Mariana Brozmanova - Academia.edu (original) (raw)

Papers by Mariana Brozmanova

Research paper thumbnail of afferent neurons in the antitussive effects of menthol The role of trigeminal nasal TRPM8-expressing

Research paper thumbnail of Differences in oxidative status, lung function, and pulmonary surfactant during long-term inhalation of medical oxygen and partially ionized oxygen in guinea pigs

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2008

Inhalation of partially ionized oxygen may have less adverse effects on lung functions than medic... more Inhalation of partially ionized oxygen may have less adverse effects on lung functions than medical oxygen. Guinea pigs inhaled air, 100% molecular medical oxygen (O(2)mol), partially negatively (O(2)neg) or positively (O(2)posit) ionized oxygen during 17 and 60 h. After 17 h, dityrosines, markers of oxidative injury, in lung homogenate increased in O(2)neg and decreased in O(2)posit groups vs. controls. After 60 h, dityrosines rose after inhalation of O(2)mol and O(2)neg, but not in the O(2)posit group. Lysine-LPO products increased and lung wet/dry weight ratio decreased in O(2)mol and O(2)neg, and not in O(2)posit group. Relative neutrophil count in BALF was elevated in all oxygen-treated groups with lower numbers in O(2)posit vs.O(2)mol and O(2)neg groups. After 60 h, surfactant activity was better in O(2)posit vs. O(2)mol group. In conclusion, long-term inhalation of partially positively ionized oxygen is associated with less oxidative stress, milder lung inflammatory response,...

Research paper thumbnail of The effect of the voltage-gated sodium channel NaV1.7 blocker PF-05089771 on cough in the guinea pig

Respiratory Physiology & Neurobiology, 2022

Cough in chronic respiratory diseases is a common symptom associated with significant comorbiditi... more Cough in chronic respiratory diseases is a common symptom associated with significant comorbidities including visceral pain. Available antitussive therapy still has limited efficacy. Recent advances in the understanding of voltage-gated sodium channels (NaVs) lead to the rational hypothesis that subtype NaV1.7 is involved in initiating cough and thus may present a promising therapeutic target for antitussive therapy. We evaluated the antitussive effect of NaV1.7 blocker PF-05089771 administered systemically and topically in awake guinea pigs using capsaicin cough challenge. Compared to vehicle, peroral or inhaled PF-05089771 administration caused about 50-60% inhibition of cough at the doses that did not alter respiratory rate. We conclude that the NaV1.7 blocker PF-05089771 inhibits cough in a manner consistent with its electrophysiological effect on airway C-fibre nerve terminals.

Research paper thumbnail of Various Aspects of Sex and Gender Bias in Biomedical Research

Physiological Research, 2021

The main role of research in medicine is to provide relevant knowledge which, after successful tr... more The main role of research in medicine is to provide relevant knowledge which, after successful translation to clinical practice, improves the quality of healthcare. The sex bias which is still present in the majority of research disciplines prefers male subjects despite legislation changes in the US grant agencies and European research programme Horizon 2020. Male subjects (cells, animals) still dominate in preclinical research and it has detrimental consequences for women’s health and the quality of science. Opposite bias exists for data obtained mainly in animal models utilizing female subjects (e.g. research in multiple sclerosis, osteoporosis) with skewed outcomes for men affected by these diseases. Either way, scientists are producing results which compromise half of the population. Assumptions that females as cohorts are more variable and another assumption that the oestrous cycle should be tracked in case the females are enrolled in preclinical studies were proven wrong. Vari...

Research paper thumbnail of Effects of inhaled corticosteroids on cough in awake guinea pigs with experimental allergic rhinitis--the first experience

Journal of Physiology and Pharmacology, 2004

Allergic rhinitis is a common cause of chronic cough. Topical corticosteroids are regarded as the... more Allergic rhinitis is a common cause of chronic cough. Topical corticosteroids are regarded as the most effective first-time treatment in allergic rhinitis. In this study we evaluated the cough sensitivity during the early and late allergic responses in guinea pigs with experimental allergic rhinitis. Another aim of the study was to follow up the effect of inhaled beclomethasone dipropionate on the cough in guinea pigs with allergic rhinitis. 31 guinea pigs were sensitized with ovalbumin (OA). Animals were intranasally challenged with OA (experiment) or saline (control) in 7-day intervals for 9 weeks. Cough was induced by inhalation of citric acid aerosols in gradually increasing concentrations for 30 s and was evaluated 1 h after the 8(th) nasal challenge (NCH) and 17 h after the 9(th) NCH. Cough was significantly increased only during an early allergic response, 1 h after repeated NCH [18 (14-23) vs. 8 (3-10); P<0.001]. Five experimental animals were inhaling aerosol of beclomet...

Research paper thumbnail of The interaction of dietary antioxidant vitamins and oxidative stress on cough reflex in guinea-pigs after long term oxygen therapy

Journal of Physiology and Pharmacology, 2006

Inhalation of high concentration of oxygen produces oxidative stress in men and experimental anim... more Inhalation of high concentration of oxygen produces oxidative stress in men and experimental animals. Our previous experiments showed that the cough reflex is suppressed in guinea pigs after exposure to 100% O(2) for 60 hours. The aim of this study was to determine the effects of dietary antioxidant supplementation with vitamins C and E on hyperoxia-induced oxidative stress in airway and lung tissues directed on cough reflex. The experimental group (T-H, n=8) was pretreated with vitamins C (500 mg/kg) and E (300 mg/kg) for 4 weeks and subsequently exposed to 100% O(2) for 60 hours. Hyperoxic group (H, n=8) received saline instead of antioxidants and then inhaled 100% O(2) for 60 hours. Cough was induced by inhalation of citric acid aerosol in gradually increased concentration (0.05-1.6 M) at the end of antioxidant therapy and then at the end of exposure to 100% O(2). Cough was also induced by mechanical stimulation of laryngopharyngeal (LPh) and tracheobronchial (TBr) region in anae...

