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Journal of Biological Rhythms Aug 2014The circadian clock generates daily cycles of gene expression that regulate physiological processes. The liver plays an important role in xenobiotic metabolism and also...
The circadian clock generates daily cycles of gene expression that regulate physiological processes. The liver plays an important role in xenobiotic metabolism and also has been shown to possess its own cell-based clock. The liver clock is synchronized by the master clock in the brain, and a portion of rhythmic gene expression can be driven by behavior of the organism as a whole even when the hepatic clock is suppressed. So far, however, there is relatively little evidence indicating whether the liver clock is functionally important in modulating xenobiotic metabolism. Thus, mice lacking circadian clock function in the whole body or specifically in liver were challenged with pentobarbital and acetaminophen, and pentobarbital sleep time (PBST) and acetaminophen toxicity, respectively, was assessed at different times of day in mutant and control mice. The results suggest that the liver clock is essential for rhythmic changes in xenobiotic detoxification. Surprisingly, it seems that the way in which the clock is disrupted determines the rate of xenobiotic metabolism in the liver. CLOCK-deficient mice are remarkably resistant to acetaminophen and exhibit a longer PBST, while PERIOD-deficient mice have a short PBST. These results indicate an essential role of the tissue-intrinsic peripheral circadian oscillator in the liver in regulating xenobiotic metabolism.
Topics: Acetaminophen; Animals; Circadian Clocks; Circadian Rhythm; Gene Expression; Liver; Male; Mice; Mice, Inbred C57BL; Pentobarbital; Periodicity; Xenobiotics
PubMed: 25238856
DOI: 10.1177/0748730414544740 -
Journal of Neurotrauma Jan 2019Treatment of severe traumatic brain injury (TBI) in the intensive care unit focuses on controlling intracranial pressure, ensuring sufficient cerebral perfusion, and... (Comparative Study)
Comparative Study Observational Study
Treatment of severe traumatic brain injury (TBI) in the intensive care unit focuses on controlling intracranial pressure, ensuring sufficient cerebral perfusion, and monitoring for secondary injuries. However, there are limited prognostic tools and no biomarkers or tests of the evolving neuropathology. Metabolomics has the potential to be a powerful tool to indirectly monitor evolving dysfunctional metabolism. We compared metabolite levels in simultaneously collected arterial and jugular venous samples in acute TBI patients undergoing intensive care as well as in healthy control volunteers. Our results show that, first, many circulating metabolites are decreased in TBI patients compared with healthy controls days after injury; both proline and hydroxyproline were depleted by ≥60% compared with healthy controls, as was gluconate. Second, both arterial and jugular venous plasma metabolomic analysis separates TBI patients from healthy controls and shows that distinct combinations of metabolites are driving the group separation in the two blood types. Third, TBI patients under heavy sedation with pentobarbital at the time of blood collection were discernibly different from patients not receiving pentobarbital. These results highlight the importance of accounting for medications in metabolomics analysis. Jugular venous plasma metabolomics shows potential as a minimally invasive tool to identify and study dysfunctional cerebral metabolism after TBI.
Topics: Adolescent; Adult; Aged; Biomarkers; Brain Injuries, Traumatic; Cohort Studies; Female; Humans; Hypnotics and Sedatives; Jugular Veins; Male; Metabolomics; Middle Aged; Pentobarbital; Young Adult
PubMed: 29901425
DOI: 10.1089/neu.2018.5674 -
Biological & Pharmaceutical Bulletin 2014The effects of inhalation anesthesia (2% isoflurane, sevoflurane, or enflurane) and intraperitoneal anesthesia with pentobarbital (65 mg/kg) were compared in rats... (Comparative Study)
Comparative Study
The effects of inhalation anesthesia (2% isoflurane, sevoflurane, or enflurane) and intraperitoneal anesthesia with pentobarbital (65 mg/kg) were compared in rats using an electrocardiogram (ECG) and determination of blood oxygen saturation (SPO2) levels. Following inhalation anesthesia, heart rate (HR) and SPO2 were acceptable while pentobarbital anesthesia decreased HR and SPO2 significantly. This indicates that inhalation anesthesia is more preferable than pentobarbital anesthesia when evaluating cardiovascular factors. Additionally, pentobarbital significantly increased HR variability (HRV), suggesting a regulatory effect of pentobarbital on the autonomic nervous system, and resulted in a decreased response of the baro-reflex system. Propranolol or atropine had limited effects on ECG recording following pentobarbital anesthesia. Taken together, these data suggest that inhalation anesthesia is suitable for conducting hemodynamic analyses in the rat.
