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The adaptation of olfaction to extreme environments is an area of limited understanding. This study aimed to get insights into the factors that constrain olfactory function at high altitudes. To this end, we compared the results of smell tests performed on the same subjects at low (665 m) and high altitude (4,780 m) during the "Kanchenjunga Exploration and Physiology" project in the Himalayas. The most distinct adaptive differences found at high altitude were reductions in the odor intensity, color-odor bimodal association, and memory, and increases in flavor perception. Physiological adaptations of the sense of smell resulting from exposure to hypoxia at altitude may have explanatory validity in unraveling the mechanisms that shape changes in olfactory function in the processes of aging and neurodegenerative diseases., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Altitude exposure affects hormonal homeostasis, but the adaptation of different populations is still not finely defined. This study aims to compare the mid-term effects of combining physical activity and altitude hypoxia on hormonal profiles in foreign trekkers coming from Italy versus indigenous Nepalese porters during a Himalayan trek. Participants (6 Italians and 6 Nepalese) completed a 300 km distance in 19 days of an accumulated altitude difference of 16,000 m, with an average daily walk of 6 h. The effect of high altitude on hormonal pathways was assessed by collecting blood samples the day before the expedition and the day after its completion. Foreign trekkers had an additional follow-up sample collected after 10 days. The findings revealed a different adaptation of thyroidal and gonadal axes to mid-term strenuous physical activity combined with high-altitude hypobaric hypoxia. The thyroid function shifted to the protective mechanism of low free triiodothyronine (FT3), whereas the gonadal axis was suppressed. The Italian trekkers and Nepalese porters had lower total testosterone and 17-β-estradiol levels after the expedition. At the follow-up, the Italians had increased testosterone values. Prolactin secretion decreased in the Italians but increased in the Nepalese. We conclude that exposure to high-altitude affects the hormonal axes. The effect seems notably pronounced for the hypothalamus-pituitary gonadal axis, suppressed after high-altitude exposure., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The "Endless Diving Project-Step 36" took place in the harbor waters of the town of Maratea in Italy in September 2014. The goal of the project was an attempt by an experienced male diver, equipped with a wet 7-mm suit and a normal gas tank, to set the world record-breaking of nonstop underwater performance. We studied inflammatory, hematological, and endocrine responses during the extreme condition of the attempt. Venous blood samples were collected at baseline, the day before the attempt; immediately after the return from underwater; then at Day 1, Day 4, and Day 12; and later at Month 1 and Month 41 of follow-up. We found that there was an increase in the content of blood neutrophils, monocytes, and eosinophils and a decrease in lymphocytes at Day 1 and a late increase in basophils at Day 12 after the dive. Inflammatory markers and hematocrit and hemoglobin increased immediately after the dive, dropped at Day 1, and reverted gradually to the control level from Day 4 to Day 12. Serotonin and dopamine decreased, while adrenaline increased at Day 1, gradually recovering in the days of follow-up. Insulin, luteinizing hormone, growth hormone, and prolactin increased, while testosterone, cortisol, 17β-estradiol, thyroid-stimulating hormone, and adrenocorticotropic hormone decreased at Day 1, with a partial recovery at Day 4. We conclude that the homeostatic response to the extreme, prolonged underwater performance showed signs of psychological and pro-inflammatory stress. The hormonal response reflected an acute testicular insufficiency. These responses resembled those characteristics for ultra-endurance exercise accompanied by vasculitis and dehydration.

Hypoxia alters micturition, which influences bladder function by involving different neurological and humoral systems. In this study we assessed the mid-term effects of altitude hypoxia on uroflowmetry in healthy male lowlander native Nepali porters and Italian trekkers, four each, who coattended a Himalayan expedition. All the participants completed a 19-day trek along a demanding route with ascent and descent at the Kanchenjunga Mountain. They underwent micturition and urodynamic analysis twice, at low altitude of 665 m a.s.l. and high altitude of 4,750 m a.s.l. Statistical comparisons considered the altitude effects (low vs. high) and ethnicity (Italian vs. Nepali). Food consumption was recorded, and water and energy intake were calculated. We found trends of borderline significance in the mean urinary flow rate (Q mean ) (p = 0.058; effect size η 2 p = 0.478) and in Q max to the advantage of the Nepali. There was no evidence of differences when comparing time to Q max and urine volume at Q max and Q mean for altitude or altitude × ethnicity. In addition, there was a lonely female participant, who, analyzed as a case report, showed increased Q mean at high altitude. Older age mitigated while energy intake potentiated the ethnic differences noted in uroflowmetry. We conclude that altitude hypoxia rather inappreciably affects micturition in healthy men. However, a trend for possible ethnic differences raises worthy of note perspectives on adaptive ability of micturition. Also, dietary intake and age should be considered as confounding elements when evaluating micturition.

