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Moringa is a type of plant that is used both for medicinal and food. Moringa seed (MS) are rich in volatile oil and have initially been employed to treat diseases of the nervous system. Insomnia, a prevalent neurological disorder, has led to this study's aim: to extract the essential oil from MS and analyze its potential to improve sleep. This study utilized petroleum ether for the thermal extraction of the essential oil from MS, which was then subjected to compositional analysis using Gas Chromatograph Mass Spectrometer (GC–MS). P‐chlorophenyl alanine (PCPA) was used to induce an insomnia model in Sprague–Dawley (SD) rats. Following the successful establishment of the model, the MS essential oil was administered at concentrations of 10%, 5%, and 2.5% to investigate its sedative and hypnotic effects. The efficacy of the MS essential oil was assessed by observing the general condition of rats in each group, conducting an open field test, a pentobarbital sodium righting test, and measuring the serum 5‐HT (5‐hydroxytryptamine) levels and hypothalamic GABA (γ‐aminobutyric acid) content. GC–MS analysis of the MS essential oil revealed a rich composition, including oleic acid, palmitoleic acid, stigmasterol, and γ‐stigmasterol, among other substances. Through the assessment of the rats' general condition, behavioral tests, and blood biochemical assays, it was inferred that MS essential oil aromatherapy can reduce the rat's locomotor activity, increase their interest in activity and exploration, enhance the serum 5‐HT levels, and elevate hypothalamic GABA content. Consequently, it can be concluded that MS essential oil has a sedative and hypnotic effect. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic made it difficult to obtain pharmaceutical‐grade injectable anaesthetics used in animal experiments in Japan. To address this problem, it is worth the effort to evaluate whether the use of non‐pharmaceutical‐grade sodium pentobarbital (PBNa) water solution can be an alternative one from the perspective of stability, physicochemical properties, bioavailability and so on. In this article, as a first step, we examined the stability of PBNa 5w/v% aqueous solution (PBNa 5% AS). PBNa 5% AS sample was prepared simply by dissolving non‐pharmaceutical‐grade PBNa into water and was stored at 25°C and 5°C for 15 days. Visual appearance, pH, osmolality and assay (contents of PBNa and related substances) were tested. The stability test results indicated that there was no profound change in these test items of the PBNa 5% AS under either storage condition, suggesting that the formulation was sufficiently stable in such a short term. The only observable change was an increase of an impurity under 25°C storage; however, it was at a negligible level. Moreover, as the pH of the formulation remained <10.0 throughout the storage period in both conditions, the irritant level of the pH is considered to be acceptable. Therefore, from the viewpoint of the stability and physicochemical properties, PBNa 5% AS can be an alternative injectable anaesthetic when access to pharmaceutical‐grade anaesthetics is limited, as long as used in short‐term from its preparation. [ABSTRACT FROM AUTHOR]

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Here we describe a pediatric patient with febrile infection–related epilepsy syndrome with a good functional and neurologic outcome after treatment with early and aggressive cytokine-directed immunomodulatory therapy and a seizure management strategy that intentionally avoided a barbiturate coma. A 5-year-old previously healthy male presented with staring, behavioral arrest, and encephalopathy evolving to super-refractory status epilepticus. He had had onset of fever 5 days prior. He was treated with early and aggressive immunomodulatory therapy targeted to his evolving cytokine profile. He was also treated with the ketogenic diet, antiseizure medications, and continuous anesthetic infusions. Pentobarbital was purposely avoided. Now, 2½ years later, he attends mainstream school, has attention-deficit hyperactivity disorder (ADHD), mild neurocognitive impairment, and well-controlled epilepsy. By using cytokine-directed immunotherapy and avoiding a barbiturate coma, we were able to successfully treat a pediatric patient with febrile infection-related epilepsy syndrome and achieve a good outcome. [ABSTRACT FROM AUTHOR]

Objective: Compared with the use of ultrasound for noninvasive monitoring of the anesthetic sodium pentobarbital versus tribromoethanol in an animal model of renal ischemia‐reperfusion injury in rats. Methods: Adult rats were randomly assigned to a renal ischemia‐reperfusion injury model, and preoperative anesthetics were administered as either sodium pentobarbital or tribromoethanol. Color Doppler ultrasound and spectral Doppler ultrasound were used to detect changes in respiratory rate and heart rate during and after the surgery, as well as measure renal hemodynamic parameters including peak systolic velocity, end‐diastolic velocity, and resistance index. Results: The frequency of changes in respiration and heart rate was significantly higher in the sodium pentobarbital anesthesia group compared to the tribromoethanol anesthesia group. The peak systolic velocity and end‐diastolic velocity values in the sodium pentobarbital anesthesia group were significantly lower than those in the tribromoethanol group. However, the resistance index in the sodium pentobarbital group was higher than that in the tribromoethanol group. Conclusion: Ultrasound can be used to dynamically monitor the effects of anesthesia during the experiment, including changes in respiratory rate and heart rate, as well as semi‐quantitatively monitor hemodynamic changes in the kidneys, which indirectly reflects whole‐body hemodynamic changes in rats. [ABSTRACT FROM AUTHOR]

Background and Objective: The alteration of mitochondrial functions, especially the opening of the mitochondrial permeability transition pore (mPTP), has been proposed as a key mechanism in the development of lesions in cerebral ischemia, wherefore it is considered as an important target for drugs against ischemic injury. In this study, we aimed to investigate the effects of mitochondrial complex I inhibitors as possible regulators of mPTP using an in vitro brain ischemia model of the pentobarbital/ketamine (PBK)-anesthetized rats. Results: We found that PBK anesthesia itself delayed Ca2+-induced mPTP opening and partially recovered the respiratory functions of mitochondria, isolated from rat brain cortex and cerebellum. In addition, PBK reduced cell death in rat brain slices of cerebral cortex and cerebellum. PBK inhibited the adenosine diphosphate (ADP)-stimulated respiration of isolated cortical and cerebellar mitochondria respiring with complex I-dependent substrates pyruvate and malate. Moreover, pentobarbital alone directly increased the resistance of isolated cortex mitochondria to Ca2+-induced activation of mPTP and inhibited complex I-dependent respiration and mitochondrial complex I activity. In contrast, ketamine had no direct effect on functions of isolated normal cortex and cerebellum mitochondria. Conclusions: Altogether, this suggests that modulation of mitochondrial complex I activity by pentobarbital during PBK anesthesia may increase the resistance of mitochondria to mPTP opening, which is considered the key event in brain cell necrosis during ischemia. [ABSTRACT FROM AUTHOR]

Scale-free statistics of coordinated neuronal activity, suggesting a universal operating mechanism across spatio-temporal scales, have been proposed as a necessary condition of healthy resting-state brain activity. Recent studies have focused on anesthetic agents to induce distinct neural states in which consciousness is altered to understand the importance of critical dynamics. However, variation in experimental techniques, species, and anesthetics, have made comparisons across studies difficult. Here we conduct a survey of several common anesthetics (isoflurane, pentobarbital, ketamine) at multiple dosages, using calcium wide-field optical imaging of the mouse cortex. We show that while low-dose anesthesia largely preserves scale-free statistics, surgical plane anesthesia induces multiple dynamical modes, most of which do not maintain critical avalanche dynamics. Our findings indicate multiple pathways away from default critical dynamics associated with quiet wakefulness, not only reflecting differences between these common anesthetics but also showing significant variations in individual responses. This is suggestive of a non-trivial relationship between criticality and the underlying state of the subject. The significance of deviations from scale-free (SF) neural activity for consciousness is unclear. Using anesthetics, the authors show multiple paths from SF activity, indicating a complex relationship between non-SF activity and the participant's state. [ABSTRACT FROM AUTHOR]

