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Physiological Reports Sep 2023The aim of our study is to investigate the electrophysiological and anti-inflammatory effects of diclofenac potassium on epileptiform activity, which is the liquid form...
The aim of our study is to investigate the electrophysiological and anti-inflammatory effects of diclofenac potassium on epileptiform activity, which is the liquid form of diclofenac, and frequently used clinically for inflammatory process by inhibiting cyclooxygenase enzyme (COX). Wistar rats aged 2-4 months were divided into Epilepsy, Diazepam, Diclofenac potassium, and Diazepam+diclofenac potassium groups. Diazepam and diclofenac potassium were administered intraperitoneally 30 min after the epileptiform activity was created with penicillin injected intracortically under anesthesia. After the electrophysiological recording was taken in the cortex for 125 min, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated by the ELISA in the serums. No change was observed between the groups in serum IL-1β, IL-6, and TNF-α values. It was observed that the co-administration of diclofenac potassium and diazepam at 51-55, 56-60, 61-65, 111-115, and 116-120 min was more effective in reducing spike amplitude than diclofenac potassium alone (p < 0.05). Single-dose diclofenac potassium did not have an anti-inflammatory effect in epileptiform activity but both diazepam and diclofenac potassium reduced the epileptiform activity.
Topics: Rats; Animals; Rats, Wistar; Diclofenac; Interleukin-6; Tumor Necrosis Factor-alpha; Cyclooxygenase 2; Diazepam; Anti-Inflammatory Agents
PubMed: 37688418
DOI: 10.14814/phy2.15800 -
Journal of Pain Research 2024Skeletal muscle relaxants (SMRs) are widely used in treating musculoskeletal conditions. All SMRs, with the exception of baclofen and tizanidine, are on the list of 2023... (Review)
Review
BACKGROUND
Skeletal muscle relaxants (SMRs) are widely used in treating musculoskeletal conditions. All SMRs, with the exception of baclofen and tizanidine, are on the list of 2023 American Geriatrics Society Beers Criteria for potentially inappropriate medication use in older adults. In our geriatric practice, off-label use of tizanidine as preemptive analgesia drove us to find recent advances in its pharmacology and therapeutics. An update review of tizanidine was thus presented, aiming to bring the latest knowledge to clinicians and promote further research and practical exploration.
METHODS
Relevant literature up to December 2023 was identified through searches of PubMed, Web of Science, and Embase.
RESULTS
Tizanidine, a centrally acting alpha-2 adrenoceptor agonist with both antispastic and antispasmodic activity, shows efficacy in the common indications for all SMRs. From the perspective of drug safety, tizanidine has lower incidences of adverse events (injury, delirium, encephalopathy, falls, and opioid overdose) compared to baclofen, no association with risk of Alzheimer's disease as with orphenadrine, no risk of serotonin syndrome like metaxalone when comedicated with serotonergic drugs, no significant pharmacokinetic changes in CYP2C19 poor metabolizers unlike diazepam and carisoprodol, and no physically addictive or abuse properties like carisoprodol and diazepam. From the perspective of new and potential therapeutic uses, tizanidine has additional benefits (eg, gastroprotection that can improve patient tolerance to nonsteroidal anti-inflammatory agents, anti-neuropathic pain, a key component of multimodal analgesia strategy to reduce early postoperative pain, and anti-tumor effects). New delivery systems of tizanidine are developing to improve the pharmacokinetics of oral products, including buccal patches, transdermal delivery systems, nasal spray, and in situ rectal gel.
CONCLUSION
Tizanidine is an SMR with unique features and may be an optimal initial choice for older adults. There would be more scientific studies, wider therapeutic applications, and new drug formulations in the future.
PubMed: 38529017
DOI: 10.2147/JPR.S461032 -
Epilepsy & Behavior : E&B Nov 2023Status epilepticus (SE) is defined by abnormally prolonged seizures that may lead to brain damage and death. Our aim was to evaluate the efficacy and tolerability...
PURPOSE
Status epilepticus (SE) is defined by abnormally prolonged seizures that may lead to brain damage and death. Our aim was to evaluate the efficacy and tolerability (effectiveness) of intravenous brivaracetam (BRV) as a second-line treatment.
METHODS
Twenty-one patients (median age 68 years ± 17.28) were prospectively recruited between June 2019 and December 2022. Patients were treated with BRV (50-200 mg) as a second-line add-on therapy for SE. We evaluated the response of SE to the administration of BRV in terms of SE termination and recurrence of epileptic seizures at 6, 12, and 24 h, also monitoring safety. The first-line therapy was represented by intravenous benzodiazepines (mainly diazepam).
