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International Journal of Experimental... Feb 2021This study aims to compare the influence of different anaesthesia methods on the mechanisms involved in the development of hepatoblastoma (HB). HB rabbit models were...
This study aims to compare the influence of different anaesthesia methods on the mechanisms involved in the development of hepatoblastoma (HB). HB rabbit models were constructed and divided into three groups: disoprofol, pentobarbital sodium and HB groups. After anaesthesia, rabbit blood was collected from the tail vein. Haematological analysis (platelets) and an ELISA was used to measure the thrombopoietin (TPO) and 5-hydroxytryptamine (5-HT). Flow cytometry was used to determine expression of P-selectin and PAF. The expression of 5-HTR2B, PCNA, vWF, P70s6k, 4E-BP1, mTOR and FRAP was determined in the tumour itself or in vascular tissues obtained from the rabbits. The platelet content in the disoprofol group. The content or expression of TPO, 5-HT, P-selectin, PAF, 5-HTR2B, PCNA, vWF, P70s6k, 4E-BP1, mTOR and FRAP was significantly higher in the disoprofol group compared to pentobarbital sodium and HB groups. Expression of these molecules was much higher in the pentobarbital sodium group compared with the HB group. These findings suggest that disoprofol anaesthesia can promote HB development via the mTOR/p70S6K1 and FRAP signalling pathway.
Topics: Animals; Hepatoblastoma; Hypnotics and Sedatives; Liver Neoplasms; Pentobarbital; Platelet Activation; Propofol; Rabbits; Signal Transduction
PubMed: 33410572
DOI: 10.1111/iep.12378 -
International Journal of Surgery Case... 2020Intracranial hypertension that is not responsive to other therapies can be managed through the use of a barbiturate induced coma. Although potentially effective, there...
INTRODUCTION
Intracranial hypertension that is not responsive to other therapies can be managed through the use of a barbiturate induced coma. Although potentially effective, there are known complications associated with this treatment, and as such it is typically reserved for the most severe cases. One such sequela of barbiturate induced coma therapy is refractory hypokalemia and subsequent rebound hyperkalemia.
PRESENTATION OF CASE
This case report discusses a patient who experienced hypokalemia during pentobarbital induced coma for unmanageable elevations in intracranial pressure and was treated conservatively to avoid rebound hyperkalemia depicting successful deployment of permissive hypokalemia.
DISCUSSION
It is vital that clinicians understand the possible adverse effects associated with barbiturate induced coma therapy, and that a careful balance be struck between hypokalemia and potassium supplementation to avoid rebound hyperkalemia.
CONCLUSION
Given that the risk of rebound hyperkalemia is of significant concern in patients who experience hypokalemia on barbiturate induced coma therapy, permissive hypokalemia can be a viable treatment option achieved by lowering the potassium replacement target threshold in such patients.
PubMed: 32492644
DOI: 10.1016/j.ijscr.2020.05.032 -
PloS One 2020Microglia, the resident immune cells of the brain, are highly ramified and motile and their morphology is strongly linked to their function. Microglia constantly monitor...
Microglia, the resident immune cells of the brain, are highly ramified and motile and their morphology is strongly linked to their function. Microglia constantly monitor the brain parenchyma and are crucial for maintaining brain homeostasis and fine-tuning neuronal networks. Besides affecting neurons, anesthetics may have wide-ranging effects mediated by non-neuronal cells and in particular microglia. We thus examined the effect of two commonly used anesthetic agents, ketamine/xylazine and barbiturates, on microglial motility and morphology. A combination of two-photon in vivo imaging and electroencephalography (EEG) recordings in unanesthetized and anesthetized mice as well as automated analysis of ex vivo sections were used to assess morphology and dynamics of microglia. We found that administration of ketamine/xylazine and pentobarbital anesthesia resulted in quite distinct EEG profiles. Both anesthetics reduced microglial motility, but only ketamine/xylazine administration led to reduction of microglial complexity in vivo. The change of cellular dynamics in vivo was associated with a region-dependent reduction of several features of microglial cells ex vivo, such as the complexity index and the ramification length, whereas thiopental altered the size of the cytoplasm. Our results show that anesthetics have considerable effects on neuronal activity and microglial morphodynamics and that barbiturates may be a preferred anesthetic agent for the study of microglial morphology. These findings will undoubtedly raise compelling questions about the functional relevance of anesthetics on microglial cells in neuronal physiology and anesthesia-induced neurotoxicity.
