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Frontiers in Veterinary Science 2023Exotic companion animals have had an important role in our society since ancient times. Preserving animal health is necessary to do a responsible use of veterinary...
Exotic companion animals have had an important role in our society since ancient times. Preserving animal health is necessary to do a responsible use of veterinary medicines. This study aimed to describe the prescription patterns of drugs in exotic pets and wildlife animals attending the Veterinary Teaching Hospital of the University of León (HVULE). A retrospective study was carried out between 2018 and 2022. Birds were the largest group of exotic animals attending the HVULE. Visits were related to emergency reasons and for musculoskeletal disorders. One-third of the animals were eventually euthanised. Regarding pharmacological treatments, the most frequently active ingredients used were pentobarbital, isoflurane, meloxicam, and within antibiotics, marbofloxacin (category B in the classification of European Medicines Agency).
PubMed: 38260200
DOI: 10.3389/fvets.2023.1328698 -
Biomedicines Dec 2023There is a need for research addressing the functional characteristics of the motor end-plate in diabetes to identify mechanisms contributing to neuromuscular...
There is a need for research addressing the functional characteristics of the motor end-plate in diabetes to identify mechanisms contributing to neuromuscular dysfunction. Here, we investigated the effect of diabetes on spontaneous acetylcholine release in the rat neuromuscular junction. We studied two randomized groups of male Wistar rats (n = 7 per group, 350 ± 50 g, 12-16 weeks of age): one with streptozotocin-induced experimental diabetes, and a healthy control group without diabetes. After 8 weeks of monitoring after diabetes induction, rats in both groups were anesthetized with pentobarbital. Then, the diaphragm muscle was dissected for electrophysiological recordings of miniature end-plate potentials (MEPPs) using a single electrode located at the region of the muscle end-plate. All experiments were conducted at environmental temperature (20-22 °C) in rat Ringer solution with constant bubbling carbogen (95% O, 5% CO). Compared to healthy controls, in the diaphragm neuromuscular end-plate derived from diabetic rats, the MEPPs were higher in amplitude and frequency, and the proportion of giant MEPPs was elevated (7.09% vs. 1.4% in controls). Our results showed that diabetes affected the acetylcholine MEPP pattern and increased the number of giant potentials compared to healthy controls.
PubMed: 38255175
DOI: 10.3390/biomedicines12010068 -
Experimental and Clinical... Jan 2024Gabapentin is used for the treatment of many conditions, including seizures, pain, and anxiety. Increasing reports of nonprescribed use suggest that gabapentin may...
Gabapentin is used for the treatment of many conditions, including seizures, pain, and anxiety. Increasing reports of nonprescribed use suggest that gabapentin may elicit positive subjective effects. The present study was conducted to examine the subjective effects of gabapentin using rats trained to discriminate either a 30.0 mg/kg or 300.0 mg/kg dose of gabapentin versus vehicle on a two-choice drug discrimination task. Both doses of gabapentin were established as discriminative stimuli, and the 300.0 mg/kg dose was more readily established compared to the 30.0 mg/kg dose. Full substitution (> 80% gabapentin-lever responding) occurred by the training drug and by the gabapentinoid compound pregabalin. Partial substitution (> 20% gabapentin-lever responding) was shown by the opioid compounds morphine and fentanyl, and dose combinations of the opioid receptor antagonist naltrexone with the gabapentin training doses reduced the percentage of gabapentin-lever responding to below 80%. Partial substitution for both training doses of gabapentin occurred with the cannabinoid Δ⁹-tetrahydrocannabinol. The barbiturate compound pentobarbital and the benzodiazepine compound diazepam were only tested for substitution for the 300.0 mg/kg dose of gabapentin and these compounds produced full substitution. These findings demonstrate that gabapentin establishes a robust discriminative cue and exhibits stimulus effects closely similar to pregabalin, pentobarbital, and diazepam. Since pregabalin, pentobarbital, and diazepam carry a risk of problematic use and are classified as controlled substances, further evaluations of gabapentin's risks in this regard are warranted. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
PubMed: 38236222
DOI: 10.1037/pha0000704 -
Journal of Ethnopharmacology Apr 2024Qizhuyanggan Decoction (QZD), a traditional Chinese medicine formula, is frequently utilized in clinical practice for managing hepatic fibrosis. However, the specific...