Topics: Administration, Inhalation; Anesthesia, Inhalation; Animals; Atropine; Blood Pressure; Electrocardiography; Enflurane; Heart Rate; Hemodynamics; Injections, Intraperitoneal; Isoflurane; Male; Methyl Ethers; Oxygen; Pentobarbital; Propranolol; Rats; Sevoflurane
PubMed: 24790005
DOI: 10.1248/bpb.b14-00012 -
Psychopharmacology 1980Pigeons were trained to discriminate the IM injection of pentobarbital (5 or 10 mg/kg) from saline in a task in which 20 consecutive pecks on one of two response keys...
Pigeons were trained to discriminate the IM injection of pentobarbital (5 or 10 mg/kg) from saline in a task in which 20 consecutive pecks on one of two response keys produced access to mixed grain. Pentobarbital (1.0--17.8 mg/kg) produced a dose-related increase in the percentage of the total session responses that occurred on the pentobarbital-appropriate key. The concomitant administration of bemegride (5.6--17.8 mg/kg) antagonized the discriminative control of behavior exerted by the training dose of pentobarbital. Benzodiazepines, diazepam (1.0 mg/kg) and clobazam (3.2 mg/kg), and barbiturates, methohexital (10 mg/kg), phenobarbital (56 mg/kg), and barbital (56 mg/kg), produced responding on the pentobarbital-appropriate key similar to that produced by pentobarbital. In contrast, narcotics such as morphine, ethylketazocine, cyclazocine, and SKF-10,047, at doses up to and including those that markedly suppressed response rates, produced responding predominantly on the saline-appropriate key. Similarly, the anticonvulsants, valproate, phenytoin, and ethosuximide occasioned only saline-appropriate behavior, indicating that not all anticonvulsants share discriminative stimulus effects with pentobarbital. Muscimol, a direct GABA agonist, and baclofen, a structural analogue of GABA, also failed to produce pentobarbital-appropriate responding. Ketamine, dextrorphan, and ethanol (0.3--3.2 g/kg, orally) produced intermediate levels of pentobarbital-appropriate responding, suggesting that the discriminative effects of these drugs may be somewhat like those of pentobarbital.
Topics: Animals; Baclofen; Bemegride; Columbidae; Ethanol; Muscimol; Pentobarbital; Prejudice; gamma-Aminobutyric Acid
PubMed: 6779321
DOI: 10.1007/BF00433247 -
American Journal of Veterinary Research Nov 2021To determine whether intrarenal injection of sodium pentobarbital is a viable method for euthanasia in anesthetized client-owned cats and assess potential factors...
OBJECTIVE
To determine whether intrarenal injection of sodium pentobarbital is a viable method for euthanasia in anesthetized client-owned cats and assess potential factors associated with time to cardiopulmonary arrest (TCPA) for such treated cats.
ANIMALS
131 client-owned cats.
PROCEDURES
In this retrospective study, client-owned cats presented for euthanasia between March 1, 2009, and January 15, 2010, were evaluated by veterinarians to determine suitability of intrarenal injection versus other methods of euthanasia. Cats included were anesthetized and then received 6 mL of sodium pentobarbital (390 mg/mL) by intrarenal injection. Results for TCPA were compared for cats grouped on the basis of variables of interest.
RESULTS
131 cats were included, of which 74 (79%) had a TCPA < 1 minute and 28 (21%) had a TCPA between 1.5 and 8 minutes after intrarenal injection. Most (124/131 [95%]) cats had no observable reaction to the intrarenal injection other than cardiopulmonary arrest. Median TCPA was longer for cats without (1 min; 25/131 [19%]) versus with (0 min; 106/131 [81%]) palpable kidney swelling upon injection.
CLINICAL RELEVANCE
The effects of intrarenal injection of sodium pentobarbital in cats of the present study were similar to those typically observed with IV administration of euthanasia solution. When this intrarenal injection method is used, cardiopulmonary arrest with few agonal reactions can be expected to occur quickly in most patients. The intrarenal injection method is suited for euthanasia of anesthetized cats with easily located kidneys when IV access may be difficult.
