Hypoxia-Induced Oxidative Stress Modulation with Physical Activity.

Increased oxidative stress, defined as an imbalance between prooxidants and antioxidants, resulting in molecular damage and disruption of redox signaling, is associated with numerous pathophysiological processes and known to exacerbate chronic diseases. Prolonged systemic hypoxia, induced either by exposure to terrestrial altitude or a reduction in ambient O2 availability is known to elicit oxidative stress and thereby alter redox balance in healthy humans. The redox balance modulation is also highly dependent on the level of physical activity. For example, both high-intensity exercise and inactivity, representing the two ends of the physical activity spectrum, are known to promote oxidative stress. Numerous to-date studies indicate that hypoxia and exercise can exert additive influence upon redox balance alterations. However, recent evidence suggests that moderate physical activity can attenuate altitude/hypoxia-induced oxidative stress during long-term hypoxic exposure. The purpose of this review is to summarize recent findings on hypoxia-related oxidative stress modulation by different activity levels during prolonged hypoxic exposures and examine the potential mechanisms underlying the observed redox balance changes. The paper also explores the applicability of moderate activity as a strategy for attenuating hypoxia-related oxidative stress. Moreover, the potential of such moderate intensity activities used to counteract inactivity-related oxidative stress, often encountered in pathological, elderly and obese populations is also discussed. Finally, future research directions for investigating interactive effects of altitude/hypoxia and exercise on oxidative stress are proposed

Microvascular and oxidative stress responses to acute high-altitude exposure in prematurely born adults.

Premature birth is associated with endothelial and mitochondrial dysfunction, and chronic oxidative stress, which might impair the physiological responses to acute altitude exposure. We assessed peripheral and oxidative stress responses to acute high-altitude exposure in preterm adults compared to term born controls. Post-occlusive skeletal muscle microvascular reactivity and oxidative capacity from the muscle oxygen consumption recovery rate constant (k) were determined by Near-Infrared Spectroscopy in the vastus lateralis of seventeen preterm and seventeen term born adults. Measurements were performed at sea-level and within 1 h of arrival at high-altitude (3375 m). Plasma markers of pro/antioxidant balance were assessed in both conditions. Upon acute altitude exposure, compared to sea-level, preterm participants exhibited a lower reperfusion rate (7 ± 31% vs. 30 ± 30%, p = 0.046) at microvascular level, but higher k (6 ± 32% vs. -15 ± 21%, p = 0.039), than their term born peers. The altitude-induced increases in plasma advanced oxidation protein products and catalase were higher (35 ± 61% vs. -13 ± 48% and 67 ± 64% vs. 15 ± 61%, p = 0.034 and p = 0.010, respectively) and in xanthine oxidase were lower (29 ± 82% vs. 159 ± 162%, p = 0.030) in preterm compared to term born adults. In conclusion, the blunted microvascular responsiveness, larger increases in oxidative stress and skeletal muscle oxidative capacity may compromise altitude acclimatization in healthy adults born preterm

Increased Mortality Rate Associated with Chikungunya Epidemic, Ahmedabad, India

A total of 3,056 excess deaths epidemiologically linked to chikungunya occurred in 2006

Preterm birth and oxidative stress: Effects of acute physical exercise and hypoxia physiological responses.

Preterm birth is a global health issue that can induce lifelong medical sequela. Presently, at least one in ten newborns are born prematurely. At birth, preterm newborns exhibit higher levels of oxidative stress (OS) due to the inability to face the oxygen rich environment in which they are born into. Moreover, their immature respiratory, digestive, immune and antioxidant defense systems, as well as the potential numerous medical interventions following a preterm birth, such as oxygen resuscitation, nutrition, phototherapy and blood transfusion further contribute to high levels of OS. Although the acute effects seem well established, little is known regarding the long-term effects of preterm birth on OS. This matter is especially important given that chronically elevated OS levels may persist into adulthood and consequently contribute to the development of numerous non-communicable diseases observed in people born preterm such as diabetes, hypertension or lung disorders. The purpose of this review is to summarize the current knowledge regarding the consequences of preterm birth on OS levels from newborn to adulthood. In addition, the effects of physical activity and hypoxia, both known to disrupt redox balance, on OS modulation in preterm individuals are also explored

O415 Efficacy and safety of 48-week maintenance with QD ATV vs ATV/r (both + 2NRTIs) in patients with VL <50 c/mL after induction with ATV/r + 2NRTIs: study AI424136

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Exercise Overrides Blunted Hypoxic Ventilatory Response in Prematurely Born Men.

