scholarly journals Regulatory Role of Orexin in the Antistress Effect of “Press Tack Needle” Acupuncture Treatment

Healthcare ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 503
Author(s):  
Aki Fujiwara ◽  
Mana Tsukada ◽  
Hideshi Ikemoto ◽  
Takuji Izuno ◽  
Satoshi Hattori ◽  
...  
Keyword(s):  
Aggressive Behavior ◽  
Receptor Antagonist ◽  
Sham Group ◽  
Acupuncture Treatment ◽  
Plasma Corticosterone ◽  
Orexin A ◽  
Stress Group ◽  
Antistress Effect ◽  
Prolonged Duration ◽  
Group A

The aim of this research was to investigate the antistress effect of press tack needle (PTN) acupuncture treatment using rats with social isolation stress (SIS). Rats were divided into non-stress group (Grouped+sham), stress group (SIS+sham), and PTN-treated SIS group (SIS+PTN). Rats in the SIS+PTN and SIS+sham groups were housed alone for eight days. For the SIS+PTN group, a PTN (length, 0.3 or 1.2 mm) was fixed on the GV20 acupoint on day 7. We measured stress behavior based on the time the rats showed aggressive behavior and the levels of plasma corticosterone and orexin A on day 8. In addition, the orexin-1 receptor or orexin-2 receptor antagonist was administered to rats that were exposed to SIS. The duration of aggressive behavior was significantly prolonged in the SIS+sham group, and the prolonged duration was inhibited in the SIS+PTN (1.2 mm) group. The levels of plasma corticosterone and orexin A were significantly increased in the SIS+sham group; however, these increases were inhibited in the SIS+PTN group. The aggressive behavior was significantly reduced after the orexin-2 receptor antagonist was administered. These findings suggest that PTN treatment at GV20 may have an antistress effect, and the control of orexin is a mechanism underlying this phenomenon.

scholarly journals 0004 TS-142: A Novel and Potent Dual Orexin Receptor Antagonist with Sleep-Promoting Effects in Rats

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A2-A2
Author(s):  
D Kambe ◽  
H Hikichi ◽  
Y Tokumaru ◽  
M Ohmichi ◽  
Y Konno ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Half Life ◽  
Sleep Onset ◽  
Sleep Time ◽  
Sleep Onset Latency ◽  
Orexin A ◽  
Pharmacokinetic Profiles ◽  
Orexin Receptors ◽  
Elimination Half ◽  
Emg Electrodes

Abstract Introduction The orexin system plays a pivotal role in regulating sleep and wakefulness, thus, orexin receptors (OX1 and OX2 receptors) have gained much attention as promising therapeutic targets for the treatment of insomnia. We synthesized a novel and potent dual orexin receptor antagonist (DORA), ORN0829 (investigation code name as TS-142), which was designed to have short-acting effects. Here we report pharmacological and pharmacokinetic profiles of ORN0829 in rats. Methods The antagonistic activities of ORN0829 were assessed using calcium mobilization assays. Ala-orexin A-induced [Ca2+]i response was measured with CHO-K1 cells stably expressing human/rat orexin receptor. Rats implanted the EEG/EMG electrodes were orally administrated ORN0829 at doses of 1, 3 or 10 mg/kg at the dark onset and sleep-wake stages were inspected visually. In addition, pharmacokinetic profiles of ORN0829 were investigated in rats. Results ORN0829 inhibited Ala-orexin A-increased [Ca2+]i response with a Kb of 0.67/0.44 nmol/L (for human/rat OX1 receptor), and with a Kb of 0.84/0.80 nmol/L (for human/rat OX2 receptor), respectively, indicating that ORN0829 is a potent DORA with no species differences. ORN0829 dose-dependently increased total sleep time and reduced sleep onset latency at doses of 1, 3 and 10 mg/kg. Importantly, the ORN0829 levels in plasma and cerebrospinal fluid rapidly reached a maximum concentration, and decreased with an elimination half-life of less than 1 h. Conclusion The present study indicates that ORN0829 is a novel and potent DORA with sleep-promoting effects, and that it exhibits ideal pharmacokinetic profiles (rapid absorption and short half-life) in rats. A phase 2a study of TS-142 using patients with insomnia has been completed, which is presented in a separate poster. Support Taisho Pharmaceutical. Co., Ltd.

