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1.
Experimental Neurobiology ; : 320-328, 2019.
Article in English | WPRIM | ID: wpr-763772

ABSTRACT

The basolateral amygdala (BLA) receives dense projections from cholinergic neurons of the basal forebrain. Acetylcholine can contributes to amygdala-dependent behaviors: formation and extinction of fear memory and appetitive instrumental learning. However, the cholinergic mechanism at the circuit level has not been defined yet. We demonstrated that cholinergic-induced di-synaptic inhibition of BLA pyramidal neurons exhibits a retrograde form of short-term synaptic inhibition, depolarization-induced suppression of inhibition (DSI). Activation of nicotinic receptors was sufficient to evoke action potentials in cholecystokinin (CCK)-positive inhibitory neurons, which strongly inhibit pyramidal neurons through their perisomatic synapses. Our cell type-specific monosynaptic retrograde tracing also revealed that CCK neurons are innervated by basal forebrain cholinergic neurons. Therefore, our data indicated that CCK inhibitory neurons mediate the cholinergic-induced di-synaptic inhibition of BLA pyramidal neurons.


Subject(s)
Acetylcholine , Action Potentials , Basal Forebrain , Basolateral Nuclear Complex , Cholecystokinin , Cholinergic Neurons , Conditioning, Operant , Iontophoresis , Memory , Neurons , Pyramidal Cells , Receptors, Nicotinic , Synapses
2.
Article in English | WPRIM | ID: wpr-764072

ABSTRACT

BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) are used to treat autoimmune or inflammatory diseases. Our aim was to determine the immunomodulatory mechanisms elicited by MSCs during inflammation. METHODS AND RESULTS: We cocultured MSCs with peripheral blood mononuclear cells for a mixed lymphocyte reaction or stimulated them by phytohemagglutinin. Morphological changes of MSCs and secretion of acetylcholine (ACh) from MSCs were measured. The effects of an ACh antagonist and ACh agonist on lymphocyte proliferation and proinflammatory-cytokine production were determined. The inflammatory milieu created by immune-cell activation caused MSCs to adopt a neuronlike phenotype and induced them to release ACh. Additionally, nicotinic acetylcholine receptors (nAChRs) were upregulated in activated peripheral blood mononuclear cells. We observed that ACh bound to nAChR on activated immune cells and led to the inhibition of lymphocyte proliferation and of proinflammatory-cytokine production. MSC-mediated immunosuppression through ACh activity was reversed by an ACh antagonist called α-bungarotoxin, and lymphocyte proliferation was inhibited by an ACh agonist, ACh chloride. CONCLUSIONS: Our findings point to a novel immunomodulatory mechanism in which ACh secreted by MSCs under inflammatory conditions might modulate immune cells. This study may provide a novel method for the treatment of autoimmune diseases by means of MSCs.


Subject(s)
Acetylcholine , Autoimmune Diseases , Humans , Immunosuppression Therapy , Inflammation , Lymphocyte Culture Test, Mixed , Lymphocytes , Mesenchymal Stem Cells , Methods , Phenotype , Receptors, Nicotinic
3.
Article in English | WPRIM | ID: wpr-764038

ABSTRACT

Melatonin is a neurotransmitter that modulates various physiological phenomena including regulation and maintenance of the circadian rhythm. Nicotinic acetylcholine receptors (nAChRs) play an important role in oral functions including orofacial muscle contraction, salivary secretion, and tooth development. However, knowledge regarding physiological crosstalk between melatonin and nAChRs is limited. In the present study, the melatonin-mediated modulation of nAChR functions using bovine adrenal chromaffin cells, a representative model for the study of nAChRs, was investigated. Melatonin inhibited the nicotinic agonist dimethylphenylpiperazinium (DMPP) iodide-induced cytosolic free Ca²⁺ concentration ([Ca²⁺](i)) increase and norepinephrine secretion in a concentration-dependent manner. The inhibitory effect of melatonin on the DMPP-induced [Ca²⁺](i) increase was observed when the melatonin treatment was performed simultaneously with DMPP. The results indicate that melatonin inhibits nAChR functions in both peripheral and central nervous systems.


