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1

Role of afferent nerves and sensory peptides in the mediation of hepatic artery buffer response

100%

Biernat J., Pawlik W. W., Sendur R., Dembinski A., Brzozowski T., Konturek S. J.

Journal of Physiology and Pharmacology

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2005

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tom 56

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nr 1

Intrahepatic arteries are richly innervated by both adrenergic and sensory vanilloid-sensitive (capsaicin-sensitive) fibers. Stimulation of capsaicin sensitive fibers has been shown to dilate the intrahepatic vessels by both releasing sensory neuropeptides and by modulating the adrenergic tone. However the participation of capsaicin-sensitive fibers in the mediation of the hepatic artery buffer response (HABR) has not been investigated yet. To explore the involvement of sensory innervation and sensory neuropeptides in the HABR, the experiments were performed on capsaicin-denervated Wistar rats. In addition, we used selective CGRP and tachykinin receptor antagonists to test the participation of CGRP, substance P and NK-A in HABR in the rat. In anesthetized rats the hepatic artery blood flow (HABF), microcirculatory hepatic blood flow (HBF) and portal blood flow (PBF) were determined. The HABR was induced by partial occlusion of the portal vein and maintaining the PBF at 10% of its control preocclusive value. In the control HABR the hepatic artery blood flow increased by 89% (p< 0.005) whilst the HBF at the same time decreased by 32% (p< 0.005) in comparison to preocclusive HABF and HBF values. In sensory-denervated rats the resting HBF and PBF were increased by 23% (p< 0.05) and 34% (p< 0.05), respectively in comparison to the control HBF and PBF values. In this group the induction of the HABR increased the hepatic artery blood flow by only 55% (p< 0.05), whilst the HBF was reduced by 45% (p< 0.05). Pretreatment with CGRP 8-37 (CGRP receptor antagonist) and NK-1 but not NK-2 nor NK-3 receptor antagonists significantly reduced the HABF by 43% (p< 0.05) and 25 % (p< 0.05) as compared to the HABF value in the control HABR group. These findings support the hypothesis that the hepatic artery buffer response induced by reduction of the portal inflow to the liver by 90% is partially mediated by activation of capsaicin-sensitive sensory fibers in the liver, probably due to local tissue ischemia and hypoxia. The observed vasodilation in the vascular bed of the hepatic artery is due to stimulation of CGRP and NK-1 receptors.

2

Endotoxin-induced airway hyperresponsiveness in rabbits: contribution of neuropeptides

86%

Marek W., Ozyurt M., Potthast J., Mensing T.

Journal of Physiology and Pharmacology. Supplement

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2008

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tom 59

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nr 6

421-432

3

Cough sensitivity in localized sclerodermia with no clinical symptoms from lower airways

86%

Pecova R., Frlickova Z., Pec J., Tatar M.

Journal of Physiology and Pharmacology. Supplement

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2003

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tom 54

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nr 1

25-28

Cough sensitivity is increased in patients with atopic dermatitis, although they have no clinical symptoms from the lower airways. In the present study we examined the cough sensitivity to capsaicin in patients, who had no clinical respiratory symptoms, with sclerodermia localized to the skin. Cough sensitivity was defined as the lowest capsaicin concentration, which evokes 2 or more coughs. Twelve patients and 12 healthy matched volunteers, as a comparison group, inhaled deep breaths (2 L) of a capsaicin aerosol in doubled concentrations (from 0.02 to 200 µmol/L). Cough sensitivity, expressed as a geometric mean (95% CI) of capsaicin concentration, was 0.15 µmol/L (0.04 to 0.56) in the patients with localized sclerodermia and 4.96 µmol/L (2.50 to 9.85) in controls, which made a significant difference towards higher cough sensitivity in sclerodemia, respiratory symptom-free patients. Thus, disease processes localized outside the respiratory tract may have surreptitious pulmonary manifestation that is brought to light by the capsaicin cough test.

4

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Pharmacological profile of three different gamma-butyrolactone derivatives in mice

86%

Salat K., Librowski T., Filipek B.

