lipoic acid or vanadyl sulphate. Treating diabetic rats with a-lipoic acid and vanadyl sulphate partially improved liver No*VlC-ATPase activity and sorbitol and myo-inositol contents. The increase in liver sorbitol levels in diabetic rats was ameliorated by either treatment. These studies suggest that diabetes-induced oxidative stress may be partially responsible for the development of diabetic complications and the treatment with vanadyl sulphate was more advantageous than a-lipoic acid in handling these complications

  6. Adapting radiotherapy to hypoxic tumours

    Science.gov (United States)

    Malinen, Eirik; Søvik, Åste; Hristov, Dimitre; Bruland, Øyvind S.; Rune Olsen, Dag

    2006-10-01

    In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO2-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO2-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields

  7. Adapting radiotherapy to hypoxic tumours

    International Nuclear Information System (INIS)

    Malinen, Eirik; Soevik, Aste; Hristov, Dimitre; Bruland, Oeyvind S; Olsen, Dag Rune

    2006-01-01

    In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO 2 -related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO 2 -related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO 2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO 2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure

  8. Turnover rate of hypoxic cells in solid tumors

    International Nuclear Information System (INIS)

    Ljungkvist, A.S.E.; Bussink, J.; Rijken, P.F.J.W.; Van Der Kogel, A.J.

    2003-01-01

    Most solid tumors contain hypoxic cells, and both the amount and duration of tumor hypoxia has been shown to influence the effect of radiation treatment negatively. It is important to understand the dynamic processes within the hypoxic cell population in non-treated tumors, and the effect of different treatment modalities on the kinetics of hypoxic cells to be able to design optimal combined modality treatments. The turnover rate of hypoxic cells was analyzed in three different solid tumor models with a double bio-reductive hypoxic marker assay with sequential injection of the two hypoxic markers. Previously it was shown that this assay could be used to detect both a decrease and an increase of tumor hypoxia in relation to the tumor vasculature with high spatial resolution. In this study the first hypoxic marker, pimonidazole, was administered at variable times relative to tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. The hypoxic cell turnover rate was calculated as the loss of pimonidazole positive cells relative to CCI-103F. The murine C38 line had the fastest hypoxic turnover rate of 60% /24h and the human xenograft line SCCNij3 had the slowest hypoxic turnover rate of 30% /24 h. The hypoxic turnover rate was most heterogeneous in the SCCNij3 line that even contained viable groups of cells that had been hypoxic for at least 5 days. The human xenograft line MEC82 fell in between with a hypoxic turnover rate of 50% /24 h. The hypoxic cell turnover was related to the potential tumor volume doubling time (Tpot) with a Tpot of 26h in C38 and 103h in SCCNij3. The dynamics of hypoxic cells, quantified with a double hypoxic marker method, showed large differences in hypoxic cell turnover rate and were related to Tpot

  9. Cytotoxic properties of a 4-nitroimidazole (NSC 38087): a radiosensitizer of hypoxic cells in vitro

    International Nuclear Information System (INIS)

    Stratford, I.J.; Williamson, C.; Hardy, C.

    1981-01-01

    5-Phenoxysulphonyl-1-methyl-4-nitroimidazole (NSC 38087) can act as a sensitizer of hypoxic mammalian cells to radiation in vitro. The degree of sensitization achieved is greater than would be predicted from the drug's electron affinity. Cytotoxicity studies have shown that 5sub(μM) NSC 38087 can reduce the surviving fraction of log-phase V79 cells in air at 37 0 C to 10 -2 after 2 h exposure. This toxicity is considerably increased by small rises in temperature. In contrast to other nitroheterocyclic radiosensitizers, NSC 38087 and related 5-substituted 4-nitroimidazoles show greater toxicity towards aerobic than to hypoxic cells. Log-phase cells show the highest sensitivity to the toxic action of NSC 38087, with plateau-phase cells, cells with a history of chronic hypoxia, and thermotolerant cells showing greater resistance. These toxicity data are compared to those for the 2-nitroimidazole hypoxic-cell sensitizer misonidazole. (author)

  10. Quasistatic Dynamics with Intermittency

    International Nuclear Information System (INIS)

    Leppänen, Juho; Stenlund, Mikko

    2016-01-01

    We study an intermittent quasistatic dynamical system composed of nonuniformly hyperbolic Pomeau–Manneville maps with time-dependent parameters. We prove an ergodic theorem which shows almost sure convergence of time averages in a certain parameter range, and identify the unique physical family of measures. The theorem also shows convergence in probability in a larger parameter range. In the process, we establish other results that will be useful for further analysis of the statistical properties of the model.

  11. Quasistatic Dynamics with Intermittency

    Energy Technology Data Exchange (ETDEWEB)

    Leppänen, Juho; Stenlund, Mikko, E-mail: mikko.stenlund@helsinki.fi [University of Helsinki, Department of Mathematics and Statistics (Finland)

    2016-06-15

    We study an intermittent quasistatic dynamical system composed of nonuniformly hyperbolic Pomeau–Manneville maps with time-dependent parameters. We prove an ergodic theorem which shows almost sure convergence of time averages in a certain parameter range, and identify the unique physical family of measures. The theorem also shows convergence in probability in a larger parameter range. In the process, we establish other results that will be useful for further analysis of the statistical properties of the model.

  12. Developmental hyperoxia alters CNS mechanisms underlying hypoxic ventilatory depression in neonatal rats.

    Science.gov (United States)

    Hill, Corey B; Grandgeorge, Samuel H; Bavis, Ryan W

    2013-12-01

    Newborn mammals exhibit a biphasic hypoxic ventilatory response (HVR), but the relative contributions of carotid body-initiated CNS mechanisms versus central hypoxia on ventilatory depression during the late phase of the HVR are not well understood. Neonatal rats (P4-5 or P13-15) were treated with a nonselective P2 purinergic receptor antagonist (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, or PPADS; 125mgkg(-1), i.p.) to pharmacologically denervate the peripheral chemoreceptors. At P4-5, rats reared in normoxia showed a progressive decline in ventilation during a 10-min exposure to 12% O2 (21-28% decrease from baseline). No hypoxic ventilatory depression was observed in the older group of neonatal rats (i.e., P13-15), suggesting that the contribution of central hypoxia to hypoxic ventilatory depression diminishes with age. In contrast, rats reared in moderate hyperoxia (60% O2) from birth exhibited no hypoxic ventilatory depression at either age studied. Systemic PPADS had no effect on the ventilatory response to 7% CO2, suggesting that the drug did not cross the blood-brain barrier. These findings indicate that (1) CNS hypoxia depresses ventilation in young, neonatal rats independent of carotid body activation and (2) hyperoxia alters the development of CNS pathways that modulate the late phase of the hypoxic ventilatory response. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Chronic intermittent ethanol exposure and withdrawal alters (3α,5α)-3-hydroxy-pregnan-20-one immunostaining in cortical and limbic brain regions of C57BL/6J mice.

    Science.gov (United States)

    Maldonado-Devincci, Antoniette M; Cook, Jason B; O'Buckley, Todd K; Morrow, Danielle H; McKinley, Raechel E; Lopez, Marcelo F; Becker, Howard C; Morrow, A Leslie

    2014-10-01

    The GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP; allopregnanolone) has been studied during withdrawal from ethanol (EtOH) in humans, rats, and mice. Serum 3α,5α-THP levels decreased, and brain levels were not altered following acute EtOH administration (2 g/kg) in male C57BL/6J mice; however, the effects of chronic intermittent ethanol (CIE) exposure on 3α,5α-THP levels have not been examined. Given that CIE exposure changes subsequent voluntary EtOH drinking in a time-dependent fashion following repeated cycles of EtOH exposure, we conducted a time-course analysis of CIE effects on 3α,5α-THP levels in specific brain regions known to influence drinking behavior. Adult male C57BL/6J mice were exposed to 4 cycles of CIE to induce EtOH dependence. All mice were sacrificed and perfused at 1 of 2 time points, 8 or 72 hours following the final exposure cycle. Free-floating brain sections (40 μm; 3 to 5 sections/region/animal) were immunostained and analyzed to determine relative levels of cellular 3α,5α-THP. Withdrawal from CIE exposure produced time-dependent and region-specific effects on immunohistochemical detection of 3α,5α-THP levels across cortical and limbic brain regions. A transient reduction in 3α,5α-THP immunoreactivity was observed in the central nucleus of the amygdala 8 hours after withdrawal from CIE (-31.4 ± 9.3%). Decreases in 3α,5α-THP immunoreactivity were observed 72 hours following withdrawal in the medial prefrontal cortex (-25.0 ± 9.3%), nucleus accumbens core (-29.9 ± 6.6%), and dorsolateral striatum (-18.5 ± 6.0%), while an increase was observed in the CA3 pyramidal cell layer of the hippocampus (+42.8 ± 19.5%). Sustained reductions in 3α,5α-THP immunoreactivity were observed at both time points in the lateral amygdala (8 hours -28.3 ± 12.8%; 72 hours -27.5 ± 12.4%) and in the ventral tegmental area (8 hours -26.5 ± 9.9%; 72 hours -31.6 ± 13.8%). These data

  14. Astrocyte-derived proinflammatory cytokines induce hypomyelination in the periventricular white matter in the hypoxic neonatal brain.

    Directory of Open Access Journals (Sweden)

    Yiyu Deng

    Full Text Available Hypoxic exposure in the perinatal period causes periventricular white matter damage (PWMD, a condition associated with myelination abnormalities. Under hypoxic conditions, glial cells were activated and released a large number of inflammatory mediators in the PWM in neonatal brain, which may result in oligodendrocyte (OL loss and axonal injury. This study aims to determine if astrocytes are activated and generate proinflammatory cytokines that may be coupled with the oligodendroglial loss and hypomyelination observed in hypoxic PWMD. Twenty-four 1-day-old Wistar rats were exposed to hypoxia for 2 h. The rats were then allowed to recover under normoxic conditions for 7 or 28 days before being killed. Another group of 24 rats kept outside the chamber was used as age-matched controls. Upregulated expression of TNF-α and IL-1β was observed in astrocytes in the PWM of P7 hypoxic rats by double immunofluorescence, western blotting and real time RT-PCR. This was linked to apoptosis and enhanced expression of TNF-R1 and IL-1R1 in APC(+ OLs. PLP expression was decreased significantly in the PWM of P28d hypoxic rats. The proportion of myelinated axons was markedly reduced by electron microscopy (EM and the average g-ratios were higher in P28d hypoxic rats. Upregulated expression of TNF-α and IL-1β in primary cultured astrocytes as well as their corresponding receptors in primary culture APC(+ oligodendrocytes were detected under hypoxic conditions. Our results suggest that following a hypoxic insult, astrocytes in the PWM of neonatal rats produce inflammatory cytokines such as TNF-α and IL-1β, which induce apoptosis of OLs via their corresponding receptors associated with them. This results in hypomyelination in the PWM of hypoxic rats.

  15. Intermittent Hypoxia Enhances Functional Connectivity of Midcervical Spinal Interneurons

    Science.gov (United States)

    Streeter, Kristi A.; Sunshine, Michael D.; Patel, Shreya; Gonzalez-Rothi, Elisa J.; Reier, Paul J.

    2017-01-01

    Brief, intermittent oxygen reductions [acute intermittent hypoxia (AIH)] evokes spinal plasticity. Models of AIH-induced neuroplasticity have focused on motoneurons; however, most midcervical interneurons (C-INs) also respond to hypoxia. We hypothesized that AIH would alter the functional connectivity between C-INs and induce persistent changes in discharge. Bilateral phrenic nerve activity was recorded in anesthetized and ventilated adult male rats and a multielectrode array was used to record C4/5 spinal discharge before [baseline (BL)], during, and 15 min after three 5 min hypoxic episodes (11% O2, H1–H3). Most C-INs (94%) responded to hypoxia by either increasing or decreasing firing rate. Functional connectivity was examined by cross-correlating C-IN discharge. Correlograms with a peak or trough were taken as evidence for excitatory or inhibitory connectivity between C-IN pairs. A subset of C-IN pairs had increased excitatory cross-correlations during hypoxic episodes (34%) compared with BL (19%; p phrenic motoneurons and excitatory inputs to these “pre-phrenic” cells increased during AIH. We conclude that AIH alters connectivity of the midcervical spinal network. To our knowledge, this is the first demonstration that AIH induces plasticity within the propriospinal network. SIGNIFICANCE STATEMENT Acute intermittent hypoxia (AIH) can trigger spinal plasticity associated with sustained increases in respiratory, somatic, and/or autonomic motor output. The impact of AIH on cervical spinal interneuron (C-IN) discharge and connectivity is unknown. Our results demonstrate that AIH recruits excitatory C-INs into the spinal respiratory (phrenic) network. AIH also enhances excitatory and reduces inhibitory connections among the C-IN network. We conclude that C-INs are part of the respiratory, somatic, and/or autonomic response to AIH, and that propriospinal plasticity may contribute to sustained increases in motor output after AIH. PMID:28751456

  16. Pulmonary capillary recruitment in response to hypoxia in healthy humans: a possible role for hypoxic pulmonary venoconstriction?

    DEFF Research Database (Denmark)

    Taylor, Bryan J; Kjaergaard, Jesper; Snyder, Eric M

    2011-01-01

    We examined mechanisms by which hypoxia may elicit pulmonary capillary recruitment in humans. On separate occasions, twenty-five healthy adults underwent exposure to intravenous saline infusion (30 ml/kg ∼ 15 min) or 17-h normobaric hypoxia ( [FIO2 = 12.5%). Cardiac output (Q) and pulmonary...... capillary blood volume (Vc) were measured before and after saline infusion and hypoxic-exposure by a rebreathing method. Pulmonary artery systolic pressure (sPpa) and left ventricular (LV) diastolic function were assessed before and after hypoxic-exposure via echocardiography. Saline infusion increased Q......Ppa and LV diastolic function. In conclusion, hypoxia-induced pulmonary capillary recruitment in humans is only partly accounted for by changes in Q, sPpa and LV diastolic function. We speculate that hypoxic pulmonary venoconstriction may play a role in such recruitment....

  17. Intermittent hypoxia increases insulin resistance in genetically obese mice.

    Science.gov (United States)

    Polotsky, Vsevolod Y; Li, Jianguo; Punjabi, Naresh M; Rubin, Arnon E; Smith, Philip L; Schwartz, Alan R; O'Donnell, Christopher P

    2003-10-01

    Obstructive sleep apnoea, a syndrome that leads to recurrent intermittent hypoxia, is associated with insulin resistance in obese individuals, but the mechanisms underlying this association remain unknown. We utilized a mouse model to examine the effects of intermittent hypoxia on insulin resistance in lean C57BL/6J mice and leptin-deficient obese (C57BL/6J-Lepob) mice. In lean mice, exposure to intermittent hypoxia for 5 days (short term) resulted in a decrease in fasting blood glucose levels (from 173 +/- 11 mg dl-1 on day 0 to 138 +/- 10 mg dl-1 on day 5, P obese mice, short-term intermittent hypoxia led to a decrease in blood glucose levels accompanied by a 607 +/- 136 % (P intermittent hypoxia was completely abolished by prior leptin infusion. Obese mice exposed to intermittent hypoxia for 12 weeks (long term) developed a time-dependent increase in fasting serum insulin levels (from 3.6 +/- 1.1 ng ml-1 at baseline to 9.8 +/- 1.8 ng ml-1 at week 12, P intermittent hypoxia is dependent on the disruption of leptin pathways.

  18. Daily intermittent hypoxia enhances walking after chronic spinal cord injury

    Science.gov (United States)

    Hayes, Heather B.; Jayaraman, Arun; Herrmann, Megan; Mitchell, Gordon S.; Rymer, William Z.

    2014-01-01

    Objectives: To test the hypothesis that daily acute intermittent hypoxia (dAIH) and dAIH combined with overground walking improve walking speed and endurance in persons with chronic incomplete spinal cord injury (iSCI). Methods: Nineteen subjects completed the randomized, double-blind, placebo-controlled, crossover study. Participants received 15, 90-second hypoxic exposures (dAIH, fraction of inspired oxygen [Fio2] = 0.09) or daily normoxia (dSHAM, Fio2 = 0.21) at 60-second normoxic intervals on 5 consecutive days; dAIH was given alone or combined with 30 minutes of overground walking 1 hour later. Walking speed and endurance were quantified using 10-Meter and 6-Minute Walk Tests. The trial is registered at ClinicalTrials.gov (NCT01272349). Results: dAIH improved walking speed and endurance. Ten-Meter Walk time improved with dAIH vs dSHAM after 1 day (mean difference [MD] 3.8 seconds, 95% confidence interval [CI] 1.1–6.5 seconds, p = 0.006) and 2 weeks (MD 3.8 seconds, 95% CI 0.9–6.7 seconds, p = 0.010). Six-Minute Walk distance increased with combined dAIH + walking vs dSHAM + walking after 5 days (MD 94.4 m, 95% CI 17.5–171.3 m, p = 0.017) and 1-week follow-up (MD 97.0 m, 95% CI 20.1–173.9 m, p = 0.014). dAIH + walking increased walking distance more than dAIH after 1 day (MD 67.7 m, 95% CI 1.3–134.1 m, p = 0.046), 5 days (MD 107.0 m, 95% CI 40.6–173.4 m, p = 0.002), and 1-week follow-up (MD 136.0 m, 95% CI 65.3–206.6 m, p walking improved walking speed and distance in persons with chronic iSCI. The impact of dAIH is enhanced by combination with walking, demonstrating that combinatorial therapies may promote greater functional benefits in persons with iSCI. Classification of evidence: This study provides Class I evidence that transient hypoxia (through measured breathing treatments), along with overground walking training, improves walking speed and endurance after iSCI. PMID:24285617

  19. Intermittency in Complex Flows

    Science.gov (United States)

    Ben Mahjoub, Otman; Redondo, Jose M.

    2017-04-01

    Experimental results of the complex turbulent wake of a cilinder in 2D [1] and 3D flows [2] were used to investigate the scaling of structure functions, similar research was also performed on wave propagation and breaking in the Ocean [3], in the the stratified Atmosphere (ABL) [4] and in a 100large flume (UPC) for both regular and irregular waves, where long time series of waves propagating and generating breaking turbulence velocity rms and higher order measurements were taken in depth. [3,5] by means of a velocimeter SONTEK3-D. The probability distribution functions of the velocity differences and their non Gaussian distribution related to the energy spectrum indicate that irregularity is an important source of turbulence. From Kolmogorov's K41 and K61 intermittency correction: the p th-order longitudinal velocity structure function δul at scale l in the inertial range of three-dimensional fully developed turbulence is related by ⟨δup⟩ = ⟨(u(x+ l)- u(x))p⟩ ˜ ɛp0/3lp/3 l where ⟨...⟩ represents the spatial average over flow domain, with ɛ0 the mean energy dissipation per unit mass and l is the separation distance. The importance of the random nature of the energy dissipation led to the K62 theory of intermittency, but locality and non-homogeneity are key issues. p p/3 p/3 ξd ⟨δul⟩ ˜ ⟨ɛl ⟩l ˜ l and ξp = p 3 + τp/3 , where now ɛl is a fractal energy dissipation at scale l, τp/3 is the scaling of and ξp is the scaling exponent of the velocity structure function of order p. Both in K41 and K62, the structure functions of third order related to skewness is ξ3 = 1. But this is not true either. We show that scaling exponents ξp do deviate from early studies that only investigated homogeneous turbulence, where a large inertial range dominates. The use of multi-fractal analysis and improvements on Structure function calculations on standard Enhanced mixing is an essential property of turbulence and efforts to alter and to control

  20. Intermittency in nuclear multifragmentation

    International Nuclear Information System (INIS)

    Ploszajczak, M.; Tucholski, A.

    1990-07-01

    Fluctuations of the fragment size distribution in a percolation model and in nuclear multifragmentation following the breakup of high energy nuclei in the nuclear emulsion are studied using the method of scaled factorial moments. An intermittent patern of fluctuations is found in the data as well as in the percolation lattice calculation. This is a consequence of both a self-similarity in the fragment size distribution and a random character for the scaling law. These fluctuations are in general well-described by percolation model. The multifractal dimensions are calculated and their relevance to the study of possible critical behaviour is pointed out. (orig.)

  1. Multidimensional intermittency in hadronic collisions

    International Nuclear Information System (INIS)

    Pan, J.; Hwa, R.C.

    1992-06-01

    The study of intermittency in high-energy hadronic collisions by the Monte Carlo code ECCO is extended to 3-dimensional phase space. Strong intermittency is found in agreement with the data. Fluctuation in the impact parameter is responsible for the intermittency in lnp T , and the transverse-momentum conservation leads to negative intermittency slopes in the azimuthal angle φ. The Ochs-Wosiek plots are linear in all dimensions having universal slopes. An exponent ν = 1.448 emerges to characterize multiparticle production in pp collisions. The properties of G moments are also examined, and the fractal dimensions determined

  2. Hypoxic hypoxia as a means of modifying radiosensibility

    International Nuclear Information System (INIS)

    Neumeister, K.; Niemiec, C.; Bolck, M.; Jahns, J.; Kamprad, F.; Arnold, P.; Johannsen, U.; Koch, F.; Mehlhorn, G.

    1977-01-01

    Following an overview of the various possibilities of creating hypoxia in mammals, the problem of reducing radioresistance of hypoxic tumor cells is treated. Furthermore, the results of irradiation experiments with mice, rats and pigs breathing hypoxic mixtures of O 2 and N 2 are given and discussed with a view to applying hypoxic hypoxia in the radiotherapy of human tumors. (author)

  3. Tracking hypoxic signaling within encapsulated cell aggregates.

    Science.gov (United States)

    Skiles, Matthew L; Sahai, Suchit; Blanchette, James O

    2011-12-16

    In Diabetes mellitus type 1, autoimmune destruction of the pancreatic β-cells results in loss of insulin production and potentially lethal hyperglycemia. As an alternative treatment option to exogenous insulin injection, transplantation of functional pancreatic tissue has been explored. This approach offers the promise of a more natural, long-term restoration of normoglycemia. Protection of the donor tissue from the host's immune system is required to prevent rejection and encapsulation is a method used to help achieve this aim. Biologically-derived materials, such as alginate and agarose, have been the traditional choice for capsule construction but may induce inflammation or fibrotic overgrowth which can impede nutrient and oxygen transport. Alternatively, synthetic poly(ethylene glycol) (PEG)-based hydrogels are non-degrading, easily functionalized, available at high purity, have controllable pore size, and are extremely biocompatible. As an additional benefit, PEG hydrogels may be formed rapidly in a simple photo-crosslinking reaction that does not require application of non-physiological temperatures. Such a procedure is described here. In the crosslinking reaction, UV degradation of the photoinitiator, 1-[4-(2-Hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one (Irgacure 2959), produces free radicals which attack the vinyl carbon-carbon double bonds of dimethacrylated PEG (PEGDM) inducing crosslinking at the chain ends. Crosslinking can be achieved within 10 minutes. PEG hydrogels constructed in such a manner have been shown to favorably support cells, and the low photoinitiator concentration and brief exposure to UV irradiation is not detrimental to viability and function of the encapsulated tissue. While we methacrylate our PEG with the method described below, PEGDM can also be directly purchased from vendors such as Sigma. An inherent consequence of encapsulation is isolation of the cells from a vascular network. Supply of nutrients, notably oxygen

  4. CT diagnosis of hypoxic ischemic encephalopathy

    International Nuclear Information System (INIS)

    Zhao Xiang; Ma Jiwei; Wu Lide

    2004-01-01

    Objective: To explore CT characteristics of hypoxic ischemic encephalopathy (HIE), and to improve the accuracy of CT diagnosis. Methods: 50 cases of neonatal asphyxia in perinatal period diagnosed as hypoxic ischemic encephalopathy by CT was analyzed. Results: The main manifestation of hypoxic ischemic encephalopathy is cerebral edema and intracranial hemorrhage. Focal or diffuse hypo-dense lesion and hyper-dense area in various location and morphology were seen on CT images. (1) Localized diffuse hypo-dense area in 1 or 2 cerebral lobe were found in 17 cases, and the lesions were localized in frontal lobe (n=6), in frontotemporal lobe (n=5), and in temporo-occipital lobe (n=6). (2) Hypo-density region involving more than three cerebral lobes were found in 18 cases, and abnormalities were found in frontotemporal and parietal lobe (n=8), accompanying with subarachnoid hemorrhage (n=2); in frontal, temporal and occipital lobe (n=6), in which cerebral hemorrhage was complicated (n=1); and in other cerebral lobe (n=4). (3) Diffuse low-density region in all cerebral lobe were found in 15 cases, in which subarachnoid hemorrhage was complicated in 4 cases, and ventricular hemorrhage was found in 2 case. Conclusion: CT imaging plays an important role in diagnosis of hypoxic ischemic encephalopathy and has shown its clinical value

  5. Hypoxic challenge test applied to healthy children

    DEFF Research Database (Denmark)

    Kobbernagel, Helene Elgaard; Nielsen, Kim Gjerum; Hanel, Birgitte

    2013-01-01

    BACKGROUND: Commercial aircraft are pressurised to ~2438 m (8000 ft) above sea level that equates breathing 15% oxygen at sea level. A preflight hypoxic challenge test (HCT) is therefore recommended for children with cystic fibrosis or other chronic lung diseases and inflight oxygen is advised if...

  6. Hypoxic survival strategies in two fishes: extreme anoxia tolerance in the North European crucian carp and natural hypoxic preconditioning in a coral-reef shark.

    Science.gov (United States)

    Nilsson, Göran E; Renshaw, Gillian M C

    2004-08-01

    Especially in aquatic habitats, hypoxia can be an important evolutionary driving force resulting in both convergent and divergent physiological strategies for hypoxic survival. Examining adaptations to anoxic/hypoxic survival in hypoxia-tolerant animals may offer fresh ideas for the treatment of hypoxia-related diseases. Here, we summarise our present knowledge of two fishes that have evolved to survive hypoxia under very different circumstances. The crucian carp (Carassius carassius) is of particular interest because of its extreme anoxia tolerance. During the long North European winter, it survives for months in completely oxygen-deprived freshwater habitats. The crucian carp also tolerates a few days of anoxia at room temperature and, unlike anoxia-tolerant freshwater turtles, it is still physically active in anoxia. Moreover, the crucian carp does not appear to reduce neuronal ion permeability during anoxia and may primarily rely on more subtle neuromodulatory mechanisms for anoxic metabolic depression. The epaulette shark (Hemiscyllium ocellatum) is a tropical marine vertebrate. It lives on shallow reef platforms that repeatedly become cut off from the ocean during periods of low tides. During nocturnal low tides, the water [O(2)] can fall by 80% due to respiration of the coral and associated organisms. Since the tides become lower and lower over a period of a few days, the hypoxic exposure during subsequent low tides will become progressively longer and more severe. Thus, this shark is under a natural hypoxic preconditioning regimen. Interestingly, hypoxic preconditioning lowers its metabolic rate and its critical P(O(2)). Moreover, repeated anoxia appears to stimulate metabolic depression in an adenosine-dependent way.

  7. An innovative intermittent hypoxia model for cell cultures allowing fast Po2 oscillations with minimal gas consumption.

    Science.gov (United States)

    Minoves, Mélanie; Morand, Jessica; Perriot, Frédéric; Chatard, Morgane; Gonthier, Brigitte; Lemarié, Emeline; Menut, Jean-Baptiste; Polak, Jan; Pépin, Jean-Louis; Godin-Ribuot, Diane; Briançon-Marjollet, Anne

    2017-10-01

    Performing hypoxia-reoxygenation cycles in cell culture with a cycle duration accurately reflecting what occurs in obstructive sleep apnea (OSA) patients is a difficult but crucial technical challenge. Our goal was to develop a novel device to expose multiple cell culture dishes to intermittent hypoxia (IH) cycles relevant to OSA with limited gas consumption. With gas flows as low as 200 ml/min, our combination of plate holders with gas-permeable cultureware generates rapid normoxia-hypoxia cycles. Cycles alternating 1 min at 20% O 2 followed by 1 min at 2% O 2 resulted in Po 2 values ranging from 124 to 44 mmHg. Extending hypoxic and normoxic phases to 10 min allowed Po 2 variations from 120 to 25 mmHg. The volume of culture medium or the presence of cells only modestly affected the Po 2 variations. In contrast, the nadir of the hypoxia phase increased when measured at different heights above the membrane. We validated the physiological relevance of this model by showing that hypoxia inducible factor-1α expression was significantly increased by IH exposure in human aortic endothelial cells, murine breast carcinoma (4T1) cells as well as in a blood-brain barrier model (2.5-, 1.5-, and 6-fold increases, respectively). In conclusion, we have established a new device to perform rapid intermittent hypoxia cycles in cell cultures, with minimal gas consumption and the possibility to expose several culture dishes simultaneously. This device will allow functional studies of the consequences of IH and deciphering of the molecular biology of IH at the cellular level using oxygen cycles that are clinically relevant to OSA. Copyright © 2017 the American Physiological Society.

  8. Sex, stress and sleep apnoea: Decreased susceptibility to upper airway muscle dysfunction following intermittent hypoxia in females.

    Science.gov (United States)

    O'Halloran, Ken D; Lewis, Philip; McDonald, Fiona

    2017-11-01

    Obstructive sleep apnoea syndrome (OSAS) is a devastating respiratory control disorder more common in men than women. The reasons for the sex difference in prevalence are multifactorial, but are partly attributable to protective effects of oestrogen. Indeed, OSAS prevalence increases in post-menopausal women. OSAS is characterized by repeated occlusions of the pharyngeal airway during sleep. Dysfunction of the upper airway muscles controlling airway calibre and collapsibility is implicated in the pathophysiology of OSAS, and sex differences in the neuro-mechanical control of upper airway patency are described. It is widely recognized that chronic intermittent hypoxia (CIH), a cardinal feature of OSAS due to recurrent apnoea, drives many of the morbid consequences characteristic of the disorder. In rodents, exposure to CIH-related redox stress causes upper airway muscle weakness and fatigue, associated with mitochondrial dysfunction. Of interest, in adults, there is female resilience to CIH-induced muscle dysfunction. Conversely, exposure to CIH in early life, results in upper airway muscle weakness equivalent between the two sexes at 3 and 6 weeks of age. Ovariectomy exacerbates the deleterious effects of exposure to CIH in adult female upper airway muscle, an effect partially restored by oestrogen replacement therapy. Intriguingly, female advantage intrinsic to upper airway muscle exists with evidence of substantially greater loss of performance in male muscle during acute exposure to severe hypoxic stress. Sex differences in upper airway muscle physiology may have relevance to human OSAS. The oestrogen-oestrogen receptor α axis represents a potential therapeutic target in OSAS, particularly in post-menopausal women. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Metabolic Effects of Intermittent Fasting.

    Science.gov (United States)

    Patterson, Ruth E; Sears, Dorothy D

    2017-08-21

    The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved health outcomes. A MEDLINE search was performed using PubMed and the terms "intermittent fasting," "fasting," "time-restricted feeding," and "food timing." Modified fasting regimens appear to promote weight loss and may improve metabolic health. Several lines of evidence also support the hypothesis that eating patterns that reduce or eliminate nighttime eating and prolong nightly fasting intervals may result in sustained improvements in human health. Intermittent fasting regimens are hypothesized to influence metabolic regulation via effects on (a) circadian biology, (b) the gut microbiome, and (c) modifiable lifestyle behaviors, such as sleep. If proven to be efficacious, these eating regimens offer promising nonpharmacological approaches to improving health at the population level, with multiple public health benefits.

  10. Intermittent Hypoxia Affects the Spontaneous Differentiation In Vitro of Human Neutrophils into Long-Lived Giant Phagocytes

    Directory of Open Access Journals (Sweden)

    Larissa Dyugovskaya

    2016-01-01

    Full Text Available Previously we identified, for the first time, a new small-size subset of neutrophil-derived giant phagocytes (Gϕ which spontaneously develop in vitro without additional growth factors or cytokines. Gϕ are CD66b+/CD63+/MPO+/LC3B+ and are characterized by extended lifespan, large phagolysosomes, active phagocytosis, and reactive oxygen species (ROS production, and autophagy largely controls their formation. Hypoxia, and particularly hypoxia/reoxygenation, is a prominent feature of many pathological processes. Herein we investigated Gϕ formation by applying various hypoxic conditions. Chronic intermittent hypoxia (IH (29 cycles/day for 5 days completely abolished Gϕ formation, while acute IH had dose-dependent effects. Exposure to 24 h (56 IH cycles decreased their size, yield, phagocytic ability, autophagy, mitophagy, and gp91-phox/p22-phox expression, whereas under 24 h sustained hypoxia (SH the size and expression of LC3B and gp91-phox/p22-phox resembled Gϕ formed in normoxia. Diphenyl iodide (DPI, a NADPH oxidase inhibitor, as well as the PI3K/Akt and autophagy inhibitor LY294002 abolished Gϕ formation at all oxygen conditions. However, the potent antioxidant, N-acetylcysteine (NAC abrogated the effects of IH by inducing large CD66b+/LC3B+ Gϕ and increased both NADPH oxidase expression and phagocytosis. These findings suggest that NADPH oxidase, autophagy, and the PI3K/Akt pathway are involved in Gϕ development.

  11. Fate in intermittent claudication

    DEFF Research Database (Denmark)

    Jelnes, Rolf; Gaardsting, O; Hougaard Jensen, K

    1986-01-01

    , or an ankle/arm pressure index below 50% were individually significantly associated with progression of the arteriosclerotic disease. These findings show the importance of peripheral blood pressure measurements in the management of patients with intermittent claudication due to arteriosclerotic disease........ The rate of clinical progression of the arteriosclerotic disease (that is, rest pain or gangrene) of the worst affected leg was 7.5% in the first year after referral. Thereafter the rate was 2.2% a year. An ankle systolic blood pressure below 70 mm Hg, a toe systolic blood pressure below 40 mm Hg...... 113 of the patients (44%) had died. Causes of death were no different from those in the general population. Mortality was twice that of the general population matched for age and sex. Mortality among the men was twice that among the women. In men under 60 mortality was four times that expected...

  12. ANESTHETIC MANAGEMENT FOR A PATIENT WITH ACUTE INTERMITTENT PORPHYRIA

    Directory of Open Access Journals (Sweden)

    Nenad Savić

    2010-09-01

    Full Text Available Acute intermittent porphyria is a rare metabolic disorder resulting from a partial deficiency of porphobilinogen deaminase, enzyme in the heme biosynthetic pathway. Its inheritance is autosomal dominant. A deficiency of porphobilinogen deaminase is not sufficient by its self to produce acute intermittent porphyria, and other activating factors must also be present. These include some drugs, hormones, infection, injury and alcohol. Besides others, anesthetics have been implicated in the triggering of a number of severe porphyric reactions. Although there is no clinical evidence, the fear of hypothesized porphyrinogenicity of repetitive anesthetics exposures still remains. Despite these doubts, we report here the case of uneventful repeated exposure to anesthetics in a patient suffering from acute intermittent porphyria, within a fifteen- month period. On both occasions, the patient was safely exposed to certain anesthetics included: propofol, sevoflurane, rocuronium, midazolam and fentanyl.

  13. Retinal neuroprotection by hypoxic preconditioning is independent of hypoxia-inducible factor-1 alpha expression in photoreceptors.

    Science.gov (United States)

    Thiersch, Markus; Lange, Christina; Joly, Sandrine; Heynen, Severin; Le, Yun Zheng; Samardzija, Marijana; Grimm, Christian

    2009-06-01

    Hypoxic preconditioning stabilizes hypoxia-inducible factor (HIF) 1 alpha in the retina and protects photoreceptors against light-induced cell death. HIF-1 alpha is one of the major transcription factors responding to low oxygen tension and can differentially regulate a large number of target genes. To analyse whether photoreceptor-specific expression of HIF-1 alpha is essential to protect photoreceptors by hypoxic preconditioning, we knocked down expression of HIF-1 alpha specifically in photoreceptor cells, using the cyclization recombinase (Cre)-lox system. The Cre-mediated knockdown caused a 20-fold reduced expression of Hif-1 alpha in the photoreceptor cell layer. In the total retina, RNA expression was reduced by 65%, and hypoxic preconditioning led to only a small increase in HIF-1 alpha protein levels. Accordingly, HIF-1 target gene expression after hypoxia was significantly diminished. Retinas of Hif-1 alpha knockdown animals did not show any pathological alterations, and tolerated hypoxic exposure in a comparable way to wild-type retinas. Importantly, the strong neuroprotective effect of hypoxic preconditioning against light-induced photoreceptor degeneration persisted in knockdown mice, suggesting that hypoxia-mediated survival of light exposure does not depend on an autocrine action of HIF-1 alpha in photoreceptor cells. Hypoxia-mediated stabilization of HIF-2 alpha and phosphorylation of signal transducer and activator of transcription 3 (STAT 3) were not affected in the retinas of Hif-1 alpha knockdown mice. Thus, these factors are candidates for regulating the resistance of photoreceptors to light damage after hypoxic preconditioning, along with several potentially neuroprotective genes that were similarly induced in hypoxic knockdown and control mice.

  14. Hypoxic cell radiosensitization by moderate hyperthermia and glucose deprivation

    International Nuclear Information System (INIS)

    Kim, J.H.; Kim, S.H.; Hahn, E.W.

    1983-01-01

    Cell culture studies were carried out to determine whether moderate hyperthermia reduces the oxygen enhancement ratio of cells under well-defined cultural conditions. Using asynchronously growing HeLa cells, the OER of cells with and without glucose was determined following exposure of cells to moderate hyperthermia, 40.5omicronC for 1 hr, immediately after X irradiation. The OER of cells with 5 mM glucose was 3.2, whereas the OER of glucose-deprived cells was reduced to 2.0. The pH of the cell culture medium was kept at 7.4 throughtout the experiments. The present finding may provide a clue toward further enhancing the radiosensitization of hypoxic cells by heat

  15. Hypoxic cell radiosensitization by moderate hyperthermia and glucose deprivation

    International Nuclear Information System (INIS)

    Kim, J.H.; Kim, S.H.; Hahn, E.W.

    1983-01-01

    Cell culture studies were carried out to determine whether moderate hyperthermia reduces the oxygen enhancement ratio of cells under well-defined cultural conditions. Using asynchronously growing HeLa cells, the OER of cells with and without glucose was determined following exposure of cells to moderate hyperthermia, 40.5 degrees C for 1 hr, immediately after X irradiation. The OER of cells with 5 mM glucose was 3.2, whereas the OER of glucose-deprived cells was reduced to 2.0. The pH of the cell culture medium was kept at 7.4 throughout the experiments. The present finding may provide a clue toward further enhancing the radiosensitization of hypoxic cells by heat

  16. Hypoxic-induced stress protein expression in rat cardiac myocytes

    International Nuclear Information System (INIS)

    Howard, G.; Geoghegan, T.E.

    1986-01-01

    Mammalian stress proteins can be induced in cells and tissues exposed to a variety of conditions including hyperthermia and diminished O 2 supply. The authors have previously shown that the expression of three stress proteins (71, 85, and 95 kDa) was induced in cardiac tissue from mice exposed to hypoxic conditions. The expression of mRNAs coding for the 85 and 95 kDa proteins increase with time of exposure to hypoxia, while the mRNA coding for the 71 kDa protein is transiently induced. The authors extended these studies to investigate the expression of stress proteins in isolated rat cardiac myocytes. Freshly prepared myocytes were exposed to control, hypoxic, anoxic, or heat-shock environments for up to 16 h. The proteins were then labeled for 6 hours with [ 35 S]methionine. Analysis of the solubilized proteins by SDS-PAGE and autoradiography showed that there was a 6-fold increase in synthesis of the 85 kDa protein upon exposure to hypoxia but not heat-shock conditions. The 71 kDa protein was present at high levels in both control and treated myocyte protein preparations, and presumably had been induced during the isolation procedure. Total RNA isolated from intact rat heart and isolated myocytes was compared by cell-free translation analysis and showed induction of RNAs coding for several stress proteins in the myocyte preparation. The induced proteins at 85 and 95 kDa have molecular weights similar to reported cell stress and/or glucose-regulated proteins

  17. Differential uptake and metabolism of nitrite in normoxic and hypoxic goldfish

    DEFF Research Database (Denmark)

    Jensen, Frank Bo; Hansen, Marie N.

    2011-01-01

    extracellular and intracellular compartments, revealing nitrosative stress with extensive nitros(yl)ation of thiols, amines and heme groups. The degree of nitrosative stress correlated with nitrite load. Nitrate levels increased in all compartments, reflecting that a significant fraction of the nitrite taken up...... was converted to non-toxic nitrate. The generation of methemoglobin and nitrosylhemoglobin (assessed by spectral deconvolution) was more pronounced during normoxic nitrite exposure than during hypoxic nitrite exposure, in agreement with the higher nitrite load in normoxic fish. However, at any given nitrite......Nitrite is a physiological important nitric oxide donor at low concentrations but becomes toxic at high concentrations, as develops in freshwater fish exposed to environmental nitrite. We hypothesized that nitrite uptake across the gills differs between normoxic and hypoxic fish and that nitrite...

  18. The response of hypoxic cells in SCCVII murine tumors to treatment with cisplatin and x rays

    International Nuclear Information System (INIS)

    Yan, R.D.; Durand, R.E.

    1991-01-01

    Possible mechanisms of enhancement of radiation effects by cisplatin, including radiosensitization of hypoxic cells, drug-induced tumor reoxygenation, and inhibition of repair of sublethal radiation damage, were examined in the murine SCCVII model. Combination radiation/drug treatments were most effective when drug exposure preceded irradiation of animals breathing a reduced oxygen atmosphere, indicating that the primary interaction between the modalities was a cisplatin-induced increase in the oxygenation status of the acutely hypoxic cells in those tumors. Delivering cisplatin prior to or immediately after the first of two 5 Gy fractions was more effective than combinations with a single x-ray exposure, suggesting that proper sequences of the combined modalities may augment natural reoxygenation processes

  19. Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

    Directory of Open Access Journals (Sweden)

    Ding F

    2014-09-01

    Full Text Available Fengan Ding,1 Yiping Li,1 Jing Liu,1 Lei Liu,1 Wenmin Yu,1 Zhi Wang,1 Haifeng Ni,2 Bicheng Liu,2 Pingsheng Chen1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Institute of Nephrology, The Affiliated Zhongda Hospital, Southeast University, Nanjing, People’s Republic of China Background: Gold nanoparticles (GNPs can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells.Results: Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM to human renal proximal tubular cells (HK-2 by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the

  20. Current Theory on the Cerebral Mechanisms of Hypoxic PRE- and Postconditioning.

    Science.gov (United States)

    Rybnikova, E A; Samoilov, M O

    2016-01-01

    An exposure of the organism to several episodes of mild hypoxia results in the development of brain hypoxic/ischemic tolerance, as well as cross-tolerance to the stressful factors of psychoemotional nature. Such kind of preconditioning by mild hypoxia functions as “alarm signalization” by I.P. Pavlov, preparing the organism and, in particularly, brain to the forthcoming harmful event. Dose-dependent action of hypoxia on the brain can be considered as one particular case of the general phenomenon termed hormesis, or neurohormesis. Endogenous defense processes launched by the hypoxic preconditioning and leading to the development of cerebral tolerance are associated with activation of intracellular signal cascades, transcriptional factors, regulatory proteins and expression of pro-adaptive genes and their products in the susceptible brain regions. Important mechanism of systemic adaptation induced by hypoxic preconditioning includes modifications of pituitary-adrenal axis aimed at enhancement of its adaptive resources. All these components are involved in the neuroprotective processes in three sequential phases - initiation, induction, and expression. Important role belongs also to epigenetic mechanisms controlling the activity of pro-adaptive genes. In contrast to the preconditioning, hypoxic postconditioning is comparatively novel phenomenon and therefore its mechanisms are less studied. The involvement of hypoxia-inducible factor HIF-1, and non-specific protective processes as up-regulation of anti-apoptotic factors and neurotrophines.

