Overview of Curcumin and Piperine Effects on Glucose Metabolism: The Case of an Insulinoma Patient's Loss of Consciousness.

The hypoglycemic properties of curcumin supplements in therapeutic doses are well-known and may represent a useful tool for the treatment of chronic diseases such as metabolic syndrome, insulin resistance and type 2 diabetes. The poor bioavailability of curcumin can be improved with the concomitant administration of piperine, with no severe adverse effects on glycemia reported so far in the literature. In this article, we further discuss a previously reported case of a helicopter pilot, affected by grade I obesity who, under curcumin and piperine treatment, experienced a transient loss of consciousness (TLOC), during a low-altitude flight. This episode led to a diagnosis of insulinoma, previously asymptomatic. We hypothesized that the combined effects of curcumin and piperine might have caused a severe hypoglycemic episode and subsequent TLOC. Therefore, further studies should be conducted to evaluate the safety of curcumin and piperine supplementation in subjects with impaired glucose metabolism and insulin secretion.

Microgravity and the intervertebral disc: The impact of space conditions on the biomechanics of the spine.

The environmental conditions to which astronauts and other military pilots are subjected represent a unique example for understanding and studying the biomechanical events that regulate the functioning of the human body. In particular, microgravity has shown a significant impact on various biological systems, such as the cardiovascular system, immune system, endocrine system, and, last but not least, musculoskeletal system. Among the potential risks of flying, low back pain (LBP) has a high incidence among astronauts and military pilots, and it is often associated with intervertebral disc degeneration events. The mechanisms of degeneration determine the loss of structural and functional integrity and are accompanied by the aberrant production of pro-inflammatory mediators that exacerbate the degenerative environment, contributing to the onset of pain. In the present work, the mechanisms of disc degeneration, the conditions of microgravity, and their association have been discussed in order to identify possible molecular mechanisms underlying disc degeneration and the related clinical manifestations in order to develop a model of prevention to maintain health and performance of air- and space-travelers. The focus on microgravity also allows the development of new proofs of concept with potential therapeutic implications.

Space flight and central nervous system: Friends or enemies? Challenges and opportunities for neuroscience and neuro-oncology.

Space environment provides many challenges to pilots, astronauts, and space scientists, which are constantly subjected to unique conditions, including microgravity, radiations, hypoxic condition, absence of the day and night cycle, etc. These stressful stimuli have the potential to affect many human physiological systems, triggering physical and biological adaptive changes to re-establish the homeostatic state. A particular concern regards the risks for the effects of spaceflight on the central nervous system (CNS), as several lines of evidence reported a great impact on neuroplasticity, cognitive functions, neurovestibular system, short-term memory, cephalic fluid shift, reduction in motor function, and psychological disturbances, especially during long-term missions. Aside these potential detrimental effects, the other side of the coin reflects the potential benefit of applicating space-related conditions on Earth-based life sciences, as cancer research. Here, we focused on examining the effect of real and simulated microgravity on CNS functions, both in humans and in cellular models, browsing the different techniques to experience or mime microgravity on-ground. Increasing evidence demonstrate that cancer cells, and brain cancer cells in particular, are negatively affected by microgravity, in terms of alteration in cell morphology, proliferation, invasion, migration, and apoptosis, representing an advancing novel side of space-based investigations. Overall, deeper understandings about the mechanisms by which space environment influences CNS and tumor biology may be promisingly translated into many clinical fields, ranging from aerospace medicine to neuroscience and oncology, representing an enormous pool of knowledge for the implementation of countermeasures and therapeutic applications.

Loss of consciousness in a helicopter pilot as plausible first sign of insulinoma: a case report.

