Isotonic Saline Nebulization and Lung Function in Children With Mild Respiratory Ailments.

Nebulization with saline solution, although commonly used to alleviate respiratory symptoms, particularly in children, is often questioned concerning its effectiveness. In this study, we investigated the effects of isotonic saline nebulization on lung function in 40 children (mean age of 14±1 years) suffering from different types of airway disorders. Measurements were carried out directly before and up to 15 min after nebulization, for six days in a row, always on the same day time in the morning. The children were divided into two study groups according to the baseline ratio of forced expired volume in one second/forced vital capacity (FEV1/FVC), below and above 80 %. We found significant improvements after saline nebulization in FEV1, mid-expiratory flow at 50 % and 75 % of FVC (MEF50 and MEF75), and peak expiratory flow (PEF) in the group with the baseline FEV1/FVC less than 80 %. In contradistinction, children with an index greater than 80 % displayed no appreciable changes in the lung function variables when compared with the baseline level before saline nebulization. We conclude that isotonic saline nebulization might mitigate the functional signs of threatening pulmonary obstruction and as such may be clinically useful in pediatric patients with mild respiratory problems.

Influence of Sensory Stimulation on Exhaled Volatile Organic Compounds.

The real-time exhaled volatile organic compounds (VOCs) have been suggested as a new biomarker to detect and monitor physiological processes in the respiratory system. The VOCs profile in exhaled breath reflects the biochemical alterations related to metabolic changes, organ failure, and neuronal activity, which are, at least in part, transmitted via the lungs to the alveolar exhaled breath. Breath analysis has been applied to investigate cancer, lung failure, and neurodegenerative diseases. There are by far no studies on the real-time monitoring of VOCs in sensory stimulation in healthy subjects. Therefore, in this study we investigated the breath parameters and exhaled VOCs in humans during sensory stimulation: smell, hearing, sight, and touch. Responses sensory stimulations were recorded in 12 volunteers using an iAQ-2000 sensor. We found significant effects of sensory stimulation. In particular, olfactory stimulation was the most effective stimulus that elicited the greatest VOCs variations in the exhaled breath. Since the olfactory pathway is distinctly driven by the hypothalamic and limbic circuitry, while other senses project first to the thalamic area and then re-project to other brain areas, the findings suggest the importance of olfaction and chemoreception in the regulation lung gas exchange. VOCs variations during sensory activation may become putative indicators of neural activity.

Hypoxic Ventilatory Reactivity in Experimental Diabetes.

Diabetes, apart from generalized neuropathy and microangiopathy, involves tissue hypoxia, which may drive chronic proinflammatory state. However, studies on the ventilatory control in diabetes are sparse and conflicting. In this study we examined the function and morphology of diabetic carotid bodies (CBs). Diabetes was evoked in Wistar rats with streptozotocin (70 mg/kg, i.p.). The acute hypoxic ventilatory responses (HVR) to 12 and 8 % O(2) were investigated in conscious untreated rats after 2 and 4 weeks in a plethysmographic chamber. CBs were dissected and subjected to morphologic investigations: (1) electron transmission microscopy for ultrastructure and (2) laser scanning confocal microscopy to visualize the microvascular bed in sections labeled with the lectin Griffonia simplicifolia-I (GSI), an endothelial cell marker, and fluorescein isothiocyanate (FITC). All findings were referenced to the normal healthy rats. We found that diabetes distinctly dampened the HVR. At the ultrastructural level, the diabetic CB displayed proliferation of connective tissue and neovascularization deranging the interglomal structure, and lengthening the O(2) diffusion path from capillaries to chemoreceptor cells. The chemoreceptor cells remained largely unchanged. The endothelial cell labeling confirmed the intensive angiopathy and the induction of microvessel growth. We conclude that diabetes hampers the chemical regulation of ventilation due to remodeling of CB parenchyma, which may facilitate chronic hypoxia and inflammation in the organ.

Cytokines and toll-like receptors in the immune response to influenza vaccination.

