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Frontiers in Microbiology 2024Porcine 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...
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 × 10 TCID) 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 PEDV-infected 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-1β 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.
PubMed: 38655081
DOI: 10.3389/fmicb.2024.1378070 -
Journal of Medicinal Food Apr 2024We investigated the effects of L. extracts (Lactuc) on pentobarbital-induced sleep in mice to elucidate the mechanisms underlying its impact on sleep quality. Mice were...
We investigated the effects of 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 GABA receptors subunits 2, 2, 1, and, 2 in the brain tissue. Therefore, we suggest that Lactuc could be used to develop natural products that effectively improve sleep quality and duration.
PubMed: 38603571
DOI: 10.1089/jmf.2023.K.0250 -
Seminars in Neurology Jun 2024Status epilepticus (SE) is a neurological emergency that requires timely pharmacological therapy to cease seizure activity. The treatment approach varies based on the... (Review)
Review
Status epilepticus (SE) is a neurological emergency that requires timely pharmacological therapy to cease seizure activity. The treatment approach varies based on the time and the treatment stage of SE. Benzodiazepines are considered the first-line therapy during the emergent treatment phase of SE. Antiseizure medicines such as phenytoin, valproic acid, and levetiracetam are recommended during the urgent treatment phase. These drugs appear to have a similar safety and efficacy profile, and individualized therapy should be chosen based on patient characteristics. Midazolam, propofol, pentobarbital, and ketamine are continuous intravenous infusions of anesthetic medications utilized in the refractory SE (RSE) period. The most efficacious pharmacotherapeutic treatments for RSE and superrefractory status epilepticus are not clearly defined.
Topics: Status Epilepticus; Humans; Anticonvulsants
PubMed: 38580318
DOI: 10.1055/s-0044-1785503 -
American Journal of Veterinary Research Jun 2024To assess the efficacy of transmucosal euthanasia solution to induce euthanasia.
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.
Topics: Animals; Phenytoin; Lizards; Pentobarbital; Euthanasia, Animal; Male; Female; Administration, Mucosal; Hypnotics and Sedatives
PubMed: 38569538
DOI: 10.2460/ajvr.24.02.0026 -
Histology and Histopathology Mar 2024Severe acute pancreatitis-acute lung injury (SAP-ALI) is a disease with high mortality. This study aims to explore the mechanism of baicalein on SAP-ALI in rats by...
Severe acute pancreatitis-acute lung injury (SAP-ALI) is a disease with high mortality. This study aims to explore the mechanism of baicalein on SAP-ALI in rats by blocking toll-like receptor-4 (TLR4)/myeloid differentiation primary response gene 88 (MyD88)/TIR-domain-containing adapter-inducing interferon-β (TRIF) signal pathway. The SAP-ALI rat model was established by intraperitoneal injection of 3% pentobarbital sodium (30 mg/kg), with pancreas and intestines turned over, injected with 3.5% sodium taurocholate backward into the bile-pancreatic duct at 0.1 mL/100 g for 12h, and treated with baicalein, lipopolysaccharide (LPS), miR-182 agomir, or miR-182 antagomir. The TLR4/MyD88/TRIF pathway was activated using LPS in SAP-ALI rats after baicalein treatment. Baicalein attenuated inflammatory cell infiltration, alveolar wall edema, decreased W/D ratio and levels of TLR4, MyD88, and TRIF in the lung tissues, reduced levels of inflammatory factors in pancreatic and lung tissues and BALF, diminished ROS, and elevated GSH, SOD and CAT in pancreatic and lung tissues of SAP-ALI rats. Activation of the TLR4/MyD88/TRIF pathway partly abrogated baicalein-mediated improvements in inflammation and oxidative stress in SAP-ALI rats. miR-182 targeted TLR4. miR-182 suppressed inflammation and oxidative stress in SAP-ALI rats by targeting TLR4. Inhibition of miR-182 partly nullified baicalein-mediated attenuation on inflammation and oxidative stress in SAP-ALI rats. In conclusion, baicalein can inhibit the TLR4/MyD88/TRIF pathway and alleviate inflammatory response and oxidative stress in SAP-ALI rats by upregulating miR-182 and suppressing TLR4, thus ameliorating SAP-ALI.
