Inhibitory effect of chronic oral treatment with fluoxetine on capsaicin-induced external carotid vasodilatation in anaesthetised dogs

Cephalalgia ◽  
2015 ◽  
Vol 35 (12) ◽  
pp. 1041-1053 ◽  
Author(s):  
Enriqueta Muñoz-Islas ◽  
Abimael González-Hernández ◽  
Jair Lozano-Cuenca ◽  
Martha Beatríz Ramírez-Rosas ◽  
Roberto Medina-Santillán ◽  
...  
Keyword(s):  
Oral Treatment ◽  
Inhibitory Effect ◽  
Migraine Prophylaxis ◽  
Sensory Nerves ◽  
External Carotid ◽  
Measure Blood Pressure ◽  
Calcitonin Gene ◽  
Before And After ◽  
Underlying Mechanisms ◽  
Lines Of Evidence

Background During migraine, capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), resulting in cranial vasodilatation and central nociception. Moreover, 5-HT is involved in the pathophysiology of migraine and depression. Interestingly, some limited lines of evidence suggest that fluoxetine may be effective in migraine prophylaxis, but the underlying mechanisms are uncertain. Hence, this study investigated the canine external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine before and after acute and chronic oral treatment with fluoxetine. Methods Forty-eight vagosympathectomised male mongrel dogs were prepared to measure blood pressure, heart rate and external carotid blood flow. The thyroid artery was cannulated for infusions of agonists. In 16 of these dogs, a spinal cannula was inserted (C1–C3) for infusions of 5-HT. Results The external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine remained unaffected after intracarotid or i.v. fluoxetine. In contrast, the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine, were inhibited after chronic oral treatment with fluoxetine (300 µg/kg; for 90 days) or intrathecal 5-HT. Conclusions Chronic oral fluoxetine inhibited capsaicin-induced external carotid vasodilatation, and this inhibition could partly explain its potential prophylactic antimigraine action.

Reversal of isoprenaline-induced cardiac remodeling by rutaecarpine via stimulation of calcitonin gene-related peptide production

2010 ◽  
Vol 88 (10) ◽  
pp. 949-959 ◽  
Author(s):  
Jian-Zhe Li ◽  
Jun Peng ◽  
Li Xiao ◽  
Yi-Shuai Zhang ◽  
Mei-Chun Liao ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Inhibitory Effect ◽  
Calcitonin Gene Related Peptide ◽  
Sensory Nerves ◽  
Cross Sectional ◽  
Beneficial Effects ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Underlying Mechanisms ◽  
Stimulation Of

Dysfunction of capsaicin-sensitive sensory nerves is involved in cardiac remodeling, and rutaecarpine has been shown to exert a beneficial effect on cardiac function through activating the sensory nerves. This study was conducted to explore the potential inhibitory effect of rutaecarpine on cardiac remodeling and the underlying mechanisms. A rat cardiac remodeling model was established by injection of isoprenaline (5 mg/kg per day, s.c.) for 10 days. Rutaecarpine (10 or 40 mg/kg, i.g.) was coadministrated with isoprenaline to evaluate the effect of rutaecarpine on cardiac remodeling. After echocardiographic analysis was performed, blood samples were collected to quantify calcitonin gene-related peptide (CGRP), dorsal root ganglia were isolated for examining CGRP mRNA expression, and the hearts were weighed and saved for evaluating the parameters related to apoptosis and hypertrophy. Isoprenaline significantly increased the ratio of left ventricle weight to body weight, the cross-sectional area of cardiomyocytes, cardiac apoptosis, and collagen deposition concomitantly with decreased CGRP production, which were reversed by rutaecarpine treatment. The beneficial effects of rutaecarpine were attenuated by pretreatment with capsaicin, which selectively depleted CGRP. These results suggest that rutaecarpine was able to reverse isoprenaline-induced cardiac remodeling through stimulating CGRP production.

