scholarly journals A Single Low Dose of Dexmedetomidine Efficiently Attenuates Esketamine-Induced Overactive Behaviors and Neuronal Hyperactivities in Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Qinjun Chu ◽  
Kuicheng Zhu ◽  
Yafan Bai ◽  
Huijie Shang ◽  
Dongqing Zhang ◽  
...  
Keyword(s):  
Side Effects ◽  
Western Blot ◽  
Recovery Time ◽  
Low Dose ◽  
Intraperitoneal Administration ◽  
Racemic Mixture ◽  
Righting Reflex ◽  
Mice Brain ◽  
Fos Expression ◽  
The Brain

Introduction: Esketamine (Esk) (S(+)-ketamine) is now used as an alternative to its racemic mixture, i. e., ketamine in anesthesia. Esk demonstrated more powerful potency and rapid recovery in anesthesia and less psychotomimetic side effects comparing with ketamine, but Esk could still induce psychological side effects in patients. This study was to investigate whether dexmedetomidine (Dex) can attenuate the Esk-induced neuronal hyperactivities in Kunming mice.Methods: Dexmedetomidine 0.25, 0.5, and 1 mg/kg accompanied with Esk 50 mg/kg were administrated on Kunming mice to assess the anesthesia quality for 1 h. The indicators, such as time to action, duration of agitation, duration of ataxia, duration of loss pedal withdrawal reaction (PWR), duration of catalepsy, duration of righting reflex (RR) loss, duration of sedation, were recorded for 1 h after intraperitoneal administration. The c-Fos expression in the brain was detected by immunohistochemistry and Western Blot after 1 h of administration. Considering the length of recovery time for more than 1 h in Dex and Dex with Esk groups, other mice were repeatedly used to evaluate recovery time from the administration to emerge from anesthesia.Results: Dexmedetomidine dose-dependently increased recovery time when administrated with Esk or alone. Dex combined with Esk efficiently attenuated the duration of agitation, ataxia, and catalepsy. Dex synergically improved the anesthesia of Esk by increasing the duration of sedation, loss of RR, and loss of PWR. Esk induced the high expression of c-Fos in the cerebral cortex, hippocampus, thalamus, amygdala, hypothalamus, and cerebellum 1 h after administration. Western Blot results indicated that Dex at doses of 0.25, 0.5, and 1 mg/kg could significantly alleviate the Esk-induced c-Fos expression in the mice brain.Conclusion: Dexmedetomidine ranged from 0.25 to 1 mg/kg could improve the anesthesia quality and decreased the neuronal hyperactivities and the overactive behaviors when combined with Esk. However, Dex dose-dependently increased the recovery time from anesthesia. It demonstrated that a small dose of Dex 0.25 mg/kg could be sufficient to attenuate Esk-induced psychotomimetic side effects without extension of recovery time in Kunming mice.

Use of Melatonin to Promote Sleep in Older People

2012 ◽  
Vol 7 (2) ◽  
pp. 90 ◽  
Author(s):  
Richard J Wurtman ◽  
Keyword(s):  
Side Effects ◽  
Older People ◽  
Low Dose ◽  
Sleep Onset ◽  
Melatonin Receptors ◽  
Older Americans ◽  
Exogenous Melatonin ◽  
Plasma Melatonin ◽  
The Brain

Many older Americans purchase the hormone melatonin and take it orally, nightly, to promote sleep onset and to help them fall back asleep after the frequent nocturnal awakenings associated with ageing. This need for exogenous melatonin reflects the fact that the progressive calcification of the human pineal diminishes the organ’s ability to secrete its hormone, so that instead of plasma melatonin levels rising normally by 10-fold or more around bedtime the rise may be only by twofold, or even less. The quantity of melatonin that most ageing people need to restore nocturnal plasma melatonin levels to what they are in youth – and, concurrently, to promote sleep – is tiny, only about 0.2–0.5 mg. However, this dosage is generally unavailable, so patients may take doses 10-fold greater, or more, producing side-effects (e.g., hypothermia; hypoprolactinaemia; morning grogginess) and ultimately desensitising melatonin receptors in the brain. The reasons why low-dose melatonin is generally unavailable are described and a strategy is proposed for enabling patients to consume the correct dosage even when preparations containing that dosage cannot be obtained.

scholarly journals Effects of Resveratrol on the Mechanisms of Antioxidants and Estrogen in Alzheimer’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Danli Kong ◽  
Yan Yan ◽  
Xiao-Yi He ◽  
Huihuang Yang ◽  
BiYu Liang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Western Blot ◽  
Brain Tissue ◽  
Low Dose ◽  
Mrna Level ◽  
High Dose ◽  
Model Group ◽  
Protein Levels ◽  
Mda Content ◽  
The Brain