Journal of Pre-Clinical and Clinical Research

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2010

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tom 04

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nr 1

5

Reliability of the capsaicin cough reflex sensitivity test in healthy children

86%

Verechova S., Plevkova J., Javorka M., Hanacek J.

Journal of Physiology and Pharmacology. Supplement

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2006

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tom 57

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nr 4

365-373

Testing cough reflex sensitivity (CRS) in children requires suitable methodology. A CRS test performed under control of inspiratory flow rate (IFR) shows excellent reliability in children, but it is difficult to perform, especially in younger children. The aim of the present study was to find whether the capsaicin CRS test performed without direct control of constant IFR in healthy children is reliable enough for practical use. The CRS test was performed in 27 healthy children, aged 7-17 yr three times within 8 days. Cough was induced by inhalation of capsaicin aerosol in doubling concentrations (0.61-1250 µmol/l) for 400 ms each. CRS was defined as the lowest capsaicin concentration that evoked 2 or more coughs (C2). Although the intraclass correlation coefficient values showed good to excellent reliability of this test, the within-subject standard deviation values revealed lower reliability of this method compared to the CRS test performed under control of IFR. From the results obtained it is reasonable to conclude that the method using uncontrolled IFR in CRS testing provides acceptable precision only when a bigger sample size is used or more tests are performed. Good to excellent reliability of this method was found in children with higher values of C2 and in those aged 13-17 yr.

6

Effect of sensory nerves and CGRP on the development of caerulein-induced pancreatitis and pancreatic recovery

86%

Warzecha Z., Dembinski A., Ceranowicz P., Stachura J., Tomaszewska R., Konturek S. J.

Journal of Physiology and Pharmacology

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2001

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tom 52

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nr 4,1

The function of primary sensory neurons is to receive and transmit information from external environment and these neurons are able to release neuromediators from the activated peripheral endings. The aim of this study was to determine the influence of sensory nerves and administration of their mediator — calcitonin gene related peptide (CGRP) on the course of acute pancreatitis (AP). Ablation of sensory nerves was performed by neurotoxic dose of capsaicin (100 mg/kg). Single or repeated episodes of AP were induced by caerulein infusion (10 µg/kg/h for 5 h). Five repeated AP were performed once a week. Capsaicin at the dose which stimulates sensory nerves (0.5 mg/kg/dose) or CGRP (10 µg/kg/dose) was administrated before and during or after single induction of AP, as well as, after each induction of repeated AP. Rats were killed at the time 0, 3 or 9 h after single induction of AP or two weeks after last induction of repeated AP. Ablation of sensory nerves aggravated pancreatic damage in caerulein-induced AP. Treatment with stimulatory doses of capsaicin or CGRP before and during single induction of AP attenuated the pancreatic damage in morphological examination. This effect was also manifested by partial reversion of AP evoked drop in DNA synthesis and pancreatic blood flow (PBF). Administration of CGRP after single AP induction aggravated histologically manifested pancreatic damage. The further decrease in PBF and DNA synthesis was also observed. Animals with five episodes of AP showed almost full pancreatic recovery two weeks after last induction of AP concerning all parameters tested. In stimulatory doses of capsaicin treated rats, we observed the decrease in pancreatic amylase and fecal chymotrypsin activity, as well as, the drop in DNA synthesis. Similar but less pronounced effects were observed after treatment with CGRP. We conclude that effect of sensory nerves and CGRP on AP is two-phase and time dependent. Stimulation of sensory nerves or the administration of CGRP during development of AP exhibits protective effects against pancreatic damage induced by caerulein overstimulation. After induction of AP, persistent activity of sensory nerves and presence of CGRP aggravate pancreatic damage and lead to functional insufficiency typical for chronic pancreatitis.

7

Expression of vanilloid receptor-1 in the duodenum of the capsaicin treated rat

86%

Zik B., Ozguden C., Tutuncu S., Ilhan T.

