- Molecular Features Underlying Selectivity in Chicken Bitter Taste Receptors. [Journal Article]
- FMFront Mol Biosci 2018; 5:6
- Chickens sense the bitter taste of structurally different molecules with merely three bitter taste receptors (Gallus gallustaste 2 receptors, ggTas2rs), representing a minimal case of bitter percepti...
Chickens sense the bitter taste of structurally different molecules with merely three bitter taste receptors (Gallus gallustaste 2 receptors, ggTas2rs), representing a minimal case of bitter perception. Some bitter compounds like quinine, diphenidol and chlorpheniramine, activate all three ggTas2rs, while others selectively activate one or two of the receptors. We focus on bitter compounds with different selectivity profiles toward the three receptors, to shed light on the molecular recognition complexity in bitter taste. Using homology modeling and induced-fit docking simulations, we investigated the binding modes of ggTas2r agonists. Interestingly, promiscuous compounds are predicted to establish polar interactions with position 6.51 and hydrophobic interactions with positions 3.32 and 5.42 in all ggTas2rs; whereas certain residues are responsible for receptor selectivity. Lys3.29and Asn3.36are suggested as ggTas2r1-specificity-conferring residues; Gln6.55as ggTas2r2-specificity-conferring residue; Ser5.38and Gln7.42as ggTas2r7-specificity conferring residues. The selectivity profile of quinine analogs, quinidine, epiquinidine and ethylhydrocupreine, was then characterized by combining calcium-imaging experiments andin silicoapproaches. ggTas2r models were used to virtually screen BitterDB compounds. ~50% of compounds known to be bitter to human are likely to be bitter to chicken, with 25, 20, 37% predicted to be ggTas2r1, ggTas2r2, ggTas2r7 agonists, respectively. Predicted ggTas2rs agonists can be tested within vitroandin vivoexperiments, contributing to our understanding of bitter taste in chicken and, consequently, to the improvement of chicken feed.
- Potentially inappropriate medication and hospitalization/emergency department visits among the elderly in Korea. [Journal Article]
- IJInt J Qual Health Care 2018 Feb 01; 30(1):50-56
- CONCLUSIONS: Our findings indicate that PIM use can lead to negative health consequences, providing further evidence of the inappropriateness of these medications. Thus, pharmaceutical policies regarding PIM use may need to be implemented for elderly adults in Korea.
- Spectrophotometric method development and validation for determination of chlorpheniramine maleate in bulk and controlled release tablets. [Journal Article]
- PJPak J Pharm Sci 2018; 31(1(Suppl.)):353-358
- Spectrophotometric technique is considered to be the simplest and operator friendly among other available analytical methods for pharmaceutical analysis. The objective of the study was to develop a p...
Spectrophotometric technique is considered to be the simplest and operator friendly among other available analytical methods for pharmaceutical analysis. The objective of the study was to develop a precise, accurate and rapid UV-spectrophotometric method for the estimation of chlorpheniramine maleate (CPM) in pure and solid pharmaceutical formulation. Drug absorption was measured in various solvent systems including 0.1N HCl (pH 1.2), acetate buffer (pH 4.5), phosphate buffer (pH 6.8) and distil water (pH 7.0). Method validation was performed as per official guidelines of ICH, 2005. High drug absorption was observed in 0.1N HCl medium with λmaxof 261nm. The drug showed the good linearity from 20 to 60μg/mL solution concentration with the correlation coefficient linear regression equation Y= 0.1853 X + 0.1098 presenting R2value of 0.9998. The method accuracy was evaluated by the percent drug recovery, presents more than 99% drug recovery at three different levels assessed. The % RSD value <1 was computed for inter and intraday analysis indicating the high accuracy and precision of the developed technique. The developed method is robust because it shows no any significant variation in with minute changes. The LOD and LOQ values were assessed to be 2.2μg/mL and 6.6μg/mL respectively. The investigated method proved its sensitivity, precision and accuracy hence could be successfully used to estimate the CPM content in bulk and pharmaceutical matrix tablets.
- The Histamine H1 Receptor Participates in the Increased Dorsal Telencephalic Neurogenesis in Embryos from Diabetic Rats. [Journal Article]
- FNFront Neurosci 2017; 11:676
- Increased neuron telencephalic differentiation during deep cortical layer formation has been reported in embryos from diabetic mice. Transitory histaminergic neurons within the mesencephalon/rhombenc...