Mechanisms mediating gastric hyperemic and acid responses to central TRH analog at a cytoprotective dose

1997 ◽  
Vol 273 (1) ◽  
pp. G31-G38
Author(s):  
A. Kiraly ◽  
G. Suto ◽  
P. H. Guth ◽  
Y. Tache
Keyword(s):  
Acid Secretion ◽  
Vagal Stimulation ◽  
Mucosal Blood Flow ◽  
Hydrogen Gas ◽  
Inhibitory Influence ◽  
Hydrogen Gas Clearance ◽  
Afferent Fibers ◽  
Calcitonin Gene ◽  
Before And After ◽  
Underlying Mechanisms

Gastric hyperemic and acid responses to the stable thyrotropin-releasing hormone (TRH) analog RX-77368 injected intracisternally at a cytoprotective dose were investigated, as well as the underlying mechanisms of the responses. Gastric acid secretion (GAS), mucosal blood flow (GMBF; measured by the hydrogen gas clearance technique), and mucosal vascular resistance (GMVR) and mean arterial pressure (MAP) were assessed simultaneously for 30 min before and after RX-77368 (1.5 ng) administration in urethan-anesthetized rats. RX-77368 increased GMBF from 46.8 +/- 5.3 to 100.6 +/- 20.9 ml.min-1.100 g-1 and MAP from 70.3 +/- 2.1 to 84.3 +/- 5.9 mmHg and decreased GMVR from 1.50 +/- 0.33 to 0.84 +/- 0.08 mmHg.ml-1.min.100 g, whereas GAS was not significantly altered (1.8 +/- 0.4 vs. 4.7 +/- 1.7 mumol/30 min) in vehicle-pretreated rats. The GMBF, MAP, and GMVR responses to RX-77368 were not modified by indomethacin (5 mg/kg ip), whereas GAS was increased. In rats pretreated with capsaicin (125 mg/kg sc) or calcitonin gene-related peptide (CGRP) antagonist hCGRP-(8-37), intracisternal RX-77368 did not increase GMBF or decrease GMVR but did stimulate GAS. These data show that vagal stimulation by the TRH analog RX-77368 injected intracisternally at a nonacid secretory dose increases GMBF. Gastric hyperemia is mediated by CGRP contained in capsaicin-sensitive afferent fibers, whereas acid secretion is under the inhibitory influence of prostaglandins and CGRP.

Transcerebral net exchange of vasoactive peptides and catecholamines during lipopolysaccharide-induced systemic inflammation in healthy humans

2018 ◽  
Vol 96 (3) ◽  
pp. 313-316
Author(s):  
Ronan M.G. Berg ◽  
Sarah Taudorf ◽  
Damian M. Bailey ◽  
Rasmus H. Dahl ◽  
Carsten Lundby ◽  
...  
Keyword(s):  
Venous Blood ◽  
Blood Samples ◽  
Fick Principle ◽  
Vasoactive Peptides ◽  
Healthy Humans ◽  
Cerebral Vasoconstriction ◽  
Calcitonin Gene ◽  
Human Volunteers ◽  
Before And After ◽  
Underlying Mechanisms

The systemic inflammatory response triggered by lipopolysaccharide (LPS) is associated with cerebral vasoconstriction, but the underlying mechanisms are unknown. We therefore examined whether a 4-hour intravenous LPS infusion (0.3 ng·kg−1) induces any changes in the transcerebral net exchange of the vasoactive peptides endothelin-1 (ET-1) and calcitonin-gene related peptide (CGRP) and catecholamines in human volunteers. Cerebral blood flow was measured by the Kety–Schmidt technique, and paired arterial-to-jugular venous blood samples were obtained for estimating the transcerebral exchange of ET-1, CGRP, and catecholamines by the Fick principle in 12 volunteers before and after LPS infusion. The cerebrovascular release of ET-1 was enhanced, whereas the transcerebral net exchange of CGRP and catecholamines was unaffected. Our findings thus point towards locally produced ET-1 within the cerebrovasculature as a contributor to cerebral vasoconstriction after LPS infusion.

