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  1. Management of status epilepticus in Malaysia: A national survey of current practice and treatment gap
    Lim KS, Khoo CS, Fong SL, Tan HJ, Fong CY, Mohamed AR, et al.
    J Clin Neurosci, 2023 Aug;114:25-31.
    PMID: 37279626 DOI: 10.1016/j.jocn.2023.05.006
    INTRODUCTION: Early and effective treatment is fundamental in status epilepticus (SE) management. At the initiative of the Epilepsy Council of Malaysia, this study aimed to determine the treatment gap in SE across different healthcare settings in Malaysia.

    METHODS: A web-based survey was sent to clinicians involved in the management of SE, across all states and at all levels of healthcare services.

    RESULTS: A total of 158 responses were received from 104 health facilities, including 23 tertiary government hospitals (95.8% of all government tertiary hospitals in Malaysia), 4 (80.0%) universities, 14 (6.7%) private, 15 (11.5%) district hospitals and 21 clinics. Intravenous (IV) diazepam was available in 14 (93.3%) district and 33 (80.5%) tertiary hospitals for prehospital management. Non-IV benzodiazepine (rectal diazepam and intramuscular midazolam) was not widely available in prehospital services (75.8% and 51.5%). Intramuscular midazolam was underutilised (60.0% in district and 65.9% in tertiary hospitals). IV sodium valproate and levetiracetam were only available in 66.7% and 53.3% of the district hospitals, respectively. Electroencephalogram (EEG) services were available in only 26.7% of the district hospitals. Non-pharmacological therapies such as ketogenic diet, electroconvulsive therapy, and therapeutic hypothermia were not available in most district and tertiary hospitals for refractory and super-refractory SE.

    CONCLUSIONS: We identified several gaps in the current practice of SE management, including limited availability and underutilization of non-IV midazolam in prehospital services, underutilization of non-IV midazolam and other second-line ASMs, and lack of EEG monitoring in district hospitals and limited treatment options for refractory and super-refractory SE in tertiary hospitals.