  1. Contrasting hypoxic effects on breast cancer stem cell hierarchy is dependent on ER-α status.

    Science.gov (United States)

    Harrison, Hannah; Rogerson, Lynsey; Gregson, Hannah J; Brennan, Keith R; Clarke, Robert B; Landberg, Göran

    2013-02-15

    Tumor hypoxia is often linked to decreased survival in patients with breast cancer and current therapeutic strategies aim to target the hypoxic response. One way in which this is done is by blocking hypoxia-induced angiogenesis. Antiangiogenic therapies show some therapeutic potential with increased disease-free survival, but these initial promising results are short lived and followed by tumor progression. We hypothesized that this may be due to altered cancer stem cell (CSC) activity resulting from increased tumor hypoxia. We studied the effects of hypoxia on CSC activity, using in vitro mammosphere and holoclone assays as well as in vivo limiting dilution experiments, in 13 patient-derived samples and four cell lines. There was a HIF-1α-dependent CSC increase in ER-α-positive cancers following hypoxic exposure, which was blocked by inhibition of estrogen and Notch signaling. A contrasting decrease in CSC was seen in ER-α-negative cancers. We next developed a xenograft model of cell lines and patient-derived samples to assess the hypoxic CSC response. Varying sizes of xenografts were collected and analyzed for HIF1-α expression and CSC. The same ER-α-dependent contrasting hypoxic-CSC response was seen validating the initial observation. These data suggest that ER-α-positive and negative breast cancer subtypes respond differently to hypoxia and, as a consequence, antiangiogenic therapies will not be suitable for both subgroups.

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

    Science.gov (United States)

    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. Copyright © 2014 the American Physiological Society.

  3. Activation of radiosensitizers by hypoxic cells

    International Nuclear Information System (INIS)

    Olive, P.L.; Durand, R.E.

    1978-01-01

    Hypoxic cells metabolize nitroheterocyclic compounds to produce toxic intermediates capable of affecting the survival of neighboring oxygenated cells. Mutagenesis experiments with E. coli WP-2 343 (deficient in nitro-reductase) indicated that reduction of nitroheterocyclics outside bacteria causes killing and mutations within bacteria, presumably due to the transfer of the 'active' specie(s). Using animal tissue slices to reduce nitrofurans, cultured L-929 cells incubated under aerobic conditions were far more sensitive to the toxic and DNA damaging effects of these drugs. Transfer of the active species also occurs in a tissue-like environment in multicell spheroids where the presence of a hypoxic central core served to convert the nitroheterocyclics to intermediates which also damaged the neighbouring oxygenated cells. (author)

  4. Activation of radiosensitizers by hypoxic cells

    Energy Technology Data Exchange (ETDEWEB)

    Olive, P L; Durand, R E [Wisconsin Clinical Cancer Center, Madison (USA). Dept. of Human Oncology

    1978-06-01

    Hypoxic cells metabolize nitroheterocyclic compounds to produce toxic intermediates capable of affecting the survival of neighboring oxygenated cells. Mutagenesis experiments with E. coli WP-2 343 (deficient in nitro-reductase) indicated that reduction of nitroheterocyclics outside bacteria causes killing and mutations within bacteria, presumably due to the transfer of the 'active' specie(s). Using animal tissue slices to reduce nitrofurans, cultured L-929 cells incubated under aerobic conditions were far more sensitive to the toxic and DNA damaging effects of these drugs. Transfer of the active species also occurs in a tissue-like environment in multicell spheroids where the presence of a hypoxic central core served to convert the nitroheterocyclics to intermediates which also damaged the neighbouring oxygenated cells.

  5. Acute kidney injury with hypoxic respiratory failure

    OpenAIRE

    Neubert, Zachary; Hoffmann, Paul; Owshalimpur, David

    2014-01-01

    A 27-year-old Caucasian man was transferred from a remote clinic with acute kidney injury for the prior 7–10 days preceded by gastroenteritis. His kidney biopsy showed non-specific mesangiopathic glomerular changes, minimal tubulointerstitial disease without sclerosis, crescents, nor evidence of vasculitis. On his third hospital day, he developed acute hypoxic respiratory failure requiring intubation and mechanical ventilation. Pulmonary renal syndromes ranked highest on his differential diag...

  6. Naftidrofuryl for intermittent claudication.

    Science.gov (United States)

    De Backer, T L M; Vander Stichele, R; Lehert, P; Van Bortel, L

    2008-04-16

    Lifestyle changes and cardiovascular prevention measures are a primary treatment for intermittent claudication (IC). Symptomatic treatment with vasoactive agents (Anatomic Therapeutic Chemical Classification (ATC) for medicines from the World Health Organisation class CO4A) is controversial. To evaluate evidence on the efficacy and safety of oral naftidrofuryl (ATC CO4 21) versus placebo on the pain-free walking distance (PFWD) of people with IC by using a meta-analysis based on individual patient data (IPD). The Cochrane Peripheral Vascular Diseases Group searched their Trials Register (last searched December 2007) and CENTRAL (last searched 2007, Issue 4). We searched MEDLINE, EMBASE, International Pharmaceutical Abstracts, the Science Citation Index and contacted the authors and checked the reference lists of retrieved articles. We asked the manufacturing company for IPD. We included only randomized controlled trials (RCTs) with low or moderate risk of bias for which the IPD were available. We collected data from the electronic data file or from the case report form and checked the data by a statistical quality control procedure. All randomized patients were analyzed following the intention-to-treat (ITT) principle. The geometric mean of the relative improvement in PFWD was calculated for both treatment groups in all identified studies. The effect of the drug was assessed compared with placebo on final walking distance (WDf) using multilevel and random-effect models and adjusting for baseline walking distance (WD0). For the responder analysis, therapeutic success was defined as an improvement of walking distance of at least 50%. We included seven studies in the IPD (n = 1266 patients). One of these studies (n = 183) was only used in the sensitivity analysis so that the main analysis included 1083 patients. The ratio of the relative improvement in PFWD (naftidrofuryl compared with placebo) was 1.37 (95% confidence interval (CI) 1.32 to 1.51, P < 0.001). The

  7. The age dependent characteristics of the metabolic syndrome manifestation in animals exposed to ionized radiation in hypoxic conditions

    International Nuclear Information System (INIS)

    Gorban', Je.M.; Topol'nyikova, N.V.; Pod'yachenko, O.V.; Osipovyich, M.V.

    2011-01-01

    To study the influence of combination a single x-ray irradiation at a sublethal dose of adult and old rats with simultaneous hypoxic exposure to a number of manifestations of radioinduced changes, typical for metabolic syndrome (MS), 30 days after ionizing irradiation.

  8. Intermedia and Intermittency

    Directory of Open Access Journals (Sweden)

    Veres Bálint

    2014-12-01

    Full Text Available It is commonly known that medial reflections have been initiated by attempts to secure the borders of discrete medial forms and to define the modus operandi of each essentialized medial area. Later on, the focus of study has shifted to plurimedial formations and the interactions between predefined medial genres. In the last few decades, taxonomic approaches to various multi-, inter-, and transmedial phenomena dominated the discussions, which offered invaluable support in mapping the terrain, but at the same time hindered the analysis of the ephemeral, time-dependent aspects of plurimedial operations. While we explore the properties of each medial configuration, we lose sight of the actual historical drivers that produce ever-new configurations. My thesis is that any discourse on intermediality should be paralleled by a discourse on cultural intermittency, and consequently, media studies should involve an approach that focuses on the “ecosystem” of the constantly renewing media configurations from the point of view of their vitalizing potential and capability to trigger heightened experiences. This approach draws much inspiration from K. Ludwig Pfeiffer’s media anthropology that gives orientation in my paper.

  9. Intermittent hypoxia increases melanoma metastasis to the lung in a mouse model of sleep apnea.

    Science.gov (United States)

    Almendros, Isaac; Montserrat, Josep M; Torres, Marta; Dalmases, Mireia; Cabañas, Maria L; Campos-Rodríguez, Francisco; Navajas, Daniel; Farré, Ramon

    2013-05-01

    Obstructive sleep apnea (OSA) has recently been associated with an increased risk of cancer incidence and mortality in humans. Experimental data in mice have also shown that intermittent hypoxia similar to that observed in OSA patients enhances tumor growth. The aim of this study was to test the hypothesis that intermittent hypoxia mimicking OSA enhances lung metastasis. A total of 75 C57BL/6J male mice (10-week-old) were subjected to either spontaneous or induced melanoma lung metastasis. Normoxic animals breathed room air and intermittent hypoxic animals were subjected to cycles of 20s of 5% O2 followed by 40s of room air for 6h/day. Spontaneous and induced lung metastases were studied after subcutaneous and intravenous injection of B16F10 melanoma cells, respectively. Compared with normoxia, intermittent hypoxia induced a significant increase in melanoma lung metastasis. These animal model results suggest that intermittent hypoxia could contribute to cancer metastasis in patients with OSA. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Chronic Intermittent Hypoxia Induces Atherosclerosis

    OpenAIRE

    Savransky, Vladimir; Nanayakkara, Ashika; Li, Jianguo; Bevans, Shannon; Smith, Philip L.; Rodriguez, Annabelle; Polotsky, Vsevolod Y.

    2007-01-01

    Rationale: Obstructive sleep apnea, a condition leading to chronic intermittent hypoxia (CIH), is associated with hyperlipidemia, atherosclerosis, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has not been established.

  11. Dynamic characterizers of spatiotemporal intermittency

    OpenAIRE

    Gupte, Neelima; Jabeen, Zahera

    2006-01-01

    Systems of coupled sine circle maps show regimes of spatiotemporally intermittent behaviour with associated scaling exponents which belong to the DP class, as well as regimes of spatially intermittent behaviour (with associated regular dynamical behaviour) which do not belong to the DP class. Both types of behaviour are seen along the bifurcation boundaries of the synchronized solutions, and contribute distinct signatures to the dynamical characterizers of the system, viz. the distribution of...

  12. Distinct mechanisms underlying tolerance to intermittent and constant hypoxia in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Priti Azad

    Full Text Available BACKGROUND: Constant hypoxia (CH and intermittent hypoxia (IH occur during several pathological conditions such as asthma and obstructive sleep apnea. Our research is focused on understanding the molecular mechanisms that lead to injury or adaptation to hypoxic stress using Drosophila as a model system. Our current genome-wide study is designed to investigate gene expression changes and identify protective mechanism(s in D. melanogaster after exposure to severe (1% O(2 intermittent or constant hypoxia. METHODOLOGY/PRINCIPAL FINDINGS: Our microarray analysis has identified multiple gene families that are up- or down-regulated in response to acute CH or IH. We observed distinct responses to IH and CH in gene expression that varied in the number of genes and type of gene families. We then studied the role of candidate genes (up-or down-regulated in hypoxia tolerance (adult survival for longer periods (CH-7 days, IH-10 days under severe CH or IH. Heat shock proteins up-regulation (specifically Hsp23 and Hsp70 led to a significant increase in adult survival (as compared to controls of P-element lines during CH. In contrast, during IH treatment the up-regulation of Mdr49 and l(208717 genes (P-element lines provided survival advantage over controls. This suggests that the increased transcript levels following treatment with either paradigm play an important role in tolerance to severe hypoxia. Furthermore, by over-expressing Hsp70 in specific tissues, we found that up-regulation of Hsp70 in heart and brain play critical role in tolerance to CH in flies. CONCLUSIONS/SIGNIFICANCE: We observed that the gene expression response to IH or CH is specific and paradigm-dependent. We have identified several genes Hsp23, Hsp70, CG1600, l(208717 and Mdr49 that play an important role in hypoxia tolerance whether it is in CH or IH. These data provide further clues about the mechanisms by which IH or CH lead to cell injury and morbidity or adaptation and survival.

  13. Hypoxia-inducible factor-dependent production of profibrotic mediators by hypoxic hepatocytes.

    Science.gov (United States)

    Copple, Bryan L; Bustamante, Juan J; Welch, Timothy P; Kim, Nam Deuk; Moon, Jeon-Ok

    2009-08-01

    During the development of liver fibrosis, mediators are produced that stimulate cells in the liver to differentiate into myofibroblasts and to produce collagen. Recent studies demonstrated that the transcription factor, hypoxia-inducible factor-1alpha (HIF-1alpha), is critical for upregulation of profibrotic mediators, such as platelet-derived growth factor-A (PDGF-A), PDGF-B and plasminogen activator inhibitor-1 (PAI-1) in the liver, during the development of fibrosis. What remains unknown is the cell type-specific regulation of these genes by HIF-1alpha in liver cell types. Accordingly, the hypothesis was tested that HIF-1alpha is activated in hypoxic hepatocytes and regulates the production of profibrotic mediators by these cells. In this study, hepatocytes were isolated from the livers of control and HIF-1alpha- or HIF-1beta-deficient mice and exposed to hypoxia. Exposure of primary mouse hepatocytes to 1% oxygen stimulated nuclear accumulation of HIF-1alpha and upregulated PAI-1, vascular endothelial cell growth factor and the vasoactive peptides adrenomedullin-1 (ADM-1) and ADM-2. In contrast, the levels of PDGF-A and PDGF-B mRNAs were unaffected in these cells by hypoxia. Exposure of HIF-1alpha-deficient hepatocytes to 1% oxygen only partially prevented upregulation of these genes, suggesting that other hypoxia-regulated transcription factors, such as HIF-2alpha, may also regulate these genes. In support of this, HIF-2alpha was activated in hypoxic hepatocytes, and exposure of HIF-1beta-deficient hepatocytes to 1% oxygen completely prevented upregulation of PAI-1, vascular endothelial cell growth factor and ADM-1, suggesting that HIF-2alpha may also contribute to upregulation of these genes in hypoxic hepatocytes. Collectively, our results suggest that HIFs may be important regulators of profibrotic and vasoactive mediators by hypoxic hepatocytes.

  14. Hypoxic cell turnover in different solid tumor lines

    International Nuclear Information System (INIS)

    Ljungkvist, Anna S.E.; Bussink, Johan; Kaanders, Johannes H.A.M.; Rijken, Paulus F.J.W.; Begg, Adrian C.; Raleigh, James A.; Kogel, Albert J. van der

    2005-01-01

    Purpose: Most solid tumors contain hypoxic cells, and the amount of tumor hypoxia has been shown to have a negative impact on the outcome of radiotherapy. The efficacy of combined modality treatments depends both on the sequence and timing of the treatments. Hypoxic cell turnover in tumors may be important for optimal scheduling of combined modality treatments, especially when hypoxic cell targeting is involved. Methods and Materials: Previously we have shown that a double bioreductive hypoxic marker assay could be used to detect changes of tumor hypoxia in relation to the tumor vasculature after carbogen and hydralazine treatments. This assay was used in the current study to establish the turnover rate of hypoxic cells in three different tumor models. The first hypoxic marker, pimonidazole, was administered at variable times before tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. Hypoxic cell turnover was defined as loss of pimonidazole (first marker) relative to CCI-103F (second marker). Results: The half-life of hypoxic cell turnover was 17 h in the murine C38 colon carcinoma line, 23 h and 49 h in the human xenograft lines MEC82 and SCCNij3, respectively. Within 24 h, loss of pimonidazole-stained areas in C38 and MEC82 occurred concurrent with the appearance of pimonidazole positive cell debris in necrotic regions. In C38 and MEC82, most of the hypoxic cells had disappeared after 48 h, whereas in SCCNij3, viable cells that had been labeled with pimonidazole were still observed after 5 days. Conclusions: The present study demonstrates that the double hypoxia marker assay can be used to study changes in both the proportion of hypoxic tumor cells and their lifespan at the same time. The present study shows that large differences in hypoxic cell turnover rates may exist among tumor lines, with half-lives ranging from 17-49 h

  15. Further evidence for the absence of a hypoxic fraction in the 9L rat tumour multicellular spheroid system

    International Nuclear Information System (INIS)

    Gutin, P.H.; Barcellos, M.H.; Shrieve, D.C.; Sano, Y.; Bernstein, M.; Deen, D.F.

    1982-01-01

    The 9L gliosarcoma is an N-methylnitrosourea-induced rat brain tumour that has served as a predictive model for the efficacy of various chemotherapeutic agents against human brain tumours. Because it is one of two known animal tumour models that has no hypoxic fraction, the 9L model is of questionable value for the study of the radiobiology of hypoxic cell sensitizers. Hypoxic 9L monolayer cells are sensitive to misonidazole, as shown by the abrupt decrease in survival after a 2-4 h radiation exposure. However, when 9L spheroids in the size ranges of 200-300, 300-400, 500-600 and 1027+-33μm were incubated in euoxic spinner culture for up to 96 h in 1.5 or 3.0 mM misonidazole, there was no effect on the survival of the dissociated cells over a dose range 0-20 Gy. It is concluded that, in view of the demonstrated sensitivity to misonidazole of hypoxic 9L cells in monolayer culture, this finding provides further evidence that there are no hypoxic cells even in large 9L spheroids with a histologically distinct zone of central necrosis. Moreover, 9L spheroids irradiated in the presence of 3.0 mM misonidazole showed no dose enhancement. (U.K.)

  16. [Autonomic regulation at emotional stress under hypoxic conditions in the elderly with physiological and accelerated aging: effect of hypoxic training].

    Science.gov (United States)

    Os'mak, E D; Asanov, É O

    2014-01-01

    The effect of hypoxic training on autonomic regulation in psycho-emotional stress conditions in hypoxic conditions in older people with physiological (25 people) and accelerated (28 people) aging respiratory system. It is shown that hypoxic training leads to an increase in vagal activity indicators (HF) and reduced simpatovagal index (LF/HF), have a normalizing effect on the autonomic balance during stress loads in older people with different types of aging respiratory system.

  17. Neurological Effects of Exposure to Non-Hypoxic Hypobaria

    Science.gov (United States)

    2014-04-16

    be at risk for subclinical brain injury, raising concern about the long-term impact in aircrew. Altitude chamber personnel are a second...flight surgeon FSL BET brain extraction tool FSL FLIRT FMRIB’s linear image registration tool IQ intelligence quotient IRB Institutional Review...population would potentially have similar risks and findings. Chronic brain injury in other neurological diseases is associated with lower

  18. Intermittency in 197Au fragmentation

    International Nuclear Information System (INIS)

    Dabrowska, A.; Holynski, R.; Olszewski, A.; Szarska, M.; Wilczynska, B.; Wolter, W.; Wosiek, B.; Cherry, M.L.; Deines-Jones, P.; Jones, W.V.; Sengupta, K.; Wefel, B.

    1995-07-01

    The concept of factorial moments was applied to an analysis of the dynamical fluctuations in the charge distributions of the fragments emitted from gold nuclei with energies 10.6 and < 1.0 GeV/n interacting with emulsion nuclei. Clear evidence for intermittent fluctuations has been found in an analysis using all the particles released from the gold projectile, with a stronger effect observed below 1 GeV/n than at 10.6 GeV/n. For the full data sets, however, the intermittency effect was found to be very sensitive to the singly charged particles, and neglecting these particles strongly reduces the intermittency signal. When the analysis is restricted to the multiply charged fragments, an intermittency effect is revealed only for multifragmentation events, although one that is enhanced as compared to the analysis of all, singly and multiply charged, particles. The properties of the anomalous fractal dimensions suggest a sequential decay mechanism, rather than the existence of possible critical behaviour in the process of nuclear fragmentation. The likely influence of the charge conservation effects and the finite size of decaying systems on the observed intermittency signals was pointed out. (author). 37 refs, 9 figs, 5 tabs

  19. Intermittent Hypoxia Causes Inflammation and Injury to Human Adult Cardiac Myocytes.

    Science.gov (United States)

    Wu, Jing; Stefaniak, Joanna; Hafner, Christina; Schramel, Johannes Peter; Kaun, Christoph; Wojta, Johann; Ullrich, Roman; Tretter, Verena Eva; Markstaller, Klaus; Klein, Klaus Ulrich

    2016-02-01

    Intermittent hypoxia may occur in a number of clinical scenarios, including interruption of myocardial blood flow or breathing disorders such as obstructive sleep apnea. Although intermittent hypoxia has been linked to cardiovascular and cerebrovascular disease, the effect of intermittent hypoxia on the human heart is not fully understood. Therefore, in the present study, we compared the cellular responses of cultured human adult cardiac myocytes (HACMs) exposed to intermittent hypoxia and different conditions of continuous hypoxia and normoxia. HACMs were exposed to intermittent hypoxia (0%-21% O2), constant mild hypoxia (10% O2), constant severe hypoxia (0% O2), or constant normoxia (21% O2), using a novel cell culture bioreactor with gas-permeable membranes. Cell proliferation, lactate dehydrogenase release, vascular endothelial growth factor release, and cytokine (interleukin [IL] and macrophage migration inhibitory factor) release were assessed at baseline and after 8, 24, and 72 hours of exposure. A signal transduction pathway finder array was performed to determine the changes in gene expression. In comparison with constant normoxia and constant mild hypoxia, intermittent hypoxia induced earlier and greater inflammatory response and extent of cell injury as evidenced by lower cell numbers and higher lactate dehydrogenase, vascular endothelial growth factor, and proinflammatory cytokine (IL-1β, IL-6, IL-8, and macrophage migration inhibitory factor) release. Constant severe hypoxia showed more detrimental effects on HACMs at later time points. Pathway analysis demonstrated that intermittent hypoxia primarily altered gene expression in oxidative stress, Wnt, Notch, and hypoxia pathways. Intermittent and constant severe hypoxia, but not constant mild hypoxia or normoxia, induced inflammation and cell injury in HACMs. Cell injury occurred earliest and was greatest after intermittent hypoxia exposure. Our in vitro findings suggest that intermittent hypoxia

  20. Protective effects of intermittent hypoxia on brain and memory in a mouse model of apnea of prematurity.

    Science.gov (United States)

    Bouslama, Myriam; Adla-Biassette, Homa; Ramanantsoa, Nelina; Bourgeois, Thomas; Bollen, Bieke; Brissaud, Olivier; Matrot, Boris; Gressens, Pierre; Gallego, Jorge

    2015-01-01

    Apnea of prematurity (AOP) is considered a risk factor for neurodevelopmental disorders in children based on epidemiological studies. This idea is supported by studies in newborn rodents in which exposure to intermittent hypoxia (IH) as a model of AOP significantly impairs development. However, the severe IH used in these studies may not fully reflect the broad spectrum of AOP severity. Considering that hypoxia appears neuroprotective under various conditions, we hypothesized that moderate IH would protect the neonatal mouse brain against behavioral stressors and brain damage. On P6, each pup in each litter was randomly assigned to one of three groups: a group exposed to IH while separated from the mother (IH group), a control group exposed to normoxia while separated from the mother (AIR group), and a group of untreated unmanipulated pups left continuously with their mother until weaning (UNT group). Exposure to moderate IH (8% O2) consisted of 20 hypoxic events/hour, 6 h per day from postnatal day 6 (P6) to P10. The stress generated by maternal separation in newborn rodents is known to impair brain development, and we expected this effect to be smaller in the IH group compared to the AIR group. In a separate experiment, we combined maternal separation with excitotoxic brain lesions mimicking those seen in preterm infants. We analyzed memory, angiogenesis, neurogenesis and brain lesion size. In non-lesioned mice, IH stimulated hippocampal angiogenesis and neurogenesis and improved short-term memory indices. In brain-lesioned mice, IH decreased lesion size and prevented memory impairments. Contrary to common perception, IH mimicking moderate apnea may offer neuroprotection, at least in part, against brain lesions and cognitive dysfunctions related to prematurity. AOP may therefore have beneficial effects in some preterm infants. These results support the need for stratification based on AOP severity in clinical trials of treatments for AOP, to determine whether in

  1. Protective effects of intermittent hypoxia on brain and memory in a mouse model of apnea of prematurity

    Directory of Open Access Journals (Sweden)

    Myriam eBouslama

    2015-11-01

    Full Text Available Apnea of prematurity (AOP is considered a risk factor for neurodevelopmental disorders in children based on epidemiological studies. This idea is supported by studies in newborn rodents in which exposure to intermittent hypoxia (IH as a model of AOP significantly impairs development. However, the severe IH used in these studies may not fully reflect the broad spectrum of AOP severity. Considering that hypoxia appears neuroprotective under various conditions, we hypothesized that moderate IH would protect the neonatal mouse brain against behavioral stressors and brain damage. On P6, each pup in each litter was randomly assigned to one of three groups: a group exposed to IH while separated from the mother (IH group, a control group exposed to normoxia while separated from the mother (AIR group, and a group of untreated unmanipulated pups left continuously with their mother until weaning (UNT group. Exposure to moderate IH consisted of 20 hypoxic events/hour, 6 hours per day from postnatal day 6 (P6 to P10. The stress generated by maternal separation in newborn rodents is known to impair brain development, and we expected this effect to be smaller in the IH group compared to the AIR group. In a separate experiment, we combined maternal separation with excitotoxic brain lesions mimicking those seen in preterm infants. We analyzed memory, angiogenesis, neurogenesis and brain lesion size. In non-lesioned mice, IH stimulated hippocampal angiogenesis and neurogenesis and improved short-term memory indices. In brain-lesioned mice, IH decreased lesion size and prevented memory impairments. Contrary to common perception, IH mimicking moderate apnea may offer neuroprotection, at least in part, against brain lesions and cognitive dysfunctions related to prematurity. AOP may therefore have beneficial effects in some preterm infants. These results support the need for stratification based on AOP severity in clinical trials of treatments for AOP, to determine

  2. A novel adjustable automated system for inducing chronic intermittent hypoxia in mice.

    Directory of Open Access Journals (Sweden)

    Dora Polšek

    Full Text Available Sleep apnea is a chronic, widely underdiagnosed condition characterized by disruption of sleep architecture and intermittent hypoxia due to short cessations of breathing. It is a major independent risk factor for myocardial infarction, congestive heart failure and stroke as well as one of the rare modifiable risk factors for Alzheimer's Dementia. Reliable animal disease models are needed to understand the link between sleep apnea and the various clinically linked disorders.An automated system for inducing hypoxia was developed, in which the major improvement was the possibility to efficiently adjust the length and intensity of hypoxia in two different periods. The chamber used a small volume of gas allowing for fast exchanges of different oxygen levels. The mice were kept in their cages adapted with the system on the cage lid. As a proof of principle, they were exposed to a three week period of intermittent hypoxia for 8 hours a day, with 90 s intervals of 5, 7% and 21% oxygen to validate the model. Treated (n = 8 and control mice (no hypoxia, n = 7 were handled in the same manner and their hippocampal brain regions compared by histology.The chamber provided a fast, reliable and precise intermittent hypoxia, without inducing noticeable side effects to the animals. The validation experiment showed that apoptotic neurons in the hippocampus were more numerous in the mice exposed to intermittent hypoxia than in the control group, in all tested hippocampal regions (cornu ammonis 1 (CA1 P <0.001; cornu ammonis 3 (CA3 P <0.001; and dentate gyrus (DG P = 0.023. In both, control and hypoxic conditions, there was a significantly higher number of apoptotic neurons in the DG compared to the CA1 and CA3 subfields (P <0.001.The new design of a hypoxic chamber provides a fast, adjustable and reliable model of obstructive sleep apnea, which was validated by apoptosis of hippocampal neurons.

  3. Evaluation of nitrobenzimidazoles as hypoxic cell radiosensitizers

    International Nuclear Information System (INIS)

    Wright, J.; Frank, L.R.; Bush, D.; Harrison, G.H.

    1983-01-01

    Radiobiological and pharmacokinetic assays were performed to determine the potential of 2-nitrobenzimidazole (NBI) as a hypoxic cell radiosensitizing agent. As judged by comparing survival curve slopes of Serratia marcescens irradiated under aerated and hypoxic conditions, the NBI enhancement ratio (ER) at 2 mM concentration was 2.4 +- 0.2, compared with an oxygen enhancement ratio of 3.3 +- 0.3. 2,5-Dinitrobenzimidazole (DNBI) was investigated in vitro; its ER was 3.0 +- 0.3 at 4 mM concentration. Very poor tissue penetration of DNBI precluded further testing in vivo. Acute toxic signs appeared in C3H/HeJ mice following ip injection of NBI at 100 mg/kg. These would be partly attributable to the stress caused by the high pH of the injection vehicle. The LD 50 was estimated to be 125 to 150 mg/kg. Mammary adenocarcinoma tumors grown in the flanks of these mice exhibited maximum NBI levels at 5 min postinjection (ip). Peak tumor radiosensitization occurred in the interval between 5 and 10 min postinjection. The ER for tumor regrowth delay was 2.1 +- 0.3 following 50 mg/kg injected into mice 5 min before irradiation. Functional evaluation up to 40 days after treatment revealed no evidence of neurological deficit

  4. Evaluation of nitrobenzimidazoles as hypoxic cell radiosensitizers

    International Nuclear Information System (INIS)

    Wright, J.; Frank, L.R.; Bush, D.; Harrison, G.H.

    1983-01-01

    Radiobiological and pharmacokinetic assays were performed to determine the potential of 2-nitrobenzimidazole (NBI) as a hypoxic cell radiosensitizing agent. As judged by comparing survival curve slopes of Serratia marcescens irradiated under aerated and hypoxic conditions, the NBI enhancement ratio (ER) at 2 mM concentration was 2.4 +/- 0.2, compared with an oxygen enhancement ratio of 3.3 +/- 0.3. 2,5-Dinitrobenzimidazole (DNBI) was investigated in vitro; its ER was 3.0 +/- 0.3 at 4 mM concentration. Very poor tissue penetration of DNBI precluded further testing in vivo. Acute toxic signs appeared in C3H/HeJ mice following ip injection of NBI at 100 mg/kg. These would be partly attributable to the stress caused by the high pH of the injection vehicle. The LD50 was estimated to be 125-150 mg/kg. Mammary adenocarcinoma tumors grown in the flanks of these mice exhibited maximum NBI levels at 5 min postinjection (ip). Peak tumor radiosensitization occurred in the interval between 5 and 10 min postinjection. The ER for tumor regrowth delay was 2.1 +/- 0.3 following 50 mg/kg injected into mice 5 min before irradiation. Functional evaluation up to 40 days after treatment revealed no evidence of neurological deficit

  5. Biomarkers of Hypoxic Ischemic Encephalopathy in Newborns

    Directory of Open Access Journals (Sweden)

    Martha V. Douglas-Escobar

    2012-11-01

    Full Text Available As neonatal intensive care has evolved, the focus has shifted from improving mortality alone to an effort to improve both mortality and morbidity. The most frequent source of neonatal brain injury occurs as a result of hypoxic-ischemic injury. Hypoxic-ischemic injury occurs in about 2 of 1,000 full-term infants and severe injured infants will have lifetime disabilities and neurodevelopmental delays. Most recently, remarkable efforts toward neuroprotection have been started with the advent of therapeutic hypothermia and a key step in the evolution of neonatal neuroprotection is the discovery of biomarkers that enable the clinician-scientist to screen infants for brain injury, monitor progression of disease, identify injured brain regions, and assess efficacy of neuroprotective clinical trials. Lastly, biomarkers offer great hope identifying when an injury occurred shedding light on the potential pathophysiology and the most effective therapy. In this article, we will review biomarkers of HIE including S100b, neuron specific enolase, umbilical cord IL-6, CK-BB, GFAP, myelin basic protein, UCHL-1, and pNF-H. We hope to contribute to the awareness, validation and clinical use of established as well as novel neonatal brain injury biomarkers.

  6. Selective toxicity of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide toward hypoxic mammalian cells

    International Nuclear Information System (INIS)

    Rauth, A.M.; Mohindra, J.K.

    1981-01-01

    The chemotherapeutic agent 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) is used in the treatment of malignant melanoma where response rates of 15 to 30% have been reported. Some current interest exists in combining DTIC chemotherapy with localized high-dose (800 rads)-per-fraction radiotherapy in the treatment of unresectable metastatic melanoma. The present work investigates the radiosensitizing and chemotherapeutic properties of DTIC in an in vitro system using Chinese hamster ovary or HeLa cells and in vivo, using the KHT transplantable murine tumor. No evidence of a radiosensitizing effect of DTIC was found towards hypoxic or aerobic cells either in vitro or in vivo. In vitro, high drug concentrations (1 mg/ml) were approximately 5 times more effective in killing hypoxic Chinese hamster ovary or HeLa cells than in killing aerobic cells over exposure times of 0 to 12 hr. The degree of toxicity was drug dose and temperature dependent but was not highly dependent on cell number or cell type. In vivo plasma levels of DTIC were measured with high-pressure liquid chromatography after i.p. injection of drug into C3H mice. At the highest drug doses tested, near the 50% lethal dose in mice for DTIC (0.5 mg/g), the drug was toxic to both aerobic and hypoxic tumor cells with some evidence of increased toxicity towards hypoxic cells. The present work suggests that DTIC may be more efficiently activated under hypoxic conditions as compared to aerobic conditions. The increased toxicity of DTIC under hypoxic versus aerobic conditions may prove to be a feature of this drug that can be exploited in its clinical use and in the design of new analogs of DTIC

  7. Fit for high altitude: are hypoxic challenge tests useful?

    Directory of Open Access Journals (Sweden)

    Matthys Heinrich

    2011-02-01

    Full Text Available Abstract Altitude travel results in acute variations of barometric pressure, which induce different degrees of hypoxia, changing the gas contents in body tissues and cavities. Non ventilated air containing cavities may induce barotraumas of the lung (pneumothorax, sinuses and middle ear, with pain, vertigo and hearing loss. Commercial air planes keep their cabin pressure at an equivalent altitude of about 2,500 m. This leads to an increased respiratory drive which may also result in symptoms of emotional hyperventilation. In patients with preexisting respiratory pathology due to lung, cardiovascular, pleural, thoracic neuromuscular or obesity-related diseases (i.e. obstructive sleep apnea an additional hypoxic stress may induce respiratory pump and/or heart failure. Clinical pre-altitude assessment must be disease-specific and it includes spirometry, pulsoximetry, ECG, pulmonary and systemic hypertension assessment. In patients with abnormal values we need, in addition, measurements of hemoglobin, pH, base excess, PaO2, and PaCO2 to evaluate whether O2- and CO2-transport is sufficient. Instead of the hypoxia altitude simulation test (HAST, which is not without danger for patients with respiratory insufficiency, we prefer primarily a hyperoxic challenge. The supplementation of normobaric O2 gives us information on the acute reversibility of the arterial hypoxemia and the reduction of ventilation and pulmonary hypertension, as well as about the efficiency of the additional O2-flow needed during altitude exposure. For difficult judgements the performance of the test in a hypobaric chamber with and without supplemental O2-breathing remains the gold standard. The increasing numbers of drugs to treat acute pulmonary hypertension due to altitude exposure (acetazolamide, dexamethasone, nifedipine, sildenafil or to other etiologies (anticoagulants, prostanoids, phosphodiesterase-5-inhibitors, endothelin receptor antagonists including mechanical aids to

  8. Fit for high altitude: are hypoxic challenge tests useful?

    Science.gov (United States)

    Matthys, Heinrich

    2011-02-28

    Altitude travel results in acute variations of barometric pressure, which induce different degrees of hypoxia, changing the gas contents in body tissues and cavities. Non ventilated air containing cavities may induce barotraumas of the lung (pneumothorax), sinuses and middle ear, with pain, vertigo and hearing loss. Commercial air planes keep their cabin pressure at an equivalent altitude of about 2,500 m. This leads to an increased respiratory drive which may also result in symptoms of emotional hyperventilation. In patients with preexisting respiratory pathology due to lung, cardiovascular, pleural, thoracic neuromuscular or obesity-related diseases (i.e. obstructive sleep apnea) an additional hypoxic stress may induce respiratory pump and/or heart failure. Clinical pre-altitude assessment must be disease-specific and it includes spirometry, pulsoximetry, ECG, pulmonary and systemic hypertension assessment. In patients with abnormal values we need, in addition, measurements of hemoglobin, pH, base excess, PaO2, and PaCO2 to evaluate whether O2- and CO2-transport is sufficient.Instead of the hypoxia altitude simulation test (HAST), which is not without danger for patients with respiratory insufficiency, we prefer primarily a hyperoxic challenge. The supplementation of normobaric O2 gives us information on the acute reversibility of the arterial hypoxemia and the reduction of ventilation and pulmonary hypertension, as well as about the efficiency of the additional O2-flow needed during altitude exposure. For difficult judgements the performance of the test in a hypobaric chamber with and without supplemental O2-breathing remains the gold standard. The increasing numbers of drugs to treat acute pulmonary hypertension due to altitude exposure (acetazolamide, dexamethasone, nifedipine, sildenafil) or to other etiologies (anticoagulants, prostanoids, phosphodiesterase-5-inhibitors, endothelin receptor antagonists) including mechanical aids to reduce periodical or

  9. Ischemic preconditioning of the lower extremity attenuates the normal hypoxic increase in pulmonary artery systolic pressure.

    Science.gov (United States)

    Foster, Gary P; Westerdahl, Daniel E; Foster, Laura A; Hsu, Jeffrey V; Anholm, James D

    2011-12-15

    Ischemic pre-condition of an extremity (IPC) induces effects on local and remote tissues that are protective against ischemic injury. To test the effects of IPC on the normal hypoxic increase in pulmonary pressures and exercise performance, 8 amateur cyclists were evaluated under normoxia and hypoxia (13% F(I)O(2)) in a randomized cross-over trial. IPC was induced using an arterial occlusive cuff to one thigh for 5 min followed by deflation for 5 min for 4 cycles. In the control condition, the resting pulmonary artery systolic pressure (PASP) increased from a normoxic value of 25.6±2.3 mmHg to 41.8±7.2 mmHg following 90 min of hypoxia. In the IPC condition, the PASP increased to only 32.4±3.1 mmHg following hypoxia, representing a 72.8% attenuation (p=0.003). No significant difference was detected in cycle ergometer time trial duration between control and IPC conditions with either normoxia or hypoxia. IPC administered prior to hypoxic exposure was associated with profound attenuation of the normal hypoxic increase of pulmonary artery systolic pressure. Published by Elsevier B.V.

  10. Neuroprotective actions of taurine on hypoxic-ischemic brain damage in neonatal rats.

    Science.gov (United States)

    Zhu, Xiao-Yun; Ma, Peng-Sheng; Wu, Wei; Zhou, Ru; Hao, Yin-Ju; Niu, Yang; Sun, Tao; Li, Yu-Xiang; Yu, Jian-Qiang

    2016-06-01

    Taurine is an abundant amino acid in the nervous system, which has been proved to possess antioxidation, osmoregulation and membrane stabilization. Previously it has been demonstrated that taurine exerts ischemic brain injury protective effect. This study was designed to investigate whether the protective effect of taurine has the possibility to be applied to treat neonatal hypoxic-ischemic brain damage. Seven-day-old Sprague-Dawley rats were treated with left carotid artery ligation followed by exposure to 8% oxygen to generate the experimental group. The cerebral damage area was measured after taurine post-treatment with 2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxyline-Eosin (HE) staining and Nissl staining. The activities of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), myeloperoxtidase (MPO), ATP and Lactic Acid productions were assayed with ipsilateral hemisphere homogenates. Western-blot and immunofluorescence assay were processed to detect the expressions of AIF, Cyt C, Bax, Bcl-2 in brain. We found that taurine significantly reduced brain infarct volume and ameliorated morphological injury obviously reversed the changes of SOD, MDA, GSH-Px, T-AOC, ATP, MPO, and Lactic Acid levels. Compared with hypoxic-ischemic group, it showed marked reduction of AIF, Cyt C and Bax expressions and increase of Bcl-2 after post-treatment. We conclude that taurine possesses an efficacious neuroprotective effect after cerebral hypoxic-ischemic damage in neonatal rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Angiotensin II prevents hypoxic pulmonary hypertension and vascular changes in rat

    International Nuclear Information System (INIS)

    Rabinovitch, M.; Mullen, M.; Rosenberg, H.C.; Maruyama, K.; O'Brodovich, H.; Olley, P.M.

    1988-01-01

    Angiotensin II, a vasoconstrictor, has been previously demonstrated to produce a secondary vasodilatation due to release of prostaglandins. Because of this effect, the authors investigated whether infusion of exogenous angiotensin II via miniosmopumps in rats during a 1-wk exposure to chronic hypobaric hypoxia might prevent pulmonary hypertension, right ventricular hypertrophy, and vascular changes. They instrumented the rats with indwelling cardiovascular catheters and compared the hemodynamic and structural response in animals given angiotensin II, indomethacin in addition to angiotensin II (to block prostaglandin production), or saline with or without indomethacin. They then determine whether angiotensin II infusion also prevents acute hypoxic pulmonary vasoconstriction. They observed that exogenous angiotensin II infusion abolished the rise in pulmonary artery pressure, the right ventricular hypertrophy, and the vascular changes induced during chronic hypoxia in control saline-infused rats with or without indomethacin. The protective effects of angiotensin II was lost when indomethacin was given to block prostaglandin synthesis. During acute hypoxia, both antiotensin II and prostacyclin infusion similarly prevented the rise in pulmonary artery pressure observed in saline-infused rats and in rats given indomethacin or saralasin in addition to angiotensin II. Thus exogenous angiotensin II infusion prevents chronic hypoxic pulmonary hypertension, associated right ventricular hypertrophy, and vascular changes and blocks acute hypoxic pulmonary hypertension, and this is likely related to its ability to release vasodilator prostaglandins

  12. Intermittent hypercapnic hypoxia during sleep does not induce ventilatory long-term facilitation in healthy males.

    Science.gov (United States)

    Deacon, Naomi L; McEvoy, R Doug; Stadler, Daniel L; Catcheside, Peter G

    2017-09-01

    Intermittent hypoxia-induced ventilatory neuroplasticity is likely important in obstructive sleep apnea pathophysiology. Although concomitant CO 2 levels and arousal state critically influence neuroplastic effects of intermittent hypoxia, no studies have investigated intermittent hypercapnic hypoxia effects during sleep in humans. Thus the purpose of this study was to investigate if intermittent hypercapnic hypoxia during sleep induces neuroplasticity (ventilatory long-term facilitation and increased chemoreflex responsiveness) in humans. Twelve healthy males were exposed to intermittent hypercapnic hypoxia (24 × 30 s episodes of 3% CO 2 and 3.0 ± 0.2% O 2 ) and intermittent medical air during sleep after 2 wk washout period in a randomized crossover study design. Minute ventilation, end-tidal CO 2 , O 2 saturation, breath timing, upper airway resistance, and genioglossal and diaphragm electromyograms were examined during 10 min of stable stage 2 sleep preceding gas exposure, during gas and intervening room air periods, and throughout 1 h of room air recovery. There were no significant differences between conditions across time to indicate long-term facilitation of ventilation, genioglossal or diaphragm electromyogram activity, and no change in ventilatory response from the first to last gas exposure to suggest any change in chemoreflex responsiveness. These findings contrast with previous intermittent hypoxia studies without intermittent hypercapnia and suggest that the more relevant gas disturbance stimulus of concomitant intermittent hypercapnia frequently occurring in sleep apnea influences acute neuroplastic effects of intermittent hypoxia. These findings highlight the need for further studies of intermittent hypercapnic hypoxia during sleep to clarify the role of ventilatory neuroplasticity in the pathophysiology of sleep apnea. NEW & NOTEWORTHY Both arousal state and concomitant CO 2 levels are known modulators of the effects of intermittent hypoxia on

  13. The hypoxic tumour cell in radiation therapy

    International Nuclear Information System (INIS)

    Trott, K.R.; Gesellschaft fuer Strahlen- und Umweltforschung m.b.H., Neuherberg/Muenchen

    1976-01-01

    In most tumours there is a disproportion between the tumour cells and vascular connective tissue. A lack of oxygen depending on extent and duration, leads to changes of the metabolism and of the proliferative properties of the cells, to an increase of radiation resistance and to a reduction of the ability to recover from radiation injuries. Finally with longer duration, hypoxy leads to cell killing. As a result of irradiation, a reoxygenation of a part of the previous hypoxic tumour cell occurs more or less quickly. The time and topographic changes of these factors are involved in a complex manner in the radiotherapy of malignant tumours and essentially share the responsibility regarding the curative success of radiotherapy. (orig./LH) [de

  14. Clinical evaluation of hypoxic cell sensitizer (Misonidazole)

    Energy Technology Data Exchange (ETDEWEB)

    Asakawa, Hiroshi (Miyagi Prefectural Adult Disease Center, Natori (Japan)); Watarai, Jiro; Hoshino, Toshiaki

    1984-06-01

    Clinical effectiveness and toxicity of Misonidazole were analyzed and discussed in 22 cases of carcinoma of uterine cervix, 17 cases of esophageal cancer and 11 with other malignancies treated by radiation. By clinical and histologic examination in the controlled trial, it was shown that radiation response of tumor was slightly sensitized in the treated group with this drug, compared with that in the control group. It was confirmed that there was no significant difference between radiation response of tumor in both groups. Peripheral neuropathy was a complication in 10% and toxicodermatitis in 12% even if the total dose administered was below 10 g/m/sup 2/. From these results, it was strongly suggested that this drug is not suitable in combination with simple fractionated irradiation as a hypoxic cell sensitizer.