Integration of network pharmacology and serum medicinal chemistry to investigate the pharmacological mechanisms of QiZhuYangGan Decoction in the treatment of hepatic fibrosis.
ETHNOPHARMACOLOGICAL RELEVANCE
Qizhuyanggan Decoction (QZD), a traditional Chinese medicine formula, is frequently utilized in clinical practice for managing hepatic fibrosis. However, the specific target and mechanism of action of QZD for hepatic fibrosis treatment remain unknown.
AIM OF THE STUDY
By combining network pharmacology, serum medicinal chemistry, and experimental validation methods, our study aimed to investigate the therapeutic effects of QZD on hepatic fibrosis, the anti-hepatic fibrosis active ingredients, and the possible mechanism of anti-hepatic fibrosis action.
MATERIALS AND METHODS
The study aimed to investigate the therapeutic effect of QZD on hepatic fibrosis induced by CCl in SD rats, as well as its mechanism of action. The rats were anesthetized intraperitoneally using 3% pentobarbital and were executed after asphyxiation with high concentrations of carbon dioxide. Several techniques were employed to evaluate the efficacy of QZD, including ELISA, Western blot, HYP reagent assay, and various pathological examinations such as HE, Masson, Sirius Red staining, and immunohistochemistry (IHC). Additionally, serum biochemical assays were conducted to assess the effect of QZD on liver injury. Network pharmacology, UPLC, molecular docking, and molecular dynamics simulation were utilized to explore the mechanism of QZD in treating hepatic fibrosis. Finally, experimental validation was performed through ELISA, IHC, RT-qPCR, and Western blot analysis.
RESULT
Liver histopathology showed that QZD reduced inflammation and inhibited collagen production, and QZD significantly reduced HA and LN content to treat hepatic fibrosis. Serum biochemical analysis showed that QZD improved liver injury. Network pharmacology combined with UPLC screened six active ingredients and obtained 87 targets for the intersection of active ingredients and diseases. The enrichment analysis results indicated that the PI3K/AKT pathway might be the mechanism of action of QZD in the treatment of hepatic fibrosis, and counteracting the inflammatory response might be one of the pathways of action of QZD. Molecular docking and molecular dynamics simulations showed that the active ingredient had good binding properties with PI3K, AKT, and mTOR proteins. Western blot, ELISA, PCR, and IHC results indicated that QZD may treat hepatic fibrosis by inhibiting the PI3K/AKT/mTOR pathway and suppressing M1 macrophage polarization, while also promoting M2 macrophage polarization.
CONCLUSIONS
QZD may be effective in the treatment of hepatic fibrosis by inhibiting the PI3K/AKT/mTOR signaling pathway and M1 macrophage polarization, while promoting M2 macrophage polarization. This provides a strong basis for the clinical application of QZD.
Topics: Animals; Rats; Rats, Sprague-Dawley; Chemistry, Pharmaceutical; Molecular Docking Simulation; Network Pharmacology; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Liver Cirrhosis; TOR Serine-Threonine Kinases; Drugs, Chinese Herbal
PubMed: 38190954
DOI: 10.1016/j.jep.2024.117730 -
Nutrients Dec 2023exhibits various biological activities; however, their sleep-promoting effects have not been previously reported. In this study, we evaluated the hypnotic effects and...