Topics: Anesthetics; Animals; Cell Movement; GABA Modulators; Ketamine; Male; Mice; Mice, Transgenic; Microglia; Pentobarbital; Receptors, N-Methyl-D-Aspartate; Thiopental; Xylazine
PubMed: 32760073
DOI: 10.1371/journal.pone.0236594 -
Respiratory Physiology & Neurobiology Jan 2021The study investigates the effects of 6 occlusion conditions on the mechanically induced cough reflex in 15 anesthetized (pentobarbital) spontaneously breathing cats...
The study investigates the effects of 6 occlusion conditions on the mechanically induced cough reflex in 15 anesthetized (pentobarbital) spontaneously breathing cats (14♂, 1♀). Esophageal pressure and integrated EMG activities of inspiratory (I) diaphragm and expiratory (E) abdominal muscles were recorded and analyzed. Occlusions: inspiratory (Io), continual I (cIo), during I and active E (I+Eo) cough phase, during I and then E phase with short releasing of airflow before each phase (I-Eo), and E occlusion (Eo) had little influence on cough number. Only continual E occlusion (cEo) reduced the number of coughs by 19 % (to 81 %, p < 0.05). Cough I esophageal pressure reached higher amplitudes under all conditions, but only Eo caused increased I diaphragm motor drive (p < 0.05). Cough E efforts (abdominal motor drive and E amplitudes of esophageal pressure) increased during Eo, decreased during I+Eo (p < 0.05), and did not change significantly under other conditions (p > 0.05). All I blocks resulted in prolonged I cough characteristics (p < 0.05) mainly cough I phase (incrementing part of the diaphragm activity). Shorter I phase occurred with cEo (p < 0.05). Cough cycle time and active E phase (from the I maximum to the end of cough E motor drive) prolonged (p < 0.05) during all occlusions (E phase duration statistically non-significantly for I+Eo). Airflow block during cough (occlusions) results in secondary changes in the cough response due to markedly altered function of cough central pattern generator and cough motor pattern produced. Cough compensatory effects during airflow resistances are more favorable compared to occlusions. Volume feedback represents significant factor of cough modulation under various pathological obstruction and/or restriction conditions of the respiratory system.
Topics: Airway Obstruction; Animals; Cats; Cough; Disease Models, Animal; Feedback, Physiological; Pulmonary Stretch Receptors; Respiratory Mechanics
PubMed: 32942050
DOI: 10.1016/j.resp.2020.103547 -
Journal of Food Science May 2023Among natural products with sleep-promoting activity, hops have been used since ancient times as a tranquilizer and hypnotic agent. This study investigated the...
Among natural products with sleep-promoting activity, hops have been used since ancient times as a tranquilizer and hypnotic agent. This study investigated the sleep-promoting effects of extracts of various hop (Humulus lupulus L.) varieties in invertebrate and vertebrate models. The content of α-acids, β-acids, and xanthohumol was higher in hop 70% alcohol extracts than in hop hot water extracts. Among the alcohol extracts, Citra contained a high α-acid content (229.32 µg/mg), while Saphir showed high β-acid and xanthohumol content (66.37 and 4.23 µg/mg, respectively). In Drosophila melanogaster, Simcoe and Mosaic water extracts and Saphir and Simcoe alcohol extracts significantly increased total nighttime sleep. Total sleep time of mice with pentobarbital-induced sleep was significantly increased by Simcoe and Mosaic water extracts and Saphir and Simcoe ethanol extracts compared to the normal group. Oral administration of Simcoe water extract and Saphir alcohol extract improved sleep in the caffeine-induced insomnia model and upregulated the mRNA expression of GABA (gamma 2 subunit) and GABA receptors in mouse brains. Additionally, Saphir alcohol extract significantly increased the GABA content in mouse brains. Simcoe water extract and Saphir ethanol extract modulated GABAergic signaling to improve sleep-related behaviors, including sleep duration.