Bulletin of the Veterinary Institute in Puławy

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2007

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tom 51

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nr 1

The aim of the presented investigation was to identify different vanilloid receptor-1 (VR1) immunoreactivity after application of low dose of capsaicin (0.5 mg/kg) for a prolonged period in the rat's duodenum. Paraffin-embedded sections were processed for standard immunohistochemistry by the labelled streptavidin-biotin technique. The VR1 localisations were identified on the epithelial layers of the villi, in the Brunner's glands, smooth muscles layer, and the neurons of the myenteric plexus of the duodenum. While VR1 immunoreactivity was identified in small quantities in the control group, VR1 expression was strong both in the experimental and in the vehicle treated group. These results indicate that prolonged administration of a low dose of capsaicin may not be sufficient to stimulate VR1. Also the vehicle additives, Tween 80 and 10% ethanol, which are used to solubilize capsaicin, may activate the protection mechanism in the mucosa epithelium and stimulate the capsaicin sensitive afferent neurons by VR1 to increase mucus secretion.

8

Capsaicin induced deafferentiation enhances the effect of electrical vagal nerve stimulation on food intake and body mass

86%

Laskiewicz J., Krolczyk G., Zurowski D., Enck P., Thor P. J.

Journal of Physiology and Pharmacology

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2004

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tom 55

|

nr 1,2

Study was based on hypothesis that electrical stimulation (ES) with parameters obtained from analysis of vagal afferent discharge fed state may fake brain with satiety state. We evaluated effect of denervation of vagal capsaicin-sensitive afferents on food intake and body weight in rats with ES of vagal nerves using microchip (MC). Group A was scheduled to MC implantation, B to sham operation only, C to MC implantation and capsaicin vagal deafferentation, and D to capsaicin denervation only. ES lasted 24 days. MC parameters were 0.05Hz, 0.1s, 0.55V. ES of left vagus significantly reduced total food intake as well as the mean daily intake in groups A and C in comparison to control and D group (ANOVA, F=18.55, p=0.0038). Body weight was lower in group A (346,2 g) and C (272,7 g) then in control (381,4 g) and D (356,8 g) (F=25.68, p=0.00068). Leptin decreased in C (165 pg/mL) in comparison to A (625 pg/mL), B (677 pg/mL), and D (612 pg/mL) (p<0,05), mainly due to ES (F=7.27, p=0.019). Glucose was decreased in A (F=5.55, p=0.036) - by 11 % and by 16% in C group. Proper vagal neuromodulation results in central and peripheral effects causing food intake and body weight downregulation.

9

Effect of capsaicin and dimethyl sulphoxide [DMSO] on ion transport in isolated skin of frog [Rana esculenta L.]

86%

Kosik- Bogacka D. I., Tyrakowski T.

Folia Biologica

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2003

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tom 51

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nr 1-2

10

Capsaicinoids in hot pepper depending on fruit maturity stage and harvest date

72%

Buczkowska H., Dyduch J., Najda A.

Acta Scientiarum Polonorum. Hortorum Cultus

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2013

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tom 12

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nr 6

The pharmacological and culinary usefulness of hot pepper fruits is determined, among others, by the content of capsaicinoids that give hot peppers a pungent burning taste. The content of these compounds in hot pepper is primarily determined by the genetic traits of a cultivar and is modified by various factors: weather conditions during the growing season, fertilization, harvest time, and fruit maturity stage. The aim of the present study was to evaluate the effect of fruit maturity stage: green fruits, fruits turning colour as well as physiologically mature fruits (red), and fruit harvest date: the first and third decade of September, on the content of capsaicinoids in four hot pepper cultivars: ‘Cyklon’, ‘Orkan’, ‘Rokita’, and ‘Bronowicka Ostra’. In this study, which was carried out in 2005 and 2006, the content of capsaicinoids (capsaicin and dihydrocapsaicin) was measured by HPLC. The highest amount of capsaicinoids was obtained in the fruits of hot pepper that were harvested at the initial stage of maturity – in green fruits (on average 309 mg·kg⁻¹), compared to fruits turning red (258) and red fruits (250 mg·kg⁻¹). Peppers selected in the third decade of September contained more capsaicinoids (on average 301 mg·kg⁻¹) than those harvested in the first decade of this month (243 mg·kg⁻¹). Fruits of the evaluated cultivars differed in capsaicinoids content; on average it ranged from 212 (‘Cyklon’) to 326 mg·kg⁻¹ (‘Bronowicka Ostra’). In fruits of all the quantitative ratio of capsaicin to dihydrocapsaicin was at a similar level, ranging between 11.9 and 12.9. The capsaicinoids content in fruits of the investigated cultivars differed between years 2005 (302) and 2006 (243 mg·kg⁻¹).