Blockade of CGRP Receptors in the Intracranial Vasculature: A New Target in the Treatment of Headache

Cephalalgia ◽  
2004 ◽  
Vol 24 (8) ◽  
pp. 611-622 ◽  
Author(s):  
L Edvinsson
Keyword(s):  
Inhibitory Effect ◽  
Sensory Nerves ◽  
Primary Headaches ◽  
Cardiovascular Side Effects ◽  
Calcitonin Gene ◽  
Acute Attacks ◽  
Cgrp Receptor Antagonist ◽  
Intracranial Circulation ◽  
Intracranial Vasculature

In primary headaches, there is a clear association between the headache and the release of calcitonin gene-related peptide (CGRP) but not with any of the other neuronal messengers. The purpose of this review is to describe the role of CGRP in the intracranial circulation and to elucidate a possible role for a specific CGRP receptor antagonist in the treatment of primary headaches. Acute treatment with a 5-HT1B/1D agonist (triptan) results in alleviation of the headache and normalization of the cranial venous CGRP levels, in part due to a presynaptic inhibitory effect on sensory nerves. The central role of CGRP in migraine and cluster headache pathophysiology has led to the search for small molecule CGRP antagonists with few cardiovascular side-effects. The initial pharmacological profile of such a group of compounds has recently been disclosed. One of these compounds has been found to be efficacious in the relief of acute attacks of migraine.

scholarly journals Chloroplast Hsp70 Isoform Is Required for Age-Dependent Tissue Preference of Bamboo mosaic virus in Mature Nicotiana benthamiana Leaves

2017 ◽  
Vol 30 (8) ◽  
pp. 631-645 ◽  
Author(s):  
Ying Wen Huang ◽  
Chung Chi Hu ◽  
Ching Hsiu Tsai ◽  
Na Sheng Lin ◽  
Yau Heiu Hsu
Keyword(s):  
Mosaic Virus ◽  
Nicotiana Benthamiana ◽  
Transit Peptide ◽  
Plant Viruses ◽  
Age Dependent ◽  
Efficient Replication ◽  
Underlying Mechanisms ◽  
Lines Of Evidence ◽  
Suitable Environment

Plant viruses may exhibit age-dependent tissue preference in their hosts but the underlying mechanisms are not well understood. In this study, we provide several lines of evidence to reveal the determining role of a protein of the Nicotiana benthamiana chloroplast Hsp70 (NbcpHsp70) family, NbcpHsp70-2, involved in the preference of Bamboo mosaic virus (BaMV) to infect older tissues. NbcpHsp70 family proteins were identified in complexes pulled down with BaMV replicase as the bait. Among the isoforms of NbcpHsp70, only the specific silencing of NbcpHsp70-2 resulted in the significant decrease of BaMV RNA in N. benthamiana protopalsts, indicating that NbcpHsp70-2 is involved in the efficient replication of BaMV RNA. We further identified the age-dependent import regulation signal contained in the transit peptide of NbcpHsp70-2. Deletion, overexpression, and substitution experiments revealed that the signal in the transit peptide of NbcpHsp70-2 is crucial for both the import of NbcpHsp70-2 into older chloroplasts and the preference of BaMV for infecting older leaves of N. benthamiana. Together, these data demonstrated that BaMV may exploit a cellular age-dependent transportation mechanism to target a suitable environment for viral replication.

Cross-talk along gastrointestinal tract during electrical stimulation: effects and mechanisms of gastric/colonic stimulation on rectal tone in dogs

2005 ◽  
Vol 288 (6) ◽  
pp. G1195-G1198 ◽  
Author(s):  
Shi Liu ◽  
Lijie Wang ◽  
J. D. Z. Chen
Keyword(s):  
Electrical Stimulation ◽  
Inhibitory Effect ◽  
Adrenergic Blockade ◽  
Rectal Compliance ◽  
Rectal Tone ◽  
Before And After ◽  
Sensory Functions ◽  
Sympathetic Pathway ◽  
Colonic Electrical Stimulation ◽  
Stimulation Of