  15. Effects of intermittent training on anaerobic performance and MCT transporters in athletes.

    Directory of Open Access Journals (Sweden)

    Grégoire Millet

    Full Text Available This study examined the effects of intermittent hypoxic training (IHT on skeletal muscle monocarboxylate lactate transporter (MCT expression and anaerobic performance in trained athletes. Cyclists were assigned to two interventions, either normoxic (N; n = 8; 150 mmHg PIO2 or hypoxic (H; n = 10; ∼3000 m, 100 mmHg PIO2 over a three week training (5×1 h-1h30 x week(-1 period. Prior to and after training, an incremental exercise test to exhaustion (EXT was performed in normoxia together with a 2 min time trial (TT. Biopsy samples from the vastus lateralis were analyzed for MCT1 and MCT4 using immuno-blotting techniques. The peak power output (PPO increased (p<0.05 after training (7.2% and 6.6% for N and H, respectively, but VO2max showed no significant change. The average power output in the TT improved significantly (7.3% and 6.4% for N and H, respectively. No differences were found in MCT1 and MCT4 protein content, before and after the training in either the N or H group. These results indicate there are no additional benefits of IHT when compared to similar normoxic training. Hence, the addition of the hypoxic stimulus on anaerobic performance or MCT expression after a three-week training period is ineffective.

  16. CAROTID BODY POTENTIATION DURING CHRONIC INTERMITTENT HYPOXIA: IMPLICATION FOR HYPERTENSION

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    Rodrigo eDel Rio

    2014-11-01

    Full Text Available Autonomic dysfunction is involved in the development of hypertension in humans with obstructive sleep apnea, and animals exposed to chronic intermittent hypoxia (CIH. It has been proposed that a crucial step in the development of the hypertension is the potentiation of the carotid body (CB chemosensory responses to hypoxia, but the temporal progression of the CB chemosensory, autonomic and hypertensive changes induced by CIH are not known. We tested the hypothesis that CB potentiation precedes the autonomic imbalance and the hypertension in rats exposed to CIH. Thus, we studied the changes in CB chemosensory and ventilatory responsiveness to hypoxia, the spontaneous baroreflex sensitivity (BRS, heart rate variability (HRV and arterial blood pressure in pentobarbital anesthetized rats exposed to CIH for 7, 14 and 21 days. After 7 days of CIH, CB chemosensory and ventilatory responses to hypoxia were enhanced, while BRS was significantly reduced by 2-fold in CIH-rats compared to sham-rats. These alterations persisted until 21 days of CIH. After 14 days, CIH shifted the HRV power spectra suggesting a predominance of sympathetic over parasympathetic tone. In contrast, hypertension was found after 21 days of CIH. Concomitant changes between the gain of spectral HRV, BRS and ventilatory hypoxic chemoreflex showed that the CIH-induced BRS attenuation preceded the HRV changes. CIH induced a simultaneous decrease of the BRS gain along with an increase of the hypoxic ventilatory gain. Present results show that CIH-induced persistent hypertension was preceded by early changes in CB chemosensory control of cardiorespiratory and autonomic function.

  17. A Time- and Compartment-Specific Activation of Lung Macrophages in Hypoxic Pulmonary Hypertension.

    Science.gov (United States)

    Pugliese, Steven C; Kumar, Sushil; Janssen, William J; Graham, Brian B; Frid, Maria G; Riddle, Suzette R; El Kasmi, Karim C; Stenmark, Kurt R

    2017-06-15

    Studies in various animal models suggest an important role for pulmonary macrophages in the pathogenesis of pulmonary hypertension (PH). Yet, the molecular mechanisms characterizing the functional macrophage phenotype relative to time and pulmonary localization and compartmentalization remain largely unknown. In this study, we used a hypoxic murine model of PH in combination with FACS to quantify and isolate lung macrophages from two compartments over time and characterize their programing via RNA sequencing approaches. In response to hypoxia, we found an early increase in macrophage number that was restricted to the interstitial/perivascular compartment, without recruitment of macrophages to the alveolar compartment or changes in the number of resident alveolar macrophages. Principal component analysis demonstrated significant differences in overall gene expression between alveolar and interstitial macrophages (IMs) at baseline and after 4 and 14 d hypoxic exposure. Alveolar macrophages at both day 4 and 14 and IMs at day 4 shared a conserved hypoxia program characterized by mitochondrial dysfunction, proinflammatory gene activation, and mTORC1 signaling, whereas IMs at day 14 demonstrated a unique anti-inflammatory/proreparative programming state. We conclude that the pathogenesis of vascular remodeling in hypoxic PH involves an early compartment-independent activation of lung macrophages toward a conserved hypoxia program, with the development of compartment-specific programs later in the course of the disease. Thus, harnessing time- and compartment-specific differences in lung macrophage polarization needs to be considered in the therapeutic targeting of macrophages in hypoxic PH and potentially other inflammatory lung diseases. Copyright © 2017 by The American Association of Immunologists, Inc.

  18. Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

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    Huang Yen

    2011-09-01

    Full Text Available Abstract Background Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE. Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE. Methods We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7 rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry. Results Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. Conclusion These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.

  19. Hypoxic training: Clinical benefits on cardiometabolic risk factors.

    Science.gov (United States)

    Wee, Justin; Climstein, Mike

    2015-01-01

    The main aim of this review was to evaluate the effectiveness of hypoxic training on the modulation of cardiometabolic risk factors. Literature review. An electronic search encompassing five databases (PUBMED, EMBASE, MEDLINE, CINAHL, and SPORTDiscus) was conducted. A total of 2138 articles were retrieved. After excluding non-relevant articles, duplications and outcomes not related to cardiometabolic risk factors, 25 articles were chosen for review. Body weight and body composition were reported to be significantly improved when hypoxic training (≥1700 m) was used in conjunction with exercise regimes, at least three times a week, however extreme altitudes (>5000 m) resulted in a loss of fat-free muscle mass. Fasting blood glucose levels generally improved over time (≥21 days) at moderate levels of altitude (1500 m-3000 m), although reductions in blood glucose tolerance were observed when subjects were exposed to extreme hypoxia (>4000 m). Resting systolic and diastolic blood pressure levels improved as much as 26 mmHg and 13 mmHg respectively, with hypoxic training (1285 m-2650 m) in medicated, stable hypertensive subjects. Effects of hypoxic training when used in combination with exercise training on cholesterol levels were mixed. While there were improvements in total cholesterol (-4.2% to -30%) and low-density lipoprotein (-2.6% to -14.3%) reported as a result of hypoxic training, available evidence does not substantiate hypoxic training for the improvement of high-density lipoprotein and triglycerides. In conclusion, hypoxic training may be used as an adjunct treatment to modify some cardiometabolic risk factors. Measurement of hypoxic load may be used to individualize and ascertain appropriate levels of hypoxic training. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  20. Extracellular nucleotide derivatives protect cardiomyctes against hypoxic stress

    DEFF Research Database (Denmark)

    Golan, O; Issan, Y; Isak, A

    2011-01-01

    assures cardioprotection. Treatment with extracellular nucleotides, or with tri/di-phosphate, administered under normoxic conditions or during hypoxic conditions, led to a decrease in reactive oxygen species production. CONCLUSIONS: Extracellular tri/di-phosphates are apparently the molecule responsible...

  1. [Follow-up of newborns with hypoxic-ischaemic encephalopathy].

    Science.gov (United States)

    Martínez-Biarge, M; Blanco, D; García-Alix, A; Salas, S

    2014-07-01

    Hypothermia treatment for newborn infants with hypoxic-ischemic encephalopathy reduces the number of neonates who die or have permanent neurological deficits. Although this therapy is now standard of care, neonatal hypoxic-ischaemic encephalopathy still has a significant impact on the child's neurodevelopment and quality of life. Infants with hypoxic-ischaemic encephalopathy should be enrolled in multidisciplinary follow-up programs in order to detect impairments, to initiate early intervention, and to provide counselling and support for families. This article describes the main neurodevelopmental outcomes after term neonatal hypoxic-ischaemic encephalopathy. We offer recommendations for follow-up based on the infant's clinical condition and other prognostic indicators, mainly neonatal neuroimaging. Other aspects, such as palliative care and medico-legal issues, are also briefly discussed. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  2. Gold nanoparticle cellular uptake, toxicity and radiosensitisation in hypoxic conditions

    International Nuclear Information System (INIS)

    Jain, Suneil; Coulter, Jonathan A.; Butterworth, Karl T.; Hounsell, Alan R.; McMahon, Stephen J.; Hyland, Wendy B.; Muir, Mark F.; Dickson, Glenn R.; Prise, Kevin M.; Currell, Fred J.; Hirst, David G.; O’Sullivan, Joe M.

    2014-01-01

    Background and purpose: Gold nanoparticles (GNPs) are novel agents that have been shown to cause radiosensitisation in vitro and in vivo. Tumour hypoxia is associated with radiation resistance and reduced survival in cancer patients. The interaction of GNPs with cells in hypoxia is explored. Materials and methods: GNP uptake, localization, toxicity and radiosensitisation were assessed in vitro under oxic and hypoxic conditions. Results: GNP cellular uptake was significantly lower under hypoxic than oxic conditions. A significant reduction in cell proliferation in hypoxic MDA-MB-231 breast cancer cells exposed to GNPs was observed. In these cells significant radiosensitisation occurred in normoxia and moderate hypoxia. However, in near anoxia no significant sensitisation occurred. Conclusions: GNP uptake occurred in hypoxic conditions, causing radiosensitisation in moderate, but not extreme hypoxia in a breast cancer cell line. These findings may be important for the development of GNPs for cancer therapy

  3. Cooling for newborns with hypoxic ischaemic encephalopathy.

    Science.gov (United States)

    Jacobs, Susan E; Berg, Marie; Hunt, Rod; Tarnow-Mordi, William O; Inder, Terrie E; Davis, Peter G

    2013-01-31

    Newborn animal studies and pilot studies in humans suggest that mild hypothermia following peripartum hypoxia-ischaemia in newborn infants may reduce neurological sequelae without adverse effects. To determine the effect of therapeutic hypothermia in encephalopathic asphyxiated newborn infants on mortality, long-term neurodevelopmental disability and clinically important side effects. We used the standard search strategy of the Cochrane Neonatal Review Group as outlined in The Cochrane Library (Issue 2, 2007). Randomised controlled trials evaluating therapeutic hypothermia in term and late preterm newborns with hypoxic ischaemic encephalopathy were identified by searching the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2007, Issue 2), MEDLINE (1966 to June 2007), previous reviews including cross-references, abstracts, conferences, symposia proceedings, expert informants and journal handsearching. We updated this search in May 2012. We included randomised controlled trials comparing the use of therapeutic hypothermia with standard care in encephalopathic term or late preterm infants with evidence of peripartum asphyxia and without recognisable major congenital anomalies. The primary outcome measure was death or long-term major neurodevelopmental disability. Other outcomes included adverse effects of cooling and 'early' indicators of neurodevelopmental outcome. Four review authors independently selected, assessed the quality of and extracted data from the included studies. Study authors were contacted for further information. Meta-analyses were performed using risk ratios (RR) and risk differences (RD) for dichotomous data, and weighted mean difference for continuous data with 95% confidence intervals (CI). We included 11 randomised controlled trials in this updated review, comprising 1505 term and late preterm infants with moderate/severe encephalopathy and evidence of intrapartum asphyxia

  4. Radiosensitization of hypoxic tumor cells in vitro by nitric oxide

    International Nuclear Information System (INIS)

    Griffin, Robert J.; Makepeace, Carol M.; Hur, Won-Joo; Song, Chang W.

    1996-01-01

    Purpose: The effects of nitric oxide (NO) on the radiosensitivity of SCK tumor cells in oxic and hypoxic environments in vitro were studied. Methods and Materials: NO was delivered to cell suspensions using the NO donors 2,2-diethyl-1-nitroso-oxyhydrazine sodium salt (DEA/NO), and a spermine/nitric oxide complex (SPER/NO), which release NO at half-lives of 2.1 min and 39 min at pH 7.4, respectively. The cells were suspended in media containing DEA/NO or SPER/NO for varying lengths of time under oxic or hypoxic conditions, irradiated, and the clonogenicity determined. Results: Both compounds markedly radiosensitized the hypoxic cells. The drug enhancement ratios (DER) for 0.1, 1.0, and 2.0 mM DEA/NO were 2.0, 2.3 and 3.0, respectively, and those for 0.1, 1.0, and 2.0 mM SPER/NO were 1.6, 2.3, and 2.8, respectively. Aerobic cells were not radiosensitized by DEA/NO or SPER/NO. When DEA/NO and SPER/NO were incubated in solution overnight to allow release of NO, they were found to have no radiosensitizing effect under hypoxic or oxic conditions indicating the sensitization by the NO donors was due to the NO molecule released from these drugs. At the higher concentrations, SPER/NO was found to be cytotoxic in aerobic conditions but not in hypoxic conditions. DEA/NO was only slightly toxic to the cells in both aerobic and hypoxic conditions. Conclusions: NO released from NO donors DEA/NO and SPER/NO is as effective as oxygen to radiosensitize hypoxic cells in vitro. Its application to the radiosensitization of hypoxic cells in solid tumors remains to be investigated

  5. Effect of fractionated hyperthermia on hypoxic cells in vitro

    International Nuclear Information System (INIS)

    Nielson, O.S.

    1981-01-01

    The lethal response of asynchronous exponentially growing mouse lung (L1A2) cells heated to 42 0 C under hypoxic conditions was demonstrated in vitro. Acutely hypoxic cells (i.e. heated immediately after 30 min of N 2 +CO 2 gassing) and aerobic cells treated under the same extracellular pH were equally sensitive to a single hyperthermic treatment, and incubation under hypoxia for up to 24 hours prior to treatment did not influence cell survival. Similarly, under controlled pH conditions (pH within 7.0 to 7.4) recovery from hyperthermic damage demonstrated by two-dose hyperthermic fractionation (each of 1.5 hours at 42 0 C) was identical in hypoxic and aerobic cells, and the highest recovery was found at a 10-hour interval Preheating for 1.5 hours at 42 0 C induced thermal resistance. to a second treatment at 42 0 C (thermotolerance). At the 10-hour interval the degree of thermotolerance was not influenced by incubation under hypoxic conditions (thermotolerance ratio, TTR = 4.7 in both aerobic and hypoxic cells). The data indicate that hypoxic conditions do not influence the heat response in L1A2 cells to either a single or a two-dose fractionated hyperthermic treatment in which hypoxia or aerobic conditions were maintained in the interval between the heat treatments. (author)

  6. Sex differences associated with intermittent swim stress.

    Science.gov (United States)

    Warner, Timothy A; Libman, Matthew K; Wooten, Katherine L; Drugan, Robert C

    2013-11-01

    Various animal models of depression have been used to seek a greater understanding of stress-related disorders. However, there is still a great need for novel research in this area, as many individuals suffering from depression are resistant to current treatment methods. Women have a higher rate of depression, highlighting the need to investigate mechanisms of sex differences. Therefore, we employed a new animal model to assess symptoms of depression, known as intermittent swim stress (ISS). In this model, the animal experiences 100 trials of cold water swim stress. ISS has already been shown to cause signs of behavioral depression in males, but has yet to be assessed in females. Following ISS exposure, we looked at sex differences in the Morris water maze and forced swim test. The results indicated a spatial learning effect only in the hidden platform task between male and female controls, and stressed and control males. A consistent spatial memory effect was only seen for males exposed to ISS. In the forced swim test, both sexes exposed to ISS exhibited greater immobility, and the same males and females also showed attenuated climbing and swimming, respectively. The sex differences could be due to different neural substrates for males and females. The goal of this study was to provide the first behavioral examination of sex differences following ISS exposure, so the stage of estrous cycle was not assessed for the females. This is a necessary future direction for subsequent experiments. The current article highlights the importance of sex differences in response to stress.

  7. Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues

    Directory of Open Access Journals (Sweden)

    Emara Marwan

    2010-09-01

    Full Text Available Abstract Background Cytoglobin (Cygb and neuroglobin (Ngb are recently identified globin molecules that are expressed in vertebrate tissues. Upregulation of Cygb and Ngb under hypoxic and/or ischemic conditions in vitro and in vivo increases cell survival, suggesting possible protective roles through prevention of oxidative damage. We have previously shown that Ngb is expressed in human glioblastoma multiforme (GBM cell lines, and that expression of its transcript and protein can be significantly increased after exposure to physiologically relevant levels of hypoxia. In this study, we extended this work to determine whether Cygb is also expressed in GBM cells, and whether its expression is enhanced under hypoxic conditions. We also compared Cygb and Ngb expression in human primary tumor specimens, including brain tumors, as well as in human normal tissues. Immunoreactivity of carbonic anhydrase IX (CA IX, a hypoxia-inducible metalloenzyme that catalyzes the hydration of CO2 to bicarbonate, was used as an endogenous marker of hypoxia. Results Cygb transcript and protein were expressed in human GBM cells, and this expression was significantly increased in most cells following 48 h incubation under hypoxia. We also showed that Cygb and Ngb are expressed in both normal tissues and human primary cancers, including GBM. Among normal tissues, Cygb and Ngb expression was restricted to distinct cell types and was especially prominent in ductal cells. Additionally, certain normal organs (e.g. stomach fundus, small bowel showed distinct regional co-localization of Ngb, Cygb and CA IX. In most tumors, Ngb immunoreactivity was significantly greater than that of Cygb. In keeping with previous in vitro results, tumor regions that were positively stained for CA IX were also positive for Ngb and Cygb, suggesting that hypoxic upregulation of Ngb and Cygb also occurs in vivo. Conclusions Our finding of hypoxic up-regulation of Cygb/Ngb in GBM cell lines and human

  8. Developmental Expression and Hypoxic Induction of Hypoxia Inducible Transcription Factors in the Zebrafish.

    Science.gov (United States)

    Köblitz, Louise; Fiechtner, Birgit; Baus, Katharina; Lussnig, Rebecca; Pelster, Bernd

    2015-01-01

    The hypoxia inducible transcription factor (HIF) has been shown to coordinate the hypoxic response of vertebrates and is expressed in three different isoforms, HIF-1α, HIF-2α and HIF-3α. Knock down of either Hif-1α or Hif-2α in mice results in lethality in embryonic or perinatal stages, suggesting that this transcription factor is not only controlling the hypoxic response, but is also involved in developmental phenomena. In the translucent zebrafish embryo the performance of the cardiovascular system is not essential for early development, therefore this study was designed to analyze the expression of the three Hif-isoforms during zebrafish development and to test the hypoxic inducibility of these transcription factors. To complement the existing zfHif-1α antibody we expressed the whole zfHif-2α protein and used it for immunization and antibody generation. Similarly, fragments of the zfHif-3α protein were used for immunization and generation of a zfHif-3α specific antibody. To demonstrate presence of the Hif-isoforms during development [between 1 day post fertilization (1 dpf) and 9 dpf] affinity-purified antibodies were used. Hif-1α protein was present under normoxic conditions in all developmental stages, but no significant differences between the different developmental stages could be detected. Hif-2α was also present from 1 dpf onwards, but in post hatching stages (between 5 and 9 dpf) the expression level was significantly higher than prior to hatching. Similarly, Hif-3α was expressed from 1 dpf onwards, and the expression level significantly increased until 5 dpf, suggesting that Hif-2α and Hif-3α play a particular role in early development. Hypoxic exposure (oxygen partial pressure = 5 kPa) in turn caused a significant increase in the level of Hif-1α protein even at 1 dpf and in later stages, while neither Hif-2α nor Hif-3α protein level were affected. In these early developmental stages Hif-1α therefore appears to be more important for

  9. Glyoxylic compounds as radiosensitizers of hypoxic cells

    International Nuclear Information System (INIS)

    Cornago, M.P.; Lopez Zumel, M.C.; Alvarez, M.V.; Izquierdo, M.C.

    1990-01-01

    The radiosensitizing effect of five glyoxal derivatives on the survival of TC-SV40 cells has been measured, under aerobic and hypoxic conditions. A toxicity study was previously performed in order to use nontoxic concentrations. The OER for the TC-SV40 cells was 2.74. None of the glyoxylic compounds showed radiosensitizing activity under aerobic conditions while in hypoxia their radiosensitizing factors decreased in the order phenylglyoxylic acid (1.68 at 8 x 10(-3) mole dm-3) greater than phenylglyoxal (1.55 at 5 x 10(-6) mole dm-3) greater than 2-2' furil (1.48 at 5 x 10(-5) mole dm-3) greater than glyoxylic acid (1.39 at 1 x 10(-3) mole dm-3) greater than glyoxal (1.30 at 5 x 10(-5) mole dm-3). The dose-modifying factors were also determined at two equimolar concentrations 5 x 10(-5) and 5 x 10(-6) mole dm-3. A concentration effect was noticed for all the compounds although their relative radiosensitizing activity kept, independently of the concentration, the same order noted above. Glyoxals with aromatic or heterocyclic rings exert a greater radiosensitization than the others. The acidic compounds have less radiosensitizing activity than their aldehydic counterparts. Interaction of these glyoxals with NPSH cellular groups was tested and the low degree of inhibition shows that this mechanism would contribute very little, if any, to the radiosensitization effect

  10. The influence of continuous and intermittent traffic noise on sleep

    Science.gov (United States)

    Eberhardt, J. L.; Stråle, L.-O.; Berlin, M. H.

    1987-08-01

    The effects of road traffic noise on sleep were studied in the laboratory using nine young male adults (aged 20-26). The subjects were exposed to noise with different temporal characteristics: (i) continuous traffic noise of 36 dB(A) or 45 dB(A), (ii) intermittent noise of 50 truck passages with L pmax = 45 dB(A) ( L eq = 29 dB(A)) or L pmax = 55 dB(A) ( L eq = 36 dB(A)), and (iii) a combination of continuous (45 dB(A)) and intermittent ( L pmax = 55 dB(A)) traffic noise. For one noise condition (intermittent 55 dB(A)) the effect of the use of ear plugs was also studied. The intermittent noise of L pmax = 45 dB(A) caused transitions towards lighter sleep, whereas 55 dB(A) was needed to induce awakening effects. It could be shown that the probability for arousal reactions depends on the emergence of the noise peaks from the background, rather than the absolute noise peak level. Continuous traffic noise of 45 dB(A) caused REM sleep deficits, while intermittent traffic noise of L pmax = 45 dB(A) caused stage III+IV deficits. The night with ear plugs was virtually undisturbed. After nights with REM sleep deficits the subjective sleep quality was rated lower and mood was influenced adversely. For the types of exposure used in the present investigation L eq alone is not an adequate descriptor of the noise dose, relating to the sleep disturbances observed. From the present experiment, together with other existing data, it might be concluded that the WHO recommendation of L eq = 35 dB(A) is adequate, but should be supplemented with a maximum noise level, as expressed for example in L pmax or LI, that should not be exceeded.

  11. Effectiveness of beneficial plant-microbe interactions under hypobaric and hypoxic conditions in an advanced life support system

    Science.gov (United States)

    MacIntyre, Olathe; Stasiak, Michael; Cottenie, Karl; Trevors, Jack; Dixon, Mike

    An assembled microbial community in the hydroponics solution of an advanced life support system may improve plant performance and productivity in three ways: (1) exclusion of plant pathogens from the initial community, (2) resistance to infection, and (3) plant-growth promotion. However, the plant production area is likely to have a hypobaric (low pressure) and hypoxic (low oxygen) atmosphere to reduce structural mass and atmosphere leakage, and these conditions may alter plant-microbe interactions. Plant performance and productivity of radish (Raphanus sativus L. cv. Cherry Bomb II) grown under hypobaric and hypoxic conditions were investigated at the University of Guelph's Controlled Environment Systems Research Facility. Changes in the microbial communities that routinely colonized the re-circulated nutrient solution, roots, and leaves of radishes in these experiments were quantified in terms of similarity in community composition, abundance of bacteria, and community diversity before and after exposure to hypobaric and hypoxic conditions relative to communities maintained at ambient growth conditions. The microbial succession was affected by extreme hypoxia (2 kPa oxygen partial pressure) while hypobaria as low as 10 kPa total pressure had little effect on microbial ecology. There were no correlations found between the physiological profile of these unintentional microbial communities and radish growth. The effects of hypobaric and hypoxic conditions on specific plant-microbe interactions need to be determined before beneficial gnotobiotic communities can be developed for use in space. The bacterial strains Tal 629 of Bradyrhizobium japonicum and WCS417 of Pseudomonas fluorescens, and the plant pathogen Fusarium oxysporum f. sp. raphani will be used in future experiments. B. japonicum Tal 629 promotes radish growth in hydroponics systems and P. fluorescens WCS417 induces systemic resistance to fusarium wilt (F. oxysporum f. sp. raphani) in radish under ambient

  12. MicroRNA-195 induced apoptosis in hypoxic chondrocytes by targeting hypoxia-inducible factor 1 alpha.

    Science.gov (United States)

    Bai, R; Zhao, A-Q; Zhao, Z-Q; Liu, W-L; Jian, D-M

    2015-02-01

    The chondrocytes, the resident cells of cartilage, are maintained and take effects in the whole life upon chronic hypoxic exposure, which hypoxia-inducible factor 1 alpha (HIF-1α) play pivotal roles in response to. Dysregulation of some microRNA (miRNAs) have also been identified to be involved in hypoxia-related physiologic and pathophysiologic responses in some tissues or cell lines. However, the mechanism of miRNAs reponse to hypoxia remain largely unknown in chondrocytes, including the microRNA-195 (miR-195). AIM To investigate the effects of microRNAs (miRNAs) and hypoxia-inducible factor 1 alpha (HIF-1α) on chondrocytes in physiologic environment. We compared the expression of miR-195 and HIF-1α mRNA on hypoxia with that on normoxia in ATDC 5 cells by qRT-PCR. Further experiments was performed to confirmed the relationships of miR-195 and HIF-1α by bioinformatics analysis and dual reporter gene assay. we also assessed the effect of miR-195 on apoptosis in hypoxic ATDC 5 cells by transfect with miR-195 mimics. It was found the downregulated miR-195 and upregulated HIF-1α were present in hypoxic ATDC 5 cells. miR-195 negatively regulated HIF-1α by targeting its 3'-untranslated region. Moreover, the founding indicated miR-195 greatly increased apoptosis and downregulated HIF-1α mRNA occurred simultaneously in hypoxic chondrocytes. We concluded that miR-195 induced apoptosis in hypoxic chondrocytes by directly targeting HIF-1α.

  13. Intermittent Hypoxia Alters Gene Expression in Peripheral Blood Mononuclear Cells of Healthy Volunteers.

    Science.gov (United States)

    Polotsky, Vsevolod Y; Bevans-Fonti, Shannon; Grigoryev, Dmitry N; Punjabi, Naresh M

    2015-01-01

    Obstructive sleep apnea is associated with high cardiovascular morbidity and mortality. Intermittent hypoxia of obstructive sleep apnea is implicated in the development and progression of insulin resistance and atherosclerosis, which have been attributed to systemic inflammation. Intermittent hypoxia leads to pro-inflammatory gene up-regulation in cell culture, but the effects of intermittent hypoxia on gene expression in humans have not been elucidated. A cross-over study was performed exposing eight healthy men to intermittent hypoxia or control conditions for five hours with peripheral blood mononuclear cell isolation before and after exposures. Total RNA was isolated followed by gene microarrays and confirmatory real time reverse transcriptase PCR. Intermittent hypoxia led to greater than two fold up-regulation of the pro-inflammatory gene toll receptor 2 (TLR2), which was not increased in the control exposure. We hypothesize that up-regulation of TLR2 by intermittent hypoxia may lead to systemic inflammation, insulin resistance and atherosclerosis in patients with obstructive sleep apnea.

  14. Effects of chronic pollution and water flow intermittency on stream biofilms biodegradation capacity.

    Science.gov (United States)

    Rožman, Marko; Acuña, Vicenç; Petrović, Mira

    2018-02-01

    A mesocosm case study was conducted to gain understanding and practical knowledge on biofilm emerging contaminants biodegradation capacity under stressor and multiple stressor conditions. Two real life scenarios: I) biodegradation in a pristine intermittent stream experiencing acute pollution and II) biodegradation in a chronically polluted intermittent stream, were examined via a multifactorial experiment using an artificial stream facility. Stream biofilms were exposed to different water flow conditions i.e. permanent and intermittent water flow. Venlafaxine, a readily biodegradable pharmaceutical was used as a measure of biodegradation capacity while pollution was simulated by a mixture of four emerging contaminants (erythromycin, sulfisoxazole, diclofenac and imidacloprid in addition to venlafaxine) in environmentally relevant concentrations. Biodegradation kinetics monitored via LC-MS/MS was established, statistically evaluated, and used to link biodegradation with stress events. The results suggest that the effects of intermittent flow do not hinder and may even stimulate pristine biofilm biodegradation capacity. Chronic pollution completely reduced biodegradation in permanent water flow experimental treatments while no change in intermittent streams was observed. A combined effect of water flow conditions and emerging contaminants exposure on biodegradation was found. The decrease in biodegradation due to exposure to emerging contaminants is significantly greater in streams with permanent water flow suggesting that the short and medium term biodegradation capacity in intermittent systems may be preserved or even greater than in perennial streams. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Priming of the Cells: Hypoxic Preconditioning for Stem Cell Therapy.

    Science.gov (United States)

    Wei, Zheng Z; Zhu, Yan-Bing; Zhang, James Y; McCrary, Myles R; Wang, Song; Zhang, Yong-Bo; Yu, Shan-Ping; Wei, Ling

    2017-10-05

    Stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and pathological responses. A hypoxic insult might act as a double-edged sword, it induces cell death and brain damage, but on the other hand, sublethal hypoxia can trigger an adaptation response called hypoxic preconditioning or hypoxic tolerance that is of immense importance for the survival of cells and tissues. This review was based on articles published in PubMed databases up to August 16, 2017, with the following keywords: "stem cells," "hypoxic preconditioning," "ischemic preconditioning," and "cell transplantation." Original articles and critical reviews on the topics were selected. Hypoxic preconditioning has been investigated as a primary endogenous protective mechanism and possible treatment against ischemic injuries. Many cellular and molecular mechanisms underlying the protective effects of hypoxic preconditioning have been identified. In cell transplantation therapy, hypoxic pretreatment of stem cells and neural progenitors markedly increases the survival and regenerative capabilities of these cells in the host environment, leading to enhanced therapeutic effects in various disease models. Regenerative treatments can mobilize endogenous stem cells for neurogenesis and angiogenesis in the adult brain. Furthermore, transplantation of stem cells/neural progenitors achieves therapeutic benefits via cell replacement and/or increased trophic support. Combinatorial approaches of cell-based therapy with additional strategies such as neuroprotective protocols, anti-inflammatory treatment, and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the recent progress regarding cell types and applications in regenerative medicine as well as future applications.

  16. Early Cerebral Hemodynamic, Metabolic, and Histological Changes in Hypoxic-Ischemic Fetal Lambs during Postnatal Life.

    Science.gov (United States)

    Rey-Santano, Carmen; Mielgo, Victoria E; Gastiasoro, Elena; Murgia, Xabier; Lafuente, Hector; Ruiz-Del-Yerro, Estibaliz; Valls-I-Soler, Adolf; Hilario, Enrique; Alvarez, Francisco J

    2011-01-01

    The hemodynamic, metabolic, and biochemical changes produced during the transition from fetal to neonatal life may be aggravated if an episode of asphyxia occurs during fetal life. The aim of the study was to examine regional cerebral blood flow (RCBF), histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress in the first hours of postnatal life following severe fetal asphyxia. Eighteen chronically instrumented newborn lambs were randomly assigned to either a control group or the hypoxic-ischemic (HI) group, in which case fetal asphyxia was induced just before delivery. All the animals were maintained on intermittent positive pressure ventilation for 3 h after delivery. During the HI insult, the injured group developed acidosis, hypoxia, hypercapnia, lactic acidosis, and tachycardia (relative to the control group), without hypotension. The intermittent positive pressure ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilatory support, there continued to be an increased RCBF in inner regions among the HI group, but no significant differences were detected in cortical flow compared to the control group. Also, the magnitude of the increase in TUNEL positive cells (apoptosis) and antioxidant enzymes, and decrease of ATP reserves was significantly greater in the brain regions where the RCBF was not higher. In conclusion, our findings identify early metabolic, histological, and hemodynamic changes involved in brain damage in premature asphyxiated lambs. Such changes have been described in human neonates, so our model could be useful to test the safety and the effectiveness of different neuroprotective or ventilation strategies applied in the first hours after fetal HI injury.

  17. Transcriptional signature of human adipose tissue-derived stem cells (hASCs) preconditioned for chondrogenesis in hypoxic conditions

    International Nuclear Information System (INIS)

    Pilgaard, L.; Lund, P.; Duroux, M.; Lockstone, H.; Taylor, J.; Emmersen, J.; Fink, T.; Ragoussis, J.; Zachar, V.

    2009-01-01

    Hypoxia is an important factor involved in the control of stem cells. To obtain a better insight into the phenotypical changes brought about by hypoxic preconditioning prior to chondrogenic differentiation; we have investigated growth, colony-forming and chondrogenic capacity, and global transcriptional responses of six adipose tissue-derived stem cell lines expanded at oxygen concentrations ranging from ambient to 1%. The assessment of cell proliferation and colony-forming potential revealed that the hypoxic conditions corresponding to 1% oxygen played a major role. The chondrogenic inducibility, examined by high-density pellet model, however, did not improve on hypoxic preconditioning. While the microarray analysis revealed a distinctive inter-donor variability, the exposure to 1% hypoxia superseded the biological variability and produced a specific expression profile with 2581 significantly regulated genes and substantial functional enrichment in the pathways of cell proliferation and apoptosis. Additionally, exposure to 1% oxygen resulted in upregulation of factors related to angiogenesis and cell growth. In particular, leptin (LEP), the key regulator of body weight and food intake was found to be highly upregulated. In conclusion, the results of this investigation demonstrate the significance of donor demographics and the importance of further studies into the use of regulated oxygen tension as a tool for preparation of ASCs in order to exploit their full potential.

  18. A low protein diet increases the hypoxic tolerance in Drosophila.

    Directory of Open Access Journals (Sweden)

    Paul Vigne

    2006-12-01

    Full Text Available Dietary restriction is well known to increase the life span of a variety of organisms from yeast to mammals, but the relationships between nutrition and the hypoxic tolerance have not yet been considered. Hypoxia is a major cause of cell death in myocardial infarction and stroke. Here we forced hypoxia-related death by exposing one-day-old male Drosophila to chronic hypoxia (5% O(2 and analysed their survival. Chronic hypoxia reduced the average life span from 33.6 days to 6.3 days when flies were fed on a rich diet. A demographic analysis indicated that chronic hypoxia increased the slope of the mortality trajectory and not the short-term risk of death. Dietary restriction produced by food dilution, by yeast restriction, or by amino acid restriction partially reversed the deleterious action of hypoxia. It increased the life span of hypoxic flies up to seven days, which represented about 25% of the life time of an hypoxic fly. Maximum survival of hypoxic flies required only dietary sucrose, and it was insensitive to drugs such as rapamycin and resveratrol, which increase longevity of normoxic animals. The results thus uncover a new link between protein nutrition, nutrient signalling, and resistance to hypoxic stresses.

  19. Toxic clinical hypoxic radiation sensitizers plus radiation-induced toxicity

    International Nuclear Information System (INIS)

    Richmond, R.C.

    1984-01-01

    The operational definition espoused twelve years ago that clinical hypoxic radiation sensitizers should be nontoxic interferes with the recognition and research of useful radiation sensitizers. Eight years ago the toxic antitumor drug cis-dichlorodiammineplatinum(II) was reported to be a hypoxic radiation sensitizer and the selective antitumor action of this drug was stressed as potentially creating tumor-targeted radiation sensitization. This rationale of oxidative antitumor drugs as toxic and targeted clinical sensitizers is useful, and has led to the study reported here. The antitumor drug cis-(1,1-cyclobutane-dicarboxylato)diammineplatinum(II), or JM-8, is being tested in clinical trials. Cells of S. typhimurium in PBS in the presence of 0.2mM JM-8 are found to be sensitized to irradiation under hypoxic, but not oxic, conditions. JM-8 is nontoxic to bacteria at this concentration, but upon irradiation the JM-8 solution becomes highly toxic. This radiation induced toxicity of JM-8 preferentially develops from hypoxic solution, and thus contributes to the rationale of hypoxic tumor cell destruction

  20. Hypothermia therapy for newborns with hypoxic ischemic encephalopathy.

    Science.gov (United States)

    Silveira, Rita C; Procianoy, Renato S

    2015-01-01

    Therapeutic hypothermia reduces cerebral injury and improves the neurological outcome secondary to hypoxic ischemic encephalopathy in newborns. It has been indicated for asphyxiated full-term or near-term newborn infants with clinical signs of hypoxic-ischemic encephalopathy (HIE). A search was performed for articles on therapeutic hypothermia in newborns with perinatal asphyxia in PubMed; the authors chose those considered most significant. There are two therapeutic hypothermia methods: selective head cooling and total body cooling. The target body temperature is 34.5 °C for selective head cooling and 33.5 °C for total body cooling. Temperatures lower than 32 °C are less neuroprotective, and temperatures below 30 °C are very dangerous, with severe complications. Therapeutic hypothermia must start within the first 6h after birth, as studies have shown that this represents the therapeutic window for the hypoxic-ischemic event. Therapy must be maintained for 72 h, with very strict control of the newborn's body temperature. It has been shown that therapeutic hypothermia is effective in reducing neurologic impairment, especially in full-term or near-term newborns with moderate hypoxic-ischemic encephalopathy. Therapeutic hypothermia is a neuroprotective technique indicated for newborn infants with perinatal asphyxia and hypoxic-ischemic encephalopathy. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  1. Inhibition of glycolysis by misonidazole in hypoxic cells

    International Nuclear Information System (INIS)

    Ling, L.; Sutherland, R.

    1984-01-01

    Inhibition of glycolysis has been postulated to be a mechanism of misonidazole (MISO) toxicity in hypoxic cells. To investigate the effect of MISO on glycolysis, glucose transport and its consumption and lactate formation were measured. Exponential EMT6 cells (10/sup 6/ cells/ml) were made hypoxix by continuous gassing in 3% CO/sub 2/ in N/sub 2/. They were then treated with 5mM MISO for various times, then washed and analysed for their rates of anaerobic glycolysis. Glucose and lactate content were determined enzymatically. The rates of both glucose consumption and lactate formation decreased after 30 min hypoxic incubation with MISO. After 90 min, the rates were not measurable even though the cells still excluded Trypan Blue. There was, however, a parallel decrease in plating efficiency. These data suggest that the inhibition of glycolysis is an important mechanism of hypoxic toxicity of MISO. To locate the site of inhibition, studies were initiated to look at glucose transport by following the uptake of /sup 14/-C-3-0-methyl-glucose, a nonmetabolised glucose analog. Results obtained so far indicate that up to 90 min of hypoxic incubation with MISO, there was no change in the kinetics of the uptake of his analog. Therefore, the results showed that in hypoxic cells treated with MISO, the glucose transport system was unaffected. However, there was a rapid decrease in anaerobic glycolysis

  2. The Yo-Yo intermittent recovery test

    DEFF Research Database (Denmark)

    Bangsbo, Jens; Iaia, F. Marcello; Krustrup, Peter

    2008-01-01

    The two Yo-Yo intermittent recovery (IR) tests evaluate an individual's ability to repeatedly perform intense exercise. The Yo-Yo IR level 1 (Yo-Yo IR1) test focuses on the capacity to carry out intermittent exercise leading to a maximal activation of the aerobic system, whereas Yo-Yo IR level 2...

  3. Intermittent behavior of the logistic system

    Science.gov (United States)

    Mayer-Kress, G.; Haken, H.

    1981-03-01

    In the discrete logistic model a transition to chaotic behavior via intermittency occurs in a neighborhood of periodic bands. Intermittent behavior is also induced if a stable periodic orbit is perturbed by low-level external noise, whereas alterations due to computer digitalisation produce remarkable periodicities. We compare our numerical results with the predictions of Pomeau and Manneville for the Lorenz system.

  4. Nebulization of the acidified sodium nitrite formulation attenuates acute hypoxic pulmonary vasoconstriction

    Directory of Open Access Journals (Sweden)

    Surber Mark W

    2010-06-01

    Full Text Available Abstract Background Generalized hypoxic pulmonary vasoconstriction (HPV occurring during exposure to hypoxia is a detrimental process resulting in an increase in lung vascular resistance. Nebulization of sodium nitrite has been shown to inhibit HPV. The aim of this project was to investigate and compare the effects of nebulization of nitrite and different formulations of acidified sodium nitrite on acute HPV. Methods Ex vivo isolated rabbit lungs perfused with erythrocytes in Krebs-Henseleit buffer (adjusted to 10% hematocrit and in vivo anesthetized catheterized rabbits were challenged with periods of hypoxic ventilation alternating with periods of normoxic ventilation. After baseline hypoxic challenges, vehicle, sodium nitrite or acidified sodium nitrite was delivered via nebulization. In the ex vivo model, pulmonary arterial pressure and nitric oxide concentrations in exhaled gas were monitored. Nitrite and nitrite/nitrate were measured in samples of perfusion buffer. Pulmonary arterial pressure, systemic arterial pressure, cardiac output and blood gases were monitored in the in vivo model. Results In the ex vivo model, nitrite nebulization attenuated HPV and increased nitric oxide concentrations in exhaled gas and nitrite concentrations in the perfusate. The acidified forms of sodium nitrite induced higher levels of nitric oxide in exhaled gas and had longer vasodilating effects compared to nitrite alone. All nitrite formulations increased concentrations of circulating nitrite to the same degree. In the in vivo model, inhaled nitrite inhibited HPV, while pulmonary arterial pressure, cardiac output and blood gases were not affected. All nitrite formulations had similar potency to inhibit HPV. The tested concentration of appeared tolerable. Conclusion Nitrite alone and in acidified forms effectively and similarly attenuates HPV. However, acidified nitrite formulations induce a more pronounced increase in nitric oxide exhalation.

  5. Participation of the dorsal periaqueductal grey matter in the hypoxic ventilatory response in unanaesthetized rats.

    Science.gov (United States)

    Lopes, L T; Biancardi, V; Vieira, E B; Leite-Panissi, C; Bícego, K C; Gargaglioni, L H

    2014-07-01

    Although periaqueductal grey matter activation is known to elicit respiratory and cardiovascular responses, the role of this midbrain area in the compensatory responses to hypoxia is still unknown. To test the participation of the periaqueductal grey matter in cardiorespiratory and thermal responses to hypoxia in adult male Wistar rats, we performed a chemical lesion of the dorsolateral/dorsomedial or the ventrolateral/lateral periaqueductal grey matter using ibotenic acid. Pulmonary ventilation, mean arterial pressure, heart rate and body temperature were measured in unanaesthetized rats during normoxic and hypoxic exposure (5, 15, 30 min, 7% O2). An ibotenic acid lesion of the dorsolateral/dorsomedial periaqueductal grey matter caused a higher increase in pulmonary ventilation (67.1%, 1730±282.5 mL kg(-1) min(-1)) compared to the Sham group (991.4±194 mL kg(-1) min(-1)) after 15 min in hypoxia, whereas for the ventrolateral/Lateral periaqueductal grey matter lesion, no differences were observed between groups. Mean arterial pressure, heart rate and body temperature were not affected by a dorsolateral/dorsomedial or ventrolateral/lateral periaqueductal grey matter lesion. Middle to caudal portions of the dorsolateral/dorsomedial periaqueductal grey matter neurones modulate the hypoxic ventilatory response, exerting an inhibitory modulation during low O2 situations. In addition, the middle to caudal portions of the dorsolateral/dorsomedial or ventrolateral/lateral periaqueductal grey matter do not appear to exert a tonic role on cardiovascular or thermal parameters during normoxic and hypoxic conditions. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  6. Hypoxic stress induces, but cannot sustain trophoblast stem cell differentiation to labyrinthine placenta due to mitochondrial insufficiency

    Directory of Open Access Journals (Sweden)

    Yufen Xie

    2014-11-01

    Full Text Available Dysfunctional stem cell differentiation into placental lineages is associated with gestational diseases. Of the differentiated lineages available to trophoblast stem cells (TSC, elevated O2 and mitochondrial function are necessary to placental lineages at the maternal–placental surface and important in the etiology of preeclampsia. TSC lineage imbalance leads to embryonic failure during uterine implantation. Stress at implantation exacerbates stem cell depletion by decreasing proliferation and increasing differentiation. In an implantation site O2 is normally ~2%. In culture, exposure to 2% O2 and fibroblast growth factor 4 (FGF4 enabled the highest mouse TSC multipotency and proliferation. In contrast, hypoxic stress (0.5% O2 initiated the most TSC differentiation after 24 h despite exposure to FGF4. However, hypoxic stress supported differentiation poorly after 4–7 days, despite FGF4 removal. At all tested O2 levels, FGF4 maintained Warburg metabolism; mitochondrial inactivity and aerobic glycolysis. However, hypoxic stress suppressed mitochondrial membrane potential and maintained low mitochondrial cytochrome c oxidase (oxidative phosphorylation/OxPhos, and high pyruvate kinase M2 (glycolysis despite FGF4 removal. Inhibiting OxPhos inhibited optimum differentiation at 20% O2. Moreover, adding differentiation-inducing hyperosmolar stress failed to induce differentiation during hypoxia. Thus, differentiation depended on OxPhos at 20% O2; hypoxic and hyperosmolar stresses did not induce differentiation at 0.5% O2. Hypoxia-limited differentiation and mitochondrial inhibition and activation suggest that differentiation into two lineages of the labyrinthine placenta requires O2 > 0.5–2% and mitochondrial function. Stress-activated protein kinase increases an early lineage and suppresses later lineages in proportion to the deviation from optimal O2 for multipotency, thus it is the first enzyme reported to prioritize differentiation.

