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Altitude hypoxia is often associated with impairment of human reproduction. In this study, hormones and macrophage migration inhibitory factor (MIF, a proinflammatory cytokine with key roles in human reproduction) were determined in seven regularly menstruating, lowlander native women living at sea level participating in 14 days of trekking at moderate and high altitude. Blood and saliva samples were collected from each subject at high altitude (5050 m a.s.l. [above sea level]), and at sea level before and after the expedition. Testosterone level was lowered by high altitude and was restored after the end of the expedition, while progesterone decreased significantly in all participants at the end of the expedition, although most of the participants were in the luteal phase. The salivary concentration of MIF decreased greatly at altitude, but its levels were completely restored after the return to sea level. Our findings showed high sensitivity and rapid changes in the determined parameters in response to the high-altitude hypoxic environment, particularly MIF., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

The aim of this study was to determine whether neuromuscular electrical stimulation (NMES) affects skeletal muscle regeneration through a reduction of oxidative status in satellite cells of healthy elderly subjects. Satellite cells from the vastus lateralis skeletal muscle of 12 healthy elderly subjects before and after 8 wk of NMES were allowed to proliferate to provide myogenic populations of adult stem cells [myogenic precursor cells (MPCs)]. These MPCs were then investigated in terms of their proliferation, their basal cytoplasmic free Ca 2+ concentrations, and their expression of myogenic regulatory factors ( PAX3, PAX7, MYF5, MYOD , and MYOG ) and micro-RNAs (miR-1, miR-133a/b, and miR-206). The oxidative status of these MPCs was evaluated through superoxide anion production and superoxide dismutase and glutathione peroxidase activities. On dissected single skeletal myofibers, the nuclei were counted to determine the myonuclear density, the fiber phenotype, cross-sectional area, and tension developed. The MPCs obtained after NMES showed increased proliferation rates along with increased cytoplasmic free Ca 2+ concentrations and gene expression of MYOD and MYOG on MPCs. Muscle-specific miR-1, miR-133a/b, and miR-206 were upregulated. This NMES significantly reduced superoxide anion production, along with a trend to reduction of superoxide dismutase activity. The NMES-dependent stimulation of muscle regeneration enhanced satellite cell fusion with mature skeletal fibers. NMES improved the regenerative capacity of skeletal muscle in elderly subjects. Accordingly, the skeletal muscle strength and mobility of NMES-stimulated elderly subjects significantly improved. NMES may thus be further considered for clinical or ageing populations. NEW & NOTEWORTHY The neuromuscular electrical stimulation (NMES) effect on skeletal muscle regeneration was assessed in healthy elderly subjects for the first time. NMES improved the regenerative capacity of skeletal muscle through increased myogenic precursor cell proliferation and fusion with mature myofibers. The increased cytoplasmic free Ca 2+ concentration along with MYOD , MYOG , and micro-RNA upregulation could be related to reduced O 2 ·- production, which, in turn, favors myogenic regeneration. Accordingly, the skeletal muscle strength of NMES-stimulated lower limbs of healthy elderly subjects improved along with their mobility., (Copyright © 2017 the American Physiological Society.)

The purpose of this study was to analyze the physiological features of peripheral blood mononuclear cells (PBMCs) isolated from healthy female trekkers before and after physical activity carried out under both normoxia (low altitude, < 2000 m a.s.l.) and hypobaric hypoxia (high altitude, > 3700 m a.s.l.). The experimental design was to differentiate effects induced by exercise and those related to external environmental conditions. PBMCs were isolated from seven female subjects before and after each training period. The PBMCs were phenotypically and functionally characterized using fluorimetric and densitometric analyses, to determine cellular activation, and their intracellular Ca(2+) levels and oxidative status. After a period of normoxic physical exercise, the PBMCs showed an increase in fully activated T lymphocytes (CD3(+) CD69(+) ) and a reduction in intracellular Ca(2+) levels. On the other hand, with physical exercise performed under hypobaric hypoxia, there was a reduction in T lymphocytes and an increase in nonactivated B lymphocytes, accompanied by a reduction in O2 (-) levels in the mitochondria. These outcomes reveal that in women, low- to moderate-intensity aerobic trekking induces CD69 T cell activation and promotes anti-stress effects on the high-altitude-induced impairment of the immune responses and the oxidative balance., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