Subject(s)
Calcium Signaling , Central Nervous System , Chromaffin Cells , Circadian Rhythm , Cytosol , Dimethylphenylpiperazinium Iodide , Melatonin , Muscle Contraction , Neurotransmitter Agents , Nicotinic Agonists , Norepinephrine , Physiological Phenomena , Receptors, Nicotinic , Tooth
4.
Article in English | WPRIM | ID: wpr-759012

ABSTRACT

The autonomic nervous system plays critical roles in maintaining homeostasis in humans, directly regulating inflammation by altering the activity of the immune system. The cholinergic anti-inflammatory pathway is a well-studied neuroimmune interaction involving the vagus nerve. CD4-positive T cells expressing β2 adrenergic receptors and macrophages expressing the alpha 7 subunit of the nicotinic acetylcholine receptor in the spleen receive neurotransmitters such as norepinephrine and acetylcholine and are key mediators of the cholinergic anti-inflammatory pathway. Recent studies have demonstrated that vagus nerve stimulation, ultrasound, and restraint stress elicit protective effects against renal ischemia-reperfusion injury. These protective effects are induced primarily via activation of the cholinergic anti-inflammatory pathway. In addition to these immunological roles, nervous systems are directly related to homeostasis of renal physiology. Whole-kidney three-dimensional visualization using the tissue clearing technique CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis) has illustrated that renal sympathetic nerves are primarily distributed around arteries in the kidneys and denervated after ischemia-reperfusion injury. In contrast, artificial renal sympathetic denervation has a protective effect against kidney disease progression in murine models. Further studies are needed to elucidate how neural networks are involved in progression of kidney disease.


Subject(s)
Acetylcholine , Arteries , Autonomic Nervous System , Cholinergic Neurons , Homeostasis , Humans , Immune System , Inflammation , Kidney Diseases , Kidney , Macrophages , Nervous System , Neurotransmitter Agents , Norepinephrine , Optogenetics , Physiology , Receptors, Adrenergic , Receptors, Nicotinic , Reperfusion Injury , Spleen , Sympathectomy , Sympathetic Nervous System , T-Lymphocytes , Ultrasonography , Vagus Nerve , Vagus Nerve Stimulation
5.
Article in Chinese | WPRIM | ID: wpr-781309

ABSTRACT

OBJECTIVE@#To assess the association of single nucleotide polymorphisms (SNPs) CHRNA4 gene with response to selective serotonin re-uptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD).@*METHODS@#For 304 patients receiving drug treatment for major depression, 2 SNPs, namely rs4522666 and rs4603829, of the CHRNA4 gene were determined by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry. HAMD-17 was adopted as the primary rating tool to evaluate the severity of depression on the baseline and at the end of 1st, 2nd, 4th and 6th weeks treatment.@*RESULTS@#The frequency of GG genotype/G allele for rs4522666 differed significantly from that of TT and GT genotypes/T allele between responders and non-responders (P=0.015 and P=0.006, respectively). No significant difference was found in genotypic and allelic frequencies of rs4603829 between the two groups (P> 0.05).@*CONCLUSION@#SNPs of the CHRNA4 gene may play an important role in the response to antidepressant drugs among ethnic Han Chinese with MDD.


Subject(s)
Antidepressive Agents , Pharmacology , Asians , China , Depressive Disorder, Major , Drug Therapy , Genetics , Gene Frequency , Genotype , Humans , Polymorphism, Single Nucleotide , Receptors, Nicotinic , Genetics
6.
Protein & Cell ; (12): 675-685, 2017.
Article in English | WPRIM | ID: wpr-756968

ABSTRACT

The α3* nAChRs, which are considered to be promising drug targets for problems such as pain, addiction, cardiovascular function, cognitive disorders etc., are found throughout the central and peripheral nervous system. The α-conotoxin (α-CTx) LvIA has been identified as the most selective inhibitor of α3β2 nAChRs known to date, and it can distinguish the α3β2 nAChR subtype from the α6/α3β2β3 and α3β4 nAChR subtypes. However, the mechanism of its selectivity towards α3β2, α6/α3β2β3, and α3β4 nAChRs remains elusive. Here we report the co-crystal structure of LvIA in complex with Aplysia californica acetylcholine binding protein (Ac-AChBP) at a resolution of 3.4 Å. Based on the structure of this complex, together with homology modeling based on other nAChR subtypes and binding affinity assays, we conclude that Asp-11 of LvIA plays an important role in the selectivity of LvIA towards α3β2 and α3/α6β2β3 nAChRs by making a salt bridge with Lys-155 of the rat α3 subunit. Asn-9 lies within a hydrophobic pocket that is formed by Met-36, Thr-59, and Phe-119 of the rat β2 subunit in the α3β2 nAChR model, revealing the reason for its more potent selectivity towards the α3β2 nAChR subtype. These results provide molecular insights that can be used to design ligands that selectively target α3β2 nAChRs, with significant implications for the design of new therapeutic α-CTxs.


