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International Journal of Molecular... Sep 2023In this study, atomistic simulations were carried out to study the difference in the adsorption process between two similar molecules, diazepam and oxazepam, on...
In this study, atomistic simulations were carried out to study the difference in the adsorption process between two similar molecules, diazepam and oxazepam, on Na-montmorillonite. Kinetic and XRD measurements showed a contrasting adsorption mechanism of these two molecules, differing only by the presence/absence of methyl and hydroxyl groups, with a larger adsorption amount and intercalation for the oxazepam. The structural characterization of these molecules was investigated through DFT calculations and showed the vicinity of hydroxyl and carbonyl groups for only the chair conformation of oxazepam compared to the boat conformation. Classical molecular dynamics simulations of diazepam and the two forms of oxazepam on the external surface of Na-montmorillonite highlighted the better coordination of the oxazepam-chair conformation, compared to its boat counterpart and diazepam. This has been confirmed through DFT calculations, from which a coordination energy that is greater by 10 kcal·mol is observed. This strongly suggests that the experimentally observed intercalation of oxazepam occurs only in the chair form because of the strong coordination with the Na cation present in the Na-Mt interlayer. Classical MD simulations of the intercalated oxazepam chair molecule in the Na-Mt interlayer allowed the evaluation of the interlayer spacing d001, which was in very good agreement with the experimental XRD measurement.
Topics: Clay; Bentonite; Adsorption; Oxazepam; Diazepam
PubMed: 37834226
DOI: 10.3390/ijms241914781 -
Acta Medica Academica Dec 2023This study investigated several inflammatory markers' gene and protein expression in status epilepticus (SE) and their correlation with diazepam resistance.
OBJECTIVE
This study investigated several inflammatory markers' gene and protein expression in status epilepticus (SE) and their correlation with diazepam resistance.
MATERIALS AND METHODS
Peripheral blood samples were collected from 18 adult patients with SE in Cipto Mangunkusumo Central Hospital, consisting of 12 diazepam-responsive and six diazepam-resistant samples, within 72 hours of the onset of the seizure. We collected baseline demographic and clinical data from each subject. Peripheral blood mononuclear cells (PBMCs) were isolated, cultured, stimulated with lipopolysaccharide (LPS) 1 mg/ml, and harvested for RNA isolation. The RNA was used to determine the expression of Human Mobility Group Box 1 (HMGB1), Interleukin- 6 (IL-6), IL-10, Toll-like Receptor 4 (TLR4), and Glial fibrillary acidic protein (GFAP). In addition, we performed serum protein assay of HMGB1, IL-6, IL-10, TLR4, and GFAP to compare with gene expression.
RESULTS
We found a significant difference between the responsive and resistant groups for serum HMGB1 and IL-6 concentration. The mRNA expression of HMGB1 and IL-6 was significantly higher in LPS-stimulated samples in the responsive but not in the resistant groups. The ratio of IL-6 to IL-10 showed a significant difference between LPS and control in the responsive group. Diazepam response was significantly correlated with seizure duration and serum protein concentration of HMGB1.
CONCLUSION
HMGB1 was highly expressed in the resistant group and strongly correlated with diazepam response, and there was a significant increase in HMGB1 mRNA expression in response to LPS stimulation. These findings suggest that targeting HMGB1 may be a promising therapeutic strategy and that HMGB1 levels could be a valuable biomarker for predicting diazepam resistance in SE.
Topics: Adult; Humans; Diazepam; Interleukin-10; Toll-Like Receptor 4; HMGB1 Protein; Interleukin-6; Leukocytes, Mononuclear; Lipopolysaccharides; Status Epilepticus; Seizures; Blood Proteins; RNA; RNA, Messenger
PubMed: 38407083
DOI: 10.5644/ama2006-124.423 -
JACC. Basic To Translational Science Sep 2023
PubMed: 37791300
DOI: 10.1016/j.jacbts.2023.07.015 -
Neurology Sep 2023Antiseizure medications (ASMs) are among the most commonly prescribed teratogenic drugs in women of childbearing age. Limited data exist on utilization patterns across...
