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EN
Capsaicin has been reported to exhibit an inhibitory effect on the P-glycoprotein (P-gp) function in vitro. To investigate its concentration-dependent effect in vivo, a sensitive assay that can characterize the absorption and disposition of capsaicin needs to be developed. This study reports the development of a sensitive LC-MS/MS assay for the determination of capsaicin in mouse plasma. The sample pretreatment involved a one-step extraction of 20 μL plasma with t-butyl methyl ether. Separations were achieved on a C18 column and the detection was performed on an LC-ESI-MS/MS by multiple reaction monitoring. The assay was linear over a wide concentration range from 0.325 to 650 ng mL-1 (r > 0.999), with a LLOQ of 0.325 ng mL-1. The developed method was applied to i.v. (dose 0.325 and 0.65 mg kg) and oral absorption (dose 40 mg kg) studies in mice. After i.v. injection, the t1/2,λz, Vz and CLs ranged from 0.13–0.16 h, 127.6–141.8 mL, and 547.3–775.4 mL/h, respectively. After oral administration, a secondary peak was observed and the terminal half-life was prolonged (1.51 h). Capsaicin was poorly absorbed, with the absolute oral bioavailability (F) ranging from 1.02% to 1.56%. The developed assay may be useful in studies where sample volumes are limited.
EN
Diethylnitrosamine (DEN) is proven to be toxic to kidneys and liver and to act as a potent carcinogen mainly in liver. Capsaicin (CAP) is an alkaloid produced by Capsicum genus plants and is considered to be a protective agent against toxicity and carcinogenicity of many substances including DEN. The aim of this study was to assess the toxicity of DEN and CAP in liver and kidneys in mice. The experiment started after two weeks of acclimatisation and was conducted according to the Czech animal welfare protection legal guidelines. At the end of the experiment the mice were sacrificed and the toxicity of DEN and CAP in liver and kidneys were analysed. The histopathological examination of the liver revealed multifocal lymphoplasmacytic reaction in parenchyma in DEN treated group. CAP used as both preventive and therapeutic agent caused reduction in number and extent of lesions. In CAP group mitotic figures were found indicating xenobiotic-induced hepatotoxicity or regenerative changes. In the kidneys DEN revealed also multifocal lymphoplasmacytic reaction that has been mitigated by CAP. Moreover histopathological observation of the kidney in DEN group has revealed granular dystrophy of the renal tubules which has not been presented in CAP treated mice. Levels of ALT, AST activity, total protein and albumin concentration was not statistically different among control and experimental groups. In this study mild protective effect of CAP on DEN-induced hepatotoxicity and nephrotoxicity was shown only in histopathological changes. The toxicity of CAP itself is questionable and further studies should be performed to verify its chemopreventive potential.
EN
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.
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EN
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.
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Content available remote Reliability of the capsaicin cough reflex sensitivity test in healthy children
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EN
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.
EN
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.
EN
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.
EN
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.
EN
In the research presented the effect of Bulldock insecticide and capsaicin on CO2 release in mealworm Tenebrio molitor was assessed. Metabolic rates of insects intoxicated with tested substances were measured using flow-through respirometry. The results obtained showed considerable increase in CO2 release after application both pyrethroid and capsaicin. The highest metabolic rates were observed after simultaneous intoxication with capsaicin and insecticide. These results suggest that capsaicin enhances the toxic effect of Bulldock and may be used as this insecticide’s synergist against mealworms.
PL
W prezentowanych badaniach określano wpływ insektycydu Bulldock i kapsaicyny na tempo uwalniania CO2u larw mącznika młynarka Tenebrio molitor. Tempo metabolizmu owadów intoksykowanych badanymi substancjami mierzono przy użyciu układu respirometrycznego, służącego do pomiarów w układzie przepływowym. Uzyskane wyniki wykazały znaczący wzrost ilooeci uwalnianego CO2 po aplikacji zarówno pyretroidu, jak i kapsaicyny. Najwyższe tempo metabolizmu odnotowano po jednoczesnej intoksykacji kapsaicyną i insektycydem. Przedstawione wyniki sugerują, że kapsaicyna zwiększa toksyczny wpływ pestycydu Bulldock i prawdopodobnie może być używana jako synergetyk dla tego insektycydu przeciwko larwom mącznika młynarka.