PubMed: 38557861
DOI: 10.14670/HH-18-733 -
The Journal of Veterinary Medical... May 2024Euthanasia agents should rapidly induce death and loss of consciousness without causing pain or distress. Various methods exist for the euthanasia of laboratory animals,...
Euthanasia agents should rapidly induce death and loss of consciousness without causing pain or distress. Various methods exist for the euthanasia of laboratory animals, and injectable anesthetics, particularly barbiturate derivatives, are widely used due to the rapid onset of unconsciousness induced by these agents. Moreover, pharmaceutical-grade drugs should be used to eliminate undesirable side effects as much as possible. However, in Japan, the sale of pharmaceutical-grade pentobarbital sodium (PB) ended in 2019, and that of secobarbital sodium (SB) ended in 2023, leading to a demand for new pharmaceutical-grade injectable euthanasia drugs. This study evaluates thiamylal sodium (TM), a barbiturate derivative that is available domestically, as a euthanasia agent for mice. The results showed that when administered at dosages of 200 mg/kg or more, TM exhibited effects equivalent to those of PB and SB. In addition, the impact of TM administration on hematological characteristics was examined. In female mice administered TM, decreased blood chloride and calcium levels and increased aspartate aminotransferase and alanine aminotransferase levels, which are markers of liver damage, were observed. These findings suggest that high concentrations of TM may affect renal and liver function. This study revealed that TM is effective as a euthanasia agent at dosages of 200 mg/kg or more. However, considering the potential risks of renal and liver damage due to TM administration, it may be preferable to use alternative euthanasia drugs when these risks could affect the objectives or outcomes of the research.
Topics: Animals; Female; Euthanasia, Animal; Mice; Male; Pentobarbital
PubMed: 38556347
DOI: 10.1292/jvms.24-0041 -
Phytomedicine : International Journal... Jun 2024Five Polyporales mushrooms, namely Amauroderma rugosum, Ganoderma lucidum, G. resinaceum, G. sinense and Trametes versicolor, are commonly used in China for managing...
BACKGROUND
Five Polyporales mushrooms, namely Amauroderma rugosum, Ganoderma lucidum, G. resinaceum, G. sinense and Trametes versicolor, are commonly used in China for managing insomnia. However, their active components for this application are not fully understood, restricting their universal recognition.
PURPOSE
In this study, we aimed to identify sedative-hypnotic compounds shared by these five Polyporales mushrooms.
STUDY DESIGN AND METHODS
A UPLC-Q-TOF-MS/MS-based untargeted metabolomics, including OPLS-DA (orthogonal projection of potential structure discriminant analysis) and OPLS (orthogonal projections to latent structures) analysis together with mouse assays, were used to identify the main sedative-hypnotic compounds shared by the five Polyporales mushrooms. A pentobarbital sodium-induced sleeping model was used to investigate the sedative-hypnotic effects of the five mushrooms and their sedative-hypnotic compounds.
RESULTS
Ninety-two shared compounds in the five mushrooms were identified. Mouse assays showed that these mushrooms exerted sedative-hypnotic effects, with different potencies. Six triterpenes [four ganoderic acids (B, C1, F and H) and two ganoderenic acids (A and D)] were found to be the main sedative-hypnotic compounds shared by the five mushrooms.
CONCLUSION
We for the first time found that these six triterpenes contribute to the sedative-hypnotic ability of the five mushrooms. Our novel findings provide pharmacological and chemical justifications for the use of the five medicinal mushrooms in managing insomnia.
