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Journal of Food and Drug Analysis Jun 2023Ashwagandha (Withania somnifera L. Dunal), an Indian medicinal plant that has been used for centuries to treat insomnia, exhibits a variety of biological activities,...
Ashwagandha (Withania somnifera L. Dunal), an Indian medicinal plant that has been used for centuries to treat insomnia, exhibits a variety of biological activities, such as improving cognitive function, immunity and anxiety. In this study, the effect of enzyme-treated Ashwagandha root extract (EA) and on sleep was evaluated using rodent models. Starch contained in the Ashwagandha root extract was removed by amylase treatment to prepare EA. To evaluate the sleep-promoting activity of EA, a pentobarbital-induced sleep test and electroencephalogram analysis were performed. In addition, the sleep-promoting mechanism of EA was elucidated by analyzing the expression of sleep-related receptors. In the pentobarbital-induced sleep test, EA dose-dependently increased sleep duration. Additionally, electroencephalogram analysis revealed that EA significantly increased δ-wave and non-rapid eye movement sleep times, which are involved in deep sleep, thereby improving sleep quality and quantity. EA also effectively relieved caffeine-induced insomnia symptoms. Furthermore, the γ-aminobutyric acid (GABA) content in the brain and mRNA and protein expression of GABA, GABA, and serotonin receptors were significantly increased by EA compared to the normal group. In particular, EA showed sleep-promoting activity by binding to various GABAA receptor sites. Collectively, EA exhibited sleep-promoting activity through the GABAergic system and may be used as a functional material to improve sleep deprivation.
Topics: Receptors, GABA; Withania; Sleep Initiation and Maintenance Disorders; Pentobarbital; Amylases; Plant Extracts; Sleep; gamma-Aminobutyric Acid
PubMed: 37335157
DOI: 10.38212/2224-6614.3456 -
Journal of Controlled Release :... Apr 2021Focused ultrasound (FUS) offers an attractive tool for non-invasive neuromodulation, addressing a clinical need to develop more minimally invasive approaches that are...
Focused ultrasound (FUS) offers an attractive tool for non-invasive neuromodulation, addressing a clinical need to develop more minimally invasive approaches that are safer, more tolerable and versatile. In combination with a cavitation agent, the effects of ultrasound can be amplified and localized for therapy. Using c-Fos expression mapping, we show how ultrasound-sensitive nanodroplets can be used to induce either neurosuppression or neurostimulation, without disrupting the blood-brain barrier in rats. By repurposing a commercial ultrasound contrast agent, Definity, lipid-shell decafluorobutane-core nanodroplets of 212.5 ± 2.0 nm were fabricated and loaded with or without pentobarbital. FUS was delivered with an atlas-based targeting system at 1.66 MHz to the motor cortex of rats, using a feedback-controller to detect successful nanodroplet vaporization and drug release. Neuromodulation was quantified through changes in sensorimotor function and c-Fos expression. Following FUS-triggered delivery, sham nanodroplets induced a 22.6 ± 21% increase in local c-Fos expression, whereas pentobarbital-loaded nanodroplets induced a 21.7 ± 13% decrease (n = 6). Nanodroplets, combined with FUS, offer an adaptable tool for neuromodulation, through local delivery of small molecule anesthetics or targeted mechanical effects.
Topics: Animals; Blood-Brain Barrier; Contrast Media; Drug Delivery Systems; Drug Liberation; Pentobarbital; Rats; Ultrasonography
PubMed: 33600879
DOI: 10.1016/j.jconrel.2021.02.010 -
Molecules (Basel, Switzerland) Apr 2023Neophytadiene (NPT) is a diterpene found in the methanolic extracts of and , plants reported with anxiolytic-like activity, sedative properties, and antidepressant-like...