Research paper thumbnail of Oral N-acetylcysteine reverses hyperoxia-related cough suppression in guinea pigs

Journal of Physiology and Pharmacology, 2007

Hyperoxia-induced lung injury is well known in animal and human studies. We have previously shown... more Hyperoxia-induced lung injury is well known in animal and human studies. We have previously shown that hyperoxic exposure of guinea pigs is associated with suppression of cough reflex. The goal of this study was to determine the effects of oral N-acetylcysteine (NAC) on hyperoxia-induced oxidative stress in lung tissue directed on cough reflex. The experimental group was pretreated with NAC daily for 7 days and subsequently exposed to 100% O2 for 60 h. Hyperoxic group inhaled 100% O2 only. The control group was exposed to normoxia. Cough was induced by inhalation of citric acid aerosol before and after exposure to oxygen. Cough was also induced by mechanical stimulation of airways in anesthetized animals just after the end of oxygen exposure. Our results showed a significant decrease (P=0.002) in citric acid-induced cough in hyperoxic animals and reversal of that effect in animals pretreated with NAC. In addition, there was a significant interaction between antioxidant therapy and h...

Research paper thumbnail of Experimental allergic rhinitis-related cough and airway eosinophilia in sensitized guinea pigs

Journal of Physiology and Pharmacology, 2007

Allergic rhinitis is one of the most common causes of chronic cough. The characteristic feature o... more Allergic rhinitis is one of the most common causes of chronic cough. The characteristic feature of allergic rhinitis is eosinophilic nasal inflammation. This study was determined to find the relation between airway eosinophils and chemically-induced cough in guinea pigs with antigen-induced rhinitis at the early and late allergic phases. Forty animals were sensitized with ovalbumin (OVA) and divided into four separated groups. Four weeks later, the sensitized animals were either once or repeatedly (6 times at 7-day intervals) intranasally challenged with OVA to develop experimental allergic rhinitis. The control group was given saline. Cough was elicited by inhalation of citric acid aerosols and evaluated at 30 min (early phase) or 24 h (late phase) after the 1st or 6th nasal challenge (NC) in the sensitized animals. The citric acid-induced cough was significantly increased in the sensitized animals in the early allergic phase after the first and repeated NC compared with the contro...

Research paper thumbnail of The Prospect for Potent Sodium Voltage-Gated Channel Blockers to Relieve an Excessive Cough

Physiological Research, Mar 27, 2020

An excessive, irritable, productive or non-productive coughing associated with airway inflammatio... more An excessive, irritable, productive or non-productive coughing associated with airway inflammation belongs to pathological cough. Increased activation of airway vagal nociceptors in pathological conditions results from dysregulation of the neural pathway that controls cough. A variety of mediators associated with airway inflammation overstimulate these vagal airway fibers including C-fibers leading to hypersensitivity and hyperreactivity. Because current antitussives have limited efficacy and unwanted side effects there is a continual demand for the development of a novel more effective antitussives for a new efficacious and safe cough treatment. Therefore, inhibiting the activity of these vagal C-fibers represents a rational approach to the development of effective antitussive drugs. This may be achieved by blocking inflammatory mediator receptors or by blocking the generator potential associated with the specific ion channels. Because voltage-gated sodium channels (NaVs) are absolutely required for action potentials initiation and conduction irrespective of the stimulus, NaVs become a promising neural target. There is evidence that NaV1.7, 1.8 and 1.9 subtypes are predominantly expressed in airway cough-triggering nerves. The advantage of blocking these NaVs is suppressing C-fiber irrespective to stimuli, but the disadvantage is that by suppressing the nerves is may also block beneficial sensations and neuronal reflex behavior. The concept is that new antitussive drugs would have the benefit of targeting peripheral airway nociceptors without inhibiting the protective cough reflex.

Research paper thumbnail of Antileukotriene treatment and allergic rhinitis-related cough in guinea pigs

Journal of Physiology and Pharmacology, 2005

Experimental allergic rhinitis produces enhanced cough response in awake guinea pigs. Leukotriene... more Experimental allergic rhinitis produces enhanced cough response in awake guinea pigs. Leukotriene receptor antagonists, as anti-inflammatory agents, have been effective in treatment of asthma and allergic rhinitis to inhibit the early and late allergic response. In the present study, we evaluated the effect of montelukast (Singulair, Merck, USA) on the cough reflex in an experimental model of allergen-induced rhinitis in guinea pigs. Guinea pigs (n=16) were sensitized with intraperitoneal ovalbumin (OVA). The animals were then used to develop a model of allergic rhinitis by repeated intranasal instillation of 0.5% OVA at weekly intervals for 8 weeks. Allergic rhinitis was evaluated from the occurrence of typical clinical symptoms including sneezing, conjunctival and nasal secretion, or nasal acoustic phenomenon. Between the 6(th) and 8(th) nasal challenge (NCh) the animals (n=8) were treated daily for 14 days with oral montelukast (10mg/kg). Cough was induced by citric acid aerosol ...