RESULTS
Almost a quarter of patients had generalized seizures, whereas the vast majority (76.2%) presented focal seizures. In 52.4% of patients, the underlying cause was cerebrovascular. Fourteen (66.7%) patients displayed a good early response in the subsequent 6 h. At 12 and 24 h, 8 (38%) and 11 (52.4%) patients, respectively, did not present seizures.
CONCLUSION
The present study highlights the potential of BRV when used as an early add-on therapy in SE, further confirming its good safety profile.
Topics: Humans; Aged; Anticonvulsants; Treatment Outcome; Status Epilepticus; Seizures; Pyrrolidinones; Drug Therapy, Combination
PubMed: 37839249
DOI: 10.1016/j.yebeh.2023.109464 -
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 -
Sleep Medicine: X Dec 2023To investigate the real-world effectiveness and safety of lemborexan for treating comorbid insomnia associated with other psychiatric disorders, and whether lemborexant...
AIM
To investigate the real-world effectiveness and safety of lemborexan for treating comorbid insomnia associated with other psychiatric disorders, and whether lemborexant helps reduce the dose of benzodiazepines (BZs).
METHODS
This retrospective observational study was conducted on outpatients and inpatients treated by physicians of Juntendo University Hospital Mental Clinic between April 2020 and December 2021.
RESULTS
Data of 649 patients who were treated with lemborexant were eventually enrolled. About 64.5% of patients were classified as the responder group. Response rates of ≥60% were recorded for most psychiatric disorders. Upon administration of lemborexant, diazepam-equivalent dose of BZs had been significantly reduced in participants (3.7 ± 8.2 vs. 2.9 ± 7.9, p < 0.001). The results of logistic regression analysis showed that outpatient (odds ratios: 2.310; 95% confidence interval [CI]: 1.32-4.05), shorter duration of BZ use (<1 year) (odds ratios: 1.512; 95% CI: 1.02-2.25), no adverse events (odds ratios: 10.369; 95% CI: 6.13-17.54), larger reduction of diazepam-equivalent dose of BZs upon introducing lemborexant prescription (odds ratios: 1.150; 95% CI: 1.04-1.27), and suvorexant was the replacement drug (odds ratios: 2.983; 95% CI: 1.44-6.19), which were significant predictors of good response.
CONCLUSION
Although this is a retrospective and observational study with many limitations, our study results suggest that lemborexant is effective and safe.
PubMed: 37065177
DOI: 10.1016/j.sleepx.2023.100070 -
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 -
Dermatologic Surgery : Official... Nov 2023Patient anxiety can complicate surgical outcomes by elevating blood pressure, increasing the need for postoperative pain management, and reducing overall patient... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patient anxiety can complicate surgical outcomes by elevating blood pressure, increasing the need for postoperative pain management, and reducing overall patient satisfaction. Despite the use of anxiolytic medications in outpatient procedures, there is limited comparative evidence on the efficacy and safety of these agents in Mohs micrographic surgery.
OBJECTIVE
To compare the effectiveness and safety of different preprocedural anxiolytic agents in Mohs surgery on perioperative patient anxiety and patient satisfaction.
MATERIALS AND METHODS
A double-blinded, randomized, placebo-controlled trial was conducted of 6 different preprocedural anxiolytic agents (lorazepam, diazepam, alprazolam, gabapentin, pregabalin, and melatonin) in 350 patients undergoing Mohs surgery. Anxiety and vital signs were recorded.
RESULTS
Diazepam demonstrated a statistically significant, sustained reduction in anxiety levels compared with placebo ( p = .03). Gabapentin significantly reduced early anxiety ( p = .02). Alprazolam showed a trend to early anxiety reduction ( p = .08). Lorazepam ( p = .73), pregabalin ( p = .53), and melatonin ( p = .24) failed to reduce patient anxiety compared with placebo at any time point. No anxiolytic significantly impacted any patient vital sign or cognition.
CONCLUSION
Although short-acting benzodiazepines and gamma-aminobutyric acid medications may have transient anxiolytic effects, a single oral dose of 5 mg of diazepam can provide a sustained anxiolytic effect in Mohs surgery, with excellent patient safety.