Topics: Animals; Cats; Euthanasia, Animal; Injections; Pentobarbital; Retrospective Studies; Sodium
PubMed: 34757922
DOI: 10.2460/ajvr.21.08.0123 -
Theranostics 2020: Targeted neuromodulation is a valuable technique for the study and treatment of the brain. Using focused ultrasound to target the local delivery of anesthetics in the...
: Targeted neuromodulation is a valuable technique for the study and treatment of the brain. Using focused ultrasound to target the local delivery of anesthetics in the brain offers a safe and reproducible option for suppressing neuronal activity. : To develop a potential new tool for localized neuromodulation through the triggered release of pentobarbital from ultrasound-responsive nanodroplets. : The commercial microbubble contrast agent, Definity, was filled with decafluorobutane gas and loaded with a lipophilic anesthetic drug, before being condensed into liquid-filled nanodroplets of 210 ± 80 nm. Focused ultrasound at 0.58 MHz was found to convert nanodroplets into microbubbles, simultaneously releasing the drug and inducing local anesthesia in the motor cortex of rats (n=8). : Behavioral analysis indicated a 19.1 ± 13% motor deficit on the contralateral side of treated animals, assessed through the cylinder test and gait analysis, illustrating successful local anesthesia, without compromising the blood-brain barrier. : Pentobarbital-loaded decafluorobutane-core Definity-based nanodroplets are a potential agent for ultrasound-triggered and targeted neuromodulation.
Topics: Anesthesia; Animals; Drug Delivery Systems; Fluorocarbons; Hypnotics and Sedatives; Male; Microbubbles; Nanoparticles; Pentobarbital; Rats; Rats, Sprague-Dawley; Ultrasonography
PubMed: 32194839
DOI: 10.7150/thno.41566 -
Experimental Animals 2012Pentobarbital (PB) and ketamine (Ket) influence the concentration of neurotransmitters in the brain. PB has been reported to decrease the extracellular nitric oxide (NO)...
Pentobarbital (PB) and ketamine (Ket) influence the concentration of neurotransmitters in the brain. PB has been reported to decrease the extracellular nitric oxide (NO) concentration through a decrease in acetylcholine (ACh) release, while Ket has been shown to increase the NO concentration via an increase in ACh release. Here, we investigated effects of PB and Ket on NO release and the relationship between NO and ACh in the rat striatum by in vivo microdialysis experiments. Male Sprague-Dawley rats were used. A microdialysis probe was inserted into the right striatum and perfused with modified Ringer's solution. Samples were collected every 15 min and injected into an HPLC system. The rats were freely moving, and PB and Ket were administered intraperitoneally. Neostigmine (1 and 10 µM) and mecamylamine (100 µM) were added to the perfusate. Calcium and magnesium concentrations were modified for each anesthetic to influence ACh release. PB decreased NO products (NOx) while Ket increased them. While perfusion with neostigmine showed no effect on baseline NOx concentrations, it diminished the PB-induced NOx reduction at low concentrations and abolished it at high concentrations. Magnesium-free perfusion had no effect on baseline NOx concentrations, whereas perfusion at a low magnesium concentration antagonized the PB-induced NOx reduction. Mecamylamine and calcium-free perfusion had no effect on baseline NOx concentrations and Ket-induced NOx increases. PB may decrease NO release through reduction in ACh release, whereas Ket may increase NO release independent of ACh regulation.
Topics: Acetylcholine; Animals; Cholinergic Neurons; Chromatography, High Pressure Liquid; Corpus Striatum; Excitatory Amino Acid Antagonists; Hypnotics and Sedatives; Injections, Intraperitoneal; Ketamine; Male; Mecamylamine; Microdialysis; Neostigmine; Nicotinic Antagonists; Nitric Oxide; Parasympathomimetics; Pentobarbital; Rats; Rats, Sprague-Dawley
PubMed: 22531732
DOI: 10.1538/expanim.61.165 -
Journal of the American Association For... Jan 2018All currently accepted methods of euthanasia for laboratory mice involve some degree of stress, fear, anxiety, or pain. We evaluated the voluntary oral administration of...