Research paper thumbnail of Bidirectional modulation of urge to cough by nasal TRPA1 and TRPM8 agonists in healthy human subjects

European Respiratory Journal, 2012

Cough, the most important airways defensive mechanism is modulated by many afferent inputs either... more Cough, the most important airways defensive mechanism is modulated by many afferent inputs either from respiratory tussigenic areas, but also by afferent drive from other organs. Modulation of cough by nasal afferent inputs could either facilitate cough response or inhibit it in animal models, depending on the type of trigeminal afferents which are stimulated. In recent study we addressed the question of possible bidirectional modulation of cough response in human healthy volunteers by nasal challenges with TRPA1 and TRPM8 agonists respectively. After nasal challenges with AITC, cinnamaldehe, (-) menthol and (+) menthol (all 10-3 M, nasal symptom score, cough threshold (C2), urge to cough (Cu) and cumulative cough response had been tested). Nasal challenges of TRPA1 relevant agonists induced considerable nasal symptoms, significantly enhanced urge to cough (p Except the role of trigeminal afferents expressing TRP channels, also olfactory nerve endings, trigemino – olfactoric relatio...

Research paper thumbnail of Antileukotriene treatment and allergic rhinitis-related cough in guinea pigs

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2005

Experimental allergic rhinitis produces enhanced cough response in awake guinea pigs. Leukotriene... more Experimental allergic rhinitis produces enhanced cough response in awake guinea pigs. Leukotriene receptor antagonists, as anti-inflammatory agents, have been effective in treatment of asthma and allergic rhinitis to inhibit the early and late allergic response. In the present study, we evaluated the effect of montelukast (Singulair, Merck, USA) on the cough reflex in an experimental model of allergen-induced rhinitis in guinea pigs. Guinea pigs (n=16) were sensitized with intraperitoneal ovalbumin (OVA). The animals were then used to develop a model of allergic rhinitis by repeated intranasal instillation of 0.5% OVA at weekly intervals for 8 weeks. Allergic rhinitis was evaluated from the occurrence of typical clinical symptoms including sneezing, conjunctival and nasal secretion, or nasal acoustic phenomenon. Between the 6(th) and 8(th) nasal challenge (NCh) the animals (n=8) were treated daily for 14 days with oral montelukast (10mg/kg). Cough was induced by citric acid aerosol ...

Research paper thumbnail of Effects of inhaled corticosteroids on cough in awake guinea pigs with experimental allergic rhinitis--the first experience

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2004

Allergic rhinitis is a common cause of chronic cough. Topical corticosteroids are regarded as the... more Allergic rhinitis is a common cause of chronic cough. Topical corticosteroids are regarded as the most effective first-time treatment in allergic rhinitis. In this study we evaluated the cough sensitivity during the early and late allergic responses in guinea pigs with experimental allergic rhinitis. Another aim of the study was to follow up the effect of inhaled beclomethasone dipropionate on the cough in guinea pigs with allergic rhinitis. 31 guinea pigs were sensitized with ovalbumin (OA). Animals were intranasally challenged with OA (experiment) or saline (control) in 7-day intervals for 9 weeks. Cough was induced by inhalation of citric acid aerosols in gradually increasing concentrations for 30 s and was evaluated 1 h after the 8(th) nasal challenge (NCH) and 17 h after the 9(th) NCH. Cough was significantly increased only during an early allergic response, 1 h after repeated NCH [18 (14-23) vs. 8 (3-10); P<0.001]. Five experimental animals were inhaling aerosol of beclomet...

Research paper thumbnail of Oral N-acetylcysteine reverses hyperoxia-related cough suppression in guinea pigs

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2007

Hyperoxia-induced lung injury is well known in animal and human studies. We have previously shown... more Hyperoxia-induced lung injury is well known in animal and human studies. We have previously shown that hyperoxic exposure of guinea pigs is associated with suppression of cough reflex. The goal of this study was to determine the effects of oral N-acetylcysteine (NAC) on hyperoxia-induced oxidative stress in lung tissue directed on cough reflex. The experimental group was pretreated with NAC daily for 7 days and subsequently exposed to 100% O2 for 60 h. Hyperoxic group inhaled 100% O2 only. The control group was exposed to normoxia. Cough was induced by inhalation of citric acid aerosol before and after exposure to oxygen. Cough was also induced by mechanical stimulation of airways in anesthetized animals just after the end of oxygen exposure. Our results showed a significant decrease (P=0.002) in citric acid-induced cough in hyperoxic animals and reversal of that effect in animals pretreated with NAC. In addition, there was a significant interaction between antioxidant therapy and h...