Subject(s)
Animals , Aplysia , Binding Sites , Conotoxins , Chemistry , Crystallography, X-Ray , Humans , Protein Structure, Quaternary , Receptors, Nicotinic , Chemistry
7.
Article in Chinese | WPRIM | ID: wpr-300829

ABSTRACT

Epilepsy is a chronic neurological disorder, which is not only related to the imbalance between excitatory glutamic neurons and inhibitory GABAergic neurons, but also related to abnormal central cholinergic regulation. This article summarizes the scientific background and experimental data about cholinergic dysfunction in epilepsy from both cellular and network levels, further discusses the exact role of cholinergic system in epilepsy. In the cellular level, several types of epilepsy are believed to be associated with aberrant metabotropic muscarinic receptors in several different brain areas, while the mutations of ionotropic nicotinic receptors have been reported to result in a specific type of epilepsy-autosomal dominant nocturnal frontal lobe epilepsy. In the network level, cholinergic projection neurons as well as their interaction with other neurons may regulate the development of epilepsy, especially the cholinergic circuit from basal forebrain to hippocampus, while cholinergic local interneurons have not been reported to be associated with epilepsy. With the development of optogenetics and other techniques, dissect and regulate cholinergic related epilepsy circuit has become a hotspot of epilepsy research.


Subject(s)
Acetylcholine , Physiology , Basal Forebrain , Pathology , Brain Chemistry , Genetics , Physiology , Cholinergic Neurons , Chemistry , Classification , Pathology , Physiology , Epilepsy , Genetics , Pathology , Epilepsy, Frontal Lobe , Genetics , GABAergic Neurons , Physiology , Hippocampus , Pathology , Humans , Mutation , Genetics , Physiology , Neurons , Non-Neuronal Cholinergic System , Genetics , Physiology , Receptors, Muscarinic , Genetics , Physiology , Receptors, Nicotinic , Genetics , Physiology , Synaptic Transmission , Genetics , Physiology
8.
Article in English | WPRIM | ID: wpr-166104

ABSTRACT

Neuromuscular blockade plays an important role in the safe management of patient airways, surgical field improvement, and respiratory care. Rapid-sequence induction of anesthesia is indispensable to emergency surgery and obstetric anesthesia, and its purpose is to obtain a stable airway, adequate depth of anesthesia, and appropriate respiration within a short period of time without causing irritation or damage to the patient. There has been a continued search for new neuromuscular blocking drugs (NMBDs) with a rapid onset of action. Factors that affect the onset time include the potency of the NMBDs, the rate of NMBDs reaching the effect site, the onset time by dose control, metabolism and elimination of NMBDs, buffered diffusion to the effect site, nicotinic acetylcholine receptor subunit affinity, drugs that affect acetylcholine (ACh) production and release at the neuromuscular junction, drugs that inhibit plasma cholinesterase, presynaptic receptors responsible for ACh release at the neuromuscular junction, anesthetics or drugs that affect muscle contractility, site and methods for monitoring neuromuscular function, individual variability, and coexisting disease. NMBDs with rapid onset without major adverse events are expected in the next few years, and the development of lower potency NMBDs will continue. Anesthesiologists should be aware of the use of NMBDs in the management of anesthesia. The choice of NMBD and determination of the appropriate dosage to modulate neuromuscular blockade characteristics such as onset time and duration of neuromuscular blockade should be considered along with factors that affect the effects of the NMBDs. In this review, we discuss the factors that affect the onset time of NMBDs.


Subject(s)
Acetylcholine , Anesthesia , Anesthesia, Obstetrical , Anesthetics , Cholinesterases , Diffusion , Drug Interactions , Emergencies , Humans , Metabolism , Neuromuscular Blockade , Neuromuscular Blocking Agents , Neuromuscular Junction , Neuromuscular Monitoring , Pharmacokinetics , Plasma , Receptors, Nicotinic , Receptors, Presynaptic , Respiration
9.
Med. U.P.B ; 35(1): 41-46, ene.-jun. 2016.
Article in Spanish | LILACS, COLNAL | ID: biblio-837067

ABSTRACT

Las intoxicaciones por plaguicidas son la segunda causa de intoxicación en Colombia. Los neonicotinoides son un nuevo grupo de insecticidas que actúa a través de los receptores nicotínicos. Las principales manifestaciones clínicas que se han asociado con dicha intoxicación son alteraciones neurológicas y autonómicas. En este reporte se presentan dos casos de pacientes que ingirieron tiametoxan e imidacloprid y presentaron compromiso del sensorio y de sus signos vitales, por lo que se acudió a manejo en unidad de cuidados intensivos. El objetivo de este reporte es sensibilizar sobre el creciente uso de estos plaguicidas y la necesidad de identificarlos para hacer un diagnóstico diferencial con otras sustancias, realizar un uso adecuado de ayudas diagnósticas y un manejo inicial pertinente para asegurar la vía área y corregir alteraciones hemodinámicas para prevenir complicaciones.