Topics: Animals; Hypnotics and Sedatives; Mice; Metabolomics; Tandem Mass Spectrometry; Chromatography, High Pressure Liquid; Polyporales; Male; Agaricales; Sleep; Sleep Initiation and Maintenance Disorders; Reishi
PubMed: 38555773
DOI: 10.1016/j.phymed.2024.155355 -
Journal of Ethnopharmacology Jun 2024Sleep problems, according to Traditional Chinese medicine (TCM) philosophy, are attributed to the imbalance between yin and yang. Zhumian Granules, also known as...
ETHNOPHARMACOLOGICAL RELEVANCE
Sleep problems, according to Traditional Chinese medicine (TCM) philosophy, are attributed to the imbalance between yin and yang. Zhumian Granules, also known as Sleep-aid Granules or ZG, are a traditional Chinese herbal remedy specifically designed to alleviate insomnia. This formula consists of many components, including Wu Wei Zi (Schisandrae Chinensis Fructus), Suan Zao Ren (Ziziphi Spinosae Semen), and other medicinal plants. According to the pharmacology of Traditional Chinese Medicine (TCM), Wu Wei Zi and Suan Zao Ren have the ability to relax the mind and promote sleep. When taken together, they may balance the opposing forces of yin and yang. Therefore, ZG may potentially be used as a therapeutic treatment for insomnia.
AIM OF THE STUDY
This research was specifically developed to establish a strong empirical basis for the subsequent advancement and utilization of ZG in the management of insomnia. This research aimed to gather empirical data to support the effectiveness of ZG, thereby providing useful insights into its potential therapeutic advantages for persons with insomnia.
MATERIALS AND METHODS
This study utilized Zhumian Granules (ZG), a traditional Chinese herbal decoction, to examine its sedative and hypnotic effects on mice with PCPA-induced insomnia. The effects were assessed using the pentobarbital-induced sleep test (PIST), Morris water maze test (MWM), and autonomic activity test. The levels of neurotransmitters in each group of mice were evaluated using UPLC-QQQ-MS. The impact of ZG on the quantity and structure of hippocampal neurons was seen in brain tissue slices using immunofluorescence labeling.
RESULTS
ZG was shown to possess active sedative properties, effectively lowering the distance of movement and lengthening the duration of sleep. ZG mitigated the sleeplessness effects of PCPA by elevating the levels of 5-hydroxytryptamine (5-HT), 4-aminobutyric acid (GABA), and 5-hydroxyindoleacetic acid (5-HIAA), while reducing the levels of dopamine (DA) and norepinephrine (NE), as well as decreasing neuronal death.
CONCLUSIONS
This research confirmed the sedative and hypnotic properties of ZG and elucidated its probable mechanism involving neurotransmitters.
Topics: Mice; Animals; Sleep Initiation and Maintenance Disorders; Medicine, Chinese Traditional; Hypnotics and Sedatives; gamma-Aminobutyric Acid; Serotonin; Neurotransmitter Agents; Schisandra; Apoptosis
PubMed: 38484955
DOI: 10.1016/j.jep.2024.118048 -
Clinical NeuropharmacologyRefractory status epilepticus (RSE) treated with anesthetic agents can be associated with complications including respiratory depression and hypotension. Ketamine is an... (Review)
Review
OBJECTIVE
Refractory status epilepticus (RSE) treated with anesthetic agents can be associated with complications including respiratory depression and hypotension. Ketamine is an emerging RSE treatment, but optimal dosing and timing are unknown. We studied provider attitudes and practices regarding the use of ketamine for RSE.
METHODS
A literature review informed the creation of the survey, developed by professionals in epilepsy, pharmacy, and neurocritical care. The survey was distributed to members of the Critical Care EEG Monitoring and Research Consortium, Neurocritical Care Society, American Academy of Neurology Synapse community, American Epilepsy Society, and the Canadian League Against Epilepsy. Descriptive statistics were calculated.
