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Anti cholinergics

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https://www.readbyqxmd.com/read/29661827/oral-nahco-3-activates-a-splenic-anti-inflammatory-pathway-evidence-that-cholinergic-signals-are-transmitted-via-mesothelial-cells
#1
Sarah C Ray, Babak Baban, Matthew A Tucker, Alec J Seaton, Kyu Chul Chang, Elinor C Mannon, Jingping Sun, Bansari Patel, Katie Wilson, Jacqueline B Musall, Hiram Ocasio, Debra Irsik, Jessica A Filosa, Jennifer C Sullivan, Brendan Marshall, Ryan A Harris, Paul M O'Connor
We tested the hypothesis that oral NaHCO3 intake stimulates splenic anti-inflammatory pathways. Following oral NaHCO3 loading, macrophage polarization was shifted from predominantly M1 (inflammatory) to M2 (regulatory) phenotypes, and FOXP3+ CD4+ T-lymphocytes increased in the spleen, blood, and kidneys of rats. Similar anti-inflammatory changes in macrophage polarization were observed in the blood of human subjects following NaHCO3 ingestion. Surprisingly, we found that gentle manipulation to visualize the spleen at midline during surgical laparotomy (sham splenectomy) was sufficient to abolish the response in rats and resulted in hypertrophy/hyperplasia of the capsular mesothelial cells...
April 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29625471/an-anatomic-characterization-of-the-midbrain-near-response-neurons-in-the-macaque-monkey
#2
Paul J May, Susan Warren, Paul D R Gamlin, Isabelle Billig
Purpose: These experiments were designed to reveal the location of the premotor neurons that have previously been designated physiologically as the midbrain near response cells controlling vergence, lens accommodation, and pupillary constriction in response to target distance. Methods: To identify this population, the fixed N2c strain of rabies virus was injected into the ciliary body of seven Macaca fascicularis monkeys. The virus was trans-synaptically transported to the brain...
March 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29609270/-effect-of-%C3%AE-7nachr-mediated-cholinergic-anti-inflammatory-pathway-on-inhibition-of-atrial-fibrillation-by-low-level-vagus-nerve-stimulation
#3
Y S Qian, Q Y Zhao, S J Zhang, Y J Zhang, Y C Wang, H Y Zhao, Z X Dai, Y H Tang, X Wang, T Wang, C X Huang
Objective: To investigate the effect of α7nAChR mediated cholinergic anti-inflammatory pathway on inhibition of atrial fibrillation by low-level vagus nerve stimulation(LL-VNS). Methods: Eighteen beagles were randomized into control group ( n =6), LL-VNS group ( n =6) and methyllycaconitine (MLA) + LL-VNS group ( n =6). All the beagles were subjected to rapid atrial pacing at 800 beats/min for 6 hours.And the effective refractory period (ERP) of atriums and pulmonary veins and induced atrial fibrillation (AF) were measured hourly during non-pacing...
March 20, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29608552/gts-21-reduces-inflammation-in-acute-lung-injury-by-regulating-m1-polarization-and-function-of-alveolar-macrophages
#4
Jing Wang, Ruiting Li, Zhiyong Peng, Wenhai Zhou, Bo Hu, Xin Rao, Xiao Yang, Jianguo Li
BACKGROUND: Acute lung injury (ALI) is a severe outcome of sepsis. Alveolar macrophages (AMs) play key roles in defense, resolution in ALI. The polarization of AMs is dependent on micro environmental stimuli and might influence the progression of ALI. GTS-21, a selective α7 nicotinic acetylcholine receptor agonist of the cholinergic anti-inflammatory pathway (CAP), has recently been established to be promising in the treatment of ALI. However, the molecular mechanism underlying the GTS-21-mediated suppression of inflammatory responses has been explored only partially...
March 30, 2018: Shock
https://www.readbyqxmd.com/read/29597336/comparative-evaluation-of-the-antioxidant-and-anti-alzheimer-s-disease-potential-of-coumestrol-and-puerarol-isolated-from-pueraria-lobata-using-molecular-modeling-studies
#5
Prashamsa Koirala, Su Hui Seong, Hyun Ah Jung, Jae Sue Choi
The current study assesses the antioxidant effects of two similar isoflavonoids isolated from Pueraria lobata , coumestrol and puerarol, along with the cholinergic and amyloid-cascade pathways to mitigate Alzheimer's disease (AD). Antioxidant activity was evaluated via 1,1-diphenyl-2-picryhydrazyl (DPPH) and peroxynitrite (ONOO- ) scavenging ability further screened via ONOO- -mediated nitrotyrosine. Similarly, acetyl- and butyrylcholinesterase (AChE/BChE) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities were assessed together with docking and kinetic studies...