Topics: Mice; Animals; Plant Extracts; Humulus; Drosophila melanogaster; Flavonoids; Sleep; Ethanol; gamma-Aminobutyric Acid
PubMed: 37038885
DOI: 10.1111/1750-3841.16544 -
Clinical NeuropharmacologyIntracranial hypertension is a life-threatening condition that requires emergent diagnosis and management. Although pentobarbital coma for refractory intracranial...
OBJECTIVE
Intracranial hypertension is a life-threatening condition that requires emergent diagnosis and management. Although pentobarbital coma for refractory intracranial hypertension has been studied in the general population, this study is the first reported case of pentobarbital coma use in a pregnant patient.
METHODS
We performed a retrospective chart review of a pregnant patient with refractory intracranial hypertension and reviewed the current literature on the role of pentobarbital coma.
RESULTS
We present the case of a 35-year-old woman at 26 weeks of gestation who developed refractory intracranial hypertension secondary to rupture of a dural arteriovenous fistula. The patient was taken to surgery for decompressive hemicraniectomy, clot evacuation, and dural arteriovenous fistula resection. Subsequently, the patient was treated with pentobarbital coma for 5 days and achieved adequate control of her intracranial pressures. The patient and fetus were closely monitored by the obstetrics team with no apparent harm to fetal well-being during her hospital stay. The patient underwent planned cesarean delivery at term, and both the mother and newborn were discharged in stable condition with no known pentobarbital-related complications.
CONCLUSIONS
Thus, we present the first case report demonstrating that pentobarbital coma may be a safe and efficacious option for treating pregnant patients with life-threatening refractory intracranial hypertension. We also provide dosing information for pentobarbital administration. Additional studies and reports involving pregnant patients are needed to better understand the impact of pentobarbital on both the mother and fetus. Furthermore, long-term follow-up of both the mother and newborn is critical to identifying any delayed sequelae of neonatal exposure to pentobarbital.
Topics: Adult; Central Nervous System Vascular Malformations; Coma; Female; Humans; Infant, Newborn; Intracranial Hypertension; Pentobarbital; Pregnancy; Retrospective Studies
PubMed: 35195548
DOI: 10.1097/WNF.0000000000000496 -
Journal of the American Veterinary... Nov 2023To assess (1) veterinarians' knowledge and practices regarding disposal of euthanized animals, (2) the extent to which veterinarians communicate with their clients about...
OBJECTIVE
To assess (1) veterinarians' knowledge and practices regarding disposal of euthanized animals, (2) the extent to which veterinarians communicate with their clients about potential risks of rendering pentobarbital-euthanized animals, and (3) the extent to which veterinarians communicate potential relay toxicosis and environmental risks of pentobarbital-euthanized animals to clients.
SAMPLE
A stratified random sample of AVMA members.
METHODS
Over a 3-week period in early 2021, 16,831 of the AVMA's 99,500 members were surveyed, with 2,093 responses (a 12% response rate). Respondents were assigned to 1 of 3 categories on the basis of their answers: veterinarians euthanizing only food-producing species, veterinarians euthanizing only non-food-producing species, and veterinarians euthanizing both food-producing and non-food-producing species (ie, veterinarians euthanizing mixed species).
RESULTS
Veterinarians responding to this survey appeared to be aware of the major methods of animal disposal, and about 89% reported communicating the method of euthanasia with clients to help ensure appropriate animal disposal. However, the need for additional education on local, state, and federal laws and rendering, as well as on risks of relay toxicosis including wildlife predation and environmental impacts, was reported.
CLINICAL RELEVANCE
Survey results identified gaps in veterinarians' knowledge regarding animal disposal following pentobarbital euthanasia. Further education on this topic may be beneficial, particularly for early- and midcareer veterinarians who euthanize non-food-producing species and for veterinarians who euthanize mixed species in urban and suburban communities.