11

Cough sensitivity in allergic rhinitis

72%

Pecova R., Vrlik M., Tatar M.

Journal of Physiology and Pharmacology. Supplement

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2005

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tom 56

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nr 4

171-178

The objective of this study was to evaluate capsaicin cough sensitivity in pollen sensitive patients with allergic rhinitis at the time of grass pollen season and out of it. Cough reflex sensitivity was defined as the lowest capsaicin concentration that evoked 2 or more coughs (C2). Capsaicin aerosol in doubled concentrations (from 0.02 to 200 µmol) was inhaled by a single breath. Two groups of pollen sensitive rhinitis subjects and a group of healthy controls were studied. The C2 for the 23 pollen sensitive patients of the first group, studied out of pollen season (January-February), was 0.22 µmol/l (0.06-0.76) (geometric mean + 95% CI), which was substantially lower than the 4.29 µmol/l (2.54-7.26) in 24 healthy volunteers (P=0.0001). In another group of 15 pollen sensitive patients, C2 was 0.84 µmol/l (0.14-5.20) out of pollen season and 0.11 µmol/l (0.03-0.33) during the pollen season (May-June) (P=0.04). We conclude that pollen-sensitive subjects who suffer of seasonal allergic rhinitis have significantly greater capsaicin cough sensitivity, regardles of them being in or out of pollen season. Subclinical inflammatory changes in the lower airways are probably responsible for this effect.

12

Tussigenic agents in the measurement of cough reflex sensitivity

72%

Pecova R., Javorkova N., Kudlicka J., Tatar M.

Journal of Physiology and Pharmacology. Supplement

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2007

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tom 58

|

nr 5

13

Technological characteristics of fruit as an average of 25 soft-flesh Capsicum spp. genotypes

72%

Nowaczyk L.

Herba Polonica

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2011

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tom 57

|

nr 2

The research material used to evaluate the relationship between technological features of soft-flesh fruit involved the lines derived from the interspecific hybrid Capsicum frutescens L. x C. annuum L. The genotypes differed in their yielding, morphological features of fruit, technological efficiency and the content of capsaicinoids, which ranged from 20 to 770 and from 10 to 330 mg.kg-1, respectively, of capsaicin and dihydrocapsaicin in the pericarp, from 60 to 3870 and from 30 to 1550 mg.kg-1 in the puree produced as a result of mechanical separation of the soft tissue of the pericarp from the inedible parts (placenta, seeds, septa and the peel). There was found a negative correlation between the fruit average weight and length and the content of capsaicin in the pericarp and in the puree and for the capsaicinoids sum in the puree. The contents of the two compounds were positively correlated in each material researched, both when individual capsaicinoids were compared and when their sum was given.

14

Neural control of the release and action of secretin

72%

Chey W. Y., Chang T-M.