Introduction: Sodium pentobarbital (SP), a short- to intermediate-acting barbiturate, has limited information in the existing literature. The objectives of this study are to describe (a) the effect of intravenous (IV) SP infusion on pain and sensory abnormalities, and (b) its utility in the diagnosis and management of patients with chronic pain. Methods: A narrative review of barbiturate applications for chronic pain was followed by a pragmatic study of 176 consecutive patients admitted to an inpatient pain unit (2004–2009). We collected demographic information upon admission, diagnoses retrieved from chart review, and pain ratings and sensory abnormalities at baseline and after blinded infusion of normal saline (NS) followed by SP. Results: The study group consisted of 83 men and 93 women (mean age 41 ± 11 years); the mean NS dose was 7.8 ± 2.3 (range 2–10 ml), the SP dose was 223.8 ± 88 mg (range 40–420), and the numeric rating scale (NRS) baseline pain score was 6.0 ± 2. The mean reduction in NRS reached both statistical and clinical significance in 150 responders to either NS/SP or SP only. Collectively, we found (a) an extremely high rate of response to IV SP irrespective of the underlying pathology, (b) greater response for pain than for sensory abnormalities (sensory gains or deficits), (c) greater response for sensory gain than for sensory deficit, and (d) greater response for allodynia than for pinprick hyperalgesia. Illustrative case reports are also presented. Discussion: IV SP infusion is a diagnostic tool that assists in elucidating pain generators and the nature of sensory abnormalities (central vs. peripheral), with effects similar to those of IV sodium amytal. The test cannot be viewed as a tell-all diagnostic modality and must be used in conjunction with clinical judgment, investigations, and psychological reports. [ABSTRACT FROM AUTHOR]

Phytolacca dodecandra (L' Herit), or 'Endod', is one of the widely known medicinal plants in Ethiopia. Berries of the endod have been used as a detergent for centuries. The present study was aimed to test the hepatoprotective effects of the plant against acetaminophen (APAP)-induced liver injury in rats. Mice of either sex were used for oral acute toxicity tests and APAP-induced lethality tests. Hepatoprotective experiments were done on male rats using 2 g/kg of APAP to induce liver damage. Liver enzymes, total bilirubin (TB), and lipid profile were determined. Liver tissues were also examined histopathologically to see a morphologic change in the control and experiment groups. The protective effect of the plant extract was also tested through sodium pentobarbital (SPB)-induced sleeping time. A significant increase in serum levels of liver enzymes, TB, low-density lipoprotein (LDL), and triglycerides (TGs) was seen from oral administration of 2 g/kg APAP. Total cholesterol (TC) and high-density lipoprotein (HDL) levels were decreased. Serum levels of all parameters were reversed to normal after administration of silymarin 100 mg/kg and, 100, 200, and 400 mg/kg doses of the extract. A significant dose-dependent hepatoprotective effect of Phytolacca dodecandra Methanol Root Extract (PDME) was seen in terms of LDL. Histopathological investigations and SPB-induced sleeping time confirmed the findings of biochemical analysis. The findings of the present study indicate that PDME protected the liver from APAP injury. [ABSTRACT FROM AUTHOR]

We investigated the effects of Lactuca sativa L. extracts (Lactuc) on pentobarbital-induced sleep in mice to elucidate the mechanisms underlying its impact on sleep quality. Mice were randomly assigned to five groups: control, positive control (diazepam 2 mg/kg b.w.), and three groups orally administered with Lactuc (50, 100, and 200 mg/kg b.w.). After 2 weeks of oral administration and intraperitoneal injections, the mice were killed. We found that the Lactuc-administered groups had significantly reduced sleep latency and increased sleep duration compared with the control group. Furthermore, the oral administration of Lactuc induced a significant increase in mRNA expression and protein expression of adenosine A1 receptor in the brains compared with the expressions in the control group. In addition, the Lactuc-administered groups exhibited significantly higher levels of mRNA expressions of GABAA receptors subunits α2, β2, γ1, and, γ2 in the brain tissue. Therefore, we suggest that Lactuc could be used to develop natural products that effectively improve sleep quality and duration. [ABSTRACT FROM AUTHOR]

Objective(s): Slit guidance ligand 3 (SLIT3) has been identified as a potential therapeutic regulator against fibroblast activity and fibrillary collagen production in an autocrine manner. However, this research aims to investigate the potential role of SLIT3 in cardiac fibrosis and fibroblast differentiation and its underlying mechanism. Materials and Methods: C57BL/6 mice (male, 8-10 weeks, n=47) were subcutaneously infused with Ang II (2.0 mg/kg/day) for 4 weeks. One to two-day-old Sprague-Dawley (SD) rats were anesthetized by intraperitoneal injection of 1% pentobarbital sodium (60 mg/kg) and ketamine (50 mg/kg) and the cardiac fibroblast was isolated aseptically. The mRNA and protein expression were analyzed using RT-qPCR and Western blotting. Results: The SLIT3 expression level was increased in Ang II-induced mice models and cardiac fibroblasts. SLIT3 significantly increased migrated cells and α-smooth muscle actin (α-SMA) expression in cardiac fibroblasts. Ang II-induced increases in mRNA expression of collagen I (COL1A1), and collagen III (COL3A1) was attenuated by SLIT3 inhibition. SLIT3 knockdown attenuated the Ang II-induced increase in mRNA expression of ACTA2 (α-SMA), Fibronectin, and CTGF. SLIT3 suppression potentially reduced DHE expression and decreased malondialdehyde (MDA) content, and the superoxide dismutase (SOD) and catalase (CAT) levels were significantly increased in cardiac fibroblasts. Additionally, SLIT3 inhibition markedly decreased RhoA and ROCK1 protein expression, whereas ROCK inhibitor Y-27632 (10 μM) markedly attenuated the migration of cardiac fibroblasts stimulated by Ang II and SLIT3. Conclusion: The results speculate that SLIT3 could significantly regulate cardiac fibrosis and fibroblast differentiation via the RhoA/ROCK1 signaling pathway. [ABSTRACT FROM AUTHOR]

OBJECTIVE To assess the efficacy of transmucosal euthanasia solution to induce euthanasia. ANIMALS 6 bearded dragons (Pogona vitticeps). METHODS An initial dose of euthanasia solution containing pentobarbital and phenytoin sodium was administered transmucosally in conscious lizards (100 mg/kg pentobarbital dose), followed by a second dose 20 minutes later (400 mg/kg pentobarbital dose). The presence of movement, leakage of euthanasia solution, behaviors consistent with oral irritation, respiratory rate, heart rate, palpebral and corneal reflex, and response to noxious stimuli were recorded until death, confirmed by the absence of Doppler cardiac flow and cardiac electrical activity. The time to loss of all parameters was calculated. Postmortem evaluation allowed for histopathologic evaluation of the oral cavity and gastrointestinal tract to detect potential mucosal damage from the alkaline euthanasia solution. RESULTS The median time to death was 300 minutes (range, 300 to 360 minutes), median time to respiratory arrest was 30 minutes (range, 30 to 50 minutes), and median time to loss of deep pain response was 30 minutes (range, 20 to 50 minutes). Signs consistent with oral irritation occurred in 4 of 6 (66.7%) lizards, including 2 lizards that exhibited whole-body spasms after euthanasia solution administration. Histopathologic changes indicating peracute mucosal ulceration, suspected to be from caustic causes, were identified in 1 (1/6 [16.7%]) lizard. CLINICAL RELEVANCE Transmucosal euthanasia solution administration resulted in clinical euthanasia within 6 hours. This method should be utilized only after premedication with analgesic and/or anesthetic medications due to the potential for acute mucosal ulceration and behaviors that may be distressing in client-owned animals. [ABSTRACT FROM AUTHOR]