A 50-year-old man who worked as a helicopter rescue pilot transiently lost consciousness while piloting a helicopter rescue. In the diagnostic process, all tests for the main possible differential diagnoses of loss of consciousness (cardiological and neurological) were performed and yielded normal results. Blood chemistry tests revealed recurrent fasting hypoglycemia and Chromogranin A was at the upper limit of normal. Fine needle aspiration guided by endoscopic ultrasonography was used to diagnose insulinoma-type neuroendocrine tumor of the pancreas. According to the Italian policies, the occupational physician aims to maintain professional skills without neglecting flight safety. A careful analysis of the relationship between the characteristics of the state of health of the aviator and his specific work needs was carried out, and he was given the opportunity to continue working as a rescue pilot thanks to medical therapies associated with organizational interventions in the workplace.

Inflammatory interactions between degenerated intervertebral discs and microglia: Implication of sphingosine-1-phosphate signaling.

The etiology of intervertebral disc degeneration is largely unknown, but local neuroinflammation may exert a crucial role through activation of cells as microglia and pro-inflammatory cytokines production. We aimed to compare the effect of degenerated and normal intervertebral disc microenvironment on microglial cells and the potential role of sphingosine-1-phosphate, a pro-inflammatory sphingolipid, in their crosstalk. Human degenerated intervertebral discs (Pfirrmann grade IV) were obtained at surgery for spondylolisthesis. Normal intervertebral discs were collected from cadaveric normal lumbar spines. Normal and degenerated-intervertebral discs were kept in culture to obtain media conditioning. Then, microglial cells were cocultured with conditioned media and viability, proliferation, migration, chemotaxis, and inflammatory gene expression were evaluated. The results demonstrate that conditioned media from degenerated intervertebral discs activate microglial cells, increasing chemotaxis, migration, and pro-inflammatory mediators release to a great extent than normal discs. In addition, we show that the administration of sphingosine-1-phosphate to normal intervertebral disc/microglia coculture mimicked degenerative effects. Interestingly, sphingosine-1-phosphate content in conditioned media from degenerated discs was significantly higher than that from normal ones. In addition, FTY720, a functional antagonist of sphingosine-1-phosphate, potently inhibited the effect of degenerated intervertebral discs on microglial inflammatory factor transcription and migration. Our data report, for the first time, that sphingosine-1-phosphate is involved as signal in the microenvironment of human degenerated intervertebral discs. Sphingosine-1-phosphate signaling modulation by FTY720 may induce beneficial effects in counteracting microglial activation during intervertebral disc degeneration.

Decreased serum level of sphingosine-1-phosphate: a novel predictor of clinical severity in COVID-19.

The severity of coronavirus disease 2019 (COVID-19) is a crucial problem in patient treatment and outcome. The aim of this study is to evaluate circulating level of sphingosine-1-phosphate (S1P) along with severity markers, in COVID-19 patients. One hundred eleven COVID-19 patients and forty-seven healthy subjects were included. The severity of COVID-19 was found significantly associated with anemia, lymphocytopenia, and significant increase of neutrophil-to-lymphocyte ratio, ferritin, fibrinogen, aminotransferases, lactate dehydrogenase (LDH), C-reactive protein (CRP), and D-dimer. Serum S1P level was inversely associated with COVID-19 severity, being significantly correlated with CRP, LDH, ferritin, and D-dimer. The decrease in S1P was strongly associated with the number of erythrocytes, the major source of plasma S1P, and both apolipoprotein M and albumin, the major transporters of blood S1P. Not last, S1P was found to be a relevant predictor of admission to an intensive care unit, and patient's outcome. Circulating S1P emerged as negative biomarker of severity/mortality of COVID-19 patients. Restoring abnormal S1P levels to a normal range may have the potential to be a therapeutic target in patients with COVID-19.

Predictors of ear barotrauma in aircrews exposed to simulated high altitude.