Toll-like receptors (TLRs) are involved in immunogenicity. However, little information is available on the role of TLRs in the immune response to vaccination against influenza virus. The aim of the study was to analyze the relationship between the immunogenic response to influenza vaccine and the presence of soluble forms of TLRs and selected cytokines in the serum. There were two groups of subjects participating in the main protocol of the study: 55 chronically hemodialyzed patients (Group A) and 55 healthy volunteers (Group B) participated in the study. Both groups were vaccinated against influenza using a subunit Agrippal vaccine. The concentrations of human TNF-α, IL-1ß/IL-1F2, IL-6, and IL-10 were measured by a high sensitivity enzyme-linked immunosorbent assay. The soluble forms of TLR-2, TLR-4, and TLR-7 were determined in serum samples by ELISA as well. The findings were that vaccination did not appreciably influence the level soluble TRL-2, TRL-4, and TRL-7 or the cytokines investigated either in patients on hemodialysis or in healthy volunteers. Nor were there any relevant correlations between Toll-like receptors or pro-inflammatory cytokines and the immune response to influenza vaccination. On the other hand, the study showed that Toll-like receptors are increased in hemodialyzed patients, which may enhance the anti-inflammatory IL-10 and counter the downgrade of the immune response to influenza vaccine.

Adaptation of olfactory threshold at high altitude.

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.

The hypoxic ventilatory response and TRPA1 antagonism in conscious mice.

AIM: 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). METHODS: We examined the chemosensory ventilatory responses in conscious mice before and after intraperitoneal administration of the specific TRPA1 antagonist HC-030031 in two doses of 50 and 200 (cumulative dose 250) mg kg(-1) . Ventilation and its responses to mild 13% and severe 7% hypoxia, pure O2 , and 5% CO2 in O2 were recorded in a whole-body plethysmograph. RESULTS: TRPA1 antagonism caused a dose-dependent attenuation of the HVR. Ventilatory stimulation was virtually abrogated in response to the mild, but it remained viable, albeit slashed, at severe hypoxia after the bigger dose of HC-030031. The TRPA1 function seemed specific for the hypoxic chemoreflex as neither the response to pure O2 nor hypercapnia was appreciably influenced by the TRPA1 antagonist. CONCLUSIONS: The study unravelled the role of TRPA1 in shaping the ventilatory response to low-intensity hypoxia, liable to be mediated by vagally innervated respiratory chemosensors of lower functional rank, but contradicted the TRPA1 being indispensable for the powerful carotid body chemoreflex in face of a severe hypoxic threat.

Development and aging are oxygen-dependent and correlate with VEGF and NOS along life span.

During development and aging, vascular remodeling represents a critical adaptive response to modifications in oxygen supply to tissues. Hypoxia inducible factor (HIF) has a crucial role and is modulated by oxygen levels, with an age-dependent response in neonates, adult, and aged people. ROS are generated under hypoxic conditions and the accumulation of free radicals during life reduces the ability of tissues to their removal. In this immunohistochemical study we investigated the presence and localization of VEGF and iNOS in human carotid bodies (CB) sampled at autopsy from three children (mean age - 2 years), four adult young subjects (mean age - 44.3 years), and four old subjects (mean age - 67.3 years). VEGF immunoreactivity was significantly enhanced in CB tissues from the children (7.2 ± 1.2%) and aged subjects (4.7 ± 1.7%) compared with the young adults (1.4 ± 0.7%). On the other hand, iNOS immunoreactivity was enhanced in CB tissues from the children (0.4 ± 0.04%) and young adult subjects (0.3 ± 0.02%) compared with the old subjects (0.2 ± 0.02%). Prevention of oxygen desaturation, reducing all causes of hypoxemia from neonatal life to aging would decrease the incidence of diseases in the elderly population with lifespan extension.

Proteomic analysis of the carotid body: a preliminary study.

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.

Hypoxic ventilatory response in limited iron in the rat.

