Mieczyslaw Pokorski

Obstructive sleep apnea and type 2 diabetes

Type 2 diabetes and obstructive sleep apnea (OSA) are diseases with high prevalence and major public health impact. There is evidence that regular snoring and OSA are independently associated with alterations in glucose metabolism. Thus, OSA might be a risk factor for the development of type 2 diabetes. Possible causes might be intermittent hypoxia and sleep fragmentation, which are typical features of OSA. OSA might also be a reason of ineffective treatment of type 2 diabetes. There is further evidence that the treatment of OSA by continuous positive airway pressure (CPAP) therapy might correct metabolic abnormalities in glucose metabolism. It is assumed that this depends on therapy compliance to CPAP. On the other hand, there are also hints in the literature that type 2 diabetes per se might induce sleep apnea, especially in patients with autonomic neuropathy. Pathophysiological considerations open up new insights into that problem. Based on the current scientific data, clinicians have to be aware of the relations between the two diseases, both from the sleep medical and the diabetological point of view. The paper summarizes the most important issues concerning the different associations of OSA and type 2 diabetes.

Pathologies currently identified by exhaled biomarkers.

Ancient Greek physicians already knew that the smell of human breath could provide a clue to the pathology. Nowadays, volatile breath biomarkers are known to be released in a broad range of diseases. However, their identification, isolation, and quantification as indicative of relevant alterations in clinical status have required the development of new techniques and analytical methods. Breath sample analysis encounters several obstacles. Particularly, there is a need of a system that could work in a continuous manner, with the low concentration and small volume of a sample. Herein we review, in the light of literature and our experience, clinical applications of the metal oxide semiconductor (MOS) sensor for breath analysis to distinguish between health and disease in some conditions, e.g., diabetes, multiple chemical sensitivity (MCS) syndrome, or in tracing the central neural fatigue resulting from cognitive performance. We submit that exhaled breath analysis holds promise in the diagnosis and treatment of genetic or neurodegenerative diseases which involve cognitive derangements.

Depressive symptoms in schizophrenic patients

Distinction between true negative and depressive symptoms in schizophrenia is difficult. In the present study we seek to establish the psychological profile of depression-prone schizophrenic patients. We addressed the issue by comparing the expression of psychological indices, such as the feelings of being in control of events, anxiety, mood, and the style of coping with stress in depressive and non-depressive schizophrenics. We also analyzed the strength of the association of these indices with the presence of depressive symptoms. A total of 49 patients (18 women and 31 men, aged 23-59) were enrolled into the study, consisting of a self-reported psychometric survey. We found that the prevalence of clinically significant depression in schizophrenic patients was 61%. The factors which contributed to the intensification of depressive symptoms were the external locus of control, anxiety, gloomy mood, and the emotion-oriented coping with stress. We conclude that psychological testing may discern those schizophrenic patients who would be at risk of depression development and may help separate the blurred boundaries between depressive and negative symptoms of schizophrenia.

Volatile organic compounds (VOCs) fingerprint of Alzheimer's disease

Alzheimers disease (AD) is a profoundly life changing condition and once diagnosis occurs, this is typically at a relatively late stage into the disease process. Therefore, a shift to earlier diagnosis, which means several decades before the onset of the typical manifestation of the disease, will be an important step forward for the patient. A promising diagnostic and screening tool to answer this purpose is represented by breath and exhaled volatile organic compounds (VOCs) analysis. In fact, human exhaled breath contains several thousand of VOCs that vary in abundance and number in correlation with the physiological status. The exhaled VOCs reflect the metabolism, including the neuronal ones, in healthy and pathological conditions. A growing number of studies clearly demonstrate the effectiveness of VOCs analysis in identifying pathologies, including neurodegenerative diseases. In the present study we recorded, in real time, breath parameters and exhaled VOCs. We were able to demonstrate a significant alteration in breath parameters induced by the pathology of AD. Further, we provide the putative VOCs fingerprint of AD. These vital findings are an important step toward the early diagnosis of AD.

Region-specific effects on brain metabolites of hypoxia and hyperoxia overlaid on cerebral ischemia in young and old rats: a quantitative proton magnetic resonance spectroscopy study

BackgroundBoth hypoxia and hyperoxia, deregulating the oxidative balance, may play a role in the pathology of neurodegenerative disorders underlain by cerebral ischemia. In the present study, quantitative proton magnetic resonance spectroscopy was used to evaluate regional metabolic alterations, following a 24-hour hypoxic or hyperoxic exposure on the background of ischemic brain insult, in two contrasting age-groups of rats: young - 3 months old and aged - 24 months old.MethodsCerebral ischemia was induced by ligation of the right common carotid artery. Concentrations of eight metabolites (alanine, choline-containing compounds, total creatine, γ-aminobutyric acid, glutamate, lactate, myo-inositol and N-acetylaspartate) were quantified from extracts in three different brain regions (fronto-parietal and occipital cortices and the hippocampus) from both hemispheres.ResultsIn the control normoxic condition, there were significant increases in lactate and myo-inositol concentrations in the hippocampus of the aged rats, compared with the respective values in the young ones. In the ischemia-hypoxia condition, the most prevalent changes in the brain metabolites were found in the hippocampal regions of both young and aged rats; but the effects were more evident in the aged animals. The ischemia-hyperoxia procedure caused less dedicated changes in the brain metabolites, which may reflect more limited tissue damage.ConclusionsWe conclude that the hippocampus turns out to be particularly susceptible to hypoxia overlaid on cerebral ischemia and that old age further increases this susceptibility.