March 28, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29545933/endogenous-chrna7-ligand-slurp1-as-a-potential-tumor-suppressor-and-anti-nicotinic-factor-in-pancreatic-cancer
#6
Verena M Throm, David Männle, Thomas Giese, Andrea S Bauer, Matthias M Gaida, Juergen Kopitz, Thomas Bruckner, Konstanze Plaschke, Svetlana P Grekova, Klaus Felix, Thilo Hackert, Nathalia A Giese, Oliver Strobel
Smoking is associated with increased risk and poorer prognosis of pancreatic ductal adenocarcinoma (PDAC). Nicotine acts through cholinergic nicotinic receptors, preferentially α7 (CHRNA7) that also binds the endogenous ligand SLURP1 (Secreted Ly-6/uPAR-Related Protein 1). The clinical significance of SLURP1 and its interaction with nicotine in PDAC are unclear. We detected similar levels of SLURP1 in sera from healthy donors and patients with chronic pancreatitis or PDAC; higher preoperative values were associated with significantly better survival in patients with resected tumors...
February 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29510125/6-7-4-trihydroxyisoflavone-a-major-metabolite-of-daidzein-improves-learning-and-memory-via-the-cholinergic-system-and-the-p-creb-bdnf-signaling-pathway-in-mice
#7
Yong-Hyun Ko, Sun Yeou Kim, Seok-Yong Lee, Choon-Gon Jang
Daidzein is one of the major isoflavones found in soy food and plants. Following ingestion, daidzein is readily converted to hydroxylated metabolites in the human body. 6,7,4'-Trihydroxyisoflavone (THIF), one of the metabolites of daidzein, has several pharmacological activities, including anti-cancer and anti-obesity properties. However, no reports exist on the effects of 6,7,4'-THIF for cognitive function in mice. The present study aimed to investigate the effects of 6,7,4'-THIF against scopolamine-induced learning and memory impairments using the Y-maze and passive avoidance test...
March 3, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29487062/anti-inflammatory-and-autonomic-effects-of-electroacupuncture-in-a-rat-model-of-diet-induced-obesity
#8
Xiaoyan Jie, Xu Li, Jian-Qing Song, Dan Wang, Jian-Hua Wang
OBJECTIVE: To study the effect of electroacupuncture (EA) on the cholinergic anti-inflammatory pathway (CAP) by measurement of vagal activity in rats with high-fat diet (HFD)-induced obesity. METHODS: Diet-induced obesity (DIO) was induced in 30 rats by feeding them a HFD for 12 weeks. A further 10 rats fed normal food comprised the lean diet (LD) control group. DIO rats were further subdivided into three groups that received a HFD only (HFD group, n=10), a HFD plus electroacupuncture (HFD+EA group, n=10) or a HFD plus minimal acupuncture (HFD+MA group, n=10)...
February 27, 2018: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
https://www.readbyqxmd.com/read/29473731/in-silico-identification-and-experimental-validation-of-novel-anti-alzheimer-s-multitargeted-ligands-from-marine-source-featuring-a-2-amino-imidazole-plus-aromatic-group-scaffold
#9
Rosa Maria Vitale, Vincenzo Rispoli, Doriana Desiderio, Roberta Sgammato, Stefano Thellung, Claudio Canale, Massimo Vassalli, Marianna Carbone, Maria Letizia Ciavatta, Ernesto Mollo, Vera Felicità, Rosaria Arcone, Margherita Gavagnin, Mariorosario Masullo, Tullio Florio, Pietro Amodeo
Multitargeting/polypharmacological approaches, looking for single chemical entities retaining the ability to bind two or more molecular targets, are a potentially powerful strategy to fight complex, multifactorial pathologies. Unfortunately, the search for multiligand agents is challenging, because only a small subset of molecules contained in molecular databases are bioactive, and even fewer are active on a preselected set of multiple targets. However, collections of natural compounds feature a significantly higher fraction of bioactive molecules than synthetic ones...