Long-term exposure to high altitude causes adaptive changes in several blood biochemical markers along with a marked body mass reduction involving both the lean and fat components. The aim of this study was to evaluate the impact of extended physical strain, due to extensive trekking at high altitude, on body composition, selected biomarkers in the blood, and the protective role of a high-protein diet in muscle dysfunction. We found that physical strain at high altitude caused a significant reduction in body mass and body fat, with a concomitant increase in the cross-sectional area of thigh muscles and an unchanged total lean body mass. Further, we found reductions in plasma leptin and homocysteine, while myoglobin, insulin, and C-reactive protein significantly increased. Creatine kinase, lactate dehydrogenase, and leptin normalized per body fat were unchanged. These findings demonstrate that high-altitude hypoxia, involving extended physical effort, has an impact on muscle function and body composition, facilitating sarcopenia and affecting body mass and fat distribution. It also activates pro-inflammatory metabolic pathways in response to muscular distress. These changes can be mitigated by a provision of a high-protein diet.

The use of hyperbaric oxygen plays a significant role in many aspects of medicine. However, there are few studies that analyzed the role of hyperbaric oxygen, in addition to physical exercise, on the endocrine profile. The aim of this study was to compare changes in plasma male sex hormones after hyperbaric physical exercise with different hyperbaric oxygen pre-conditionings. We recruited six healthy, well-trained recreational male divers. Concentrations of prolactin (PRL), follicle-stimulating hormone (FSH), luteotrophic hormone (LH), cortisol, 17-β estradiol (E2), and total testosterone (TT) were measured in venous blood immediately after four different study conditions. Exercise increased PRL and hyperbaric oxygen potentiated this effect. Hyperbaria stimulated the E2 reduction and hyperoxia partially inhibited this reduction. Hyperbaria, but not hyperoxia, stimulated the TT reduction. There were no changes in FSH, LH, and cortisol. The increase in PRL likely reflects a stress response after physical exercise, amplified by hyperbaric oxygen. TT reduction may be interpreted as an acute and transient fertility impairment. Age, blood pressure, and BMI were taken into account as covariates for statistical analyses, and they significantly affected the results, in particular TT. These data open new insight into the role of E2 and PRL in male endocrine adaptive responses.

The aim of this study was to investigate the effects of the extreme environment of high altitude hypoxia on olfactory threshold. The study was conducted before, during, and after a scientific expedition to Mera Peak (5,800 m). The n-butanol test was used for the assessment of the magnitude of the olfactory threshold. The finding was that the olfactory threshold dramatically increased at high altitude. We conclude that there is a physiological adaptation of olfaction due to altitude-hypoxia.

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.

Aging is characterized by a lower homeostatic capacity and the carotid body (CB) plays an important role during aging. Here, we sought to elucidate whether the aging effects on the oxygen-sensitive mechanisms in CB cells occur through a reduction of the contact surfaces in the synaptic junctions. The hypothesis was that the CB would undergo a "physiological denervation" in old age. Two groups of male Wistar rats, young (2-3 months old) and senescent (22 months old) were used. CBs were rapidly dissected and the specimens were subjected to a routine transmission electron microscopic procedure. Expressions of HIF-1 proportional, variant, VEGF and NOS-1 were evaluated by immunohistochemical analysis. Our results show that in the old CB, HIF-1 proportional, variant, VEGF and NOS-1 expressions decrease. The cell volume, the number of mitochondria and that of dense-cored vesicles were reduced, and the nucleus shrank. There also was an accumulation of lipofuscin and a proliferation of extracellular matrix. Most importantly, there were fewer synaptic connections between chemoreceptor cells. The total number of synapses observed in all electronograms decreased from 125 in the young to 28 in the old CB. These results suggest the aging CB undergoes a "physiological denervation" leading to a reduction in homeostatic capacity. The age-related reduction of synaptic junctions may be a self-protective mechanism through which cells buffer themselves against reactive oxygen species accumulation during aging.

Neuroglobin (Ngb) is a member of the vertebrate globin family expressed particularly in the brain and in the retina. Ngb is concentrated in the mitochondria-containing areas of neurons, and its distribution is correlated with oxygen consumption rates. Previously we have shown that Ngb is expressed in carotid body (CB) tissues. Considering that hypoxia and aging may be linked through a series of adaptive and protective mechanisms (e.g. reduction in mitochondrial numbers), we investigate the role of Ngb during aging and hypoxia. Two groups of six rats (age-matched 3 and 24 months old) were kept in room air as a control groups, the others two groups were kept in a Plexiglas chamber for 12 days in chronic hypoxia (10-12% inspired oxygen). The presence of Ngb in the CB tissue was detected by immunohistochemistry using a polyclonal antibody. Ngb immunoreactivity was significantly higher in CB tissues from young rats exposed to chronic intermittent hypoxia, whereas CB tissues from old rats did not show any significant increase in Ngb levels after hypoxia. Similar to hemoglobin, Ngb may act as a respiratory protein by reversibly binding gaseous ligands NO and O(2) and could act as a NO scavenger and participate in detoxification of Reactive Oxygen Species (ROS) generated under hypoxic conditions.