Neophytadiene (NPT) is a diterpene found in the methanolic extracts of and , plants reported with anxiolytic-like activity, sedative properties, and antidepressant-like actions; however, the contribution of neophytadiene to these effects is unknown. This study determined the neuropharmacological (anxiolytic-like, antidepressant-like, anticonvulsant, and sedative) effects of neophytadiene (0.1-10 mg/kg p.o.) and determined the mechanisms of action involved in the neuropharmacological actions using inhibitors such as flumazenil and analyzing the possible interaction of neophytadiene with GABA receptors using a molecular docking study. The behavioral tests were evaluated using the light-dark box, elevated plus-maze, open field, hole-board, convulsion, tail suspension, pentobarbital-induced sleeping, and rotarod. The results showed that neophytadiene exhibited anxiolytic-like activity only to the high dose (10 mg/kg) in the elevated plus-maze and hole-board tests, and anticonvulsant actions in the 4-aminopyridine and pentylenetetrazole-induced seizures test. The anxiolytic-like and anticonvulsant effects of neophytadiene were abolished with the pre-treatment with 2 mg/kg flumazenil. In addition, neophytadiene showed low antidepressant effects (about 3-fold lower) compared to fluoxetine. On other hand, neophytadiene had no sedative or locomotor effects. In conclusion, neophytadiene exerts anxiolytic-like and anticonvulsant activities with the probable participation of the GABAergic system.
Topics: Animals; Anti-Anxiety Agents; Anticonvulsants; Flumazenil; Molecular Docking Simulation; Hypnotics and Sedatives; Seizures; Plant Extracts; Antidepressive Agents; Behavior, Animal
PubMed: 37110691
DOI: 10.3390/molecules28083457 -
Methods in Molecular Biology (Clifton,... 2024In the method described here, an aliquot of a urine sample is analyzed to detect barbiturates through dilution and ultra-high-performance chromatography-tandem mass...
In the method described here, an aliquot of a urine sample is analyzed to detect barbiturates through dilution and ultra-high-performance chromatography-tandem mass spectrometry (UPLC-MS/MS) using deuterated internal standards. This assay detects the presence of nine barbiturate drugs-amobarbital, barbital, butalbital, butabarbital, mephobarbital, secobarbital, pentobarbital, phenobarbital, and thiopental. This protocol describes two LC separation methods-first LC method (2.2 min/sample) is intended to be used as a first step of the analysis that does not separate amobarbital and pentobarbital, and a second, longer (2.7 min/sample) LC method is intended to be used only for samples which have a peak in the amobarbital/pentobarbital retention time on the shorter LC method. Since the frequency at which amobarbital and pentobarbital are observed in clinical populations is low, the shorter LC method helps gain efficiency in a high-volume laboratory environment. Additional features of this protocol that help in efficiency gain are automated extraction using Hamilton™ liquid handling system and algorithmic data review using Ascent™ software.
Topics: Pentobarbital; Amobarbital; Chromatography, Liquid; Tandem Mass Spectrometry; Barbiturates
PubMed: 38036812
DOI: 10.1007/978-1-0716-3541-4_8 -
Journal of Equine Veterinary Science Jul 2022Recent changes in rendering availability for chemically-euthanized animals have created a need to explore composting as an equine mortality management method. The...
Recent changes in rendering availability for chemically-euthanized animals have created a need to explore composting as an equine mortality management method. The objectives of this study were to evaluate equine mortality composting in the Upper Midwest during fall and spring, document sodium pentobarbital concentrations throughout the process, and determine nutrient content of finished compost. During each season, four horses were euthanized by intravenous administration of sodium pentobarbital. Carcasses were positioned at the center of a woodchip and shavings base and covered with a 2:1 mixture of horse stall waste and cattle feedlot waste. Data loggers were placed at 46- and 91cm depths to record pile temperatures every 8 hours. At turning (44-50 days) and trial conclusion (181-216 days), compost piles were sampled for sodium pentobarbital and nutrient composition. Piles contained large bones after 6 months of composting. Sodium pentobarbital remained detectable at trial conclusion (<0.002-1.49 mg kg dry matter); however, composting reduced the estimated quantities of sodium pentobarbital by ≥94% (P ≤ .001). Compost from each season met ideal land application values for organic matter (45%-48%), pH (7.3-7.6), and electrical conductivity (3.3-3.4 mm hos cm). Low NPK and high C:N ratio (20-30) indicate compost could partially replace synthetic fertilizers when land applied. These findings suggest equine mortality composting is an effective management practice during fall and spring in the Upper Midwest. While remaining sodium pentobarbital residues were minimal, further research is needed to determine environmental implications of composting chemically-euthanized equines.