    Matched MeSH terms: Diazepam
  2. Characterization of Oil Palm Acyl-CoA-Binding Proteins and Correlation of Their Gene Expression with Oil Synthesis
    Amiruddin N, Chan PL, Azizi N, Morris PE, Chan KL, Ong PW, et al.
    Plant Cell Physiol, 2020 Apr 01;61(4):735-747.
    PMID: 31883014 DOI: 10.1093/pcp/pcz237
    Acyl-CoA-binding proteins (ACBPs) are involved in binding and trafficking acyl-CoA esters in eukaryotic cells. ACBPs contain a well-conserved acyl-CoA-binding domain. Their various functions have been characterized in the model plant Arabidopsis and, to a lesser extent, in rice. In this study, genome-wide detection and expression analysis of ACBPs were performed on Elaeis guineensis (oil palm), the most important oil crop in the world. Seven E. guineensis ACBPs were identified and classified into four groups according to their deduced amino acid domain organization. Phylogenetic analysis showed conservation of this family with other higher plants. All seven EgACBPs were expressed in most tissues while their differential expression suggests various functions in specific tissues. For example, EgACBP3 had high expression in inflorescences and stalks while EgACBP1 showed strong expression in leaves. Because of the importance of E. guineensis as an oil crop, expression of EgACBPs was specifically examined during fruit development. EgACBP3 showed high expression throughout mesocarp development, while EgACBP1 had enhanced expression during rapid oil synthesis. In endosperm, both EgACBP1 and EgACBP3 exhibited increased expression during seed development. These results provide important information for further investigations on the biological functions of EgACBPs in various tissues and, in particular, their roles in oil synthesis.
    Matched MeSH terms: Diazepam Binding Inhibitor/genetics*; Diazepam Binding Inhibitor/metabolism
  3. Stabilization of Human Serum Albumin against Urea Denaturation by Diazepam and Ketoprofen
    Manoharan P, Wong YH, Tayyab S
    Protein Pept Lett, 2015;22(7):611-7.
    PMID: 25961707
    Stabilizing effect of diazepam and ketoprofen, Sudlow's site II markers on human serum albumin (HSA) against urea denaturation was studied using fluorescence spectroscopy. The two-step, three-state urea transition of HSA was transformed into a single-step, two-state transition with the abolishment of the intermediate state along with a shift of the transition curve towards higher urea concentrations in the presence of diazepam or ketoprofen. Interestingly, a greater shift in the transition curve of HSA was observed in the presence of ketoprofen compared to diazepam. A comparison of the intrinsic fluorescence and three-dimensional fluorescence spectra of HSA and partially-denatured HSAs, obtained in the absence and the presence of diazepam or ketoprofen suggested significant retention of native-like conformation in the partially-denatured states of HSA in the presence of Sudlow's site II markers. Taken together, all these results suggested stabilization of HSA in the presence of diazepam or ketoprofen, being greater in the presence of ketoprofen.
    Matched MeSH terms: Diazepam/pharmacology*
  4. Febrile convulsions: acute seizure characteristics and anti-convulsant therapy
    Ling SG
    Ann Trop Paediatr, 2000 Sep;20(3):227-30.
    PMID: 11064777 DOI: 10.1080/02724936.2000.11748139
    A descriptive study using data from the medical records of 448 children with febrile convulsion was carried out to determine the seizure characteristics and use of anti-convulsant therapy for febrile convulsions in a Malaysian hospital. There was a higher incidence of multiple seizures and a lower incidence of focal seizures in the local population than in studies done among Western populations. The majority of initial seizures occurred within 24 h of fever onset. Transient neurological abnormalities following an acute seizure were common. A quarter of children referred by general practitioners had been given anti-convulsants prior to referral but up to 20% of general practitioners had used ineffective routes for administering diazepam. However, diazepam used in the hospital was found to be effective in controlling acute febrile seizures.
    Matched MeSH terms: Diazepam/therapeutic use
  5. Fulltext Studies on the anxiolytic activity of Eurycoma longifolia Jack roots in mice
    Ang HH, Cheang HS
    Jpn. J. Pharmacol., 1999 Apr;79(4):497-500.
    PMID: 10361892 DOI: 10.1254/jjp.79.497
    The anxiolytic effect of Eurycoma longifolia Jack in mice was examined. Fractions of E. longifolia Jack extract produced a significant increase in the number of squares crossed (controls= 118.2 +/- 10.2 squares), but significantly decreased both the immobility (controls = 39.4+/- 4.0 sec) and fecal pellets (controls= 12.3 +/-2.1 fecal pellets) when compared with control mice in the open-field test; they significantly increased the number of entries (controls=6.7+/-0.5 entries) and time spent (controls=42.9+/-0.1 sec) in the open arms, but decreased both the number of entries (controls= 13.2+/-0.7 entries) and time spent (controls= 193.4+/-0.7 sec) when compared with the control mice in the closed arms of the elevated plus-maze test. Furthermore, fractions of E. longifolia Jack extract decreased the fighting episodes significantly (controls= 18.0+/-0.4 fighting episodes) when compared with control mice. In addition, these results were found to be consistent with anxiolytic effect produced by diazepam. Hence, this study supports the medicinal use of this plant for anxiety therapy.
    Matched MeSH terms: Diazepam/pharmacology
  6. Fulltext Phenotypic subgrouping and multi-omics analyses reveal reduced diazepam-binding inhibitor (DBI) protein levels in autism spectrum disorder with severe language impairment
    Pichitpunpong C, Thongkorn S, Kanlayaprasit S, Yuwattana W, Plaingam W, Sangsuthum S, et al.
    PLoS One, 2019;14(3):e0214198.
    PMID: 30921354 DOI: 10.1371/journal.pone.0214198
    BACKGROUND: The mechanisms underlying autism spectrum disorder (ASD) remain unclear, and clinical biomarkers are not yet available for ASD. Differences in dysregulated proteins in ASD have shown little reproducibility, which is partly due to ASD heterogeneity. Recent studies have demonstrated that subgrouping ASD cases based on clinical phenotypes is useful for identifying candidate genes that are dysregulated in ASD subgroups. However, this strategy has not been employed in proteome profiling analyses to identify ASD biomarker proteins for specific subgroups.