There is scientific evidence to suggest a correlation between hypoxia and the physiology of micturition. During a Himalayan Scientific and Mountaineering Expedition, we performed tests to investigate the functional interactions between altitude hypoxia and uroflowmetry parameters in women. The tests were carried out in seven women (36.3 ± 7.1 yr) from normoxic [1,340 meters above sea level (m a.s.l.)] to hypoxic conditions (up to 5,050 m a.s.l.) and during the return descent. The following measures were determined: uroflowmetry parameters and saturation of peripheral oxygen (SpO2 ). As expected, SpO2 decreased from 97.7 to 77.8% with increasing altitude. Micturition flow time, flow volume, and voiding time increased with altitude (P < 0.04 for all), indicating a negative correlation with SpO2 In conclusion, in young adult women, micturition physiological parameters were affected during adaptation to hypoxia; the correlation with SpO2 strongly suggests a role of hypoxia in these changes. These data could help to support the design of new strategies for both prevention and medical treatment. An example of the latter might be hyperbaric oxygen therapy, which in some studies has proved able to reduce the symptoms in patients with hypoxic bladder., (Copyright © 2016 the American Physiological Society.)

Aim: The aim of this study was to determine whether a 14-day trekking expeditions, in high altitude hypoxic environment, triggers redox disturbance at the level of satellite cells (adult stem cells) in young women., Methods: We collected muscle biopsies from Vastus Lateralis muscle for both single fiber analysis and satellite cells isolation. The samples collected before (PRE-Hypoxia) and after (POST-Hypoxia) the trekking in the Himalayas were compared. Satellite cells were investigated for oxidative stress (oxidant production, antioxidant enzyme activity, and lipid damage), mitochondrial potential variation, gene profile of HIF, and myogenic transcription factors (Pax7, MyoD, myogenin), and miRNA expression (miR-1, miR-133, miR-206)., Results: The nuclear domain analysis showed a significant fusion and consequent reduction of the Pax7(+) satellite cells in the single mature fibers. The POST-Hypoxia myoblasts obtained by two out of six volunteers showed high superoxide anion production and lipid peroxidation along with impaired dismutase and catalase and mitochondrial potential. The transcription profile and miRNA expression were different for oxidized and non-oxidized cells., Conclusions: The present study supports the phenomenon of hypobaric-hypoxia-induced oxidative stress and its role in the impairment of the regenerative capacity of satellite cells derived from the V. Lateralis muscle of young adult female subjects.

Difficulties in handwriting are often reported in children with developmental coordination disorder, and they represent an important element in the diagnosis. The present study was aimed at investigating the relation between motor coordination and handwriting skills, and to identify differences in handwriting between children without and with coordination difficulties. In particular, we asked whether visual-spatial skills have a role as mediating variables between motor coordination and handwriting. We assessed motor coordination as well as graphic abilities in children aged 7-10 years. Moreover, we evaluated their visual-motor integration, visual-spatial skills, and other cognitive abilities (memory and planning). We found no relation between motor coordination and handwriting skills, while visual-spatial skills (measured by a visual-constructive task) were related with both. Our conclusion is that visual-spatial skills are involved both in general motor coordination and in handwriting, but the relationship involves different aspects in the two cases.

The effect of the combination of trekking and balanced appropriated diet were studied in mountaineers who spent 6 days at an altitude ranging from 900 to 5895 m above sea level (a.s.l.), during the Kilimanjaro Abruzzo Expedition. This study explored whether anthropometric, cardiovascular and blood biochemical parameters were significantly changed by a regular trekking performed at high altitude, with reduced oxygen levels, together with a macronutrient-containing balanced diet (total daily caloric intake: 3000-3500 Kcals). In consideration of the short period of high-altitude exposure, high-altitude exercise appeared to provide beneficial and rapid effects on the lipid profile and to modulate cardiovascular functions. These effects rely on both high-altitude hypoxia and physical activity. The most interesting observation is that even just a few days of high-altitude exercise, along with a balanced diet, was able to improve plasma lipid profiles.

We present a proteomic analysis of the rat carotid body (CB) preparation by comparison between normoxia and hypoxia. Proteomic investigation would be helpful to identify the stress-induced protein during hypoxia and to know what O(2) species are being sensed by CB cells. Adult Wistar rats were used, one group was kept in room air (21% O(2)) as control, and the other was kept in a Plexiglas chamber for 12 days in chronic hypoxia (10-11% inspired oxygen). A total protein extract for each lysated tissue was separated using a broad pH range no-linear IPG strip (3-10) and the second dimension was performed on a 9-16% polyacrylamide gel. Exposure to hypoxia for 12 days produced significant changes in protein expression, providing an initial insight into the mechanism underlying differences in susceptibility to hypoxia. Further investigation is needed to have an overview of the specific set of proteins present in the CB and the functions of such proteins in signal transduction and adaptation during hypoxia.