  7. Cosmic Rays in Intermittent Magnetic Fields

    International Nuclear Information System (INIS)

    Shukurov, Anvar; Seta, Amit; Bushby, Paul J.; Wood, Toby S.; Snodin, Andrew P.

    2017-01-01

    The propagation of cosmic rays in turbulent magnetic fields is a diffusive process driven by the scattering of the charged particles by random magnetic fluctuations. Such fields are usually highly intermittent, consisting of intense magnetic filaments and ribbons surrounded by weaker, unstructured fluctuations. Studies of cosmic-ray propagation have largely overlooked intermittency, instead adopting Gaussian random magnetic fields. Using test particle simulations, we calculate cosmic-ray diffusivity in intermittent, dynamo-generated magnetic fields. The results are compared with those obtained from non-intermittent magnetic fields having identical power spectra. The presence of magnetic intermittency significantly enhances cosmic-ray diffusion over a wide range of particle energies. We demonstrate that the results can be interpreted in terms of a correlated random walk.

  8. Cosmic Rays in Intermittent Magnetic Fields

    Energy Technology Data Exchange (ETDEWEB)

    Shukurov, Anvar; Seta, Amit; Bushby, Paul J.; Wood, Toby S. [School of Mathematics and Statistics, Newcastle University, Newcastle Upon Tyne NE1 7RU (United Kingdom); Snodin, Andrew P., E-mail: a.seta1@ncl.ac.uk, E-mail: amitseta90@gmail.com [Department of Mathematics, Faculty of Applied Science, King Mongkut’s University of Technology North Bangkok, Bangkok 10800 (Thailand)

    2017-04-10

    The propagation of cosmic rays in turbulent magnetic fields is a diffusive process driven by the scattering of the charged particles by random magnetic fluctuations. Such fields are usually highly intermittent, consisting of intense magnetic filaments and ribbons surrounded by weaker, unstructured fluctuations. Studies of cosmic-ray propagation have largely overlooked intermittency, instead adopting Gaussian random magnetic fields. Using test particle simulations, we calculate cosmic-ray diffusivity in intermittent, dynamo-generated magnetic fields. The results are compared with those obtained from non-intermittent magnetic fields having identical power spectra. The presence of magnetic intermittency significantly enhances cosmic-ray diffusion over a wide range of particle energies. We demonstrate that the results can be interpreted in terms of a correlated random walk.

  9. Application of altitude/hypoxic training by elite athletes.

    Science.gov (United States)

    Wilber, Randall L

    2007-09-01

    At the Olympic level, differences in performance are typically less than 0.5%. This helps explain why many contemporary elite endurance athletes in summer and winter sport incorporate some form of altitude/hypoxic training within their year-round training plan, believing that it will provide the "competitive edge" to succeed at the Olympic level. The purpose of this paper is to describe the practical application of altitude/hypoxic training as used by elite athletes. Within the general framework of the paper, both anecdotal and scientific evidence will be presented relative to the efficacy of several contemporary altitude/hypoxic training models and devices currently used by Olympic-level athletes for the purpose of legally enhancing performance. These include the three primary altitude/hypoxic training models: 1) live high+train high (LH+TH), 2) live high+train low (LH+TL), and 3) live low+train high (LL+TH). The LH+TL model will be examined in detail and will include its various modifications: natural/terrestrial altitude, simulated altitude via nitrogen dilution or oxygen filtration, and hypobaric normoxia via supplemental oxygen. A somewhat opposite approach to LH+TL is the altitude/hypoxic training strategy of LL+TH, and data regarding its efficacy will be presented. Recently, several of these altitude/hypoxic training strategies and devices underwent critical review by the World Anti-Doping Agency (WADA) for the purpose of potentially banning them as illegal performance-enhancing substances/methods. This paper will conclude with an update on the most recent statement from WADA regarding the use of simulated altitude devices.

  10. Hypoxic contraction of cultured pulmonary vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Murray, T.R.; Chen, L.; Marshall, B.E.; Macarak, E.J.

    1990-01-01

    The cellular events involved in generating the hypoxic pulmonary vasoconstriction response are not clearly understood, in part because of the multitude of factors that alter pulmonary vascular tone. The goal of the present studies was to determine if a cell culture preparation containing vascular smooth muscle (VSM) cells could be made to contract when exposed to a hypoxic atmosphere. Cultures containing only fetal bovine pulmonary artery VSM cells were assessed for contractile responses to hypoxic stimuli by two methods. In the first, tension forces generated by cells grown on a flexible growth surface (polymerized polydimethyl siloxane) were manifested as wrinkles and distortions of the surface under the cells. Wrinkling of the surface was noted to progressively increase with time as the culture medium bathing the cells was made hypoxic (PO2 approximately 25 mmHg). The changes were sometimes reversible upon return to normoxic conditions and appeared to be enhanced in cells already exhibiting evidence of some baseline tone. Repeated passage in culture did not diminish the hypoxic response. Evidence for contractile responses to hypoxia was also obtained from measurements of myosin light chain (MLC) phosphorylation. Conversion of MLC to the phosphorylated species is an early step in the activation of smooth muscle contraction. Lowering the PO2 in the culture medium to 59 mmHg caused a 45% increase in the proportion of MLC in the phosphorylated form as determined by two-dimensional gel electrophoresis. Similarly, cultures preincubated for 4 h with 32P and then exposed to normoxia or hypoxia for a 5-min experimental period showed more than twice as much of the label in MLCs of the hypoxic cells

  11. ANISOTROPIC INTERMITTENCY OF MAGNETOHYDRODYNAMIC TURBULENCE

    International Nuclear Information System (INIS)

    Osman, K. T.; Kiyani, K. H.; Chapman, S. C.; Hnat, B.

    2014-01-01

    A higher-order multiscale analysis of spatial anisotropy in inertial range magnetohydrodynamic turbulence is presented using measurements from the STEREO spacecraft in fast ambient solar wind. We show for the first time that, when measuring parallel to the local magnetic field direction, the full statistical signature of the magnetic and Elsässer field fluctuations is that of a non-Gaussian globally scale-invariant process. This is distinct from the classic multiexponent statistics observed when the local magnetic field is perpendicular to the flow direction. These observations are interpreted as evidence for the weakness, or absence, of a parallel magnetofluid turbulence energy cascade. As such, these results present strong observational constraints on the statistical nature of intermittency in turbulent plasmas

  12. Prolonged Intermittent Renal Replacement Therapy.

    Science.gov (United States)

    Edrees, Fahad; Li, Tingting; Vijayan, Anitha

    2016-05-01

    Prolonged intermittent renal replacement therapy (PIRRT) is becoming an increasingly popular alternative to continuous renal replacement therapy in critically ill patients with acute kidney injury. There are significant practice variations in the provision of PIRRT across institutions, with respect to prescription, technology, and delivery of therapy. Clinical trials have generally demonstrated that PIRRT is non-inferior to continuous renal replacement therapy regarding patient outcomes. PIRRT offers cost-effective renal replacement therapy along with other advantages such as early patient mobilization and decreased nursing time. However, due to lack of standardization of the procedure, PIRRT still poses significant challenges, especially pertaining to appropriate drug dosing. Future guidelines and clinical trials should work toward developing consensus definitions for PIRRT and ensure optimal delivery of therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  13. Intermittent hypoxia induces hyperlipidemia in lean mice.

    Science.gov (United States)

    Li, Jianguo; Thorne, Laura N; Punjabi, Naresh M; Sun, Cheuk-Kwan; Schwartz, Alan R; Smith, Philip L; Marino, Rafael L; Rodriguez, Annabelle; Hubbard, Walter C; O'Donnell, Christopher P; Polotsky, Vsevolod Y

    2005-09-30

    Obstructive sleep apnea, a syndrome leading to recurrent intermittent hypoxia (IH), has been associated previously with hypercholesterolemia, independent of underlying obesity. We examined the effects of experimentally induced IH on serum lipid levels and pathways of lipid metabolism in the absence and presence of obesity. Lean C57BL/6J mice and leptin-deficient obese C57BL/6J-Lep(ob) mice were exposed to IH for five days to determine changes in serum lipid profile, liver lipid content, and expression of key hepatic genes of lipid metabolism. In lean mice, exposure to IH increased fasting serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, phospholipids (PLs), and triglycerides (TGs), as well as liver TG content. These changes were not observed in obese mice, which had hyperlipidemia and fatty liver at baseline. In lean mice, IH increased sterol regulatory element binding protein 1 (SREBP-1) levels in the liver, increased mRNA and protein levels of stearoyl-coenzyme A desaturase 1 (SCD-1), an important gene of TG and PL biosynthesis controlled by SREBP-1, and increased monounsaturated fatty acid content in serum, which indicated augmented SCD-1 activity. In addition, in lean mice, IH decreased protein levels of scavenger receptor B1, regulating uptake of cholesterol esters and HDL by the liver. We conclude that exposure to IH for five days increases serum cholesterol and PL levels, upregulates pathways of TG and PL biosynthesis, and inhibits pathways of cholesterol uptake in the liver in the lean state but does not exacerbate the pre-existing hyperlipidemia and metabolic disturbances in leptin-deficient obesity.

  14. Contractile Activity Is Necessary to Trigger Intermittent Hypobaric Hypoxia-Induced Fiber Size and Vascular Adaptations in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    David Rizo-Roca

    2018-05-01

    Full Text Available Altitude training has become increasingly popular in recent decades. Its central and peripheral effects are well-described; however, few studies have analyzed the effects of intermittent hypobaric hypoxia (IHH alone on skeletal muscle morphofunctionality. Here, we studied the effects of IHH on different myofiber morphofunctional parameters, investigating whether contractile activity is required to elicit hypoxia-induced adaptations in trained rats. Eighteen male Sprague-Dawley rats were trained 1 month and then divided into three groups: (1 rats in normobaria (trained normobaric inactive, TNI; (2 rats subjected daily to a 4-h exposure to hypobaric hypoxia equivalent to 4,000 m (trained hypobaric inactive, THI; and (3 rats subjected daily to a 4-h exposure to hypobaric hypoxia just before performing light exercise (trained hypobaric active, THA. After 2 weeks, the tibialis anterior muscle (TA was excised. Muscle cross-sections were stained for: (1 succinate dehydrogenase to identify oxidative metabolism; (2 myosin-ATPase to identify slow- and fast-twitch fibers; and (3 endothelial-ATPase to stain capillaries. Fibers were classified as slow oxidative (SO, fast oxidative glycolytic (FOG, fast intermediate glycolytic (FIG or fast glycolytic (FG and the following parameters were measured: fiber cross-sectional area (FCSA, number of capillaries per fiber (NCF, NCF per 1,000 μm2 of FCSA (CCA, fiber and capillary density (FD and CD, and the ratio between CD and FD (C/F. THI rats did not exhibit significant changes in most of the parameters, while THA animals showed reduced fiber size. Compared to TNI rats, FOG fibers from the lateral/medial fields, as well as FIG and FG fibers from the lateral region, had smaller FCSA in THA rats. Moreover, THA rats had increased NCF in FG fibers from all fields, in medial and posterior FIG fibers and in posterior FOG fibers. All fiber types from the three analyzed regions (except the posterior FG fibers displayed a

  15. Satellite-based empirical models linking river plume dynamics with hypoxic area andvolume

    Science.gov (United States)

    Satellite-based empirical models explaining hypoxic area and volume variation were developed for the seasonally hypoxic (O2 < 2 mg L−1) northern Gulf of Mexico adjacent to the Mississippi River. Annual variations in midsummer hypoxic area and ...

  16. Chronic hypoxic incubation blunts a cardiovascular reflex loop in embryonic American alligator (Alligator mississippiensis).

    Science.gov (United States)

    Eme, John; Hicks, James W; Crossley, Dane A

    2011-10-01

    Hypoxia is a naturally occurring environmental challenge for embryonic non-avian reptiles, and this study is the first to investigate the impact of chronic hypoxia on a possible chemoreflex loop in a developing non-avian reptile. We measured heart rate and blood pressure in normoxic and hypoxic-incubated (10% O(2)) American alligator embryos (Alligator mississippiensis) at 70 and 90/95% of development. We hypothesized that hypoxic incubation would blunt embryonic alligators' response to a reflex loop stimulated by phenylbiguanide (PBG), a 5-HT(3) receptor agonist that stimulates vagal pulmonary C-fiber afferents. PBG injection caused a hypotensive bradycardia in 70 and 95% of development embryos (paired t tests, P alligator, with an extended length of time between each developmental stage relative to avian species, may provide an excellent model to test the cardiorespiratory effects of prolonged exposure to changes in atmospheric gases. This extended period allows for lengthy studies at each stage without the transition to a new stage, and the natural occurrence of hypoxia and hypercapnia in crocodilian nests makes this stress ecologically and evolutionarily relevant.

  17. Perinatal intermittent hypoxia alters γ-aminobutyric acid: a receptor levels in rat cerebellum.

    Science.gov (United States)

    Pae, Eung-Kwon; Yoon, Audrey J; Ahuja, Bhoomika; Lau, Gary W; Nguyen, Daniel D; Kim, Yong; Harper, Ronald M

    2011-12-01

    Perinatal hypoxia commonly causes brain injury in infants, but the time course and mechanisms underlying the preferential male injury are unclear. Intermittent hypoxia disturbs cerebellar γ-aminobutyric (GABA)-A receptor profiles during the perinatal period, possibly responding to transient excitatory processes associated with GABA(A) receptors. We examined whether hypoxic insults were particularly damaging to the male rodent cerebellum during a specific developmental time window. We evaluated cerebellar injury and GABA(A) receptor profiles following 5-h intermittent hypoxia (IH: 20.8% and 10.3% ambient oxygen, switched every 240s) or room-air control in groups of male and female rat pups on postnatal d 1-2, wk 1, or wk 3. The cerebella were harvested and compared between groups. The mRNA levels of GABA(A) receptors α6, normalized to a house-keeping gene GAPDH, and assessed using real-time reverse-transcriptase PCR assays were up-regulated by IH at wk 1, more extensively in male rats, with sex influencing the regulatory time-course. In contrast, GABA(A) α6 receptor protein expression levels, assessed using Western blot assays, reached a nadir at wk 1 in both male and female rats, possibly indicating involvement of a post-transcriptional mechanism. The extent of cerebellar damage and level of apoptosis, assessed by DNA fragmentation, were greatest in the wk 3 IH-exposed group. The findings suggest partial protection for female rats against early hypoxic insult in the cerebellum, and that down-regulation of GABA(A) receptors, rather than direct neural injury assessed by DNA fragmentation may modify cerebellar function, with potential later motor and other deficits. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

  18. NF-κB-dependent transcriptional upregulation of cyclin D1 exerts cytoprotection against hypoxic injury upon EGFR activation

    International Nuclear Information System (INIS)

    Chen, Zhi-Dong; Xu, Liang; Tang, Kan-Kai; Gong, Fang-Xiao; Liu, Jing-Quan; Ni, Yin; Jiang, Ling-Zhi; Hong, Jun; Han, Fang; Li, Qian; Yang, Xiang-Hong; Sun, Ren-Hua; Mo, Shi-Jing

    2016-01-01

    Apoptosis of neural cells is one of the main pathological features in hypoxic/ischemic brain injury. Nuclear factor-κB (NF-κB) might be a potential therapeutic target for hypoxic/ischemic brain injury since NF-κB has been found to be inactivated after hypoxia exposure, yet the underlying molecular mechanisms of NF-κB inactivation are largely unknown. Here we report that epidermal growth factor receptor (EGFR) activation prevents neuron-like PC12 cells apoptosis in response to hypoxia via restoring NF-κB-dependent transcriptional upregulation of cyclin D1. Functionally, EGFR activation by EGF stimulation mitigates hypoxia-induced PC12 cells apoptosis in both dose- and time-dependent manner. Of note, EGFR activation elevates IKKβ phosphorylation, increases IκBα ubiquitination, promotes P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as upregulates cyclin D1 expression. EGFR activation also abrogates the decrease of IKKβ phosphorylation, reduction of IκBα ubiquitination, blockade of P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as downregulation of cyclin D1 expression induced by hypoxia. Furthermore, NF-κB-dependent upregulation of cyclin D1 is instrumental for the EGFR-mediated cytoprotection against hypoxic apoptosis. In addition, the dephosphorylation of EGFR induced by either EGF siRNA transfection or anti-HB-EGF neutralization antibody treatment enhances hypoxic cytotoxicity, which are attenuated by EGF administration. Our results highlight the essential role of NF-κB-dependent transcriptional upregulation of cyclin D1 in EGFR-mediated cytoprotective effects under hypoxic preconditioning and support further investigation of EGF in clinical trials of patients with hypoxic/ischemic brain injury. - Highlights: • EGFR activation significantly decreases hypoxia-induced PC12 cells injury. • EGFR activation abrogates the transcriptional repression of cyclin D1 induced by hypoxia in a NF

  19. NF-κB-dependent transcriptional upregulation of cyclin D1 exerts cytoprotection against hypoxic injury upon EGFR activation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhi-Dong [Department of Critical Care Medicine, The First Affiliated Hospital of Huzhou Normal College, Huzhou 313000, Zhejiang (China); Xu, Liang [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China); Tang, Kan-Kai [Department of Critical Care Medicine, The First Affiliated Hospital of Huzhou Normal College, Huzhou 313000, Zhejiang (China); Gong, Fang-Xiao; Liu, Jing-Quan; Ni, Yin; Jiang, Ling-Zhi; Hong, Jun; Han, Fang; Li, Qian; Yang, Xiang-Hong [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China); Sun, Ren-Hua, E-mail: jqin168@hotmail.com [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China); Mo, Shi-Jing, E-mail: msj860307@163.com [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China)

    2016-09-10

    Apoptosis of neural cells is one of the main pathological features in hypoxic/ischemic brain injury. Nuclear factor-κB (NF-κB) might be a potential therapeutic target for hypoxic/ischemic brain injury since NF-κB has been found to be inactivated after hypoxia exposure, yet the underlying molecular mechanisms of NF-κB inactivation are largely unknown. Here we report that epidermal growth factor receptor (EGFR) activation prevents neuron-like PC12 cells apoptosis in response to hypoxia via restoring NF-κB-dependent transcriptional upregulation of cyclin D1. Functionally, EGFR activation by EGF stimulation mitigates hypoxia-induced PC12 cells apoptosis in both dose- and time-dependent manner. Of note, EGFR activation elevates IKKβ phosphorylation, increases IκBα ubiquitination, promotes P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as upregulates cyclin D1 expression. EGFR activation also abrogates the decrease of IKKβ phosphorylation, reduction of IκBα ubiquitination, blockade of P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as downregulation of cyclin D1 expression induced by hypoxia. Furthermore, NF-κB-dependent upregulation of cyclin D1 is instrumental for the EGFR-mediated cytoprotection against hypoxic apoptosis. In addition, the dephosphorylation of EGFR induced by either EGF siRNA transfection or anti-HB-EGF neutralization antibody treatment enhances hypoxic cytotoxicity, which are attenuated by EGF administration. Our results highlight the essential role of NF-κB-dependent transcriptional upregulation of cyclin D1 in EGFR-mediated cytoprotective effects under hypoxic preconditioning and support further investigation of EGF in clinical trials of patients with hypoxic/ischemic brain injury. - Highlights: • EGFR activation significantly decreases hypoxia-induced PC12 cells injury. • EGFR activation abrogates the transcriptional repression of cyclin D1 induced by hypoxia in a NF

  20. The effects of intermittent, CD4-guided antiretroviral therapy on body composition and metabolic parameters

    NARCIS (Netherlands)

    Martinez, Esteban; Visnegarwala, Fehmida; Grund, Birgit; Thomas, Avis; Gibert, Cynthia; Shlay, Judith; Drummond, Fraser; Pearce, Daniel; Edwards, Simon; Reiss, Peter; El-Sadr, Wafaa; Carr, Andrew

    2010-01-01

    Objective: To assess the effects of decreased antiretroviral therapy exposure on body fat and metabolic parameters. Design: Substudy of the Strategies for Management of Anti-Retroviral Therapy study, in which participants were randomized to intermittent CD4-guided [Drug Conservation (DC) group] or

  1. Intermittent cranial lung herniation in two dogs.

    Science.gov (United States)

    Guglielmini, Carlo; De Simone, Antonio; Valbonetti, Luca; Diana, Alessia

    2007-01-01

    Two aged dogs with chronic obstructive airway disease were evaluated because of intermittent swelling of the ventral cervical region. Radiographs made at expiration and caudal positioning of the forelimbs allowed identification of intermittent cervical lung herniation of the left and right cranial lung lobe in both dogs. Pulmonary hyperinflation, increased expiratory effort, and chronic coughing were considered responsible for the lung herniation. Cervical lung hernia should be included in the differential diagnoses of intermittent cervical swelling in dogs with chronic respiratory disorders associated with increased expiratory effort and chronic coughing.

  2. Nitrous oxide emissions from the Gulf of Mexico Hypoxic Zone

    Science.gov (United States)

    The production of nitrous oxide (N2O), a potent greenhouse gas, in hypoxic coastal zones remains poorly characterized due to a lack of data, though large nitrogen inputs and deoxygenation typical of these systems create the potential for large N2O emissions. We report the first N...

  3. Perinatal Hypoxic-Ischemic brain injury; MR findings

    International Nuclear Information System (INIS)

    Park, Dong Woo; Seo, Chang Hye

    1994-01-01

    To characterize the MR findings of hypoxic-ischemic brain injury and to assess the value of the MR imaging. SE T1-, T2-weighted, and IR brain MR images of 44 infants and children with the past history of perinatal hypoxic insults were reviewed. Abnormal brain MR findings of 8 patients with birth history of prematurity and 36 patients with birth history of full-term/posterm including 7 with severe anoxic insult history, were compared in regard to the location and the character of the lesions. MRI demonstrated the followings; (1)abnormal signal intensity lesions of subcortical and/or deep cerebral white matter, cortex, and deep gray matter, (2)atrophy of the cerebral white matter, cortex and corpus callosum, with/without ventriculomegaly, and (3)delay in myelination. Periventricular and deep white matter lesions were demonstrated in the prematurity, the deep white matter lesions and/ or subcortical white matter lesions in the term/post-term, and deep gray matter lesions in the 7 patients with severe anoxic insults history. MR imaging was useful in the diagnosis of the hypoxic-ischemic brain injury, and the white and gray matter lesions were correlated with the time of the injury and the severity of hypoxic insult

  4. Patterns of neonatal hypoxic-ischaemic brain injury

    International Nuclear Information System (INIS)

    Vries, Linda S. de; Groenendaal, Floris

    2010-01-01

    Enormous progress has been made in assessing the neonatal brain, using magnetic resonance imaging (MRI). In this review, we will describe the use of MRI and proton magnetic resonance spectroscopy in detecting different patterns of brain injury in (full-term) human neonates following hypoxic-ischaemic brain injury and indicate the relevance of these findings in predicting neurodevelopmental outcome. (orig.)

  5. Patterns of neonatal hypoxic-ischaemic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Linda S. de [University Medical Centre, Department of Neonatology, Wilhelmina Children' s Hospital, Utrecht (Netherlands); Wilhelmina Children' s Hospital, University Medical Centre, Department of Neonatology, KE 04.123.1, P.O. Box 85090, Utrecht (Netherlands); Groenendaal, Floris [University Medical Centre, Department of Neonatology, Wilhelmina Children' s Hospital, Utrecht (Netherlands)

    2010-06-15

    Enormous progress has been made in assessing the neonatal brain, using magnetic resonance imaging (MRI). In this review, we will describe the use of MRI and proton magnetic resonance spectroscopy in detecting different patterns of brain injury in (full-term) human neonates following hypoxic-ischaemic brain injury and indicate the relevance of these findings in predicting neurodevelopmental outcome. (orig.)

  6. Neuroprotective effects of Ellagic acid on Neonatal Hypoxic Brain ...

    African Journals Online (AJOL)

    Purpose: To investigate if ellagic acid exerts neuroprotective effects in hypoxic ischemic (HI) brain injury by inhibiting apoptosis and inflammatory responses. Methods: Separate groups of rat pups from post-natal day 4 (D4) were administered with ellagic acid (10, 20 or 40 mg/kg body weight) orally till post- natal day 10 ...

  7. SUMO Signaling by Hypoxic Inactivation of SUMO-Specific Isopeptidases

    Directory of Open Access Journals (Sweden)

    Kathrin Kunz

    2016-09-01

    Full Text Available Post-translational modification of proteins with ubiquitin-like SUMO modifiers is a tightly regulated and highly dynamic process. The SENP family of SUMO-specific isopeptidases comprises six cysteine proteases. They are instrumental in counterbalancing SUMO conjugation, but their regulation is not well understood. We demonstrate that in hypoxic cell extracts, the catalytic activity of SENP family members, in particular SENP1 and SENP3, is inhibited in a rapid and fully reversible process. Comparative mass spectrometry from normoxic and hypoxic cells defines a subset of hypoxia-induced SUMO1 targets, including SUMO ligases RanBP2 and PIAS2, glucose transporter 1, and transcriptional regulators. Among the most strongly induced targets, we identified the transcriptional co-repressor BHLHE40, which controls hypoxic gene expression programs. We provide evidence that SUMOylation of BHLHE40 is reversed by SENP1 and contributes to transcriptional repression of the metabolic master regulator gene PGC-1α. We propose a pathway that connects oxygen-controlled SENP activity to hypoxic reprogramming of metabolism.

  8. Hybrid TiO2 -Ruthenium Nano-photosensitizer Synergistically Produces Reactive Oxygen Species in both Hypoxic and Normoxic Conditions.

    Science.gov (United States)

    Gilson, Rebecca C; Black, Kvar C L; Lane, Daniel D; Achilefu, Samuel

    2017-08-28

    Photodynamic therapy (PDT) is widely used to treat diverse diseases, but its dependence on oxygen to produce cytotoxic reactive oxygen species (ROS) diminishes the therapeutic effect in a hypoxic environment, such as solid tumors. Herein, we developed a ROS-producing hybrid nanoparticle-based photosensitizer capable of maintaining high levels of ROS under both normoxic and hypoxic conditions. Conjugation of a ruthenium complex (N3) to a TiO 2 nanoparticle afforded TiO 2 -N3. Upon exposure of TiO 2 -N3 to light, the N3 injected electrons into TiO 2 to produce three- and four-fold more hydroxyl radicals and hydrogen peroxide, respectively, than TiO 2 at 160 mmHg. TiO 2 -N3 maintained three-fold higher hydroxyl radicals than TiO 2 under hypoxic conditions via N3-facilitated electron-hole reduction of adsorbed water molecules. The incorporation of N3 transformed TiO 2 from a dual type I and II PDT agent to a predominantly type I photosensitizer, irrespective of the oxygen content. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the neonatal brain: mechanisms and possible interventions.

    Science.gov (United States)

    Li, Yong; Gonzalez, Pablo; Zhang, Lubo

    2012-08-01

    Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxic-ischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other brain disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Tissue oxygenation in brain, muscle, and fat in a rat model of sleep apnea: differential effect of obstructive apneas and intermittent hypoxia.

    Science.gov (United States)

    Almendros, Isaac; Farré, Ramon; Planas, Anna M; Torres, Marta; Bonsignore, Maria R; Navajas, Daniel; Montserrat, Josep M

    2011-08-01

    To test the hypotheses that the dynamic changes in brain oxygen partial pressure (PtO(2)) in response to obstructive apneas or to intermittent hypoxia differ from those in other organs and that the changes in brain PtO(2) in response to obstructive apneas is a source of oxidative stress. Prospective controlled animal study. University laboratory. 98 Sprague-Dawley rats. Cerebral cortex, skeletal muscle, or visceral fat tissues were exposed in anesthetized animals subjected to either obstructive apneas or intermittent hypoxia (apneic and hypoxic events of 15 s each and 60 events/h) for 1 h. Arterial oxygen saturation (SpO(2)) presented a stable pattern, with similar desaturations during both stimuli. The PtO(2) was measured by a microelectrode. During obstructive apneas, a fast increase in cerebral PtO(2) was observed (38.2 ± 3.4 vs. 54.8 ± 5.9 mm Hg) but not in the rest of tissues. This particular cerebral response was not found during intermittent hypoxia. The cerebral content of reduced glutathione was decreased after obstructive apneas (46.2% ± 15.2%) compared to controls (100.0% ± 14.7%), but not after intermittent hypoxia. This antioxidant consumption after obstructive apneas was accompanied by increased cerebral lipid peroxidation under this condition. No changes were observed for these markers in the other tissues. These results suggest that cerebral cortex could be protected in some way from hypoxic periods caused by obstructive apneas. The increased cerebral PtO(2) during obstructive apneas may, however, cause harmful effects (oxidative stress). The obstructive apnea model appears to be more adequate than the intermittent hypoxia model for studying brain changes associated with OSA.

  11. Intermittent sea-level acceleration

    Science.gov (United States)

    Olivieri, M.; Spada, G.

    2013-10-01

    Using instrumental observations from the Permanent Service for Mean Sea Level (PSMSL), we provide a new assessment of the global sea-level acceleration for the last ~ 2 centuries (1820-2010). Our results, obtained by a stack of tide gauge time series, confirm the existence of a global sea-level acceleration (GSLA) and, coherently with independent assessments so far, they point to a value close to 0.01 mm/yr2. However, differently from previous studies, we discuss how change points or abrupt inflections in individual sea-level time series have contributed to the GSLA. Our analysis, based on methods borrowed from econometrics, suggests the existence of two distinct driving mechanisms for the GSLA, both involving a minority of tide gauges globally. The first effectively implies a gradual increase in the rate of sea-level rise at individual tide gauges, while the second is manifest through a sequence of catastrophic variations of the sea-level trend. These occurred intermittently since the end of the 19th century and became more frequent during the last four decades.

  12. Social Smoking among Intermittent Smokers

    Science.gov (United States)

    Shiffman, Saul; Li, Xiaoxue; Dunbar, Michael S.; Ferguson, Stuart G.; Tindle, Hilary A.; Scholl, Sarah M.

    2015-01-01

    Background “Social smoking” - smoking mostly or even only with others – may be an important pattern that implies smoking motivated extrinsically by social influences. Non-daily smokers (intermittent smokers; ITS) are often assumed to be social smokers, with some authors even assuming that all ITS are social smokers (SS+). We sought to identify and characterize social smokers in a sample of ITS. Methods 204 adult ITS (smoking 4–27 days/month) recorded the circumstances of smoking in their natural settings using Ecological Momentary Assessment, while also recording their circumstances in nonsmoking moments. SS+ were defined as ITS who were with others when they smoked most of their cigarettes, and who were ≥ 50% more likely to be with others when smoking than when not. Results Only 13% of ITS were SS+. Although defined solely on the basis of presence of others, SS+ showed a distinct pattern of smoking across multiple dimensions: Compared to other ITS (who were significantly less likely to smoke when with others), SS+ smoking was more associated with socializing, being with friends and acquaintances, drinking alcohol, weekends, evening or nighttime, being in other people’s homes, but not their own home. SS+ smoking was low in the morning and increased in the evening. SS+ smoked fewer days/week and were less dependent, but did not differ demographically. Conclusions Social smoking does constitute a highly distinct smoking pattern, but is not common among adult ITS. PMID:26205313

  13. Intermittent ileocoecal intususception in adult

    International Nuclear Information System (INIS)

    Cambal, M.; Zonca, P.; Maly, T.

    2013-01-01

    Aim: Aim of our paper is to present a case-report of chronic invagination in adult patient. Material: 28-years old woman with one year history of intermittent abdominal pain with symptoms of subileus state. She has underwent abdominal ultrasonography, abdominal X-ray, colonoscopy, irigography and abdominal CT. Appendectomy indicated for diagnosis of chronic appendicitis did not improve symptoms. Consecutively during acute problems were irigography and CT performed and diagnosis of an incomplete colon transversum obstruction of uncertain origin was established. There was stated suspicion of an intususception and patient was due to a repeated gastrointestinal passage indicated for an explorative laparotomy. During operation there was identified threefold invagination – colo-colonic, ileo-colonic and ileo-ileal. As a leading point of invagination was found in terminal ileum intraluminal polypous tumor 5 cm in diameter. Because of the secondary chronic changes of right colon wall and terminal ileum wall, after partial desinvagination right hemicolectomy was performed. Results: Patient was primary healed and now is without any subjective problems. Conclusion: Invagination is an acute abdominal event of obturative-strangulative type and it mainly occurs in infantile age. It is astonishing how long were patient´s difficulties lasting without obvious acute ileus. It is necessary in clinical practice to think on these rare reasons of gastrointestinal passage disorders. (author)

  14. White adipose tissue coloring by intermittent fasting.

    Science.gov (United States)

    Kivelä, Riikka; Alitalo, Kari

    2017-11-01

    Intermittent fasting (IF) has been shown to promote metabolic health in several organisms. Two recent papers show that IF induces white adipose tissue beiging and increases thermogenesis, which improves metabolic health in mice.

  15. On-line intermittent connector anomaly detection

    Data.gov (United States)

    National Aeronautics and Space Administration — This paper investigates a non-traditional use of differential current sensor and current sensor to detect intermittent disconnection problems in connectors. An...

  16. Intermittent chaotic chimeras for coupled rotators

    DEFF Research Database (Denmark)

    Olmi, Simona; Martens, Erik Andreas; Thutupalli, Shashi

    2015-01-01

    Two symmetrically coupled populations of N oscillators with inertia m display chaotic solutions with broken symmetry similar to experimental observations with mechanical pendulums. In particular, we report evidence of intermittent chaotic chimeras, where one population is synchronized and the other...

  17. Feigenbaum attractor and intermittency in particle collisions

    International Nuclear Information System (INIS)

    Batunin, A.V.

    1992-01-01

    The hypothesis is proposed that the Feigenbaum attractor arising as a limit set in an infinite pichfork bifurcation sequence for unimodal one-dimensional maps underlies the intermittency phenomena in particle collisions. 23 refs.; 8 figs

  18. Intermittent morphine treatment induces a long-lasting increase in cholinergic modulation of GABAergic synapses in nucleus accumbens of adult rats

    NARCIS (Netherlands)

    de Rover, M.; Lodder, J.C.; Schoffelmeer, A.N.M.; Brussaard, A.B.

    2005-01-01

    Repeated exposure to drugs of abuse causes persistent behavioral sensitization and associated adaptations of striatal neurotransmission, which is thought to play an important role in certain aspects of drug addiction. Microdialysis and neurochemical studies suggest that intermittent morphine

  19. Epigenetic regulation of hypoxic sensing disrupts cardiorespiratory homeostasis

    OpenAIRE

    Nanduri, Jayasri; Makarenko, Vladislav; Reddy, Vaddi Damodara; Yuan, Guoxiang; Pawar, Anita; Wang, Ning; Khan, Shakil A.; Zhang, Xin; Kinsman, Brian; Peng, Ying-Jie; Kumar, Ganesh K.; Fox, Aaron P.; Godley, Lucy A.; Semenza, Gregg L.; Prabhakar, Nanduri R.

    2012-01-01

    Recurrent apnea with intermittent hypoxia is a major clinical problem in preterm infants. Recent studies, although limited, showed that adults who were born preterm exhibit increased incidence of sleep-disordered breathing and hypertension, suggesting that apnea of prematurity predisposes to autonomic dysfunction in adulthood. Here, we demonstrate that adult rats that were exposed to intermittent hypoxia as neonates exhibit exaggerated responses to hypoxia by the carotid body and adrenal chro...

  20. Continuous and intermittent exposure of neonatal rat calvarial cells to PTHrP (1-36 inhibits bone nodule mineralization in vitro by downregulating bone sialoprotein expression via the cAMP signaling pathway [v2; ref status: indexed, http://f1000r.es/18x

    Directory of Open Access Journals (Sweden)

    Suzan A Kamel

    2013-06-01

    Full Text Available The development and growth of the skeleton in the absence of parathyroid-hormone-related protein (PTHrP is abnormal.  The shortening of appendicular bones in PTHrP gene null mice is explained by an effect of PTHrP on endochondral bone growth.  Whether or not PTHrP influences intramembranous ossification is less clear.  The purpose of this study was to determine the effect of exogenous PTHrP on intramembranous ossification in vitro.  Neonatal rat calvarial cells maintained in primary cell culture conditions that permit spontaneous formation of woven bone nodules by intramembranous ossification were studied. The expression of PTHrP, parathyroid hormone 1 receptor (PTH1R, and alkaline phosphatase (AP by osteogenic cells in developing nodules and the effects of PTHrP (1-36 on nodule development was determined over 3-18 days. PTHrP and PTH1R were detected colonies of osteogenic cells on culture day three, and AP was detected on day six. PTHrP and its receptor were localized in pre-osteoblasts, osteoblasts, and osteocytes, and AP activity was detected in pre-osteoblasts and osteoblasts but not osteocytes. Continuous and intermittent exposure to PTHrP (1-36 decreased the number of mineralized bone nodules and bone sialoprotein (BSP mRNA and protein, but had no effect on the number of AP-positive osteogenic cell colonies, cell proliferation, apoptosis, or osteopontin (OPN mRNA. These results demonstrate that osteogenic cells that participate in the formation of woven bone nodules in vitro exhibit PTHrP and PTH1R before they demonstrate AP activity. Exogenous PTHrP (1-36 inhibits the mineralization of woven bone deposited during bone nodule formation in vitro, possibly by reducing the expression of BSP.

  1. Hot and Hypoxic Environments Inhibit Simulated Soccer Performance and Exacerbate Performance Decrements When Combined

    Science.gov (United States)

    Aldous, Jeffrey W. F.; Chrismas, Bryna C. R.; Akubat, Ibrahim; Dascombe, Ben; Abt, Grant; Taylor, Lee

    2016-01-01

    The effects of heat and/or hypoxia have been well-documented in match-play data. However, large match-to-match variation for key physical performance measures makes environmental inferences difficult to ascertain from soccer match-play. Therefore, the present study aims to investigate the hot (HOT), hypoxic (HYP), and hot-hypoxic (HH) mediated-decrements during a non-motorized treadmill based soccer-specific simulation. Twelve male University soccer players completed three familiarization sessions and four randomized crossover experimental trials of the intermittent Soccer Performance Test (iSPT) in normoxic-temperate (CON: 18°C 50% rH), HOT (30°C; 50% rH), HYP (1000 m; 18°C 50% rH), and HH (1000 m; 30°C; 50% rH). Physical performance and its performance decrements, body temperatures (rectal, skin, and estimated muscle temperature), heart rate (HR), arterial blood oxygen saturation (SaO2), perceived exertion, thermal sensation (TS), body mass changes, blood lactate, and plasma volume were all measured. Performance decrements were similar in HOT and HYP [Total Distance (−4%), High-speed distance (~−8%), and variable run distance (~−12%) covered] and exacerbated in HH [total distance (−9%), high-speed distance (−15%), and variable run distance (−15%)] compared to CON. Peak sprint speed, was 4% greater in HOT compared with CON and HYP and 7% greater in HH. Sprint distance covered was unchanged (p > 0.05) in HOT and HYP and only decreased in HH (−8%) compared with CON. Body mass (−2%), temperatures (+2–5%), and TS (+18%) were altered in HOT. Furthermore, SaO2 (−8%) and HR (+3%) were changed in HYP. Similar changes in body mass and temperatures, HR, TS, and SaO2 were evident in HH to HOT and HYP, however, blood lactate (p physical performance during iSPT. Future interventions should address the increases in TS and body temperatures, to attenuate these decrements on soccer performance. PMID:26793122

  2. Preclinical assessment of hypoxic marker specificity and sensitivity

    International Nuclear Information System (INIS)

    Iyer, Renuka V.; Engelhardt, Edward L.; Stobbe, Corinne C.; Schneider, Richard F.; Chapman, J. Donald

    1998-01-01

    Purpose: In the search for a sensitive, accurate, and noninvasive technique for quantifying human tumor hypoxia, our laboratory has synthesized several potential radiodiagnostic agents. The purpose of this study was to assess and compare the hypoxic marking properties of both radioiodinated and Tc-99m labeled markers in appropriate test systems which can predict for in vivo activity. Materials and Methods: Preclinical assessment of hypoxic marker specificity and sensitivity employed three laboratory assays with tumor cells in vitro and in vivo. Radiolabeled marker uptake and/or binding to whole EMT-6 tumor cells under extremely hypoxic and aerobic conditions was measured and their ratio defined hypoxia-specific factor (HSF). Marker specificity to hypoxic tumor tissue was estimated from its selective avidity to two rodent tumors in vivo, whose radiobiologic hypoxic fractions (HF) had been measured. The ratios of % injected dose/gram (%ID/g) of marker at various times in EMT-6 tumor tissue relative to that in the blood and muscle of scid mice were used to quantify hypoxia-specific activity. This tumor in this host exhibited an average radiobiologic HF of ∼35%. As well, nuclear medicine images were acquired from R3327-AT (HF ≅15%) and R3327-H (no measurable HF) prostate carcinomas growing in rats to distinguish between marker avidity due to hypoxia versus perfusion. Results: The HSF for FC-103 and other iodinated markers were higher (5-40) than those for FC-306 and other Tc-99m labeled markers. The latter did not show hypoxia-specific uptake into cells in vitro. Qualitative differences were observed in the biodistribution and clearance kinetics of the iodinated azomycin nucleosides relative to the technetium chelates. The largest tumor/blood (T/B) and tumor/muscle (T/M) ratios were observed for compounds of the azomycin nucleoside class in EMT-6 tumor-bearing scid mice. These markers also showed a 3-4 x higher uptake into R3327-AT tumors relative to the well

  3. Intermittent but not sustained hypoxia activates orexin-containing neurons in mice.

    Science.gov (United States)

    Yamaguchi, Keiji; Futatsuki, Takahiro; Ushikai, Jumpei; Kuroki, Chiharu; Minami, Toshiaki; Kakihana, Yasuyuki; Kuwaki, Tomoyuki

    2015-01-15

    Hypothalamic orexin-containing neurons are activated by CO2 and contribute to hypercapnic ventilatory activation. However, their role in oxygen-related regulation of breathing is not well defined. In this study, we examined whether an experimental model mimicking apnea-induced repetitive hypoxemia (intermittent hypoxia [IH]) activates orexin-containing neurons. Mice were exposed to IH (5×5min at 10% O2), intermittent hyperoxia (IO; 5×5min at 50% O2), sustained hypoxia (SH; 25min at 10% O2), or sham stimulation. Their brains were examined using double immunohistochemical staining for orexin and c-Fos. The results indicated that IH (25.8±3.0%), but not SH (9.0±1.5%) activated orexin-containing neurons when compared to IO (5.5±0.6%) and sham stimulation (5.9±1.4%). These results correlate with those of our previous work showing that IH-induced respiratory long-term facilitation is dependent on orexin-containing neurons. Taken together, orexin contributes to repetitive hypoxia-induced respiratory activation and the hypoxic activation of orexin-containing neurons is pattern dependent. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Enhanced carotid body chemosensory activity and the cardiovascular alterations induced by intermittent hypoxia

    Directory of Open Access Journals (Sweden)

    Rodrigo eIturriaga

    2014-12-01

    Full Text Available The carotid body (CB plays a main role in the maintenance of the oxygen homeostasis. The hypoxic stimulation of the CB increases the chemosensory discharge, which in turn elicits reflex sympathetic, cardiovascular and ventilatory adjustments. An exacerbate carotid chemosensory activity has been associated with human sympathetic-mediated diseases such as hypertension, insulin resistance, heart failure and obstructive sleep apnea (OSA. Indeed, the CB chemosensory discharge becomes tonically hypereactive in experimental models of OSA and heart failure. Chronic intermittent hypoxia (CIH, a main feature of OSA, enhances CB chemosensory baseline discharges in normoxia and in response to hypoxia, inducing sympathetic overactivity and hypertension. Oxidative stress, increased levels of ET-1, Angiotensin II and pro-inflammatory cytokines, along with a reduced production of NO in the CB, have been associated with the enhanced carotid chemosensory activity. In this review, we will discuss new evidence supporting a main role for the CB chemoreceptor in the autonomic and cardiorespiratory alterations induced by intermittent hypoxia, as well as the molecular mechanisms involved in the CB chemosensory potentiation.