scholarly journals Social instigation and repeated aggressive confrontations in male Swiss mice: analysis of plasma corticosterone, CRF and BDNF levels in limbic brain areas

2017 ◽  
Vol 39 (2) ◽  
pp. 98-105 ◽  
Author(s):  
Paula Madeira Fortes ◽  
Lucas Albrechet-Souza ◽  
Mailton Vasconcelos ◽  
Bruna Maria Ascoli ◽  
Ana Paula Menegolla ◽  
...  
Keyword(s):  
Aggressive Behavior ◽  
Physiological Responses ◽  
Plasma Corticosterone ◽  
Corticotropin Releasing Factor ◽  
Brain Areas ◽  
Social Stressors ◽  
Swiss Mice ◽  
The Brain ◽  
Over Time ◽  
Resident Intruder

Abstract Introduction: Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. Objectives: To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. Methods: Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation), or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF) and brain-derived neurotrophic factor (BNDF) were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. Results: Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. Conclusion: Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.

scholarly journals Correlation between Duration of Oral Contraceptives and Hypercoagulability in Bangladeshi Women

2017 ◽  
Vol 26 (Number 1) ◽  
pp. 21-26
Author(s):  
Samsunnahar ◽  
Q S Akhter ◽  
N Akhter ◽  
K Sultana ◽  
Md. Atiquzzaman ◽  
...  
Keyword(s):  
Oral Contraceptives ◽  
Oral Contraceptive Pill ◽  
Study Groups ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Medical College ◽  
Prolonged Duration ◽  
Group A ◽  
The Mean ◽  
Student’S T

This study was done to assess the hypercoagulability and the risk of thromboembolism in women taking oral contraceptive pill for prolonged period of time. This cross sectional study was done in the department of Physiology, Dhaka Medical College, Dhaka from Jan 2012 to Dec 2012. Ninety female subjects with the age range from 25-45 years, were taken as a study population. Among them, 60 women taking oral contraceptives for prolonged period of time ( > 1 years) were included for the study group and age matched 30 women of OCP nonusers were taken as a control. Study subjects were divided into two groups according to their duration of oral pill use: group BI ( 1 to 5 years users) were 30 women and group B2 ( >5 to 10 years users) were 30 women. Prothrombin time and activated partial thromboplastin time were estimated in all groups. Statistical analysis was done by unpaired Student's ? t' test and Pearson's Correlation Coefficient test. In this study, the mean (*SD) PT levels in group B1 & B2 were shortened than that of group A which were statistically highly significant (P < 0.001). Within the study groups, PT levels were positively correlated (r=+0.027) with the group B1 and negatively correlated (r= -0.163) with the group B2. But both the relationships were statistically non significant. The mean (+SD) AM' level in group B1 was shortened than that of group A but the result was not statistically significant. The mean (*SD) AM' level in group B2 was shortened than that of group A but the result was statistically highly significant (P<0.001). Within the study groups, APPT levels were negatively correlated with the group B1 (r= -0.268) and also group B2 (r= -0.122). But both the relationships were statistically non significant. My present study revealed that prolonged duration of OCP use ( at least for 5 years) increases the risk of hypercoagulable state and thromboembolism in women.

scholarly journals Exendin-4 improves neuron protection and functional recovery in experimental spinal cord injury in rats through regulating PCBP2 expression

2020 ◽  
Author(s):  
Huaichao Luo ◽  
Qingwei Wang ◽  
Lei Wang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Apoptosis ◽  
Sham Group ◽  
Sham Operation ◽  
Therapeutic Effects ◽  
Rat Models ◽  
Apoptosis Rate ◽  
Cord Injury ◽  
Group A

