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The Veterinary Clinics of North... May 2020The history of companion animal euthanasia includes a blend of good and bad methodology, the shifting landscape of the human-animal bond, and maturation of the... (Review)
Review
The history of companion animal euthanasia includes a blend of good and bad methodology, the shifting landscape of the human-animal bond, and maturation of the veterinary euthanasia experience. Time has shown us that critical exploration of what once was acceptable will lead the way to modern best practices. Animal welfare remains at the heart of the procedure, with equally matched attention now given to client and veterinary team well-being. Although euthanasia will continue to evolve, it is clear through the twenty-first century advancements, a tipping point of necessary change is upon us.
Topics: Animal Welfare; Animals; Animals, Domestic; Euthanasia, Animal; History, 19th Century; History, 20th Century; History, 21st Century; Human-Animal Bond; Terminology as Topic; Veterinary Medicine
PubMed: 32115283
DOI: 10.1016/j.cvsm.2019.12.001 -
Chinese Journal of Integrative Medicine Aug 2022To explore the synergic mechanism of ginsenoside Rg (Rg) and aconitine (AC) by acting on normal neonatal rat cardiomyocytes (NRCMs) and pentobarbital sodium (PS)-induced...
OBJECTIVE
To explore the synergic mechanism of ginsenoside Rg (Rg) and aconitine (AC) by acting on normal neonatal rat cardiomyocytes (NRCMs) and pentobarbital sodium (PS)-induced damaged NRCMs.
METHODS
The toxic, non-toxic, and effective doses of AC and the most suitable compatibility concentration of Rg for both normal and damaged NRCMs exposed for 1 h were filtered out by 3- (4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide, respectively. Then, normal NRCMs or impaired NRCMs were treated with chosen concentrations of AC alone or in combination with Rg for 1 h, and the cellular activity, cellular ultrastructure, apoptosis, leakage of acid phosphatase (ACP) and lactate dehydrogenase (LDH), intracellular sodium ions [Na], potassium ions [K] and calcium ions [Ca] levels, and Nav1.5, Kv4.2, and RyR genes expressions in each group were examined.
RESULTS
For normal NRCMs, 3000 µ mol/L AC significantly inhibited cell viability (P<0.01), promoted cell apoptosis, and damaged cell structures (P<0.05), while other doses of AC lower than 3000 µ mol/L and the combinations of AC and Rg had little toxicity on NRCMs. Compared with AC acting on NRCMs alone, the co-treatment of 3000 and 10 µ mol/L AC with 1 µ mol/L Rg significantly decreased the level of intracellular Ca (P<0.01 or P<0.05), and the co-treatment of 3000 µ mol/L AC with 1 µ mol/L Rg significantly decreased the level of intracellular Ca via regulating Nav1.5, RyR expression (P<0.01). For damaged NRCMs, 1500 µ mol/L AC aggravated cell damage (P<0.01), and 0.1 and 0.001 µ mol/L AC showed moderate protective effect. Compared with AC used alone, the co-treatment of Rg with AC reduced the cell damage, 0.1 µ mol/L AC with 1 µ mol/L Rg significantly inhibited the level of intracellular Na (P<0.05), 1500 µ mol/L AC with 1 µ mol/L Rg significantly inhibited the level of intracellular K (P<0.01) via regulating Nav1.5, Kv4.2, RyR expressions in impaired NRCMs.
CONCLUSION
Rg inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of [Na], [K], and [Ca].