  5. Enhanced carotid body chemosensory activity and the cardiovascular alterations induced by intermittent hypoxia

    Science.gov (United States)

    Iturriaga, Rodrigo; Andrade, David C.; Del Rio, Rodrigo

    2014-01-01

    The carotid body (CB) plays a main role in the maintenance of the oxygen homeostasis. The hypoxic stimulation of the CB increases the chemosensory discharge, which in turn elicits reflex sympathetic, cardiovascular, and ventilatory adjustments. An exacerbate carotid chemosensory activity has been associated with human sympathetic-mediated diseases such as hypertension, insulin resistance, heart failure, and obstructive sleep apnea (OSA). Indeed, the CB chemosensory discharge becomes tonically hypereactive in experimental models of OSA and heart failure. Chronic intermittent hypoxia (CIH), a main feature of OSA, enhances CB chemosensory baseline discharges in normoxia and in response to hypoxia, inducing sympathetic overactivity and hypertension. Oxidative stress, increased levels of ET-1, Angiotensin II and pro-inflammatory cytokines, along with a reduced production of NO in the CB, have been associated with the enhanced carotid chemosensory activity. In this review, we will discuss new evidence supporting a main role for the CB chemoreceptor in the autonomic and cardiorespiratory alterations induced by intermittent hypoxia, as well as the molecular mechanisms involved in the CB chemosensory potentiation. PMID:25520668

  6. Effects of temperature and hypoxic stress on the oxygen ...

    African Journals Online (AJOL)

    The specific oxygen consumption rate (VO2lMb) of Labeo capensis, the freshwater mudsucker, was determined for small and large fish at winter (8°C) and summer (23°C) temperatures. VO2lMb was also determined during hypoxic conditions of the experimental water. It was found that VO2lMb does not differ substantially ...

  7. Intermittent ephemeral river-breaching

    Science.gov (United States)

    Reniers, A. J.; MacMahan, J. H.; Gallagher, E. L.; Shanks, A.; Morgan, S.; Jarvis, M.; Thornton, E. B.; Brown, J.; Fujimura, A.

    2012-12-01

    In the summer of 2011 we performed a field experiment in Carmel River State Beach, CA, at a time when the intermittent natural breaching of the ephemeral Carmel River occurred due to an unusually rainy period prior to the experiment associated with El Nino. At this time the river would fill the lagoon over the period of a number of days after which a breach would occur. This allowed us to document a number of breaches with unique pre- and post-breach topographic surveys, accompanying ocean and lagoon water elevations as well as extremely high flow (4m/s) velocities in the river mouth during the breaching event. The topographic surveys were obtained with a GPS-equipped backpack mounted on a walking human and show the evolution of the river breaching with a gradually widening and deepening river channel that cuts through the pre-existing beach and berm. The beach face is qualified as a steep with an average beach slope of 1:10 with significant reflection of the incident waves (MacMahan et al., 2012). The wave directions are generally shore normal as the waves refract over the deep canyon that is located offshore of the beach. The tide is mixed semi-diurnal with a range on the order of one meter. Breaching typically occurred during the low-low tide. Grain size is highly variable along the beach with layers of alternating fine and coarse material that could clearly be observed as the river exit channel was cutting through the beach. Large rocky outcroppings buried under the beach sand are also present along certain stretches of the beach controlling the depth of the breaching channel. The changes in the water level measured within the lagoon and the ocean side allows for an estimate of the volume flux associated with the breach as function of morphology, tidal elevation and wave conditions as well as an assessment of the conditions and mechanisms of breach closure, which occurred on the time scale of O(0.5 days). Exploratory model simulations will be presented at the

  8. Low-dose radiation suppresses Pokemon expression under hypoxic conditions.

    Science.gov (United States)

    Kim, Seung-Whan; Yu, Kweon; Shin, Kee-Sun; Kwon, Kisang; Hwang, Tae-Sik; Kwon, O-Yu

    2014-01-01

    Our previous data demonstrated that CoCl2-induced hypoxia controls endoplasmic reticulum (ER) stress-associated and other intracellular factors. One of them, the transcription factor Pokemon, was differentially regulated by low-dose radiation (LDR). There are limited data regarding how this transcription factor is involved in expression of the unfolded protein response (UPR) under hypoxic conditions. The purpose of this study was to obtain clues on how Pokemon is involved in the UPR. Pokemon was selected as a differentially expressed gene under hypoxic conditions; however, its regulation was clearly repressed by LDR. It was also demonstrated that both expression of ER chaperones and ER stress sensors were affected by hypoxic conditions, and the same results were obtained when cells in which Pokemon was up- or down-regulated were used. The current state of UPR and LDR research associated with the Pokemon pathway offers an important opportunity to understand the oncogenesis, senescence, and differentiation of cells, as well as to facilitate introduction of new therapeutic radiopharmaceuticals.

  9. Radioprotection of normal tissues of the mouse by hypoxic breathing

    International Nuclear Information System (INIS)

    Stevens, G.N.; Joiner, B.; Denekamp, J.

    1989-01-01

    Hypoxic breathing during irradiation has been advocated as a therapeutic modality, to increase the efficacy of radiotherapy. In this form of treatment, the total and daily X-ray dose is increased by a factor of 1.25, on the assumption that all normal tissues in the beam will be protected to a similar extent by breathing gas containing a reduced oxygen concentration (usually 10%). To test this concept, we have determined the effect of varying the inspired oxygen tension on the radiosensitivity of 3 normal tissues in the mouse (kidney, jejunum and skin), and have compared these results with data from the literature for mouse lung. Reduction of the inspired oxygen tension from 21% (air) to 7-8% led to much greater radioprotection of skin (protection factor 1.37) than of lung (1.09). Protection factors for jejunum and kidney were 1.16 and 1.36 respectively. The results show that the extent of radioprotection afforded by hypoxic breathing is tissue dependent, and that great care must be taken clinically in choosing the increased radiation dose to be used in conjunction with hypoxic breathing

  10. Hypoxic ischemic encephalopathy in children : CT findings related to prognosis

    International Nuclear Information System (INIS)

    Cho, Jae Min; Il, Yim Byung; Kim, Ok Hwa; Kang, Doo Kyoung; Suh, Jung Ho

    1997-01-01

    To evaluate prognosis-related CT findings in hypoxic ischemic encephalopathy. For the purpose of prognosis, 28 children with a clinical history and CT findings suggestive of hypoxic ischemic encephalopathy (HIE) were restrospectively reviewed. The diagnostic criteria for HIE, as seen on CT scanning, were as follows : 1, ventricular collapse;2, effacement of cortical sulci;3, prominent enhancement of cortical vessels;4, poor differentiation of gray and white matter;5, reversal sign;6, obliteration of perimesencephalic cistern;7, high density on tentorial edge, as seen on precontrast scans;and 8, low density in thalamus, brain stem and basal ganglia. On the basis of clinical outcome, we divided the patients into three groups, as follows:group I(good prognosis);group II(neurologic sequelae), and group III(vegetative state or expire), and among these, compared CT findings. There were thirteen patients in group I, six in group II, and nine in group III. Ventricular collapse, effacement of cortical sulci, and prominent enhancement of cortical vessels were noted in all groups, whereas poor differentiation of gray and white matter, reversal sign, obliteration of perimesencephalic cistern, high density on tentorial edge, on precontrast scan, and low density in brain stem and basal ganglia were observed only in groups II and III. CT findings showed distinct differences between groups in whom prognosis was good, and in whom it was poor. An awareness of poor prognostic CT findings may be clinically helpful in the evaluation of patients with hypoxic ischemic encephalopathy

  11. Cerebral blood flow autoregulation during intracranial hypertension in hypoxic lambs

    International Nuclear Information System (INIS)

    Borel, C.O.; Backofen, J.E.; Koehler, R.C.; Jones, M.D. Jr.; Traystman, R.J.

    1987-01-01

    The authors tested the hypothesis that hypoxic hypoxia interferes with cerebral blood flow (CBF) autoregulation when intracranial pressure (ICP) is elevated in pentobarbital-anesthetized lambs (3 to 9 days old). Cerebral perfusion pressure (CPP) was lowered stepwise from 73 to 23 mmHg in eight normoxic lambs and from 65 to 31 mmHg in eight other hypoxic lambs by ventricular infusion of artificial cerebrospinal fluid. In normoxic lambs, CBF measured by microspheres labeled with six different radioisotopes was not significantly changed over this range of CPP. In animals made hypoxic, base-line CBF was twice that of normoxic lambs. CBF was unchanged as CPP was reduced to 31 mmHg. Lower levels of CPP were not attained because a pressor response occurred with further elevations of ICP. No regional decrements in blood flow to cortical arterial watershed areas or to more caudal regions, such as cerebellum, brain stem, or thalamus, were detected with elevated ICP. Cerebral O 2 uptake was similar in both groups and did not decrease when CPP was reduced. These results demonstrate that normoxic lambs have a considerable capacity for effective autoregulation of CBF when ICP is elevated. Moreover, cerebral vasodilation in response to a level of hypoxia approximating that normally seen prenatally does not abolish CBF autoregulation when ICP is elevated during the first postnatal week

  12. Hypoxic Response of Tumor Tissues in a Microfluidic Environment

    Science.gov (United States)

    Morshed, Adnan; Dutta, Prashanta

    2017-11-01

    Inside a tumor tissue, cells growing further away from the blood vessel often suffer from low oxygen levels known as hypoxia. Cancer cells have shown prolonged survival in hostile hypoxic conditions by sharply changing the cellular metabolism. In this work, different stages of growth of the tumor tissue and the oxygen transport across the tissue are investigated. The tissue was modeled as a contiguous block of cells inside a microfluidic environment with nutrient transport through advection and diffusion. While oxygen uptake inside the tissue is through diffusion, ascorbate transport from the extracellular medium is addressed by a concentration dependent uptake model. By varying the experimentally observed oxygen consumption rate, different types of cancer cells and their normoxic and hypoxic stages were studied. Even when the oxygen supply in the channel is maintained at normoxic levels, our results show the onset of hypoxia within minutes inside the cellblock. Interestingly, modeled cell blocks with and without a structured basal layer showed less than 5% variation in hypoxic response in chronic hypoxia. Results also indicate that the balance of cell survival and growth are affected by the flow rate of nutrients and the oxygen consumption rate. This work was supported in part by the National Science Foundation under Grant No. DMS 1317671.

  13. Anti hypoxic and antioxidant activity of Hibiscus esculentus seeds

    Energy Technology Data Exchange (ETDEWEB)

    Ebrahimzadeh, M. A.; Nabavi, S. F.; Nabavi, S. M.; Eslami, B.

    2010-07-01

    The anti hypoxic and antioxidant activities of Hibiscus esculentus seeds were investigated employing eight in vitro assay systems. Anti hypoxic activity was investigated in two models, haemic and circulatory. The effects were pronounced in both models of hypoxia. The anti hypoxic effects were dose-dependent. The results indicated that the extracts have a protective effect against hypoxia induced lethality in mice. The extracts showed antioxidant activity in some models. IC{sub 5}0 for DPPH radical-scavenging activity was 234 {+-} 8.9 {mu}g ml{sup 1}. The extracts showed weak nitric oxide-scavenging activity between 0.1 and 1.6 mg ml{sup -}1. The extracts showed weak Fe{sup 2}+ chelating ability. IC{sub 5}0 were 150 {+-} 13 {mu}g ml{sup -}1. The extracts also exhibited low antioxidant activity in the linoleic acid model but were capable of scavenging hydrogen peroxide in a concentration dependent manner. The total amount of phenolic compounds in each extract was determined as gallic acid equivalents and total flavonoid contents were calculated as quercetin equivalents from a calibration curve. Pharmacological effects may be attributed, at least in part, to the presence of phenols and flavonoids in the extracts. (Author) 40 refs.

  14. Cerebral circulation and prognosis of the patients with hypoxic encephalopathy

    International Nuclear Information System (INIS)

    Nogami, Kenichiro; Fujii, Masami; Kashiwagi, Shiro; Sadamitsu Daikai; Maekawa, Tsuyoshi

    2000-01-01

    Recent progress in cardiopulmonary resuscitation techniques improved the survival rate of patients with acute cardiopulmonary disturbances. However, severe cerebral complications remained frequently in patients who survived the acute stage. Early prediction of cerebral prognosis is important to optimize the management of these patients. We examined the relations between radiological findings (Xe-CT and MRI) and cerebral prognosis. Patients included in this study were selected from all patients with hypoxic encephalopathy admitted to our hospital. There were 11 men and 10 women. Causes of hypoxic encephalopathy were heart disease (11 cases), suffocation (4 cases), CO intoxication (2 cases), asthma (1 case), pneumothorax (1 case), anaphyraxy shock (1 case) and electric shock (1 case). Xe-CT and MRI were carried out 3 weeks after the onset. Cerebral blood flow (CBF) of the patients was measured at rest and 15 minutes after intravenous administration of acetazolamide (1 g). The prognosis was evaluated 3 months after the onset in accordance with Glasgow Outcome Scale (GOS). Low hemispheric CBF (30 ml/100 g/min), poor reactivity of acetazolamide challenge test (10 ml/100 g/min), presence of hyperintensity areas in the basal ganglia in T1 weighted images (T1WI) and T2 weighted images (T2WI) are the factors associated with poor outcome in hypoxic encephalopathy. (author)

  15. Coherent Structures and Intermittency in Plasma Turbulence

    International Nuclear Information System (INIS)

    Das, Amita; Kaw, Predhiman; Sen, Abhijit

    2008-01-01

    The paper discusses some fundamental issues related to the phenomenon of intermittency in plasma turbulence with particular reference to experimental observations in fusion devices. Intermittency is typically associated with the presence of coherent structures in turbulence. Since coherent structures can play an important role in governing the transport properties of a system they have received a great deal of attention in fusion research. We review some of the experimental measurements and numerical simulation studies on the presence and formation of coherent structures in plasmas and discuss their relevance to intermittency. Intermittency, as widely discussed in the context of neutral fluid turbulence, implies multiscaling behaviour in contrast to self-similar scaling patterns observed in self organized criticality (SOC) phenomenon. The experimental evidence from plasma turbulence measurements reveal a mixed picture--while some observations support the SOC model description others indicate the presence of multiscaling behaviour. We discuss these results in the light of our present understanding of plasma turbulence and in terms of certain unique aspects of intermittency as revealed by fluid models of plasmas.

  16. Intermittency in {sup 197}Au fragmentation

    Energy Technology Data Exchange (ETDEWEB)

    Dabrowska, A; Holynski, R; Olszewski, A; Szarska, M; Wilczynska, B; Wolter, W; Wosiek, B [Institute of Nuclear Physics, Cracow (Poland); Cherry, M L; Deines-Jones, P; Jones, W V; Sengupta, K; Wefel, B [Louisiana State Univ., Baton Rouge, LA (United States). Dept. of Physics and Astronomy; Waddington, C J [Minnesota Univ., Minneapolis, MN (United States). School of Physics and Astronomy; Pozharova, E A; Skorodko, T Yu [Inst. of Theoretical and Experimental Physics, Moscow (Russian Federation); KLMM Collaboration

    1995-07-01

    The concept of factorial moments was applied to an analysis of the dynamical fluctuations in the charge distributions of the fragments emitted from gold nuclei with energies 10.6 and < 1.0 GeV/n interacting with emulsion nuclei. Clear evidence for intermittent fluctuations has been found in an analysis using all the particles released from the gold projectile, with a stronger effect observed below 1 GeV/n than at 10.6 GeV/n. For the full data sets, however, the intermittency effect was found to be very sensitive to the singly charged particles, and neglecting these particles strongly reduces the intermittency signal. When the analysis is restricted to the multiply charged fragments, an intermittency effect is revealed only for multifragmentation events, although one that is enhanced as compared to the analysis of all, singly and multiply charged, particles. The properties of the anomalous fractal dimensions suggest a sequential decay mechanism, rather than the existence of possible critical behaviour in the process of nuclear fragmentation. The likely influence of the charge conservation effects and the finite size of decaying systems on the observed intermittency signals was pointed out. (author). 37 refs, 9 figs, 5 tabs.

  17. Forces and energetics of intermittent swimming

    Science.gov (United States)

    Floryan, Daniel; Van Buren, Tyler; Smits, Alexander J.

    2017-08-01

    Experiments are reported on intermittent swimming motions. Water tunnel experiments on a nominally two-dimensional pitching foil show that the mean thrust and power scale linearly with the duty cycle, from a value of 0.2 all the way up to continuous motions, indicating that individual bursts of activity in intermittent motions are independent of each other. This conclusion is corroborated by particle image velocimetry (PIV) flow visualizations, which show that the main vortical structures in the wake do not change with duty cycle. The experimental data also demonstrate that intermittent motions are generally energetically advantageous over continuous motions. When metabolic energy losses are taken into account, this conclusion is maintained for metabolic power fractions less than 1.

  18. Chaos synchronization based on intermittent state observer

    Institute of Scientific and Technical Information of China (English)

    Li Guo-Hui; Zhou Shi-Ping; Xu De-Ming

    2004-01-01

    This paper describes the method of synchronizing slave to the master trajectory using an intermittent state observer by constructing a synchronizer which drives the response system globally tracing the driving system asymptotically. It has been shown from the theory of synchronization error-analysis that a satisfactory result of chaos synchronization is expected under an appropriate intermittent period and state observer. Compared with continuous control method,the proposed intermittent method can target the desired orbit more efficiently. The application of the method is demonstrated on the hyperchaotic Rossler systems. Numerical simulations show that the length of the synchronization interval rs is of crucial importance for our scheme, and the method is robust with respect to parameter mismatch.

  19. Ventilation and hypoxic ventilatory responsiveness in Chinese-Tibetan residents at 3,658 m.

    Science.gov (United States)

    Curran, L S; Zhuang, J; Sun, S F; Moore, L G

    1997-12-01

    When breathing ambient air at rest at 3,658 m altitude, Tibetan lifelong residents of 3,658 m ventilate as much as newcomers acclimatized to high altitude; they also ventilate more and have greater hypoxic ventilatory responses (HVRs) than do Han ("Chinese") long-term residents at 3,658 m. This suggests that Tibetan ancestry is advantageous in protecting resting ventilation levels during years of hypoxic exposure and is of interest in light of the permissive role of hypoventilation in the development of chronic mountain sickness, which is nearly absent among Tibetans. The existence of individuals with mixed Tibetan-Chinese ancestry (Han-Tibetans) residing at 3,658 m affords an opportunity to test this hypothesis. Eighteen men born in Lhasa, Tibet, China (3,658 m) to Tibetan mothers and Han fathers were compared with 27 Tibetan men and 30 Han men residing at 3,658 m who were previously studied. We used the same study procedures (minute ventilation was measured with a dry-gas flowmeter during room air breathing and hyperoxia and with a 13-liter spirometer-rebreathing system during the hypoxic and hypercapnic tests). During room air breathing at 3,658 m (inspired O2 pressure = 93 Torr), Han-Tibetans resembled Tibetans in ventilation (12.1 +/- 0.6 vs. 11.5+/- 0.5 l/min BTPS, respectively) but had HVR that were blunted (63 +/- 16 vs. 121 +/- 13, respectively, for HVR shape parameter A) and declined with increasing duration of high-altitude residence. During administered hyperoxia (inspired O2 pressure = 310 Torr) at 3,658 m, the paradoxical hyperventilation previously seen in Tibetan but not Han residents at 3,658 m (11.8 +/- 0.5 vs. 10.1 +/- 0.5 l/min BTPS) was absent in these Han-Tibetans (9.8 +/- 0.6 l/min BTPS). Thus, although longer duration of high-altitude residence appears to progressively blunt HVR among Han-Tibetans born and residing at 3, 658 m, their Tibetan ancestry appears protective in their maintenance of high resting ventilation levels despite

  20. Quantifying Physiological, Behavioral and Ecological Consequences of Hypoxic Events in Kelp Forest

    Science.gov (United States)

    Litvin, S. Y.; Beers, J. M.; Woodson, C. B.; Leary, P.; Fringer, O. B.; Goldbogen, J. A.; Micheli, F.; Monismith, S. G.; Somero, G. N.

    2016-02-01

    Rocky reef kelp forests that extend along the coast of central California, like many habitats in upwelling systems, often experience inundations of low dissolved oxygen (DO) or hypoxic waters. These events have the potential to influence the structure and function of coastal ecosystems. The ecological consequences of hypoxia for these systems will be mediated by physiological thresholds and behavioral responses of resident organisms in the context of the spatial and temporal variability of DO, and other potential stressors. Our research focuses on Sebastes (i.e. rockfish) because of their commercial, recreational and ecological importance, high abundance across near shore habitats and the potentially severe impacts of physiological stress due to hypoxia. In the lab, to investigate how hypoxic events physiologically effect rockfish, we exposed young of the year (YOY) of 5 species and two life stages of blue rockfish, S. mystinus (YOY and 1+), to DO concentrations representative of upwelling conditions and measured a suite of whole organisms and tissue level responses including metabolic rate, ventilation, tissue-level metabolism, and blood biochemistry. Results demonstrate species and life stage specific differences in physiological stress under upwelling driven hypoxic conditions and suggest YOY rockfishes may currently be living near their physiological limits. In the laboratory we further explored if physiological impacts result in behavioral consequences by examining the startle response of YOY rockfish, a relative measure of predator avoidance ability, under a range of DO concentrations and exposure durations. To further explore behavioral responses of rockfish to low in DO within the kelp forest we are using two approaches, monitoring the vertical distribution of fish communities across the water column using an acoustic imaging camera (ARIS 3000, Soundmetrics Inc.) and acoustic tagging, with 3-D positioning ability (VPS, VEMCO Inc.), of larger blue rockfish

  1. Unsteady propulsion by an intermittent swimming gait

    Science.gov (United States)

    Akoz, Emre; Moored, Keith W.

    2018-01-01

    Inviscid computational results are presented on a self-propelled swimmer modeled as a virtual body combined with a two-dimensional hydrofoil pitching intermittently about its leading edge. Lighthill (1971) originally proposed that this burst-and-coast behavior can save fish energy during swimming by taking advantage of the viscous Bone-Lighthill boundary layer thinning mechanism. Here, an additional inviscid Garrick mechanism is discovered that allows swimmers to control the ratio of their added mass thrust-producing forces to their circulatory drag-inducing forces by decreasing their duty cycle, DC, of locomotion. This mechanism can save intermittent swimmers as much as 60% of the energy it takes to swim continuously at the same speed. The inviscid energy savings are shown to increase with increasing amplitude of motion, increase with decreasing Lighthill number, Li, and switch to an energetic cost above continuous swimming for sufficiently low DC. Intermittent swimmers are observed to shed four vortices per cycle that form into groups that are self-similar with the DC. In addition, previous thrust and power scaling laws of continuous self-propelled swimming are further generalized to include intermittent swimming. The key is that by averaging the thrust and power coefficients over only the bursting period then the intermittent problem can be transformed into a continuous one. Furthermore, the intermittent thrust and power scaling relations are extended to predict the mean speed and cost of transport of swimmers. By tuning a few coefficients with a handful of simulations these self-propelled relations can become predictive. In the current study, the mean speed and cost of transport are predicted to within 3% and 18% of their full-scale values by using these relations.

  2. Does “Live High-Train Low (and High)” Hypoxic Training Alter Running Mechanics In Elite Team-sport Players?

    Science.gov (United States)

    Girard, Olivier; Millet, Grégoire P.; Morin, Jean-Benoit; Brocherie, Franck

    2017-01-01

    This study aimed to investigate if “Live High-Train Low (and High)” hypoxic training alters constant-velocity running mechanics. While residing under normobaric hypoxia (≥14 h·d-1; FiO2 14.5-14.2%) for 14 days, twenty field hockey players performed, in addition to their usual training in normoxia, six sessions (4 × 5 × 5-s maximal sprints; 25 s passive recovery; 5 min rest) under either normobaric hypoxia (FiO2 ~14.5%, n = 9) or normoxia (FiO2 20.9%, n = 11). Before and immediately after the intervention, their running pattern was assessed at 10 and 15 km·h-1 as well as during six 30-s runs at ~20 km·h-1 with 30-s passive recovery on an instrumented motorised treadmill. No clear changes in running kinematics and spring-mass parameters occurred globally either at 10, 15 or ~20 km·h-1, with also no significant time × condition interaction for any parameters (p > 0.14). Independently of the condition, heart rate (all p < 0.05) and ratings of perceived exertion decreased post-intervention (only at 15 km·h-1, p < 0.05). Despite indirect signs for improved psycho-physiological responses, no forthright change in stride mechanical pattern occurred after “Live High-Train Low (and High)” hypoxic training. Key points There are indirect signs for improved psycho-physiological responses in responses to “Live High-Train Low (and High)” hypoxic training. This hypoxic training regimen, however, does not modify the running mechanics of elite team-sport players at low and high velocities. Coaches can be confident that this intervention, known for inducing significant metabolic benefits, is appropriate for athletes since their running kinetics and kinematics are not negatively affected by chronic hypoxic exposure. PMID:28912649

  3. Shape of power spectrum of intermittent chaos

    International Nuclear Information System (INIS)

    So, B.C.; Mori, H.

    1984-01-01

    Power spectra of intermittent chaos are calculated analytically. It is found that the power spectrum near onset point consists of a large number of Lorentzian lines with two peaks around frequencies ω = 0 and ω = ω 0 , where ω 0 is a fundamental frequency of a periodic orbit before the onset point, and furthermore the envelope of lines around ω = 0 obeys the power law 1/ + ω +2 , whereas the envelope around ω 0 obeys 1/ + ω-ω 0 +4 . The universality of these power law dependence in a certain class of intermittent chaos are clarified from a phenomenological view point. (author)

  4. microRNA regulation of the embryonic hypoxic response in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Kagias, Konstantinos; Pocock, Roger

    2015-01-01

    Layered strategies to combat hypoxia provide flexibility in dynamic oxygen environments. Here we show that multiple miRNAs are required for hypoxic survival responses during C. elegans embryogenesis. Certain miRNAs promote while others antagonize the hypoxic survival response. We found...... of the full mRNA target repertoire of these miRNAs will reveal the miRNA-regulated network of hypoxic survival mechanisms in C. elegans....

  5. Intermittent hypoxia in obese Zucker rats: cardiometabolic and inflammatory effects.

    Science.gov (United States)

    Briançon-Marjollet, Anne; Monneret, Denis; Henri, Marion; Joyeux-Faure, Marie; Totoson, Perle; Cachot, Sandrine; Faure, Patrice; Godin-Ribuot, Diane

    2016-11-01

    What is the central question of this study? This study addresses the relative impact of obesity and intermittent hypoxia in the pathophysiological process of obstructive sleep apnoea by investigating the metabolic, inflammatory and cardiovascular consequences of intermittent hypoxia in lean and obese Zucker rats. What is the main finding and its importance? We found that obesity and intermittent hypoxia have mainly distinct consequences on the investigated inflammatory and cardiometabolic parameters in Zucker rats. This suggests that, for a given severity of sleep apnea, the association of obesity and obstructive sleep apnoea may not necessarily be deleterious. Obstructive sleep apnoea is associated with obesity with a high prevalence, and both co-morbidities are independent cardiovascular risk factors. Intermittent hypoxia (IH) is thought to be the main factor responsible for the obstructive sleep apnoea-related cardiometabolic alterations. The aim of this study was to assess the respective impact of obesity and IH on the inflammatory and cardiometabolic state in rats. Lean and obese Zucker rats were exposed to normoxia or chronic IH, and we assessed metabolic and inflammatory parameters, such as plasma lipids and glucose, serum leptin and adiponectin, liver cytokines, nuclear factor-κB activity and cardiac endothelin-1 levels. Myocardial infarct size was also evaluated following in vitro ischaemia-reperfusion. Circulating lipids, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), leptin and adiponectin levels were higher in obese versus lean rats. Chronic IH did not have a significant impact on metabolic parameters in lean rats. In obese rats, IH increased glycaemia and HOMA-IR. Liver interleukin-6 and tumour necrosis factor-α levels were elevated in lean rats exposed to IH; obesity prevented the increase in interleukin-6 but not in tumour necrosis factor-α. Finally, IH exposure enhanced myocardial sensitivity to infarction in both lean and

  6. The effect of normobaric hypoxic confinement on metabolism, gut hormones and body composition

    Directory of Open Access Journals (Sweden)

    Igor B. Mekjavic

    2016-06-01

    Full Text Available To assess the effect of normobaric hypoxia on metabolism, gut hormones and body composition, eleven normal weight, aerobically trained ( O2peak: 60.6±9.5 ml·kg-1·min-1 men (73.0±7.7 kg; 23.7±4.0 yrs, BMI 22.2±2.4 kg·m-2 were confined to a normobaric (altitude⋍940m normoxic (NORMOXIA; PIO2⋍133.2 mmHg or normobaric hypoxic (HYPOXIA; PIO was reduced from 105.6 to 97.7 mmHg over 10 days environment for 10 days in a randomized cross-over design. The wash-out period between confinements was 3 weeks. During each 10-day period, subjects avoided strenuous physical activity and were under continuous nutritional control. Before, and at the end of each exposure, subjects completed a meal tolerance test, during which blood glucose, insulin, GLP-1, ghrelin, peptide-YY, adrenaline, noradrenaline, leptin, and gastro-intestinal blood flow and appetite sensations were measured. There was no significant change in body weight in either of the confinements (NORMOXIA: -0.7±0.2 kg; HYPOXIA: -0.9±0.2 kg, but a significant increase in fat mass in NORMOXIA (0.23±0.45 kg, but not in HYPOXIA (0.08±0.08 kg. HYPOXIA confinement increased fasting noradrenaline and decreased energy intake, the latter most likely associated with increased fasting leptin. The majority of all other measured variables/responses were similar in NORMOXIA and HYPOXIA. To conclude, normobaric hypoxic confinement without exercise training results in negative energy balance due to primarily reduced energy intake.

  7. Role of magnetic resonance imaging in biometric evaluation of corpus callosum in hypoxic ischemic encephalopathy patients

    Directory of Open Access Journals (Sweden)

    Amit Garhwal

    2017-01-01

    Full Text Available Background: Corpus callosum (CC has an important role in establishing hemispheric lateralization of function. Significance of this structure which is the primary white matter commissure of the brain lies in the fact that damage to the CC during development has been found to be associated with poor neurological outcome and neuropsychological performance. Magnetic resonance imaging (MRI can precisely detect, localize, and evaluate damage to CC in hypoxic-ischemic encephalopathy (HIE patients and assist in reaching to at an accurate anatomical diagnosis, thus heeling in further management of the patient. Objectives: The objective of this study is to analyze the effect of HIE on CC morphometry by assessing various diameters of CC. Materials and Methods: Fifty-four patients with history of hypoxic-ischemic injury referred to the Department of Radiodiagnosis were included in the study. All the patients were made to undergo MRI of the brain using Siemens Symphony Magnetom 1.5 Tesla scanner after taking informed consent for the same. The findings of MRI brain were assessed and analyzed. Data analysis was done using percentages of different diagnosis and outcomes made by MRI brain were computed and compiled. Results: In the present study, male predominance is seen, 77.78% patients were male and 22.22% were female. In the present study, maximum numbers of patients were <1 year of age (37.04%. In the present study, we see that the isthmus was the most commonly affected portion of CC. Children who did not cry at birth, born with low birth weight, low Apgar score were positively correlated with severity of damage to CC. Conclusion: From the present study, it was noted that MRI is very efficient tool in evaluating morphometry of CC in HIE. Its noninvasiveness and no exposure to ionizing radiation is an added advantage. However, experience and understanding of the principles are essential for accurate diagnosis.

  8. Development of a real-time imaging system for hypoxic cell apoptosis

    Directory of Open Access Journals (Sweden)

    Go Kagiya

    2016-01-01

    Full Text Available Hypoxic regions within the tumor form due to imbalances between cell proliferation and angiogenesis; specifically, temporary closure or a reduced flow due to abnormal vasculature. They create environments where cancer cells acquire resistance to therapies. Therefore, the development of therapeutic approaches targeting the hypoxic cells is one of the most crucial challenges for cancer regression. Screening potential candidates for effective diagnostic modalities even under a hypoxic environment would be an important first step. In this study, we describe the development of a real-time imaging system to monitor hypoxic cell apoptosis for such screening. The imaging system is composed of a cyclic luciferase (luc gene under the control of an improved hypoxic-responsive promoter. The cyclic luc gene product works as a caspase-3 (cas-3 monitor as it gains luc activity in response to cas-3 activation. The promoter composed of six hypoxic responsible elements and the CMV IE1 core promoter drives the effective expression of the cyclic luc gene in hypoxic conditions, enhancing hypoxic cell apoptosis visualization. We also confirmed real-time imaging of hypoxic cell apoptosis in the spheroid, which shares properties with the tumor. Thus, this constructed system could be a powerful tool for the development of effective anticancer diagnostic modalities.

  9. [3H]-nitrendipine binding in membranes obtained from hypoxic and reoxygenated heart.

    Science.gov (United States)

    Matucci, R; Bennardini, F; Sciammarella, M L; Baccaro, C; Stendardi, I; Franconi, F; Giotti, A

    1987-04-01

    We compared the binding properties of [3H]-nitrendipine in heart membranes from normal guinea-pig heart and from hypoxic or hypoxic and reoxygenated heart. The [3H]-nitrendipine binds a single class of high capacity (Bmax 667.2 +/- 105.2) with high affinity (KD 0.14 +/- 0.02) binding sites. By contrast, in membranes of hypoxic and reoxygenated heart the Bmax decreases significantly while it remains unaffected during hypoxia. Xanthinoxidase activity is increased in hypoxic-reoxygenated hearts.

  10. Considerations on hypoxic conditions. On the past setback of classic radiation biology

    International Nuclear Information System (INIS)

    Nakatsugawa, Shigekazu; Klimova, S.V.; Tamasu, Shogo; Nakamura, Hideaki; Murayama, Chieko

    2002-01-01

    Considerations on hypoxic cancer cell environment are made on classic radiation biology concept and on a new proposal of the anti-cancer strategy. Classic radiation biology knowledge of hypoxic cancer cells has produced many of clinical trials, which, however, have failed after all. This is because the knowledge is that the cells are recognized to be in a rather static hypoxic condition. Based on authors' investigations, made is the proposal that improvement of dynamic, acute hypoxic conditions yielded via blood circulation between the heterogeneous malignant cancer cells and the dynamic homeostatic systems of normal cells including immunity is important as one of cancer therapy approaches. (N.I.)

  11. Which factors make clean intermittent (self) catheterisation successful?

    NARCIS (Netherlands)

    Cobussen-Boekhorst, H.; Beekman, J.; Wijlick, E. van; Schaafstra, J.; Kuppevelt, D. van; Heesakkers, J.P.

    2016-01-01

    AIMS AND OBJECTIVES: To explore which factors determine successful intermittent catheterisation. BACKGROUND: Intermittent catheterisation is a safe, effective treatment and is associated with improved quality of life, although negative issues are reported. Factors which determine adherence are

  12. The effects of pentoxifylline on the survival of human glioma cells with continuous and intermittent stereotactic radiosurgery irradiation

    International Nuclear Information System (INIS)

    Eley, Kerry W.; Benedict, Stanley H.; Chung, Theodore D.K.; Kavanagh, Brian D.; Broaddus, William C.; Schmidt-Ullrich, Rupert K.A.; Lin, P.-S.

    2002-01-01

    effects were replicated in the spheroid outgrowth assays. Conclusion: In human glioma cells, PTX abrogates the radiation-induced G2/M block observed after either continuous radiation exposure or intermittent exposures modeling clinical linac-based radiosurgery. The PTX-mediated reduction of the G2/M block translates into radiosensitization, most notably during intermittent exposures, and is presumably a consequence of diminished DNA damage repair at the G2/M checkpoint, though other contributing effects cannot be ruled out. The radiosensitization effect of PTX is sustained under low oxygen conditions. These results support consideration of the clinical evaluation of PTX to enhance the efficacy of linac-based radiosurgery involving intermittent irradiation through multiple arcs

  13. Fractal structures and intermittency in QCD

    International Nuclear Information System (INIS)

    Gustafson, Goesta.

    1990-04-01

    New results are presented for fractal structures and intermittency in QCD parton showers. A geometrical interpretation of the anomalous dimension in QCD is given. It is shown that model predications for factorial moments in the PEP-PETRA energy range are increased. if the properties of directly produced pions are more carefully taken into account

  14. Intermittent demand : Linking forecasting to inventory obsolescence

    NARCIS (Netherlands)

    Teunter, Ruud H.; Syntetos, Aris A.; Babai, M. Zied

    2011-01-01

    The standard method to forecast intermittent demand is that by Croston. This method is available in ERP-type solutions such as SAP and specialised forecasting software packages (e.g. Forecast Pro), and often applied in practice. It uses exponential smoothing to separately update the estimated demand

  15. Acute intermittent porphyria presenting as progressive muscular ...

    African Journals Online (AJOL)

    Acute intermittent porphyria, the most common porphyria affecting the nervous system, typically presents with neurovisceral crises followed by a motor neuropathy. We describe a 23-year-old black South African man presenting with a progressive stuttering, lower motor neuron syndrome developing over months. He had not ...

  16. Cooling tower modification for intermittent operation

    International Nuclear Information System (INIS)

    Midkiff, W.S.

    1975-03-01

    One of the cooling towers at Los Alamos Scientific Laboratory is being operated intermittently. The cooling tower has been modified to restrict air flow and to keep the tower from drying out. The modifications are relatively inexpensive, simple to operate, and have proved effective. (U.S.)

  17. Intermittent preventive treatment of malaria in pregnancy

    DEFF Research Database (Denmark)

    Mbonye, A.K.; Hansen, Kristian Schultz; Bygbjerg, Ib Christian

    2008-01-01

    The main objective of this study was to assess whether traditional birth attendants, drug-shop vendors, community reproductive health workers and adolescent peer mobilisers could administer intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) to pregnant women. The study w...

  18. Management of patients with intermittent claudication

    NARCIS (Netherlands)

    S. Spronk (Sandra)

    2008-01-01

    textabstractIntermittent claudication is the first and mildest manifestation of peripheral arterial disease, caused by the atherosclerotic process of progressive narrowing of one or more of the arteries of the peripheral circulation.1 If the arterial system fails, it results in a progressive oxygen

  19. Intermittent resistive faults in digital cmos circuits

    NARCIS (Netherlands)

    Kerkhoff, Hans G.; Ebrahimi, Hassan

    2015-01-01

    A major threat in extremely dependable high-end process node integrated systems in e.g. Avionics are no failures found (NFF). One category of NFFs is the intermittent resistive fault, often originating from bad (e.g. Via or TSV-based) interconnections. This paper will show the impact of these faults

  20. Intermittent and global transitions in plasma turbulence

    International Nuclear Information System (INIS)

    Vlad, M.; Spineanu, F.; Itoh, K.; Itoh, S.-I.

    2003-07-01

    The dynamics of the transition processes in plasma turbulence described by the nonlinear Langevin equation (1) is studied. We show that intermittent or global transitions between metastable states can appear. The conditions for the generation of these transitions and their statistical characteristics are determined. (author)

  1. Intermittency in the particle production and in the nuclear multifragmentation

    International Nuclear Information System (INIS)

    Bozek, P.; Ploszajczak, M.