INTRODUCTION: Ear barotrauma is an adverse effect related to hypobaric exposure. Ear, nose, and throat (ENT) diseases are risk factors for barotrauma in aircrews trained in a hypobaric chamber, but excluding affected subjects from exposure does not abolish the risk in asymptomatic trainees. We investigated other possible predictors, including history of ENT diseases, ENT clinical abnormalities, altitude, and subject's age. METHODS: After a complete ENT evaluation including otoscopy and tympanometry, 314 aircrews underwent hypobaric chamber training. Two altitude training profiles up to 35,000 ft (10,668 m) and 25,000 ft (7620 m), respectively, were used. Subjects were grouped according to if they were asymptomatic, had acute barotitis, or reported delayed ear pain the day after the exposure. RESULTS: There were 7 men who had acute barotitis (incidence of 2.3%) and 28 men who had delayed ear pain (incidence of 9.2%). A significant association resulted between history of ENT diseases and delayed ear pain and between abnormal ENT findings and acute barotitis in subjects exposed to the higher profile. Altitude was associated with increased risk of delayed ear pain. Delayed ear pain was associated with older age in subjects exposed to the lower altitude and younger age in subjects exposed to the higher altitude. DISCUSSION: Our data suggest that in subjects exposed to 35,000 ft (10,668 m), the history of previous ENT diseases and younger age may be valid predictors of delayed ear pain, while abnormal ENT findings may predict acute barotitis. At 25,000 ft (7620 m), subjects with older age may have increased risk of delayed ear pain.

Acute hypobaric-hypoxia challenge and salivary cortisol and DHEA-S in healthy male subjects.

BACKGROUND: Hypobaric hypoxia is a stressful emergency situation that can cause a degradation of the sensory, motor, and higher cognitive functions necessary for safe flight. METHODS: We studied the salivary cortisol and dehydroepiandrosterone-sulfate (DHEA-S) concentrations of 12 healthy male military aviators (AV) exposed to an altitude-induced hypoxia challenge in a hypobaric chamber. A matched control group (C) of eight flight physiology instructors wearing oxygen masks during the challenge was studied. Salivary samples were collected every 2 h on 3 experimental days (the day before, the day of, and the day after the hypobaric chamber challenge). RESULTS: In the AV group, salivary cortisol concentrations showed a statistically significant increase from 5.42 +/- 0.15 measured at 08:30 to 11.37 +/- 1.86 ng ml(-1) during the hypobaric chamber challenge and a statistically significant increase in DHEA-S was also measured (from 3.15 +/- 0.42 ng x ml(-1) at 08:30 to 5.99 +/- 0.15 ng x ml(-1)). The day after the challenge, the concentrations of both hormones were comparable to those measured the day before; neither C nor AV showed any disturbances of the physiological diurnal fluctuations of cortisol and DHEA-S. No differences were found among the cortisol/DHEA-S ratios measured during the 3 experimental days in the AV group. DISCUSSION: In spite of having experienced a psycho-physical stress, the AVs did not show any dysregulation of the diurnal fluctuations of cortisol and DHEA-S, thus presenting a good level of stress resilience. Data presented in this paper are consistent with recent literature suggesting a stress-buffering role of DHEA-S.

Altitude chamber related adverse effects among 1241 airmen.

INTRODUCTION: Altitude chambers are used for training aircrews, but incidents have been reported, including decompression sickness (DCS) and barotrauma. To minimize chamber-related adverse effects we implemented a set of measures, including altitude restriction and a pre-chamber clinical selection (PCS) of subjects before exposure. METHODS: We reviewed our records regarding 1254 individuals who were trained from 2003 to 2009. After the first 3 subjects, the maximum altitude of the highest training profile was limited to 43,000 ft (13,106.4 m) instead of 45,000 ft (13,716 m) and, after the first 327 subjects, a clinical evaluation of each trainee was performed by an otolaryngologist before altitude exposure. The evaluation included otoscopy and tympanometry, and subjects with abnormal results were not cleared for altitude exposure. Subjects were grouped by having undergone the highest profile before (3 subjects) or after altitude restriction (8 subjects) and received clinical selection (PCS group, 927 subjects) or not (control group, 327 subjects). RESULTS: We recorded 32 total adverse effects (overall incidence 2.6%), 21 in the PCS group (2.3%) and 11 in the control group (3.4%). The difference between groups was not significant. Adverse effects included 19 cases of acute barotitis (1.5%), 1 case of DCS (0.08%), and 4 cases of syncope (0.3%). The incidence of barotitis was 1.1% in the PCS group and 2.7% in the control group. The altitude restriction was ineffective in preventing both barotrauma and DCS. CONCLUSIONS: The incidence of adverse effects in our subjects was low and pre-chamber clinical selection appeared to be effective in reducing the risk of barotitis.