Gastric electrical stimulation (GES) has been shown to alter motor and sensory functions of the stomach. However, its effects on other organs of the gut have rarely been investigated. The study was performed in 12 dogs implanted with two pairs of electrodes, one on the serosa of the stomach and the other on the colon. The study was composed of two experiments. Experiment 1 was designed to study the effects of GES on rectal tone and compliance in nine dogs compared with colonic electrical stimulation (CES). Rectal tone and compliance were assessed before and after GES or CES. Experiment 2 was performed to study the involvement of sympathetic pathway in 8 of the 12 dogs. The rectal tone was recorded for 30–40 min at baseline and 20 min after intravenous guanethidine. GES or CES was given for 20 min 20 min after the initiation of the infusion. It was found that both GES and CES reduced rectal tone with comparable potency. Rectal compliance was altered neither with GES, nor with CES. The inhibitory effect of GES but not CES on rectal tone was abolished by an adrenergic blockade, guanethidine. GES inhibited rectal tone with a comparable potency with CES but did not alter rectal compliance. The inhibitory effect of GES on rectal tone is mediated by the sympathetic pathway. It should be noted that electrical stimulation of one organ of the gut may have a beneficial or adverse effect on another organ of the gut.

Early Experiences in Switching between Monoclonal Antibodies in Patients with Nonresponsive Migraine in Spain: A Case Series

2021 ◽  
pp. 1-4
Author(s):  
Ignacio Patier Ruiz ◽  
Javier Sánchez-Rubio Ferrández ◽  
Alba Cárcamo Fonfría ◽  
Teresa Molina García
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Therapeutic Targets ◽  
Case Series ◽  
Similar Efficacy ◽  
Migraine Prophylaxis ◽  
Therapeutic Failure ◽  
Related Peptide ◽  
Early Experiences ◽  
Calcitonin Gene

Monoclonal antibodies targeting the calcitonin gene-related peptide have been introduced into the therapeutic arsenal of migraine prophylaxis. Clinical trials report similar efficacy between them, and there is no evidence of switching to another one after failure. We aim to describe our experience in switching from erenumab to galcanezumab after therapeutic failure. We retrospectively reviewed 30 migraine patients who received monoclonal antibodies, with 15 of them switched after failure to achieve reduction in migraine days per month ≥30%. A ≥30% reduction in migraine days per month compared to baseline was observed in 8/15 (4/15 ≥ 50%) patients after switch. Some nonresponsive patients may benefit from switching between monoclonal antibodies with different therapeutic targets.

Synthesis, Quantum Chemical Calculations, Molecular Docking and Studying the Effect of High Energetic Gamma Irradiation on Cu(I, II), Zn(II) and Cd(II) Complexes with their Antibacterial Activity.

2021 ◽  
Author(s):  
Hussein Elganzory
Keyword(s):  
Molecular Docking ◽  
Gamma Irradiation ◽  
Density Functional ◽  
Topoisomerase Ii ◽  
Gamma Ray ◽  
Inhibitory Effect ◽  
Molar Conductance ◽  
Basis Set ◽  
Conformational Structure ◽  
Before And After

Abstract New complexes of Cu(I,II), Zn(II) and Cd(II) of thiosemicarbazide ligand 1-(p-(methylanilinocetyl-4-phenyl-thiosemicarbazide)(H2LB) have been prepared and characterized by 1HNMR, Mass spectra, FT-IR, elemental analyses, molar conductance, UV-visible spectra, magnetic susceptibility measurements, thermogravimetric analysis (TGA/DTG) and X-ray diffraction pattern before and after irradiation. The results confirmed that gamma ray enhanced the stability of irradiated compounds as compared to non-irradiated compounds. XRD patterns proved that increasing the crystallinity of the samples and the particles in nano range after gamma irradiation. The obtained data indicated that the Cu(I) and Cd(II) ions coordinated to the ligand through the (C = O), N(2)H and (C = S), the ligand behaves as neutral tridentate. While in complexes Cu(II) and Zn(II)complexes (B2 and B3) the ligand behave as neutral tetradentate and coordination take place via (C = O) and two N(2)H. These studies revealed that, two kinds of stereochemical geometries; Cu(II) and Zn(II) complexes were predicted to be octahedral, Cu(I) and Cd(II)complexes were found to be tetrahedral. The theoretical conformational structure analyses were performed using density functional theory for ligand and complexes at B3LYP functional with 6-31G(++)d,p basis set for ligand and LANL2DZ basis set for complexes. The ligand and its metal complexes have been tested for their inhibitory effect on the growth of bacteria against gram-positive (Streptococcus pyogenes) and gram-negative (Escherichia coli). Results suggested that in case of 1µg/ml and 5µg/ml for Cu(II) and Zn(II) complexes have higher activity than other complexes. The chelation could facilitate the ability to cross the cell membrane of E. coli and can be explained by Tweedy’s chelation theory. Molecular docking investigation proved that; the Zn(II) complex had interesting interactions with active site amino acids of topoisomerase II DNA gyrase enzymes (code: 2XCT).