Pre-term birth provokes life-long anatomical and functional respiratory system sequelae. Although blunted hypoxic ventilatory response (HVR) is consistently observed in pre-term infants, it remains unclear if it persists with aging and, moreover, if it influences hypoxic exercise capacity. In addition, it remains unresolved whether the previously observed prematurity-related alterations in redox balance could contribute to HVR modulation. Twenty-one prematurely born adult males (gestational age = 29 ± 4 weeks], and 14 age matched controls born at full term (gestational age = 39 ± 2 weeks) underwent three tests in a randomized manner: (1) hypoxia chemo-sensitivity test to determine the resting and exercise poikilocapnic HVR and a graded exercise test to volitional exhaustion in (2) normoxia (F &lt;sub&gt;i&lt;/sub&gt; O &lt;sub&gt;2&lt;/sub&gt; = 0.21), and (3) normobaric hypoxia (F &lt;sub&gt;i&lt;/sub&gt; O &lt;sub&gt;2&lt;/sub&gt; = 0.13) to compare the hypoxia-related effects on maximal aerobic power (MAP). Selected prooxidant and antioxidant markers were analyzed from venous samples obtained before and after the HVR tests. Resting HVR was lower in the pre-term (0.21 ± 0.21 L ⋅ min &lt;sup&gt;-1&lt;/sup&gt; ⋅ kg &lt;sup&gt;-1&lt;/sup&gt; ) compared to full-term born individuals (0.47 ± 0.23 L ⋅ min &lt;sup&gt;-1&lt;/sup&gt; ⋅ kg &lt;sup&gt;-1&lt;/sup&gt; ; p &lt; 0.05). No differences were noted in the exercise HVR or in any of the measured oxidative stress markers before or after the HVR test. Hypoxia-related reduction of MAP was comparable between the groups. These findings indicate that blunted resting HVR in prematurely born men persists into adulthood. Also, active adults born prematurely seem to tolerate hypoxic exercise well and should, hence, not be discouraged to engage in physical activities in hypoxic environments. Nevertheless, the blunted resting HVR and greater desaturation observed in the pre-term born individuals warrant caution especially during prolonged hypoxic exposures

Commentary on Viewpoint: Human skeletal muscle wasting in hypoxia: a matter of hypoxic dose?: Skeletal muscle wasting in hypoxia; a matter of altitude.

SKELETAL MUSCLE WASTING IN HYPOXIA; A MATTER OF ALTITUDE TO THE EDITOR: D’Hulst and Deldicque (1) argue that the severity of muscle atrophy incurred at high altitude is dependent on the combined effect of duration and degree of hypoxia exposure, or “hypoxic dose” (1). We do see a limitation of this concept, as it implies that someone residing in Leuven (altitude: 28 m) for 10 years would be subjected to a hypoxic dose of 2,454 km·h and incur 5% atrophy. Although the authors wrote that “it is unknown which parameter, altitude, or time spent at altitude is most decisive in the overall metric of hypoxic dose,” our illustration suggests that altitude is the prime determinant. This is further supported by the cut-off point at 4,000 m in a plot of the degree of atrophy vs. altitude (using the data in Table 1), whereas there was no clear relationship with duration of altitude residence. This cut-off point is likely related to the shape of the hemoglobin dissociation curve, where the oxygen tension at 4,000 m is such that physiologically significant arterial hemoglobin desaturation occurs (2). We acknowledge that one cannot entirely dismiss the importance of duration of hypoxic exposure, simply because skeletal muscle atrophy can only be noticed some time after net protein breakdown is initiated. However, muscle atrophy will not continue indefinitely, but will reach a new steady state (how otherwise can Tibetans still have muscle?). Finally, other adaptations than atrophy, such as an increase in hematocrit and capillarization, serve to attenuate muscle tissue hypoxia and atrophy (3) during residence at altitude. REFERENCES 1. D=Hulst G, Deldicque L. Viewpoint: Human skeletal muscle wasting in hypoxia: a matter of hypoxic dose? J Appl Physiol. doi:10.1152/ japplphysiol.00264.2016. 2. Wagner PD, Wagner HE, Groves BM, Cymerman A, Houston CS. Hemoglobin P(50) during a simulated ascent of Mt. Everest, Operation Everest II. High Alt Med Biol 8: 32–42, 2007. doi:10.1089/ham.2006. 1049. 3. Wüst RCI, Jaspers RT, van Heijst AF, Hopman MT, Hoofd LJ, van der Laarse WJ, Degens H. Region-specific adaptations in determinants of rat skeletal muscle oxygenation to chronic hypoxia. Am J Physiol Heart Circ Physiol 297: H364–H374, 2009. doi:10.1152/ajpheart.00272.2009