Topics: Animals; Humans; Pentobarbital; Euthanasia, Animal; Veterinarians; Animals, Wild; Surveys and Questionnaires
PubMed: 37562784
DOI: 10.2460/javma.23.03.0161 -
Pharmaceutical Biology Dec 2022Paeonol (PAE) is the main phytochemical from . Its main pharmacological effects are anti-inflammatory and antioxidant, but its cardioprotective effect is unclear.
CONTEXT
Paeonol (PAE) is the main phytochemical from . Its main pharmacological effects are anti-inflammatory and antioxidant, but its cardioprotective effect is unclear.
OBJECTIVE
The study investigates the effects and underlying mechanisms of PAE on transverse aortic constriction (TAC)-induced heart failure (HF) in mice.
MATERIALS AND METHODS
C57BL/6 mice were randomly divided into five groups: sham, TAC, PAE10 (TAC + PAE 10 mg/kg), PAE20 (TAC + PAE 20 mg/kg) and PAE 50 (TAC + PAE 50 mg/kg). Paeonol was intragastrically administered to mice for 4 weeks. Mice were anaesthetized with pentobarbital sodium and underwent cardiac echocardiography using echocardiography system. Serum levels of atrial natriuretic peptide (ANP), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Myocardial apoptosis was detected with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. Haematoxylin-eosin (H&E) and Masson's staining were used for histopathological evaluation. Western and quantitative real-time PCR (qRT-PCR) were performed to detect levels of apoptosis and fibrosis-related proteins.
RESULTS
Echocardiography showed PAE improved cardiac function (LVEF: TAC, 52.3±6.8%; PAE20, 65.8±3.6%; PAE50, 71.4±2.5%) and H&E staining showed PAE alleviated myocardial injury (TAC: 1170.3 ± 134.6 μm; PAE50: 576.0 ± 53.5 μm). Western and qRT-PCR results showed that PAE down-regulated the levels of ANP, BNP and α-MHC. In addition, TUNEL and western results showed PAE significantly inhibited apoptosis. Masson and western results showed PAE inhibited cardiac hypertrophy. Western results showed the ERK1/2/JNK pathway could be inhibited by PAE.
DISCUSSION AND CONCLUSIONS
Paeonol regulates ERK1/2/JNK to improve cardiac function, which provides theoretical support for the extensive clinical treatment of HF.
Topics: Acetophenones; Animals; Aorta; Apoptosis; Cardiomegaly; Cardiotonic Agents; Constriction, Pathologic; Disease Models, Animal; Heart Failure; MAP Kinase Signaling System; Male; Mice; Mice, Inbred C57BL; Signal Transduction
PubMed: 35249458
DOI: 10.1080/13880209.2022.2040543 -
Current Research in Toxicology 2023This study evaluated nickel and aluminium-induced neurotoxicity, as a binary metal mixture. Twenty-eight male Sprague Dawley albino rats were weight-matched and divided...
Nickel and aluminium mixture elicit memory impairment by activation of oxidative stress, COX-2, and diminution of AChE, BDNF and NGF levels in cerebral cortex and hippocampus of male albino rats.