    1991-01-01

    Intermittency is a manifestation of scale invariance and randomness in physical systems. Intermittency in relativistic heavy-ion collisions and, in particular, the projectile dependence, multiplicity dependence and source-size dependence are discussed in the frame of the model of spatio-temporal intermittency. Moreover, recent theoretical results in intermittency studies of the nuclear multifragmentation are presented. (author) 35 refs., 4 figs., 1 tab

  2. Exercise training during normobaric hypoxic confinement does not alter hormonal appetite regulation.

    Directory of Open Access Journals (Sweden)

    Tadej Debevec

    Full Text Available Both exposure to hypoxia and exercise training have the potential to modulate appetite and induce beneficial metabolic adaptations. The purpose of this study was to determine whether daily moderate exercise training performed during a 10-day exposure to normobaric hypoxia alters hormonal appetite regulation and augments metabolic health.Fourteen healthy, male participants underwent a 10-day hypoxic confinement at ∼ 4000 m simulated altitude (FIO2 = 0.139 ± 0.003% either combined with daily moderate intensity exercise (Exercise group; N = 8, Age = 25.8 ± 2.4 yrs, BMI = 22.9 ± 1.2 kg · m(-2 or without any exercise (Sedentary group; N = 6 Age = 24.8 ± 3.1 yrs, BMI = 22.3 ± 2.5 kg · m(-2. A meal tolerance test was performed before (Pre and after the confinement (Post to quantify fasting and postp randial concentrations of selected appetite-related hormones and metabolic risk markers. 13C-Glucose was dissolved in the test meal and 13CO2 determined in breath samples. Perceived appetite ratings were obtained throughout the meal tolerance tests.While body mass decreased in both groups (-1.4 kg; p = 0.01 following the confinement, whole body fat mass was only reduced in the Exercise group (-1.5 kg; p = 0.01. At Post, postprandial serum insulin was reduced in the Sedentary group (-49%; p = 0.01 and postprandial plasma glucose in the Exercise group (-19%; p = 0.03. Fasting serum total cholesterol levels were reduced (-12%; p = 0.01 at Post in the Exercise group only, secondary to low-density lipoprotein cholesterol reduction (-16%; p = 0.01. No differences between groups or testing periods were noted in fasting and/or postprandial concentrations of total ghrelin, peptide YY, and glucagon-like peptide-1, leptin, adiponectin, expired 13CO2 as well as perceived appetite ratings (p>0.05.These findings suggest that performing daily moderate intensity exercise training during continuous hypoxic exposure does not alter hormonal appetite regulation but

  3. Exercise training during normobaric hypoxic confinement does not alter hormonal appetite regulation.

    Science.gov (United States)

    Debevec, Tadej; Simpson, Elizabeth J; Macdonald, Ian A; Eiken, Ola; Mekjavic, Igor B

    2014-01-01

    Both exposure to hypoxia and exercise training have the potential to modulate appetite and induce beneficial metabolic adaptations. The purpose of this study was to determine whether daily moderate exercise training performed during a 10-day exposure to normobaric hypoxia alters hormonal appetite regulation and augments metabolic health. Fourteen healthy, male participants underwent a 10-day hypoxic confinement at ∼ 4000 m simulated altitude (FIO2 = 0.139 ± 0.003%) either combined with daily moderate intensity exercise (Exercise group; N = 8, Age = 25.8 ± 2.4 yrs, BMI = 22.9 ± 1.2 kg · m(-2)) or without any exercise (Sedentary group; N = 6 Age = 24.8 ± 3.1 yrs, BMI = 22.3 ± 2.5 kg · m(-2)). A meal tolerance test was performed before (Pre) and after the confinement (Post) to quantify fasting and postp randial concentrations of selected appetite-related hormones and metabolic risk markers. 13C-Glucose was dissolved in the test meal and 13CO2 determined in breath samples. Perceived appetite ratings were obtained throughout the meal tolerance tests. While body mass decreased in both groups (-1.4 kg; p = 0.01) following the confinement, whole body fat mass was only reduced in the Exercise group (-1.5 kg; p = 0.01). At Post, postprandial serum insulin was reduced in the Sedentary group (-49%; p = 0.01) and postprandial plasma glucose in the Exercise group (-19%; p = 0.03). Fasting serum total cholesterol levels were reduced (-12%; p = 0.01) at Post in the Exercise group only, secondary to low-density lipoprotein cholesterol reduction (-16%; p = 0.01). No differences between groups or testing periods were noted in fasting and/or postprandial concentrations of total ghrelin, peptide YY, and glucagon-like peptide-1, leptin, adiponectin, expired 13CO2 as well as perceived appetite ratings (p>0.05). These findings suggest that performing daily moderate intensity exercise training during continuous hypoxic exposure does not alter hormonal appetite regulation but can

  4. Mouse Intermittent Hypoxia Mimicking Apnea of Prematurity: Effects on Myelinogenesis and Axonal Maturation

    Science.gov (United States)

    CAI, JUN; TUONG, CHI MINH; ZHANG, YIPING; SHIELDS, CHRISTOPHER B.; GUO, GANG; FU, HUI; GOZAL, DAVID

    2014-01-01

    Premature babies are at high risk for both infantile apnea and long-term neurobehavioral deficits. Recent studies suggest that diffuse structural changes in brain white matter are a positive predictor of poor cognitive outcomes. Since oligodendrocyte maturation, myelination, axon development and synapse formation mainly occur in the 3rd trimester of gestation and 1st postnatal year, infantile apnea could lead to and/or exaggerate white matter impairments in preterm neonates. Therefore, we investigated oligodendroglia and axon development in a neonatal mouse model of intermittent hypoxia between postnatal days 2 to 10. During critical phases of central nervous system development, intermittent hypoxia induced hypomyelination in the corpus callosum, striatum, fornix and cerebellum, but not the pons or spinal cord. Intermittent hypoxia-elicited alterations in myelin-forming processes were reflected by decreased expression of myelin proteins, including MBP, PLP, MAG and CNPase, possibly due to arrested maturation of oligodendrocytes. Ultra-structural abnormalities were apparent in the myelin sheath and axon. Immature oligodendrocytes were more vulnerable to neonatal intermittent hypoxia exposures than developing axons, suggesting that hypomyelination may contribute, at least partially, to axonal deficits. Insufficient neurofilament synthesis with anomalous components of neurofilament subunits, β-tubulin and MAP2 isoforms indicated immaturity of axons in intermittent hypoxia-exposed mouse brains. In addition, down-regulation of Synapsin I, Synaptophysin and Gap-43 phosphorylation suggested a potential stunt in axonogenesis and synaptogenesis. The region-selective and complex impairment in brain white matter induced by intermittent hypoxia was further associated with electrophysiological changes that may underlie long-term neurobehavioral sequelae. PMID:21953180

  5. Sirtuin 6 protects the heart from hypoxic damage

    International Nuclear Information System (INIS)

    Maksin-Matveev, Anna; Kanfi, Yariv; Hochhauser, Edith; Isak, Ahuva; Cohen, Haim Y.; Shainberg, Asher

    2015-01-01

    Sirtuin 6 (SIRT6) is a protein associated with prolonged life expectancy. We investigated whether life extension is associated with cardioprotection against hypoxia. The proposed study is to develop approaches to reduce hypoxic damage through the use of the sirtuin pathway and to elucidate the mechanism involved. For that purpose we subjected cardiomyocytes from transgenic mice (TG) with over-expression of SIRT6, to hypoxic stress in cell cultures. We hypothesized that cardiomyocytes from transgenic mice subjected to prolonged hypoxia may release survival factors or fewer damage markers to protect them from hypoxic stress compared with wild type (WT) mice. Lactate dehydrogenase (LDH) and creatine kinase (CK) released to the medium and propidium iodide (PI) binding, were markedly decreased following hypoxia in TG cardiomyocytes. The protective mechanism of SIRT6 over-expression includes the activation of pAMPKα pathway, the increased protein level of B-cell lymphoma 2 (Bcl2), the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), the decrease of reactive oxygen species (ROS) and the reduction in the protein level of phospho-protein kinase B (pAkt) during hypoxia. Together, all these processes impede the necrosis/apoptosis pathways leading to the improved survival of cardiomyocytes following hypoxia, which might explain life extension. - Highlights: • Sirtuin 6 is a protein associated with prolonged life expectancy. • Over-expression of sirtuin 6 protects cardiocytes from hypoxia and oxidative stress. • Over-expression of sirtuin 6 activates the pAMPKα pathway and the Bcl2 expression. • Over-expression of sirtuin 6 decreases ROS formation and pAkt level during hypoxia. • These pathways protect cardiocytes from hypoxia and might explain lifespan extension

  6. Sirtuin 6 protects the heart from hypoxic damage

    Energy Technology Data Exchange (ETDEWEB)

    Maksin-Matveev, Anna; Kanfi, Yariv [The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900 (Israel); Hochhauser, Edith [The Laboratory of the Department of Cardiothoracic Surgery, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva (Israel); Isak, Ahuva; Cohen, Haim Y. [The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900 (Israel); Shainberg, Asher, E-mail: asher.shainberg@gmail.com [The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900 (Israel)

    2015-01-01

    Sirtuin 6 (SIRT6) is a protein associated with prolonged life expectancy. We investigated whether life extension is associated with cardioprotection against hypoxia. The proposed study is to develop approaches to reduce hypoxic damage through the use of the sirtuin pathway and to elucidate the mechanism involved. For that purpose we subjected cardiomyocytes from transgenic mice (TG) with over-expression of SIRT6, to hypoxic stress in cell cultures. We hypothesized that cardiomyocytes from transgenic mice subjected to prolonged hypoxia may release survival factors or fewer damage markers to protect them from hypoxic stress compared with wild type (WT) mice. Lactate dehydrogenase (LDH) and creatine kinase (CK) released to the medium and propidium iodide (PI) binding, were markedly decreased following hypoxia in TG cardiomyocytes. The protective mechanism of SIRT6 over-expression includes the activation of pAMPKα pathway, the increased protein level of B-cell lymphoma 2 (Bcl2), the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), the decrease of reactive oxygen species (ROS) and the reduction in the protein level of phospho-protein kinase B (pAkt) during hypoxia. Together, all these processes impede the necrosis/apoptosis pathways leading to the improved survival of cardiomyocytes following hypoxia, which might explain life extension. - Highlights: • Sirtuin 6 is a protein associated with prolonged life expectancy. • Over-expression of sirtuin 6 protects cardiocytes from hypoxia and oxidative stress. • Over-expression of sirtuin 6 activates the pAMPKα pathway and the Bcl2 expression. • Over-expression of sirtuin 6 decreases ROS formation and pAkt level during hypoxia. • These pathways protect cardiocytes from hypoxia and might explain lifespan extension.

  7. Risk factor for hypoxic ischemic encephalopathy in children

    International Nuclear Information System (INIS)

    Butt, T.K.; Farooqui, R.; Khan, U.; Farooqui, R.

    2008-01-01

    To determine underlying risk factors in neonates with hypoxic ischemic encephalopathy. All neonates (153) with the diagnosis of Hypoxic Ischemic Encephalopathy (HIE) were included in the study. Controls (187) were selected from admissions on the same day. Possible risk factors such as maternal age, parity, antenatal monitoring, place of delivery, prolonged second stage of labour, type of delivery, type of attendant at delivery and the gestational age were noted and compared. Sixty one (39.9%) mothers of asphyxiated babies reported no antenatal visits compared to 24.1% in the control group (OR 2.1, 95% CI 1.3-3.2; p=0.002). Only 6.5% of cases were born in government hospitals (teaching and district) in comparison to 20.9% of controls (OR 3.8, 95% CI 1.9-7.6; p=0.001). In 28.1% of cases, mothers had history of prolonged 2nd stage of labour in comparison to 5.9% of controls (OR 6.3, 95% CI 3.3-11.9; p<0.001). Fifty five cases (35.9%) were delivered by unskilled birth attendants compared to 28 (14.9%) controls (OR 3.2, 95% CI 1.9-5.3; p<0.001). No significant difference was found in maternal age, maternal parity, gestational age and the mode of delivery between the two groups. Delivery by unskilled birth attendant, prolonged second stage of labour, birth in a non-government hospital setup and absence of antenatal care were significant risk factors for hypoxic ischemic encephalopathy in neonates. Improvement in antenatal and intrapartum care may be helpful in decreasing the frequency of this problem. (author)

  8. Vasotrophic Regulation of Age-Dependent Hypoxic Cerebrovascular Remodeling

    Science.gov (United States)

    Silpanisong, Jinjutha; Pearce, William J.

    2015-01-01

    Hypoxia can induce functional and structural vascular remodeling by changing the expression of trophic factors to promote homeostasis. While most experimental approaches have been focused on functional remodeling, structural remodeling can reflect changes in the abundance and organization of vascular proteins that determine functional remodeling. Better understanding of age-dependent hypoxic macrovascular remodeling processes of the cerebral vasculature and its clinical implications require knowledge of the vasotrophic factors that influence arterial structure and function. Hypoxia can affect the expression of transcription factors, classical receptor tyrosine kinase factors, non-classical G-protein coupled factors, catecholamines, and purines. Hypoxia’s remodeling effects can be mediated by Hypoxia Inducible Factor (HIF) upregulation in most vascular beds, but alterations in the expression of growth factors can also be independent of HIF. PPARγ is another transcription factor involved in hypoxic remodeling. Expression of classical receptor tyrosine kinase ligands, including vascular endothelial growth factor, platelet derived growth factor, fibroblast growth factor and angiopoietins, can be altered by hypoxia which can act simultaneously to affect remodeling. Tyrosine kinase-independent factors, such as transforming growth factor, nitric oxide, endothelin, angiotensin II, catecholamines, and purines also participate in the remodeling process. This adaptation to hypoxic stress can fundamentally change with age, resulting in different responses between fetuses and adults. Overall, these mechanisms integrate to assure that blood flow and metabolic demand are closely matched in all vascular beds and emphasize the view that the vascular wall is a highly dynamic and heterogeneous tissue with multiple cell types undergoing regular phenotypic transformation. PMID:24063376

  9. Hypoxic-ischemic encefalopathy: Clinical course and prognosis

    Directory of Open Access Journals (Sweden)

    Ćosić-Cerovac Nataša

    2003-01-01

    Full Text Available Background. Establishing the value of neurological examination, and additional diagnostic methods (ultrasonography and magnetic resonance imaging of the brain in the diagnosis and prognosis of hypoxic-ischemic encephalopathy and its treatment, tracking the clinical course, and making the prognosis of neurological development in newborn infants with hypoxic-ischemic encefalopathy. Methods. The group of 40 term newborn infants with suspected intrauterine asphyxia was examined. All the infants were prospectivelly followed untill the 3rd year of age at the Clinic for Neurology and Psychiatry for Children and Youth in order to estimate their neurological development and to diagnose the occurence of persistent neurological disorders. All the infants were analyzed by their gestational age and Apgar score in the 1st and the 5th minute of life. They were all examined neurologically and by ultrasonography in the first week of life and, repeatedly, at the age of 1, 3, 6, 9, 12, 18, as well as in the 24th month of life. They were treated by the standard methods for this disease. Finally, all the infants were examined neurologically and by magnetic resonance imaging of the brain in their 3rd year of age. On the basis of neurological finding infants were devided into 3 groups: infants with normal neurological finding, infants with mild neurological symptomatology, and infants with severe neurological disorders. Results. It was shown that neurological finding, ultrasonography and magnetic resonance imaging of the brain positively correlated with the later neurological development of the infants with hypoxic-ischemic encephalopathy. Conclusion. Only the combined use of these techniques had full diagnostic and prognostic significance emphasizing that the integrative approach was very important in the diagnosis of brain lesions in infants.

  10. Intermittent Rivers and Biodiversity. Large scale analyses between hydrology and ecology in intermittent rivers

    OpenAIRE

    Blanchard, Q.

    2014-01-01

    Intermittent rivers are characterized by a temporary interruption of their flow which can manifest in a variety of ways, as much on a spatial scale as on a temporal one. This particular aspect of intermittent river hydrology gives rise to unique ecosystems, combining both aquatic and terrestrial habitats. Neglected for a long time by scientists and once considered biologically depauperate and ecologically unimportant, these fragile habitats are nowadays acknowledged for their rendered service...

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

    Science.gov (United States)

    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. Copyright © 2015 the American Physiological Society.

  12. Induction of long noncoding RNA MALAT1 in hypoxic mice

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    Lelli A

    2015-10-01

    Full Text Available Aurelia Lelli,1,2,* Karen A Nolan,1,2,* Sara Santambrogio,1,2 Ana Filipa Gonçalves,1,2 Miriam J Schönenberger,1,2 Anna Guinot,1,2 Ian J Frew,1,2 Hugo H Marti,3 David Hoogewijs,1,2,4 Roland H Wenger1,2 1Institute of Physiology and Zurich Center for Human Physiology (ZIHP, University of Zurich, Zurich, Switzerland; 2National Center of Competence in Research "Kidney.CH", Zurich, Switzerland; 3Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany; 4Institute of Physiology, University of Duisburg-Essen, Essen, Germany *These authors contributed equally to this work Abstract: Long thought to be “junk DNA”, in recent years it has become clear that a substantial fraction of intergenic genomic DNA is actually transcribed, forming long noncoding RNA (lncRNA. Like mRNA, lncRNA can also be spliced, capped, and polyadenylated, affecting a multitude of biological processes. While the molecular mechanisms underlying the function of lncRNAs have just begun to be elucidated, the conditional regulation of lncRNAs remains largely unexplored. In genome-wide studies our group and others recently found hypoxic transcriptional induction of a subset of lncRNAs, whereof nuclear-enriched abundant/autosomal transcript 1 (NEAT1 and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1 appear to be the lncRNAs most ubiquitously and most strongly induced by hypoxia in cultured cells. Hypoxia-inducible factor (HIF-2 rather than HIF-1 seems to be the preferred transcriptional activator of these lncRNAs. For the first time, we also found strong induction primarily of MALAT1 in organs of mice exposed to inspiratory hypoxia. Most abundant hypoxic levels of MALAT1 lncRNA were found in kidney and testis. In situ hybridization revealed that the hypoxic induction in the kidney was confined to proximal rather than distal tubular epithelial cells. Direct oxygen-dependent regulation of MALAT1 lncRNA was confirmed using isolated primary

  13. Biophysical basis of hypoxic radioprotection by deoxygenated dextran-hemoglobin

    International Nuclear Information System (INIS)

    Wong, J.T.; Hill, R.P.

    1986-01-01

    Perfusion with deoxygenated dextran-hemoglobin provides an effective method for inducing hypoxic radioprotection of normal tissues during radiation treatment of tumors. In this study, the dependence of P50, the half-saturation pressure of oxygen binding to dextran-hemoglobin, was analyzed as a function of solution temperature and pH. The variation of attainable radioprotection with P50, and with the amount of collateral blood entering into the perfused region, was calculated. Upon perfusion of canine gracilis muscle with deoxygenated dextran-hemoglobin, a rapid onset of extensive venous hypoxia was observed

  14. Impaired gamete production and viability in Atlantic croaker collected throughout the 20,000 km(2) hypoxic region in the northern Gulf of Mexico.

    Science.gov (United States)

    Thomas, Peter; Rahman, Md Saydur; Picha, Matthew E; Tan, Wenxian

    2015-12-15

    The long-term impacts of recent marked increases in the incidence and extent of hypoxia (dissolved oxygen Gulf of Mexico. Potential fecundity was significantly lower in croaker collected throughout the ~20,000 km(2) hypoxic region than in croaker from normoxic sites. In vitro bioassays of gamete viability showed reductions in oocyte maturation and sperm motility in croaker collected from the hypoxic sites in response to reproductive hormones which were accompanied by decreases in gonadal levels of membrane progestin receptor alpha, the receptor regulating these processes. The finding that environmental hypoxia exposure reduces oocyte viability in addition to decreasing oocyte production in croaker suggests that fecundity estimates need to be adjusted to account for the decrease in oocyte maturation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Long-Term Chronic Intermittent Hypobaric Hypoxia Induces Glucose Transporter (GLUT4 Translocation Through AMP-Activated Protein Kinase (AMPK in the Soleus Muscle in Lean Rats

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    Patricia Siques

    2018-06-01

    Full Text Available Background: In chronic hypoxia (CH and short-term chronic intermittent hypoxia (CIH exposure, glycemia and insulin levels decrease and insulin sensitivity increases, which can be explained by changes in glucose transport at skeletal muscles involving GLUT1, GLUT4, Akt, and AMPK, as well as GLUT4 translocation to cell membranes. However, during long-term CIH, there is no information regarding whether these changes occur similarly or differently than in other types of hypoxia exposure. This study evaluated the levels of AMPK and Akt and the location of GLUT4 in the soleus muscles of lean rats exposed to long-term CIH, CH, and normoxia (NX and compared the findings.Methods: Thirty male adult rats were randomly assigned to three groups: a NX (760 Torr group (n = 10, a CIH group (2 days hypoxia/2 days NX; n = 10 and a CH group (n = 10. Rats were exposed to hypoxia for 30 days in a hypobaric chamber set at 428 Torr (4,600 m. Feeding (10 g daily and fasting times were accurately controlled. Measurements included food intake (every 4 days, weight, hematocrit, hemoglobin, glycemia, serum insulin (by ELISA, and insulin sensitivity at days 0 and 30. GLUT1, GLUT4, AMPK levels and Akt activation in rat soleus muscles were determined by western blot. GLUT4 translocation was measured with confocal microscopy at day 30.Results: (1 Weight loss and increases in hematocrit and hemoglobin were found in both hypoxic groups (p < 0.05. (2 A moderate decrease in glycemia and plasma insulin was found. (3 Insulin sensitivity was greater in the CIH group (p < 0.05. (4 There were no changes in GLUT1, GLUT4 levels or in Akt activation. (5 The level of activated AMPK was increased only in the CIH group (p < 0.05. (6 Increased GLUT4 translocation to the plasma membrane of soleus muscle cells was observed in the CIH group (p < 0.05.Conclusion: In lean rats experiencing long-term CIH, glycemia and insulin levels decrease and insulin sensitivity increases. Interestingly, there

  16. The dietary flavonoid kaempferol effectively inhibits HIF-1 activity and hepatoma cancer cell viability under hypoxic conditions

    International Nuclear Information System (INIS)

    Mylonis, Ilias; Lakka, Achillia; Tsakalof, Andreas; Simos, George

    2010-01-01

    Research highlights: → Kaempferol inhibits HIF-1 activity in hepatocarcinoma cells; → Kaempferol causes cytoplasmic mislocalization of HIF-1α by impairing the MAPK pathway. → Viability of hepatocarcinoma cells under hypoxia is reduced by kaempferol. -- Abstract: Hepatocellular carcinoma (HCC) is characterized by high mortality rates and resistance to conventional treatment. HCC tumors usually develop local hypoxia, which stimulates proliferation of cancer cells and renders them resilient to chemotherapy. Adaptation of tumor cells to the hypoxic conditions depends on the hypoxia-inducible factor 1 (HIF-1). Over-expression of its regulated HIF-1α subunit, an important target of anti-cancer therapy, is observed in many cancers including HCC and is associated with severity of tumor growth and poor patient prognosis. In this report we investigate the effect of the dietary flavonoid kaempferol on activity, expression levels and localization of HIF-1α as well as viability of human hepatoma (Huh7) cancer cells. Treatment of Huh7 cells with kaempferol under hypoxic conditions (1% oxygen) effectively inhibited HIF-1 activity in a dose-dependent manner (IC 50 = 5.16 μM). The mechanism of this inhibition did not involve suppression of HIF-1α protein levels but rather its mislocalization into the cytoplasm due to inactivation of p44/42 MAPK by kaempferol (IC 50 = 4.75 μM). Exposure of Huh7 cells to 10 μΜ kaempferol caused significant reduction of their viability, which was remarkably more evident under hypoxic conditions. In conclusion, kaempferol, a non-toxic natural food component, inhibits both MAPK and HIF-1 activity at physiologically relevant concentrations (5-10 μM) and suppresses hepatocarcinoma cell survival more efficiently under hypoxia. It has, therefore, potential as a therapeutic or chemopreventive anti-HCC agent.

  17. The dietary flavonoid kaempferol effectively inhibits HIF-1 activity and hepatoma cancer cell viability under hypoxic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Mylonis, Ilias; Lakka, Achillia; Tsakalof, Andreas [Laboratory of Biochemistry, School of Medicine, University of Thessaly, BIOPOLIS, 41110 Larissa (Greece); Institute of Biomedical Research and Technology (BIOMED), 51 Papanastasiou str., 41222 Larissa (Greece); Simos, George, E-mail: simos@med.uth.gr [Laboratory of Biochemistry, School of Medicine, University of Thessaly, BIOPOLIS, 41110 Larissa (Greece); Institute of Biomedical Research and Technology (BIOMED), 51 Papanastasiou str., 41222 Larissa (Greece)

    2010-07-16

    Research highlights: {yields} Kaempferol inhibits HIF-1 activity in hepatocarcinoma cells; {yields} Kaempferol causes cytoplasmic mislocalization of HIF-1{alpha} by impairing the MAPK pathway. {yields} Viability of hepatocarcinoma cells under hypoxia is reduced by kaempferol. -- Abstract: Hepatocellular carcinoma (HCC) is characterized by high mortality rates and resistance to conventional treatment. HCC tumors usually develop local hypoxia, which stimulates proliferation of cancer cells and renders them resilient to chemotherapy. Adaptation of tumor cells to the hypoxic conditions depends on the hypoxia-inducible factor 1 (HIF-1). Over-expression of its regulated HIF-1{alpha} subunit, an important target of anti-cancer therapy, is observed in many cancers including HCC and is associated with severity of tumor growth and poor patient prognosis. In this report we investigate the effect of the dietary flavonoid kaempferol on activity, expression levels and localization of HIF-1{alpha} as well as viability of human hepatoma (Huh7) cancer cells. Treatment of Huh7 cells with kaempferol under hypoxic conditions (1% oxygen) effectively inhibited HIF-1 activity in a dose-dependent manner (IC{sub 50} = 5.16 {mu}M). The mechanism of this inhibition did not involve suppression of HIF-1{alpha} protein levels but rather its mislocalization into the cytoplasm due to inactivation of p44/42 MAPK by kaempferol (IC{sub 50} = 4.75 {mu}M). Exposure of Huh7 cells to 10 {mu}{Mu} kaempferol caused significant reduction of their viability, which was remarkably more evident under hypoxic conditions. In conclusion, kaempferol, a non-toxic natural food component, inhibits both MAPK and HIF-1 activity at physiologically relevant concentrations (5-10 {mu}M) and suppresses hepatocarcinoma cell survival more efficiently under hypoxia. It has, therefore, potential as a therapeutic or chemopreventive anti-HCC agent.

  18. The dietary flavonoid kaempferol effectively inhibits HIF-1 activity and hepatoma cancer cell viability under hypoxic conditions.

    Science.gov (United States)

    Mylonis, Ilias; Lakka, Achillia; Tsakalof, Andreas; Simos, George

    2010-07-16

    Hepatocellular carcinoma (HCC) is characterized by high mortality rates and resistance to conventional treatment. HCC tumors usually develop local hypoxia, which stimulates proliferation of cancer cells and renders them resilient to chemotherapy. Adaptation of tumor cells to the hypoxic conditions depends on the hypoxia-inducible factor 1 (HIF-1). Over-expression of its regulated HIF-1alpha subunit, an important target of anti-cancer therapy, is observed in many cancers including HCC and is associated with severity of tumor growth and poor patient prognosis. In this report we investigate the effect of the dietary flavonoid kaempferol on activity, expression levels and localization of HIF-1alpha as well as viability of human hepatoma (Huh7) cancer cells. Treatment of Huh7 cells with kaempferol under hypoxic conditions (1% oxygen) effectively inhibited HIF-1 activity in a dose-dependent manner (IC(50)=5.16microM). The mechanism of this inhibition did not involve suppression of HIF-1alpha protein levels but rather its mislocalization into the cytoplasm due to inactivation of p44/42 MAPK by kaempferol (IC(50)=4.75microM). Exposure of Huh7 cells to 10microM kaempferol caused significant reduction of their viability, which was remarkably more evident under hypoxic conditions. In conclusion, kaempferol, a non-toxic natural food component, inhibits both MAPK and HIF-1 activity at physiologically relevant concentrations (5-10microM) and suppresses hepatocarcinoma cell survival more efficiently under hypoxia. It has, therefore, potential as a therapeutic or chemopreventive anti-HCC agent. Copyright 2010 Elsevier Inc. All rights reserved.

  19. Impact of Mental and Physical Stress on Blood Pressure and Pulse Pressure under Normobaric versus Hypoxic Conditions

    Science.gov (United States)

    Trapp, Michael; Trapp, Eva-Maria; Egger, Josef W.; Domej, Wolfgang; Schillaci, Giuseppe; Avian, Alexander; Rohrer, Peter M.; Hörlesberger, Nina; Magometschnigg, Dieter; Cervar-Zivkovic, Mila; Komericki, Peter; Velik, Rosemarie; Baulmann, Johannes

    2014-01-01

    Objective Hypobaric hypoxia, physical and psychosocial stress may influence key cardiovascular parameters including blood pressure (BP) and pulse pressure (PP). We investigated the effects of mild hypobaric hypoxia exposure on BP and PP reactivity to mental and physical stress and to passive elevation by cable car. Methods 36 healthy volunteers participated in a defined test procedure consisting of a period of rest 1, mental stress task (KLT-R), period of rest 2, combined mental (KLT-R) and physical task (bicycle ergometry) and a last period of rest both at Graz, Austria (353 m asl) and at the top station Dachstein (2700 m asl). Beat-to-beat heart rate and BP were analysed both during the test procedures at Graz and at Dachstein and during passive 1000 m elevation by cable car (from 1702 m to 2700 m). Results A significant interaction of kind of stress (mental vs. combined mental and physical) and study location (Graz vs. Dachstein) was found in the systolic BP (p = .007) and PP (p = .002) changes indicating that during the combined mental and physical stress task sBP was significantly higher under hypoxic conditions whereas sBP and PP were similar during mental stress both under normobaric normoxia (Graz) and under hypobaric hypoxia (Dachstein). During the passive ascent in cable car less trivialization (psychological coping strategy) was associated with an increase in PP (p = .004). Conclusion Our data show that combined mental and physical stress causes a significant higher raise in sBP and PP under hypoxic conditions whereas isolated mental stress did not affect sBP and PP under hypoxic conditions. PP-reaction to ascent in healthy subjects is not uniform. BP reactions to ascent that represents an accumulation of physical (mild hypobaric hypoxia) and psychological stressors depend on predetermined psychological traits (stress coping strategies). Thus divergent cardiovascular reactions can be explained by applying the multidimensional aspects of the

  20. Impact of mental and physical stress on blood pressure and pulse pressure under normobaric versus hypoxic conditions.

    Directory of Open Access Journals (Sweden)

    Michael Trapp

    Full Text Available Hypobaric hypoxia, physical and psychosocial stress may influence key cardiovascular parameters including blood pressure (BP and pulse pressure (PP. We investigated the effects of mild hypobaric hypoxia exposure on BP and PP reactivity to mental and physical stress and to passive elevation by cable car.36 healthy volunteers participated in a defined test procedure consisting of a period of rest 1, mental stress task (KLT-R, period of rest 2, combined mental (KLT-R and physical task (bicycle ergometry and a last period of rest both at Graz, Austria (353 m asl and at the top station Dachstein (2700 m asl. Beat-to-beat heart rate and BP were analysed both during the test procedures at Graz and at Dachstein and during passive 1000 m elevation by cable car (from 1702 m to 2700 m.A significant interaction of kind of stress (mental vs. combined mental and physical and study location (Graz vs. Dachstein was found in the systolic BP (p = .007 and PP (p = .002 changes indicating that during the combined mental and physical stress task sBP was significantly higher under hypoxic conditions whereas sBP and PP were similar during mental stress both under normobaric normoxia (Graz and under hypobaric hypoxia (Dachstein. During the passive ascent in cable car less trivialization (psychological coping strategy was associated with an increase in PP (p = .004.Our data show that combined mental and physical stress causes a significant higher raise in sBP and PP under hypoxic conditions whereas isolated mental stress did not affect sBP and PP under hypoxic conditions. PP-reaction to ascent in healthy subjects is not uniform. BP reactions to ascent that represents an accumulation of physical (mild hypobaric hypoxia and psychological stressors depend on predetermined psychological traits (stress coping strategies. Thus divergent cardiovascular reactions can be explained by applying the multidimensional aspects of the biopsychosocial concept.

  1. Effect of Rho kinase inhibitor fasudil on the expression ET-1 and NO in rats with hypoxic pulmonary hypertension.

    Science.gov (United States)

    Sun, Xing-Zhen; Li, Shu-Yan; Tian, Xiang-Yang; Hong, Ze; Li, Jia-Xin

    2018-04-12

    This study aims to study the effect of Rho kinase inhibitor fasudil on the expression endothelin-1 (ET-1) and nitric oxide (NO) in rats with hypoxic pulmonary hypertension (HPH). Twenty-four male SD rats were randomly divided into three groups: control group, model group (HPH group) and HPH+fasudil group. The rat HPH model was established by intermittent hypoxia (IH) at atmospheric pressure. Mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI), ET-1 and NO levels, and pulmonary vascular structural changes were observed in all groups. MPAP, RVHI and ET-1 levels were significantly higher in HPH group than in control group, while NO was significantly lower than in control group. In addition, mPAP, RVHI and ET-1 were significantly lower in the HPH+fasudil group than in the HPH group. In the HPH group, ET-1 level was significantly and positively correlated with mPAP and RVHI, NO was negatively correlated with mPAP and RVHI levels, and ET-1 level was significantly and negatively correlated with NO level. In the HPH group, pulmonary arteriolar walls were generally thickened, and lumen stenosis was obvious; while after fasudil treatment, pulmonary arteriolar wall thickening and stenosis degree were significantly reduced. Fasudil can significantly reduce ET-l level and increase NO level in HPH rats, suppressing the development of pulmonary arterial hypertension.

  2. In vivo assay of the radiation sensitivity of hypoxic tumour cells. Influence of radiation quality and hypoxic sensitization

    International Nuclear Information System (INIS)

    Porschen, W.; Bosiljanoff, P.; Gewehr, K.; Muehlensiepen, H.; Feinendegen, L.E.

    1977-01-01

    In order to measure quantitatively tumour cell kinetics in living mice, tumour bearing animals (sarcoma-180) received intravenously 5-iodo-2'-deoxyuridine (IUdR), a thymidine analogue, which was labelled with 125 I or with 131 I, both of which can be easily externally counted by their gamma emission. IUdR is stably bound to DNA, reutilization is minimal and the measured activity loss from the tumour later than 50 hours after injection signals cell loss or cell death. The effect of irradiation on euoxic and average tumour cells was studied by sequentially labelling the tumour bearing animals first with 125 IUdR and, 70 hours later, with 131 IUdR. At the time of the second injection the average tumour cell population is labelled by the first injection of 125 IUdR, and the second injection of 131 IUdR nearly exclusively tags the perivascular tumour cells; these are euoxic in contrast to the average tumour cell, a large proportion of which is hypoxic. The radiation-induced activity loss rates from the two labelled tumour cell populations indicate the sensitivities of the two populations. At dose levels that cause identical effects on euoxic cells, the ratio of radiation-induced enhancement of cell loss rates for euoxic cells to average cells was 2.6 for 60 Co gamma radiation, 1.4 for 15MeV neutron irradiation, and 1.0 for alpha irradiation (1.5.MeV). The effect of five hypoxic cell sensitizers was analysed. The sensitization was limited to hypoxic cells, and the most effective drug was Ro-07-0582, showing at the 50% level of maximum effect a dose modifying factor of 1.5. Sensitization was highest when the drug was given 15 min prior to irradiation. Hyperthermia affected nearly exclusively hypoxic cells and showed a dose modifying factor of about 2 when the tumours were heated at 42 0 C for 30 min immediately after irradiation. The resulting enhancement of effect was reduced when hyperthermia was applied prior to irradiation. (author)

  3. Sulphonylurea drugs reduce hypoxic damage in the isolated perfused rat kidney.

    Science.gov (United States)

    Engbersen, R; Moons, M M; Wouterse, A C; Dijkman, H B; Kramers, C; Smits, P; Russel, F G

    2000-08-01

    Sulphonylurea drugs have been shown to protect against hypoxic damage in isolated proximal tubules of the kidney. In the present study we investigated whether these drugs can protect against hypoxic damage in a whole kidney preparation. Tolbutamide (200 microM) and glibenclamide (10 microM) were applied to the isolated perfused rat kidney prior to changing the gassing from oxygen to nitrogen for 30 min. Hypoxic perfusions resulted in an increased fractional excretion of glucose (FE % glucose 14.3+/-1.5 for hypoxic perfusions vs 4.9+/-1.6 for normoxic perfusions, mean +/- s.e. mean, P<0.05), which could be completely restored by 200 microM tolbutamide (5.7+/-0.4 for tolbutamide vs 14.3+/-1.5 for untreated hypoxic kidneys, P<0.01). Furthermore, tolbutamide reduced the total amount of LDH excreted in the urine (220+/-100 mU for tolbutamide vs. 1220+/-160 mU for untreated hypoxic kidneys, P<0.01). Comparable results were obtained with glibenclamide (10 microM). In agreement with the effect on functional parameters, ultrastructural analysis of proximal tubules showed increased brush border preservation in tolbutamide treated kidneys compared to untreated hypoxic kidneys. We conclude that glibenclamide and tolbutamide are both able to reduce hypoxic damage to proximal tubules in the isolated perfused rat kidney when applied in the appropriate concentrations.

  4. Hypoxic tumor environments exhibit disrupted collagen I fibers and low macromolecular transport.

    Directory of Open Access Journals (Sweden)

    Samata M Kakkad

    Full Text Available Hypoxic tumor microenvironments result in an aggressive phenotype and resistance to therapy that lead to tumor progression, recurrence, and metastasis. While poor vascularization and the resultant inadequate drug delivery are known to contribute to drug resistance, the effect of hypoxia on molecular transport through the interstitium, and the role of the extracellular matrix (ECM in mediating this transport are unexplored. The dense mesh of fibers present in the ECM can especially influence the movement of macromolecules. Collagen 1 (Col1 fibers form a key component of the ECM in breast cancers. Here we characterized the influence of hypoxia on macromolecular transport in tumors, and the role of Col1 fibers in mediating this transport using an MDA-MB-231 breast cancer xenograft model engineered to express red fluorescent protein under hypoxia. Magnetic resonance imaging of macromolecular transport was combined with second harmonic generation microscopy of Col1 fibers. Hypoxic tumor regions displayed significantly decreased Col1 fiber density and volume, as well as significantly lower macromolecular draining and pooling rates, than normoxic regions. Regions adjacent to severely hypoxic areas revealed higher deposition of Col1 fibers and increased macromolecular transport. These data suggest that Col1 fibers may facilitate macromolecular transport in tumors, and their reduction in hypoxic regions may reduce this transport. Decreased macromolecular transport in hypoxic regions may also contribute to poor drug delivery and tumor recurrence in hypoxic regions. High Col1 fiber density observed around hypoxic regions may facilitate the escape of aggressive cancer cells from hypoxic regions.

  5. [Hypoxic brain injuries notified to the Danish Patient Insurance Association during 1992-2004. Secondary publication

    DEFF Research Database (Denmark)

    Bock, J.; Christoffersen, J.K.; Hedegaard, M.

    2008-01-01

    We investigated the files of the Danish Patient Insurance Association for newborns suffering from hypoxic brain injuries. From 1992 to 2004, a total of 127 approved claims concerning peripartum hypoxic injury were registered. Thirty-eight newborns died and the majority of the 89 surviving children...

  6. Evaluation of 80 Term Neonates with Hypoxic Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Selahattin Katar

    2007-01-01

    Full Text Available This study aimed to review the etiology, clinical - laboratory features and mortality rate of term 80 neonates with perinatal asphyxia admitted to our neonatal unit between January 2005-April 2006. The sex distribution was 24 (%30 female and 56 (% 70 male. The mean gestational age was 38.6±1.3 weeks and weight 3156±561 gram. Of the patients % 46.25 were delivered with a cesarean section and % 53.75 with spontaneous vaginal delivery. The etiologic factors for hypoxic ischemic encephalopathy were % 31.25 force delivery, meconium aspiration, and % 66.25 preeclampsia, eclampsia and diabetic mother’s infant. The distribution of patients according to HIE statging system (Sarnat&Sarnat were as follows: 33 patients (% 41.25 in stage 1, 20 (% 25 in stage 2 and 27 (% 33.75 in stage 3. Seizures were observed in % 33.75 of patients. The mean duration of hospital stay was 10.6±7.7 days for the surviving patients and 4.2±3.4 days for patients who died. Except from central nervous system, liver and kidney were the most involved organs.Perinatal asphyxia remains to be leading cause of neonatal mortality. Hypoxic ischemic encephalopathy is a common newborn problem and cause important mortality and morbidity where low-social –cultural –education conditions with in regions.

  7. Therapeutic hypothermia for neonates with hypoxic ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Ming-Chou Chiang

    2017-12-01

    Full Text Available Therapeutic hypothermia (TH is a recommended regimen for newborn infants who are at or near term with evolving moderate-to-severe hypoxic ischemic encephalopathy (HIE. The Task Force of the Taiwan Child Neurology Society and the Taiwan Society of Neonatology held a joint meeting in 2015 to establish recommendations for using TH on newborn patients with HIE. Based on current evidence and experts' experiences, this review article summarizes the key points and recommendations regarding TH for newborns with HIE, including: (1 selection criteria for TH; (2 choices of method and equipment for TH; (3 TH prior to and during transport; (4 methods for temperature maintenance, monitoring, and rewarming; (5 systemic care of patients during TH, including the care of respiratory and cardiovascular systems, management of fluids, electrolytes, and nutrition, as well as sedation and drug metabolism; (6 monitoring and management of seizures; (7 neuroimaging, prognostic factors, and outcomes; and (8 adjuvant therapy for TH. Key Words: hypoxic ischemic encephalopathy, neonate, patient care, perinatal asphyxia, therapeutic hypothermia

  8. Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury

    Directory of Open Access Journals (Sweden)

    Eridan Rocha-Ferreira

    2016-01-01

    Full Text Available Hypoxic-ischaemic damage to the developing brain is a leading cause of child death, with high mortality and morbidity, including cerebral palsy, epilepsy, and cognitive disabilities. The developmental stage of the brain and the severity of the insult influence the selective regional vulnerability and the subsequent clinical manifestations. The increased susceptibility to hypoxia-ischaemia (HI of periventricular white matter in preterm infants predisposes the immature brain to motor, cognitive, and sensory deficits, with cognitive impairment associated with earlier gestational age. In term infants HI causes selective damage to sensorimotor cortex, basal ganglia, thalamus, and brain stem. Even though the immature brain is more malleable to external stimuli compared to the adult one, a hypoxic-ischaemic event to the neonate interrupts the shaping of central motor pathways and can affect normal developmental plasticity through altering neurotransmission, changes in cellular signalling, neural connectivity and function, wrong targeted innervation, and interruption of developmental apoptosis. Models of neonatal HI demonstrate three morphologically different types of cell death, that is, apoptosis, necrosis, and autophagy, which crosstalk and can exist as a continuum in the same cell. In the present review we discuss the mechanisms of HI injury to the immature brain and the way they affect plasticity.

  9. Concordance between hypoxic challenge testing and predictive equations for hypoxic flight assessment in chronic obstructive pulmonary disease patients prior to air travel

    Directory of Open Access Journals (Sweden)

    Mohie Aldeen Abd Alzaher Khalifa

    2016-10-01

    Conclusions: The present study supports on-HCT as a reliable, on-invasive and continuous methods determining the requirement for in-flight O2 are relatively constant. Predictive equations considerably overestimate the need for in-flight O2 compared to hypoxic inhalation test. Predictive equations are cheap, readily available methods of flight assessment, but this study shows poor agreement between their predictions and the measured individual hypoxic responses during HCT.

  10. Intermittent control: a computational theory of human control.

    Science.gov (United States)

    Gawthrop, Peter; Loram, Ian; Lakie, Martin; Gollee, Henrik

    2011-02-01

    The paradigm of continuous control using internal models has advanced understanding of human motor control. However, this paradigm ignores some aspects of human control, including intermittent feedback, serial ballistic control, triggered responses and refractory periods. It is shown that event-driven intermittent control provides a framework to explain the behaviour of the human operator under a wider range of conditions than continuous control. Continuous control is included as a special case, but sampling, system matched hold, an intermittent predictor and an event trigger allow serial open-loop trajectories using intermittent feedback. The implementation here may be described as "continuous observation, intermittent action". Beyond explaining unimodal regulation distributions in common with continuous control, these features naturally explain refractoriness and bimodal stabilisation distributions observed in double stimulus tracking experiments and quiet standing, respectively. Moreover, given that human control systems contain significant time delays, a biological-cybernetic rationale favours intermittent over continuous control: intermittent predictive control is computationally less demanding than continuous predictive control. A standard continuous-time predictive control model of the human operator is used as the underlying design method for an event-driven intermittent controller. It is shown that when event thresholds are small and sampling is regular, the intermittent controller can masquerade as the underlying continuous-time controller and thus, under these conditions, the continuous-time and intermittent controller cannot be distinguished. This explains why the intermittent control hypothesis is consistent with the continuous control hypothesis for certain experimental conditions.

  11. CONDITIONED ANALYSIS OF HIGH-LATITUDE SOLAR WIND INTERMITTENCY

    International Nuclear Information System (INIS)

    D'Amicis, R.; Consolini, G.; Bavassano, B.; Bruno, R.

    2012-01-01

    The solar wind is a turbulent medium displaying intermittency. Its intermittent features have been widely documented and studied, showing how the intermittent character is different in fast and slow wind. In this paper, a statistical conditioned analysis of the solar wind intermittency for a period of high-latitude fast solar wind is presented. In particular, the intermittent features are investigated as a function of the Alfvénic degree of fluctuations at a given scale. The results show that the main contribution to solar wind intermittency is due to non-Alfvénic structures, while Alfvénic increments are found to be characterized by a smaller level of intermittency than the previous ones. Furthermore, the lifetime statistics of Alfvénic periods are discussed in terms of a multiscale texture of randomly oriented flux tubes.

  12. Reconstitution activity of hypoxic cultured human cord blood CD34-positive cells in NOG mice

    International Nuclear Information System (INIS)

    Shima, Haruko; Takubo, Keiyo; Iwasaki, Hiroko; Yoshihara, Hiroki; Gomei, Yumiko; Hosokawa, Kentaro; Arai, Fumio; Takahashi, Takao; Suda, Toshio

    2009-01-01

    Hematopoietic stem cells (HSCs) reside in hypoxic areas of the bone marrow. However, the role of hypoxia in the maintenance of HSCs has not been fully characterized. We performed xenotransplantation of human cord blood cells cultured in hypoxic or normoxic conditions into adult NOD/SCID/IL-2Rγ null (NOG) mice. Hypoxic culture (1% O 2 ) for 6 days efficiently supported the maintenance of HSCs, although cell proliferation was suppressed compared to the normoxic culture. In contrast, hypoxia did not affect in vitro colony-forming ability. Upregulation of a cell cycle inhibitor, p21, was observed in hypoxic culture. Immunohistochemical analysis of recipient bone marrow revealed that engrafted CD34 + CD38 - cord blood HSCs were hypoxic. Taken together, these results demonstrate the significance of hypoxia in the maintenance of quiescent human cord blood HSCs.

  13. Intermittent character of interplanetary magnetic field fluctuations

    International Nuclear Information System (INIS)

    Bruno, Roberto; Carbone, Vincenzo; Chapman, Sandra; Hnat, Bogdan; Noullez, Alain; Sorriso-Valvo, Luca

    2007-01-01

    Interplanetary magnetic field magnitude fluctuations are notoriously more intermittent than velocity fluctuations in both fast and slow wind. This behavior has been interpreted in terms of the anomalous scaling observed in passive scalars in fully developed hydrodynamic turbulence. In this paper, the strong intermittent nature of the interplanetary magnetic field is briefly discussed comparing results performed during different phases of the solar cycle. The scaling properties of the interplanetary magnetic field magnitude show solar cycle variation that can be distinguished in the scaling exponents revealed by structure functions. The scaling exponents observed around the solar maximum coincide, within the errors, to those measured for passive scalars in hydrodynamic turbulence. However, it is also found that the values are not universal in the sense that the solar cycle variation may be reflected in dependence on the structure of the velocity field

  14. Intermittency exponent of the turbulent energy cascade

    International Nuclear Information System (INIS)

    Cleve, J.; Greiner, M.; Pearson, B.R.; Sreenivasan, K.R.