Topics: Aconitine; Animals; Apoptosis; Cardiotonic Agents; Cardiotoxicity; Cell Survival; Ginsenosides; Rats
PubMed: 35723815
DOI: 10.1007/s11655-022-3509-0 -
Journal of Clinical Medicine Jul 2021Refractory and super-refractory status epilepticus (RSE and SRSE) are life-threatening conditions requiring prompt initiation of appropriate treatment to avoid permanent... (Review)
Review
Refractory and super-refractory status epilepticus (RSE and SRSE) are life-threatening conditions requiring prompt initiation of appropriate treatment to avoid permanent neurological damage and reduce morbidity and mortality. RSE is defined as status epilepticus that persists despite administering at least two appropriately dosed parenteral medications, including a benzodiazepine. SRSE is status epilepticus that persists at least 24 h after adding at least one appropriately dosed continuous anesthetic (i.e., midazolam, propofol, pentobarbital, and ketamine). Other therapeutic interventions include immunotherapy, neuromodulation, ketogenic diet, or even surgical intervention in certain cases. Continuous electroencephalogram is an essential monitoring tool for diagnosis and treatment. In this review, we focus on the diagnosis and treatment of RSE and SRSE.
PubMed: 34300194
DOI: 10.3390/jcm10143028 -
Journal of Molecular Neuroscience : MN Mar 2021KLF4 is a zinc-finger transcription factor that plays an essential role in many biological processes, including neuroinflammation, neuron regeneration, cell...
KLF4 is a zinc-finger transcription factor that plays an essential role in many biological processes, including neuroinflammation, neuron regeneration, cell proliferation, and apoptosis. Through effects on these processes, KLF4 has likely roles in Alzheimer's disease, Parkinson's disease, and traumatic brain injury. However, little is known about the role of KLF4 in more immediate behavioral processes that similarly depend upon broad changes in brain excitability, such as the sleep process. Here, behavioral approaches, western blot, and immunohistochemical experiments were used to explore the role of KLF4 on sedation and the potential mechanisms of those effects. The results showed that overexpression of KLF4 prolonged loss of righting reflex (LORR) duration in pentobarbital-treated mice and increased c-Fos expression in the lateral hypothalamus (LH) and the ventrolateral preoptic nucleus (VLPO), while it decreased c-Fos expression in the tuberomammillary nucleus (TMN). Moreover, overexpression of KLF4 reduced the expression of p53 in the hypothalamus and increased the expression of STAT3 in the hypothalamus. Therefore, these results suggest that KLF4 exerts sedative effects through the regulation of p53 and STAT3 expression, and it indicates a role of KLF4 ligands in the treatment of sleep disorders.
Topics: Animals; Hypnotics and Sedatives; Hypothalamus; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Male; Mice; Mice, Inbred ICR; Pentobarbital; Proto-Oncogene Proteins c-fos; Reflex; STAT3 Transcription Factor; Tumor Suppressor Protein p53
PubMed: 32789565
DOI: 10.1007/s12031-020-01680-y -
American Journal of Physiology. Heart... Jul 2022Cardiac fibrosis is thought to be the hallmark of pathological hypertrophic remodeling, of which the myofibroblast transdifferentiation is the key cell biological event....
Cardiac fibrosis is thought to be the hallmark of pathological hypertrophic remodeling, of which the myofibroblast transdifferentiation is the key cell biological event. However, there is still no specific and effective therapeutic agent approved for cardiac fibrosis. To investigate the effects of belumosudil, the first ρ-associated kinase-2 (ROCK2)-specific inhibitor, on cardiac hypertrophy, fibrosis, and dysfunction induced by pressure overload, the transverse aortic constriction (TAC) or sham operation was carried out on wild-type C57BL/6 mice (male, 6-8 wk old) under pentobarbital anesthesia. After that, mice were randomly divided into three groups: sham operation + vehicle, TAC + vehicle, TAC + 50 mg·kg·day belumosudil. We found that belumosudil effectively ameliorated cardiac hypertrophy, fibrosis, and dysfunction in TAC mice. To elucidate the underlying mechanism, we inhibited the expression of ROCK2 in vitro by either belumosudil or siRNA. We showed that the inhibition of ROCK2 by either belumosudil or knockdown suppressed cardiac fibroblasts activation and proliferation significantly induced by transforming growth factor-β1 (TGF-β1). Furthermore, our study confirmed ROCK2 mediates cardiac fibrosis by interacting with TGF-β1/mothers against decapentaplegic homolog 2 (Smad2) pathway. Taken together, we demonstrated that belumosudil ameliorates cardiac hypertrophy and fibrosis induced by TAC via inhibiting cardiac fibroblasts activation. In conclusion, belumosudil may be a promising therapeutic drug for cardiac hypertrophy and fibrosis induced by myocardial pressure overload. Although ρ-associated kinase-2 (ROCK2) is the main isoform of ρ-associated kinases (ROCKs) in the heart and more important in cardiac hypertrophy and fibrosis than ρ-associated kinase-1 (ROCK1), there has not been any pharmacological approach to inhibit ROCK2 selectively. Our study demonstrates for the first time that belumosudil, the first ROCK2-specific inhibitor, effectively ameliorates cardiac hypertrophy, fibrosis, and dysfunction induced by TAC via inhibiting cardiac fibroblasts activation.