Journal of Physiology and Pharmacology. Supplement

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2003

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tom 54

|

nr 4

105-112

The release and physiological actions of secretin on pancreatic exocrine secretion and gastric secretion of acid and motility are regulated by neuro-hormonal control. The release of secretin by duodenal acidification is mediated by a secretin releasing peptide (SRP). The release and action of SRP are neurally mediated depending on vagal afferent pathway. SRP activity in acid perfusate of the duodenum was substantially decreased when rats were treated with tetradotoxin (TTX), perivagal application of capsaicin, a ß-adrenergic blocker, Met-enkephalin (MEK) or vagotomy. The release of secretin by SRP was abolished in rats treated with TTX, mucosal or perivagal application of capsaicin, MEK or vagotomy. Both release of secretin and pancreatic exocrine secretion (PES) elicited by duodenal acidification were also inhibited dose-dependently by Met-enkepahlin, 5-HT2 antagonist, ketanserin and 5-HT3 antagonist, ondansetron. Stimulation of PES and inhibition of gastric acid secretion and motility by secretin in a physiological dose are also dependent on the vagal afferent pathway as these effects of secretin are abolished by perivagal capsaicin treatment or vagotomy. In conscious rats, vagotomy, vagal ligation, or perivagal colchicine but not capsaicin treatment reduced the number of secretin binding sites in the forestomach suggesting another mode of neural regulation that affects gastric motility. Except in the rat, stimulation of PES by secretin in a physiological dose is profoundly inhibited by atropine indicating the importance of a cholinergic input. In isolated and perfused rat pancreas, electrical field stimulation potentiated secretin-stimulated PES that was suppressed by atropine and anti-GRP serum, suggesting the roles of intrapancreatic cholinergic and GRP-containing neurons. In rats, secretin-stimulated PES was inhibited by a NO synthase inhibitor suggesting mediation by NO. However, the neuropeptides and neurotransmitters involved in regulation of the release and action of secretin and their sites of action remain to be elucidated.

15

Cough reflex sensitivity testing in seasonal allergic rhinitis patients and healthy volunteers

72%

Pecova R., Zucha J., Pec M., Neuschlova M., Hanzel P., Tatar M.

Journal of Physiology and Pharmacology. Supplement

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2008

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tom 59

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nr 6

557-564

16

Urodynamic effects of the bladder C-fiber afferent activity modulation in chronic model of overactive bladder in rats

72%

Juszczak K., Ziomber A., Wyczolkowski M., Thor P. J.

Journal of Physiology and Pharmacology

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2009

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tom 60

|

nr 4

85-91

Previous studies have suggested that, different types of unmyelinated bladder afferent C-fibres, such as capsaicin-sensitive and capsaicin-resistant mediate the voiding reflex in overactive bladder (OAB). Considering its polymodal features, we explored the urodynamic effect of primary afferent neurons modulation on detrusor activity in normal and OAB rats. Experiments were performed on 48 female rats. OAB was induced by intraperitoneal administration of cyclophosphamide. All the surgical procedures and urodynamic studies were performed under urethane anaesthesia. Cystometry was done after a 1 h recovery period from the surgical procedure. All animals were randomly divided into six groups: control, chronic OAB, chronic OAB after capsaicin or lidocaine instillation, control capsaicin or lidocaine instillation. The measurements represent the average of five bladder micturition cycles. We analyzed: basal, threshold, micturition voiding pressure; intercontraction interval; compliance; functional bladder capacity; motility index; detrusor overactivity index. We used chronic cyclophosphamide OAB model for further investigations. In healthy rats, intravesical instillation of capsaicin caused complete inhibition of detrusor contractility preventing from proper voiding function of the bladder. Contrary, lidocaine has no influence on micturition cycles in intact animals. Also, intravesical instillation of capsaicin and lidocaine reduced the severity of detrusor overactivity of OAB rats leading to improvement of cystometric parameters.

17

Systemic and local effects of intragastric administration of the habanero fruit (Capsicum chinense jacquin c.v.) in rats

72%

Golynski M., Balicki I., Lutnicki K., Smiech A., Adamek L., Szczepanik M., Wilkolek P., Brodzki A., Adaszek L.

Journal of Physiology and Pharmacology

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2015

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tom 66

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nr 2

18

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

72%

Plevkova J., Antosiewicz J., Verechova S., Poliacek I., Jakus J., Tatar M., Pokorski M.

Journal of Physiology and Pharmacology

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2009

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tom 60

|

nr 2

89-93

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.

19

Relationships between capsaicinoids in the soft-flesh genotypes of Capsicum spp.

72%

Nowaczyk L., Nowaczyk P., Banach-Szott M.