Topics: Animals; Composting; Euthanasia, Animal; Horses; Midwestern United States; Pentobarbital
PubMed: 35490974
DOI: 10.1016/j.jevs.2022.104000 -
Legal Medicine (Tokyo, Japan) Nov 2021A study was undertaken of 51 cases where barbiturates were detected in post-mortem blood samples from 2000 to 2019 at Forensic Science South Australia, Adelaide,... (Review)
Review
A study was undertaken of 51 cases where barbiturates were detected in post-mortem blood samples from 2000 to 2019 at Forensic Science South Australia, Adelaide, Australia. The cause of death was drug toxicity in only 27 (53%) (M:F = 19:8; age range 19-74yrs, mean 46yrs). In 17 cases, barbiturate toxicity was the primary cause of death, 14 due to pentobarbitone and 3 to phenobarbitone. All were suicides. Barbiturates were obtained by online purchase from overseas sources in 9 cases (33%), and through veterinary practice in 2 cases (7%). Drug toxicity deaths where barbiturates were detected rose from 1 in 2000-2004 to 11 in 2015-2019, and those where deaths were primarily due to barbiturate toxicity rose from 1 in 2000-2004 to 9 in 2015-2019. However, the mere detection of barbiturates in post mortem samples did not equate with illicit use, as 23 of the deaths (45%) were due to natural causes in individuals prescribed barbiturates for epilepsy. The usefulness of examining subset populations separate from accrued national data is also demonstrated in the significantly younger age of decedents in South Australia dying from deliberately administered barbiturates (46 yrs) compared to the national average of 57.9 yrs. The reasons for this difference will require further investigation as this may impact upon local suicide prevention strategies.
Topics: Adult; Aged; Australia; Barbiturates; Humans; Middle Aged; Pentobarbital; Suicide; Young Adult
PubMed: 34119997
DOI: 10.1016/j.legalmed.2021.101928 -
Pediatrics May 2020Pediatric subspecialists routinely provide procedural sedation outside the operating room. No large study has reported trends in outpatient pediatric procedural... (Observational Study)
Observational Study
BACKGROUND
Pediatric subspecialists routinely provide procedural sedation outside the operating room. No large study has reported trends in outpatient pediatric procedural sedation. Our purpose in this study was to identify significant trends in outpatient procedural sedation using the Pediatric Sedation Research Consortium.
METHODS
Prospectively collected data from 2007 to 2018 were used for trending procedural sedation. Patient characteristics, medications, type of providers, serious adverse events, and interventions were reported. The Cochran-Armitage test for trend was used to explore the association between the year and a given characteristic.
RESULTS
A total of 432 842 sedation encounters were identified and divided into 3 4-year epochs (2007-2011, 2011-2014, and 2014-2018). There was a significant decrease in infants <3 months of age receiving procedural sedation (odds ratio = 0.97; 95% confidence interval, 0.96-0.98). A large increase was noticed in pediatric hospitalists providing procedural sedation (0.6%-9.5%; < .001); there was a decreasing trend in sedation by other providers who were not in emergency medicine, critical care, or anesthesiology (13.9%-3.9%; < .001). There was an increasing trend in the use of dexmedetomidine (6.3%-9.3%; < .001) and a decreasing trend in the use of chloral hydrate (6.3%-0.01%; < .001) and pentobarbital (7.3%-0.5%; < .001). Serious adverse events showed a nonsignificant increase overall (1.35%-1.75%).
CONCLUSIONS
We report an increase in pediatric hospitalists providing sedation and a significant decrease in the use of chloral hydrate and pentobarbital by providers. Further studies are required to see if sedation services decrease costs and optimize resource use.
