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The Journal of Maternal-fetal &... Dec 2021Psychological stress is an important factor triggering depression and anxiety. Infertility is known to cause stress; however, it is not clearly known whether stress...
OBJECTIVE
Psychological stress is an important factor triggering depression and anxiety. Infertility is known to cause stress; however, it is not clearly known whether stress causes infertility as well. In addition, there are different opinions accounting for the relation of stress-induced oxidative stress to infertility and intrauterine growth restriction. The aim of the study is to examine the effect of sertraline, diazepam and melatonin on the infertility, intrauterine growth restriction and oxidative stress that can be caused by forced immobilization stress management (FISM) in female rats.
MATERIALS AND METHODS
Wistar rats were grouped as healthy rats (HG) applied distilled water, stress treated control group (SC), and 20 mg/kg sertraline + stress (SS), 2 mg/kg diazepam + stress (DS) and 10 mg/kg melatonin + stress (MS) treated rats. The medicines were administered orally once a day for 30 days. At the end of this period, oxidant/antioxidant parameters were measured through the blood samples collected from the tail veins of all rats. Then the rats were kept in a suitable environment for 2 months for breeding.
RESULTS
FISM caused oxidative stress in blood serum of animals, infertility and intrauterine growth restriction (decrease in birth weight of the baby). Best medicines to suppress FISM-related oxidative stress are melatonin > diazepam > sertraline respectively, while sertraline > diazepam > melatonin were most successful in terms of preventing infertility. The best medicines preventing the FISM-caused intrauterine growth restriction were found to be melatonin > diazepam > sertraline, respectively.
CONCLUSION
FISM causes oxidative stress in animals. Oxidative stress is understood to affect the intrauterine growth negatively although it is not a major component in the pathogenesis of infertility. While melatonin is only effective in preventing the oxidative stress-related intrauterine growth restriction, antidepressants and anxiolytic treatment were found to be helpful in preventing both infertility and intrauterine growth restriction.
Topics: Animals; Antioxidants; Diazepam; Female; Fetal Growth Retardation; Melatonin; Oxidative Stress; Rats; Rats, Wistar; Sertraline
PubMed: 31875735
DOI: 10.1080/14767058.2019.1706469 -
Neuron Oct 2022Earlier work has implicated the neurotransmitter GABA in controlling forebrain progenitor proliferation. In this issue of Neuron, Everlien et al. (2022) demonstrate...
Earlier work has implicated the neurotransmitter GABA in controlling forebrain progenitor proliferation. In this issue of Neuron, Everlien et al. (2022) demonstrate that diazepam binding inhibitor acts to keep the neurogenesis-promoting effect of GABA at bay.
Topics: Diazepam; Diazepam Binding Inhibitor; Neurogenesis; Neurons; Receptors, GABA-A; gamma-Aminobutyric Acid
PubMed: 36202087
DOI: 10.1016/j.neuron.2022.08.030 -
Journal of Clinical Psychopharmacology 2020
Topics: Aged; Aged, 80 and over; Anxiety Disorders; Central Nervous System Sensitization; Diazepam; Female; Forecasting; Humans; Male
PubMed: 32332456
DOI: 10.1097/JCP.0000000000001213 -
Epilepsy & Behavior : E&B Dec 2022We aimed to inquire whether any seizure rescue medications are included in the in-flight medical emergency kits of the main airlines in the world. This data could help... (Review)
Review
OBJECTIVE
We aimed to inquire whether any seizure rescue medications are included in the in-flight medical emergency kits of the main airlines in the world. This data could help the airline authorities update their strategies in light of any shortcomings.
METHODS
First, we identified ten major airlines in the world. Then, we searched the Google engine with the following keywords: "name of the airline" and "in-flight medical emergency" or "first aid kit" or "emergency kit". In case there was no information on the web, we emailed the airlines and inquired about the contents of their in-flight medical emergency kits. We also investigated some of the major aviation organizations' websites [i.e., Aerospace Medical Association (AsMA), International Civil Aviation Organization (ICAO), and International Air Transport Association (IATA)].