ABSTRACT The COVID‐19 pandemic made it difficult to obtain pharmaceutical‐grade injectable anaesthetics used in animal experiments in Japan. To address this problem, it is worth the effort to evaluate whether the use of non‐pharmaceutical‐grade sodium pentobarbital (PBNa) water solution can be an alternative one from the perspective of stability, physicochemical properties, bioavailability and so on. In this article, as a first step, we examined the stability of PBNa 5w/v% aqueous solution (PBNa 5% AS). PBNa 5% AS sample was prepared simply by dissolving non‐pharmaceutical‐grade PBNa into water and was stored at 25°C and 5°C for 15 days. Visual appearance, pH, osmolality and assay (contents of PBNa and related substances) were tested. The stability test results indicated that there was no profound change in these test items of the PBNa 5% AS under either storage condition, suggesting that the formulation was sufficiently stable in such a short term. The only observable change was an increase of an impurity under 25°C storage; however, it was at a negligible level. Moreover, as the pH of the formulation remained

ObjectiveTo describe the clinical signs, electroencephalographic (EEG) findings, treatment, and outcome in a dog after successful resuscitation from out-of-hospital cardiopulmonary arrest (OHCA) induced by pentobarbital intoxication.Case summaryA 10-year-old, male intact Jack Russell Terrier was referred for management of refractory status epilepticus and presented dead on arrival. After 7 minutes of cardiopulmonary resuscitation, return of spontaneous circulation was achieved, but the dog remained comatose, apneic, and lacked brainstem reflexes on neurological examination 6 hours following resuscitation. Magnetic resonance imaging showed polioencephalomalacia consistent with prolonged epileptiform activity, and EEG was initially concerning for electrocerebral inactivity. Following supportive care that included short-term mechanical ventilation, the dog made a full recovery and was discharged from the hospital alive 7 days postresuscitation. It was later revealed that the dog had been administered an unknown amount of pentobarbital during transportation, which likely contributed to the OHCA, clinical, and EEG findings.New information providedThis is the first report to describe the full recovery and hospital discharge of a dog suffering OHCA and the first description of EEG findings in a clinical veterinary patient following cardiopulmonary arrest and successful resuscitation. Factors likely contributing to successful patient outcome and potential benefits and limitations of EEG in monitoring postcardiac arrest patients are discussed.

Porcine epidemic diarrhea virus (PEDV) has caused huge economic losses to the pig industry. Yeast polysaccharides (YP) has been used as a feed additive in recent years and poses good anti-inflammatory and antiviral effects. The present study aimed to explore the protective effect of YP on intestinal damage in PEDV-infected piglets. Eighteen 7-day-old piglets with similar body weights were randomly divided into three groups: Control group (basal diet), PEDV group (basal diet), and PEDV+YP group (basal diet +20 mg/kg BW YP), six replicates per group and one pig per replicate. Piglets in PEDV group and PEDV+YP group were orally given PEDV (dose: 1 × 106 TCID50) at 19:30 PM on the 8th day of the experiment. The control group received the same volume of PBS solution. Weight was taken on an empty stomach in the morning of the 11th day, blood was collected and then anesthetic was administered with pentobarbital sodium (50 mg/kg·BW) by intramuscular injection, and samples were slaughtered after the anesthetic was complete. The results showed that YP could alleviate the destruction of intestinal villus morphology of piglets caused by PEDV. Meanwhile, PEDV infection can reduce the activity of glutathione peroxidase, superoxide dismutase and catalase, and increase the content of malondialdehyde. YP can improve the antioxidative capacity in the serum and small intestine of PEDVinfected piglets. In addition, YP inhibited the replication of PEDV in the jejunum ileum and colon. Moreover, YP can regulate the mRNA levels of inflammatory genes (IL-1ß and iNOS) and lipid metabolic genes (APOA4 and APOC3) in the small intestine. In summary, YP could inhibit virus replicates, improve intestinal morphology, enhance antioxidant capacity, relieve inflammation and regulate the metabolism of the intestine in PEDV-infected piglets. [ABSTRACT FROM AUTHOR]

The administration of the α2-adrenergic receptor agonist clonidine via intracerebroventricular route produces hypotension in pentobarbital-anesthetized rats and pressor responses in conscious normotensive rats. We explored the impact of different anesthetics on the central nervous system-dependent cardiovascular effects of clonidine. Normotensive male Wistar rats with guide cannulas previously implanted in the cerebroventricular system were anesthetized with pentobarbital or ketamine/xylazine and prepared for blood pressure measurement. The animals received intracerebroventricular injections of 10 μg clonidine or 0.6 μg dexmedetomidine, and the effects on the systolic, diastolic, mean arterial pressure, and heart rate were evaluated. The influence of 5 μg yohimbine, a selective α2-adrenergic receptor antagonist, was also assessed. The i.c.v. microinjection of clonidine decreased all three components of systemic arterial pressure and the heart rate of pentobarbital-anesthetized rats. On the other hand, clonidine increased the blood pressure and generated a less intense reduction in the heart rate of ketamine/xylazine-anesthetized rats. The pressor and bradycardic effects of clonidine in ketamine/xylazine-anesthetized animals were reproduced by dexmedetomidine, a more selective α2-adrenergic receptor agonist. Notably, the previous intracerebroventricular injection of yohimbine significantly inhibited the hypertensive effect of clonidine and dexmedetomidine. This study discloses that while normotensive rats anesthetized with pentobarbital show hypotensive responses, the stimulation of α2-adrenergic receptors increases the blood pressure in rats under ketamine/xylazine-induced anesthesia, reproducing the effects seen in conscious normotensive animals. Recognizing the mechanisms involved in these differences may allow us to understand better the final effects of clonidine and other α2-adrenergic receptor agonists in the central nervous system, contributing to the repurposing of these drugs. [ABSTRACT FROM AUTHOR]

Background and Aim: The objective was to evaluate the effect of a cream based on the essential oil of Origanum vulgare on skin lesions induced in Mus musculus Balb/c. Materials and Methods: The experimental animals were divided into four groups of 6 specimens each, in which skin lesions of approximately 1 cm in diameter were induced. Group I (Control) received no treatment, Group II (0.1% Origanum vulgare cream), Group III (0.5% Origanum vulgare cream), and Group IV (1% Origanum vulgare cream) received treatment for eight days. Skin lesions were measured on days 4 and 7. At the end of treatment, they were euthanized using sodium pentobarbital 60 m/kg v.ip. Skin samples were obtained and preserved in 10% formalin for histopathological analysis. Results: When measuring the size of the skin lesions induced in the study groups, it was observed that in the control group, the decrease in the length of the lesions occurred on the fifth day; in group II, III, and IV, the lesions length decrease occurs on the second day. At the end of the experience, the measurements of the lesions were much smaller for the III and IV groups (0.33 and 0.41, respectively) compared to the control group (0.40 cm). On day seven, statistically significant difference was found on skin lesion measure between Group IV and the Control, with a significance level of p<0.05. Conclusion: It is concluded that the 1% Origanum vulgare essential oil-based cream has a healing effect on dermal lesions induced in Mus musculus Balb/c. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pentobarbital and isoflurane are commonly used veterinary anesthetics. Due to the dangers of overdose by repeat-bolus regimen of pentobarbital, isoflurane has been recommended. However, literature suggests isoflurane-induced inhibition of cytokine and adhesion molecule release, impacting leukocyte adhesion. OBJECTIVE: This study aims to characterize the impacts of pentobarbital versus isoflurane on leukocyte interactions within the intestinal microcirculation with and without endotoxin challenge. METHODS: Female BALB/c mice were subjected to pentobarbital or isoflurane (N = 20) and challenged with endotoxin or saline by intraperitoneal injection. The mice were kept under anesthesia for 2 hours. Fluorochromes, rhodamine-6 G and fluorescein isothiocyanate, were injected intravenously. To visualize leukocyte adhesion within the intestinal microcirculation, laparotomy and intravital microscopy was performed. Leukocyte rolling and adhesion was quantified offline in a blinded fashion. RESULTS: Within collecting venules, leukocyte rolling and adhesion showed no significant differences between pentobarbital and isoflurane anesthesia under basal conditions. Endotoxin challenge caused a similar response in both anesthetic groups. Within postcapillary venules, no statistical differences between the two anesthetics were found for adhering leukocytes under basal conditions or following endotoxin challenge either. However, leukocyte rolling after LPS-challenge was significantly decreased in postcapillary venules during isoflurane anesthesia compared to pentobarbital anesthesia. CONCLUSIONS: Isoflurane anesthesia showed only minor differences in the immune response to endotoxin within the intestinal microcirculation compared to pentobarbital anesthesia. Due to the superior safety profile of volatile anesthetics, immunological studies may choose isoflurane over pentobarbital as the veterinary anesthetic of choice. [ABSTRACT FROM AUTHOR]