Topics: Acetamides; Animals; Cardiomegaly; Fibroblasts; Fibrosis; Male; Mice; Mice, Inbred C57BL; Myocardium; Myofibroblasts; Signal Transduction; Transforming Growth Factor beta1; rho-Associated Kinases
PubMed: 35657612
DOI: 10.1152/ajpheart.00014.2022 -
Chinese Journal of Integrative Medicine Nov 2022To evaluate the protective function of Babao Dan (BBD) on 5-flurouracil (5-FU)-induced intestinal mucositis (IM) and uncover the underlying mechanism.
OBJECTIVE
To evaluate the protective function of Babao Dan (BBD) on 5-flurouracil (5-FU)-induced intestinal mucositis (IM) and uncover the underlying mechanism.
METHODS
A total of 18 male mice were randomly divided into 3 groups by a random number table, including control, 5-FU and 5-FU combined BBD groups, 6 mice in each group. A single intraperitoneal injection of 5-FU (150 mg/kg) was performed in 5-FU and 5-FU combined BBD groups on day 0. Mice in 5-FU combined BBD group were gavaged with BBD (250 mg/kg) daily from day 1 to 6. Mice in the control group were gavaged with saline solution for 6 days. The body weight and diarrhea index of mice were recorded daily. On the 7th day, the blood from the heart of mice was collected to analyze the proportional changes of immunological cells, and the mice were subsequently euthanized by mild anesthesia with 2% pentobarbital sodium. Colorectal lengths and villus heights were measured. Intestinal-cellular apoptosis and proliferation were evaluated by Tunel assay and immunohistochemical staining of proliferating cell nuclear antigen, respectively. Immunohistochemistry and Western blot were performed to investigate the expressions of components in Wnt/β-catenin pathway (Wnt3, LRP5, β-catenin, c-Myc, LRG5 and CD44).
RESULTS
BBD obviously alleviated 5-FU-induced body weight loss and diarrhea, and reversed the decrease in the number of white blood cells, including monocyte, granulocyte and lymphocyte, and platelet (P<0.01). The shortening of colon caused by 5-FU was also reversed by BBD (P<0.01). Moreover, BBD inhibited apoptosis and promoted proliferation in jejunum tissues so as to reduce the intestinal mucosal damage and improve the integrity of villus and crypts. Mechanically, the expression levels of Wnt/β -catenin mediators such as Wnt3, LRP5, β-catenin were upregulated by BBD, activating the transcription of c-Myc, LRG5 and CD44 (P<0.01).
CONCLUSIONS
BBD attenuates the adverse effects induced by 5-FU via Wnt/β-catenin pathway, suggesting it may act as a potential agent against chemotherapy-induced intestinal mucositis.
Topics: Animals; Male; Mice; Antineoplastic Agents; beta Catenin; Diarrhea; Fluorouracil; Intestinal Mucosa; Mucositis; Pentobarbital; Proliferating Cell Nuclear Antigen; Saline Solution
PubMed: 33420580
DOI: 10.1007/s11655-021-3282-0 -
Neuroscience Letters Apr 2023Pentobarbital-induced anesthesia is believed to be mediated by enhancement of the inhibitory action of γ-aminobutyric acid (GABA)ergic neurons in the central nervous...