Ascorbyl Palmitate as a Carrier of Ascorbate into Neural Tissues

We have investigated the hypothesis that a lipid-soluble derivative of ascorbic acid, ascorbyl-6-palmitate (AP), could serve as a carrier of ascorbate into neural tissues. Ascorbate could then exert its physiological effects in the biomembranes that are the target sites of the cellular signaling pathways which are normally hardly accessible to this water-soluble compound. The potential role of AP would require that it penetrates into tissues. The major objective of the study was to determine whether ascorbate could be recovered from cerebral cortex and carotid body tissues, both sensitive to the hypoxic stimulus, after AP given by gavage. Biological samples were analyzed by HPLC for the determination of ascorbate. We found that ascorbate was recovered from the tissues studied. Its content was higher in both tissues, by nearly an order of magnitude, after ingestion of AP than after ingestion of ascorbic acid, and the ascorbate level was higher in the carotid body than in the cortex. Hypoxia decreased the ascorbate content which implies physiological activity of ascorbate carried alongside the AP molecule. The lipophilic AP was able to cross biological barriers and satisfied the tissue demand for ascorbate better than the hydrophilic form. AP should be considered as the preferred form of transport of ascorbate into neural tissues. The results of this study suggest wider pharmacological applications of ascorbyl palmitate.

The hypoxic ventilatory response and TRPA1 antagonism in conscious mice.

Recently, TRPA1 channels, richly expressed in both peripheral and central neural systems, have been proposed as novel sensors of changes in oxygen concentration along the hypoxic–hyperoxic continuum. In this study, we investigated the hypothesis that TRPA1 channels blockade should profoundly affect the hypoxic ventilatory response (HVR).

Non-invasive Assessment of Exhaled Breath Pattern in Patients with Multiple Chemical Sensibility Disorder

Multiple chemical sensitivity (MCS) is a complex disorder initiated by chemical exposure, particularly through the airways. MCS patients report sensitivity or intolerance to low levels of a wide spectrum of chemicals. Symptoms could include asthma-like signs, rhinitis, fatigue, cognitive dysfunction, psycho-physiological alteration, and other specific tissue reactions resembling hypoxic and oxidative stress effects. To recognize physiological signs that would allow the diagnosis of MCS in a non-invasive way we investigated the potential application of a new sensor system. In healthy volunteers, we measured exhaled breath content in the control condition and under exposure to olfactory stressors that mimic hypoxic or pollutant stressors playing a potential role in the generation of the MCS disorder. The recording system used is based on metal oxide semiconductor (MOS) sensor having a sensing range of 450-2,000 ppm CO(2) equivalents, which is able to detect a broad range of compounds playing a potential role in the generation of the MCS disorder, while correlating directly with the CO(2) levels. The results indicate that the recording system employed was suitable for the analysis of exhaled breath content in humans. Interestingly, the system was able to detect and discriminate between the exhaled breath content taken from the control condition and those from conditions under stress that mimicked exposures to pollutant or hypoxia. The results suggest that chronic hypoxia could be involved in the MCS disorder.

Human Carotid Body HIF and NGB Expression During Human Development and Aging

Hypoxia inducible factor 1(HIF-1α) is the regulator of oxygen homeostasis in tissue correlated with neuroglobin (NGB) a member of the family of globins in vertebrates. The present study investigates, the expression and the location of NGB, HIF-1α in human carotid bodies, sampled at autopsy from children (mean age: 2 year ±), young (mean age: 27.5) and 4 old subjects (mean age: 73.5). The percentage of NGB positive area was higher in the old subjects (4.4 ±2.8%), as compared with the young ones (2.4 ±1.8%) and children (1.0 ±1.8%). Positive HIF-1α nuclei were detected in young and old subjects (1.0 ±0.14% vs 3.0 ±0.28%, respectively), whereas CB tissues from children did not show any HIF-1α reaction. The increase of NGB and HIF-1α expression suggests a possible role of the two oxygen sensors in the aging processes. Even though the physiological role of NGB is not well understood, it could be suggested that is act as a respiratory protein connected with HIF.

Computer games and fine motor skills.

The study seeks to determine the influence of computer games on fine motor skills in young adults, an area of incomplete understanding and verification. We hypothesized that computer gaming could have a positive influence on basic motor skills, such as precision, aiming, speed, dexterity, or tremor. We examined 30 habitual game users (F/M - 3/27; age range 20-25 years) of the highly interactive game Counter Strike, in which players impersonate soldiers on a battlefield, and 30 age- and gender-matched subjects who declared never to play games. Selected tests from the Vienna Test System were used to assess fine motor skills and tremor. The results demonstrate that the game users scored appreciably better than the control subjects in all tests employed. In particular, the players did significantly better in the precision of arm-hand movements, as expressed by a lower time of errors, 1.6 ± 0.6 vs. 2.8 ± 0.6 s, a lower error rate, 13.6 ± 0.3 vs. 20.4 ± 2.2, and a shorter total time of performing a task, 14.6 ± 2.9 vs. 32.1 ± 4.5 s in non-players, respectively; p < 0.001 all. The findings demonstrate a positive influence of computer games on psychomotor functioning. We submit that playing computer games may be a useful training tool to increase fine motor skills and movement coordination.