Myocardial ischemia/reperfusion (I/R) injury is the leading cause of death worldwide. Ginsenoside Rd (GRd) has cardioprotective properties but its efficacy and mechanism of action in myocardial I/R injury have not been clarified. This study investigated GRd as a potent therapeutic agent for myocardial I/R injury. Oxygen-glucose deprivation and reperfusion (OGD/R) and left anterior descending (LAD) coronary artery ligation were used to establish a myocardial I/R injury model in vitro and in vivo. In vivo, GRd significantly reduced the myocardial infarct size and markers of myocardial injury and improved the cardiac function in myocardial I/R injury mice. In vitro, GRd enhanced cell viability and protected the H9c2 rat cardiomyoblast cell line from OGD-induced injury GRd. The network pharmacology analysis predicted 48 potential targets of GRd for the treatment of myocardial I/R injury. GO and KEGG enrichment analysis indicated that the cardioprotective effects of GRd were closely related to inflammation and apoptosis mediated by the PI3K/Akt signaling pathway. Furthermore, GRd alleviated inflammation and cardiomyocyte apoptosis in vivo and inhibited OGD/R-induced apoptosis and inflammation in cardiomyocytes. GRd also increased PI3K and Akt phosphorylation, suggesting activation of the PI3K/Akt pathway, whereas LY294002, a PI3K inhibitor, blocked the GRd-induced inhibition of OGD/R-induced apoptosis and inflammation in H9c2 cells. The therapeutic effect of GRd in vivo and in vitro against myocardial I/R injury was primarily dependent on PI3K/Akt pathway activation to inhibit inflammation and cardiomyocyte apoptosis. This study provides new evidence for the use of GRd as a cardiovascular drug. [ABSTRACT FROM AUTHOR]

aimei Lun,3 Yaoli Liu,1 Shangyong Zhu11Department of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China; 2Department of Traditional Chinese Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China; 3Department of Ultrasound, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People's Republic of China Correspondence: Shangyong Zhu, Department of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China, Email [email protected] Purpose: Few studies have assessed the effects of sphingosine kinase 1/sphingosine-1-phosphate (SPHK1/S1P) on microangiogenesis at rat myofascial trigger points (MTrPs) using contrast-enhanced ultrasonography (CEUS). This study aimed to address these deficiencies. Here, we investigated the effects of SPHK1/S1P on MTrP microangiogenesis and the value of CEUS in evaluating these effects. Methods: Forty Sprague‒Dawley rats were subdivided into two groups: control and MTrP groups. MTrPs were established by 8 weeks of the strike procedure combined with eccentric motion and 4 weeks of recovery. All rats were euthanized after having undergone CEUS with an overdose of pentobarbital sodium. MTrP and control tissue samples were removed for haematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) imaging. The tissue was dehydrated, cleared, and embedded before sectioning. The sections were then incubated overnight at 4°C, and immunohistochemistry was carried out with primary antibodies including rabbit anti-CD31, rabbit anti-SPHK1and rabbit anti-S1PR1. Results: MTrP rats exhibited spontaneous electrical activity (SEA) and a local twitch response (LTR) during electromyography (EMG) examination. The CEUS time-intensity curves (TICs) showed that the perfusion intensity in the MTrPs and surrounding tissue area was increased, with faster perfusion than in normal sites, while the TICs in the control group slowly increased and then slowly decreased. The correlation coefficient between the microvessel density (MVD) and sphingosine 1-phosphate receptor 1 (S1PR1) was 0.716 (p < 0.01). Spearman correlation analysis revealed that Spearman's rho (ρ) values between the MVD and peak intensity (PI), between the MVD and area under the curve (AUC), and between the MVD and SPHK1 were > 0.5 (p < 0.05), > 0.7 (p < 0.01), and > 0.7 (p < 0.01), respectively. Conclusion: CEUS is valuable for detecting microangiogenesis within MTrPs, and SPHK1/S1P plays an important role in promoting MTrP tissue microangiogenesis. [ABSTRACT FROM AUTHOR]

Neuroscience, which covers the molecular mechanisms employed by the brain to cause neurological diseases and how they can be treated, remains current as the subject of high-budget investigations to develop early diagnosis and new treatment modalities with multidisciplinary approaches. For this purpose, creating the appropriate model with the correct modality and anesthesia in neurological in vivo experimental models is the most important phase to obtain accurate results and ensure animal welfare. To manage anesthesia in rodents, knowing the physiological characteristics of anesthetics and their risks will strengthen experimental procedures. Among the injectable anesthetics, ketamine, xylazine, and pentobarbital are the most frequently preferred agents for general anesthesia in short surgical procedures. Isoflurane and sevoflurane are inhaler anesthetics that are administered through a vaporizer because they are liquids. Important advantages of inhaled anesthetics, such as rapid induction and rapid withdrawal, make inhaled anesthetics stand out in neuroscience studies. In this review, the properties of frequently used anesthetic agents in rodents, their usage methods, and which model they are preferred will be discussed. For this purpose, the selection of appropriate anesthetics in animal models such as epilepsy, Alzheimer's disease, ischemia-reperfusion injury, traumatic brain injury, ischemic stroke, experimental autoimmune encephalomyelitis, and ophthalmic surgical procedures and their side effects will be reviewed. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Difficult analgosedation is common and challenging in the pediatric intensive care unit (PICU). It is important to study alternative and supplemental sedatives for when the first-line agents become insufficient. METHODS: In this retrospective chart-review study, we report our center's experience in using intermittent doses of enteral pentobarbital as an adjunct sedative in 13 difficult to sedate critically ill and mechanically ventilated children. We compare the average sedation score and cumulative doses of other sedatives (opioids, benzodiazepines and alpha-2 agonists) in the 24 hours before and 24 hours after enteral pentobarbital initiation. RESULTS: The addition of enteral pentobarbital was associated with lower State Behavioral State (SBS) scores in 8 out of the 13 patients and on average smaller doses of opioids (decreased by 11%), benzodiazepines (BZD) (decreased by 5%) and alpha-agonists (decreased by 20%). No adverse effects were noted attributable to pentobarbital administration. CONCLUSION: Enteral pentobarbital seems to be safe and effective agent in the difficult to sedate critically ill child. [ABSTRACT FROM AUTHOR]