BACKGROUND AND OBJECTIVES
Antiseizure medications (ASMs) are among the most commonly prescribed teratogenic drugs in women of childbearing age. Limited data exist on utilization patterns across different indications for therapy and for the newer-generation ASMs in this population. Thus, we assessed the pattern of ASM use in women of childbearing age with epilepsy and nonepilepsy indications (pain and psychiatric disorders).
METHODS
We conducted a retrospective analysis of deidentified administrative data submitted to the Optum Clinformatics database. Eligible participants included women aged 12-50 years who filled ASMs between year 2011 and 2017. Participants were followed from date of index prescription filled to study end or insurance disenrollment, whichever came first. For the overall cohort and potential therapy indications, we assessed the type and frequency of ASMs filled; proportion of participants on monotherapy, polytherapy, or treatment switching; and duration of continuous use. Trends were characterized using annual percent change from study start to study end.
RESULTS
Our analysis included 465,131 participants who filled 603,916 distinct ASM prescriptions. At baseline, most of the participants had chronic pain (51.0%) and psychiatric disorders (32.7%), with epilepsy the least common (0.9%). The most frequently dispensed were diazepam (24.3%), lorazepam (20.1%), gabapentin (17.4%), clonazepam (12.7%), topiramate (11.3%), and lamotrigine (4.6%). Significant linear increase in trends were observed with gabapentin (annual percent change [95% CI]: 8.4 [7.3-9.4]; < 0.001) and levetiracetam (3.4 [0.7-6.2]; = 0.022) and decreasing trends for diazepam (-3.5 [-2.4 to 4.5]; < 0.001) and clonazepam (-3.4 [-2.3 to 4.5]; = 0.001). No significant change in trend was observed with valproate (-0.4 [-2.7 to 1.9]; = 0.651), while nonlinear changes in trends were observed with lorazepam, topiramate, lamotrigine, and pregabalin.
DISCUSSION
Decreasing trends were observed with older ASMs in the overall cohort and across the potential indications for therapy. Conversely, increasing trends were seen with the newer ASMs. Considering the risk of teratogenicity associated with the newer medications largely unknown, counseling and education in addition to a careful consideration of the benefits vs potential risks should remain pivotal when prescribing ASMs for women of childbearing age.
Topics: Female; Humans; Lamotrigine; Retrospective Studies; Gabapentin; Topiramate; Clonazepam; Lorazepam; Epilepsy; Anticonvulsants; Valproic Acid; Diazepam
PubMed: 37407266
DOI: 10.1212/WNL.0000000000207580 -
Frontiers in Pharmacology 2024Diazepam, one of the benzodiazepines, is widely used clinically to treat anxiety, for termination of epilepsy, and for sedation. However, the reports of its adverse...
Diazepam, one of the benzodiazepines, is widely used clinically to treat anxiety, for termination of epilepsy, and for sedation. However, the reports of its adverse events (AEs) have been numerous, and even fatal complications have been reported. In this study, we investigated the AEs of diazepam based on real data from the U.S. Food and Drug Administration (FDA) adverse event reporting system (FAERS). Disproportionality in diazepam-associated AEs was assessed through the calculation of reporting odds ratios (RORs), proportional reporting ratios (PRRs), Bayesian confidence-propagation neural networks (BCPNNs), and gamma-Poisson shrinkage (GPS). Among the 19,514,140 case reports in the FAERS database, 15,546 reports with diazepam as the "principal suspect (PS)" AEs were identified. Diazepam-induced AEs occurred targeting 27 system organ categories (SOCs). Based on four algorithms, a total of 391 major disproportionate preferred terms (PTs) were filtered out. Unexpectedly significant AEs such as congenital nystagmus, developmental delays, and rhabdomyolysis were noted, which were not mentioned in the drug insert. Our study identified potential signals of new AEs that could provide strong support for clinical monitoring and risk identification of diazepam.