    2006-12-01

    We consider the turbulent energy dissipation from one-dimensional records in experiments using air and gaseous helium at cryogenic temperatures, and obtain the intermittency exponent via the two-point correlation function of the energy dissipation. The air data are obtained in a number of flows in a wind tunnel and the atmospheric boundary layer at a height of about 35 m above the ground. The helium data correspond to the centerline of a jet exhausting into a container. The air data on the intermittency exponent are consistent with each other and with a trend that increases with the Taylor microscale Reynolds number, R λ , of up to about 1000 and saturates thereafter. On the other hand, the helium data cluster around a constant value at nearly all R λ , this being about half of the asymptotic value for the air data. Some possible explanation is offered for this anomaly. (author)

  15. Effects of intermittent hypoxia on running economy.

    Science.gov (United States)

    Burtscher, M; Gatterer, H; Faulhaber, M; Gerstgrasser, W; Schenk, K

    2010-09-01

    We investigated the effects of two 5-wk periods of intermittent hypoxia on running economy (RE). 11 male and female middle-distance runners were randomly assigned to the intermittent hypoxia group (IHG) or to the control group (CG). All athletes trained for a 13-wk period starting at pre-season until the competition season. The IHG spent additionally 2 h at rest on 3 days/wk for the first and the last 5 weeks in normobaric hypoxia (15-11% FiO2). RE, haematological parameters and body composition were determined at low altitude (600 m) at baseline, after the 5 (th), the 8 (th) and the 13 (th) week of training. RE, determined by the relative oxygen consumption during submaximal running, (-2.3+/-1.2 vs. -0.3+/-0.7 ml/min/kg, Ptraining phase. Georg Thieme Verlag KG Stuttgart . New York.

  16. Optimal intermittent search strategies: smelling the prey

    International Nuclear Information System (INIS)

    Revelli, J A; Wio, H S; Rojo, F; Budde, C E

    2010-01-01

    We study the kinetics of the search of a single fixed target by a searcher/walker that performs an intermittent random walk, characterized by different states of motion. In addition, we assume that the walker has the ability to detect the scent left by the prey/target in its surroundings. Our results, in agreement with intuition, indicate that the prey's survival probability could be strongly reduced (increased) if the predator is attracted (or repelled) by the trace left by the prey. We have also found that, for a positive trace (the predator is guided towards the prey), increasing the inhomogeneity's size reduces the prey's survival probability, while the optimal value of α (the parameter that regulates intermittency) ceases to exist. The agreement between theory and numerical simulations is excellent.

  17. Optimal intermittent search strategies: smelling the prey

    Energy Technology Data Exchange (ETDEWEB)

    Revelli, J A; Wio, H S [Instituto de Fisica de Cantabria, Universidad de Cantabria and CSIC, E-39005 Santander (Spain); Rojo, F; Budde, C E [Fa.M.A.F., Universidad Nacional de Cordoba, Ciudad Universitaria, X5000HUA Cordoba (Argentina)

    2010-05-14

    We study the kinetics of the search of a single fixed target by a searcher/walker that performs an intermittent random walk, characterized by different states of motion. In addition, we assume that the walker has the ability to detect the scent left by the prey/target in its surroundings. Our results, in agreement with intuition, indicate that the prey's survival probability could be strongly reduced (increased) if the predator is attracted (or repelled) by the trace left by the prey. We have also found that, for a positive trace (the predator is guided towards the prey), increasing the inhomogeneity's size reduces the prey's survival probability, while the optimal value of {alpha} (the parameter that regulates intermittency) ceases to exist. The agreement between theory and numerical simulations is excellent.

  18. Optimal Dynamics of Intermittent Water Supply

    Science.gov (United States)

    Lieb, Anna; Wilkening, Jon; Rycroft, Chris

    2014-11-01

    In many urban areas of the developing world, piped water is supplied only intermittently, as valves direct water to different parts of the water distribution system at different times. The flow is transient, and may transition between free-surface and pressurized, resulting in complex dynamical features with important consequences for water suppliers and users. These consequences include degradation of distribution system components, compromised water quality, and inequitable water availability. The goal of this work is to model the important dynamics and identify operating conditions that mitigate certain negative effects of intermittent water supply. Specifically, we will look at valve parameters occurring as boundary conditions in a network model of transient, transition flow through closed pipes. Optimization will be used to find boundary values to minimize pressure gradients and ensure equitable water availability.

  19. Neuroprotection of lamotrigine on hypoxic-ischemic brain damage in neonatal rats: Relations to administration time and doses

    Directory of Open Access Journals (Sweden)

    Yong-Hong Yi

    2008-06-01

    Full Text Available Yong-Hong Yi1, Wen-Chao Guo1, Wei-Wen Sun1, Tao Su1, Han Lin1, Sheng-Qiang Chen1, Wen-Yi Deng1, Wei Zhou2, Wei-Ping Liao11Department of Neurology, Institute of Neurosciences and the Second Affiliated Hospital, 2Department of Neonatology, Affiliated Guangzhou Children’s Hospital, Guangzhou Medical College, Guangzhou, Guangdong Province, P.R. ChinaAbstract: Lamotrigine (LTG, an antiepileptic drug, has been shown to be able to improve cerebral ischemic damage by limiting the presynaptic release of glutamate. The present study investigated further the neuroprotective effect of LTG on hypoxic-ischemic brain damage (HIBD in neonatal rats and its relations to administration time and doses. The HIBD model was produced in 7-days old SD rats by left common carotid artery ligation followed by 2 h hypoxic exposure (8% oxygen. LTG was administered intraperitoneally with the doses of 5, 10, 20, and 40 mg/kg 3 h after operation and the dose of 20 mg/kg 1 h before and 3 h, 6 h after operation. Blood and brain were sampled 24 h after operation. Nissl staining, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL, and neuron-specific enolase (NSE immunohistochemical staining were used for morphological studies. Water content in left cortex and NSE concentration in serum were determined. LTG significantly reduced water content in the cerebral cortex, as well as the number of TUNEL staining neurons in the dentate gyrus and cortex in hypoxic-ischemia (HI model. Furthermore, LTG significantly decreased the NSE level in serum and increased the number of NSE staining neurons in the cortex. These effects, except that on water content, were dose-dependent and were more remarkable in the pre-treated group than in the post-treated groups. These results demonstrate that LTG may have a neuroprotective effect on acute HIBD in neonates. The effect is more prominent when administrated with higher doses and before HI.Keywords: hypoxic-ischemic brain

  20. Hypoxia modifies the feeding preferences of Drosophila. Consequences for diet dependent hypoxic survival

    Directory of Open Access Journals (Sweden)

    Frelin Christian

    2010-05-01

    Full Text Available Abstract Background Recent attention has been given to the relationships between diet, longevity, aging and resistance to various forms of stress. Flies do not simply ingest calories. They sense different concentrations of carbohydrate and protein macronutrients and they modify their feeding behavior in response to changes in dietary conditions. Chronic hypoxia is a major consequence of cardiovascular diseases. Dietary proteins have recently been shown to decrease the survival of chronically hypoxic Drosophila. Whether flies modify their feeding behavior in response to hypoxia is not currently known. This study uses the recently developed capillary feeding assay to analyze the feeding behavior of normoxic and chronically hypoxic Drosophila melanogaster. Results The intakes rates of sucrose and yeast by normoxic or chronically hypoxic flies (5% O2 were analyzed under self selecting and "no choice" conditions. Chronically hypoxic flies fed on pure yeast diets or mixed diets under self selection conditions stopped feeding on yeast. Flies fed on mixed diets under "no choice" conditions reduced their food intakes. Hypoxia did not modify the adaptation of flies to diluted diets or to imbalanced diets. Mortality was assessed in parallel experiments. Dietary yeast had two distinct effects on hypoxic flies (i a repellent action which eventually led to starvation and which was best observed in the absence of dietary sucrose and (ii a toxic action which led to premature death. Finally we determined that hypoxic survivals were correlated to the intakes of sucrose, which suggested that dietary yeast killed flies by reducing their intake of sucrose. The feeding preferences of adult Drosophila were insensitive to NO scavengers, NO donor molecules and inhibitors of phosphodiesterases which are active on Drosophila larvae. Conclusion Chronically hypoxic flies modify their feeding behavior. They avoid dietary yeast which appears to be toxic. Hypoxic survival is

  1. AN ELDERLY WOMAN WITH INTERMITTENT CLAUDICATION

    Directory of Open Access Journals (Sweden)

    Nayyer Naveed Wazir

    2006-01-01

    Full Text Available This case report illustrates the misdiagnosis of intermittent claudication in an elderly with multiple cardiac risk factors. Careful clinical evaluation and imaging shifts the diagnosis from peripheral vascular disease to spinal stenosis. The decision whether to offer conservative therapy or proceed to spinal surgery requires an accurate assessment of the severity of the symptoms without ignoring the important role of patient preferences.

  2. Long-range forecasting of intermittent streamflow

    OpenAIRE

    F. F. van Ogtrop; R. W. Vervoort; G. Z. Heller; D. M. Stasinopoulos; R. A. Rigby

    2011-01-01

    Long-range forecasting of intermittent streamflow in semi-arid Australia poses a number of major challenges. One of the challenges relates to modelling zero, skewed, non-stationary, and non-linear data. To address this, a statistical model to forecast streamflow up to 12 months ahead is applied to five semi-arid catchments in South Western Queensland. The model uses logistic regression through Generalised Additive Models for Location, Scale and Shape (GAMLSS) to determine th...

  3. Long-range forecasting of intermittent streamflow

    OpenAIRE

    F. F. van Ogtrop; R. W. Vervoort; G. Z. Heller; D. M. Stasinopoulos; R. A. Rigby

    2011-01-01

    Long-range forecasting of intermittent streamflow in semi-arid Australia poses a number of major challenges. One of the challenges relates to modelling zero, skewed, non-stationary, and non-linear data. To address this, a probabilistic statistical model to forecast streamflow 12 months ahead is applied to five semi-arid catchments in South Western Queensland. The model uses logistic regression through Generalised Additive Models for Location, Scale and Shape (GAMLSS) to determine the probabil...

  4. Fetal Stress and Programming of Hypoxic/Ischemic-Sensitive Phenotype in the Neonatal Brain: Mechanisms and Possible Interventions

    Science.gov (United States)

    Li, Yong; Gonzalez, Pablo; Zhang, Lubo

    2012-01-01

    Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxicischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other for brain disorders. PMID:22627492

  5. Efficient search by optimized intermittent random walks

    International Nuclear Information System (INIS)

    Oshanin, Gleb; Lindenberg, Katja; Wio, Horacio S; Burlatsky, Sergei

    2009-01-01

    We study the kinetics for the search of an immobile target by randomly moving searchers that detect it only upon encounter. The searchers perform intermittent random walks on a one-dimensional lattice. Each searcher can step on a nearest neighbor site with probability α or go off lattice with probability 1 - α to move in a random direction until it lands back on the lattice at a fixed distance L away from the departure point. Considering α and L as optimization parameters, we seek to enhance the chances of successful detection by minimizing the probability P N that the target remains undetected up to the maximal search time N. We show that even in this simple model, a number of very efficient search strategies can lead to a decrease of P N by orders of magnitude upon appropriate choices of α and L. We demonstrate that, in general, such optimal intermittent strategies are much more efficient than Brownian searches and are as efficient as search algorithms based on random walks with heavy-tailed Cauchy jump-length distributions. In addition, such intermittent strategies appear to be more advantageous than Levy-based ones in that they lead to more thorough exploration of visited regions in space and thus lend themselves to parallelization of the search processes.

  6. Influence of intermittent preventive treatment on antibodies to VAR2CSA in pregnant Cameroonian women

    DEFF Research Database (Denmark)

    Babakhanyan, Anna; Tutterrow, Yeung L; Bobbili, Naveen

    2016-01-01

    Intermittent preventive treatment (IPT) and insecticide-treated bed nets are the standard of care for preventing malaria in pregnant women. Since these preventive measures reduce exposure to malaria, their influence on the antibody (Ab) response to the parasite antigen VAR2CSA was evaluated...... in pregnant Cameroonian women exposed to holoendemic malaria. Ab levels to full-length VAR2CSA (FV2), variants of the six Duffy binding like (DBL) domains, and proportion of high avidity Ab to FV2 were measured longitudinally in 92 women before and 147 women after IPT. As predicted, reduced exposure...

  7. Release from the Crabtree effect by hypoxic cell radiosensitizers

    International Nuclear Information System (INIS)

    Mustea, I.; Bara, A.

    1979-01-01

    The Crabtree effect can be observed when the 0 2 consumption of tumour cells or of mammalian cells grown in culture is measured in physiological medium containing glucose. The effect of 2 hypoxic cell radiosensitizers, misonidazole and NDPP, on the 0 2 consumption of Ehrlich ascites tumour cells was compared in media with and without glucose. A stimulatory effect on 0 2 consumption was found for 5-20 mM misonidazole as well as for 0.5mM NDPP, both in media containing 10 -2 M glucose. Thus glucose induced a Crabtree effect in Ehrlich tumour cells, expressed as 38-45% inhibition of 0 2 consumption relative to that in the same medium without glucose. The stimulatory effect of misonidazole and NDPP on 0 2 utilization in medium with glucose undoubtedly appeared as a release from the Crabtree effect. (author)

  8. Nitric oxide metabolites in goldfish under normoxic and hypoxic conditions

    DEFF Research Database (Denmark)

    Hansen, Marie N.; Jensen, Frank Bo

    2010-01-01

    – and it is metabolized to nitrite and nitrate. Nitrite is used as a marker for NOS activity but it is also a NO donor that can be activated by various cellular proteins under hypoxic conditions. Here, we report the first systematic study of NO metabolites (nitrite, nitrate, S-nitroso, N-nitroso and Fe-nitrosyl compounds...... to and below the critical PO2] for two days caused large decreases in plasma nitrite and nitrate, which suggests reduced NOS activity and increased nitrite/nitrate utilization or loss. Tissue NO metabolites were largely maintained at their tissue-specific values under hypoxia, pointing at nitrite transfer from...... extracellular to intracellular compartments and cellular NO generation from nitrite. The data highlights the preference of goldfish to defend intracellular NO homeostasis during hypoxia....

  9. The Effects of Hypoxic Hypoxia on Cognitive Performance Decay

    Science.gov (United States)

    2015-05-04

    during the hypoxic phase at all altitudes. Cognitive performance, as measured by the simple and choice reaction tasks, is significantly impacted by...abort a sortie if the SO2 drops below 90%. Given the impact such a small device can potentially have on operational effectiveness, the importance of...b13b15b17h01 h03hD&h07 h09 h11 h13 h15 h17 h18 h21 h23 h26 h27 h28 h31 1� h36 1137 h39h41 ht3h46h4-7 h48 h&1 h53 r1l1 rm rOI5 r07 r01 r11 r13 r16

  10. Analysis of Hypoxic and Hypercapnic Ventilatory Response in Healthy Volunteers

    Science.gov (United States)

    Lin, Ling; Sharifi, Husham; Rico, Tom; Andlauer, Olivier; Aran, Adi; Bloomrosen, Efrat; Faraco, Juliette; Fang, Han; Mignot, Emmanuel

    2017-01-01

    Introduction A previous study has suggested that the Human Leukocyte Antigen (HLA) allele DQB1*06:02 affects hypoxic ventilatory response (HVR) but not hypercapnic ventilatory response (HCVR) in an Asian population. The current study evaluated the relationship in Caucasians and Asians. In addition we assessed whether gender or polymorphisms in genes participating in the control of breathing affect HVR and HCVR. Methods A re-breathing system was used to measure HVR and HCVR in 551 young adults (56.8% Caucasians, 30% Asians). HLA-DQB1*06:02 and tagged polymorphisms and coding variants in genes participating in breathing (PHOX2B, GPR4 and TASK2/KCNK5) were analyzed. The associations between HVR/HCVR and HLA-DQB1*06:02, genetic polymorphisms, and gender were evaluated using ANOVA or frequentist association testing with SNPTEST. Results HVR and gender are strongly correlated. HCVR and gender are not. Mean HVR in women was 0.276±0.168 (liter/minute/%SpO2) compared to 0.429±0.266 (liter/minute/%SpO2) in men, pHVR in men). Women had lower baseline minute ventilation (8.08±2.36 l/m vs. 10.00±3.43l/m, pHVR or HCVR. Genetic analysis revealed point wise, uncorrected significant associations between two TASK2/KCNK5 variants (rs2815118 and rs150380866) and HCVR. Conclusions This is the largest study to date reporting the relationship between gender and HVR/ HCVR and the first study assessing the association between genetic polymorphisms in humans and HVR/HCVR. The data suggest that gender has a large effect on hypoxic breathing response. PMID:28045995

  11. Analysis of Hypoxic and Hypercapnic Ventilatory Response in Healthy Volunteers.

    Science.gov (United States)

    Goldberg, Shmuel; Ollila, Hanna Maria; Lin, Ling; Sharifi, Husham; Rico, Tom; Andlauer, Olivier; Aran, Adi; Bloomrosen, Efrat; Faraco, Juliette; Fang, Han; Mignot, Emmanuel

    2017-01-01

    A previous study has suggested that the Human Leukocyte Antigen (HLA) allele DQB1*06:02 affects hypoxic ventilatory response (HVR) but not hypercapnic ventilatory response (HCVR) in an Asian population. The current study evaluated the relationship in Caucasians and Asians. In addition we assessed whether gender or polymorphisms in genes participating in the control of breathing affect HVR and HCVR. A re-breathing system was used to measure HVR and HCVR in 551 young adults (56.8% Caucasians, 30% Asians). HLA-DQB1*06:02 and tagged polymorphisms and coding variants in genes participating in breathing (PHOX2B, GPR4 and TASK2/KCNK5) were analyzed. The associations between HVR/HCVR and HLA-DQB1*06:02, genetic polymorphisms, and gender were evaluated using ANOVA or frequentist association testing with SNPTEST. HVR and gender are strongly correlated. HCVR and gender are not. Mean HVR in women was 0.276±0.168 (liter/minute/%SpO2) compared to 0.429±0.266 (liter/minute/%SpO2) in men, pHVR in men). Women had lower baseline minute ventilation (8.08±2.36 l/m vs. 10.00±3.43l/m, pHVR or HCVR. Genetic analysis revealed point wise, uncorrected significant associations between two TASK2/KCNK5 variants (rs2815118 and rs150380866) and HCVR. This is the largest study to date reporting the relationship between gender and HVR/ HCVR and the first study assessing the association between genetic polymorphisms in humans and HVR/HCVR. The data suggest that gender has a large effect on hypoxic breathing response.

  12. Hypoxic stress-induced changes in ribosomes of maize seedling roots

    International Nuclear Information System (INIS)

    Bailey-Serres, J.; Freeling, M.

    1990-01-01

    The hypoxic stress response of Zea mays L. seedling roots involves regulation of gene expression at transcriptional and posttranscriptional levels. We investigated the effect of hypoxia on the translational machinery of seedling roots. The levels of monoribosomes and ribosomal subunits increased dramatically within 1 hour of stress. Prolonged hypoxia resulted in continued accumulation of nontranslating ribosomes, as well as increased levels of small polyribosomes. The return of seedlings to normal aerobic conditions resulted in recovery of normal polyribosome levels. Comparison of ribosomal proteins from control and hypoxic roots revealed differences in quantity and electrophoretic mobility. In vivo labeling of roots with [ 35 S]methionine revealed variations in newly synthesized ribosomal proteins. In vivo labeling of roots with [ 32 P]orthophosphate revealed a major reduction in the phosphorylation of a 31 kilodalton ribosomal protein in hypoxic stressed roots. In vitro phosphorylation of ribosomal proteins by endogenous kinases was used to probe for differences in ribosome structure and composition. The patterns of in vitro kinased phosphoproteins of ribosomes from control and hypoxic roots were not identical. Variation in phosphoproteins of polyribosomes from control and hypoxic roots, as well as among polyribosomes from hypoxic roots were observed. These results indicate that modification of the translational machinery occurs in response to hypoxic stress

  13. Hypoxic Living and Exercise Training Alter Adipose Tissue Leptin/Leptin Receptor in Rats

    Directory of Open Access Journals (Sweden)

    Yingli Lu

    2016-11-01

    Full Text Available Background: Hypobaric hypoxia results in weight loss in obese individuals, and exercise training is advocated for the treatment of obesity and its related metabolic dysfunctions. The purpose of this study was to investigate the effects of hypoxic living and exercise training on obesity and adipose tissue leptin/leptin receptor in dietary-induced obese rats. Methods: One hundred and thirty high-fat diet fed Sprague-Dawley rats were assigned into one of the following groups (n=10 each: control, sedentary hypoxic living for 1 to 4 weeks (SH1, SH2, SH3, and SH4, living and exercise training in normoxic conditions for 1 to 4 weeks (TN1, TN2, TN3, and TN4, and living and exercise training in hypoxic conditions for 1 to 4 weeks (TN1, TN2, TN3, and TN4. Epididymal adipose tissue expression levels of leptin and leptin receptor were determined. Results: Compared to hypoxic living and living and exercise training in normoxic conditions, living and exercise training in hypoxic conditions for 3-4 weeks resulted in lower Lee index (P<0.05 to P<0.01, and higher expression of leptin and leptin receptor (P<0.05 to P<0.01 in adipose tissue. Conclusion: In a rodent model of altitude training, living and exercise training in hypoxic conditions resulted in greater alterations in obesity and adipose tissue leptin/leptin receptor than hypoxic living alone and living and exercise training in normoxic conditions.

  14. Potentially three distinct roles for hypoxic cell sensitizers in the clinic

    International Nuclear Information System (INIS)

    Chapman, J.D.; Raleigh, J.A.; Pedersen, J.E.; Ngan, J.; Shum, F.Y.

    1979-01-01

    Nitroaromatic drugs have been applied to radiation therapy on the basis of their effectiveness to enhance radiation damages selectively in hypoxic mammalian cells at nontoxic concentration. Such sensitizers could improve the rate of local tumor control by conventional radiotherapy in such cases that the resistance due to hypoxia in a limiting factor. The selective cytotoxicity of the drug to hypoxic cells is the second distinct action. A third potential role for nitroaromatic drugs could involve their use for the diagnosis of the number and location of hypoxic cells within tumors. The gain in therapeutic ratio by a factor from 5 to 10 is necessary before the full clinical impact of hypoxic cell radiosensitizers can be evaluated. The drugs selected for the use as clinical radiosensitizers were originally developed as the antibacterial agents with selective activity against anaerobes. The hypoxic cells in tumors are usually resistant to chemotherapy as well as resistant to radiation, and this specific drug action of sensitizers combined with that of an agent effective against oxygenated and cycling cells could possibly produce improved tumor cures. Electron-affinitive chemicals become selectively bound to the macromolecules of hypoxic mammalian cells by radiation-induced chemical reaction. This technique was used to identify by autoradiographic procedures the location of the radioactive nitrofurazone bound to hypoxic cells within multicellular spheroids. (Yamashita, S.)

  15. A scenario and forecast model for Gulf of Mexico hypoxic area and volume

    Science.gov (United States)

    Scavia, Donald; Evans, Mary Anne; Obenour, Daniel R.

    2013-01-01

    For almost three decades, the relative size of the hypoxic region on the Louisiana-Texas continental shelf has drawn scientific and policy attention. During that time, both simple and complex models have been used to explore hypoxia dynamics and to provide management guidance relating the size of the hypoxic zone to key drivers. Throughout much of that development, analyses had to accommodate an apparent change in hypoxic sensitivity to loads and often cull observations due to anomalous meteorological conditions. Here, we describe an adaptation of our earlier, simple biophysical model, calibrated to revised hypoxic area estimates and new hypoxic volume estimates through Bayesian estimation. This application eliminates the need to cull observations and provides revised hypoxic extent estimates with uncertainties, corresponding to different nutrient loading reduction scenarios. We compare guidance from this model application, suggesting an approximately 62% nutrient loading reduction is required to reduce Gulf hypoxia to the Action Plan goal of 5,000 km2, to that of previous applications. In addition, we describe for the first time, the corresponding response of hypoxic volume. We also analyze model results to test for increasing system sensitivity to hypoxia formation, but find no strong evidence of such change.

  16. Effect of Simulated Intermittent Altitude on the Metabolic and Hematologic Parameters in Streptozotocin Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    mehdi Faramoushi

    2016-04-01

    Full Text Available Background & objectives: Type II diabetes is a metabolic disorder accompanied with insulin resistance of the whole body cells and is considered be the fifth cause of death in the world. Adaptation to altitude can lead to tolerance to many diseases. Therefore, the aim of this study was to determine the effect of simulated intermittent altitude on the metabolic and hematologic parameters and liver function in streptozotocin induced diabetic rats. Methods: In the current experimental study, twenty four male Wistar rats weighing 220±20 gr were randomly divided into three groups; normal control group (NC, n=8, diabetic control group (D, n=8 received fat diet for 2 weeks then were injected with streptozotocin (37 mg/kg and diabetic+hypoxia group (D+H, n=8 including diabetic rat exposed to chronic intermittent hypoxia (PiO2≈106 mm Hg, simulated altitude≈3400 m, 14% oxygen for 8 weeks. Diabetic, hematologic and lipid parameters as well as ALT and AST activities were measured in peripheral blood. Results: Our findings showed that intermittent hypoxia significantly decreased serum total cholesterol, LDL ,VLDL and triglyceride in D+H group compared to D group (p<0.05. Serum levels of fasting blood glucose and homeostatic model assessment-insulin resistance HOMA-IR( index and ALT were decreased in D+H group vs. D group p<0.05. Also, hemoglubin and hematocrite level increased in D+H group in comparison to D group p<0.05. No significant difference was detected in red blood cell count in D+H vs. D group. Conclusion: Based on resultant data, it seems that intermittent exposure to hypoxia (simulated to chronic and intermittent lodgement in altitude can be used to control of type 2 diabetes by increasing hemoglobin, decreasing insulin resistance and improving liver function as well as lipid parameters.

  17. mtDNA as a Mediator for Expression of Hypoxia-Inducible Factor 1α and ROS in Hypoxic Neuroblastoma Cells.

    Science.gov (United States)

    Kuo, Chung-Wen; Tsai, Meng-Han; Lin, Tsu-Kung; Tiao, Mao-Meng; Wang, Pei-Wen; Chuang, Jiin-Haur; Chen, Shang-Der; Liou, Chia-Wei

    2017-06-07

    Mitochondria consume O₂ to produce ATP and are critical for adaption of hypoxia, but the role of mitochondria in HIF-1α pathway is as yet unclear. In this study, mitochondrial DNA (mtDNA) enriched (SK-N-AS) and depleted (ρ⁰) cells of neuroblastoma were cultured in a hypoxic chamber to simulate a hypoxic condition and then the major components involved in mitochondrial related pathways, hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) were measured. The results showed that hypoxia-stimulated exposure elevated expression of HIF-1α, which was additionally influenced by level of generated ROS within the cytosol. Moreover, elevation of HIF-1α also resulted in increases of lactate dehydrogenase A (LDH-A) and pyruvate dehydrogenase kinase 1 (PDK1) in both hypoxic cells. The expression of mitochondrial biogenesis related proteins and metabolic components were noted to increase significantly in hypoxic SK-N-AS cells, indicating that mtDNA was involved in mitochondrial retrograde signaling and metabolic pathways. An analysis of dynamic proteins found elevated levels of HIF-1α causing an increased expression of dynamin-related protein 1 (DRP1) during hypoxia; further, the existence of mtDNA also resulted in higher expression of DRP1 during hypoxia. By using siRNA of HIF-1α or DRP1, expression of DRP1 decreased after suppression of HIF-1α; moreover, the expression of HIF-1α was also affected by the suppression of DRP1. In this study, we demonstrated that mtDNA is a mediator of HIF-1α in eliciting metabolic reprogramming, and mitochondrial biogenesis. Identification of a mutual relationship between HIF-1α and DRP1 may be a critical tool in the future development of clinical applications.

  18. The effect of intermittent dosing of Nicotiana glauca on teratogenesis in goats.

    Science.gov (United States)

    Welch, K D; Panter, K E; Lee, S T; Gardner, D R

    2015-01-01

    Sustained inhibition of fetal movement in livestock species, induced by several poisonous plants, can result in numerous skeletal-contracture malformations. Lupines are responsible for a condition in cattle referred to as "crooked calf syndrome" that occurs when pregnant cattle graze teratogenic lupines. Similar malformations are also seen in animals poisoned by Conium maculatum (coniine) and Nicotiana glauca (anabasine). A proposed management strategy to limit these types of birth defects includes utilizing an intermittent grazing schedule to allow short durations of grazing lupine-infested areas interrupted by movement to a lupine-free pasture. The objective of this study was to use a goat model to determine if an intermittent schedule of five continuous days on treatment followed by two days off treatment would be sufficient to decrease, or prevent, the incidence of anabasine-induced malformations. The data from this study suggest that, for N. glauca in goats, the intermittent grazing program of five days exposure with two days of non-exposure is insufficient to prevent significant skeletal malformations from occurring. However, this study did demonstrate an inverse relationship between the amount of serum anabasine in the dam and the extent of fetal movement. Published by Elsevier Ltd.

  19. A neonatal mouse model of intermittent hypoxia associated with features of apnea in premature infants.

    Science.gov (United States)

    Cai, Jun; Tuong, Chi Minh; Gozal, David

    2011-09-15

    A neonatal mouse model of intermittent hypoxia (IH) simulating the recurring hypoxia/reoxygenation episodes of apnea of prematurity (AOP) was developed. C57BL/6 P2 pups were culled for exposure to either intermittent hypoxia or intermittent air as control. The IH paradigms consisted of alternation cycles of 20.9% O2 and either 8.0% or 5.7% O2 every 120 or 140s for 6h a day during daylight hours from day 2 to day 10 postnatally, i.e., roughly equivalent to human brain development in the perinatal period. IH exposures elicited modest to severe decrease in oxygen saturation along with bradycardia in neonatal mice, which were severity-dependent. Hypomyelination in both central and peripheral nervous systems was observed despite the absence of visible growth retardation. The neonatal mouse model of IH in this study partially fulfills the current diagnostic criteria with features of AOP, and provides opportunities to reproduce in rodents some of the pathophysiological changes associated with this disorder, such as alterations in myelination. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Research Report: Intermittent hypobaric hypoxia and hyperbaric oxygen on GAP-43 in the rat carotid body.

    Science.gov (United States)

    Peng, Zhengwu; Fan, Juan; Liu, Ling; Kuang, Fang; Xue, Fen; Wang, Bairen

    2015-01-01

    Adaptive changes in the carotid body (CB) including the expression of the growth-associated protein-43 (GAP-43) have been studied in response to low, but not high, oxygen exposure. Expression of GAP-43 in the CB of rats under different atmospheric pressures and oxygen partial pressure (PO2) conditions was investigated. Mature male Sprague-Dawley rats were exposed to intermittent hypobaric hypoxia (IHH, 0, 1, 2 and 3 weeks), intermittent hyperbaric oxygen (IHBO2, 0, 1, 5 and 10 days, sacrificed six hours or 24 hours after the last HBO2 exposure), and intermittent hyperbaric normoxia (IHN, same treatment pattern as IHBO2). GAP-43 was highly expressed (mainly in type I cells) in the CB of normal rats. IHH u-regulated GAP-43 expression in the CB with significant differences (immunohistochemical staining [IHC]: F(3,15)=40.64, P GAP-43 expression in the CB was inhibited by IHBO2 (controls vs. IHBO2 groups, IHC: F(6,30) = 15.85, P GAP-43 expression were found for IHN. These findings indicated that different PO2 conditions, but not air pressures, played an important role in the plasticity of the CB, and that GAP-43 might be a viable factor for the plasticity of the CB.

  1. Prophylactic Edaravone Prevents Transient Hypoxic-Ischemic Brain Injury: Implications for Perioperative Neuroprotection.

    Science.gov (United States)

    Sun, Yu-Yo; Li, Yikun; Wali, Bushra; Li, Yuancheng; Lee, Jolly; Heinmiller, Andrew; Abe, Koji; Stein, Donald G; Mao, Hui; Sayeed, Iqbal; Kuan, Chia-Yi

    2015-07-01

    Hypoperfusion-induced thrombosis is an important mechanism for postsurgery stroke and cognitive decline, but there are no perioperative neuroprotectants to date. This study investigated whether prophylactic application of Edaravone, a free radical scavenger already used in treating ischemic stroke in Japan, can prevent infarct and cognitive deficits in a murine model of transient cerebral hypoxia-ischemia. Adult male C57BL/6 mice were subjected to transient hypoxic-ischemic (tHI) insult that consists of 30-minute occlusion of the unilateral common carotid artery and exposure to 7.5% oxygen. Edaravone or saline was prophylactically applied to compare their effects on cortical oxygen saturation, blood flow, coagulation, oxidative stress, metabolites, and learning-memory using methods that include photoacoustic imaging, laser speckle contrast imaging, solid-state NMR, and Morris water maze. The effects on infarct size by Edaravone application at different time points after tHI were also compared. Prophylactic administration of Edaravone (4.5 mg/kg×2, IP, 1 hour before and 1 hour after tHI) improved vascular reperfusion, oxygen saturation, and the maintenance of brain metabolites, reducing oxidative stress, thrombosis, white-matter injury, and learning impairment after tHI insult. Delayed Edaravone treatment after 3 h post-tHI became unable to reduce infarct size. Acute application of Edaravone may be a useful strategy to prevent postsurgery stroke and cognitive impairment, especially in patients with severe carotid stenosis. © 2015 American Heart Association, Inc.

  2. Nitric oxide (NO) in normal and hypoxic vascular regulation of the spiny dogfish, Squalus acanthias.

    Science.gov (United States)

    Swenson, Kai E; Eveland, Randy L; Gladwin, Mark T; Swenson, Erik R

    2005-02-01

    Nitric oxide (NO) is a potent vasodilator in terrestrial vertebrates, but whether vascular endothelial-derived NO plays a role in vascular regulation in fish remains controversial. To explore this issue, a study was made of spiny dogfish sharks (Squalus acanthias) in normoxia and acute hypoxia (60 min exposure to seawater equilibrated with 3% oxygen) with various agents known to alter NO metabolism or availability. In normoxia, nitroprusside (a NO donor) reduced blood pressure by 20%, establishing that vascular smooth muscle responds to NO. L-arginine, the substrate for NO synthase, had no hemodynamic effect. Acetylcholine, which stimulates endothelial NO and prostaglandin production in mammals, reduced blood pressure, but also caused marked bradycardia. L-NAME, an inhibitor of all NO synthases, caused a small 10% rise in blood pressure, but cell-free hemoglobin (a potent NO scavenger and hypertensive agent in mammals) had no effect. Acute hypoxia caused a 15% fall in blood pressure, which was blocked by L-NAME and cell-free hemoglobin. Serum nitrite, a marker of NO production, rose with hypoxia, but not with L-NAME. Results suggest that NO is not an endothelial-derived vasodilator in the normoxic elasmobranch. The hypertensive effect of L-NAME may represent inhibition of NO production in the CNS and nerves regulating blood pressure. In acute hypoxia, there is a rapid up-regulation of vascular NO production that appears to be responsible for hypoxic vasodilation.

  3. Relationship between 31P nuclear magnetic resonance spectra and pulmonary vasomotor tone in hypoxic pig lobes

    International Nuclear Information System (INIS)

    Buescher, P.; Pillain, R.; Pearse, D.; Eichhorn, G.; Sylvester, J.

    1986-01-01

    To investigate the relationship between lung tissue energy state and vasomotor tone, the authors measured 31 P NMR spectra during repeated exposures to hypoxia in 5 isolated degassed left lower lobes perfused with blood at a constant flow (500ml/min) and left atrial pressure ( 2 tension (PpO 2 ) was changed by varying the gas mixtures (40, 7, 0% O 2 ) flowing through a bubble oxygenator in the perfusion circuit. 31 P spectra obtained after stabilization of pulmonary artery pressure (Ppa) at each PpO 2 revealed peaks for ATP, inorganic phosphate (Pi) phosphomono and diesters (PME and PDE). During 7% O 2 , Ppa and ATP increased but Pi did not change suggesting that lung tissue energy state improved during hypoxic vasoconstriction. During 0% O 2 , there was a reversible deterioration of energy state (high Pi, low ATP). Thus, it appears that lung tissue energy state and vasomotor tone were related, but the precise nature of the relationship remains to be determined

  4. Sex-related differences in effects of progesterone following neonatal hypoxic brain injury.

    Science.gov (United States)

    Peterson, Bethany L; Won, Soonmi; Geddes, Rastafa I; Sayeed, Iqbal; Stein, Donald G

    2015-06-01

    There is no satisfactory therapeutic intervention for neonatal hypoxic-ischemic (HI) encephalopathy. Progesterone is known to be effective in treating traumatic brain injury in adult animals but its effects in neonatal brains have not been reported. Brain injuries were induced by a unilateral common carotid artery ligation plus hypoxia exposure. Progesterone was administered immediately after hypoxia and daily for 5 days at 8 mg/kg, followed by a tapered dose for two days. At six weeks post-injury, lesion size and inflammatory factors were evaluated. Progesterone-treated, HI-injured male animals, but not females, showed significant long-term tissue protection compared to vehicle, suggesting an important sex difference in neuroprotection. Progesterone-treated, HI-injured male rats had fewer activated microglia in the cortex and hippocampus compared to controls. The rats were tested for neurological reflexes, motor asymmetry, and cognitive performance at multiple time points. The injured animals exhibited few detectable motor deficits, suggesting a high level of age- and injury-related neuroplasticity. There were substantial sex differences on several behavioral tests, indicating that immature males and females should be analyzed separately. Progesterone-treated animals showed modest beneficial effects in both sexes compared to vehicle-treated injured animals. Sham animals given progesterone did not behave differently from vehicle-treated sham animals on any measures. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Cell-cycle distributions and radiation responses of Chinese hamster cells cultured continuously under hypoxic conditions

    International Nuclear Information System (INIS)

    Tokita, N.; Carpenter, S.G.; Raju, M.R.

    1984-01-01

    Cell-cycle distributions were measured by flow cytometry for Chinese hamster (CHO) cells cultured continuously under hypoxic conditions. DNA histograms showed an accumulation of cells in the early S phase followed by a traverse delay through the S phase, and a G 2 block. During hypoxic culturing, cell viability decreased rapidly to less than 0.1% at 120 h. Radiation responses for cells cultured under these conditions showed an extreme radioresistance at 72 h. Results suggest that hypoxia induces a condition similar to cell synchrony which itself changes the radioresistance of hypoxic cells. (author)

  6. Involvement of SIRT1 in hypoxic down-regulation of c-Myc and β-catenin and hypoxic preconditioning effect of polyphenols

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Kyung-Soo [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Park, Jun-Ik [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Kim, Mi-Ju; Kim, Hak-Bong; Lee, Jae-Won [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Dao, Trong Tuan; Oh, Won Keun [BK21 Project Team, College of Pharmacy, Chosun University, Gwangju (Korea, Republic of); Kang, Chi-Dug, E-mail: kcdshbw@pusan.ac.kr [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Kim, Sun-Hee, E-mail: ksh7738@pusan.ac.kr [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of)

    2012-03-01

    SIRT1 has been found to function as a Class III deacetylase that affects the acetylation status of histones and other important cellular nonhistone proteins involved in various cellular pathways including stress responses and apoptosis. In this study, we investigated the role of SIRT1 signaling in the hypoxic down-regulations of c-Myc and β-catenin and hypoxic preconditioning effect of the red wine polyphenols such as piceatannol, myricetin, quercetin and resveratrol. We found that the expression of SIRT1 was significantly increased in hypoxia-exposed or hypoxic preconditioned HepG2 cells, which was closely associated with the up-regulation of HIF-1α and down-regulation of c-Myc and β-catenin expression via deacetylation of these proteins. In addition, blockade of SIRT1 activation using siRNA or amurensin G, a new potent SIRT1 inhibitor, abolished hypoxia-induced HIF-1α expression but increased c-Myc and β-catenin expression. SIRT1 was also found to stabilize HIF-1α protein and destabilize c-Myc, β-catenin and PHD2 under hypoxia. We also found that myricetin, quercetin, piceatannol and resveratrol up-regulated HIF-1α and down-regulated c-Myc, PHD2 and β-catenin expressions via SIRT1 activation, in a manner that mimics hypoxic preconditioning. This study provides new insights of the molecular mechanisms of hypoxic preconditioning and suggests that polyphenolic SIRT1 activators could be used to mimic hypoxic/ischemic preconditioning. -- Graphical abstract: Polyphenols mimicked hypoxic preconditioning by up-regulating HIF-1α and SIRT1 and down-regulating c-Myc, PHD2, and β-catenin. HepG2 cells were pretreated with the indicated doses of myricetin (MYR; A), quercetin (QUR; B), or piceatannol (PIC; C) for 4 h and then exposed to hypoxia for 4 h. Levels of HIF-1α, SIRT1, c-Myc, β-catenin, and PHD2 were determined by western blot analysis. The data are representative of three individual experiments. Highlights: ► SIRT1 expression is increased in hypoxia

  7. Involvement of SIRT1 in hypoxic down-regulation of c-Myc and β-catenin and hypoxic preconditioning effect of polyphenols

    International Nuclear Information System (INIS)

    Hong, Kyung-Soo; Park, Jun-Ik; Kim, Mi-Ju; Kim, Hak-Bong; Lee, Jae-Won; Dao, Trong Tuan; Oh, Won Keun; Kang, Chi-Dug; Kim, Sun-Hee

    2012-01-01

    SIRT1 has been found to function as a Class III deacetylase that affects the acetylation status of histones and other important cellular nonhistone proteins involved in various cellular pathways including stress responses and apoptosis. In this study, we investigated the role of SIRT1 signaling in the hypoxic down-regulations of c-Myc and β-catenin and hypoxic preconditioning effect of the red wine polyphenols such as piceatannol, myricetin, quercetin and resveratrol. We found that the expression of SIRT1 was significantly increased in hypoxia-exposed or hypoxic preconditioned HepG2 cells, which was closely associated with the up-regulation of HIF-1α and down-regulation of c-Myc and β-catenin expression via deacetylation of these proteins. In addition, blockade of SIRT1 activation using siRNA or amurensin G, a new potent SIRT1 inhibitor, abolished hypoxia-induced HIF-1α expression but increased c-Myc and β-catenin expression. SIRT1 was also found to stabilize HIF-1α protein and destabilize c-Myc, β-catenin and PHD2 under hypoxia. We also found that myricetin, quercetin, piceatannol and resveratrol up-regulated HIF-1α and down-regulated c-Myc, PHD2 and β-catenin expressions via SIRT1 activation, in a manner that mimics hypoxic preconditioning. This study provides new insights of the molecular mechanisms of hypoxic preconditioning and suggests that polyphenolic SIRT1 activators could be used to mimic hypoxic/ischemic preconditioning. -- Graphical abstract: Polyphenols mimicked hypoxic preconditioning by up-regulating HIF-1α and SIRT1 and down-regulating c-Myc, PHD2, and β-catenin. HepG2 cells were pretreated with the indicated doses of myricetin (MYR; A), quercetin (QUR; B), or piceatannol (PIC; C) for 4 h and then exposed to hypoxia for 4 h. Levels of HIF-1α, SIRT1, c-Myc, β-catenin, and PHD2 were determined by western blot analysis. The data are representative of three individual experiments. Highlights: ► SIRT1 expression is increased in hypoxia

  8. Intermittent hypercapnia-induced phrenic long-term depression is revealed after serotonin receptor blockade with methysergide in anaesthetized rats.