exhibits various biological activities; however, their sleep-promoting effects have not been previously reported. In this study, we evaluated the hypnotic effects and sleep-wake profiles of root (KS-126) using a pentobarbital-induced sleep-acceleration test and polysomnographic recordings. Additionally, we investigated the molecular mechanism of KS-126 through patch-clamp electrophysiology. Our polysomnographic recordings revealed that KS-126 not only accelerated the onset of non-rapid eye movement sleep (NREMS) but also extends its duration. Considering the temporal dynamics of the sleep-wake stages, during the initial and subsequent periods KS-126 extended NREMS duration and decreased wakefulness, thereby enhancing sleep-promoting effects. Furthermore, the assessment of sleep quality via analysis of electroencephalogram power density indicated that KS-126 did not significantly alter sleep intensity. Finally, we found that KS-126 enhanced GABA receptor-mediated synaptic responses in primary hippocampal neurons, leading to an increase in the percentage of the GABA current. This effect was not affected by the selective benzodiazepine receptor antagonist flumazenil, but was entirely inhibited by the GABA receptor antagonist bicuculline. In conclusion, KS-126 extends the duration of NREMS without altering its intensity by prolonging GABAergic synaptic transmission, which modulates GABA receptor function.
Topics: Receptors, GABA-A; Aralia; Eye Movements; Sleep; gamma-Aminobutyric Acid
PubMed: 38140279
DOI: 10.3390/nu15245020 -
Comparative Biochemistry and... Feb 2024The crocodilian heart is unique among reptiles with its four-chambered structure and complete intracardiac separation of pulmonary and systemic blood flows and...
BACKGROUND
The crocodilian heart is unique among reptiles with its four-chambered structure and complete intracardiac separation of pulmonary and systemic blood flows and pressures. Crocodiles have retained two aortic arches; one from each ventricle, that communicate via Foramen of Panizza, immediately distally from the aortic valves. Moreover, crocodiles can regulate vascular resistance in the pulmonary portion of the right ventricular outflow tract (RVOT). These unique features allow for a complex regulation of shunting between the pulmonary and systemic circulations. Studies on crocodile shunting have predominantly been based on invasive measurements, but here we report on the use of echocardiography.
METHODS
Experiments were performed on seven pentobarbital anaesthetized juvenile Nile crocodiles (length and mass of 192 ± 13 cm and 26 ± 5 kg, respectively). Echocardiographic imaging was performed using a transesophageal (TEE) approach. All images were EKG-gated.
RESULTS
We obtain excellent views of cardiac structures and central vasculature through the esophagus. Standard imaging planes were defined for both long- and short axis views of the left ventricle and truncus arteriosus. For the RV, only a short axis view could be obtained. Color Doppler was used to visualize flow. Pulsed waved Doppler for measuring flow profiles across the atrioventricular valves, in the two RVOTs and the left ventricular outflow tract. Shunting across the Foramen of Panizza could be visualized and gated to the EKG.
CONCLUSION
TEE can be used to image the unique features of the crocodile heart and allow for in-vivo imaging of the complex shunting hemodynamics, including timing of cardiac shunts.
Topics: Animals; Echocardiography, Transesophageal; Alligators and Crocodiles; Heart; Hemodynamics; Echocardiography
PubMed: 38135145
DOI: 10.1016/j.cbpa.2023.111564 -
BMC Veterinary Research Dec 2023Toll-like receptor 8 (TLR8) can recognize specific pathogen-associated molecular patterns and exert multiple immunological functions through activation of signaling...
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.
Topics: Animals; Rabbits; Spleen; Camelus; Toll-Like Receptor 8; Immunoglobulin G; Recombinant Proteins
PubMed: 38104080
DOI: 10.1186/s12917-023-03812-z -
Journal of the American Association For... Jan 2024Mechanical ventilation can be used in mice to support high-risk anesthesia or to create clinically relevant, intensive care models. However, the choice of anesthetic and...
Mechanical ventilation can be used in mice to support high-risk anesthesia or to create clinically relevant, intensive care models. However, the choice of anesthetic and inspired oxygen concentration for prolonged procedures may affect basic physiology and lung inflammation. To characterize the effects of anesthetics and oxygen concentration in mice experiencing mechanical ventilation, mice were anesthetized with either isoflurane or pentobarbital for tracheostomy followed by mechanical ventilation with either 100% or 21% oxygen. Body temperature, oxygen saturation, and pulse rate were monitored continuously. After 6 h, mice were euthanized for collection of blood and bronchoalveolar lavage fluid for evaluation of biomarkers of inflammation and lung injury, including cell counts and cytokine levels. Overall, both isoflurane and pentobarbital provided suitable anesthesia for 6 h of mechanical ventilation with either 21% or 100% oxygen. We found no differences in lung inflammation biomarkers attributable to either oxygen concentration or the anesthetic. However, the combination of pentobarbital and 100% oxygen resulted in a significantly higher concentration of a biomarker for lung epithelial cell injury. This study demonstrates that the combination of anesthetic agent, mechanical ventilation, and inspired oxygen concentrations can alter vital signs and lung injury biomarkers during prolonged procedures. Their combined impact may influence model development and the interpretation of research results, warranting the need for preliminary evaluation to establish the baseline effects.