PubMed: 38327980
DOI: 10.3389/fphar.2024.1278442 -
Heliyon Dec 2023, known as Yarrow, is a medicinal plant in the family which is one of the oldest known botanicals used by humans and itis one of the most important medicinal plants in... (Review)
Review
BACKGROUND
, known as Yarrow, is a medicinal plant in the family which is one of the oldest known botanicals used by humans and itis one of the most important medicinal plants in the pharmaceutical field. Purpose: This review discusses pharmacodynamics, pharmacokinetics, and mechanism of action of the most important component of . There are a variety of same species such as white, red and yellow yarrow and all of these species have been discussed in this manuscript. We focus on previously discovered hormonal, antibiotic, and anticancer drug interactions with that may decrease or increase the concentration of certain drugs. We categorized different interactions of this herb into minor and serious ones, such as affecting Cytochromes P450 metabolism enzyme, resulting in a concentration rise in drugs such as Erythromycin, Diazepam, and Cyclosporine.The reason of writing a review article in this field is our enthusiasm for pharmacology of herbal ingredients and also, we want to gather other scientists' and our knowledge in this review for future researchers who like to know more about this plant pharmacological criteria in order to make their way.
METHOD
Pharmacological and phytochemical-specific details of , as well as related keywords, were used to conduct a literature search across the following essential collections of electronic databases: Web of Science, Google Scholar, PubMed, and Science Direct.
OUTCOME
medical indications are the treatment of spasmodic gastrointestinal ulcers, inflammation, wound healing, and cancers, as well as excellent antioxidant activity. Camphene, Limonene, Apigenin and some other components show anti-inflammatory effects by cyclooxygenase inhibition, prostaglandin E2 inhibition and other mechanisms. Studies showed 90 % of its essential oil consists of monoterpenes which can be mutually beneficial with extract components.
CONCLUSION
can play a significant role as a strong antioxidant and anticancer source, positively affecting gastrointestinal inflammations.
PubMed: 38076118
DOI: 10.1016/j.heliyon.2023.e22841 -
Pediatrics Aug 2023Previous evaluations of medication dosing variance for children in the prehospital setting have been limited regionally or to specific conditions. We sought to describe...
BACKGROUND
Previous evaluations of medication dosing variance for children in the prehospital setting have been limited regionally or to specific conditions. We sought to describe pediatric dosing deviations from nationally recommended guidelines for commonly administered medications from a registry of prehospital encounters.
METHODS
We evaluated prehospital patient care records for children (<18 years) from approximately 2000 emergency medical services agencies from 2020 to 2021. We investigated dosing deviations (defined as being ≥20% of the weight-appropriate dose from national guidelines) for the following: lorazepam, diazepam, and midazolam for seizures; fentanyl, hydromorphone, morphine, and ketorolac; intramuscular epinephrine and diphenhydramine for children with allergy or anaphylaxis; intravenous epinephrine; and methylprednisolone.
RESULTS
Of 990 497 pediatric encounters, 63 963 (6.4%) received at least 1 nonnebulized medication. Among nonnebulized doses, 53.9% were for the studied drugs. Among encounters who received a study drug and which had a documented weight (80.3%), the overall consistency with national guidelines was 42.6 per 100 administrations. Appropriate dosing was most common with methylprednisolone (75.1%), intramuscular epinephrine (67.9%), and ketorolac (56.4%). Medications with the lowest consistency with national guidelines were diazepam (19.5%) and lorazepam (21.2%). Most deviations represented an underdose, which was greatest with lorazepam (74.7%) and morphine (73.8%). Results were similar when estimating dosages from weights calculated by age.
CONCLUSIONS
We identified variance in weight-based dosing from national guidelines for common pediatric medications in the prehospital setting, which may be attributable to protocol differences or dosing errors. Addressing these should be a target for future educational, quality improvement, and research activities.