Objective. To observe the effects of resveratrol (Res) on the antioxidative function and estrogen level in an Alzheimer’s disease (AD) mouse model. Methods. First, we examined the effects of Res on an AD mice model. SAMP8 mice were selected as the model, and normal-aging SAMR1 mice were used as the control group. The model mice were randomly divided into three groups: a model group, high-dose Res group (40mg/kg, intraperitoneal (ip)), and low-dose Res group (20mg/kg, ip). After receiving medication for 15 days, the mice were subjected to the water maze test to assess their spatial discrimination. The spectrophotometric method was used to detect the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) as well as the malondialdehyde (MDA) content. Quantitative PCR (q-PCR) was used to detect SOD, GSH-Px, CAT, and heme oxygenase-1 (HO-1) mRNA level changes. Western blot analysis detected HO-1 and Nrf2 protein expression. Second, we researched the effect of Res on the estrogen level in the SAMP8 model mice. The model mice were randomly divided into four groups: a model group, estrogen replacement group (0.28 mg/kg, intramuscular (im), estradiol benzoate), high-dose Res group (5 mg/kg, im), and low-dose Res group (2.5 mg/kg, im). The mice were injected, once every three days, for 5 weeks. Q-PCR was used to detect brain tissue mRNA expression changes. Western blot analysis detected ERα, ERβ, and ChAT protein expression. An enzyme-linked immunosorbent assay (ELISA) kit was used to detect the expression of E2 and amyloid β protein (Aβ) in brain tissue. Results. Compared with the control treatment, Res could improve the spatial abilities of the mice to a certain extent and also increase the expression of SOD, GSH-Px, CAT, and HO-1 at the mRNA level (P<0.05). In addition, enhanced SOD, GSH-Px, and CAT activities and HO-1 protein levels and decreased MDA content (P<0.05) were detected in the brain tissue of the Res-treated mice. The cytoplasmic Nrf2 content in the Res-treated mice was also decreased while the nuclear Nrf2 content and the nuclear translation rate of Nrf2 were increased (P<0.05). Res could decrease the expression of ERβ in the brain tissue at the mRNA and protein levels and the expression of Aβ in the brain tissue at the protein level. Res could also increase the mRNA and protein expression of ERα and ChAT and the protein expression of estradiol in the brain tissue. Conclusion. Res can increase the antioxidant capacity of AD models through the Nrf2/HO-1 signaling pathway. In addition, Res can enhance estrogen levels in an AD model. These findings provide a new idea for the treatment of AD.

Use of Melatonin to Promote Sleep in Older People

US Neurology ◽  
2012 ◽  
Vol 08 (01) ◽  
pp. 10
Author(s):  
Richard J Wurtman ◽  
Keyword(s):  
Side Effects ◽  
Older People ◽  
Low Dose ◽  
Sleep Onset ◽  
Melatonin Receptors ◽  
Older Americans ◽  
Exogenous Melatonin ◽  
Plasma Melatonin ◽  
Aging People ◽  
The Brain

Many older Americans purchase the hormone melatonin and take it orally, nightly, to promote sleep onset and to help them fall back asleep after the frequent nocturnal awakenings associated with aging. This need for exogenous melatonin reflects the fact that the progressive calcification of the human pineal diminishes the organ’s ability to secrete its hormone, so that instead of plasma melatonin levels rising normally by 10-fold or more around bedtime the rise may be only by twofold, or even less. The quantity of melatonin that most aging people need to restore nocturnal plasma melatonin levels to what they are in youth—and, concurrently, to promote sleep—is tiny, only about 0.2–0.5 mg. However, this dosage is generally unavailable, so patients may take doses 10-fold greater, or more, producing side-effects (e.g., hypothermia; hypoprolactinemia; morning grogginess) and ultimately desensitizing melatonin receptors in the brain. The reasons that low-dose melatonin is generally unavailable are described and a strategy is proposed for enabling patients to consume the correct dosage even when preparations containing that dosage cannot be obtained.

The Acute Effect of Alcohol on Various Memory Processes

2010 ◽  
Vol 24 (4) ◽  
pp. 249-252 ◽  
Author(s):  
Márk Molnár ◽  
Roland Boha ◽  
Balázs Czigler ◽  
Zsófia Anna Gaál
Keyword(s):  
Low Dose ◽  
Short Term Memory ◽  
Acute Effect ◽  
Long Term Memory ◽  
Term Memory ◽  
Memory Processes ◽  
Different Types ◽  
The Brain ◽  
Legal Consequences

This review surveys relevant and recent data of the pertinent literature regarding the acute effect of alcohol on various kinds of memory processes with special emphasis on working memory. The characteristics of different types of long-term memory (LTM) and short-term memory (STM) processes are summarized with an attempt to relate these to various structures in the brain. LTM is typically impaired by chronic alcohol intake but according to some data a single dose of ethanol may have long lasting effects if administered at a critically important age. The most commonly seen deleterious acute effect of alcohol to STM appears following large doses of ethanol in conditions of “binge drinking” causing the “blackout” phenomenon. However, with the application of various techniques and well-structured behavioral paradigms it is possible to detect, albeit occasionally, subtle changes of cognitive processes even as a result of a low dose of alcohol. These data may be important for the consideration of legal consequences of low-dose ethanol intake in conditions such as driving, etc.