RESULTS
There were 109 respondents. First-line agents for RSE were midazolam (53%), propofol (42%), pentobarbital (2%), and ketamine (1%). Reasons for ketamine use included failure of midazolam/propofol to control seizures (81%) or hypotension on another anesthetic (35%). Perceived contraindications included hypertension (37%), elevated intracranial pressure (24%), and heart failure (18%). Perceived benefits included decreased use of vasopressors (53%) and more rapid RSE control when used adjunctively (49%). Routine ketamine users often treated more than 10 RSE cases per year, worked as intensivists or at academic institutions. Of the respondents, 59% found ketamine useful for RSE and 94% were interested in learning more about its use.
CONCLUSIONS
Although most participants found ketamine helpful for RSE, it is mainly used as a second-line agent adjunctively with midazolam or propofol. Perceived ketamine benefits included decreased need for hemodynamic support and more rapid seizure control when used in conjunction with other anesthetics. Perceived contraindications centered on cardiac and intracranial pressure concerns.
Topics: Humans; Midazolam; Ketamine; Propofol; Anticonvulsants; Canada; Status Epilepticus; Seizures; Hypotension; Epilepsy
PubMed: 38478363
DOI: 10.1097/WNF.0000000000000582 -
JAMA Neurology May 2024Multiple continuous intravenous anesthetic drugs (CIVADs) are available for the treatment of refractory status epilepticus (RSE). There is a paucity of data comparing...
IMPORTANCE
Multiple continuous intravenous anesthetic drugs (CIVADs) are available for the treatment of refractory status epilepticus (RSE). There is a paucity of data comparing the different types of CIVADs used for RSE.
OBJECTIVE
To systematically review and compare outcome measures associated with the initial CIVAD choice in RSE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
EVIDENCE REVIEW
Data sources included English and non-English articles using Embase, MEDLINE, PubMed, and Web of Science (January 1994-June 2023) as well as manual search. Study selection included peer-reviewed studies of 5 or more patients and at least 1 patient older than 12 years with status epilepticus refractory to a benzodiazepine and at least 1 standard antiseizure medication, treated with continuously infused midazolam, ketamine, propofol, pentobarbital, or thiopental. Independent extraction of articles was performed using prespecified data items. The association between outcome variables and CIVAD was examined with an analysis of variance or χ2 test where appropriate. Binary logistic regressions were used to examine the association between outcome variables and CIVAD with etiology, change in mortality over time, electroencephalography (EEG) monitoring (continuous vs intermittent), and treatment goal (seizure vs burst suppression) included as covariates. Risk of bias was addressed by listing the population and type of each study.
FINDINGS
A total of 66 studies with 1637 patients were included. Significant differences among CIVAD groups in short-term failure, hypotension, and CIVAD substitution during treatment were observed. Non-epilepsy-related RSE (vs epilepsy-related RSE) was associated with a higher rate of CIVAD substitution (60 of 120 [50.0%] vs 11 of 43 [25.6%]; odds ratio [OR], 3.11; 95% CI, 1.44-7.11; P = .006) and mortality (98 of 227 [43.2%] vs 7 of 63 [11.1%]; OR, 17.0; 95% CI, 4.71-109.35; P < .001). Seizure suppression was associated with mortality (OR, 7.72; 95% CI, 1.77-39.23; P = .005), but only a small subgroup was available for analysis (seizure suppression: 17 of 22 [77.3%] from 3 publications vs burst suppression: 25 of 98 [25.5%] from 12 publications). CIVAD choice and EEG type were not predictors of mortality. Earlier publication year was associated with mortality, although the observation was no longer statistically significant after adjusting SEs for clustering.
CONCLUSIONS AND RELEVANCE
Epilepsy-related RSE was associated with lower mortality compared with other RSE etiologies. A trend of decreasing mortality over time was observed, which may suggest an effect of advances in neurocritical care. The overall data are heterogeneous, which limits definitive conclusions on the choice of optimal initial CIVAD in RSE treatment.
Topics: Humans; Status Epilepticus; Anesthetics, Intravenous; Drug Resistant Epilepsy; Anticonvulsants
PubMed: 38466294
DOI: 10.1001/jamaneurol.2024.0108