Background: Toll-like receptor 8 (TLR8) can recognize specific pathogen-associated molecular patterns and exert multiple immunological functions through activation of signaling cascades. However, the precise distribution and age-related alterations of TLR8 in the spleens of Bactrian camels have not yet been investigated. This study aimed to prepare a rabbit anti-Bactrian camel TLR8 polyclonal antibody and elucidate the distribution of TLR8 in the spleens of Bactrian camels at different age groups. The methodology involved the construction of the pET-28a-TLR8 recombinant plasmid, followed by the expression of TLR8 recombinant protein via prokaryotic expression. Subsequently, rabbits were immunized with the purified protein to prepare the TLR8 polyclonal antibody. Finally, twelve Alashan Bactrian camels were categorized into four groups: young (1–2 years), pubertal (3–5 years), middle-aged (6–16 years) and old (17–20 years). These camels received intravenous sodium pentobarbital (20 mg/kg) anesthesia and were exsanguinated to collect spleen samples. Immunohistochemical techniques were employed to observe and analyze the distribution patterns and age-related changes of TLR8 in the spleen. Results: The results showed that the TLR8 recombinant protein was expressed in the form of inclusion body with a molecular weight of 52 kDa, and the optimal induction condition involved 0.3 mmol/L IPTG induction for 8 h. The prepared antibody yielded a titer of 1:32 000, and the antibody demonstrated specific binding to TLR8 recombinant protein. TLR8 positive cells exhibited a consistent distribution pattern in the spleen across different age groups of Bactrian camels, primarily scattered within the periarterial lymphatic sheath of the white pulp, marginal zone, and red pulp. The predominant cell type expressing TLR8 was macrophages, with expression also observed in neutrophils and dendritic cells. Statistical analysis revealed that there were significant differences in the distribution density of TLR8 positive cells among different spleen regions at the same age, with the red pulp, marginal zone, and white pulp showing a descending order (P<0.05). Age-related changes indicated that the distribution density in the marginal zone and red pulp exhibited a similar trend of initially increasing and subsequently decreasing from young to old camels. As camels age, there was a significant decrease in the distribution density across all spleen regions (P<0.05). Conclusions: The results confirmed that this study successfully prepared a rabbit anti-Bactrian camel TLR8 polyclonal antibody with good specificity. TLR8 positive cells were predominantly located in the red pulp and marginal zone of the spleen, signifying their pivotal role in the innate immune response of the spleen. Aging was found to significantly reduce the density of TLR8 positive cells, while leaving their scattered distribution characteristics unaffected. These findings provide valuable support for further investigations into the immunomorphology and immunosenescence of the spleen in Bactrian camels. [ABSTRACT FROM AUTHOR]

Although great progress has been made in the diagnosis and treatment of acute myocardial infarction (AMI) in recent years, its morbidity and mortality are still relatively high. In this study, we explain that the function of Sestrin2 gene in Anxiety and Depression Myocardial infarction and its possible mechanism. 26 patients with Anxiety and Depression Myocardial infarction (ADMI) and 26 normal volunteers were collected from our hospital. All mice anaesthetized using 50 mg/kg of pentobarbital sodium and the left anterior descending arteries (LAD) were ligated to induce myocardial infarction. H9c2 cells were stimulated with 5% oxygen (O2) and 5% carbon dioxide (CO2) and 90% N2 for 24 h. The serum expression of Sestrin2 in patients with ADMI was up-regulated. Sestrin2 gene up-regulation reduced collagen I/II and KEAP1 mRNA expressions, and increased GPX4 and Nrf2 mRNA expressions in vitro model of AMI. Down-regulation of Sestrin2 increased collagen I/II and KEAP1 mRNA expressions, and decreased GPX4 and Nrf2 mRNA expressions in vitro model of AMI. These data confirmed that Sestrin2 reduced inflammation and ferroptosis in model of ADMI by LKB1-mediated AMPK activation. This infers that Sestrin2 is potential target to be used in the treatment of premature AMI. [ABSTRACT FROM AUTHOR]

Background and Aim: Potato (Solanum tuberosum L.) is mainly characterized by its antioxidant and healing properties. Therefore, this study aimed to evaluate the effects of an ointment based on S. tuberosum L. “papa tumbay” on burns induced in Balb/c mice (Mus musculus). Materials and Methods: The experimental animals were divided into four groups (n = 5/group) 48 h before second-degree burns were inducted. After epilating the loin areas of the mice and anesthetizing them with ketamine/xylazine (80 mg/kg/10 mg/kg) through intraperitoneal (i.p.) route, a round metal rod (0.7 cm in diameter) was placed on the depilated skin at a temperature of 100°C for 5 s. Group I was not given any treatment, Group II was treated with silver sulfadiazine (1%), and the other two groups (III and IV) were treated with the ointment formulated based on S. tuberosum L. “papa tumbay” at 1% and 2%, respectively. After performing the treatment for 21 days, the mice were euthanized using i.p. sodium pentobarbital (185 mg/kg) to obtain skin samples. The samples were preserved in 10% neutral-buffered formalin and subjected to histopathological analysis. Results: We found statistically significant differences in the histopathological sections between the groups (p < 0.05). The abundant collagen and fibroblasts observed in the direction of the dermis in Groups III and IV indicate that the phytoconstituents present in the potato might promote the healing of the second-degree burns until day 21 of treatment. Conclusion: Our findings showed that the ointments based on the ethanolic extracts of S. tuberosum L. “papa tumbay,” especially the 2% ointment, might accelerate the healing of second-degree burns induced in Balb/c mice. [ABSTRACT FROM AUTHOR]

We previously reported that sodium pentobarbital inhibited the growth of the breast cancer associated with the normalization of microcirculatory hemodynamics and oxygenation. Here, we aimed to screen the key regulatory proteins involved in pentobarbital‐induced normalization of microcirculatory hemodynamics in the breast cancer tissues. A nude mice model of xenograft was established using triple negative breast cancer cell line MDA‐MB‐231. After tumor cell implantation, the mice were subcutaneously injected with 50 mg/kg/day of sodium pentobarbital or an equal volume of solvent adjacent to the tumor for 14 days. Liquid chromatography linked to tandem mass spectrometry (LC–MS/MS) was used to analyze the difference in protein expression profile between the two groups. Ingenuity pathway analysis (IPA) was used to perform the canonical pathway analysis, upstream regulators analysis, and protein–protein interaction networks analysis. Screened proteins were confirmed by real‐time quantitative polymerase chain reaction (RT–qPCR) and Western blot analysis. A total of 101 differentially expressed proteins were revealed between groups. Canonical pathway analysis suggested that acute phase response signaling (z = 1, p =.00208), dilated cardiomyopathy signaling pathway (z = −2, p =.00671), and ILK signaling (z = 1, p =.0172) were key pathways with highlight associations. The mRNA and protein expressions of SMTNL1 were found significantly decreased in pentobarbital‐treated tumor tissues compared with those in controls (both p <.01). Nine important protein–protein interaction networks were identified, and of which, two contained multiple downstream regulatory proteins of SMTNL1. In conclusion, SMTNL1 is revealed as a key protein involved in pentobarbital‐induced growth inhibition signaling in breast cancer. SMTNL1 may become a new potential target for tumor microcirculation research. [ABSTRACT FROM AUTHOR]

Research has shown that engaging pain (nociceptive) pathways after spinal cord injury (SCI) aggravates secondary injury and undermines locomotor recovery. This is significant because SCI is commonly accompanied by additional tissue damage (polytrauma) that drives nociceptive activity. Cutting communication with the brain by means of a surgical transection, or pharmacologically transecting the cord by slowly infusing a sodium channel blocker (lidocaine) rostral to a thoracic contusion, blocks pain-induced hemorrhage. These observations suggest that the adverse effect of pain after SCI depends on supraspinal (brain) systems. We hypothesize that inhibiting brain activity using a general anesthetic (e.g., pentobarbital, isoflurane) should have a protective effect. The present study shows that placing rats in an anesthetic state with pentobarbital or isoflurane 24 h after a lower thoracic contusion injury blocks pain-induced intraspinal inflammation and hemorrhage when administered before pain. Pentobarbital also extends protective effects against locomotor deficits produced by noxious stimulation. Inducing anesthesia after noxious stimulation, however, has no effect. Similarly, subanesthetic dosages of pentobarbital were also ineffective at blocking pain-induced hemorrhage. Also examined were the hemodynamic impacts of both pain and anesthetic delivery after SCI. Peripheral pain-input induced an acute increase in systolic blood pressure; isoflurane and pentobarbital prevent this increase, which may contribute to the protective effect of anesthesia. The results suggest that placing patients with SCI in a state akin to a medically induced coma can have a protective effect that blocks the adverse effects of pain. [ABSTRACT FROM AUTHOR]

Background Barbiturate poisoning is rare but potentially fatal. Case Report We reported a case of barbiturate poisoning in a 28-year-old woman who recovered from lethal pentobarbital deliberate self-poisoning. The initial blood pentobarbital concentration was 61 mg/L, corresponding to a potentially lethal dose. Despite the ingestion of a high dose of pentobarbital, the electroencephalogram revealed an unattended pattern compatible with possible nonconvulsive status epilepticus. Following resuscitation maneuvers, appropriate care, and antiseizure medication, the patient awakened after 7 days. The evolution was excellent without neurological deficits at 2 months. Conclusion Despite the expected and known effects of high-dose pentobarbital in reducing and suppressing cortical activity in the brain, the present case demonstrates that lethal dose of pentobarbital may have an epileptogenic effect. Our hypothesis was that the mechanism of the origin of such a picture is a relatively abrupt decrease in toxic doses of pentobarbital, resulting in a withdrawal phenomenon.