Research paper thumbnail of Suffering from Allergic Rhinitis and Common Cold

Department of Pathophysiology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak... more Department of Pathophysiology, Jessenius Faculty of Medicine, Comenius University, Martin, SlovakiaCough associated with upper respiratory tract disorders is a common andtroublesome problem in children and little is known about the etiology of this typeof cough. This study examined the capsaicin cough sensitivity (CS) in childrensuffering from allergic rhinitis (AR) and upper respiratory tract infection (URI),comparing it with that in healthy children taken as controls (C). CS to capsaicin,spirometry, skin prick tests, and nose-throat examination were performed in 61children grouped by the diagnosis of AR, URI, and C. The results, in order of C

Research paper thumbnail of Airway reactivity and neuroimmune relationships in animal model of air born irritants induced symptoms - Role of trigeminal TRPA1 channels

European Respiratory Journal, 2012

Air born pollutants modulate functions of airways. Many experimental models use inhalation of air... more Air born pollutants modulate functions of airways. Many experimental models use inhalation of air born irritants containing aerosols to mimic environmental exposure however, most exposed part is the nose. The aim of our study was to assess the general effects and modulation of airway defensive reflexes in animal model by selective nasal challenges with TRPA1 agonist AITC – allylisothiocyanate. TRPA1 is known to be relevant for most air born irritants. 15 male Dunkin Hartly guinea pigs were repeatedly exposed to 10mM AITC, 15μl administered into both nostrils and nasal symptoms, cough, specific airway resistance (Saw) and bronchoalveolar lavages (BAL) were analyzed afterwards. Nasal administration of 10 mM AITC induces reproducible nasal symptoms, sneezing, discharge, crackles and conjunctival reaction. Also, nasal application of 10mM AITC induces spontaneous rise of Saw measured by Pennock9s method in vivo and increases Saw after inhalation of methacholin (p

Research paper thumbnail of The interaction of dietary antioxidant vitamins and oxidative stress on cough reflex in guinea-pigs after long term oxygen therapy

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2006

Inhalation of high concentration of oxygen produces oxidative stress in men and experimental anim... more Inhalation of high concentration of oxygen produces oxidative stress in men and experimental animals. Our previous experiments showed that the cough reflex is suppressed in guinea pigs after exposure to 100% O(2) for 60 hours. The aim of this study was to determine the effects of dietary antioxidant supplementation with vitamins C and E on hyperoxia-induced oxidative stress in airway and lung tissues directed on cough reflex. The experimental group (T-H, n=8) was pretreated with vitamins C (500 mg/kg) and E (300 mg/kg) for 4 weeks and subsequently exposed to 100% O(2) for 60 hours. Hyperoxic group (H, n=8) received saline instead of antioxidants and then inhaled 100% O(2) for 60 hours. Cough was induced by inhalation of citric acid aerosol in gradually increased concentration (0.05-1.6 M) at the end of antioxidant therapy and then at the end of exposure to 100% O(2). Cough was also induced by mechanical stimulation of laryngopharyngeal (LPh) and tracheobronchial (TBr) region in anae...

Research paper thumbnail of Transient receptor potential ankyrin 1 (TRPA1)-mediated cough

European Respiratory Journal, 2011

TRPA1 detects many endogenous inflammatory and environmental pollutant molecules. Previous studie... more TRPA1 detects many endogenous inflammatory and environmental pollutant molecules. Previous studies implicated TRPA1 as a drug target for antitussive therapy. We evaluated relative efficacy of the TRPA1 activation in inducing cough in guinea pigs. Inhalation of the TRPA1 agonist allyl-isothiocyanate (AITC) evoked cough with a maximally effective concentration of 10mM (2.8±0.8 coughs/5min above vehicle, n=12) that was abolished by the TRPA1 selective antagonist AP-18 (1mM, n=8). AITC was ∼3-times less effective in inducing cough than the TRPV1 agonist capsaicin in the sub-maximally effective selective concentration (50μM) (8.2±2.1 coughs/5min above vehicle, n=9, p

Research paper thumbnail of Lessons learned from apnoe in cough down regulation

Afferents from the nose do not trigger cough, but the reflex is sensitized by experimental rhinit... more Afferents from the nose do not trigger cough, but the reflex is sensitized by experimental rhinitis. Most published data suggest that nasal sensory nerves are involved in up-regulation of cough, little evidence is available to support down-regulation of it from nose. Based on the data published recently about suppression of cough during water induced apnoe (Poussel et al., 2012), we decided to conduct a study on the model of irritant induced nasal apnea. Dunkin Hartley guinea pigs (n=8) were anaesthetized and tracheotomized. Trachea was lengthwise open at the proximal end and superfused with oxygenated saline. Cough was induced after nasal allylisothiocyanate AITC (TRPA1 agonist) by application of citric acid (CA) to the tracheal surface in ascending concentrations (0.001 - 2 M). Cough was also induced in conscious animals (n=22) by inhaling 0.4M CA for 10 min after nasal AITC. Cough response was estimated from the airflow traces and cough sound analysis. In anaesthesia, nasal AITC ...

Research paper thumbnail of Effects of hyperoxia and allergic airway inflammation on cough reflex intensity in guinea pigs

Toxic influence of high oxygen concentration on pulmonary function and structures has been known ... more Toxic influence of high oxygen concentration on pulmonary function and structures has been known for many years. However, the influence of high oxygen concentration breathing on defensive respiratory reflexes is still not clear. In our previous experiments, we found an inhibitory effect of 100 % oxygen breathing on cough reflex intensity in healthy guinea pigs. The present study was designed to detect the effects of hyperoxia on cough reflex in guinea pigs with allergic airway inflammation. In the first phase of our experiment, the animals were sensitized with ovalbumin. Thirty-two sensitized animals were used in two separate experiments according to oxygen concentration breathing: 100 % or 50 % oxygen for 60 h continuously. In each experiment, one group of animals was exposed to hyperoxia, another to ambient air. The cough reflex was induced both by aerosol of citric acid before sensitization, then in sensitized animals at 24 h and 60 h of exposition to oxygen/air in awake animals,...