February 23, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29470537/microsomal-prostaglandin-e-synthase-1-gene-deletion-impairs-neuro-immune-circuitry-of-the-cholinergic-anti-inflammatory-pathway-in-endotoxaemic-mouse-spleen
#10
Priya Revathikumar, Johanna Estelius, Utsa Karmakar, Erwan Le Maître, Marina Korotkova, Per-Johan Jakobsson, Jon Lampa
The cholinergic anti-inflammatory pathway (CAP) is an innate neural reflex where parasympathetic and sympathetic nerves work jointly to control inflammation. Activation of CAP by vagus nerve stimulation (VNS) has paved way for novel therapeutic strategies in treating inflammatory diseases. Recently, we discovered that VNS mediated splenic acetylcholine (ACh) release and subsequent immunosuppression in response to LPS associated inflammation is impaired in mice lacking microsomal prostaglandin E synthase-1 (mPGES-1) expression, a key enzyme responsible for prostaglandin E2 synthesis...
2018: PloS One
https://www.readbyqxmd.com/read/29468816/the-cholinergic-anti-inflammatory-pathway-revisited
#11
REVIEW
K Murray, C Reardon
Inflammatory bowel disease negatively affects the quality of life of millions of patients around the world. Although the precise etiology of the disease remains elusive, aberrant immune system activation is an underlying cause. As such, therapies that selectively inhibit immune cell activation without broad immunosuppression are desired. Inhibition of immune cell activation preventing pro-inflammatory cytokine production through neural stimulation has emerged as one such treatment. These therapeutics are based on the discovery of the cholinergic anti-inflammatory pathway, a reflex arc that induces efferent vagal nerve signaling to reduce immune cell activation and consequently mortality during septic shock...
March 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29467611/the-vagus-nerve-at-the-interface-of-the-microbiota-gut-brain-axis
#12
REVIEW
Bruno Bonaz, Thomas Bazin, Sonia Pellissier
The microbiota, the gut, and the brain communicate through the microbiota-gut-brain axis in a bidirectional way that involves the autonomic nervous system. The vagus nerve (VN), the principal component of the parasympathetic nervous system, is a mixed nerve composed of 80% afferent and 20% efferent fibers. The VN, because of its role in interoceptive awareness, is able to sense the microbiota metabolites through its afferents, to transfer this gut information to the central nervous system where it is integrated in the central autonomic network, and then to generate an adapted or inappropriate response...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29466775/novel-tacrine-hydroxyphenylbenzimidazole-hybrids-as-potential-multitarget-drug-candidates-for-alzheimer-s-disease
#13
Asha Hiremathad, Rangappa S Keri, A Raquel Esteves, Sandra M Cardoso, Sílvia Chaves, M Amélia Santos
Alzheimer's disease (AD) is a severe age-dependent neurodegenerative disorder affecting millions of people, with no cure so far. The current treatments only achieve some temporary amelioration of the cognition symptoms. The main characteristics of the patient brains include the accumulation of amyloid plaques and neurofibrillary tangles (outside and inside the neurons) but also cholinergic deficit, increased oxidative stress and dyshomeostasis of transition metal ions. Considering the multi-factorial nature of AD, we report herein the development of a novel series of potential multi-target directed drugs which, besides the capacity to recover the cholinergic neurons, can also target other AD hallmarks...
February 12, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29452108/effect-of-brimonidine-an-%C3%AE-2-adrenergic-agonist-on-human-meibomian-gland-epithelial-cells
#14
Xi Han, Yang Liu, Wendy R Kam, David A Sullivan
We recently discovered that the anti-glaucoma pharmaceuticals timolol, a β adrenergic antagonist, and pilocarpine, a cholinergic compound, negatively influence the morphology, proliferative capacity and survival of human meibomian gland epithelial cells (HMGECs). We hypothesize that another class of anti-glaucoma drugs, the α2 adrenergic agonists, also acts directly on HMGECs to affect their structure and function. We tested this hypothesis. Immortalized (i) HMGECs were cultured with brimonidine, as well as clonidine (α2 agonist), phenylephrine (α1 agonist), RX821002 (inverse α2 agonist) and MK912 (neutral α2 agonist) for up to 7 days...