Topics: Humans; Alprazolam; Anti-Anxiety Agents; Anxiety; Diazepam; Double-Blind Method; Gabapentin; Lorazepam; Melatonin; Mohs Surgery; Pregabalin
PubMed: 37606659
DOI: 10.1097/DSS.0000000000003905 -
Auris, Nasus, Larynx Apr 2024After unilateral peripheral vestibular lesions, the neural activity of neurons in the ipsi-lesional medial vestibular nucleus (ipsi-MVe) are markedly decreased,... (Review)
Review
After unilateral peripheral vestibular lesions, the neural activity of neurons in the ipsi-lesional medial vestibular nucleus (ipsi-MVe) are markedly decreased, resulting in static and dynamic asymmetries of the vestibulo-ocular and vestibulo-spinal reflexes. Consequently, static vestibular symptoms such as spontaneous nystagmus and postural deviation and dynamic vestibular symptoms such as oscillopsia and swaying gait are induced. However, these behavioral asymmetries gradually recover after the lesion. Progressive balance restoration is termed vestibular compensation, which is divided into two phases: static and dynamic. Static vestibular compensation is further divided into initial and late processes. In the initial process of static vestibular compensation after unilateral labyrinthectomy (UL) in rats, plastic changes in the cerebello-vestibular and vestibular commissural inhibitory pathways suppress neurons in the contra-lesional MVe (contra-MVe), resulting in the restoration of symmetrical resting activity of MVe neurons on both sides at low levels. The declining frequency of spontaneous nystagmus after UL is an index of the initial process, and short-term administration of diazepam, a GABA receptor agonist, has been shown to accelerate the initial process in rats. Accordingly, short-term administration of diazepam is recommended for the treatment of acute vertigo in patients with unilateral vestibular dysfunction. In the late process of static vestibular compensation after UL in rats, the resting activity of ipsi-MVe neurons gradually recovers due to changes in cell membrane properties, resulting in the reinforcement of balanced intervestibular nuclear activities to nearly normal levels without the suppression of contra-MVe neurons. The declining number of MK801-induced Fos-positive neurons in contra-MVe after UL is an index of the late process, and long-term administration of betahistine, a histamine H receptor antagonist, has been shown to accelerate the late process in rats. Accordingly, long-term administration of betahistine is recommended for the treatment of subacute vertigo in patients who were not compensated for unilateral vestibular dysfunction. In the process of dynamic vestibular compensation after UL, the sensitivity of ipsi-MVe neurons to head velocity and acceleration is restored due to synaptic changes such as long-term potentiation and sprouting of commissures, resulting in the restoration of the dynamic vestibulo-ocular and vestibulo-spinal reflexes. To facilitate dynamic vestibular compensation, early ambulation and subsequent vestibular rehabilitation exercise are recommended for the treatment of chronic vertigo in patients with uncompensated unilateral vestibular dysfunction. Although vestibular compensation after bilateral vestibular loss is not expected, vestibular rehabilitation with a sensory-substitution strategy can improve imbalance in patients with bilateral vestibular lesions.
Topics: Humans; Rats; Animals; Betahistine; Vestibule, Labyrinth; Brain; Vertigo; Nystagmus, Pathologic; Diazepam
PubMed: 38114342
DOI: 10.1016/j.anl.2023.11.009 -
Revista Medica Del Instituto Mexicano... Sep 2023The electroencephalogram (EEG) in the newborn period is highly superior to the clinical exam in the detection and prognosis of brain dysfunctions, since it allows... (Observational Study)
Observational Study
BACKGROUND
The electroencephalogram (EEG) in the newborn period is highly superior to the clinical exam in the detection and prognosis of brain dysfunctions, since it allows continuous functional documentation of the brain at the patient's bedside in a non-invasive way. However, there is still some disagreement about these findings.
OBJECTIVE
To describe the electroencephalographic findings in newborns with a history of prematurity.
MATERIAL AND METHODS
Cross-sectional, descriptive, retrospective study. The inclusion criteria were: newborns with a history of prematurity, regardless of gender, who underwent an EEG from June 2017 to June 2021. Patients with incomplete electroencephalographic records or clinical records without complete data were excluded; patients using sedatives (thiopental, fentanyl, midazolam, diazepam) were eliminated from the study.
RESULTS
107 patients (37 women and 70 men) with a history of prematurity were included, with a mean gestational age at birth of 30.9 WOG ± 3.25. Electroencephalographic findings were normal in 40%, abnormal in 32%, and immature in 28%. The most frequent abnormal finding was focal paroxysmal activity in 86%. 93.4% of the participants presented comorbidities, the most frequent being neurological.
CONCLUSION
Preterm neonates are at high risk of neurologic sequelae, and EEG is a sensitive method for assessing neuromotor and cognitive prognosis. In our study population, one-third had abnormal findings. Early postnatal screening is helpful, but additional records are usually needed to detect high-risk newborns. It would be important to continue studying this line of research in pediatrics.
Topics: Male; Infant, Newborn; Humans; Female; Child; Retrospective Studies; Cross-Sectional Studies; Infant, Premature; Gestational Age; Electroencephalography
PubMed: 37769006
DOI: 10.5281/zenodo.8316443