Pesticide poisoning is the second cause of poisoning in Colombia. Neonicotinoids are a new group of insecticides that act through nicotinic receptors. The main clinical manifestations that have been associated with such poisoning are neurological and autonomic disturbances. In this paper, we present two cases in which two patients ingested thiamethoxan and imidacloprid, showing neurologic compromise and affecting their vital signs, requiring management in the intensive care unit. The aim of this article is to raise awareness about the growing use of such pesticides and identify the need to make a differential diagnosis with other insecticides, making appropriate use of diagnostic aids and appropriate initial management of the airway and correcting the abnormalities in their hemodynamic profile to prevent complications.


As intoxicações por praguicidas são a segunda causa de intoxicação na Colômbia. Os neonicotinóides são um novo grupo de inseticidas que atua através dos receptores nicotínicos. As principais manifestações clínicas que se há associado com dita intoxicação são alterações neurológicas e autonómicas. Neste reporte se apresentam dois casos de pacientes que ingeriram tiametoxan e imidacloprid e apresentaram compromisso do sensório e de seus signos vitais, pelo que se acudiu ao manejo em unidade de tratamentos intensivos. O objetivo deste reporte é sensibilizar sobre o crescente uso destes praguicidas e a necessidade de identificá-los para fazer um diagnóstico diferencial com outras substâncias, realizar um uso adequado de ajudas diagnósticas e um manejo inicial pertinente para assegurar a via área e corrigir alterações hemodinâmicas para prevenir complicações.


Subject(s)
Humans , Animals , Neonicotinoids , Pesticides , Poisoning , Receptors, Nicotinic , Neurotoxicity Syndromes
10.
Asia Pacific Allergy ; (4): 236-244, 2016.
Article in English | WPRIM | ID: wpr-750078

ABSTRACT

BACKGROUND: Imidacloprid has been commonly used as a pesticide for crop protection and acts as nicotinic acetylcholine receptor agonists. Little information about the relationship between imidacloprid and allergy is available. OBJECTIVE: This study aims to examine the effects of imidacoprid on IgE-mediated mast cell activation. METHODS: The rat basophilic leukemia cell line RBL-2H3 (RBL-2H3 cells) were treated with 10⁻³ – 10⁻¹² mol/L imidacloprid, followed by measuring the mediator production, influx of Ca²⁺ in IgE-activated RBL-2H3 cells, and the possible effects of imidacoprid on anti-dinitrophenyl IgE-induced passive cutaneous anaphylaxis (PCA). RESULTS: It was shown that imidacoprid suppressed the production of histamine, β-hexosaminidase, leukotriene C4, interleukin-6, tumor necrosis factor-α, and Ca²⁺ mobilization in IgE-activated RBL-2H3 cells and decreased vascular extravasation in IgE-induced PCA. CONCLUSION: It is the first time to show that imidacloprid suppressed the activation of RBL-2H3 cells.


Subject(s)
Animals , Basophils , Cell Degranulation , Cell Line , Crop Protection , Histamine , Hypersensitivity , Interleukin-6 , Leukemia , Leukotriene C4 , Mast Cells , Necrosis , Passive Cutaneous Anaphylaxis , Rats , Receptors, Nicotinic
11.
Article in English | WPRIM | ID: wpr-68872

ABSTRACT

Quercetin is a flavonoid usually found in fruits and vegetables. Aside from its antioxidative effects, quercetin, like other flavonoids, has a various neuropharmacological actions. Quercetin-3-O-rhamnoside (Rham1), quercetin-3-O-rutinoside (Rutin), and quercetin-3-(2(G)-rhamnosylrutinoside (Rham2) are mono-, di-, and tri-glycosylated forms of quercetin, respectively. In a previous study, we showed that quercetin can enhance α7 nicotinic acetylcholine receptor (α7 nAChR)-mediated ion currents. However, the role of the carbohydrates attached to quercetin in the regulation of α7 nAChR channel activity has not been determined. In the present study, we investigated the effects of quercetin glycosides on the acetylcholine induced peak inward current (I(ACh)) in Xenopus oocytes expressing the α7 nAChR. I(ACh) was measured with a two-electrode voltage clamp technique. In oocytes injected with α7 nAChR copy RNA, quercetin enhanced I(ACh), whereas quercetin glycosides inhibited I(ACh). Quercetin glycosides mediated an inhibition of I(ACh), which increased when they were pre-applied and the inhibitory effects were concentration dependent. The order of I(ACh) inhibition by quercetin glycosides was Rutin≥Rham1>Rham2. Quercetin glycosides-mediated I(ACh) enhancement was not affected by ACh concentration and appeared voltage-independent. Furthermore, quercetin-mediated I(ACh) inhibition can be attenuated when quercetin is co-applied with Rham1 and Rutin, indicating that quercetin glycosides could interfere with quercetin-mediated α7 nAChR regulation and that the number of carbohydrates in the quercetin glycoside plays a key role in the interruption of quercetin action. These results show that quercetin and quercetin glycosides regulate the α7 nAChR in a differential manner.