Topics: Child; Humans; Lorazepam; Ketorolac; Emergencies; Diazepam; Epinephrine; Emergency Medical Services; Morphine; Methylprednisolone; Hospitals
PubMed: 37424429
DOI: 10.1542/peds.2023-061223 -
Current Pediatric Reviews 2024While generally self-limited, febrile seizures result in significant familial distress. Ambulatory pediatric care providers must be prepared to counsel families on the... (Review)
Review
BACKGROUND
While generally self-limited, febrile seizures result in significant familial distress. Ambulatory pediatric care providers must be prepared to counsel families on the causes, risk factors, management principles, and prognosis of children with febrile seizures.
OBJECTIVE
To provide an updated, evidence-based review of febrile seizures focused on the needs of an ambulatory pediatric care provider.
METHODS
A narrative review of the literature prioritizing landmark articles, metanalyses, longitudinal population longitudinal cohort studies and national level guidelines.
RESULTS
Febrile seizures are aberrant physiological responses to fever in children caused by complex interactions of cytokine mediated neuroinflammation, environmental triggers, and genetic predisposition. Other than investigations to determine fever etiology, routine bloodwork, lumbar punctures, neuroimaging and electroencephalograms are low yield. The general prognosis is excellent, however, clinicians should be aware of long-term outcomes including: cognitive impairment with non-simple febrile seizures; neuropsychiatric associations; recurrent febrile seizure and epilepsy risk factors; and the association between complex febrile seizures and sudden unexpected death. Children with a high risk of recurrence, complex febrile seizures, limited access to care, or extreme parental anxiety may benefit from intermittent oral diazepam prophylaxis.
CONCLUSION
Clinicians should consider four management priorities: 1) terminating the seizure; 2) excluding critical differential diagnoses; 3) investigating fever etiology; and 4) providing adequate counselling to families. The clinical approach and prognosis of febrile seizure can be based on subtype. Children with non-simple (i.e. complex or febrile status epilepticus) febrile seizures require closer care than the vast majority of children with simple febrile seizures, who have excellent outcomes.
Topics: Child; Humans; Infant; Seizures, Febrile; Longitudinal Studies; Prognosis; Risk Factors; Ambulatory Care
PubMed: 36043723
DOI: 10.2174/1573396318666220829121946 -
Psychopharmacology Dec 2023Reproductive experience (pregnancy and motherhood) leads to long-term changes in the neurobiological and hormonal features of anxiety in rats and humans. The aim of this...
OVERVIEW
Reproductive experience (pregnancy and motherhood) leads to long-term changes in the neurobiological and hormonal features of anxiety in rats and humans. The aim of this study was to examine whether reproductive experience alters the effects of two pharmacological treatments for anxiety, a benzodiazepine (diazepam) and a selective serotonin reuptake inhibitor (fluoxetine), on animal models of anxiety.
METHODS
In Experiment 1, virgin (n = 47) and age-matched mother (n = 50) rats at 1-month post-weaning were injected with diazepam (1.3 mg/kg or 1.7 mg/kg, i.p.) or vehicle, in the proestrus (high estradiol/progesterone/allopregnanolone) or metestrus (low estradiol/progesterone/allopregnanolone) phase of the estrous cycle 30 min prior to the elevated plus maze (EPM). In Experiment 2, virgin (n = 25) and mother rats (n = 20) were administered fluoxetine (10 mg/kg) or vehicle for 2 weeks prior to being tested on a Pavlovian fear conditioning and extinction protocol, and the EPM.
RESULTS
Replicating past research, in virgin rats, the low dose of diazepam produced anxiolytic-like effects in proestrus, but only the high dose was anxiolytic-like in metestrus. In contrast, in mother rats, both doses of diazepam were anxiolytic-like irrespective of estrous phase. Fluoxetine produced anxiogenic-like effects in virgin rats during fear extinction and the EPM, but had no behavioural effects in mothers. In contrast, fluoxetine increased plasma corticosterone levels measured 30-min post-EPM in mothers, but not virgin rats.
CONCLUSIONS
Reproductive experience alters the dose responsivity and efficacy of common anti-anxiety medications in female rats. These findings highlight the importance of considering reproductive status in studies on anxiety and its treatment.
