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American Journal of Veterinary Research Jul 2024Present an approach to the safe and efficient provision of anesthesia and birth control measures to a large group of primates.
OBJECTIVE
Present an approach to the safe and efficient provision of anesthesia and birth control measures to a large group of primates.
ANIMALS
98 hamadryas baboons (Papio hamadryas) held in a German zoological institution.
METHODS
A group of 12 veterinarians, 2 zookeepers, and 6 volunteers anesthetized all animals within 2 days. The baboons were orally premedicated with midazolam (0.1 to 0.5 mg/kg) and anesthetized with medetomidine (40 to 60 µg/kg, IM) and ketamine (2 to 4 mg/kg, IM); isoflurane at rates of 1.5% to 2% was used for maintaining anesthesia if necessary. All animals received a physical examination, prophylactic medication, and tuberculin testing. For population management, the animals received a contraceptive implant (adult females), orchiectomy (young males), or vasectomy (breeding males). Young males received intratesticular blocks with lidocaine. All animals received atipamezole (125 to 150 µg/kg) before recovery.
RESULTS
Premedication resulted in anxiolysis, which facilitated separating and darting. Median time from darting to access to the animal was 10 minutes. Mean anesthetic times were 25 minutes for females and 55 minutes for males. The depth of anesthesia was appropriate for the procedures. No fatalities were recorded. One animal was injured by other baboons but recovered after treatment.
CLINICAL RELEVANCE
Health management and birth control measures are necessary in baboon troops under human care. Anesthesia and/or contraception of individual animals often leads to intraspecific aggression. This case series describes how to provide anesthesia and contraception to an entire troop as an alternative approach that can be adopted to future similar interventions.
Topics: Animals; Female; Male; Papio hamadryas; Animals, Zoo; Anesthesia, General; Vasectomy; Contraception; Ketamine; Orchiectomy; Medetomidine; Midazolam; Population Control
PubMed: 38744308
DOI: 10.2460/ajvr.23.12.0274 -
PloS One 2024
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lignans; beta Catenin; Lung Neoplasms; Biphenyl Compounds; Cell Movement; Dinoprostone; Signal Transduction; Cell Line, Tumor; Allyl Compounds; Phenols
PubMed: 38739616
DOI: 10.1371/journal.pone.0303600 -
PeerJ 2024N-Ethylmaleimide (NEM), an agonist of the potassium chloride cotransporters 2 (KCC2) receptor, has been correlated with neurosuppressive outcomes, including decreased...
BACKGROUND
N-Ethylmaleimide (NEM), an agonist of the potassium chloride cotransporters 2 (KCC2) receptor, has been correlated with neurosuppressive outcomes, including decreased pain perception and the prevention of epileptic seizures. Nevertheless, its relationship with sleep-inducing effects remains unreported.
OBJECTIVE
The present study aimed to investigate the potential enhancement of NEM on the sleep-inducing properties of alprazolam (Alp).
METHODS
The test of the righting reflex was used to identify the appropriate concentrations of Alp and NEM for inducing sleep-promoting effects in mice. Total sleep duration and sleep quality were evaluated through EEG/EMG analysis. The neural mechanism underlying the sleep-promoting effect was examined through c-fos immunoreactivity in the brain using immunofluorescence. Furthermore, potential CNS-side effects of the combination Alp and NEM were assessed using LABORAS automated home-cage behavioral phenotyping.
RESULTS
Combination administration of Alp (1.84 mg/kg) and NEM (1.0 mg/kg) significantly decreased sleep latency and increased sleep duration in comparison to administering 1.84 mg/kg Alp alone. This effect was characterized by a notable increase in REM duration. The findings from c-fos immunoreactivity indicated that NEM significantly suppressed neuron activation in brain regions associated with wakefulness. Additionally, combination administration of Alp and NEM showed no effects on mouse neural behaviors during automated home cage monitoring.
CONCLUSIONS
This study is the first to propose and demonstrate a combination therapy involving Alp and NEM that not only enhances the hypnotic effect but also mitigates potential CNS side effects, suggesting its potential application in treating insomnia.