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. [ABSTRACT FROM AUTHOR]

To compare the anesthesia effect of compound ketamine and pentobarbital sodium in orthopedic surgery, 30 specific pathogen free C57BL/6J male mice were included and randomly enrolled into group A (compound ketamine group) and group B (pentobarbital sodium group). The changes of respiratory frequency, heart rate, body temperature, blood oxygen saturation, anesthesia duration, and anesthesia depth among mice in the two groups were compared. It was demonstrated that respiratory frequency declined in the two groups. Heart rate showed no apparent changes as anesthesia was continued. Heart rate was high in group A at 50 min while it was low in group B at 90 min. Body temperature among mice in the two groups generally declined. After 90 min, it dramatically declined in group A. Body temperature was the lowest in group B at 90 min. Blood oxygen saturation generally raised in the two groups. As to anesthesia duration, induction and anesthesia periods were relatively longer in group B. The score for anesthesia depth of group B remained above 3 points 20 min after rectification disappeared and anesthesia duration of group B was notably longer. The research findings revealed that compound ketamine and pentobarbital sodium showed excellent anesthesia effects and physiological indicators. The latter one was characterized by long anesthesia duration, low safety, and high fatality. [ABSTRACT FROM AUTHOR]

We aimed to investigate the effects of thymoquinone (TQ) against Doxorubicin (DOX)-induced toxicity in liver, lung, kidney, testes, diaphragm and stomach tissues of rats. Healthy twenty-eight Wistar albino male rats aged three months, were divided into four groups, each containing seven animals: Group 1: Control (C group); the rats were injected intraperitoneally with saline 5 times every other day and given by gavage to the vehicle solution Group 2 (T group): Rats treated with thymoquinone (10mg/kg given by gavage), Group 3 (D group): Rats treated with doxorubicin were injected intraperitoneally (3mg/kg) and Group 4 (DT group): Rats treated with doxorubicin (injected intraperitoneally with 3mg/kg DOX) and thymoquinone (10mg/kg given by gavage). Group 2 (T group): TQ (10mg/kg) was administered by gavage at 24-hour intervals for 4 weeks. Saline (i.p.) was injected to rats 5 times every other day. Group 3 (D group): The rats were injected with 3 mg/kg DOX (i.p.) 5 times every other day. In addition, vehicle solution was administered by gavage at 24-h intervals for 4 weeks. Group 4 (DT group): Rats were injected with 3mg/kg DOX (i.p.) 5 times every other day. TQ (10mg/kg) was administered by gavage at 24-h intervals for 4 weeks. At the end of the experiment, the animals were euthanized with sodium pentobarbital (50 mg/kg) and their lung, liver, stomach, kidney, diaphragm and testicular tissues were removed for the measurement of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) levels. It was observed that DOX administration (in group D) increased lipid peroxidation and decreased antioxidant enzyme levels in the peripheral tissues of rats. It was determined that TQ treatment (in the DT group) given with DOX decreased lipid peroxidation and increased antioxidant enzyme levels. In our study, it was determined that TQ treatment eliminated the toxic effects of DOX and the protective effects of TQ were revealed. [ABSTRACT FROM AUTHOR]

Simple Summary: The present study aimed to assess the infrared thermal response of laboratory rats (Rattus norvegicus) during the application of six euthanasia methods (injectable, inhalational, and physical) to determine the method that prevents or diminishes the stress response. The surface temperature was assessed in four thermal windows: ocular (T°ocu), auricular (T°ear), interscapular (T°dor), and caudal (T°tai). The results showed that inhalant methods (CO2 and isoflurane) had temperature alterations that could be suggestive of a marked stress response, in contrast to other methods such as pentobarbital, decapitation, and xylazine + ketamine. In conclusion, according to the thermal response of the rats, it is suggested that CO2 and isoflurane might cause distress and this needs to be considered when selecting these techniques as the method of euthanasia for laboratory rats. Refinement is one of the principles aiming to promote welfare in research animals. The techniques used during an experimental protocol, including euthanasia selection, must prevent and minimize suffering. Although the current euthanasia methods applied to laboratory rodents are accepted, the controversial findings regarding the potential stress/distress they can cause is a field of research. The objective was to assess the thermal response of Wistar rats during various euthanasia methods using infrared thermography (IRT) to determine the method that prevents or diminishes the stress response and prolonged suffering. Pentobarbital (G1), CO2 (G2), decapitation (G3), isoflurane (G4), ketamine + xylazine (G5), and ketamine + CO2 (G6) were evaluated at five evaluation times with IRT to identify changes in the surface temperature of four anatomical regions: ocular (T°ocu), auricular (T°ear), interscapular (T°dor), and caudal (T°tai). Significant differences (p < 0.05) were found in G2 and G4, registering temperature increases from the administration of the drug to the cessation of respiratory rate and heart rate. Particularly, isoflurane showed a marked thermal response in T°ocu, T°ear, T°dor, and T°tai, suggesting that, in general, inhalant euthanasia methods induce stress in rats and that isoflurane might potentially cause distress, an effect that must be considered when deciding humane euthanasia methods in laboratory rodents. [ABSTRACT FROM AUTHOR]

Simple Summary: The assessment of the depth of anaesthesia remains challenging. In experimental pigs, the use of electroencephalography-based monitors has spread to characterizing brain activity depression as a surrogate of anaesthetics' hypnotic effect. However, these devices have been validated for humans and, most of the time, a mere application has been performed in animal species including pigs with little effort made to assess their actual usability. Moreover, while artefacts within the electroencephalographic signal originating from other sources than the brain (e.g., electromyographic activity) have been extensively reported in humans, such interferences have not been characterized in this species yet. We report the contamination of the electroencephalographic signal by the electrocardiographic activity in two pigs undergoing general anaesthesia, leading to miscalculation of the variables displayed by the depth of the aesthesia monitor Sedline. Visual interpretation of the raw electroencephalogram remains necessary to avoid making wrong clinical decisions based on such electroencephalography-derived variables. Two young (11-week-old) pigs underwent sole propofol anaesthesia as part of an experimental study. The depth of anaesthesia was evaluated both clinically and using the electroencephalography(EEG)-based monitor Sedline; in particular, the patient state index, suppression ratio, raw EEG traces, and its spectrogram were assessed. Physiological parameters and electrocardiographic activity were continuously monitored. In one pig (Case 1), during the administration of high doses of propofol, the Sedline-generated variables suddenly indicated an increased EEG activity while this was not confirmed by observation of either the raw EEG or its spectrogram. In the second pig (Case 2), a similar event was recorded during euthanasia with systemic pentobarbital. Both events happened while the EEG activity was isoelectric except for signal interferences and synchronous in rhythm and shape with the electrocardiographic activity. The suggestion of increased brain activity based on the interpretation of the Sedline variables was suspected wrong; most probably due to electrocardiographic interferences. In pigs, the patient state index and suppression ratio, as calculated by the Sedline monitor, could be influenced by the electrocardiographic activity contaminating the EEG trace, especially during otherwise isoelectric periods (strong EEG depression). Visual interpretation of the raw EEG and of the spectrogram remains necessary to identify such artefacts. [ABSTRACT FROM AUTHOR]