C-fos Expression in the Brain Following Lithium Chloride Induced-Illness

2006 ◽  
Author(s):  
Katie M. Albanos ◽  
Steve Reilly ◽  
Justin R. St. Andre
Keyword(s):  
Lithium Chloride ◽  
Fos Expression ◽  
The Brain

CONTRACEPTION IN DIABETIC PATIENTS

1974 ◽  
Vol 77 (3_Suppl) ◽  
pp. S87-S94 ◽  
Author(s):  
J. Wiese ◽  
M. Osler
Keyword(s):  
Side Effects ◽  
Contraceptive Method ◽  
Low Dose ◽  
Unplanned Pregnancy ◽  
Intrauterine Device ◽  
Diabetic Patients ◽  
Intrauterine Contraception ◽  
Unwanted Pregnancies ◽  
Unreliable Method ◽  
Retrospective Investigation

ABSTRACT A retrospective investigation was made of contraception in diabetic women delivered in our department in 1969 and 1970. Seventy-nine (69 per cent) answered the questionnaires. About one third had found the contraceptive instruction insufficient. A shift from conventional to intrauterine contraception and sterilization was seen, but nearly 25% of the patients were still using conventional methods, mainly the condom. The patients consider this an unreliable method. Thirty-three patients were using intrauterine contraception. Although 10 of them had bleeding irregularities, all were satisfied with the method. Sterilization had been performed on 17 patients, all of whom were fully satisfied and had experienced no side effects. Four of 11 insulin-requiring diabetics, who have used combined oestrogen-progesterone medication have had difficulties in the regulation of the diabetes. Of 24 unwanted pregnancies 12 occurred since the hospitalization in 1969 and 1970. In diabetic women the contraceptive method should either be sterilization, intrauterine device or low dose progestagens, and only in a few cases conventional. A thorough contraceptive instruction as well as a close control of the diabetic women are of importance in order to avoid unplanned pregnancy. The best way to achieve this is by having an out-patient clinic in connection with the obstetrical department to supervise contraception in all diabetic women in the area.

Liposomes: Novel Drug Delivery Approach for Targeting Parkinson’s Disease

2020 ◽  
Vol 26 (37) ◽  
pp. 4721-4737 ◽  
Author(s):  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faheem H. Pottoo ◽  
Faizana Fayaz ◽  
Anjali Sharma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Neural Cells ◽  
Blood Brain ◽  
The Brain

Parkinson’s disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson’s disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson’s disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson’s disease.

Role of Quercetin in Mitigation of Lindane Induced Toxicity in Terms of Oxidative Responses and Metabolic Status in Mice Brain

2020 ◽  
Vol 16 ◽  
Author(s):  
Anupama Sharma ◽  
Renu Bist ◽  
Hemant Pareek
Keyword(s):  
Citrate Synthase ◽  
Thiobarbituric Acid ◽  
Tca Cycle ◽  
Treated Group ◽  
Protein Carbonyl ◽  
Protein Carbonyl Content ◽  
Mice Brain ◽  
The Brain ◽  
Oxidative Responses

Background:: Current study evaluated the protective potential of quercetin against lindane induced toxicity in mice brain. For investigation, mice were allocated into four groups; First group was control. Second group was administered with oral dose of lindane (25 mg/kg bw) for 4 consecutive days. Third group was exposed to quercetin (40 mg/kg bw) and in fourth group, quercetin was administered 1 hour prior to the exposure of lindane. Objective:: Two major objectives were decided for study. First was to create lesions in the brain by lindane and; second was to evaluate the neuroprotective potential of quercetin. Methods:: To study oxidative responses, level of thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC), reduced glutathione (GSH), superoxide dismutase (SOD), Catalase (CAT), and glutathione peroxidase (GPx) were measured in brain homogenates. Three key step regulating enzymes of tricarboxylic acid (TCA) cycle viz citrate synthase (CS), pyruvate dehydrogenase (PDH) and fumarase were also assayed. Results:: Lindane treatment significantly enhanced the levels of TBARS (P<0.001),PCC (P<0.001), GPx (P<0.001), SOD (P<0.05), PDH (P<0.05) and fumarase (P<0.001) in brains of mice compared to control. Meanwhile, it alleviated GSH, CAT and CS (P<0.05) activity. Conclusion:: Pretreatment with quercetin in lindane treated group not only restored, previously altered biochemical parameters after lindane treatment and also significantly improved them too which suggests that quercetin is not only invulnerable rather neuroprotective against lindane intoxication.

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