RESULTS
None of the major airlines were equipped with easily applicable seizure rescue medications (i.e., buccal midazolam, a nasal spray of midazolam, or intranasal diazepam). The AsMA and ICAO recommend including injectable sedative anticonvulsant drugs in the in-flight medical emergency kits without any further specifications. The IATA does not provide specific recommendations for including seizure rescue medications in the in-flight medical emergency kits.
CONCLUSION
A seizure is a significant in-flight medical emergency event. The use of easily applicable seizure rescue medications during prolonged or repeated seizures is significantly associated with fewer sequelae for the affected person. Easily applicable seizure rescue medications should be included in the in-flight medical emergency kits, and the cabin crew should receive training on how and when to use them.
Topics: Humans; Aerospace Medicine; Midazolam; First Aid; Diazepam; Seizures
PubMed: 36370544
DOI: 10.1016/j.yebeh.2022.108976 -
Physiology & Behavior Nov 2023Open-field activity is a commonly used measure of anxiety-related behavior in rodents. The inbred High and Low Activity strains of mice, selected for extreme differences...
Open-field activity is a commonly used measure of anxiety-related behavior in rodents. The inbred High and Low Activity strains of mice, selected for extreme differences in open-field activity, have been used as a genetic model of anxiety-related behaviors. These selected strains have been thoroughly studied through extensive behavioral testing, quantitative trait locus (QTL) mapping, whole-genome sequencing, and RNA sequencing, to uncover phenotypic and genotypic differences related to anxiety-related behavior. However, the effects of anxiolytic drugs on anxiety-related behavior in these strains have not been studied previously. This study allowed us to expand on previous findings to further characterize the anxiety-related behavior of these unique strains, using an anxiolytic drug. The goal of this study was to determine whether the treatment of adult male and female High Activity (low anxiety) and Low Activity (high anxiety) mice with diazepam, an agonist at the benzodiazepine allosteric site on the GABA receptor and a drug commonly prescribed to treat anxiety disorders in humans, led to decreases in anxiety-like defensive behavioral responses as assessed in the open-field test (OFT) and elevated plus-maze (EPM). We tested the effects of three doses of diazepam (0, 0.5, 1.0, 3.0 mg/kg, i.p.), given 30 min before behavioral testing to one High Activity strain (H2) and two Low Activity strains (L1 and L2). There was an anxiolytic effect of diazepam observed in the High Activity strain, with more entries into the open arms of the elevated plus-maze, an effect similar to that seen in common mouse strains. However, the only anxiolytic effect of diazepam seen in the Low Activity strains was a reduction in stretch attend posture (SAP). Low Activity strains also displayed freezing behavior in both the OFT and EPM. The combination of the observed freezing behavior, that was not reduced by diazepam, and the reduction in SAP seen with diazepam, suggests a more complex phenotype that includes a component of innate fear in addition to anxiety-related risk assessment behaviors. Since fear and anxiety are distinguishable traits, and both contribute to human anxiety disorders, these results provide novel insight about interpretation of previous genetic and phenotypic differences observed between the High and Low Activity strains.
Topics: Animals; Diazepam; Male; Anti-Anxiety Agents; Female; Anxiety; Mice; Mice, Inbred Strains; Disease Models, Animal; Open Field Test; Species Specificity; Behavior, Animal
PubMed: 37689380
DOI: 10.1016/j.physbeh.2023.114343 -
Advances in Mind-body MedicineThere is growing evidence linking epigenetic mutations to neurologic disorders such as epilepsy. The effect of the medications primarily used to treat neurologic...
There is growing evidence linking epigenetic mutations to neurologic disorders such as epilepsy. The effect of the medications primarily used to treat neurologic disorders has recently been studied, including research on epilepsy and the epigenetic process. The impact of the widely used medication diazepam on epigenomics, microRNA levels, the ensuing genetic exposure and potential clinical effects was reviewed. The action of diazepam, particularly in altering the synthesis of enzyme 5' adenosine monophosphate activated protein kinase (AMPK) was found to affect many enzymes, which changes or modifies the epigenetics. Epigenetic enzymes such as histone acetyltransferases (HATs), class II histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) are mainly activated by AMPKs, including the phosphorylate substrates, which often lead to their inhibition, although HAT1 activity may be improved. It has been reported that diazepam can reduce histone methyltransferase expression exposure, may increase class III histone deacetylases activity and may decrease the effect of DNA methyltransferases inhibitors. Diazepam has been found to contribute to mutations of the epigenome and genetic expression, and may protect against neurologic disorders, aging, dementia and several brain diseases. It has also been found that microRNA expression can be influenced by diazepam treatment and may have neurologic effects. Although the reported effects of diazepam on epigenetic enzymes of are equally effective in both amplifying and reducing acetylation of histone, histone and DNA methylation and gene expression, the effect of diazepam on the epigenome, genetic expression, and subsequent effects in all healthy diazepam users is unclear.