Topics: Animals; Alprazolam; Mice; Male; Drug Synergism; Sleep; Electroencephalography; Proto-Oncogene Proteins c-fos; Brain; Reflex, Righting; Hypnotics and Sedatives
PubMed: 38737745
DOI: 10.7717/peerj.17342 -
Journal of Veterinary Cardiology : the... Jun 2024A nine-year-old spayed female domestic shorthair cat with a previous diagnosis of hypertrophic cardiomyopathy and treated for one month with atenolol (6.25 mg q 12 h)...
A nine-year-old spayed female domestic shorthair cat with a previous diagnosis of hypertrophic cardiomyopathy and treated for one month with atenolol (6.25 mg q 12 h) was referred for respiratory distress and anorexia. The cat was diagnosed with pulmonary oedema secondary to obstructive hypertrophic cardiomyopathy. After stabilisation, she was discharged with furosemide (1 mg/kg q 12 h), clopidogrel (18.75 mg q 24 h), atenolol (6.25 mg q 12 h), and mirtazapine (2 mg/cat q 24 h) to increase appetite. At recheck, the cat was lethargic and presented with severe bradycardia with a junctional escape rhythm and ventriculoatrial conduction. The mirtazapine was discontinued due to its possible side-effects on cardiac rhythm. After three days, the atenolol was halved because the bradyarrhythmia was still present. After 10 days, the rhythm returned to sinus; atenolol was reintroduced twice daily with no further side-effects. The absence of a sinus rhythm with a junctional escape rhythm and P' retroconduction is compatible with a third-degree sinus block or a sinus standstill; the differentiation of these rhythm disturbances is impossible, based on the surface electrocardiogram (ECG). The sinus rhythm was restored after mirtazapine was withdrawn. However, it is not possible to rule out the role of the atenolol or the combined effect of the two drugs. The cat was affected by hypertrophic cardiomyopathy, and the role of myocardial remodelling cannot be excluded. This is the first time that a bradyarrhythmia consequent to the treatment with atenolol and mirtazapine was described in a cat.
Topics: Female; Mirtazapine; Animals; Atenolol; Cats; Cat Diseases; Cardiomyopathy, Hypertrophic; Bradycardia; Mianserin; Adrenergic beta-1 Receptor Antagonists
PubMed: 38735230
DOI: 10.1016/j.jvc.2024.03.003 -
Journal of Anxiety Disorders Jun 2024Exposure therapy is an evidence-based treatment option for anxiety-related disorders. Many patients also take medication that could, in principle, affect exposure... (Meta-Analysis)
Meta-Analysis
Exposure therapy is an evidence-based treatment option for anxiety-related disorders. Many patients also take medication that could, in principle, affect exposure therapy efficacy. Clinical and laboratory evidence indeed suggests that benzodiazepines may have detrimental effects. Large clinical trials with propranolol, a common beta-blocker, are currently lacking, but several preclinical studies do indicate impaired establishment of safety memories. Here, we investigated the effects of propranolol given prior to extinction training in 9 rat studies (N = 215) and one human study (N = 72). A Bayesian meta-analysis of our rat studies provided strong evidence against propranolol-induced extinction memory impairment during a drug-free test, and the human study found no significant difference with placebo. Two of the rat studies actually suggested a small beneficial effect of propranolol. Lastly, two rat studies with a benzodiazepine (midazolam) group provided some evidence for a harmful effect on extinction memory, i.e., impaired extinction retention. In conclusion, our midazolam findings are in line with prior literature (i.e., an extinction retention impairment), but this is not the case for the 10 studies with propranolol. Our data thus support caution regarding the use of benzodiazepines during exposure therapy, but argue against a harmful effect of propranolol on extinction learning.