AbstractAimsIn the present research, we assessed the therapeutic effects of Exendin-4 (Ex-4) on rat models with spinal cord injury (SCI).Materials and methods36 male Sprague–Dawley rats were randomly allocated into three groups, including sham operation group, SCI group and SCI+Ex-4 group (Ex-4 treatment (10 µg/rat) after SCI, i.p.). In the SCI group, a laminectomy was performed at the T10 vertebrae, followed by weight-drop contusion of the spinal cord. In the sham group, a laminectomy was carried out without SCI contusion.Key findingsOur results showed that Basso-Beattie-Bresnahan scale scores were significantly decreased after SCI, and were obviously improved in SCI rats with Ex-4 administration. Additionally, the water content of spinal cord in SCI group was dramatically increased than that in sham group, and after Ex-4 treatment, degree of edema of spinal cord was remarkably reduced. And also, concentration levels of inflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α) in the spinal cord were significantly elevated after SCI, and were remarkably reduced in SCI rats with Ex-4 administration. Subsequently, cell apoptosis rate in the injured spinal cord was significantly increased, and after Ex-4 treatment, cell apoptosis rate was remarkably decreased. We also revealed that levels of PCBP2 mRNA and protein were significantly up-regulated after SCI, and were dramatically dropped in SCI rats with Ex-4 administration.SignificanceTake altogether, our findings disclosed that Ex-4 plays a role in promoting neurological function recovery and inhibiting neuronal apoptosis through effecting PCBP2 expression in SCI rat models.

Stress alters cutaneous permeability barrier homeostasis

2000 ◽  
Vol 278 (2) ◽  
pp. R367-R372 ◽  
Author(s):  
Mitsuhiro Denda ◽  
Toru Tsuchiya ◽  
Peter M. Elias ◽  
Kenneth R. Feingold
Keyword(s):  
Glucocorticoid Receptor ◽  
Receptor Antagonist ◽  
Psychological Stress ◽  
Skin Disease ◽  
Barrier Function ◽  
Plasma Corticosterone ◽  
Permeability Barrier ◽  
Hairless Mice ◽  
Ru 486 ◽  
Kinetics Of

Recent studies have shown that psychological stress can influence cutaneous barrier function, suggesting that this form of stress could trigger or aggravate skin disease. In the present study, we demonstrate that transfer of hairless mice to a different cage delays barrier recovery rates. Pretreatment with a phenothiazine sedative, chlorpromazine, before transfer of animals restored the kinetics of barrier recovery toward normal, suggesting that psychological stress is the basis for this alteration in barrier homeostasis. To determine the mechanism linking psychological stress to altered barrier recovery, we first demonstrated that plasma corticosterone levels increase markedly after transfer of animals to new cages and that pretreatment with chlorpromazine blocks this increase. Second, we demonstrated that the systemic administration of corticosterone delays barrier recovery. Finally, we demonstrated that pretreatment with the glucocorticoid receptor antagonist RU-486 blocks the delay in barrier recovery produced by systemic corticosterone, change of cage, or immobilization. These results suggest that psychological stress stimulates increased production of glucocorticoids, which, in turn, adversely affects permeability barrier homeostasis.

scholarly journals The Efficacy of the Mineralcorticoid Receptor Antagonist Canrenone in COVID-19 Patients

2020 ◽  
Vol 9 (9) ◽  
pp. 2943 ◽  
Author(s):  
Marco Vicenzi ◽  
Massimiliano Ruscica ◽  
Simona Iodice ◽  
Irene Rota ◽  
Angelo Ratti ◽  
...  
Keyword(s):  
Survival Rate ◽  
Receptor Antagonist ◽  
Positive Impact ◽  
Ventilatory Support ◽  
Continuous Administration ◽  
Pharmacological Management ◽  
Group A ◽  
Group B ◽  
The Impact ◽  
Free Rate