Research paper thumbnail of afferent neurons in the antitussive effects of menthol The role of trigeminal nasal TRPM8-expressing

Research paper thumbnail of Differences in oxidative status, lung function, and pulmonary surfactant during long-term inhalation of medical oxygen and partially ionized oxygen in guinea pigs

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2008

Inhalation of partially ionized oxygen may have less adverse effects on lung functions than medic... more Inhalation of partially ionized oxygen may have less adverse effects on lung functions than medical oxygen. Guinea pigs inhaled air, 100% molecular medical oxygen (O(2)mol), partially negatively (O(2)neg) or positively (O(2)posit) ionized oxygen during 17 and 60 h. After 17 h, dityrosines, markers of oxidative injury, in lung homogenate increased in O(2)neg and decreased in O(2)posit groups vs. controls. After 60 h, dityrosines rose after inhalation of O(2)mol and O(2)neg, but not in the O(2)posit group. Lysine-LPO products increased and lung wet/dry weight ratio decreased in O(2)mol and O(2)neg, and not in O(2)posit group. Relative neutrophil count in BALF was elevated in all oxygen-treated groups with lower numbers in O(2)posit vs.O(2)mol and O(2)neg groups. After 60 h, surfactant activity was better in O(2)posit vs. O(2)mol group. In conclusion, long-term inhalation of partially positively ionized oxygen is associated with less oxidative stress, milder lung inflammatory response,...

Research paper thumbnail of The effect of the voltage-gated sodium channel NaV1.7 blocker PF-05089771 on cough in the guinea pig

Respiratory Physiology & Neurobiology, 2022

Cough in chronic respiratory diseases is a common symptom associated with significant comorbiditi... more Cough in chronic respiratory diseases is a common symptom associated with significant comorbidities including visceral pain. Available antitussive therapy still has limited efficacy. Recent advances in the understanding of voltage-gated sodium channels (NaVs) lead to the rational hypothesis that subtype NaV1.7 is involved in initiating cough and thus may present a promising therapeutic target for antitussive therapy. We evaluated the antitussive effect of NaV1.7 blocker PF-05089771 administered systemically and topically in awake guinea pigs using capsaicin cough challenge. Compared to vehicle, peroral or inhaled PF-05089771 administration caused about 50-60% inhibition of cough at the doses that did not alter respiratory rate. We conclude that the NaV1.7 blocker PF-05089771 inhibits cough in a manner consistent with its electrophysiological effect on airway C-fibre nerve terminals.

Research paper thumbnail of Various Aspects of Sex and Gender Bias in Biomedical Research

Physiological Research, 2021

The main role of research in medicine is to provide relevant knowledge which, after successful tr... more The main role of research in medicine is to provide relevant knowledge which, after successful translation to clinical practice, improves the quality of healthcare. The sex bias which is still present in the majority of research disciplines prefers male subjects despite legislation changes in the US grant agencies and European research programme Horizon 2020. Male subjects (cells, animals) still dominate in preclinical research and it has detrimental consequences for women’s health and the quality of science. Opposite bias exists for data obtained mainly in animal models utilizing female subjects (e.g. research in multiple sclerosis, osteoporosis) with skewed outcomes for men affected by these diseases. Either way, scientists are producing results which compromise half of the population. Assumptions that females as cohorts are more variable and another assumption that the oestrous cycle should be tracked in case the females are enrolled in preclinical studies were proven wrong. Vari...

Research paper thumbnail of Effects of inhaled corticosteroids on cough in awake guinea pigs with experimental allergic rhinitis--the first experience

Journal of Physiology and Pharmacology, 2004

Allergic rhinitis is a common cause of chronic cough. Topical corticosteroids are regarded as the... more Allergic rhinitis is a common cause of chronic cough. Topical corticosteroids are regarded as the most effective first-time treatment in allergic rhinitis. In this study we evaluated the cough sensitivity during the early and late allergic responses in guinea pigs with experimental allergic rhinitis. Another aim of the study was to follow up the effect of inhaled beclomethasone dipropionate on the cough in guinea pigs with allergic rhinitis. 31 guinea pigs were sensitized with ovalbumin (OA). Animals were intranasally challenged with OA (experiment) or saline (control) in 7-day intervals for 9 weeks. Cough was induced by inhalation of citric acid aerosols in gradually increasing concentrations for 30 s and was evaluated 1 h after the 8(th) nasal challenge (NCH) and 17 h after the 9(th) NCH. Cough was significantly increased only during an early allergic response, 1 h after repeated NCH [18 (14-23) vs. 8 (3-10); P<0.001]. Five experimental animals were inhaling aerosol of beclomet...

Research paper thumbnail of The interaction of dietary antioxidant vitamins and oxidative stress on cough reflex in guinea-pigs after long term oxygen therapy

Journal of Physiology and Pharmacology, 2006

Inhalation of high concentration of oxygen produces oxidative stress in men and experimental anim... more Inhalation of high concentration of oxygen produces oxidative stress in men and experimental animals. Our previous experiments showed that the cough reflex is suppressed in guinea pigs after exposure to 100% O(2) for 60 hours. The aim of this study was to determine the effects of dietary antioxidant supplementation with vitamins C and E on hyperoxia-induced oxidative stress in airway and lung tissues directed on cough reflex. The experimental group (T-H, n=8) was pretreated with vitamins C (500 mg/kg) and E (300 mg/kg) for 4 weeks and subsequently exposed to 100% O(2) for 60 hours. Hyperoxic group (H, n=8) received saline instead of antioxidants and then inhaled 100% O(2) for 60 hours. Cough was induced by inhalation of citric acid aerosol in gradually increased concentration (0.05-1.6 M) at the end of antioxidant therapy and then at the end of exposure to 100% O(2). Cough was also induced by mechanical stimulation of laryngopharyngeal (LPh) and tracheobronchial (TBr) region in anae...