Topics: Propranolol; Animals; Fear; Extinction, Psychological; Rats; Humans; Adrenergic beta-Antagonists; Male; Memory; Midazolam; Adult; Bayes Theorem; Female; Conditioning, Classical; Young Adult
PubMed: 38733644
DOI: 10.1016/j.janxdis.2024.102870 -
Rheumatology International Jul 2024Stressful events like earthquakes might worsen the symptoms of fibromyalgia, although the influence of medications on these consequences is yet uncertain. The objective... (Comparative Study)
Comparative Study
INTRODUCTION / OBJECTIVES
Stressful events like earthquakes might worsen the symptoms of fibromyalgia, although the influence of medications on these consequences is yet uncertain. The objective of this study was to examine the influence of an earthquake on the symptoms of fibromyalgia and evaluate the impacts of medications used to treat fibromyalgia on the clinical picture.
METHOD
Ninety-five fibromyalgia patients were enrolled in a comparative study and divided into two groups: medication and non-medication. Three subcategories of medication groups were established: selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and gabapentinoid drugs (GDs). Before and after the earthquake, clinical evaluations were conducted using the Fibromyalgia Impact Questionnaire (FIQ), Hospital Anxiety and Depression Scale (HADS), and Jenkins Sleep Rating Scale (JSS). Statistical analyses were conducted to compare the scores before and after the earthquake and evaluate the differences between the groups.
RESULTS
Statistically significant increases were observed in FIQ, HADS-anxiety, HADS-depression, and JSS scores in the medication and non-medication groups before and after the earthquake comparisons (p < 0.05). Non-medication group reported significantly higher post-earthquake changes in FIQ, HADS-anxiety, HADS-depression, and JSS compared to the medication group (p < 0.05). While HADS-anxiety, HADS-depression, and JSS changes after the earthquake differed according to the drug subgroups (p < 0.05), no statistically significant difference was observed in FIQ values (p > 0.05). The highest scores were detected in the GD subgroup.
CONCLUSIONS
This study highlights the substantial impact of earthquakes on fibromyalgia patients. Medication use may assist in reducing the detrimental effects of stresses like earthquakes on fibromyalgia symptomatology. Future research with larger sample sizes and more extended follow-up periods is needed to explain these findings and optimize treatment regimens for fibromyalgia patients experiencing significant stressors.
Topics: Humans; Earthquakes; Fibromyalgia; Female; Middle Aged; Adult; Male; Selective Serotonin Reuptake Inhibitors; Surveys and Questionnaires; Depression; Serotonin and Noradrenaline Reuptake Inhibitors; Anxiety; Analgesics; Gabapentin
PubMed: 38722331
DOI: 10.1007/s00296-024-05605-5 -
Clinical and Translational Science May 2024Cannabis-drug interactions have caused significant concerns, mainly due to their role in the cytochrome P450 (CYP) enzyme-mediated metabolic pathway of numerous...
Cannabis-drug interactions have caused significant concerns, mainly due to their role in the cytochrome P450 (CYP) enzyme-mediated metabolic pathway of numerous medications. A systematic review was conducted to gain an overview of the potential interactions of cannabis with different drug classes by extracting pertinent information from published study data. From the inception of the study to October 1, 2023, we performed a systematic search of PubMed, Scopus, clinicaltrials.gov, and Web of Science. We included 54 out of 464 articles, and a total of 20 drug classes were identified to have interactions with medicinal cannabis. The cannabis-drug interactions were assessed and classified according to their probability and severity. The analysis revealed that antiepileptics had the most evidence of interaction with cannabis, followed by clobazam (CLB), warfarin, and tacrolimus. Generally, cannabis-drug interactions result in pharmacokinetic (PK) or pharmacodynamic (PD) changes. Therefore, careful monitoring should be performed to detect any unusual elevations in plasma levels. In addition, dose titrations or treatment withdrawal could help mitigate the adverse effects attributed to cannabis-drug interactions. Nevertheless, novel drugs are constantly emerging, and more research is needed to further identify potential interactions with cannabis.
Topics: Humans; Anticonvulsants; Clobazam; Drug Interactions; Medical Marijuana; Warfarin
PubMed: 38720531
DOI: 10.1111/cts.13812 -
Nature Jun 2024Psychedelic substances such as lysergic acid diethylamide (LSD) and psilocybin show potential for the treatment of various neuropsychiatric disorders. These compounds...