Pentobarbital-induced anesthesia is believed to be mediated by enhancement of the inhibitory action of γ-aminobutyric acid (GABA)ergic neurons in the central nervous system. However, it is unclear whether all components of anesthesia induced by pentobarbital, such as muscle relaxation, unconsciousness, and immobility in response to noxious stimuli, are mediated only through GABAergic neurons. Thus, we examined whether the indirect GABA and glycine receptor agonists gabaculine and sarcosine, respectively, the neuronal nicotinic acetylcholine receptor antagonist mecamylamine, or the N-methyl-d-aspartate receptor channel blocker MK-801 could enhance pentobarbital-induced components of anesthesia. Muscle relaxation, unconsciousness, and immobility were evaluated by grip strength, the righting reflex, and loss of movement in response to nociceptive tail clamping, respectively, in mice. Pentobarbital reduced grip strength, impaired the righting reflex, and induced immobility in a dose-dependent manner. The change in each behavior induced by pentobarbital was roughly consistent with that in electroencephalographic power. A low dose of gabaculine, which significantly increased endogenous GABA levels in the central nervous system but had no effect on behaviors alone, potentiated muscle relaxation, unconsciousness, and immobility induced by low pentobarbital doses. A low dose of MK-801 augmented only the masked muscle-relaxing effects of pentobarbital among these components. Sarcosine enhanced only pentobarbital-induced immobility. Conversely, mecamylamine had no effect on any behavior. These findings suggest that each component of anesthesia induced by pentobarbital is mediated through GABAergic neurons and that pentobarbital-induced muscle relaxation and immobility may partially be associated with N-methyl-d-aspartate receptor antagonism and glycinergic neuron activation, respectively.
Topics: Mice; Animals; Receptors, N-Methyl-D-Aspartate; Pentobarbital; Dizocilpine Maleate; Sarcosine; Mecamylamine; gamma-Aminobutyric Acid; Unconsciousness
PubMed: 36907265
DOI: 10.1016/j.neulet.2023.137175 -
Journal of Ocular Pharmacology and... Mar 2022Anesthesia is necessary to conduct rodent electroretinograms (ERGs). We evaluated utility of the α2-agonist medetomidine versus xylazine for ERG studies in nondiabetic...
Anesthesia is necessary to conduct rodent electroretinograms (ERGs). We evaluated utility of the α2-agonist medetomidine versus xylazine for ERG studies in nondiabetic and diabetic rats. Pentobarbital was included as a comparator. Male Sprague-Dawley rats, with and without streptozotocin (STZ)-induced diabetes, were anesthetized with medetomidine (1 mg/kg), xylazine (10 mg/kg) (both with ketamine 75 mg/kg), or pentobarbital (70 mg/kg). The depth of anesthesia was assessed, and if adequate, scotopic ERGs were recorded. Blood glucose was monitored. In nondiabetic rats, all three agents induced satisfactory anesthesia, but with differing durations: medetomidine > pentobarbital > xylazine. ERG responses were similar under medetomidine and xylazine, but relatively reduced under pentobarbital. Both α2-agonists (but not pentobarbital) elicited marked hyperglycemia (peak values 316.1 ± 42.6 and 300.3 ± 29.5 mg/dL, respectively), persisting for 12 h. In diabetic rats, elevated blood glucose concentrations were not affected by any of the agents, but the depth of anesthesia under medetomidine and xylazine was inadequate for ERG recording. In nondiabetic rats, medetomidine and xylazine elicited comparable effects on ERGs that differ from pentobarbital, but both perturbed glucose metabolism, potentially confounding experimental outcomes. In STZ-diabetic rats, neither α2-agent provided adequate anesthesia, while pentobarbital did so. Problems with α2-anesthetic agents, including medetomidine, must be recognized to ensure meaningful interpretation of experimental results.