The study seeks to determine the role of iron in the ventilatory response to acute hypoxia in anesthetized, spontaneously breathing Wistar rats, using an experimental paradigm of chronic iron chelation. Since the hypoxic ventilatory response is generated by carotid body chemoreceptors, another objective of the study was to assess the hitherto unknown effects of iron chelation on carotid body ultrastructure. Minute ventilation and its tidal and frequency components' responses to acute 9% FiO2 were measured with plethysmography before and after iron chelation with ciclopirox olamine (CPX, 20 mg/kg, i.p.) for 7 days. Transmission electron microscopy was employed to assess the ultrastructure of carotid body tissue. We found that CPX pretreatment significantly decreased both resting and peak hypoxic ventilation in a range of 20-25%. Iron chelation caused degenerative changes in carotid body parenchyma, particularly affecting the chemoreceptor cell ultrastructure, consisting of cytoplasmic vacuolization, formation of lysosomes and multivesicular bodies, and damage to mitochondria. We report herein that inhibition of ventilatory responsiveness in limited iron is explicable by iron's role in maintaining carotid body ultrastructural viability rather than by emulation of hypoxic HIF-1alpha-mediated transduction pathway in chemoreceptor cells suggested by previous in vitro studies.

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.

Depression and religiosity in older age.

We investigated the hypothesis that religious commitment could help counter general affective distress, accompanying depressive symptoms, in older age. A total of 34 older adults, all catholic believers, completed self-reported questionnaires on the presence of depressive symptoms, religiosity, health, worry, and the style of coping with stress. The depressive and non-depressive subgroups were then created. The prevalence of depressive symptoms was 50%, with the substantial predominance of females. Regression analyses indicate that health expectations and worry significantly worsen with increasing intensity of depressive symptoms. The results further show that religious engagement was not different between the depressive and non-depressive subgroups. Religiosity failed to influence the intensity of depressive symptoms or the strategy of coping with stress in either subgroup, although a trend was noted for better health expectations with increasing religious engagement in depressive subjects. We conclude that religiosity is unlikely to significantly ameliorate dysphoric distress accompanying older age.

GABA representation in hypoxia sensing: a ventilatory study in the rat.

Phenibut, a nonspecific GABA derivative, is clinically used as an anxiolytic and tranquilizer in psychosomatic conditions. A GABA-ergic inhibitory pathway is engaged in respiratory control at both central and peripheral levels. However, the potential of phenibut to affect the O2-related chemoreflexes has not yet been studied. In this study we seek to determine the ventilatory responses to changes in inspired O2 content in anesthetized, spontaneously-breathing rats. Steady-state 5-min responses to 10% O2 in N2 and 100% O2 were taken in each animal before and 1 h after phenibut administration in a dose 450 mg/kg, i.p. Minute ventilation and its frequency and tidal components were obtained from the respiratory flow signal. We found that after a period of irregular extension of the respiratory cycle, phenibut stabilized resting ventilation at a lower level [20.0±3.3 (SD) vs 31.1±5.2 ml/min before phenibut; P<0.01]. The ventilatory depressant effect of phenibut was not reflected in the hypoxic response. In relative terms, this response was actually accentuated after phenibut; the peak hypoxic ventilation increased by 164% from baseline vs the 100% increase before phenibut. Regarding hyperoxia, its inhibitory effect on breathing was more expressed after phenibut. In conclusion, the GABA-mimetic phenibut did not curtail hypoxic ventilatory responsiveness, despite the presence of GABA-ergic pathways in both central and peripheral, carotid body mechanisms mediating the hypoxic chemoreflex. Thus, GABA-mediated synaptic inhibition may be elaborated in a way to sustain the primarily defensive ventilatory chemoreflex.

Personality and perception of stigma in psychiatric patients with depressive disorders.

OBJECTIVE: The study seeks to determine the relationships between neuroticism and extroversion, on the one side, and the perception of various dimensions of social stigma, on the other, in psychiatric in-patients with depressive disorders, such as depressive episodes, or mood and anxiety disorders with the presence of depressive symptoms. MATERIAL AND METHODS: A total of 72 patients were examined in the study. Twenty four of them (F/M - 12/12; age range 42-65 years) were used for assessing the reliability of a depression stigma questionnaire (DSQ) created specifically for this study. The remaining 48 patients (F/M - 31/17; age range 17-74 years) were then surveyed with the DSQ and other psychometric tools employed in the study. Self-reported data on the self-stigma, perceived stigma, public (mirrored) stigma, secrecy, treatment stigma, and the levels of neuroticism, extroversion, and depression were collected. RESULTS: The study demonstrates that treatment stigma and secrecy were the most frequent aspects of stigma experienced by the patients. Secrecy correlated negatively with age and positively with the education level. There were correlations between neuroticism and four of the stigma dimensions: treatment stigma, secrecy, perceived stigma, and self-stigma. Extroversion, in turn, correlated with perceived stigma, public stigma, and self-stigma. CONCLUSIONS: The study confirms the relevance of personality resources in the perception and coping with stigma and points to secrecy as a major underlying factor in these processes. In light of the present findings, stigma experienced by the patient is not only related to the external indicators of social stigmatization and the state of depression, but also to the personal features of an individual.