Increased neuron telencephalic differentiation during deep cortical layer formation has been reported in embryos from diabetic mice. Transitory histaminergic neurons within the mesencephalon/rhombencephalon are responsible for fetal histamine synthesis during development, fibers from this system arrives to the frontal and parietal cortex at embryo day (E) 15. Histamine is a neurogenic factor for cortical neural stem cells in vitro through H1 receptor (H1R) which is highly expressed during corticogenesis in rats and mice. Furthermore, in utero administration of an H1R antagonist, chlorpheniramine, decreases the neuron markers microtubuline associated protein 2 (MAP2) and forkhead box protein 2. Interestingly, in the diabetic mouse model of diabetes induced with streptozotocin, an increase in fetal neurogenesis in terms of MAP2 expression in the telencephalon is reported at E11.5. Because of the reported effects on cortical neuron differentiation of maternal diabetes in one hand and of histamine in the other, here the participation of histamine and H1R on the increased dorsal telencephalic neurogenesis was explored. First, the increased neurogenesis in the dorsal telencephalon at E14 in diabetic rats was corroborated by immunohistochemistry and Western blot. Then, changes during corticogenesis in the level of histamine was analyzed by ELISA and in H1R expression by qRT-PCR and Western blot and, finally, we tested H1R participation in the increased dorsal telencephalic neurogenesis by the systemic administration of chlorpheniramine. Our results showed a significant increase of histamine at E14 and in the expression of the receptor at E12. The administration of chlorpheniramine to diabetic rats at E12 prevented the increased expression of βIII-tubulin and MAP2 mRNAs (neuron markers) and partially reverted the increased level of MAP2 protein at E14, concluding that H1R have an important role in the increased neurogenesis within the dorsal telencephalon of embryos from diabetic rats. This study opens new perspective on the participation of HA and H1R receptor in early corticogenesis in health and disease.
- Histamine H1Receptor Antagonists Facilitate Electroacupuncture Analgesia. [Journal Article]
- AJAm J Chin Med 2018; 46(1):55-68
- This study investigated the influence of the histamine H1receptor antagonists, chlorpheniramine (CHL) and pyrilamine, on the analgesic effects of acupuncture in mice. Nociceptive response was evaluat...
This study investigated the influence of the histamine H1receptor antagonists, chlorpheniramine (CHL) and pyrilamine, on the analgesic effects of acupuncture in mice. Nociceptive response was evaluated by the acetic acid-induced abdominal writhe test. Electroacupuncture (EA) at bilateral ST36 reduced the manifestations of acetic acid-induced abdominal writhing, whereas needle insertion without electrostimulation had no such effect. Notably, EA treatment was not associated with any analgesic effects in mice pretreated with naloxone. Low doses of CHL (0.6[Formula: see text]mg/kg; p.o.) or pyrilamine (2.5[Formula: see text]mg/kg; i.p.) as monotherapy did not affect acetic acid-induced abdominal writhing. However, when each agent was combined with EA, acetic acid-induced abdominal writhing was reduced by a greater extent when compared with EA alone. Interestingly, the effects of CHL on acupuncture analgesia were not completely reversed by naloxone treatment. Acetic acid induced increases of phospho-p38 expression in spinal cord, as determined by immunofluorescence staining and Western blot analysis. These effects were attenuated by EA at ST36 and by low doses of histamine H1receptor antagonists, alone or in combination. Our findings show that relatively low doses of histamine H1receptor antagonists facilitate EA analgesia via non-opioid receptors. These results suggest a useful strategy for increasing the efficacy of EA analgesia in a clinical situation.
- The effect of Nesfatin-1 on food intake in neonatal chicks: role of CRF1/CRF2 and H1/ H3 receptors. [Journal Article]
- VRVet Res Commun 2018; 42(1):39-47
- The present study was designed to determine the effect of central injection of Nesfatin-1 and corticotropin and histaminergic systems on food intake in neonatal meat-type chicks. In this study, 7 exp...
The present study was designed to determine the effect of central injection of Nesfatin-1 and corticotropin and histaminergic systems on food intake in neonatal meat-type chicks. In this study, 7 experiments were designed, each with 4 treatment groups. In experiment 1, four groups of chicks received the ICV injection of (A) phosphate-buffered saline (PBS), (B) Nesfatin-1 (10 ng), (C) Nesfatin-1 (20 ng) and (D) Nesfatin-1 (40 ng). In experiment 2, (A) PBS, (B) Astressin-B (CRF1/CRF2receptors antagonist; 30 µg), (C) Nesfatin-1 (40 ng) and (D) Nesfatin-1 + Astressin-B were injected. In experiments 3-6, chicken received ICV injection of the Astressin2-B (CRF2receptor antagonist; 30 µg), α-FMH (alpha fluoromethyl histidine; as inhibitor of histidine decarboxylase, 250 nmol), Chlorpheniramine (histamine H1receptors antagonist, 300 nmol), Famotidine (histamine H2receptors antagonist, 82 nmol) and Thioperamide (histamine H3receptors antagonist, 300 nmol) instead of the Astressin-B. Then the cumulative food intake measured until 120 min post-injection. According to the results, ICV injection of Nesfatin-1 dose dependently decreased food intake in neonatal chicks (P < 0.05). Co-injection of the Nesfatin-1 and Astressin-B (CRF1/CRF2) inhibited Nesfatin-1 induced hypophagia (P < 0.05). ICV inejction of the Nesfatin-1 + Astressin-B significantly inhibited the effect of Nesfatin-1 on food intake (P < 0.05). In addition, α-FMH and chlorpheniramine attenuated Nesfatin-1-induced hypophagia in chicks (P < 0.05); while thioperamide significantly amplified the effect of Nesfatin-1 on food intake in chicks (P < 0.05). These results suggested Nesfatin-1 has an anorectic effect in 3-hour food deprived neonatal meat-type chicks and this effect was mediated by corticotropin CRF1/CRF2as well as histamine H1and H3receptors.