Objectives: It was the aim of this study to evaluate the recurrence and progression at 1, 3 and 5 years in patients with non-muscle-invasive bladder cancer (NMIBC) who underwent a transurethral resection of bladder cancer following intravesical adjuvant chemotherapy or immunotherapy if indicated and to compare them with the European Organization for Research and Treatment of Cancer (EORTC) risk tables., Patients and Methods: Between 2002 and 2011, a total of 259 patients with NMIBC were treated with transurethral resection of bladder cancer. According to the clinical and pathological factors used by the EORTC scoring system, the patients were divided into four groups, and for each group, the probabilities of recurrence and progression were calculated., Results: The recurrence and progression rates of NMIBC of our patients were similar to those in the EORTC risk score system. Moreover, in our sample group, we found a minimally significant reduction in the recurrence rate in the intermediate- and high-risk groups., Conclusion: From the results obtained, we considered it essential to introduce the use of EORTC risk tables into our clinical practice to determine the recurrence and progression of NMIBC., (Copyright © 2012 S. Karger AG, Basel.)

Introduction: High altitude environment represents a fine model to study physiological and pathophysiological effects of oxygen availability on sleep-related erections (SREs)., Aim: To describe altitude-dependent effects on quality of SREs in order to estimate the role of hypoxia in erection physiology., Methods: A healthy 37-year-old male mountain climber underwent a chronic high altitude-related hypoxia experience during the 43 days of the Manaslu expedition (Nepal). SREs were recorded by RigiScan (Timm Medical Technologies, Inc., Eden Prairie, MN, USA) at altitudes ranging from 0 to 5,800 m above sea level. The erection-related parameters assessed were: number, duration, event duration (% of session), event rigidity %, time rigidity %, tumescence and rigidity activated unit, and event tum % > bline (%)., Main Outcomes Measures: SREs were recorded by RigiScan at altitudes ranging from 0 to 5,800 m above sea level., Results: Erectile parameters showed an altitude-related reduction during the hypoxic exposure, although all functional alterations were reverted by the return to sea level., Conclusions: Our case report supports the hypothesis that oxygen availability and delivery could play an important role in the regulation of local penile erection-related mechanisms and that low oxygen levels might be considered an etiological cofactor in erectile dysfunction., (© 2011 International Society for Sexual Medicine.)

Objective: To explore the effect of physical exercise at high altitudes (HA) on male reproductive system., Design: Prospective study., Setting: Andrology Clinic, University of L'Aquila, Italy., Patient(s): Seven male mountaineers involved in an expedition at 5,900 m., Intervention(s): Semen analysis, sperm DNA fragmentation with flow cytometry, and reproductive hormone levels., Main Outcome Measure(s): Hormone levels were evaluated at sea level (SL) at baseline (SL-pre), after 22 days of exercise at HA (intermediate), and after 10 days upon reaching SL (SL-post). Sperm parameters, percentage of sperm with fragmented DNA, and body composition measures were evaluated at SL-pre and at SL-post., Result(s): A reduction of sperm concentration, of body mass index (BMI), of waist circumference, and of percentage of body fat was observed at SL-post compared with SL-pre values. Increased levels of FSH and PRL were observed at the intermediate point, and normalized at SL-post, whereas T was higher at SL-post compared with SL-pre levels., Conclusion(s): Physical exercise at HA is associated with a testicular dysfunction leading to a reduced sperm concentration probably through an altered spermiation. The improved body composition after physical exercise might explain the higher T levels observed after the expedition., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Recent studies underscore the importance of oxygen supply in bladder cancer. Tumour growth stimulates the production of vasoactive factors to increase oxygen delivery to tissues by vasodilatation. Any vasoconstrictor mediator could impair this vasodilatation reducing the oxygen supply. 8-Iso-PGF2 alpha is a potent vasoconstrictor agent. The aim of this work is to determine 8-Iso-PGF2 alpha release in healthy bladder mucosa and in superficial bladder cancer in order to investigate a pathophysiological vasoconstrictor answer of the superficial bladder cancer. The study was conducted on a sample of 12 patients; for every subject studied 8-Iso-PGF2 alpha release was assayed in healthy bladder mucosa and in superficial bladder tumour. 8-Iso-PGF2 alpha release was significantly reduced (p less than 0.001) in superficial bladder cancer compared with healthy bladder mucosa. The inhibition of the production of a powerful vasoconstrictor such as 8-Iso-PGF2 alpha in the vascular homeostatic mechanism of bladder cancer can represent a response of the tumor tending to contrast an antagonist effect of vasodilatation and the necessary to support the oxygen supply.