Topics: Anticonvulsants; DNA Methylation; Diazepam; Epigenesis, Genetic; Gene Expression Regulation; Histones; Humans; MicroRNAs
PubMed: 33513583
DOI: No ID Found -
Behavioural Pharmacology Apr 2020Developing effective analgesics with fewer unwanted side effects is a pressing concern. Due to a lack of effective nonopioid options currently available, an alternative...
Developing effective analgesics with fewer unwanted side effects is a pressing concern. Due to a lack of effective nonopioid options currently available, an alternative approach termed opioid-sparing evaluates the ability of a coadministered drug to reduce the amount of opioid needed to produce an antinociceptive effect. Opioids and benzodiazepines are often coprescribed. Although this approach is theoretically rational given the prevalent comorbidity of chronic pain and anxiety, it also has inherent risks of respiratory depression, which is likely responsible for the substantial percentage of fatal opioid overdoses that have involved benzodiazepines. Moreover, there have been no clinical trials to support the effectiveness of this drug combination nor has there been corroborative preclinical evidence using traditional animal models of nociception. The present studies examined the prescription µ-opioid analgesic oxycodone (0.003-0.1 mg/kg) and the prototypical benzodiazepine anxiolytic diazepam (0.03-1.0 mg/kg), alone and in combination, using an animal model of pain that examines the restoration of conflict-related operant behavior as evidence of analgesia. Results documented significant dose-related increases in thermal threshold following oxycodone treatment. Diazepam treatment alone did not produce significant antinociception. In combination, diazepam pretreatment shifted oxycodone functions upward in a dose-dependent manner, but the additive effects were limited to a narrow dose range. In addition, combinations of diazepam and oxycodone at higher doses abolished responding. Taken together, though intriguing, these findings do not provide sufficient evidence that coadministration of an anxiolytic will result in clinically relevant opioid-sparing for pain management, especially when considering the inherent risks of this drug class combination.
Topics: Analgesics; Animals; Conditioning, Operant; Diazepam; Drug Therapy, Combination; Male; Models, Animal; Nociception; Opioid-Related Disorders; Oxycodone; Pain; Pain Measurement; Saimiri
PubMed: 31972623
DOI: 10.1097/FBP.0000000000000542 -
Epilepsia Aug 2023In the management of epilepsy, there is an ongoing quest to discover new biomarkers to improve the diagnostic process, the monitoring of disease progression, and the...
OBJECTIVE
In the management of epilepsy, there is an ongoing quest to discover new biomarkers to improve the diagnostic process, the monitoring of disease progression, and the evaluation of treatment responsiveness. In this regard, biochemical traceability in biofluids is notably absent in contrast to other diseases. In the present preclinical study, we investigated the potential of neurofilament light chain (NfL) as a possible diagnostic and response fluid biomarker for epilepsy.
METHODS
We gained insights into NfL levels during the various phases of the intrahippocampal kainic acid mouse model of temporal lobe epilepsy-namely, the status epilepticus (SE) and the chronic phase with spontaneous seizures. To this end, NfL levels were determined directly in the cerebral interstitial fluid (ISF) with cerebral open flow microperfusion as sampling technique, as well as in cerebrospinal fluid (CSF) and plasma. Lastly, we assessed whether NfL levels diminished upon curtailing SE with diazepam and ketamine.