Psychedelic substances such as lysergic acid diethylamide (LSD) and psilocybin show potential for the treatment of various neuropsychiatric disorders. These compounds are thought to mediate their hallucinogenic and therapeutic effects through the serotonin (5-hydroxytryptamine (5-HT)) receptor 5-HT (ref. ). However, 5-HT also plays a part in the behavioural effects of tryptamine hallucinogens, particularly 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a psychedelic found in the toxin of Colorado River toads. Although 5-HT is a validated therapeutic target, little is known about how psychedelics engage 5-HT and which effects are mediated by this receptor. Here we map the molecular underpinnings of 5-MeO-DMT pharmacology through five cryogenic electron microscopy (cryo-EM) structures of 5-HT, systematic medicinal chemistry, receptor mutagenesis and mouse behaviour. Structure-activity relationship analyses of 5-methoxytryptamines at both 5-HT and 5-HT enable the characterization of molecular determinants of 5-HT signalling potency, efficacy and selectivity. Moreover, we contrast the structural interactions and in vitro pharmacology of 5-MeO-DMT and analogues to the pan-serotonergic agonist LSD and clinically used 5-HT agonists. We show that a 5-HT-selective 5-MeO-DMT analogue is devoid of hallucinogenic-like effects while retaining anxiolytic-like and antidepressant-like activity in socially defeated animals. Our studies uncover molecular aspects of 5-HT-targeted psychedelics and therapeutics, which may facilitate the future development of new medications for neuropsychiatric disorders.
Topics: Animals; Humans; Male; Mice; 5-Methoxytryptamine; Anti-Anxiety Agents; Antidepressive Agents; Cryoelectron Microscopy; Hallucinogens; Lysergic Acid Diethylamide; Methoxydimethyltryptamines; Models, Molecular; Receptor, Serotonin, 5-HT1A; Receptor, Serotonin, 5-HT2A; Serotonin Receptor Agonists; Structure-Activity Relationship
PubMed: 38720072
DOI: 10.1038/s41586-024-07403-2 -
Brain, Behavior, and Immunity Jul 2024Neuroinflammation and accumulation of Amyloid Beta (Aβ) accompanied by deterioration of special memory are hallmarks of Alzheimer's disease (AD). Effective preventative...
Neuroinflammation and accumulation of Amyloid Beta (Aβ) accompanied by deterioration of special memory are hallmarks of Alzheimer's disease (AD). Effective preventative and treatment options for AD are still needed. Microglia in AD brains are characterized by elevated levels of microRNA-17 (miR-17), which is accompanied by defective autophagy, Aβ accumulation, and increased inflammatory cytokine production. However, the effect of targeting miR-17 on AD pathology and memory loss is not clear. To specifically inhibit miR-17 in microglia, we generated mannose-coated lipid nanoparticles (MLNPs) enclosing miR-17 antagomir (Anti-17 MLNPs), which are targeted to mannose receptors readily expressed on microglia. We used a 5XFAD mouse model (AD) that recapitulates many AD-related phenotypes observed in humans. Our results show that Anti-17 MLNPs, delivered to 5XFAD mice by intra-cisterna magna injection, specifically deliver Anti-17 to microglia. Anti-17 MLNPs downregulated miR-17 expression in microglia but not in neurons, astrocytes, and oligodendrocytes. Anti-17 MLNPs attenuated inflammation, improved autophagy, and reduced Aβ burdens in the brains. Additionally, Anti-17 MLNPs reduced the deterioration in spatial memory and decreased anxiety-like behavior in 5XFAD mice. Therefore, targeting miR-17 using MLNPs is a viable strategy to prevent several AD pathologies. This selective targeting strategy delivers specific agents to microglia without the adverse off-target effects on other cell types. Additionally, this approach can be used to deliver other molecules to microglia and other immune cells in other organs.
Topics: Animals; Alzheimer Disease; MicroRNAs; Nanoparticles; Mice; Microglia; Disease Models, Animal; Mannose; Mice, Transgenic; Brain; Amyloid beta-Peptides; Lipids; Male; Antagomirs
PubMed: 38718909
DOI: 10.1016/j.bbi.2024.05.006