Topics: Mice; Animals; Isoflurane; Pentobarbital; Respiration, Artificial; Lung Injury; Anesthesia; Anesthetics; Pneumonia; Oxygen; Biomarkers; Rodent Diseases
PubMed: 38065567
DOI: 10.30802/AALAS-JAALAS-23-000014 -
American Journal of Cancer Research 2023Acute lung injury (ALI) is an acute infectious diseases caused by a variety of factors. The function of TTC4 in sepsis-induced lung injury remains largely unknown. This...
Acute lung injury (ALI) is an acute infectious diseases caused by a variety of factors. The function of TTC4 in sepsis-induced lung injury remains largely unknown. This study aimed to explore the critical role of TTC4 in sepsis-induced lung injury. Mice anaesthetized using pentobarbital sodium and subjected to cecal ligation and puncture (CLP) surgery. TTC4 expression levels in patients with sepsis-induced lung injury were down-regulated. The inhibition of TTC4 gene promoted lung injury in mice model of sepsis. TTC4 gene improved inflammation in vitro model and mice model. TTC4 gene reduced pyroptosis in macrophages of sepsis-induced lung injury by the inhibition of mitochondrial damage. TTC4 gene induced HSP70 expression to reduce NLRP3-induced pyroptosis in macrophages. TTC4 protein interlinked HSP70 protein. The activation of HSP70 reduced the effects of sh-TTC4 in model of sepsis-induced lung injury through mitochondrial damage. m6A-forming enzyme METTL3 reduced TTC4 stability. Our study suggests the m6A forming enzyme METTL3 control TTC4 reduced inflammation and pyroptosis in model of sepsis-induced lung injury through inhibition of mitochondrial damage by HSP70/ROS/NLRP3 signaling pathway, TTC4 gene as an represents a potential therapeutic strategy for the treatment of sepsis-induced lung injury.
PubMed: 38058818
DOI: No ID Found -
Methods in Molecular Biology (Clifton,... 2024Pentobarbital is a short-acting barbiturate with anticonvulsant and sedative-hypnotic properties. Pentobarbital may be used to induce sedation, control seizures, induce...
Pentobarbital is a short-acting barbiturate with anticonvulsant and sedative-hypnotic properties. Pentobarbital may be used to induce sedation, control seizures, induce coma, and to manage patients with traumatic brain injury. In traumatic brain injury, use of pentobarbital is known to reduce both cerebral blood flow and oxygen consumption, which reduces intracranial pressure and cerebral ischemia. As there are currently no known commercially available methods for quantification, a quick and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is described here for the quantification of pentobarbital. The analyte and internal standard, D5-pentobarbital, were extracted from human serum via solid phase extraction prior to LC-MS/MS analysis utilizing electrospray ionization (ESI) in negative ionization mode. Confirmation and quantitation of pentobarbital was performed using multiple reaction monitoring (MRM). The method was linear from 0.5 to 100 μg/mL with imprecision less than 5% coefficient of variability. Pentobarbital eluted at 2.61 min and the total run time was 7 min. The method only requires 100 μL of serum due to the high physiologic concentrations required for sedation/coma.
Topics: Humans; Chromatography, Liquid; Pentobarbital; Tandem Mass Spectrometry; Coma; Brain Injuries, Traumatic; Chromatography, High Pressure Liquid; Solid Phase Extraction; Spectrometry, Mass, Electrospray Ionization
PubMed: 38036840
DOI: 10.1007/978-1-0716-3541-4_36