Research paper thumbnail of Oral N-acetylcysteine reverses hyperoxia-related cough suppression in guinea pigs

Journal of Physiology and Pharmacology, 2007

Hyperoxia-induced lung injury is well known in animal and human studies. We have previously shown... more Hyperoxia-induced lung injury is well known in animal and human studies. We have previously shown that hyperoxic exposure of guinea pigs is associated with suppression of cough reflex. The goal of this study was to determine the effects of oral N-acetylcysteine (NAC) on hyperoxia-induced oxidative stress in lung tissue directed on cough reflex. The experimental group was pretreated with NAC daily for 7 days and subsequently exposed to 100% O2 for 60 h. Hyperoxic group inhaled 100% O2 only. The control group was exposed to normoxia. Cough was induced by inhalation of citric acid aerosol before and after exposure to oxygen. Cough was also induced by mechanical stimulation of airways in anesthetized animals just after the end of oxygen exposure. Our results showed a significant decrease (P=0.002) in citric acid-induced cough in hyperoxic animals and reversal of that effect in animals pretreated with NAC. In addition, there was a significant interaction between antioxidant therapy and h...

Research paper thumbnail of Experimental allergic rhinitis-related cough and airway eosinophilia in sensitized guinea pigs

Journal of Physiology and Pharmacology, 2007

Allergic rhinitis is one of the most common causes of chronic cough. The characteristic feature o... more Allergic rhinitis is one of the most common causes of chronic cough. The characteristic feature of allergic rhinitis is eosinophilic nasal inflammation. This study was determined to find the relation between airway eosinophils and chemically-induced cough in guinea pigs with antigen-induced rhinitis at the early and late allergic phases. Forty animals were sensitized with ovalbumin (OVA) and divided into four separated groups. Four weeks later, the sensitized animals were either once or repeatedly (6 times at 7-day intervals) intranasally challenged with OVA to develop experimental allergic rhinitis. The control group was given saline. Cough was elicited by inhalation of citric acid aerosols and evaluated at 30 min (early phase) or 24 h (late phase) after the 1st or 6th nasal challenge (NC) in the sensitized animals. The citric acid-induced cough was significantly increased in the sensitized animals in the early allergic phase after the first and repeated NC compared with the contro...

Research paper thumbnail of The Prospect for Potent Sodium Voltage-Gated Channel Blockers to Relieve an Excessive Cough

Physiological Research, Mar 27, 2020

An excessive, irritable, productive or non-productive coughing associated with airway inflammatio... more An excessive, irritable, productive or non-productive coughing associated with airway inflammation belongs to pathological cough. Increased activation of airway vagal nociceptors in pathological conditions results from dysregulation of the neural pathway that controls cough. A variety of mediators associated with airway inflammation overstimulate these vagal airway fibers including C-fibers leading to hypersensitivity and hyperreactivity. Because current antitussives have limited efficacy and unwanted side effects there is a continual demand for the development of a novel more effective antitussives for a new efficacious and safe cough treatment. Therefore, inhibiting the activity of these vagal C-fibers represents a rational approach to the development of effective antitussive drugs. This may be achieved by blocking inflammatory mediator receptors or by blocking the generator potential associated with the specific ion channels. Because voltage-gated sodium channels (NaVs) are absolutely required for action potentials initiation and conduction irrespective of the stimulus, NaVs become a promising neural target. There is evidence that NaV1.7, 1.8 and 1.9 subtypes are predominantly expressed in airway cough-triggering nerves. The advantage of blocking these NaVs is suppressing C-fiber irrespective to stimuli, but the disadvantage is that by suppressing the nerves is may also block beneficial sensations and neuronal reflex behavior. The concept is that new antitussive drugs would have the benefit of targeting peripheral airway nociceptors without inhibiting the protective cough reflex.

Research paper thumbnail of Antileukotriene treatment and allergic rhinitis-related cough in guinea pigs

Journal of Physiology and Pharmacology, 2005

Experimental allergic rhinitis produces enhanced cough response in awake guinea pigs. Leukotriene... more Experimental allergic rhinitis produces enhanced cough response in awake guinea pigs. Leukotriene receptor antagonists, as anti-inflammatory agents, have been effective in treatment of asthma and allergic rhinitis to inhibit the early and late allergic response. In the present study, we evaluated the effect of montelukast (Singulair, Merck, USA) on the cough reflex in an experimental model of allergen-induced rhinitis in guinea pigs. Guinea pigs (n=16) were sensitized with intraperitoneal ovalbumin (OVA). The animals were then used to develop a model of allergic rhinitis by repeated intranasal instillation of 0.5% OVA at weekly intervals for 8 weeks. Allergic rhinitis was evaluated from the occurrence of typical clinical symptoms including sneezing, conjunctival and nasal secretion, or nasal acoustic phenomenon. Between the 6(th) and 8(th) nasal challenge (NCh) the animals (n=8) were treated daily for 14 days with oral montelukast (10mg/kg). Cough was induced by citric acid aerosol ...

