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The Journal of Pediatric Pharmacology... 2024Difficult analgosedation is common and challenging in the pediatric intensive care unit (PICU). It is important to study alternative and supplemental sedatives for when...
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.
PubMed: 38332954
DOI: 10.5863/1551-6776-29.1.32 -
Veterinary World Dec 2023Potato ( L.) is mainly characterized by its antioxidant and healing properties. Therefore, this study aimed to evaluate the effects of an ointment based on L. "papa...
BACKGROUND AND AIM
Potato ( L.) is mainly characterized by its antioxidant and healing properties. Therefore, this study aimed to evaluate the effects of an ointment based on L. "papa tumbay" on burns induced in Balb/c mice ().
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 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 L. "papa tumbay," especially the 2% ointment, might accelerate the healing of second-degree burns induced in Balb/c mice.
PubMed: 38328356
DOI: 10.14202/vetworld.2023.2440-2445 -
Journal of Integrative Neuroscience Jan 2024Levodopa (L-DOPA) is the primary treatment for Parkinson's disease (PD). Nevertheless, the underlying mechanism of its action is not entirely learned. This study aims to...
Levodopa Improves Behavioral Deficits of Mice with Parkinson's Disease Symptoms via Curbing NLRP3 Inflammasome Activation and Enhancing Tyrosine Hydroxylase Levels in the Striatum and Substantia Nigra.
OBJECTIVE
Levodopa (L-DOPA) is the primary treatment for Parkinson's disease (PD). Nevertheless, the underlying mechanism of its action is not entirely learned. This study aims to probe the action of L-DOPA on NLR pyrin domain containing 3 (NLRP3) inflammasome activation and tyrosine hydroxylase (TH) levels in the striatum (STR) and substantia nigra (SN) of mice with PD symptoms.
METHODS
PD was simulated by administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 25 mg/kg/d) to induce mice, followed by L-DOPA (8 mg/kg/d) treatment. The behavioral performance of the mice was assessed using the pole test, balance beam, and rotarod test. After euthanasia with 120 mg/kg sodium pentobarbital, STR and SN were collected for evaluation of protein level of TH, NLR pyrin domain containing 3 (NLRP3), ASC and Cleaved caspase-1 using Western blot and mRNA levels of , inflammatory factors and using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).
RESULTS
Treatment with L-DOPA significantly ameliorated the behavioral deficits caused by MPTP in mice with PD symptoms. L-DOPA administration resulted in reduced levels of apoptosis-associated speck-like protein containing a CARD (caspase recruitment domain) (ASC), NLRP3, and Cleaved caspase-1 protein levels, and decreased mRNA levels of and in the STR and SN. L-DOPA increased the mRNA and TH protein levels, while suppressing NLRP3 inflammasome activation in the STR and SN of mice with PD symptoms.
CONCLUSIONS
L-DOPA improves the behavioral deficits in mice with PD symptoms possibly by suppressing NLRP3 inflammasome activation and increasing TH levels in the STR and SN TH levels. These findings provide further perceptions into the property of L-DOPA in PD.
Topics: Mice; Animals; Parkinson Disease; Levodopa; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Interleukin-18; Tyrosine 3-Monooxygenase; Substantia Nigra; RNA, Messenger; Caspases; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 38287845
DOI: 10.31083/j.jin2301002 -
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 -
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 -
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