All currently accepted methods of euthanasia for laboratory mice involve some degree of stress, fear, anxiety, or pain. We evaluated the voluntary oral administration of a euthanasia drug in 99 male and 81 female mice of various strains. We first explored the palatability of sugar-cookie dough with various flavorings added. We placed the cookie dough in the cage with an adult mouse and recorded the amount ingested after 1 h. Mice readily ingested all flavors of sugar-cookie dough. We then added a euthanasia solution containing pentobarbital and phenytoin to all flavors of cookie dough and placed a small bolus in the cage of each mouse or mouse pair. We observed the mice for 1 h for clinical signs of pentobarbital intoxication and then weighed uneaten dough to determine the dose of pentobarbital ingested. Palatability declined sharply when euthanasia solution was present. Mice ingested higher doses of pentobarbital in cookie dough during the dark phase and after fasting. Ingestion caused ataxia in some mice but was not sufficient to cause loss of righting reflex, unconsciousness, or death in any mouse. We successfully identified sugar cookie dough as a drug vehicle that was readily and rapidly eaten by mice without the need for previous exposure. Additional research is needed to identify euthanasia compounds for mice that do not affect the palatability of cookie dough.
Topics: Administration, Oral; Animals; Euthanasia, Animal; Female; Laboratory Animal Science; Male; Mice; Pain; Pentobarbital; Phenytoin
PubMed: 29402349
DOI: No ID Found -
Biochimica Et Biophysica Acta Sep 2016We study how zwitterionic and anionic biomembrane models interact with neurotransmitters (NTs) and anesthetics (ATs) in the presence of Ca(2+) and different pH...
We study how zwitterionic and anionic biomembrane models interact with neurotransmitters (NTs) and anesthetics (ATs) in the presence of Ca(2+) and different pH conditions. As NTs we used acetylcholine (ACh), γ-aminobutyric acid (GABA), and l-glutamic acid (LGlu). As ATs, tetracaine (TC), and pentobarbital (PB) were employed. By using differential scanning calorimetry (DSC), we analyzed the changes such molecules produce in the thermal properties of the membranes. We found that calcium and pH play important roles in the interactions of NTs and ATs with the anionic lipid membranes. Changes in pH promote deprotonation of the phosphate groups in anionic phospholipids inducing electrostatic interactions between them and NTs; but if Ca(2+) ions are in the system, these act as bridges. Such interactions impact the physical properties of the membranes in a similar manner that anesthetics do. Beyond the usual biochemical approach, we claim that these effects should be taken into account to understand the excitatory-inhibitory orchestrated balance in the nervous system.
Topics: Acetylcholine; Anesthetics; Calcium; Glutamic Acid; Hydrogen-Ion Concentration; Membranes, Artificial; Neurotransmitter Agents; Pentobarbital; Protons; Tetracaine; gamma-Aminobutyric Acid
PubMed: 27362370
DOI: 10.1016/j.bbamem.2016.06.017 -
Anesthesiology Mar 1975Regional and cellular distribution of pentobarbital-14C in mouse brain was determined by frozen-section radioautographic methods. The mice were studied at the times of...
Regional and cellular distribution of pentobarbital-14C in mouse brain was determined by frozen-section radioautographic methods. The mice were studied at the times of loss (WRL) and return (WRR) of withdrawal response following a single intravenous dose of either 40 or 50 mg/kg body weight. At WRL, grey matter areas had higher concentrations of pentobarbital-2-14C than white matter. At WRR grey matter concentrations were not altered, but white matter areas were now similar to the grey. At WRL pentobarbital concentration was 55 per cent higher in large pyramidal cells in the parietal cortex than in surrounding neuropil. At WRL hippocampal pyramidal cell bodies (stratum pyramidalis) and glial cells in corpus callosum had pentobarbital levels similar to that of surrounding neuropil. Levels in the neuropil of these three areas were higher at WRR than at WRL. Lipid-rich compartments had higher pentobarbital concentrations at WRR than at WRL. The results suggest that return of consciousness after pentobarbital anesthesia is associated with intracerebral redistribution of pentobarbital even while there is continuing uptake into brain. (Key words: Brain, pentobarbital uptake; hypnotics, barbiturates, pentobarbital; pharmacokinetics, pentobarbital uptake.).
Topics: Absorptiometry, Photon; Animals; Autoradiography; Brain; Carbon Radioisotopes; Cerebral Cortex; Cerebrovascular Circulation; Corpus Callosum; Frozen Sections; Histocytochemistry; Male; Methylene Blue; Mice; Pentobarbital; Photomicrography; Staining and Labeling; Thalamus; Time Factors
PubMed: 46726
DOI: 10.1097/00000542-197503000-00005