Topics: Adrenergic Agents; Anesthesia; Animals; Diabetes Mellitus, Experimental; Male; Medetomidine; Pentobarbital; Rats; Rats, Sprague-Dawley; Xylazine
PubMed: 34964655
DOI: 10.1089/jop.2021.0084 -
International Journal of Molecular... Nov 2022Sleep is a restorative period that plays a crucial role in the physiological functioning of the body, including that of the immune system, memory processing, and...
Sleep is a restorative period that plays a crucial role in the physiological functioning of the body, including that of the immune system, memory processing, and cognition. Sleep disturbances can be caused by various physical, mental, and social problems. Recently, there has been growing interest in sleep. (MS, corn silk) is a female maize flower that is traditionally used as a medicinal plant to treat many diseases, including hypertension, edema, and diabetes. It is also used as a functional food in tea and other supplements. β-Sitosterol (BS) is a phytosterol and a natural micronutrient in higher plants, and it has a similar structure to cholesterol. It is a major component of MS and has anti-inflammatory, antidepressive, and sedative effects. However, the potential effects of MS on sleep regulation remain unclear. Here, we investigated the effects of MS on sleep in mice. The effects of MS on sleep induction were determined using pentobarbital-induced sleep and caffeine-induced sleep disruption mouse models. MS extracts decreased sleep latency and increased sleep duration in both the pentobarbital-induced sleep induction and caffeine-induced sleep disruption models compared to the positive control, valerian root extract. The butanol fraction of MS extracts decreased sleep latency time and increased sleep duration. In addition, β-sitosterol enhances sleep latency and sleep duration. Both MS extract and β-sitosterol increased alpha activity in the EEG analysis. We measured the mRNA expression of melatonin receptors 1 and 2 (MT1/2) using qRT-PCR. The mRNA expression of melatonin receptors 1 and 2 was increased by MS extract and β-sitosterol treatment in rat primary cultured neurons and the brain. In addition, MS extract increased the expression of clock genes including , , and in the brain. MS extract and β-sitosterol increased the phosphorylation of ERK1/2 and αCaMKII. Our results demonstrate for the first time that MS has a sleep-promoting effect via melatonin receptor expression, which may provide new scientific evidence for its use as a potential therapeutic agent for the treatment and prevention of sleep disturbance.
Topics: Rats; Mice; Animals; Receptors, Melatonin; Plant Extracts; Sleep Wake Disorders; Sleep; RNA, Messenger
PubMed: 36498940
DOI: 10.3390/ijms232314612 -
Avicenna Journal of Phytomedicine 2020Sleep disorders are among the most common psychiatric and medical conditions. In the present study, the hypnotic effect of was studied in mice
OBJECTIVE
Sleep disorders are among the most common psychiatric and medical conditions. In the present study, the hypnotic effect of was studied in mice
MATERIALS AND METHODS
The hydro-alcoholic extract (HAE) of and three fractions of it, namely water fraction (WF), ethyl acetate fraction (EAF), and -hexane fraction (NHF), were intraperitoneally (ip) administrated to mice 30 min before injection of sodium pentobarbital (30 mg/kg, ip). Then, 30 min after administration of HAE, motor coordination (rota-rod test) was evaluated. Besides, LD of HAE was determined and the cytotoxicity of HAE was evaluated in PC12 cells using the MTT assay.
RESULTS
HAE 50-200 mg/kg increased the sleeping time. EAF was the only fraction which could prolong the sleep duration and decrease sleep latency. The LD50 value was 4.8 g/kg. The extract induced no cytotoxic effects in PC12 cell line.
CONCLUSION
The results suggested that potentiates pentobarbital hypnosis without causing toxic effects. Probably, its effects are mediated by the components present in EAF of this plant.
PubMed: 31921609
DOI: No ID Found