Subject(s)
Acetylcholine , Carbohydrates , Flavonoids , Fruit , Glycosides , Humans , Oocytes , Quercetin , Receptors, Nicotinic , RNA , Rutin , Vegetables , Xenopus
12.
Article in English | WPRIM | ID: wpr-51944

ABSTRACT

Cytisine (CYT), a partial agonist of α4β2-nicotinic receptors, has been used for antidepressant efficacy in several tests. Nicotinic receptors have been shown to be closely associated with depression. However, little is known about the effects of CYT on the depression. In the present study, a mouse model of depression, the unpredictable chronic mild stress (UCMS), was used to evaluate the activities of CYT. UCMS caused significant depression-like behaviors, as shown by the decrease of total distances in open field test, and the prolonged duration of immobility in tail suspension test and forced swimming test. Treatment with CYT for two weeks notably relieved the depression-like behaviors in the UCMS mice. Next, proteins related to depressive disorder in the brain region of hippocampus and amygdala were analyzed to elucidate the underlying mechanisms of CYT. CYT significantly reversed the decreases of 5-HT1A, BDNF, and mTOR levels in the hippocampus and amygdala. These results imply that CYT may act as a potential anti-depressant in the animals under chronic stress.


Subject(s)
Amygdala , Animals , Brain , Brain-Derived Neurotrophic Factor , Depression , Depressive Disorder , Hindlimb Suspension , Hippocampus , Mice , Physical Exertion , Receptors, Nicotinic
13.
Egyptian Journal of Medical Human Genetics [The]. 2016; 17 (1): 71-77
in English | IMEMR | ID: emr-176216

ABSTRACT

Background: Smoking behavior is influenced by both genetic and environmental factors. Nicotine is the major addictive substance in cigarettes. Nicotinic acetylcholine receptors [nAChRs] are thought to play an important role in nicotine addiction of smokers. One of the genes, alpha-4 subunit of nicotinic acetylcholine receptor [CHRNA4] gene was reported to be associated with smoking behavior in many populations


Aim: The aim of this study is to determine association between alpha-4 subunit of nicotinic acetylcholine receptor single nucleotide polymorphism [rs2236196 and rs2273502 loci] and smoking behavior among Malay Males


Methods: The study was conducted in Malay smokers [n = 248] and non-smoking controls [n = 248]. DNA was extracted from leucocytes and the two SNPs were determined by a polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] method. The PCR product was digested with restriction enzymes AfeI and Sau96I, respectively


Results and conclusion: We found that the AA genotype frequency for CHRNA4 rs2236196 polymorphism in the smoker group was 80.6% while in nonsmoker 77.0%. No mutation [GG genotype] was detected in both groups. The AG genotype for the smoker group was 19.4% while in the nonsmoker group 23.0%. There was no significant difference observed in the genotype [X[2] = 5.106, p = 0.078] and allele frequencies between both study groups. On the other hand, no mutation of CHRNA4 rs2273502 [TT genotype] was detected in the non-smoker group while the frequencies of genotype CC and heterozygous CT in non-smokers were 75.8% and 24.2%, respectively. In the smoker group, the frequencies were 73.4%, 2.0% and 24.6%, for TT, CC and CT, respectively. There was no significant difference observed in rs2273502 [X[2] = 5.16, p = 0.078] and smoking behavior of the subjects. In conclusion, the results revealed that CHRNA4 rs2273502 and rs2236196 gene polymorphisms are not statistically significantly associated with smoking behavior in our population


Subject(s)
Humans , Male , Adolescent , Adult , Middle Aged , Receptors, Nicotinic , Polymorphism, Genetic , Polymorphism, Single Nucleotide
14.
Chinese Medical Journal ; (24): 2596-2602, 2016.
Article in English | WPRIM | ID: wpr-230915