Estimating Chikungunya prevalence in La Réunion Island outbreak by serosurveys: Two methods for two critical times of the epidemic

<p>Abstract</p> <p>Background</p> <p>Chikungunya virus (CHIKV) caused a major two-wave seventeen-month-long outbreak in La Réunion Island in 2005–2006. The aim of this study was to refine clinical estimates provided by a regional surveillance-system using a two-stage serological assessment as gold standard.</p> <p>Methods</p> <p>Two serosurveys were implemented: first, a rapid survey using stored sera of pregnant women, in order to assess the attack rate at the epidemic upsurge (s1, February 2006; n = 888); second, a population-based survey among a random sample of the community, to assess the herd immunity in the post-epidemic era (s2, October 2006; n = 2442). Sera were screened for anti-CHIKV specific antibodies (IgM and IgG in s1, IgG only in s2) using enzyme-linked immunosorbent assays. Seroprevalence rates were compared to clinical estimates of attack rates.</p> <p>Results</p> <p>In s1, 18.2% of the pregnant women were tested positive for CHIKV specific antibodies (13.8% for both IgM and IgG, 4.3% for IgM, 0.1% for IgG only) which provided a congruent estimate with the 16.5% attack rate calculated from the surveillance-system. In s2, the seroprevalence in community was estimated to 38.2% (95% CI, 35.9 to 40.6%). Extrapolations of seroprevalence rates led to estimate, at 143,000 and at 300,000 (95% CI, 283,000 to 320,000), the number of people infected in s1 and in s2, respectively. In comparison, the surveillance-system estimated at 130,000 and 266,000 the number of people infected for the same periods.</p> <p>Conclusion</p> <p>A rapid serosurvey in pregnant women can be helpful to assess the attack rate when large seroprevalence studies cannot be done. On the other hand, a population-based serosurvey is useful to refine the estimate when clinical diagnosis underestimates it. Our findings give valuable insights to assess the herd immunity along the course of epidemics.</p

Unconventional Repertoire Profile Is Imprinted during Acute Chikungunya Infection for Natural Killer Cells Polarization toward Cytotoxicity

Chikungunya virus (CHIKV) is a worldwide emerging pathogen. In humans it causes a syndrome characterized by high fever, polyarthritis, and in some cases lethal encephalitis. Growing evidence indicates that the innate immune response plays a role in controlling CHIKV infection. We show here that CHIKV induces major but transient modifications in NK-cell phenotype and function soon after the onset of acute infection. We report a transient clonal expansion of NK cells that coexpress CD94/NKG2C and inhibitory receptors for HLA-C1 alleles and are correlated with the viral load. Functional tests reveal cytolytic capacity driven by NK cells in the absence of exogenous signals and severely impaired IFN-γ production. Collectively these data provide insight into the role of this unique subset of NK cells in controlling CHIKV infection by subset-specific expansion in response to acute infection, followed by a contraction phase after viral clearance

HLA Class I Restriction as a Possible Driving Force for Chikungunya Evolution

After two decades of quiescence, epidemic resurgence of Chikungunya fever (CHIKF) was reported in Africa, several islands in the Indian Ocean, South-East Asia and the Pacific causing unprecedented morbidity with some cases of fatality. Early phylogenetic analyses based on partial sequences of Chikungunya virus (CHIKV) have led to speculation that the virus behind recent epidemics may result in greater pathogenicity. To understand the reasons for these new epidemics, we first performed extensive analyses of existing CHIKV sequences from its introduction in 1952 to 2009. Our results revealed the existence of a continuous genotypic lineage, suggesting selective pressure is active in CHIKV evolution. We further showed that CHIKV is undergoing mild positive selection, and that site-specific mutations may be driven by cell-mediated immune pressure, with occasional changes that resulted in the loss of human leukocyte antigen (HLA) class I-restricting elements. These findings provide a basis to understand Chikungunya virus evolution and reveal the power of post-genomic analyses to understand CHIKV and other viral epidemiology. Such an approach is useful for studying the impact of host immunity on pathogen evolution, and may help identify appropriate antigens suitable for subunit vaccine formulations