Research paper thumbnail of Bidirectional modulation of urge to cough by nasal TRPA1 and TRPM8 agonists in healthy human subjects

European Respiratory Journal, 2012

Cough, the most important airways defensive mechanism is modulated by many afferent inputs either... more Cough, the most important airways defensive mechanism is modulated by many afferent inputs either from respiratory tussigenic areas, but also by afferent drive from other organs. Modulation of cough by nasal afferent inputs could either facilitate cough response or inhibit it in animal models, depending on the type of trigeminal afferents which are stimulated. In recent study we addressed the question of possible bidirectional modulation of cough response in human healthy volunteers by nasal challenges with TRPA1 and TRPM8 agonists respectively. After nasal challenges with AITC, cinnamaldehe, (-) menthol and (+) menthol (all 10-3 M, nasal symptom score, cough threshold (C2), urge to cough (Cu) and cumulative cough response had been tested). Nasal challenges of TRPA1 relevant agonists induced considerable nasal symptoms, significantly enhanced urge to cough (p Except the role of trigeminal afferents expressing TRP channels, also olfactory nerve endings, trigemino – olfactoric relatio...

Research paper thumbnail of Antileukotriene treatment and allergic rhinitis-related cough in guinea pigs

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2005

Experimental allergic rhinitis produces enhanced cough response in awake guinea pigs. Leukotriene... more Experimental allergic rhinitis produces enhanced cough response in awake guinea pigs. Leukotriene receptor antagonists, as anti-inflammatory agents, have been effective in treatment of asthma and allergic rhinitis to inhibit the early and late allergic response. In the present study, we evaluated the effect of montelukast (Singulair, Merck, USA) on the cough reflex in an experimental model of allergen-induced rhinitis in guinea pigs. Guinea pigs (n=16) were sensitized with intraperitoneal ovalbumin (OVA). The animals were then used to develop a model of allergic rhinitis by repeated intranasal instillation of 0.5% OVA at weekly intervals for 8 weeks. Allergic rhinitis was evaluated from the occurrence of typical clinical symptoms including sneezing, conjunctival and nasal secretion, or nasal acoustic phenomenon. Between the 6(th) and 8(th) nasal challenge (NCh) the animals (n=8) were treated daily for 14 days with oral montelukast (10mg/kg). Cough was induced by citric acid aerosol ...

Research paper thumbnail of Effects of inhaled corticosteroids on cough in awake guinea pigs with experimental allergic rhinitis--the first experience

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2004

Allergic rhinitis is a common cause of chronic cough. Topical corticosteroids are regarded as the... more Allergic rhinitis is a common cause of chronic cough. Topical corticosteroids are regarded as the most effective first-time treatment in allergic rhinitis. In this study we evaluated the cough sensitivity during the early and late allergic responses in guinea pigs with experimental allergic rhinitis. Another aim of the study was to follow up the effect of inhaled beclomethasone dipropionate on the cough in guinea pigs with allergic rhinitis. 31 guinea pigs were sensitized with ovalbumin (OA). Animals were intranasally challenged with OA (experiment) or saline (control) in 7-day intervals for 9 weeks. Cough was induced by inhalation of citric acid aerosols in gradually increasing concentrations for 30 s and was evaluated 1 h after the 8(th) nasal challenge (NCH) and 17 h after the 9(th) NCH. Cough was significantly increased only during an early allergic response, 1 h after repeated NCH [18 (14-23) vs. 8 (3-10); P<0.001]. Five experimental animals were inhaling aerosol of beclomet...

Research paper thumbnail of Oral N-acetylcysteine reverses hyperoxia-related cough suppression in guinea pigs

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2007

Hyperoxia-induced lung injury is well known in animal and human studies. We have previously shown... more Hyperoxia-induced lung injury is well known in animal and human studies. We have previously shown that hyperoxic exposure of guinea pigs is associated with suppression of cough reflex. The goal of this study was to determine the effects of oral N-acetylcysteine (NAC) on hyperoxia-induced oxidative stress in lung tissue directed on cough reflex. The experimental group was pretreated with NAC daily for 7 days and subsequently exposed to 100% O2 for 60 h. Hyperoxic group inhaled 100% O2 only. The control group was exposed to normoxia. Cough was induced by inhalation of citric acid aerosol before and after exposure to oxygen. Cough was also induced by mechanical stimulation of airways in anesthetized animals just after the end of oxygen exposure. Our results showed a significant decrease (P=0.002) in citric acid-induced cough in hyperoxic animals and reversal of that effect in animals pretreated with NAC. In addition, there was a significant interaction between antioxidant therapy and h...