Topics: Adolescent; Ambulatory Surgical Procedures; Anesthesia; Child; Child, Preschool; Cohort Studies; Conscious Sedation; Female; Humans; Hypnotics and Sedatives; Infant; Male; Outpatients; Pediatrics; Prospective Studies
PubMed: 32332053
DOI: 10.1542/peds.2019-3559 -
European Journal of Clinical... Oct 2022Management and dose adjustment are a major concern for clinicians in the absence of specific clinical outcome data for patients on antiepileptic drugs (AEDs), in the... (Review)
Review
Management and dose adjustment are a major concern for clinicians in the absence of specific clinical outcome data for patients on antiepileptic drugs (AEDs), in the event of short-term (5 days) nirmatrelvir/ritonavir co-exposure. Therefore, in this report, we identified drugs that require dose adjustment because of drug-drug interactions (DDIs) between nirmatrelvir/ritonavir and AEDs. We hereby used four databases (Micromedex Drug Interaction, Liverpool Drug Interaction Group for COVID-19 Therapies, Medscape Drug Interaction Checker, and Lexicomp Drug Interactions) and DDI-Predictor.In the light of applying the DDI-Predictor, for carbamazepine, clobazam, oxcarbazepine, eslicarbazepine, phenytoin, phenobarbital, pentobarbital, rufinamide, and valproate as CYP3A4 inducers, we recommend that a dose adjustment of short-term nirmatrelvir/ritonavir as a substrate (victim) drug would be more appropriate instead of these AEDs to avoid impending DDI-related threats in patients with epilepsy.
Topics: Anticonvulsants; Carbamazepine; Clobazam; Cytochrome P-450 CYP3A Inducers; Drug Interactions; Humans; Oxcarbazepine; Pentobarbital; Phenobarbital; Phenytoin; Ritonavir; Valproic Acid; COVID-19 Drug Treatment
PubMed: 35930055
DOI: 10.1007/s00228-022-03370-7 -
Journal of the American Veterinary... May 2023Sodium pentobarbital and pentobarbital combination products are commonly used by veterinarians throughout the US for euthanasia of their animal patients. The AVMA... (Review)
Review
A literature review on current practices, knowledge, and viewpoints on pentobarbital euthanasia performed by veterinarians and animal remains disposal in the United States.
Sodium pentobarbital and pentobarbital combination products are commonly used by veterinarians throughout the US for euthanasia of their animal patients. The AVMA Guidelines for the Euthanasia of Animals: 2020 Edition lists barbiturate acid derivatives (pentobarbital) and pentobarbital combination products as an acceptable method of euthanasia for all species when circumstances permit their use. When using pentobarbital products, a veterinarian must consider appropriate handling and disposal of animal remains to avoid the potential for environmental contamination, relay toxicosis in wildlife or domestic animals, and contamination of the animal food supply. Failure to appropriately consider these facets of pentobarbital euthanasia can result in legal and ethical consequences. Despite these concerns, to the authors' knowledge no comprehensive literature review has been published concerning pentobarbital euthanasia or handling and disposal of animal remains following pentobarbital euthanasia. The literature review that follows aims to give a descriptive narrative of the most recent information available on the knowledge, use, challenges, and issues surrounding pentobarbital euthanasia and disposal of animal remains within the US.
Topics: Animals; United States; Humans; Pentobarbital; Veterinarians; Body Remains; Euthanasia, Animal; Animals, Domestic
PubMed: 36800298
DOI: 10.2460/javma.22.08.0373 -
Legal Medicine (Tokyo, Japan) Nov 2022Suicides by pentobarbital overdose have increased since about 2012, which appear to be influenced by technical information on active euthanasia that has spread over the...
Suicides by pentobarbital overdose have increased since about 2012, which appear to be influenced by technical information on active euthanasia that has spread over the Internet. We encountered a pentobarbital poisoning case of a patient with amyotrophic lateral sclerosis. A caregiver found the patient unconscious immediately after two visitors left the room. The patient was immediately transferred to the emergency hospital but eventually declared dead. A fatal concentration of pentobarbital was detected in peripheral blood samples collected in the emergency hospital and during autopsy (53.8 μg/mL and 29.4 μg/mL, respectively). Because the ratios of pentobarbital concentrations between the gastric contents and peripheral blood were 35 and 29 in the hospital and autopsy samples, respectively, it is likely that pentobarbital was administered via the gastrostomy tube. The patient had contacted the visitors through social media. Although the patient had requested the doctor perform active euthanasia and expressed a desire to end their life on social media, nobody had noticed the plan to commit suicide.
Topics: Humans; Pentobarbital; Suicide; Drug Overdose; Gastrointestinal Contents
PubMed: 36166973
DOI: 10.1016/j.legalmed.2022.102149