Interaction of arachidonic acid with electrogenic properties of mouse chemosensory neurons.

Chemosensory neurons respond to stimulation induced by gasses, volatile and non-volatile compounds. Neuronal excitation mediated via second messengers involves typically: cGMP, cAMP, or IP⊂3. Transduction pathways based on cyclic nucleotide have three-phosphate nucleotide as substrate, while IP⊂3 has a membrane lipid substrate. These derivatives of cholesterol are signaling molecules with modulator-like effects on many proteins, including membrane ion channels. In the present study, spontaneous and induced activities were recorded in a whole-cell configuration, in current and voltage clamp modes, in isolated chemosensory neurons obtained from the mouse. Chemosensory neurons responded with an inward depolarizing current to application of arachidonic acid, which suggests a role for it in putative mechanisms of signal transduction.

Respiratory infection caused by Chlamydophila pneumoniae in children and adolescents in the Lower Silesia Region of Poland.

OBJECTIVE: To assess the incidence of Chlamydia pneumoniae respiratory tract infection in children and adolescents in the Lower Silesia Region in Poland in 2009. MATERIAL AND METHODS: 641 throat swabs obtained from 326 girls and 315 boys, aged 11 months to 18 years, were assessed diagnostically. The patients enrolled into the study were treated on an outpatient basis due to various, non-specific respiratory ailments. The most common presenting clinical symptom of a respiratory problem was dry cough, which occurred in 295 studied subjects, followed by runny nose and cough with discharge in 176 subjects, and other minor symptoms in 35 subjects. The assessment was conducted by an indirect immunofluorescence antibody (IFA) Chlamydia Testing kit (Cellabs, Sydney, Australia). RESULTS: Overall, Chlamydia infection was detected in the respiratory tract in 43.1% (276/ 641) of the children, with no clear gender differences. Of the 295 subjects presenting with dry cough, 122 (41.4%) had positive tests for Chlamydia. Of the 176 subjects with runny nose and cough and the 35 subjects with other symptoms, 83 (47.2%) and 8 (22.9%) had positive tests for Chlamydia, respectively. In the asymptomatic children who had direct contact with a Chlamydia infected person, there were 29.6% (8/27) positively tested cases, whereas in the children presenting symptoms, the percentage of positive tests was 48.3% (29/60). CONCLUSIONS: In children living in the Lower Silesia Region of Poland, there is a substantial ∼50% rate of Chlamydia infection, transmitted via airborne droplets. The finding of Chlamydia infection should be the signal for testing other subjects from the child's closest environment.

Absence of bioactivity of lipid derivatives of serotonin.