ABSTRACT

<p><b>BACKGROUND</b>Congenital myasthenic syndromes are a group of rare disorders that are clinically and genetically heterogeneous and caused by mutations in the genes encoding proteins of the neuromuscular junction. Here, we described a Chinese family that presented with phenotypes of classic slow-channel congenital myasthenic syndrome (SCCMS).</p><p><b>METHODS</b>Clinical characteristics and electrophysiological features of three patients from a Chinese family were examined, and next-generation sequencing followed by direct sequencing was carried out.</p><p><b>RESULTS</b>The patients revealed variability in clinical and electrophysiological features. However, weakness, scoliosis, and repetitive-compound muscle action potential were found in all affected members in the family. A heterozygous C>T missense mutation at nucleotide 865 in acetylcholine receptor epsilon-subunit (CHRNE) gene that causes a leucine-to-phenylalanine substitution at position 289 (L289F) was found.</p><p><b>CONCLUSIONS</b>We reported a SCCMS family of Chinese origin. In the family, classical clinical phenotype with phenotypic variability among different members was found. Genetic testing could help diagnose this rare disease.</p>


Subject(s)
Adult , DNA Mutational Analysis , Electrophysiology , Female , Humans , Male , Mutation, Missense , Genetics , Myasthenic Syndromes, Congenital , Genetics , Receptors, Nicotinic , Genetics , Young Adult
15.
Rev. méd. Chile ; 143(11): 1377-1385, nov. 2015. tab
Article in Spanish | LILACS | ID: lil-771726

ABSTRACT

Background: Several studies have reported that variants rs16969968 G>A of the CHRNA5 gene and CYP2A6*12 of the CYP2A6 gene are associated with smoking and smoking refusal, respectively. In addition, some studies report that a higher cigarette consumption is associated with low body mass index (BMI). Aim: To analyze the allele and genotypic frequencies of these variants and their impact on smoking and BMI. Material and Methods: A blood sample was obtained and a survey about smoking habits was answered by 319 university students aged 18 to 35 years (127 women, 171 smokers), living in Northeastern Mexico. Genetic variants were studied by polymerase chain reaction/restriction fragment length polymorphism and their frequencies were associated with smoking and BMI. Results: No associations were found between the analyzed variants and smoking in the study groups. However, there was an association among non-smoking subjects between the A allele of rs16969968 and high a BMI (p < 0.01). Conclusions: This last variant may be involved in food-addiction disorders.


Subject(s)
Adolescent , Adult , Female , Humans , Male , Young Adult , Body Mass Index , /genetics , Gene Frequency , Nerve Tissue Proteins/genetics , Receptors, Nicotinic/genetics , Smoking/genetics , Cross-Sectional Studies , Genotype , Genetic Variation/genetics , Mexico , Nicotine/metabolism , Polymerase Chain Reaction/methods , Polymorphism, Genetic/genetics
16.
Hist. ciênc. saúde-Manguinhos ; 22(1): 293-302, Jan-Mar/2015.
Article in Spanish | LILACS, BDS | ID: lil-741525

ABSTRACT

Durante gran parte del siglo XX tanto los gobiernos civiles como los militares no encontraron en el tabaquismo un tema prioritario. Recién en la última década del siglo el movimiento internacional contra el cigarrillo, liderado por la Organización Mundial de la Salud, organizaciones norteamericanas y académicos, empezó a tener algún impacto en la escena política argentina. Fue en ese contexto que un nuevo grupo profesional logró impulsar la constitución de un amplio bloque político antitabaco. En ese proceso, el voluntarismo centrado en programas individuales para dejar de fumar que había marcado gran parte de las iniciativas del siglo XX, terminó desplazado por políticas públicas destinadas a producir ambientes libres de humo y a combatir la exposición pasiva al humo de tabaco ajeno.


For much of the twentieth century both the civilian and military governments did not consider smoking a priority concern. It was only in the last decade of the twentieth century that the international movement against cigarettes, led by the World Health Organization, US organizations and academics, began to have some impact on Argentina's political scene. It was in this context that a new professional group managed to foment the creation of a broad anti-smoking political bloc. In this process, voluntarism focused on individual programs to quit smoking that had marked much of the initiatives of the twentieth century, ended up being replaced by public policies designed to ensure smoke free environments and combat passive smoking.