Herba Polonica

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2009

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tom 55

|

nr 3

185-192

The studies aimed at determining the levels and reciprocal proportions of capsaicinoids (capsaicin and dihydrocapsaicin) in the pericarp and puree obtained by the mechanical separation of the soft tissue from the inedible parts of fruits. The studied material involved a few lines, selected from the interspecies hybrid of Capsicum frutescens L. x C. annuum L., manifesting a soft-flesh tissue of pericarp in mature fruits. The quantitative estimation of capsaicinoids was conducted using HPLC. The capsaicin content in the studied lines ranged from 9 to 27 and from 20 to 387 mg. kg-1 in the pericarp and puree, respectively. For dihydrocapsaicin, the values ranged from 3 to 26 and from 6 to 155 mg. kg -1, respectively. Depending on the genotype group, the content of each of the compounds in the puree was 2.5- to about 10-fold higher than in the pericarp tissue. Both in the pericarp and in the puree the level of capsaicin was around 2.5-fold higher than that of dihydrocapsaicin.

20

Capsaicin induces apoptosis by generating reactive oxygen species and disrupting mitochondrial transmembrane potential in human colon cancer cell lines

72%

Yang K. M., Pyo J. O., Kim G.-Y., Yu R., Han I. S., Ju S. A., Kim W. H., Kim B.-S.

Cellular and Molecular Biology Letters

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2009

|

tom 14

|

nr 3

497-510

Although genetic factors are a well-known cause of colorectal cancer, environmental factors contribute more to its development. Despite advances in the fields of surgery, radiotherapy and chemotherapy, the cure rates for colon cancer have not substantially improved over the past few decades. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), the principal pungent ingredient of hot chili pepper, has exhibited an anti-tumor effect in many cell types. However, the mechanisms responsible for the anti-tumor effect of capsaicin are not yet completely understood. In this study, we investigated whether capsaicin induces apoptosis in colon cancer cell lines. Capsaicin decreased cell viability in a dose-dependent manner in Colo320DM and LoVo cells. In addition, capsaicin produced cell morphology changes and DNA fragmentation, decreased the DNA contents, and induced phosphatidylserine translocation, which is a hallmark of apoptotic cell death. We showed that capsaicin-induced apoptosis is associated with an increase in ROS generation and a disruption of the mitochondrial transmenbrane potential. A possible mechanism of capsaicin-induced apoptosis is the activation of caspase 3, a major apoptosis-executing enzyme. Treatment with capsaicin induced a dramatic increase in caspase 3 activity, as assessed by the cleavage of Ac-DEVD-AMC, a fluorogenic substrate. In conclusion, our results clearly showed that capsaicin induced apoptosis in colon cancer cells. Although the actual mechanisms of capsaicin-induced apoptosis remain uncertain, it may be a beneficial agent for colon cancer treatment and chemoprevention.

Ograniczanie wyników

Role of afferent nerves and sensory peptides in the mediation of hepatic artery buffer response

Endotoxin-induced airway hyperresponsiveness in rabbits: contribution of neuropeptides

Cough sensitivity in localized sclerodermia with no clinical symptoms from lower airways

Pharmacological profile of three different gamma-butyrolactone derivatives in mice

Reliability of the capsaicin cough reflex sensitivity test in healthy children

Effect of sensory nerves and CGRP on the development of caerulein-induced pancreatitis and pancreatic recovery

Expression of vanilloid receptor-1 in the duodenum of the capsaicin treated rat

Capsaicin induced deafferentiation enhances the effect of electrical vagal nerve stimulation on food intake and body mass

Effect of capsaicin and dimethyl sulphoxide [DMSO] on ion transport in isolated skin of frog [Rana esculenta L.]

Capsaicinoids in hot pepper depending on fruit maturity stage and harvest date

Cough sensitivity in allergic rhinitis

Tussigenic agents in the measurement of cough reflex sensitivity

Technological characteristics of fruit as an average of 25 soft-flesh Capsicum spp. genotypes

Neural control of the release and action of secretin