- An autopsy case of death by combined use of benzodiazepines and diphenidine. [Journal Article]
- SLSoud Lek 2017; 62(4):40-43
- We present an autopsy case involving benzodiazepines and diphenidine. Quantitative toxicological analysis showed concentrations of 7-aminoflunitrazepam (a flunitrazepam metabolite), 7-aminonimetazepa...
We present an autopsy case involving benzodiazepines and diphenidine. Quantitative toxicological analysis showed concentrations of 7-aminoflunitrazepam (a flunitrazepam metabolite), 7-aminonimetazepam (a nimetazepam metabolite), chlorpheniramine and diphenidine in femoral blood of 0.086 µg/ml, 0.027 µg/ml, 0.066 µg/ml, and 0.073 µg/ml, respectively. Death was attributed to combined toxicity due to the influence of multiple drug interactions.
- Detection of PPCPs in marine organisms from contaminated coastal waters of the Saudi Red Sea. [Journal Article]
- STSci Total Environ 2018 Apr 15; 621:654-662
- The occurrence of PPCPs in macroalgae, barnacle and fish samples from contaminated coastal waters of the Saudi Red Sea is reported. Solvent extraction followed by solid phase extraction was applied t...
The occurrence of PPCPs in macroalgae, barnacle and fish samples from contaminated coastal waters of the Saudi Red Sea is reported. Solvent extraction followed by solid phase extraction was applied to isolate the compounds, and their quantification was carried out by high performance liquid chromatography-tandem mass spectrometry. Atenolol, ranitidine, chlorpheniramine, DEET, and atrazine were detected in one or more macroalgae at <LOQ concentration, whereas caffeine, methylparaben, and carbamazepine were present atmaximum concentrations of 41.3, 44.3, and 1.7ng/g (on a dry weight basis=dw), respectively. Eleven PPCPs were detected in the barnacle samples at concentrations between <LOQ and maximum concentration of 17.9ng/g dw for amitriptyline. Furthermore, 17 compounds were detected in several or all of the five fish species studied with a maximum concentration of 82.1ng/g dw for metronidazole in Silver Biddy. The bioaccumulation factors (BAF) for selected PPCPs were determined and compared. The occurrence and enrichment of PPCPs in macroalgae and barnacles might indicate that a new route for uptake of such chemicals by marine biota is available, specifically in contaminated waters where a continuous supply of non-persistent contaminants such as PPCPs is available for long-term exposure of local benthic organisms.
- Relaxant effect of Curcuma longa on rat tracheal smooth muscle and its possible mechanisms. [Journal Article]
- PBPharm Biol 2017; 55(1):2248-2258
- CONCLUSIONS: Tracheal smooth muscle relaxant effects of C. longa, were comparable to those of theophylline, which could be due to the presence of methylxanthines or its possible interaction with non-adrenergic non-cholinergic nervous system.
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- Simultaneous determination of kaempferol, quercetin, mangiferin, gallic acid, p-hydroxybenzoic acid and chlorpheniramine maleate in rat plasma after oral administration of Mang-Guo-Zhi-Ke tablets by UHPLC-MS/MS and its application to pharmacokinetics. [Journal Article]
- BCBiomed Chromatogr 2017 Nov 23
- Mang-Guo-Zhi-Ke tablets (MGZKTs) is an effective Chinese patent medicine. It contains mango leaf extract as the main raw material and the antihistamine drug, chlorpheniramine maleate is included in t...
Mang-Guo-Zhi-Ke tablets (MGZKTs) is an effective Chinese patent medicine. It contains mango leaf extract as the main raw material and the antihistamine drug, chlorpheniramine maleate is included in the formulation. However, its pharmacokinetic effect is rarely reported. A highly sensitive, reliable and rapid high-throughput method using ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was used to simultaneously determine kaempferol, quercetin, mangiferin, p-hydroxybenzoic acid, gallic acid and chlorpheniramine maleate in rat plasma after oral administration of MGZKTs. The method was successfully developed and fully validated to investigate the pharmacokinetics of MGZKTs. Chloramphenicol and clarithromycin were used as internal standards (IS). A practicable protein precipitation procedure with methanol was adopted for sample preparation. The samples were separated on an Acquity UHPLC Syncronis C18column (100 × 2.1 mm, 1.7 μm) using 0.1% formic acid-acetonitrile as the mobile phase. The flow rate was set at 0.4 mL/min. The obtained calibration curves were linear in the concentration range of ~1-1000 ng/mL for plasma (r > 0.99). Method validation results met the criteria reported in the US Food and Drug Administration guidelines. Quercetin, p-hydroxybenzoic acid and kaempferol were absorbed rapidly and reached the peak concentration between 0.16 and 0.25 h. This validated that the UHPLC-MS/MS method was successfully applied to study the pharmacokinetic parameters of the six compounds in rat plasma after oral administration of MGZKTs. This evidence will be useful for the clinical rational use of Mang-Guo-Zhi-Ke tablets.