This study evaluated nickel and aluminium-induced neurotoxicity, as a binary metal mixture. Twenty-eight male Sprague Dawley albino rats were weight-matched and divided into four groups. Group 1 (control) received deionized water. Group 2 and 3 received Aluminium (1 mg/kg) and Nickel (0.2 mg/kg) respectively, while Group 4 received Ni and Al mixture HMM three times a week orally for 90 days. Barnes maze tests was performed. Rats were sacrificed under pentobarbital anaesthesia, cerebral cortex and hippocampus were separated, and metal levels were measured using Atomic Absorption Spectroscopy (AAS). Malondialdehyde (MDA), catalase (CAT), glutathione content (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), Brain Derived Neurotrophic Factor (BDNF), Nerve growth factor NGF, -oxygenase COX-2 and Acetylcholinesterase (AChE) were assayed using ELISA kits. Ni/Al binary mixture exposed rats showed a shorter latency period (though not significant) of 3.21 ± 1.40 s in comparison to 3.77 ± 1.11 (Ni only) and 3.99 ± 1.16(Al only). Ni/Al mixture gp had the lowest levels of Mg in both the hippocampus and frontal cortex when compared with the individual metals. In the hippocampus Al only exposed rats significantly showed p < 0.05 higher iron and Ca levels in comparison to Ni/Al mixture. Al alone significantly showed p < 0.05 lower levels of Fe but higher Ca than the Ni/Al mixture group. Exposure to Al only showed lower levels of BDNF in comparison to Ni/Al combination, whereas Ni/Al mixture gp had lower levels of NGF in comparison to the individual metals in the hippocampus. In the frontal cortex Ni only, group showed significantly lower BDNF in comparison to Ni/Al mixture whereas the mixture showed significantly lower NGF when compared with Al only group. There were higher levels of COX-2 in the Ni/Al mixture than individual metal treated rats in both hippocampus and frontal cortex. AChE levels in the Ni/Al mixture group was higher than Ni or Al only gps in the hippocampus whereas in the frontal cortex, Ni/Al exposed rats showed significantly lower AChE levels in comparison to Al only group. Ni, Al and Ni/Al mixture exhibited memory impairment by activation of oxidative stress, COX-2, and diminution of AChE, BDNF and NGF levels in cerebral cortex and hippocampus. The BDNF-COX-2 AChE signalling pathway may be involved in the neurotoxicity of Ni and Al.
PubMed: 37841055
DOI: 10.1016/j.crtox.2023.100129 -
Journal of Ethnopharmacology Dec 2021Sleep disorders are among the most common symptoms in both peri- and post-menopausal women. Kamishoyosan (KSS) is a Kampo medicine prescribed for the treatment of sleep...
ETHNOPHARMACOLOGICAL RELEVANCE
Sleep disorders are among the most common symptoms in both peri- and post-menopausal women. Kamishoyosan (KSS) is a Kampo medicine prescribed for the treatment of sleep disorders in menopausal women in Japan. However, its precise mechanism of action remains unclear.
AIM OF THE STUDY
In the present study, we developed a new animal model of menopausal sleep disorders by inducing social isolation stress in ovariectomized mice. Using pentobarbital-induced sleeping time as an index, we aimed to investigate the effects of KSS and involvement of the benzodiazepine receptors.
MATERIALS AND METHODS
Eight-week-old, female ddY mice were ovariectomized or subjected to a sham operation (control) and housed in social isolation or groups for 9 weeks. The animals were divided into four groups, group-housed sham-operated, isolated sham-operated, group-housed ovariectomized, and socially isolated ovariectomized. Pentobarbital (50 mg/kg) was administered intraperitoneally (i.p.). Sleeping time was considered the period between the loss of righting reflex and its return (up to 180 min). KSS was administered orally (p.o.) 60 min before the test. Diazepam and flumazenil were administered i.p. 30 and 45 min before the test, respectively. On the day after administration, the mice were euthanized, and their uteri were weighed.
RESULTS
Socially isolated, ovariectomized mice had shorter sleeping times than mice in all other groups. In mice with intact ovaries, diazepam (1 mg/kg, i.p.) considerably prolonged the pentobarbital-induced sleeping time, but KSS (30-1000 mg/kg, p.o.) did not. However, KSS (100 mg/kg, p.o.) significantly prolonged the pentobarbital-induced sleeping time in socially isolated ovariectomized mice. The prolongation of sleeping time mediated by KSS was reversed by flumazenil (3 mg/kg, i.p.).
CONCLUSIONS
KSS potentiated pentobarbital-induced sleep in socially isolated, ovariectomized mice, and the benzodiazepine receptors are possibly involved in its pharmacological mechanism. These findings suggest that KSS is beneficial for the treatment of menopausal sleep disorders.
Topics: Animals; Behavior, Animal; Drug Synergism; Drugs, Chinese Herbal; Female; Hypnotics and Sedatives; Mice; Ovariectomy; Pentobarbital; Sleep; Social Isolation
PubMed: 34464703
DOI: 10.1016/j.jep.2021.114585