RESULTS
NfL levels are higher during SE in both cerebral ISF and plasma in kainic acid-treated mice compared to sham-injected mice. Additionally, ISF and plasma NfL levels are lower in mice treated with diazepam and ketamine to stop SE compared with the vehicle-treated mice. In the chronic phase with spontaneous seizures, higher NfL levels could only be detected in ISF and CSF samples, and not in plasma. No correlations could be found between NfL levels and seizure burden, nor with immunohistological markers for neurodegeneration/inflammation.
SIGNIFICANCE
Our findings demonstrate the translational potential of NfL as a blood-based fluid biomarker for SE. This is less evident for chronic epilepsy, as in this case higher NfL levels could only be detected in ISF and CSF, and not in plasma, acknowledging the invasive nature of CSF sampling in chronic epilepsy follow-up.
Topics: Animals; Mice; Kainic Acid; Intermediate Filaments; Ketamine; Neurofilament Proteins; Epilepsy; Biomarkers; Seizures; Diazepam
PubMed: 37264788
DOI: 10.1111/epi.17669 -
The Analyst Dec 2022Drug abuse is a global social issue of concern. As the drug market expands, there is an urgent need for technological methods to rapidly detect drug abuse to meet the...
Drug abuse is a global social issue of concern. As the drug market expands, there is an urgent need for technological methods to rapidly detect drug abuse to meet the needs of different situations. Here, we present a strategy for the rapid identification of benzodiazepines (midazolam and diazepam) using surface-enhanced Raman scattering (SERS) combined with neural networks (CNN). The method uses a self-assembled silver nanoparticle paper-based SERS substrate for detection. Then, a SERS spectrum intelligent recognition model based on deep learning technology was constructed to realize the rapid and sensitive distinction between the two drugs. In this work, a total of 560 SERS spectra were collected, and the qualitative and quantitative identification of the two drugs in water and a beverage (Sprite) was realized by a trained convolutional neural network (CNN). The predicted concentrations for each scenario could reach 0.1-50 ppm (midazolam in water), 0.5-50 ppm (midazolam in water and diazepam in Sprite), and 5-150 ppm (diazepam in Sprite), with a strong coefficient of determination () larger than 0.9662. The advantage of this method is that the neural network can extract data features from the entire SERS spectrum, which makes up for information loss when manually identifying the spectrum and selecting a limited number of characteristic peaks. This work clearly clarifies that the combination of SERS and deep learning technology has become an inevitable development trend, and also demonstrates the great potential of this strategy in the practical application of SERS.
Topics: Benzodiazepines; Midazolam; Metal Nanoparticles; Silver; Diazepam; Technology; Neural Networks, Computer; Water
PubMed: 36426728
DOI: 10.1039/d2an01277d -
Neuroscience Nov 2019Status epilepticus (SE) is a life-threatening condition needing immediate care to prevent brain damage. SE with electrographic and behavioral features similar to those...
Status epilepticus (SE) is a life-threatening condition needing immediate care to prevent brain damage. SE with electrographic and behavioral features similar to those seen in humans is reproduced in rodents by i.p. pilocarpine injection, and can be terminated by diazepam and ketamine treatment but only behaviourally, not electrographically. Little is known on the behavioral and EEG effects induced by a delayed administration of ketamine (25 mg/kg) after diazepam (10 mg/kg) or vice versa. Therefore, we analysed behavior and EEG activity recorded from the mouse hippocampal CA3 region before, during SE and after anticonvulsant treatments. In the first group (n = 4), diazepam was administered one hour before ketamine whereas in the second group (n = 4) ketamine was administered one hour before diazepam. The EEG SE did not disappear after each of the two treatments but progressed within 4 h to a pattern of interictal discharges. However, diazepam administration before ketamine significantly shortened the time of behavioral recovery compared to when ketamine was administered before diazepam (p < 0.05). The two protocols were also associated to distinct EEG changes in gamma and high frequency oscillations. In conclusion, although diazepam and ketamine are not effective in stopping EEG SE, diazepam administration one hour before ketamine shortens behavioral recovery in pilocarpine-treated mice.
Topics: Animals; Anticonvulsants; Diazepam; Electroencephalography; Hippocampus; Ketamine; Mice; Pilocarpine; Status Epilepticus
PubMed: 31704492
DOI: 10.1016/j.neuroscience.2019.10.009