February 13, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29425796/doxycycline-prevents-and-reverses-schizophrenic-like-behaviors-induced-by-ketamine-in-mice-via-modulation-of-oxidative-nitrergic-and-cholinergic-pathways
#15
Benneth Ben-Azu, Itivere Adrian Omogbiya, Adegbuyi Oladele Aderibigbe, Solomon Umukoro, Abayomi Mayowa Ajayi, Ezekiel O Iwalewa
The involvement of oxidative/nitrosative stress, cholinergic and inflammatory pathways have been reported to contribute to the pathophysiology of schizophrenia, a debilitating neuropsychiatric disorder. Our previous studies have shown that doxycycline (DOX), a notable member of tetracyclines with proven antioxidant and anti-inflammatory properties, attenuated psychotic-like behaviors induced by apomophine and ketamine (KET) in mice. This present study was designed to further evaluate in detail the ability of DOX and its combination with risperidone (RIS) to prevent and reverse KET-induced schizophrenic-like behaviors and the role of oxidative/nitrosative and cholinergic pathways in mice...
February 6, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29423193/alzheimer-s-disease-hypothesis-and-related-therapies
#16
REVIEW
Xiaoguang Du, Xinyi Wang, Meiyu Geng
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause for dementia. There are many hypotheses about AD, including abnormal deposit of amyloid β (Aβ) protein in the extracellular spaces of neurons, formation of twisted fibers of tau proteins inside neurons, cholinergic neuron damage, inflammation, oxidative stress, etc., and many anti-AD drugs based on these hypotheses have been developed. In this review, we will discuss the existing and emerging hypothesis and related therapies...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29414243/the-underlying-physiological-mechanisms-whereby-anti-cholinergics-alleviate-asthma
#17
Morgan Gazzola, Samuel Mailhot-Larouche, Clémentine Beucher, Ynuk Bossé
The mechanisms whereby anti-cholinergics improve asthma outcomes, such as lung function, symptoms and rate of exacerbation, can be numerous. The most obvious is by affecting the contraction of airway smooth muscle (ASM). The acetylcholine released from the cholinergic nerves is the most important bronchoconstrictor that sets the baseline degree of contractile activation of ASM in healthy individuals. Although the degree of ASM's contractile activation can also be fine-tuned by a plethora of other bronchoconstrictors and bronchodilators in asthma, blocking the ceaseless effect of acetylcholine on ASM by anti-cholinergics reduces, at any given moment, the overall degree of contractile activation...
February 7, 2018: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29406911/anti-cholinergic-medications-for-bladder-dysfunction-worsen-cognition-in-persons-with-multiple-sclerosis
#18
Sarah A Morrow, Heather Rosehart, Alp Sener, Blayne Welk
Bladder dysfunction is common in persons with MS (PwMS), often due to detrusor muscle overactivity. Anticholinergic medications are considered the first line treatment for bladder dysfunction and are known to worsen cognition in healthy older adults and in persons with dementia. Yet, it is not known if these medications have the same effect on PwMS. Thus, the Objective of this prospective matched-cohort study was to determine if anticholinergic medications affect objective measures of cognition in PwMS. We recruited PwMS starting either oxybutynin or tolterodine (cases)...
February 15, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29405440/ebselen-inhibits-the-activity-of-acetylcholinesterase-globular-isoform-g4-in-vitro-and-attenuates-scopolamine-induced-amnesia-in-mice
#19
Franciele Martini, Ana Paula Pesarico, César Augusto Brüning, Gilson Zeni, Cristina Wayne Nogueira
There is a well-known relationship between the cholinergic system and learning, memory and other common cognitive processes. The process for researching and developing new drugs has lead researchers to repurpose older ones. This study investigated the effects of ebselen on the activity of acethylcholinesterase (AChE) isoforms in vitro and in an amnesia model induced by scopolamine in Swiss mice. In vitro, ebselen at concentrations equal or higher than 10 µM inhibited the activity of cortical and hippocampal G4/AChE, but not G1/AChE isoform...
February 5, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29399541/cholinergic-anti-inflammatory-pathway-and-the-liver
#20
REVIEW
Khalil Hajiasgharzadeh, Behzad Baradaran
The hepatic vagus branches innervate the liver and serve an important role in liver-brain connection. It appears that brain modulates inflammatory responses by activation of vagal efferent fibers. This activation and subsequent acetylcholine releases from vagus nerve terminals leads to inhibition of inflammatory cytokines through α7 nicotinic acetylcholine receptors (α7nAChRs) which located on the surface of different cell types such as liver Kupffer cells. This protective role of vagus-α7nAChR axis in liver diseases has been shown in several experimental studies...
December 2017: Advanced Pharmaceutical Bulletin
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