Background: In COVID-19 patients, aldosterone via angiotensin-converting enzyme-2 deregulation may be responsible for systemic and pulmonary vasoconstriction, inflammation, and oxidative organ damage. Aim: To verify retrospectively the impact of the mineralcorticoid receptor antagonist canrenone i.v. on the need of invasive ventilatory support and/or all-cause in-hospital mortality. Methods: Sixty-nine consecutive COVID-19 patients, hospitalized for moderate to severe respiratory failure at Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca’ Granda Ospedale Maggiore Policlinico of Milan, received two different therapeutic approaches in usual care according to the personal skills and pharmacological management experience of the referral medical team. Group A (n = 39) were given vasodilator agents or renin–angiotensin–aldosterone system (RAAS) inhibitors and group B (n = 30) were given canrenone i.v. Results: Among the 69 consecutive COVID-19 patients, those not receiving canrenone i.v. (group A) had an event-free rate of 51% and a survival rate of 64%. Group B (given a mean dose of 200 mg/q.d. of canrenone for at least two days of continuous administration) showed an event-free rate of 80% with a survival rate of 87%. Kaplan–Meier analysis for composite outcomes and mortality showed log rank statistics of 0.0004 and 0.0052, respectively. Conclusions: The novelty of our observation relies on the independent positive impact of canrenone on the all-cause mortality and clinical improvement of COVID-19 patients ranging from moderate to severe diseases.

scholarly journals Assessment of bioabsorbable implant treatment for nasal valve collapse compared to a sham group: a randomized control trial

2019 ◽  
Vol 9 (8) ◽  
pp. 850-856 ◽  
Author(s):  
Pablo Stolovitzky ◽  
Brent Senior ◽  
Randall A. Ow ◽  
Neelesh Mehendale ◽  
Nadim Bikhazi ◽  
...  
Keyword(s):  
Randomized Control Trial ◽  
Sham Group ◽  
Nasal Valve ◽  
Group A ◽  
Randomized Control ◽  
Nasal Valve Collapse ◽  
Implant Treatment

Effects of chronic tobacco smoke exposure on arterial blood pressure regulation

1984 ◽  
Vol 247 (4) ◽  
pp. H556-H562
Author(s):  
C. H. Bennett ◽  
D. R. Richardson
Keyword(s):  
Blood Pressure ◽  
Cardiovascular System ◽  
Arterial Blood Pressure ◽  
Tobacco Smoke ◽  
Sham Group ◽  
Lower Body ◽  
Pressure Regulation ◽  
Arterial Blood ◽  
Group A ◽  
Group B

The purpose of this study was to determine the effects of long-term consumption of tobacco smoke on arterial blood pressure regulation. Male Sprague-Dawley rats were administered tobacco smoke for 6-8 mo. Two groups of animals (A and B) received tobacco smoke containing different levels of nicotine (group A: high nicotine, 4 mg/cigarette; group B: low nicotine, 1 mg/cigarette), while a third group (C) served as a sham control by receiving only puffs of room air. Reflex adjustments in mean arterial blood pressure (MAP), heart rate (HR), lower body blood flow, and lower body vascular resistance were compared between the three groups. In the anesthetized control state, no significant difference existed for the cardiovascular parameters measured in the three groups. However, perturbating the cardiovascular system by reducing central blood volume via a 60 degrees head-up tilt elicited less of a fall in MAP in the two smoke groups compared with the sham group. Percent decreases in MAP follow: group A, 23%; group B, 22%; and group C, 48%. Increasing MAP with phenylephrine elicited a significantly greater (P less than 0.05) reduction in HR in groups A and B (smoke treated) compared with group C (sham treated). Finally, varying carotid sinus pressure elicited significantly greater (P less than 0.01) changes in MAP in the smoke-treated animals (A and B) compared with the sham group (C). It is concluded that chronic tobacco smoke administration to laboratory rats increases the sensitivity of the reflex control of the cardiovascular system.

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