Sleep improvement effect of Semen Ziziphi Spinosae extract, longan aril extract, and ã-aminobutyric acid. were compared through direct sleep, sodium pentobarbital-induced sleep extension, subthreshold dose sodium pentobarbital-induced hypnosis, and sodium barbital-induced sleep latency experiments were carried out. The results showed that all three functional formulations had no significant effect on the direct sleep and body weight of mice. However, the high (33.3 mg/kg·d), medium (16.7 mg/kg·d), and low dose (8.3 mg/kg·d) of ã-aminobutyric acid, the high (110 mg/kg·d) and medium (55 mg/kg·d dose of Semen Ziziphi Spinosae extract, as well as the low dose (66.5 mg/kg·d) of longan aril extract could significantly prolong the sodium pentobarbital-induced sleep time of mice. Further, ã-aminobutyric acid had the greatest hypnotic effect on mice treated with the subthreshold dose of sodium pentobarbital. Among the 12 mice tested, 2 fell asleep at high, medium, and low doses of ã-aminobutyric acid. Thus, the incidence of sleep reached 16.67%. The high, medium, and low dose of Semen Ziziphi Spinosae extract could shorten the sleep latency of mice hypnotized by sodium barbital, whereas only the high- and medium-dose groups were significantly different from the control group (P<0.05). [ABSTRACT FROM AUTHOR]

Insomnia leads to the development of mental problems and missing of accuracy in affected persons. Various investigations have previously revealed which medicinal plants play a role in the improvement of insomnia. In this study, we evaluated the effect of hydro-alcoholic extract of Datura stramonium on insomnia in mice. The extracts and fractions at different concentrations were injected intraperitoneally (i.p.) to mice 30 min before the sodium pentobarbital (30 mg/kg, i.p.). Additionally, the blood was collected from cardiac and serum separated to measure brain-derived neurotrophic factor (BDNF). The LC-MS was done to identify the active components. Flumazenil or naloxone were also applied to study the possible mechanism of extract. The PC12 cells were then exposed to different doses of extract and fractions, in order to evaluate cytotoxicity by MTT assay and the measured LD50. The hydro-alcoholic extracts of calyx, seed and petal elevated sleep duration and decreased sleep latency. In addition, water, ethyl acetate and n-butanol fractions of hydro-alcoholic extract of petal increased sleep duration. Of note, Naloxone significantly reversed the hypnotic effect of the extract. The extract increased the level of BDNF in serums. As well, the toxicity assessment revealed that the extracts had not toxic on PC12 cells. The LD50 value was obtained as 4.8 g/kg. This research demonstrated that D. stramonium (including seed, petal and calyx) increased the hypnotic effect without neurotoxicity on PC12 cells. Sleep induction may be related to its active ingredients as well as the effect on opioid receptors. [ABSTRACT FROM AUTHOR]

Chicoric acid (CA), a functional food ingredient, is a caffeic acid derivative that is mainly found in lettuce, pulsatilla, and other natural plants. However, the anti-inflammatory effects of CA in acute lung injury (ALI) remain poorly understood. This study was conducted to investigate potential drug usage of CA for ALI and the underlying molecular mechanisms of inflammation. C57BL/6 mice were given injections of liposaccharide (LPS) to establish the in vivo model. Meanwhile, BMDM cells were stimulated with LPS+ATP to build the in vitro model. CA significantly alleviated inflammation and oxidative stress in both the in vivo and in vitro models of ALI through the inhibition of NLR family pyrin domain-containing 3 (NLRP3)-mediated pyroptosis. In addition, CA attenuated mitochondrial damage to suppress NLRP3-mediated pyroptosis in the in vivo and in vitro models of ALI by suppressing the production of reactive oxygen species (ROS) via inhibiting the Akt/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. CA inhibited the interaction between Akt at T308 and phosphoinositide-dependent kinase-1 (PDPK1) at S549, thus promoting the phosphorylation of the Akt protein. Furthermore, CA directly targeted the PDPK1 protein and accelerated PDPK1 ubiquitination, indicating that 91-GLY, 111-LYS, 126-TYR, 162-ALA, 205-ASP, and 223-ASP might be responsible for the interaction between PDPK1 and CA. In conclusion, CA from Lettuce alleviated NLRP3-mediated pyroptosis in the ALI model through ROS-induced mitochondrial damage by activating Akt/Nrf2 pathway via PDPK1 ubiquitination. The present study suggests that CA might be a potential therapeutic drug to treat or prevent ALI in pneumonia or COVID-19. [ABSTRACT FROM AUTHOR]

Postmortem and pre-euthanasia oocyte retrieval provides the last opportunity to preserve the genetic material in mares. Pentobarbital (PB) is the most common euthanasia agent; however, its effect on the developmental competence of oocytes has not been determined. Here, we evaluated the concentration of PB in equine follicular fluid (FF) and investigated its effect on the developmental competence of oocytes using a bovine IVF model to overcome the low availability of equine oocytes. The concentration of PB was measured by gas-chromatography/mass-spectrometry in FF collected from mare ovaries immediately after euthanasia (n = 10), 24 h post-euthanasia (n = 10), and from the ovaries collected by ovariectomy (negative control; n = 10). The serum concentration of PB was also evaluated as a positive control. PB was detected in all FF samples with an average concentration of 56.5 μg/ml. Next, bovine cumulus-oocyte complexes (COC) were held in holding media with PB for 6 h at 60 μg/ml (H60, n = 196), 164 μg/ml (H164, n = 215) or without PB (control; n = 212). After holding, the oocytes were matured and fertilized in vitro , followed by in vitro culture to the blastocyst stage. The cumulus expansion grade, cleavage rate, blastocyst rate, embryo kinetic rate and the blastocyst cell numbers were compared among the experimental groups of bovine COC. Higher rates of Grade 1 cumulus expansion were found in controls (54%, 32–76%; median, min-max) in comparison to H60 and H164 (24%,11–33% and 13%, 8–44%; P < 0.001). The cleavage rate was higher in the controls than in H164 (64% vs. 44%; P < 0.01). Blastocyst rates (blastocyst/cleaved oocytes) and total cell number were not different among the groups (control 29%, H60 25%, and H164 24%). In a preliminary study, equine oocytes (n = 28) were exposed to PB in vitro for 6 h followed by intracytoplasmic sperm injection (ICSI) and in vitro embryo production. Exposed oocytes showed a numerically lower maturation rate (43% Vs 52%; P > 0.05) in comparison to the laboratory-established rate during the same timepoints. Overall, we showed that PB reaches the FF immediately after euthanasia, exposing oocytes to this drug. This exposure affected cumulus expansion and cleavage rates in a bovine model, suggesting initial damage caused by PB that may not completely impede the formation of embryos, although lower overall embryo numbers might be obtained. • Pentobarbital reaches the follicular fluid of mares after euthanasia. • Pentobarbital concentration in follicular fluid remains stable post-euthanasia. • Exposure to pentobarbital affects cumulus expansion and fertilization of oocytes in vitro. • In vitro production of equine embryos is possible after exposure to pentobarbital. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine the ability of transmucosal euthanasia solution to induce euthanasia in pond slider turtles (Trachemys scripta). ANIMALS 16 pond slider turtles (T. scripta). PROCEDURES Pentobarbital 100 mg/kg was delivered through esophageal gavage (n = 8) or cloacal administration (8). The presence of voluntary movement, heart rate (HR), respiratory rate (RR), palpebral reflex, corneal reflex, and response to noxious stimuli were recorded until death, confirmed via the absence of reflexes, movement, heartbeat, and absence of cardiac electrical activity. RESULTS No signs of irritation were observed in any turtles. Leakage after administration occurred in 75% (6/8) of the cloacal group, including 2 turtles with marked leakage or expulsion. Two of eight turtles in the cloacal group regained movement and required euthanasia by a standard method and 1 turtle in the oral group was excluded from further analysis due to a miscalculated dose. The remaining 13 turtles (7/8 oral, 6/8 cloacal) had cessation of a heartbeat at a median of 18 hours (range = 6 to 26 hours) with respiratory arrest occurring within 15 minutes. The median time to loss of corneal reflex was 45 minutes (range = 15 minutes to 4 hours). Time-to-loss of parameters was similar between oral and cloacal routes, respectively. CLINICAL RELEVANCE Transmucosally administered pentobarbital via the oral and cloacal routes both result in euthanasia within approximately 24 hours. Given that 25% of the turtles in the cloacal group required a secondary method of euthanasia, the oral route is a preferred route to induce euthanasia in pond turtles. [ABSTRACT FROM AUTHOR]