Depending on the absolute altitude and the duration of exposure, a high altitude environment induces various cellular effects that are strictly related to changes in oxidative balance. In this study, we used in vitro isolated peripheral blood lymphocytes as biosensors to test the effect of hypobaric hypoxia on seven climbers by measuring the functional activity of these cells. Our data revealed that a 21-day exposure to high altitude (5000 m) (1) increased intracellular Ca(2+) concentration, (2) caused a significant decrease in mitochondrial membrane potential, and (3) despite possible transient increases in intracellular levels of reactive oxygen species, did not significantly change the antioxidant and/or oxidative damage-related status in lymphocytes and serum, assessed by measuring Trolox-equivalent antioxidant capacity, glutathione peroxidase activity, vitamin levels, and oxidatively modified proteins and lipids. Overall, these results suggest that high altitude might cause an impairment in adaptive antioxidant responses. This, in turn, could increase the risk of oxidative-stress-induced cellular damage. In addition, this study corroborates the use of peripheral blood lymphocytes as an easily handled model for monitoring adaptive response to environmental challenge.

Hypoxia transiently increases transcription of the gene encoding heme oxygenase-1 (HO-1) and potently activates production of endothelin-1 (ET-1), the latter of which plays a central role in cellular adaptation to hypoxia. The ventilatory response to hypoxia attenuates with aging, and decreased responsiveness to hypoxia is seen in the aged vs. young rats, suggesting that the functionality of the oxygen-sensitive mechanism is age-dependent. In the present study, we examined the effects of aging on the expression of HO-1 and ET-1 in the carotid body, which is a small cluster of chemoreceptors and supporting cells that measure changes in the composition of arterial blood flowing through it. Our results revealed that HO-1 and ET-1 were expressed in carotid bodies of both young and old rats, although less so in the old ones. Exposure to chronic intermittent hypoxia significantly increased both HO-1 and ET-1 immunoreactivity in both young and old carotid body tissues, with the persisting age-dependent inequality to the disadvantage of old age. Considering that ET-1 is capable of enhancing intermittent hypoxia-induced chemosensory responses by the carotid body, our results suggest that decreased induction of ET-1 and HO-1 during aging could form the basis for age-related reductions in chemosensory discharge.

Aim: To evaluate the effect of chronic hypoxia on human spermatogenic parameters and their recovery time., Methods: Seminological parameters of six male healthy mountain trekkers were evaluated in normoxia at sea level. After 26 days exposure to altitude (ranging from 2 000 m to 5 600 m, Karakorum Expedition) the same parameters were again evaluated after returning to sea level. These parameters were once again evaluated after 1 month and then again after 6 months., Results: Sperm count was found to be lower immediately after returning to sea level (P = 0.0004) and again after a month (P = 0.0008). Normal levels were reached after 6 months. Spermatic motility (%) shows no reduction immediately after returning to sea level (P = 0.0583), whereas after 1 month this reduction was significant (P = 0.0066). After 6 months there was a recovery to pre-hypoxic exposure values. Abnormal or immature spermatozoa (%) increased immediately after returning to sea level (P = 0.0067) and then again after 1 month (P = 0.0004). After 6 months there was a complete recovery to initial values. The total number of motile sperm in the ejaculate was found to be lower immediately after returning to sea level (P = 0.0024) and then again after 1 month (P = 0.0021). After 6 months there was a recovery to pre-hypoxic exposure values., Conclusion: Chronic hypoxia induces a state of oligospermia and the normalization of such seminological parameters at the restoration of previous normoxic conditions after 6 months indicate the influence of oxygen supply in physiological mechanisms of spermatogenesis and male fertility.

The aim of the present study was to identify the effects of physical exercise on PSA serum levels and the diagnostic validity of PSA in the screening of prostate cancer in subjects undergoing physical exercise during chronic hypoxia. The study was performed during trekking between 3,200 and 5,600 meters of altitude on K2 mountain for 26 days. Mean serum PSA values before and after exposure did not show significant difference due to physical exercise. These data indicate that physical exercise or mountain hypoxia do not affect the diagnostic validity of PSA.