EN
Intensive use of insecticides has led not only to enhanced environment pollution, but most of all, to an increase in insects’ resistance to the chemicals in use. That is why presently the scientists focus on searching for new, alternative means to aid crop protection. One of the ways to achieve it is finding a compound which, when added to an insecticide, magnifies significantly its toxicity against the pests and in the same time it is safe for people. In the presented study we have attempted to analyse whether the active compound of pepper, capsaicin, increases toxicity of a pyrethroid (Bulldock 025 EC) against American cockroach, a main insect factor causing allergies and asthma in people. The effect of the tested substances was measured by means of changes observed in hemolymph pH and acute toxicity test, performed in various ambient temperatures (15 oC, 25 oC and 35 oC). The results of the experiments suggest that the tested substances affect significantly acid-base homeostasis. Moreover, it was demonstrated that different concentrations of capsaicin have different influence on insecticidal properties of the tested pesticide in higher ambient temperatures. It was established that simultaneous application of capsaicin (in 10–8 M concentration) and pyrethroid (LD50) causes an increase in death rate among the intoxicated insects. These results give hopes as for applicability of capsaicin as a synergist of pyrethroid insecticides against Periplaneta americana, especially in conditions in which the toxicity of the pesticide itself is lower (ie in higher ambient temperatures).
PL
Intensywne stosowanie insektycydów doprowadziło nie tylko do wzrostu zanieczyszczenia środowiska, ale przede wszystkim do wzrostu oporności owadów na stosowane środki. Dlatego też uwaga badaczy koncentruje się obecnie na poszukiwaniu alternatywnych metod walki ze szkodnikami. Jedną z nich może być znalezienie substancji, która dodana do insektycydu, w sposób znaczący podniesie jego toksyczność dla owadów i zarazem będzie bezpieczna dla ludzi. W prezentowanej pracy podjęto próbę oceny czy aktywny składnik papryki – kapsaicyna, zwiększy toksyczność pyretroidu (Bulldock 025EC) w stosunku do karaczana amerykańskiego, będącego głównym czynnikiem wywołującym alergie i astmę u ludzi. Toksyczność badanych substancji określano na podstawie zmian odczynu hemolimfy oraz testów toksyczności ostrej, wykonanych w trzech różnych temperaturach otoczenia (15 oC, 25 oC i 35 oC). Z przeprowadzonych doświadczeń wynika, że badane substancje w sposób znaczny zmieniają równowagę kwasowo-zasadową. Wykazano także, że testowane stężenia kapsaicyny w różny sposób wpływają na aktywność owadobójczą zastosowanego insektycydu w wyższych temperaturach otoczenia. Stwierdzono, że jednoczesna aplikacja kapsaicyny (w stężeniu 10 -8 M) i pyretroidu (LD50) powoduje wzrost śmiertelności intoksykowanych owadów. Na podstawie otrzymanych wyników można przypuszczać, że kapsaicynę będzie można stosować jako synergetyk dla insektycydów z grupy pyretroidów w stosunku do Periplaneta americana, zwłaszcza w tych warunkach środowiska, w których toksyczność pyretroidu jest mniejsza (duże temperatury otoczenia).
EN
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.
EN
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.
PL
Materiałem badawczym użytym do oceny wzajemnych zależności między cechami technologicznymi owoców soft-flesh były linie wyprowadzone z mieszańca międzygatunkowego Capsicum frutescens L. x C. annuum L. Genotypy różniły się pod względem masy owoców uzyskanych z rośliny, cech morfologicznych owoców, wydajności technologicznej oraz zawartości kapsaicynoidów, która zawierała się w granicach od 20–770 i 10–330 mg.kg-1 , odpowiednio kapsaicyny i dihydrokapsaicyny w perykarpie, do 60–3870 i 30 –1550 mg.kg-1 w przecierze uzyskanym w wyniku mechanicznej separacji miękkiej tkanki perykarpu od części niejadalnych (łożysko, nasiona, przegrody i skórka). Stwierdzono ujemną korelację między średnią masą i długością owoców a zawartością kapsaicynoidów w perykarpie i w przecierze. Zawartości obydwu omawianych związków były dodatnio skorelowane w każdym z badanych materiałów, zarówno przy porównaniu indywidualnym każdego z kapsaicynoidów, jak też dla ich sumy.
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Content available remote Trójfazowa fluidalna ekstrakcja kapsaicyny z owoców papryki Capsicum chinense
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PL
Przeprowadzono trójfazowe fluidalne ekstrakcje wysuszonych i rozdrobnionych owoców żółtej i czerwonej odmiany papryki Capsicum chinense z wykorzystaniem n-heksanu, cykloheksanu, octanu etylu, acetonu, etanolu i metanolu jako ekstrahentów. Otrzymane ekstrakty analizowano metodą chromatografii gazowej sprzężonej ze spektrometrią mas. Uzyskane wartości odzysków kapsaicyny i dihydrokapsaicyny potwierdzają celowość wykorzystywania do ekstrakcji rozpuszczalników o budowie polarnej.
EN
Fruits of yellow and red varieties of Capsicum chinense sp. peppers were dried, fragmented and extd. with n-hexane, cyclohexane, AcOEt, COMe₂, EtOH and MeOH. The exts. Were analyzed by gas chromatog. coupled to mass spectrometry. The anal. confirmed the presence of capsaicinoids in the exts. The recovery of capsaicin and dihydrocapsaicin was highest when MeOH and EtOH were used as extn. Solvents.
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Content available remote Neural control of the release and action of secretin
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EN
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.
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