scholarly journals Does Social Exclusion Alter Sensory and Pain Thresholds in Children and Adolescents with Functional Abdominal Pain? – Results from a Preliminary Study

Pain Medicine ◽  
2018 ◽  
Vol 20 (8) ◽  
pp. 1472-1478
Author(s):  
Marco Daniel Gulewitsch ◽  
Aiste Jusyte ◽  
Katja Weimer ◽  
Michael Schönenberg
Keyword(s):  
Abdominal Pain ◽  
Social Exclusion ◽  
Experimental Studies ◽  
Control Group ◽  
Childhood And Adolescence ◽  
Sensory Threshold ◽  
Functional Abdominal Pain ◽  
Pain Thresholds ◽  
Before And After ◽  
Underlying Mechanisms

Abstract Objective Functional abdominal pain (AP) is a prevalent issue in childhood and adolescence. The contribution of psychosocial factors in the development and maintenance of this health problem is rather unclear, and experimental studies about underlying mechanisms are lacking. This study investigates whether experimentally induced social exclusion decreases sensory and pain thresholds in children suffering from AP. Subjects Twenty children/adolescents with AP and 22 healthy controls. Methods Children/adolescents participated in the Cyberball paradigm, which affects an experience of social exclusion. Thermal sensory and pain thresholds were measured before and after Cyberball. Results Children/adolescents with AP showed a divergent reaction regarding their sensory threshold after social exclusion: The control group exhibited a tendency toward a decreased sensory threshold whereas the AP group remained stable. Concerning the pain threshold, no effect of social exclusion could be identified. The increase of both thresholds (“numbing”) after Cyberball was positively correlated with symptoms of mental health issues. Conclusions This is the first study to investigate changes in sensory and pain thresholds following painful social interactions in a sample of children/adolescents with a chronic pain condition. Results suggest that AP and control children differ in their reaction of sensory thresholds, which might indicate an altered processing of social exclusion. Replication and further methodological improvements are needed.

scholarly journals Chronic pain relief after the exposure of nitrous oxide during dental treatment: longitudinal retrospective study

2015 ◽  
Vol 73 (7) ◽  
pp. 578-581 ◽  
Author(s):  
Francisco Moreira Mattos Júnior ◽  
Rafael Villanova Mattos ◽  
Manoel Jacobsen Teixeira ◽  
Silvia Regina Dowgan Tesseroli de Siqueira ◽  
Jose Tadeu Tesseroli de Siqueira
Keyword(s):  
Chronic Pain ◽  
Nitrous Oxide ◽  
Dental Treatment ◽  
Chronic Pain Patients ◽  
Before And After ◽  
Nitrous Oxide Oxygen ◽  
Oxygen Nitrous Oxide ◽  
Prevalence Of Pain ◽  
Underlying Mechanisms ◽  
Pain Patients

The objective was to investigate the effect of nitrous/oxygen in chronic pain. Seventy-seven chronic pain patients referred to dental treatment with conscious sedation with nitrous oxide/oxygen had their records included in this research. Data were collected regarding the location and intensity of pain by the visual analogue scale before and after the treatment. Statistical analysis was performed comparing pre- and post-treatment findings. It was observed a remarkable decrease in the prevalence of pain in this sample (only 18 patients still had chronic pain, p < 0.001) and in its intensity (p < 0.001). Patients that needed fewer sessions received higher proportions of nitrous oxide/oxygen. Nitrous oxide may be a tool to be used in the treatment of chronic pain, and future prospective studies are necessary to understand the underlying mechanisms and the effect of nitrous oxide/oxygen in patients according to the pain diagnosis and other characteristics.

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