Subject(s)
Humans , Animals , Cognition Disorders/etiology , Endophenotypes , Nicotine/metabolism , Schizophrenia/complications , Schizophrenia/epidemiology , Tobacco Use Disorder/epidemiology , Nicotine/administration & dosage , Receptors, Nicotinic/metabolism
17.
Rev. paul. pediatr ; 33(1): 56-62, Jan-Mar/2015. tab, graf
Article in English | LILACS | ID: lil-744707

ABSTRACT

OBJECTIVE: To determine the anthropometric indicators of obesity in the prediction of high body fat in adolescents from a Brazilian State. METHODS: The study included 1,197 adolescents (15-17 years old). The following anthropometric measurements were collected: body mass (weight and height), waist circumference and skinfolds (triceps and medial calf). The anthropometric indicators analyzed were: body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) and conicity index (C-Index). Body fat percentage, estimated by the Slaughter et al equation, was used as the reference method. Descriptive statistics, U Mann-Whitney test, and ROC curve were used for data analysis. RESULTS: Of the four anthropometric indicators studied, BMI, WHtR and WC had the largest areas under the ROC curve in relation to relative high body fat in both genders. The cutoffs for boys and girls, respectively, associated with high body fat were BMI 22.7 and 20.1kg/m², WHtR 0.43 and 0.41, WC 75.7 and 67.7cm and C-Index 1.12 and 1.06. CONCLUSIONS: Anthropometric indicators can be used in screening for identification of body fat in adolescents, because they are simple, have low cost and are non-invasive. .


OBJETIVO: Determinar os indicadores antropométricos de obesidade na predição da gordura corporal elevada em adolescentes de um estado brasileiro. MÉTODOS: O estudo incluiu 1.197 adolescentes (15-17 anos). As seguintes medidas antropométricas foram coletadas: massa corporal e estatura, perímetro da cintura e dobras cutâneas (tríceps e perna medial). Os indicadores antropométricos analisados foram: índice de massa corporal (IMC), perímetro da cintura (PC), razão cintura-estatura (RCE) e índice de conicidade (IC). A gordura corporal elevada, estimada pela equação de Slaughter et al., foi usada como método de referência. Estatística descritiva, teste U de Mann-Whitney e curva ROC foram usadas para a análise dos dados. RESULTADOS: Dos quatro indicadores antropométricos estudados, o IMC, a RCE e o PC tiveram as maiores áreas sob a curva ROC em relação à gordura corporal elevada relativa em ambos os sexos. Os pontos de corte para os rapazes e as moças, respectivamente, associados com gordura corporal elevada foram IMC 22,7 e 20,1 kg/m2, RCE 0,43 e 0,41, PC 75,7 e 67,7 cm e IC 1,12 e 1,06. CONCLUSÕES: Os indicadores antropométricos podem ser usados como ferramenta para identificação da gordura corporal em adolescentes, por serem um método simples, de baixo custo e não invasivo. .


Subject(s)
Humans , Acrylamides/pharmacology , Cyclohexanecarboxylic Acids/pharmacology , Receptors, G-Protein-Coupled/agonists , Acrylamides/chemistry , Acrylamides/chemical synthesis , Cell Line , Cyclohexanecarboxylic Acids/chemistry , Cyclohexanecarboxylic Acids/chemical synthesis , Dose-Response Relationship, Drug , Molecular Structure , Receptors, Nicotinic , Structure-Activity Relationship
18.
Article in English | WPRIM | ID: wpr-728516

ABSTRACT

It is well known that cigarette smoke can cause erectile dysfunction by affecting the penile vascular system. However, the exact effects of nicotine on the corpus cavernosum remains poorly understood. Nicotine has been reported to cause relaxation of the corpus cavernosum; it has also been reported to cause both contraction and relaxation. Therefore, high concentrations of nicotine were studied in strips from the rabbit corpus cavernosum to better understand its effects. The proximal penile corpus cavernosal strips from male rabbits weighing approximately 4 kg were used in organ bath studies. Nicotine in high concentrations (10(-5)~10(-4) M) produced dose-dependent contractions of the corpus cavernosal strips. The incubation with 10(-5) M hexamethonium (nicotinic receptor antagonist) significantly inhibited the magnitude of the nicotine associated contractions. The nicotine-induced contractions were not only significantly inhibited by pretreatment with 10(-5) M indomethacin (nonspecific cyclooxygenase inhibitor) and with 10(-6) M NS-398 (selective cyclooxygenase inhibitor), but also with 10(-6) M Y-27632 (Rho kinase inhibitor). Ozagrel (thromboxane A2 synthase inhibitor) and SQ-29548 (highly selective TP receptor antagonist) pretreatments significantly reduced the nicotine-induced contractile amplitude of the strips. High concentrations of nicotine caused contraction of isolated rabbit corpus cavernosal strips. This contraction appeared to be mediated by activation of nicotinic receptors. Rho-kinase and cyclooxygenase pathways, especially cyclooxygenase-2 and thromboxane A2, might play a pivotal role in the mechanism associated with nicotine-induced contraction of the rabbit corpus cavernosum.