Ear pain after breathing oxygen at altitude: prevalence and prevention of delayed barotrauma.

INTRODUCTION: Military pilots frequently report ear pain with onset several hours after altitude exposure while breathing pure oxygen, but the prevalence of this problem is unknown. A similar problem is described in divers after breathing hyperbaric oxygen and it is related to the oxygen contained in the middle ear. METHODS: In order to assess the prevalence of delayed ear pain after altitude exposure and investigate the effectiveness of preventive use of a nasal balloon (NB), we studied 88 healthy military jet pilots who were asymptomatic after altitude chamber exposure which included 100% oxygen breathing. A group of 44 subjects received the NB shortly after the chamber and they were advised to use it every hour before going to sleep. A control group of 44 subjects was requested to perform the Valsalva maneuver alone over the same period. All subjects underwent clinical examination by an otolaryngologist and tympanometry just before the chamber exposure and again the day after. RESULTS: The day after the altitude exposure, 53.4% of subjects reported ear pain. In the treated group, 61.4% of subjects were free of symptoms, compared to 31.8% in the control group (P < 0.01). Tympanogram was abnormal in eight symptomatic subjects and in six asymptomatic. CONCLUSION: Our data suggest that in our subjects there is high prevalence of delayed ear barotrauma after altitude chamber exposure while breathing pure oxygen and the tympanogram may improve the accuracy of the diagnosis in asymptomatic subjects. The nasal balloon appears to be effective for prevention.

Acute otitic barotrauma during hypobaric chamber training: prevalence and prevention.

INTRODUCTION: Barotitis media is known to be an adverse effect of altitude changes, but few studies have investigated this condition with respect to hypobaric chamber training and the resulting estimations of prevalence vary. METHODS: In order to assess the prevalence of hypobaric chamber-related barotitis and evaluate a method of prevention, 335 healthy military pilots undergoing high altitude training were subject to clinical examination and tympanometry before entering the chamber. In order to minimize the risk of barotrauma, only subjects with normal preflight findings were cleared for altitude exposure. Barotitis media was diagnosed on the basis of ear pain and clinical findings according to Teed's classification. RESULTS: Barotitis occurred in eight subjects; seven cases were monolateral and one bilateral, prevalence was 2.4%. CONCLUSION: The prevalence of barotitis after hypobaric chamber training is low in our study, suggesting that a pre-chamber medical check including clinical examination and tympanometry could be effective in identifying subjects at risk.

Repositioning maneuver for the treatment of the apogeotropic variant of horizontal canal benign paroxysmal positional vertigo.

OBJECTIVE: The purpose of this study was to determine the effectiveness of a new physical maneuver in the treatment of the apogeotropic variant of horizontal canal benign paroxysmal positional vertigo. STUDY DESIGN: Case review. SETTING: Outpatient clinic. PATIENTS: The diagnosis of apogeotropic horizontal canal benign paroxysmal positional vertigo was based on the history of recurrent sudden crisis of vertigo associated with bursts of horizontal apogeotropic paroxysmal nystagmus provoked by turning the head from the supine to either lateral position. The patients were three men and five women ranging in age from 31 to 73 years (average, 49.2 yr). INTERVENTIONS: All patients were treated with a repositioning maneuver based on the hypothesis that the syndrome is caused by the presence of free-floating dense particles inside the endolymph of the anterior arm of the horizontal canal. The maneuver favors their shifting into the posterior arm of the canal. Patients were reexamined immediately after the treatment and underwent Gufoni's liberatory maneuver for the geotropic variant of horizontal canal benign paroxysmal positional vertigo. MAIN OUTCOME MEASURE: The treatment outcome was considered as responsive when, after one repositioning maneuver, nystagmus shifted from apogeotropic to geotropic. RESULTS: The repositioning maneuver resulted in a transformation from the apogeotropic variant into a geotropic variant of horizontal canal benign paroxysmal positional vertigo in all patients. CONCLUSION: This maneuver represents a simple and effective approach to the treatment of the apogeotropic variant of horizontal canal benign paroxysmal positional vertigo. It favors the shifting of the canaliths from the anterior into the posterior arm of the horizontal canal from where they can migrate into the utricle with Gufoni's maneuver.