BACKGROUND: Serotonin (5-HT) and its receptors are present in central, the brain stem, and peripheral, the carotid body, tissues controlling the ventilatory responses to hypoxia. The exact action of serotonin and its nature are, however, unsettled. We hypothesized that the discrepant results on the ventilatory action of serotonin could be caused by the inability of serotonin to penetrate into the brain or the plasma membrane lipid bilayers, the target site of signal transduction cascades, after its exogenous administration. OBJECTIVE: To study the penetrability of novel lipid derivatives of serotonin of varying fatty acid chain length and number of saturated/unsaturated bonds, the oleic, caprylic, and caprolic amides of 5-HT, into the brain, and their functional effects on the hypoxic ventilatory response in awake rats after systemic administration. MATERIAL AND METHODS: Adult Wistar rats were used for the experiments. In the biochemical part of the study, the presence and stability of the compounds tested, after i.p. injection, was assessed in brain extracts using spectrophotometry and thin-layered chromatography. In the functional part, the ventilatory responses to 8 and 12% hypoxia were compared before and 1 h after the compound administration using a whole body plethysmography. RESULTS: The "lipidized" serotonin compounds turned out to be stable in brain extracts in vitro for up to 3 h of the test. However, we could not substantiate the presence of any of the compounds in the brain, with either method used, after i.p. administration. Likewise, none of the compounds had any appreciable effect on the profile of the stimulatory hypoxic ventilatory response. CONCLUSIONS: Synthetically attaching lipophilic groups to the serotonin molecule does not make it penetrate into the brain. The lack of serotonin penetrability likely depends on the planarity of its molecule, as it does not seem to depend on the size, number of carbons or bond saturation of the "lipidized" molecules. Such molecules do not directly interfere with the carotid chemoreceptor-mediated hypoxic ventilatory response. The study failed to substantiate the bioactive potential of the lipid derivatives of serotonin.

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.

Alterations in the hypoxic ventilatory response with advancing age in awake rats.

This study seeks to determine the influence of aging on hypoxic ventilatory responsiveness. We addressed the issue by comparing the hypoxic ventilatory responses in three age-groups of conscious rats: 3, 12, and 24 months old animals. Ventilation was recorded in a whole body rodent plethysmograph. Minute ventilation (V(E)), respiratory rate, and tidal volume were considered for analysis. The rats were subjected to two levels of acute hypoxia: 14 and 11% O(2) in N(2). Hypoxic exposures were separated by a 15 min recovery interval in air. The part of the study between the 12 and 24 months age interval was longitudinal in that the same animals were studied twice, whereas the youngest animals belonged to a separate breed. All data were normalized to body mass. All hypoxic responses were biphasic with the stimulatory peak at 0.5 min after onset of hypoxia. The results demonstrate that there were no appreciable differences in magnitude of the peak hypoxic V(E) responses between 3 and 12 months old rats. The hypoxic V(E) responses and also the hypoxic ventilatory gain were, however, enhanced in the senescent rats. In these rats, the increment in peak V(E) from 14 to 11% hypoxia amounted to 364.1+/-95.8 ml.min(-1).kg(-1), which was more than double compared with 12 and 3 months old rats (P<0.02). We conclude that ventilatory responsiveness is not curtailed in senescent rats. The respiratory system is able to compensate for any age-related handicaps in the respiratory system to maintain a stimulatory response to ventilatory stress.

Convergence of nasal and tracheal neural pathways in modulating the cough response in guinea pigs.

In the present study we investigated the possibility of central convergence of neural pathways coming from distant anatomical regions in modulating the cough response. We addressed this issue by inducing cough from the tracheo-bronchial region on the background of capsaicin-stimulated and mesocain-blocked nasal mucosa in 14 anesthetized guinea pigs. The control group consisted of 6 guinea pigs in which the active agents, capsaicin and mesocain, were substituted for by inert physiological saline. All animals were tracheostomized, and the larynx was disconnected from the proximal part of the trachea with preserved innervations, and all were subjected to the same protocol. Cough, induced by mechanical irritation of the tracheo-bronchial mucosa, was elicited three times: in the control condition, after intranasal capsaicin challenge, and after another capsaicin challenge preceded by intranasal instillation of a local anesthetic, mesocain. The main finding of the study was that the number of cough efforts per bout, assessed from positive deflections on the intrapleural pressure recordings, was significantly enhanced by intranasal capsaicin challenge and this effect was reversed by intranasal pretreatment with the anesthetic mesocain [2.1 +/-0.2 (control) vs. 3.5 +/-0.4 (capsaicin) vs. 2.2 +/-0.2 (capsaicin after mesocain) (P<0.01)], with no appreciable changes in the magnitude of cough efforts. The cough response in the control group remained unchanged. We conclude that tracheo-bronchial cough may be modified by neural sensory input to the brain coming from nasal mucosa. Therefore, cough reflex is subject to central convergence of peripheral neural pathways originating at distant anatomical locations.

Physiological carotid body denervation during aging.

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.