Subject(s)
Baths , Cyclooxygenase 2 , Erectile Dysfunction , Hexamethonium , Humans , Indomethacin , Male , Nicotine , Phosphotransferases , Prostaglandin-Endoperoxide Synthases , Rabbits , Receptors, Nicotinic , Receptors, Thromboxane , Relaxation , rho-Associated Kinases , Smoke , Thromboxane A2 , Tobacco Products
19.
Article in English | WPRIM | ID: wpr-145433

ABSTRACT

PURPOSE: To investigate the role of alpha3 and alpha7 nicotinic acetylcholine receptor subunits (nAChRs) in the bladder, using a rat model with detrusor overactivity induced by partial bladder outlet obstruction (BOO). METHODS: Forty Sprague-Dawley rats were used: 10 were sham-operated (control group) and 30 were observed for 3 weeks after partial BOO. BOO-induced rats were further divided into 3 groups: Two groups of 10 rats each received intravesicular infusions with hexamethonium (HM group; n=10) or methyllycaconitine (MLC group; n=10), which are antagonists for alpha3 and alpha7 nAChRs, respectively. The remaining BOO-induced rats received only saline infusion (BOO group; n=10). Based on the contraction interval measurements using cystometrogram, the contraction pressure and nonvoiding bladder contractions were compared between the control and the three BOO-induced groups. Immunofluorescent staining and Western blotting were used to analyze alpha3 and alpha7 nAChRs levels. RESULTS: The contraction interval of the MLC group was higher than that of the BOO group (P<0.05). Nonvoiding bladder contraction almost disappeared in the HM and MLC groups. Contraction pressure increased in the BOO group (P<0.05) compared with the control group and decreased in the HM and MLC groups compared with the BOO group (P<0.05). Immunofluorescence staining showed that the alpha3 nAChR signals increased in the urothelium, and the alpha7 nAChR signals increased in the urothelium and detrusor muscle of the BOO group compared with the control group. Western blot analysis showed that both alpha3 and alpha7 nAChR levels increased in the BOO group (P<0.05). CONCLUSIONS: Alpha3 and alpha7 nAChRs are associated with detrusor overactivity induced by BOO. Furthermore, nAChR antagonists could help in clinically improving detrusor overactivity.


Subject(s)
alpha7 Nicotinic Acetylcholine Receptor , Animals , Blotting, Western , Fluorescent Antibody Technique , Hexamethonium , Models, Animal , Rats , Rats, Sprague-Dawley , Receptors, Nicotinic , Urinary Bladder , Urinary Bladder Neck Obstruction , Urinary Bladder, Overactive , Urothelium
20.
Article in Chinese | WPRIM | ID: wpr-335199

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the association and interaction between smoking and the nicotine acetylcholine receptor subunits alpha 5(CHRNA5) gene polymorphisms on lung cancer in Chinese men.</p><p><b>METHODS</b>A case-control study was employed with a total of 204 male lung cancer patients and 821 healthy control subjects enrolled in the study. All the subjects were interviewed under a structured questionnaire with the contents on socio-demographic status and smoking behavior. Venous blood samples were collected to measure single nucleotide polymorphism of rs17486278 in CHRNA5. A series of multivariate logistic regression models were performed to assess the association and interaction between smoking and the CHRNA5 gene polymorphisms on lung cancer.</p><p><b>RESULTS</b>After controlling for potential confounding factors, data from the multivariate logistic regression analysis showed that individuals with smoking >15 cigarettes per day would significantly increase the risk of lung cancer when compared to the non-smokers (OR = 3.49, 95%CI:2.29-5.32). However, no associations between CHRNA5 rs17486278 polymorphisms and lung cancer were found. Furthermore, those who smoked 1-15 cigarettes per day had a positive interactive effect between rs17486278 CC genotype and lung cancer (OR = 16.13, 95% CI:1.27-205.33). Results from further stratified analysis on smoking behaviors and rs17486278 genotypes indicated that when compared with non-smokers on rs17486278 AA genotype, those individuals who smoked 1-15 cigarettes per day with rs17486278 CC genotype, individuals smoking >15 cigarettes per day with AA genotype and individuals smoking >15 cigarettes per day with AC genotype, all had a higher risk of developing lung cancer, with their OR value as 8.14(95% CI:1.17-56.56), 3.84 (95% CI:1.30-11.40) and 5.32 (95% CI:1.78-15.93), respectively.</p><p><b>CONCLUSION</b>There was an interaction between smoking and CHRNA5 gene polymorphism on lung cancer.</p>


Subject(s)
Asians , Case-Control Studies , Genotype , Humans , Logistic Models , Lung Neoplasms , Genetics , Male , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Receptors, Nicotinic , Genetics , Risk , Smoking
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