Vestibular evoked myogenic potentials and glycerol testing.

OBJECTIVES/HYPOTHESIS: The objective was to evaluate dizziness as the first symptom of endolymphatic hydrops, which could provide valuable information on the initial stages of endolymphatic hydrops development. STUDY DESIGN: The present investigation was specifically designed to establish whether a combination of the traditional glycerol test and the vestibular evoked myogenic potential (VEMP) glycerol test is capable of diagnosing endolymphatic hydrops early and to identify potential Meniere's disease. The study was limited to patients who complained of dizziness as their only vestibular symptom. METHODS: Thirty-eight consecutive patients with dizziness who had received no treatment were investigated. Each patient underwent glycerol testing measured with both conventional pure-tone audiometry and vestibular evoked myogenic potential testing. For the vestibular evoked myogenic potential glycerol test, an increase of more than 20% in both latency and amplitude after glycerol intake was considered an improvement. RESULTS In one patient, the reappearance of the vestibular evoked myogenic potentials was observed. In another six patients, there was an increase in the vestibular evoked myogenic potential amplitudes, unilaterally in four cases and bilaterally in two. One patient showed a bilateral improvement in amplitude and an unilateral amelioration in latency. CONCLUSION: The assumption of saccular dilation as a sign of early Meniere's disease was not supported by the literature, which considered saccular hydrops as the final progression of the dilation of the endolymphatic compartments into the cochlea. These data seem to indicate that in our patients a saccular dysfunction rather than an early saccular hydrops has been documented, confirming vestibular evoked myogenic potential testing as an intriguing diagnostic option for a lesion of this structure. The vestibular evoked myogenic potential glycerol test proved capable of identifying dysfunctions of the saccule that were not otherwise detectable by the routine methods. Therefore, the vestibular evoked myogenic potential glycerol test should be considered as an additional method of diagnosis in patients with vertigo or dizziness.

Preservation of the saccular nerve and of the vestibular evoked myogenic potential during vestibular schwannoma surgery.

OBJECTIVE: The aim of the study was to present a case report demonstrating that vestibular evoked myogenic potentials originate from the saccular nerve. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. INTERVENTION: Vestibular evoked myogenic potentials are shown before and after operation in a patient with a surgically confirmed superior vestibular schwannoma (1.3 cm). MAIN OUTCOME MEASURES: Preoperative and postoperative audiometry, auditory brainstem response, caloric test, vestibular evoked myogenic potentials, and magnetic resonance imaging outcomes. RESULTS On preoperative audiometry, slight sensorineural hearing loss with normal auditory brainstem response could be detected. Caloric tests showed a reduced response of the right labyrinth. Vestibular evoked myogenic potentials were normal. The tumor was removed via a combined retrosigmoid and partial labyrinthectomy approach with the removal of the posterior semicircular canal. The facial, auditory, and inferior semicircular nerves were anatomically preserved. Postoperative audiometry revealed preservation of hearing and vestibular evoked myogenic potentials; caloric responses were now absent. CONCLUSION: The combined retrosigmoid and partial labyrinthectomy approach represents an ideal condition to study the influence of the saccular nerve on the origin of the vestibular evoked myogenic potentials. The maintenance of the vestibular evoked myogenic potential responses in our patient supports the concept that the vestibular evoked myogenic potential originates in the saccule and is transmitted in the saccular nerve.