    Science.gov (United States)

    Valic, Maja; Pecotic, Renata; Pavlinac Dodig, Ivana; Valic, Zoran; Stipica, Ivona; Dogas, Zoran

    2016-02-01

    What is the central question of this study? Intermittent hypercapnia is a concomitant feature of breathing disorders. Hypercapnic stimuli evoke a form of respiratory plasticity known as phrenic long-term depression in experimental animals. This study was performed to investigate the putative role of serotonin receptors in the initiation of phrenic long-term depression in anaesthetized rats. What is the main finding and its importance? Phrenic nerve long-term depression was revealed in animals pretreated with the serotonin broad-spectrum antagonist, methysergide. This study highlights that serotonin receptors modulate respiratory plasticity evoked by acute intermittent hypercapnia in anaesthetized rats. This study was performed to test the hypothesis that intermittent hypercapnia can evoke a form of respiratory plasticity known as long-term depression of the phrenic nerve (pLTD) and that 5-HT receptors play a role in the initiation of pLTD. Adult male urethane-anaesthetized, vagotomized, paralysed, mechanically ventilated Sprague-Dawley rats were exposed to an acute intermittent hypercapnia protocol. One group received i.v. injection of the non-selective 5-HT receptor antagonist methysergide and another group received i.v. injection of the selective 5-HT1A receptor antagonist WAY-100635 20 min before exposure to intermittent hypercapnia. A control group received i.v. injection of saline. Peak phrenic nerve activity and respiratory rhythm parameters were analysed at baseline (T0), during each of five hypercapnic episodes, and 15, 30 and 60 min (T60) after the last hypercapnia. Intravenous injection of methysergide before exposure to acute intermittent hypercapnia induced development of amplitude pLTD at T60 (decreased by 46.1 ± 6.9%, P = 0.003). Conversely, in control and WAY-100635-pretreated animals, exposure to acute intermittent hypercapnia did not evoke amplitude pLTD. However, a long-term decrease in phrenic nerve frequency was evoked both in control (42 ± 4

  9. Hovering and intermittent flight in birds

    International Nuclear Information System (INIS)

    Tobalske, Bret W

    2010-01-01

    Two styles of bird locomotion, hovering and intermittent flight, have great potential to inform future development of autonomous flying vehicles. Hummingbirds are the smallest flying vertebrates, and they are the only birds that can sustain hovering. Their ability to hover is due to their small size, high wingbeat frequency, relatively large margin of mass-specific power available for flight and a suite of anatomical features that include proportionally massive major flight muscles (pectoralis and supracoracoideus) and wing anatomy that enables them to leave their wings extended yet turned over (supinated) during upstroke so that they can generate lift to support their weight. Hummingbirds generate three times more lift during downstroke compared with upstroke, with the disparity due to wing twist during upstroke. Much like insects, hummingbirds exploit unsteady mechanisms during hovering including delayed stall during wing translation that is manifest as a leading-edge vortex (LEV) on the wing and rotational circulation at the end of each half stroke. Intermittent flight is common in small- and medium-sized birds and consists of pauses during which the wings are flexed (bound) or extended (glide). Flap-bounding appears to be an energy-saving style when flying relatively fast, with the production of lift by the body and tail critical to this saving. Flap-gliding is thought to be less costly than continuous flapping during flight at most speeds. Some species are known to shift from flap-gliding at slow speeds to flap-bounding at fast speeds, but there is an upper size limit for the ability to bound (∼0.3 kg) and small birds with rounded wings do not use intermittent glides.

  10. Hovering and intermittent flight in birds

    Energy Technology Data Exchange (ETDEWEB)

    Tobalske, Bret W, E-mail: bret.tobalske@mso.umt.ed [Field Research Station at Fort Missoula, Division of Biological Sciences, University of Montana, Missoula, MT 59812 (United States)

    2010-12-15

    Two styles of bird locomotion, hovering and intermittent flight, have great potential to inform future development of autonomous flying vehicles. Hummingbirds are the smallest flying vertebrates, and they are the only birds that can sustain hovering. Their ability to hover is due to their small size, high wingbeat frequency, relatively large margin of mass-specific power available for flight and a suite of anatomical features that include proportionally massive major flight muscles (pectoralis and supracoracoideus) and wing anatomy that enables them to leave their wings extended yet turned over (supinated) during upstroke so that they can generate lift to support their weight. Hummingbirds generate three times more lift during downstroke compared with upstroke, with the disparity due to wing twist during upstroke. Much like insects, hummingbirds exploit unsteady mechanisms during hovering including delayed stall during wing translation that is manifest as a leading-edge vortex (LEV) on the wing and rotational circulation at the end of each half stroke. Intermittent flight is common in small- and medium-sized birds and consists of pauses during which the wings are flexed (bound) or extended (glide). Flap-bounding appears to be an energy-saving style when flying relatively fast, with the production of lift by the body and tail critical to this saving. Flap-gliding is thought to be less costly than continuous flapping during flight at most speeds. Some species are known to shift from flap-gliding at slow speeds to flap-bounding at fast speeds, but there is an upper size limit for the ability to bound ({approx}0.3 kg) and small birds with rounded wings do not use intermittent glides.

  11. Intermittent whole-body cold immersion induces similar thermal stress but different motor and cognitive responses between males and females.

    Science.gov (United States)

    Solianik, Rima; Skurvydas, Albertas; Mickevičienė, Dalia; Brazaitis, Marius

    2014-10-01

    The main aim of this study was to compare the thermal responses and the responses of cognitive and motor functions to intermittent cold stress between males and females. The intermittent cold stress continued until rectal temperature (TRE) reached 35.5°C or for a maximum of 170 min. Thermal response and motor and cognitive performance were monitored. During intermittent cold stress, body temperature variables decreased in all subjects (P cold strain index did not differ between sexes. Maximal voluntary contraction (MVC) decreased after intermittent cold exposure only in males (P cold stress on electrically evoked muscle properties, spinal (H-reflex), and supraspinal (V-waves) reflexes did not differ between sexes. Intermittent cold-induced cognitive perturbation of attention and memory task performance was greater in males (P whole-body cold immersion. Although no sex-specific differences were observed in muscle EMG activity, involuntary muscle properties, spinal and supraspinal reflexes, some of the sex differences observed (e.g., lower isometric MVC and greater cognitive perturbation in males) support the view of sex-specific physiological responses to core temperature decrease. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Renewable energies: the cost of intermittency

    International Nuclear Information System (INIS)

    Crassous, Renaud; Roques, Fabien

    2013-01-01

    The authors indicate the different adaptations which will be required for the electric system to cope with the intermittency of solar and wind energy production, and propose an approximate assessment of the associated costs. Different types of adaptation are addressed: secure production in case of absence of wind or sun (electricity imports, construction of additional power stations), use of more flexible production means (gas turbines), grid extensions (connection to offshore production sites, routing of production one part of the country to the other). They think that beyond a 20 per cent share for renewable energies, these costs could rapidly increase

  13. Spatio-temporal intermittency on the sandpile

    International Nuclear Information System (INIS)

    Erzan, A.; Sinha, S.

    1990-08-01

    The self-organized critical state exhibited by a sandpile model is shown to correspond to motion on an attractor characterized by an invariant distribution of the height variable. The largest Lyapunov exponent is equal to zero. The model nonetheless displays intermittent chaos, with a multifractal distribution of local expansion coefficients in history space. Laminar spatio-temporal regions are interrupted by chaotic bursts caused by avalanches. We introduce the concept of local histories in configuration space and show that their expansion parameters also exhibit a multifractal distribution in time and space. (author). 22 refs, 5 figs

  14. Intermittent claudication in a professional rugby player.

    Science.gov (United States)

    Bray, A E; Lewis, W A

    1992-04-01

    Intermittent claudication in a professional rugby player is described. The typical features of a delayed and difficult diagnosis of an external iliac artery stenosis were found. The noninvasive diagnostic protocol used to investigate this young patient with a minimal arterial lesion enabled accurate localization and angioplasty to be performed at the same time as diagnostic angiography. The patient was symptom free with normal arterial pressures on follow-up. It is suggested that appropriate noninvasive investigations should be performed before angiography in young people with minimal lesions.

  15. A stochastic model for intermittent search strategies

    International Nuclear Information System (INIS)

    Benichou, O; Coppey, M; Moreau, M; Suet, P H; Voituriez, R

    2005-01-01

    It is often necessary, in scientific or everyday life problems, to find a randomly hidden target. What is then the optimal strategy to reach it as rapidly as possible? In this article, we develop a stochastic theory for intermittent search behaviours, which are often observed: the searcher alternates phases of intensive search and slow motion with fast displacements. The first results of this theory have already been announced recently. Here we provide a detailed presentation of the theory, as well as the full derivation of the results. Furthermore, we explicitly discuss the minimization of the time needed to find the target

  16. Intermittent oral iron supplementation during pregnancy (Review)

    Science.gov (United States)

    Peña-Rosas, Juan Pablo; De-Regil, Luz Maria; Dowswell, Therese; Viteri, Fernando E

    2014-01-01

    Background Anaemia is a frequent condition during pregnancy, particularly among women from developing countries who have insufficient iron intake to meet increased iron needs of both the mother and the fetus. Traditionally, gestational anaemia has been prevented with the provision of daily iron supplements throughout pregnancy, but adherence to this regimen due to side effects, interrupted supply of the supplements, and concerns about safety among women with an adequate iron intake, have limited the use of this intervention. Intermittent (i.e. one, two or three times a week on non-consecutive days) supplementation with iron alone or in combination with folic acid or other vitamins and minerals has recently been proposed as an alternative to daily supplementation. Objectives To assess the benefits and harms of intermittent supplementation with iron alone or in combination with folic acid or other vitamins and minerals to pregnant women on neonatal and pregnancy outcomes. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (23 March 2012). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) for ongoing studies and contacted relevant organisations for the identification of ongoing and unpublished studies (23 March 2012). Selection criteria Randomised or quasi-randomised trials. Data collection and analysis We assessed the methodological quality of trials using standard Cochrane criteria. Two review authors independently assessed trial eligibility, extracted data and conducted checks for accuracy. Main results This review includes 21 trials from 13 different countries, but only 18 trials (with 4072 women) reported on our outcomes of interest and contributed data to the review. All of these studies compared daily versus intermittent iron supplementation. Three studies provided iron alone, 12 iron+folic acid and three more iron plus multiple vitamins and minerals. Their methodological quality was mixed

  17. Combined effects of water stress and pollution on macroinvertebrate and fish assemblages in a Mediterranean intermittent river.

    Science.gov (United States)

    Kalogianni, Eleni; Vourka, Aikaterini; Karaouzas, Ioannis; Vardakas, Leonidas; Laschou, Sofia; Skoulikidis, Nikolaos Th

    2017-12-15

    Water stress is a key stressor in Mediterranean intermittent rivers exacerbating the negative effects of other stressors, such as pollutants, with multiple effects on different river biota. The current study aimed to determine the response of macroinvertebrate and fish assemblages to instream habitat and water chemistry, at the microhabitat scale and at different levels of water stress and pollution, in an intermittent Mediterranean river. Sampling was conducted at high and low summer discharge, at two consecutive years, and included four reaches that were targeted for their different levels of water stress and pollution. Overall, the macroinvertebrate fauna of Evrotas River indicated high resilience to intermittency, however, variation in community structure and composition occurred under acute water stress, due to habitat alteration and change in water physico-chemistry, i.e. water temperature increase. The combined effects of pollution and high water stress had, however, pronounced effects on species richness, abundance and community structure in the pollution impacted reach, where pollution sensitive taxa were almost extirpated. Fish response to drought, in reaches free of pollution, consisted of an increase in the abundance of the two small limnophilic species, coupled with their shift to faster flowing riffle habitats, and a reduction in the abundance of the larger, rheophilic species. In the pollution impacted reach, however, the combination of pollution and high water stress led to hypoxic conditions assumed to be the leading cause of the almost complete elimination of the fish assemblage. In contrast, the perennial Evrotas reaches with relatively stable physicochemical conditions, though affected hydrologically by drought, appear to function as refugia for fish during high water stress. When comparing the response of the two biotic groups to combined acute water stress and pollution, it is evident that macroinvertebrates were negatively impacted, but fish

  18. Intermittent fasting and cardiovascular disease: current evidence and unresolved questions.

    Science.gov (United States)

    Tinsley, Grant M; Horne, Benjamin D

    2018-01-01

    Intermittent fasting has produced a variety of beneficial health effects in animal models, although high-quality research in humans has been limited. This special report examines current evidences for intermittent fasting in humans, discusses issues that require further examination, and recommends new research that can improve the knowledge base in this emerging research area. While potentially useful for health improvement, intermittent fasting requires further study prior to widespread implementation for health purposes. Randomized, longer-term studies are needed to determine whether using intermittent fasting as a lifestyle rather than a diet is feasible and beneficial for the health of some members of the human population.

  19. Atomistic Model of Fluorescence Intermittency of Colloidal Quantum Dots

    KAUST Repository

    Voznyy, O.; Sargent, E. H.

    2014-01-01

    with foreign cations can stabilize the vacancies, inhibiting intermittency and improving quantum yield, providing an explanation of recent experimental observations. © 2014 American Physical Society.

  20. Randomized, controlled trial comparing synchronized intermittent mandatory ventilation and synchronized intermittent mandatory ventilation plus pressure support in preterm infants.

    Science.gov (United States)

    Reyes, Zenaida C; Claure, Nelson; Tauscher, Markus K; D'Ugard, Carmen; Vanbuskirk, Silvia; Bancalari, Eduardo

    2006-10-01

    Prolonged mechanical ventilation is associated with lung injury in preterm infants. In these infants, weaning from synchronized intermittent mandatory ventilation may be delayed by their inability to cope with increased respiratory loads. The addition of pressure support to synchronized intermittent mandatory ventilation can offset these loads and may facilitate weaning. The purpose of this work was to compare synchronized intermittent mandatory ventilation and synchronized intermittent mandatory ventilation plus pressure support in weaning from mechanical ventilation and the duration of supplemental oxygen dependency in preterm infants with respiratory failure. Preterm infants weighing 500 to 1000 g at birth who required mechanical ventilation during the first postnatal week were randomly assigned to synchronized intermittent mandatory ventilation or synchronized intermittent mandatory ventilation plus pressure support. In both groups, weaning followed a set protocol during the first 28 days. Outcomes were assessed during the first 28 days and until discharge or death. There were 107 infants enrolled (53 synchronized intermittent mandatory ventilation plus pressure support and 54 synchronized intermittent mandatory ventilation). Demographic and perinatal data, mortality, and morbidity did not differ between groups. During the first 28 days, infants in the synchronized intermittent mandatory ventilation plus pressure support group reached minimal ventilator settings and were extubated earlier than infants in the synchronized intermittent mandatory ventilation group. Total duration of mechanical ventilation, duration of oxygen dependency, and oxygen need at 36 weeks' postmenstrual age alone or combined with death did not differ between groups. However, infants in synchronized intermittent mandatory ventilation plus pressure support within the 700- to 1000-g birth weight strata had a shorter oxygen dependency. The results of this study suggest that the addition of

  1. Radiosensitization effect of CMNa on hypoxic pancreatic cancer cell in vitro

    International Nuclear Information System (INIS)

    Yin Lijie; Zhang Li; Ding Tiangui; Peng Zhaoxiang; Yu Huan; Gao Yuwei

    2006-01-01

    Objective: To investigate the effects of glycodidazolum natrium (CMNa) on pancreatic cancer cells under hypoxic condition. Methods: The human pancreatic cancer Panc-1 cells were exposed to a single fraction of high-dose γ-ray radiation either with CMNa or under hypoxic condition. The percentage of dead cells was detected with a multiwell plated reader, and fluorescence intensities of propidium iodide were measured before and after digitonin treatment. The sensitizing effect of CMNa on cell killing induced by high-dose irradiation was evaluated by time and concentration dependence. The selective radiosensitive effect of CMNa on hypoxia was evaluated by flow cytometry. Results: The death rate of pancreatic cancer Panc-1 cells paralleled with the increasing concentration of CMNa under hypoxic condition after 30 gray irradiation. The selective radiosensitive effect of CMNa on hypoxia was time-dependent. Conclusions: CMNa can enhance the radiosensitivity of pancreatic cancer Pane-1 cells under hypoxic condition with high-dose irradiation. (authors)

  2. Use of perampanel in one case of super-refractory hypoxic myoclonic status: Case report

    Directory of Open Access Journals (Sweden)

    Estevo Santamarina

    2015-01-01

    Conclusion: This case shows the potential utility of PER as a therapeutic option in super-refractory hypoxic status and even its potential use before other aggressive alternatives considering their greater morbidity.

  3. Effect of Neonatal Seizures on Cognitive Outcome of Hypoxic-Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-10-01

    Full Text Available The independent effect of clinical neonatal seizures and their treatment on longterm neurodevelopmental outcome in 77 term newborns at risk for hypoxic-ischemic encephalopathy (HIE was determined in a study at University of California San Francisco.

  4. Marine bacterioplankton community turnover within seasonally hypoxic waters of a subtropical sound

    DEFF Research Database (Denmark)

    Parsons, Rachel J.; Nelson, Craig E.; Carlson, Craig A.

    2015-01-01

    Understanding bacterioplankton community dynamics in coastal hypoxic environments is relevant to global biogeochemistry because coastal hypoxia is increasing worldwide. The temporal dynamics of bacterioplankton communities were analysed throughout the illuminated water column of Devil's Hole...

  5. Chaos as an intermittently forced linear system.

    Science.gov (United States)

    Brunton, Steven L; Brunton, Bingni W; Proctor, Joshua L; Kaiser, Eurika; Kutz, J Nathan

    2017-05-30

    Understanding the interplay of order and disorder in chaos is a central challenge in modern quantitative science. Approximate linear representations of nonlinear dynamics have long been sought, driving considerable interest in Koopman theory. We present a universal, data-driven decomposition of chaos as an intermittently forced linear system. This work combines delay embedding and Koopman theory to decompose chaotic dynamics into a linear model in the leading delay coordinates with forcing by low-energy delay coordinates; this is called the Hankel alternative view of Koopman (HAVOK) analysis. This analysis is applied to the Lorenz system and real-world examples including Earth's magnetic field reversal and measles outbreaks. In each case, forcing statistics are non-Gaussian, with long tails corresponding to rare intermittent forcing that precedes switching and bursting phenomena. The forcing activity demarcates coherent phase space regions where the dynamics are approximately linear from those that are strongly nonlinear.The huge amount of data generated in fields like neuroscience or finance calls for effective strategies that mine data to reveal underlying dynamics. Here Brunton et al.develop a data-driven technique to analyze chaotic systems and predict their dynamics in terms of a forced linear model.

  6. Transient analysis of intermittent multijet sprays

    Energy Technology Data Exchange (ETDEWEB)

    Panao, Miguel R.O.; Moreira, Antonio Luis N. [Universidade Tecnica de Lisboa, IN, Center for Innovation, Technology and Policy Research, Instituto Superior Tecnico, Lisboa (Portugal); Durao, Diamantino G. [Universidade Lusiada, Lisboa (Portugal)

    2012-07-15

    This paper analyzes the transient characteristics of intermittent sprays produced by the single-point impact of multiple cylindrical jets. The aim is to perform a transient analysis of the intermittent atomization process to study the effect of varying the number of impinging jets in the hydrodynamic mechanisms of droplet formation. The results evidence that hydrodynamic mechanisms underlying the physics of ligament fragmentation in 2-impinging jets sprays also apply to sprays produced with more than 2 jets during the main period of injection. Ligaments detaching from the liquid sheet, as well as from its bounding rim, have been identified and associated with distinct droplet clusters, which become more evident as the number of impinging jets increases. Droplets produced by detached ligaments constitute the main spray, and their axial velocity becomes more uniformly distributed with 4-impinging jets because of a delayed ligament fragmentation. Multijet spray dispersion patterns are geometric depending on the number of impinging jets. Finally, an analysis on the Weber number of droplets suggests that multijet sprays are more likely to deposit on interposed surfaces, thus becoming a promising and competitive atomization solution for improving spray cooling. (orig.)

  7. Impact of intermittent fasting on glucose homeostasis.

    Science.gov (United States)

    Varady, Krista A

    2016-07-01

    This article provides an overview of the most recent human trials that have examined the impact of intermittent fasting on glucose homeostasis. Our literature search retrieved one human trial of alternate day fasting, and three trials of Ramadan fasting published in the past 12 months. Current evidence suggests that 8 weeks of alternate day fasting that produces mild weight loss (4% from baseline) has no effect on glucose homeostasis. As for Ramadan fasting, decreases in fasting glucose, insulin, and insulin resistance have been noted after 4 weeks in healthy normal weight individuals with mild weight loss (1-2% from baseline). However, Ramadan fasting may have little impact on glucoregulatory parameters in women with polycystic ovarian syndrome who failed to observe weight loss. Whether intermittent fasting is an effective means of regulating glucose homeostasis remains unclear because of the scarcity of studies in this area. Large-scale, longer-term randomized controlled trials will be required before the use of fasting can be recommended for the prevention and treatment of metabolic diseases.

  8. Intermittency Statistics in the Expanding Solar Wind

    Science.gov (United States)

    Cuesta, M. E.; Parashar, T. N.; Matthaeus, W. H.

    2017-12-01

    The solar wind is observed to be turbulent. One of the open questions in solar wind research is how the turbulence evolves as the solar wind expands to great distances. Some studies have focused on evolution of the outer scale but not much has been done to understand how intermittency evolves in the expanding wind beyond 1 AU (see [1,2]). We use magnetic field data from Voyager I spacecraft from 1 to 10AU to study the evolution of statistics of magnetic discontinuities. We perform various statistical tests on these discontinuities and make connections to the physical processes occurring in the expanding wind.[1] Tsurutani, Bruce T., and Edward J. Smith. "Interplanetary discontinuities: Temporal variations and the radial gradient from 1 to 8.5 AU." Journal of Geophysical Research: Space Physics 84.A6 (1979): 2773-2787.[2] Greco, A., et al. "Evidence for nonlinear development of magnetohydrodynamic scale intermittency in the inner heliosphere." The Astrophysical Journal 749.2 (2012): 105.

  9. Chronic intermittent hypoxia predisposes to liver injury.

    Science.gov (United States)

    Savransky, Vladimir; Nanayakkara, Ashika; Vivero, Angelica; Li, Jianguo; Bevans, Shannon; Smith, Philip L; Torbenson, Michael S; Polotsky, Vsevolod Y

    2007-04-01

    Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH). OSA is associated with nonalcoholic steatohepatitis (NASH) in obese subjects. The aim of this study was to investigate the effects of CIH on the liver in the absence of obesity. Lean C57BL/6J mice (n = 15) on a regular chow diet were exposed to CIH for 12 weeks and compared with pair-fed mice exposed to intermittent air (IA, n = 15). CIH caused liver injury with an increase in serum ALT (224 +/- 39 U/l versus 118 +/- 22 U/l in the IA group, P fasting serum insulin levels, and mild elevation of fasting serum total cholesterol and triglycerides (TG). Liver TG content was unchanged, whereas cholesterol content was decreased. Histology showed swelling of hepatocytes, no evidence of hepatic steatosis, and marked accumulation of glycogen in hepatocytes. CIH led to lipid peroxidation of liver tissue with a malondialdehyde (MDA)/free fatty acids (FFA) ratio of 0.54 +/- 0.07 mmol/mol versus 0.30 +/- 0.01 mmol/mol in control animals (P obesity, CIH leads to mild liver injury via oxidative stress and excessive glycogen accumulation in hepatocytes and sensitizes the liver to a second insult, whereas NASH does not develop.

  10. Intermittent preventive treatment of malaria in pregnancy

    DEFF Research Database (Denmark)

    Mbonye, A.K.; Bygbjerg, Ib Christian; Magnussen, Pascal

    2008-01-01

    OBJECTIVE: To assess whether traditional birth attendants, drug-shop vendors, community reproductive-health workers, or adolescent peer mobilizers could administer intermittent preventive treatment (IPTp) for malaria with sulfadoxine-pyrimethamine to pregnant women. METHODS: A non-randomized comm......OBJECTIVE: To assess whether traditional birth attendants, drug-shop vendors, community reproductive-health workers, or adolescent peer mobilizers could administer intermittent preventive treatment (IPTp) for malaria with sulfadoxine-pyrimethamine to pregnant women. METHODS: A non......-randomized community trial was implemented in 21 community clusters (intervention) and four clusters where health units provided routine IPTp (control). The primary outcome measures were access and adherence to IPTp, number of malaria episodes, prevalence of anaemia, and birth weight. Numbers of live births, abortions......, still births, and maternal and child deaths were secondary endpoints. FINDINGS: 1404 (67.5%) of 2081 with the new delivery system received two doses of sulfadoxine-pyrimethamine versus 281 (39.9%) of 704 with health units (P malaria episodes decreased from 906 (49...

  11. Intermittent hyperthyreosis. A heat stress syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Sulman, F G; Tal, E; Pfeifer, Y; Superstine, E [Hebrew Univ., Jerusalem (Israel). Dept. of Applied Pharmacology

    1975-09-01

    Intermittent hyperthyreosis occurs under various forms of stress, especially heat stress. The clinician may diagnose such cases as masked or apathetic hyperthyroidism or 'forme fruste' hyperthyreosis or thyroid autonomy. As most routine and standard tests may here yield inconsistent results, it is the patients' anamnesis which may provide the clue. Our Bioclimatology Unit has now seen over 100 cases in which thyroid hypersensitivity towards heat was the most prominent syndrome: 10-15% of weather-sensitive patients are affected. The patients complain before or during heat spells of such contradictory symptoms as insomnia, irritability, tension, tachycardia, palpitations, precordial pain, dyspnoe, flushes with sweating or chills, tremor, abdominal pain or diarrhea, polyuria or pollakisuria, weight loss in spite of ravenous appetite, fatigue, exhaustion, depression, adynamia, lack of concentration and confusion. Determination of urinary neurohormones allows a differential diagnosis, intermittent hyperthyreosis being characterized by three cardinal symptoms: tachycardia - every case with more than 80 pulse beats being suspect (not specific); urinary histamine - every case excreting more than 90 ..mu..g/day being suspect. Again the drawback of this test is its lack of specificity, as histamine may also be increased in cases of allergy and spondylitis; urinary thyroxine - every case excreting more than 20 ..mu..g/day T-4 being suspect. This is the only specific test. Therapy should make use of lithium carbonate and betablockers. Propyl thiouracil is rarely required.

  12. Adequacy in dialysis: intermittent versus continuous therapies.

    Science.gov (United States)

    Misra, M; Nolph, K D

    2000-01-01

    A vital conceptual difference between intermittent and continuous dialysis therapies is the difference in the relationship between Kt/V urea and dietary protein intake. For a given level of protein intake the intermittent therapies require a higher Kt/V urea due to the reasons mentioned above. The recently released adequacy guidelines by DOQI for intermittent and continuous therapies are based on these assumptions. The link between adequacy targets and patient survival is well documented for an intermittent therapy like HD. For a continuous therapy like CAPD however, the evidence linking improved peritoneal clearance to better survival is not as direct. However, present consensus allows one to extrapolate results based on HD. The concept of earlier and healthier initiation of dialysis is gaining hold and incremental dialysis forms an integral aspect of the whole concept. Tools like urea kinetic modeling give us valuable insight in making mathematical projections about the timing as well as dosing of dialysis. Daily home hemodialysis is still an underutilized modality despite offering best survival figures. Hopefully, with increasing availability of better and simpler machines its use will increase. Still several questions remain unanswered. Despite availability of data in hemodialysis patients suggesting that an increased dialysis prescription leads to a better survival, optimal dialysis dose is yet to be defined. Concerns regarding methodology of such studies and conclusions thereof has been raised. Other issues relating to design of the studies, variation in dialysis delivery, use of uncontrolled historical standards and lack of patient randomization etc also need to be considered when designing such trials. Hopefully an ongoing prospective randomized trial, namely the HEMO study, looking at two precisely defined and carefully maintained dialysis prescriptions will provide some insight into adequacy of dialysis dose and survival. In diabetic patients, the

  13. Acute Effects of Carbohydrate Supplementation on Intermittent Sports Performance.

    Science.gov (United States)

    Baker, Lindsay B; Rollo, Ian; Stein, Kimberly W; Jeukendrup, Asker E

    2015-07-14

    Intermittent sports (e.g., team sports) are diverse in their rules and regulations but similar in the pattern of play; that is, intermittent high-intensity movements and the execution of sport-specific skills over a prolonged period of time (~1-2 h). Performance during intermittent sports is dependent upon a combination of anaerobic and aerobic energy systems, both of which rely on muscle glycogen and/or blood glucose as an important substrate for energy production. The aims of this paper are to review: (1) potential biological mechanisms by which carbohydrate may impact intermittent sport performance; (2) the acute effects of carbohydrate ingestion on intermittent sport performance, including intermittent high-intensity exercise capacity, sprinting, jumping, skill, change of direction speed, and cognition; and (3) what recommendations can be derived for carbohydrate intake before/during exercise in intermittent sports based on the available evidence. The most researched intermittent sport is soccer but some sport-specific studies have also been conducted in other sports (e.g., rugby, field hockey, basketball, American football, and racquet sports). Carbohydrate ingestion before/during exercise has been shown in most studies to enhance intermittent high-intensity exercise capacity. However, studies have shown mixed results with regards to the acute effects of carbohydrate intake on sprinting, jumping, skill, change of direction speed, and cognition. In most of these studies the amount of carbohydrate consumed was ~30-60 g/h in the form of a 6%-7% carbohydrate solution comprised of sucrose, glucose, and/or maltodextrin. The magnitude of the impact that carbohydrate ingestion has on intermittent sport performance is likely dependent on the carbohydrate status of the individual; that is, carbohydrate ingestion has the greatest impact on performance under circumstances eliciting fatigue and/or hypoglycemia. Accordingly, carbohydrate ingestion before and during a game

  14. Acute Effects of Carbohydrate Supplementation on Intermittent Sports Performance

    Directory of Open Access Journals (Sweden)

    Lindsay B. Baker

    2015-07-01

    Full Text Available Intermittent sports (e.g., team sports are diverse in their rules and regulations but similar in the pattern of play; that is, intermittent high-intensity movements and the execution of sport-specific skills over a prolonged period of time (~1–2 h. Performance during intermittent sports is dependent upon a combination of anaerobic and aerobic energy systems, both of which rely on muscle glycogen and/or blood glucose as an important substrate for energy production. The aims of this paper are to review: (1 potential biological mechanisms by which carbohydrate may impact intermittent sport performance; (2 the acute effects of carbohydrate ingestion on intermittent sport performance, including intermittent high-intensity exercise capacity, sprinting, jumping, skill, change of direction speed, and cognition; and (3 what recommendations can be derived for carbohydrate intake before/during exercise in intermittent sports based on the available evidence. The most researched intermittent sport is soccer but some sport-specific studies have also been conducted in other sports (e.g., rugby, field hockey, basketball, American football, and racquet sports. Carbohydrate ingestion before/during exercise has been shown in most studies to enhance intermittent high-intensity exercise capacity. However, studies have shown mixed results with regards to the acute effects of carbohydrate intake on sprinting, jumping, skill, change of direction speed, and cognition. In most of these studies the amount of carbohydrate consumed was ~30–60 g/h in the form of a 6%–7% carbohydrate solution comprised of sucrose, glucose, and/or maltodextrin. The magnitude of the impact that carbohydrate ingestion has on intermittent sport performance is likely dependent on the carbohydrate status of the individual; that is, carbohydrate ingestion has the greatest impact on performance under circumstances eliciting fatigue and/or hypoglycemia. Accordingly, carbohydrate ingestion before

  15. More than meets the eye: infant presenting with hypoxic ischaemic encephalopathy.

    Science.gov (United States)

    Sen, Kuntal; Agarwal, Rajkumar

    2018-04-05

    We report a newborn infant who presented with poor Apgar scores and umbilical artery acidosis leading to the diagnosis of hypoxic ischaemic encephalopathy. During the course of the infant's hospitalisation, subsequent workup revealed an underlying genetic cause that masqueraded as hypoxic ischaemic encephalopathy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Lethal Effect of Thermal Neutrons on Hypoxic Elirlich Ascites Tumour Cells in vitro

    OpenAIRE

    MITSUHIKO, AKABOSHI; KENICHI, KAWAI; HIROTOSHI, MAKI; Research Reactor Institute, Kyoto University; Research Reactor Institute, Kyoto University; Research Reactor Institute, Kyoto University

    1985-01-01

    Ehrlich ascites tumour cells were irradiated in vitro with thermal neutrons under aerobic and hypoxic conditions, and the survival of their reproductive capacity was assayed in vivo. Only a slight hypoxic protection was observed for thermal neutron irradiation with an oxygen enhancement ratio (OER) of 1.2, as compared with OER of 3.3 for ^Co-γ-rays. Absorbed dose of thermal neutrons was calculated by assuming that the energies of recoiled nuclei were completely absorbed within a cell nucleus....

  17. Intramucosal–arterial PCO 2 gap fails to reflect intestinal dysoxia in hypoxic hypoxia

    OpenAIRE

    Dubin, Arnaldo; Murias, Gastón; Estenssoro, Elisa; Canales, Héctor; Badie, Julio; Pozo, Mario; Sottile, Juan P; Barán, Marcelo; Pálizas, Fernando; Laporte, Mercedes

    2002-01-01

    Introduction An elevation in intramucosal–arterial PCO 2 gradient (ΔPCO 2) could be determined either by tissue hypoxia or by reduced blood flow. Our hypothesis was that in hypoxic hypoxia with preserved blood flow, ΔPCO 2 should not be altered. Methods In 17 anesthetized and mechanically ventilated sheep, oxygen delivery was reduced by decreasing flow (ischemic hypoxia, IH) or arterial oxygen saturation (hypoxic hypoxia, HH), or no intervention was made (sham). In the IH group (n = 6), blood...

  18. Superfractionation as a potential hypoxic cell radiosensitizer: prediction of an optimum dose per fraction

    International Nuclear Information System (INIS)

    Dasu, Alexandru; Denekamp, Juliana

    1999-01-01

    Purpose: A dose 'window of opportunity' has been identified in an earlier modeling study if the inducible repair variant of the LQ model is adopted instead of the pure LQ model, and if all survival curve parameters are equally modified by the presence or absence of oxygen. In this paper we have extended the calculations to consider survival curve parameters from 15 sets of data obtained for cells tested at low doses using clonogenic assays. Methods and Materials: A simple computer model has been used to simulate the response of each cell line to various doses per fraction in multifraction schedules, with oxic and hypoxic cells receiving the same fractional dose. We have then used pairs of simulated survival curves to estimate the effective hypoxic protection (OER') as a function of the dose per fraction. Results: The resistance of hypoxic cells is reduced by using smaller doses per fraction than 2 Gy in all these fractionated clinical simulations, whether using a simple LQ model, or the more complex LQ/IR model. If there is no inducible repair, the optimum dose is infinitely low. If there is inducible repair, there is an optimum dose per fraction at which hypoxic protection is minimized. This is usually around 0.5 Gy. It depends on the dose needed to induce repair being higher in hypoxia than in oxygen. The OER' may even go below unity, i.e. hypoxic cells may be more sensitive than oxic cells. Conclusions: If oxic and hypoxic cells are repeatedly exposed to doses of the same magnitude, as occurs in clinical radiotherapy, the observed hypoxic protection varies with the fractional dose. The OER' is predicted to diminish at lower doses in all cell lines. The loss of hypoxic resistance with superfractionation is predicted to be proportional to the capacity of the cells to induce repair, i.e. their intrinsic radioresistance at a dose of 2 Gy

  19. OUTCOMES in CHILDHOOD FOLLOWING THERAPEUTIC HYPOTHERMIA for NEONATAL HYPOXIC-ISCHEMIC ENCEPHALOPATHY (HIE)

    Science.gov (United States)

    Natarajan, Girija; Pappas, Athina; Shankaran, Seetha

    2017-01-01

    In this chapter we review the childhood outcomes of neonates with birth depression and/or hypoxic-ischemic encephalopathy. The outcomes of these children prior to the era of hypothermia for neuroprotection will first be summarized, followed by discussion of results from randomized controlled trials of therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy. The predictors of outcome in childhood following neonatal HIE using clinical and imaging biomarkers following hypothermia therapy will be described. PMID:27863707

  20. Outcomes in childhood following therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE).

    Science.gov (United States)

    Natarajan, Girija; Pappas, Athina; Shankaran, Seetha

    2016-12-01

    In this article, we review the childhood outcomes of neonates with birth depression and/or hypoxic-ischemic encephalopathy. The outcomes of these children prior to the era of hypothermia for neuroprotection will first be summarized, followed by discussion of results from randomized controlled trials of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy. The predictors of outcome in childhood following neonatal HIE using clinical and imaging biomarkers following hypothermia therapy will be described. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor

    Energy Technology Data Exchange (ETDEWEB)

    Toyonaga, Takuya; Hirata, Kenji; Kobayashi, Kentaro; Manabe, Osamu; Watanabe, Shiro; Hattori, Naoya; Shiga, Tohru; Tamaki, Nagara [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo, Hokkaido (Japan); Yamaguchi, Shigeru [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo, Hokkaido (Japan); Hokkaido University Graduate School of Medicine, Department of Neurosurgery, Sapporo (Japan); Terasaka, Shunsuke; Kobayashi, Hiroyuki [Hokkaido University Graduate School of Medicine, Department of Neurosurgery, Sapporo (Japan); Kuge, Yuji [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Tanaka, Shinya [Hokkaido University Graduate School of Medicine, Department of Cancer Pathology, Sapporo (Japan); Ito, Yoichi M. [Hokkaido University Graduate School of Medicine, Department of Biostatistics, Sapporo (Japan)

    2017-04-15

    Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV x FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV

  2. Analysis of Hypoxic and Hypercapnic Ventilatory Response in Healthy Volunteers.

    Directory of Open Access Journals (Sweden)

    Shmuel Goldberg

    Full Text Available A previous study has suggested that the Human Leukocyte Antigen (HLA allele DQB1*06:02 affects hypoxic ventilatory response (HVR but not hypercapnic ventilatory response (HCVR in an Asian population. The current study evaluated the relationship in Caucasians and Asians. In addition we assessed whether gender or polymorphisms in genes participating in the control of breathing affect HVR and HCVR.A re-breathing system was used to measure HVR and HCVR in 551 young adults (56.8% Caucasians, 30% Asians. HLA-DQB1*06:02 and tagged polymorphisms and coding variants in genes participating in breathing (PHOX2B, GPR4 and TASK2/KCNK5 were analyzed. The associations between HVR/HCVR and HLA-DQB1*06:02, genetic polymorphisms, and gender were evaluated using ANOVA or frequentist association testing with SNPTEST.HVR and gender are strongly correlated. HCVR and gender are not. Mean HVR in women was 0.276±0.168 (liter/minute/%SpO2 compared to 0.429±0.266 (liter/minute/%SpO2 in men, p<0.001 (55.4% higher HVR in men. Women had lower baseline minute ventilation (8.08±2.36 l/m vs. 10.00±3.43l/m, p<0.001, higher SpO2 (98.0±1.3% vs. 96.6±1.7%, p<0.001, and lower EtCO2 (4.65±0.68% vs. 4.82±1.02%, p = 0.025. One hundred and two (18.5% of the participants had HLA-DQB1*06:02. No association was seen between HLA-DQB1*06:02 and HVR or HCVR. Genetic analysis revealed point wise, uncorrected significant associations between two TASK2/KCNK5 variants (rs2815118 and rs150380866 and HCVR.This is the largest study to date reporting the relationship between gender and HVR/ HCVR and the first study assessing the association between genetic polymorphisms in humans and HVR/HCVR. The data suggest that gender has a large effect on hypoxic breathing response.

  3. Long-term effects of recurrent intermittent hypoxia and hyperoxia on respiratory system mechanics in neonatal mice.

    Science.gov (United States)

    Dylag, Andrew M; Mayer, Catherine A; Raffay, Thomas M; Martin, Richard J; Jafri, Anjum; MacFarlane, Peter M

    2017-04-01

    Premature infants are at increased risk for wheezing disorders. Clinically, these neonates experience recurrent episodes of apnea and desaturation often treated by increasing the fraction of inspired oxygen (FIO 2 ). We developed a novel paradigm of neonatal intermittent hypoxia with subsequent hyperoxia overshoots (CIH O/E ) and hypothesized that CIH O/E elicits long-term changes on pulmonary mechanics in mice. Neonatal C57BL/6 mice received CIH O/E , which consisted of 10% O2 (1 min) followed by a transient exposure to 50% FIO 2 , on 10-min repeating cycles 24 h/d from birth to P7. Baseline respiratory mechanics, methacholine challenge, RT-PCR for pro and antioxidants, radial alveolar counts, and airway smooth muscle actin were assessed at P21 after 2-wk room air recovery. Control groups were mice exposed to normoxia, chronic intermittent hyperoxia (CIH E ), and chronic intermittent hypoxia (CIH O ). CIH O/E and CIH E increased airway resistance at higher doses of methacholine and decreased baseline compliance compared with normoxia mice. Lung mRNA for NOX2 was increased by CIH O/E . Radial alveolar counts and airway smooth muscle actin was not different between groups. Neonatal intermittent hypoxia/hyperoxia exposure results in long-term changes in respiratory mechanics. We speculate that recurrent desaturation with hyperoxia overshoot may increase oxidative stress and contribute to wheezing in former preterm infants.

  4. Acute Liver Impairment in a Young, Healthy Athlete: Hypoxic Hepatitis and Rhabdomyolysis following Heat Stroke

    Directory of Open Access Journals (Sweden)

    Neville Azzopardi

    2012-08-01

    Full Text Available Any process that substantially diminishes arterial blood flow or arterial oxygen content to the liver can result in hypoxic (ischaemic hepatitis. 90% of hypoxic hepatitis occurs in unstable patients in intensive care units with haemodynamic failure secondary to heart failure, respiratory failure and toxic shock. The rate of in-hospital mortality in hypoxic hepatitis is very high with studies recording mortalities of 61.5%. It tends to be very uncommon in healthy, young patients with no underlying medical problems. We report here the case of a young healthy athlete who developed heat stroke associated with rhabdomyolysis and hypoxic hepatitis while he was running the final stages of a marathon. The patient required intensive care admission and inotropic support for a few hours after he was admitted with heat stroke. He underwent a rapid recovery after he was resuscitated with fluids. N-acetyl cysteine was also given during the acute stage of the hepatitis. This case highlights an uncommon case of hypoxic hepatitis in a young, healthy patient secondary to hypotension and heat stroke. Inotropic support might have precipitated the hypoxic hepatitis in this young patient.

  5. Hypoxic fraction and binding of misonidazole in EMT6/Ed multicellular tumor spheroids

    International Nuclear Information System (INIS)

    Franko, A.J.

    1985-01-01

    Misonidazole has been shown to bind selectively to hypoxic cells in tissue culture and to cells which are presumed to be chronically hypoxic in EMT6 spheroids and tumors. Thus it has considerable potential as a marker of hypoxic cells in vivo. To further evaluate this potential EMT6/Ed spheroids were used to quantitate misonidazole binding under conditions which resulted in hypoxic fractions between 0 and 1. The patterns of binding of 14 C-labeled misonidazole determined by autoradiography were consistent with the regions of radiobiological hypoxia as predicted by oxygen diffusion theory. The overall uptake of 3 H-labeled misonidazole by spheroids correlated well with the hypoxic fraction, although binding to aerobic cells and necrotic tissue contributed appreciably to the total label in the spheroids. It is concluded that misonidazole is an excellent marker of hypoxia in EMT6/Ed spheroids at the microscopic level, and the total amount bound per spheroid provides a potentially useful measure of the hypoxic fraction

  6. Hypoxia-activated prodrug TH-302 decreased survival rate of canine lymphoma cells under hypoxic condition.

    Science.gov (United States)

    Yamazaki, Hiroki; Lai, Yu-Chang; Tateno, Morihiro; Setoguchi, Asuka; Goto-Koshino, Yuko; Endo, Yasuyuki; Nakaichi, Munekazu; Tsujimoto, Hajime; Miura, Naoki

    2017-01-01

    We tested the hypotheses that hypoxic stimulation enhances growth potentials of canine lymphoma cells by activating hypoxia-inducible factor 1α (HIF-1α), and that the hypoxia-activated prodrug (TH-302) inhibits growth potentials in the cells. We investigated how hypoxic culture affects the growth rate, chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin (DOX)-resistant lymphoma cells, and influences of TH-302 on survival rate of the cells under hypoxic conditions. Our results demonstrated that hypoxic culture upregulated the expression of HIF-1α and its target genes, including ATP-binding cassette transporter B1 (ABCB1), ATP-binding cassette transporter G2 (ABCG2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and survivin, and enhanced the growth rat