Research paper thumbnail of Suffering from Allergic Rhinitis and Common Cold

Department of Pathophysiology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak... more Department of Pathophysiology, Jessenius Faculty of Medicine, Comenius University, Martin, SlovakiaCough associated with upper respiratory tract disorders is a common andtroublesome problem in children and little is known about the etiology of this typeof cough. This study examined the capsaicin cough sensitivity (CS) in childrensuffering from allergic rhinitis (AR) and upper respiratory tract infection (URI),comparing it with that in healthy children taken as controls (C). CS to capsaicin,spirometry, skin prick tests, and nose-throat examination were performed in 61children grouped by the diagnosis of AR, URI, and C. The results, in order of C

Research paper thumbnail of Airway reactivity and neuroimmune relationships in animal model of air born irritants induced symptoms - Role of trigeminal TRPA1 channels

European Respiratory Journal, 2012

Air born pollutants modulate functions of airways. Many experimental models use inhalation of air... more Air born pollutants modulate functions of airways. Many experimental models use inhalation of air born irritants containing aerosols to mimic environmental exposure however, most exposed part is the nose. The aim of our study was to assess the general effects and modulation of airway defensive reflexes in animal model by selective nasal challenges with TRPA1 agonist AITC – allylisothiocyanate. TRPA1 is known to be relevant for most air born irritants. 15 male Dunkin Hartly guinea pigs were repeatedly exposed to 10mM AITC, 15μl administered into both nostrils and nasal symptoms, cough, specific airway resistance (Saw) and bronchoalveolar lavages (BAL) were analyzed afterwards. Nasal administration of 10 mM AITC induces reproducible nasal symptoms, sneezing, discharge, crackles and conjunctival reaction. Also, nasal application of 10mM AITC induces spontaneous rise of Saw measured by Pennock9s method in vivo and increases Saw after inhalation of methacholin (p

Research paper thumbnail of The interaction of dietary antioxidant vitamins and oxidative stress on cough reflex in guinea-pigs after long term oxygen therapy

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2006

Inhalation of high concentration of oxygen produces oxidative stress in men and experimental anim... more Inhalation of high concentration of oxygen produces oxidative stress in men and experimental animals. Our previous experiments showed that the cough reflex is suppressed in guinea pigs after exposure to 100% O(2) for 60 hours. The aim of this study was to determine the effects of dietary antioxidant supplementation with vitamins C and E on hyperoxia-induced oxidative stress in airway and lung tissues directed on cough reflex. The experimental group (T-H, n=8) was pretreated with vitamins C (500 mg/kg) and E (300 mg/kg) for 4 weeks and subsequently exposed to 100% O(2) for 60 hours. Hyperoxic group (H, n=8) received saline instead of antioxidants and then inhaled 100% O(2) for 60 hours. Cough was induced by inhalation of citric acid aerosol in gradually increased concentration (0.05-1.6 M) at the end of antioxidant therapy and then at the end of exposure to 100% O(2). Cough was also induced by mechanical stimulation of laryngopharyngeal (LPh) and tracheobronchial (TBr) region in anae...

Research paper thumbnail of Transient receptor potential ankyrin 1 (TRPA1)-mediated cough

European Respiratory Journal, 2011

TRPA1 detects many endogenous inflammatory and environmental pollutant molecules. Previous studie... more TRPA1 detects many endogenous inflammatory and environmental pollutant molecules. Previous studies implicated TRPA1 as a drug target for antitussive therapy. We evaluated relative efficacy of the TRPA1 activation in inducing cough in guinea pigs. Inhalation of the TRPA1 agonist allyl-isothiocyanate (AITC) evoked cough with a maximally effective concentration of 10mM (2.8±0.8 coughs/5min above vehicle, n=12) that was abolished by the TRPA1 selective antagonist AP-18 (1mM, n=8). AITC was ∼3-times less effective in inducing cough than the TRPV1 agonist capsaicin in the sub-maximally effective selective concentration (50μM) (8.2±2.1 coughs/5min above vehicle, n=9, p

Research paper thumbnail of Lessons learned from apnoe in cough down regulation

Afferents from the nose do not trigger cough, but the reflex is sensitized by experimental rhinit... more Afferents from the nose do not trigger cough, but the reflex is sensitized by experimental rhinitis. Most published data suggest that nasal sensory nerves are involved in up-regulation of cough, little evidence is available to support down-regulation of it from nose. Based on the data published recently about suppression of cough during water induced apnoe (Poussel et al., 2012), we decided to conduct a study on the model of irritant induced nasal apnea. Dunkin Hartley guinea pigs (n=8) were anaesthetized and tracheotomized. Trachea was lengthwise open at the proximal end and superfused with oxygenated saline. Cough was induced after nasal allylisothiocyanate AITC (TRPA1 agonist) by application of citric acid (CA) to the tracheal surface in ascending concentrations (0.001 - 2 M). Cough was also induced in conscious animals (n=22) by inhaling 0.4M CA for 10 min after nasal AITC. Cough response was estimated from the airflow traces and cough sound analysis. In anaesthesia, nasal AITC ...

Research paper thumbnail of Effects of hyperoxia and allergic airway inflammation on cough reflex intensity in guinea pigs

Toxic influence of high oxygen concentration on pulmonary function and structures has been known ... more Toxic influence of high oxygen concentration on pulmonary function and structures has been known for many years. However, the influence of high oxygen concentration breathing on defensive respiratory reflexes is still not clear. In our previous experiments, we found an inhibitory effect of 100 % oxygen breathing on cough reflex intensity in healthy guinea pigs. The present study was designed to detect the effects of hyperoxia on cough reflex in guinea pigs with allergic airway inflammation. In the first phase of our experiment, the animals were sensitized with ovalbumin. Thirty-two sensitized animals were used in two separate experiments according to oxygen concentration breathing: 100 % or 50 % oxygen for 60 h continuously. In each experiment, one group of animals was exposed to hyperoxia, another to ambient air. The cough reflex was induced both by aerosol of citric acid before sensitization, then in sensitized animals at 24 h and 60 h of exposition to oxygen/air in awake animals,...