Simple Summary: This study was designed to determine how veterinarians define a good euthanasia experience. Our study included an online survey completed by 249 veterinarians who perform feline and/or canine euthanasia. We found very few veterinarians thought their veterinary school training left them feeling well-prepared to perform euthanasia. When asked to rank a list of factors in terms of perceived euthanasia-related concerns, participants ranked respiratory distress the highest. We found that most veterinarians preferred having owners present during euthanasia and that they want a pain-free, anxiety-free experience for the patient. We have used the results of our study to suggest a new definition of companion animal euthanasia that prioritizes patient welfare along with the needs and expectations of the pet owner. This study was designed to determine how veterinarians define a good euthanasia experience. This information is used to generate a working definition of companion animal euthanasia that aligns with animal welfare standards and pet owners' expectations. An electronic survey distributed via veterinary-related social media (Facebook, Instagram) and listservs were completed by 249 veterinarians who perform feline and/or canine euthanasia. Our results suggest that very few veterinarians feel their veterinary school training adequately prepared them for euthanasia. When veterinarians were asked to rank a list of physiologic conditions and anatomical traits in order of euthanasia-related concerns, respiratory distress was ranked the highest, while the most concerning physical changes were reported to be indications or impressions of seizures or pain. The most commonly reported euthanasia injection technique performed by participants was intravenous administration of pentobarbital sodium (97%), and most veterinarians preferred having owners present (57%) or having no preference (38%) during euthanasia. Results suggest that veterinarians want a pain-free, anxiety-free experience for the patient, appreciate the use of sedatives before euthanasia, and feel that when available and appropriate, home euthanasia offers several benefits. This understanding of the numerous aspects involved in a good euthanasia experience can help inform the creation of an updated definition of companion animal euthanasia that strives to prioritize the welfare of the patient as well as the needs and expectations of the pet owner. [ABSTRACT FROM AUTHOR]

Background: Pentobarbital pharmacokinetics (PK) remain elusive and the therapeutic windows narrow. Administration is frequent in critically ill children with refractory status epilepticus (SE) and severe traumatic brain injury (sTBI). Objectives: To investigate pentobarbital PK in SE and sTBI patients admitted to the paediatric intensive care unit (PICU) with population-based PK (PopPK) modelling and dosing simulations. Methods: Develop a PopPK model with non-linear mixed-effects modelling (NONMEM®) with retrospective data (n = 36; median age 1.3 years; median weight 10 kg; 178 blood samples) treated with continuous intravenous pentobarbital. An independent dataset was used for external validation (n = 9). Dosing simulations with the validated model evaluated dosing regimens. Results: A one-compartment PK model with allometrically scaled weight on clearance (CL; 0.75) and volume of distribution (Vd; 1) captured data well. Typical CL and Vd values were 3.59 L/70 kg/h and 142 L/70 kg, respectively. Elevated creatinine and C-reactive protein (CRP) levels significantly correlated to decreased CL, explaining 84% of inter-patient variability, and were incorporated in the final model. External validation using stratified visual predictive checks showed good results. Simulations demonstrated patients with elevated serum creatinine and CRP failed to achieve steady state yet progressed to toxic levels with current dosing regimens. Conclusions: The one-compartment PK model of intravenous pentobarbital described data well whereby serum creatinine and CRP significantly correlated with pentobarbital CL. Dosing simulations formulated adjusted dosing advice in patients with elevated creatinine and/or CRP. Prospective PK studies with pharmacodynamic endpoints, are imperative to optimise pentobarbital dosing in terms of safety and clinical efficacy in critically ill children. [ABSTRACT FROM AUTHOR]

A case of fatal poisoning involving multiple psychotropic drugs is presented. Quantitative toxicological analysis showed femoral blood concentrations of pentobarbital, phenobarbital, duloxetine, acetaminophen and tramadol were 10.39, 22.57, 0.22, 0.61 and 0.22 µg/ml, respectively. We concluded that the death was due to the additive effects of two barbiturates. As both pentobarbital and phenobarbital act on gamma-aminobutyric acid (GABA) receptors, central nervous system activity was suppressed, causing respiratory depression. Additive pharmacological effects should be considered in cases of massive ingestion of multiple drugs. [ABSTRACT FROM AUTHOR]

Suicide attempts in humans due to injections of the veterinary drug pentobarbital sodium have been rarely reported. Herein, we present a case of a suicide attempt by intramuscular injection of pentobarbital sodium into the rectus abdominis muscle, which was suggested by computed tomography (CT). A 73-year-old man was brought to the emergency department with GCS 3 (E1V1M1) and an incised wound on the right side of the neck. A bottle of Somnopentyl® (pentobarbital sodium, 64.8 mg/ml), a 20-ml empty syringe with an 18-mm needle, and no. 10 scalpel were present at the scene. At the emergency department, the patient was intubated and was admitted to the intensive care unit. A urine drug screen test by SIGNIFY® ER was positive for benzodiazepines and barbiturates, and continuous veno-venous hemofiltration (CHF) was initiated. The route of drug administration was initially unknown; however, a CT scan revealed swelling of the left rectus abdominis muscle with a wound suggestive of a needle puncture, and the CT analysis suggested 38.16 ml as the maximum dose of pentobarbital sodium. On day 3, the patient's consciousness improved, and he was weaned off CHF and mechanical ventilation. There have been several reports of postmortem CT yielding information on the site of administration of intoxicants, but there have been none for surviving intoxicated patients. This is the first report of the usefulness of CT to identify the site of administration of the causative agent of intoxication while the patient is still alive. [ABSTRACT FROM AUTHOR]

To achieve surgical anesthesia in animal experimentation, it is important to select the appropriate anesthetic dose. However, few studies have investigated the reasonable anesthetic dose in tree shrew (Tupaia belangeri). The aim of the study was to review the literature to determine the most commonly used anesthetic dose in tree shrew and to calculate the reasonable equivalent dose between tree shrew and rat based on the body surface area conversion. Two groups of 10 adult tree shrews each were anesthetized with 1% sodium pentobarbital through intraperitoneal injection separately at doses of 62 mg/kg (equivalent dose) and 40 mg/kg (reported dose). Anesthetic depth and times were assessed in addition to vital signs. The results showed that the dosage was quite different across studies, ranging from 15 mg/kg to 80 mg/kg, with 40 mg/kg being the most frequently reported dose. However, the group of tree shrews anesthetized with the commonly reported dose were unable to meet the requirements of surgery. In contrast, the equivalent dose (62 mg/kg, intraperitoneal injection with sodium pentobarbital) calculated by body surface area conversion could achieve an anesthetic time of 44.28 ± 3.95 min with no serious or fatal effects. During anesthetic monitoring, we found that sodium pentobarbital had an inhibitory effect on the blood pressure, pulse rate, respiratory rate and rectal temperature in tree shrews, especially on the respiratory rate. Thus, our study indicated that the use of the equivalent dose of sodium pentobarbital was effective in anesthetizing tree shrews. [ABSTRACT FROM AUTHOR]