Topics: Pregnancy; Humans; Rats; Female; Animals; Diazepam; Fluoxetine; Fear; Corticosterone; Anti-Anxiety Agents; Progesterone; Extinction, Psychological; Pregnanolone; Anxiety; Estradiol
PubMed: 37581635
DOI: 10.1007/s00213-023-06446-z -
Brain Research Bulletin Oct 2023Stellaria dichotoma L. var. lanceolata Bge. is renowned for its efficacy in "clearing deficiency heat" and represents a significant traditional Chinese medicine (TCM)...
The Anxiolytic Effect of Polysaccharides from Stellariae Radix through Monoamine Neurotransmitters, HPA Axis, and ECS/ERK/CREB/BDNF Signaling Pathway in Stress-induced Male Rats.
BACKGROUND
Stellaria dichotoma L. var. lanceolata Bge. is renowned for its efficacy in "clearing deficiency heat" and represents a significant traditional Chinese medicine (TCM) resource. Modern pharmacology has demonstrated the anti-anxiety effects of Stellaria dichotoma L. var. lanceolata Bge. polysaccharides (SDPs). SDPs are one of the active constituents of Stellaria dichotoma L. var. lanceolata Bge. This study presents the first extraction of SDPs and investigates their potential molecular mechanisms and anxiolytic effects that are not previously reported.
METHODS
First, SDPs were obtained by water extraction and alcohol precipitation and analyzed for their monosaccharide composition by high performance liquid chromatography (HPLC). Male SD rats were subjected to a two-week indeterminate empty bottle stress procedure and a three-day acute restraint stress procedure, during which diazepam (DZP) (1 mg/kg) and SDPs (50, 100 and 200 mg/kg, intragastrically) were administered. A number of behavioral tests, including the elevated plus maze test (EPM), the open field test (OFT) and the light/dark box test (LDB), were used to assess the anti-anxiety potential of SDPs. Serum levels of Corticosterone (CORT) and Adrenocorticotropic hormone (ACTH), as well as the levels of Dopamine (DA) and serotonin (5-HT) found in the hippocampus and frontal cortex, were quantified using commercially available enzyme-linked immunosorbent assay (ELISA) kits. In addition, protein levels of key proteins cAMP-response element binding protein (CREB), phospho-CREB (p-CREB), brain-derived neurotrophic factor (BDNF), ERK½, p-ERK½, and GAPDH expression in rat hippocampus were measured by Western blot analysis, and modulation of the endocannabinoid system was assessed by immunohistochemistry.
RESULTS
Following administration of SDPs (50, 100, 200 mg/kg) and diazepam 1 mg/kg, anxiolytic activity was exhibited through an increase in the percentage of arm opening times and arm opening time of rats in the elevated plus maze. Additionally, there was an increase in the number of times and time spent in the open field center, percentage of time spent in the open box, and shuttle times in the LDB. Furthermore, tissue levels of DA and 5-HT were increased in the hippocampus and frontal cortex of rats after treatment with SDPs. In addition, SDPs significantly decreased serum levels of CORT and ACTH in rats. SDPs also effectively regulated the phosphorylation of the extracellular regulated protein kinases (ERK) and CREB-BDNF pathway in the hippocampus. Moreover, the expression levels of CB1 and CB2 proteins were heightened due to SDPs treatment in rats.
CONCLUSIONS
The study verified that SDPs alleviate anxiety in the EBS and ARS. The neuroregulatory behavior is accomplished by regulating the Monoamine neurotransmitter, HPA axis, and ECB-ERK-CREB-BDNF signaling pathway.
Topics: Rats; Male; Animals; Anti-Anxiety Agents; Brain-Derived Neurotrophic Factor; Rats, Sprague-Dawley; Protein Kinases; Cyclic AMP Response Element-Binding Protein; Serotonin; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Signal Transduction; Hippocampus; Dopamine; Adrenocorticotropic Hormone; Diazepam; Neurotransmitter Agents
PubMed: 37739234
DOI: 10.1016/j.brainresbull.2023.110768