    METHODS: We therefore conducted a cluster analysis of the Autism Diagnostic Interview-Revised (ADI-R) scores from 85 individuals with ASD to predict subgroups and subsequently identified dysregulated genes by reanalyzing the transcriptome profiles of individuals with ASD and unaffected individuals. Proteome profiling of lymphoblastoid cell lines from these individuals was performed via 2D-gel electrophoresis, and then mass spectrometry. Disrupted proteins were identified and compared to the dysregulated transcripts and reported dysregulated proteins from previous proteome studies. Biological functions were predicted using the Ingenuity Pathway Analysis (IPA) program. Selected proteins were also analyzed by Western blotting.

    RESULTS: The cluster analysis of ADI-R data revealed four ASD subgroups, including ASD with severe language impairment, and transcriptome profiling identified dysregulated genes in each subgroup. Screening via proteome analysis revealed 82 altered proteins in the ASD subgroup with severe language impairment. Eighteen of these proteins were further identified by nano-LC-MS/MS. Among these proteins, fourteen were predicted by IPA to be associated with neurological functions and inflammation. Among these proteins, diazepam-binding inhibitor (DBI) protein was confirmed by Western blot analysis to be expressed at significantly decreased levels in the ASD subgroup with severe language impairment, and the DBI expression levels were correlated with the scores of several ADI-R items.

    CONCLUSIONS: By subgrouping individuals with ASD based on clinical phenotypes, and then performing an integrated transcriptome-proteome analysis, we identified DBI as a novel candidate protein for ASD with severe language impairment. The mechanisms of this protein and its potential use as an ASD biomarker warrant further study.

    Matched MeSH terms: Diazepam Binding Inhibitor/metabolism*
  7. Fulltext Orthosiphon stamineus Proteins Alleviate Pentylenetetrazol-Induced Seizures in Zebrafish
    Chung YS, Choo BKM, Ahmed PK, Othman I, Shaikh MF
    Biomedicines, 2020 Jul 02;8(7).
    PMID: 32630817 DOI: 10.3390/biomedicines8070191
    The anticonvulsive potential of proteins extracted from Orthosiphon stamineus leaves (OSLP) has never been elucidated in zebrafish (Danio rerio). This study thus aims to elucidate the anticonvulsive potential of OSLP in pentylenetetrazol (PTZ)-induced seizure model. Physical changes (seizure score and seizure onset time, behavior, locomotor) and neurotransmitter analysis were elucidated to assess the pharmacological activity. The protective mechanism of OSLP on brain was also studied using mass spectrometry-based label-free proteomic quantification (LFQ) and bioinformatics. OSLP was found to be safe up to 800 µg/kg and pre-treatment with OSLP (800 µg/kg, i.p., 30 min) decreased the frequency of convulsive activities (lower seizure score and prolonged seizure onset time), improved locomotor behaviors (reduced erratic swimming movements and bottom-dwelling habit), and lowered the excitatory neurotransmitter (glutamate). Pre-treatment with OSLP increased protein Complexin 2 (Cplx 2) expression in the zebrafish brain. Cplx2 is an important regulator in the trans-SNARE complex which is required during the vesicle priming phase in the calcium-dependent synaptic vesicle exocytosis. Findings in this study collectively suggests that OSLP could be regulating the release of neurotransmitters via calcium-dependent synaptic vesicle exocytosis mediated by the "Synaptic Vesicle Cycle" pathway. OSLP's anticonvulsive actions could be acting differently from diazepam (DZP) and with that, it might not produce the similar cognitive insults such as DZP.
    Matched MeSH terms: Diazepam
  8. Fulltext Anticonvulsant activity of α-terpineol isolated from myristica fragrans in GAERS model of absence epilepsy
    Islam, M.R., Muthuraju, S., Tarmizi, C.H., Zulkifli, M.M., Osman, H., Mohamad, H., et al.
    ASM Science Journal, 2012;6(2):95-102.
    MyJurnal
    Epilepsy is a neurological disorder characterized by recurrent seizures resulting from excessive abnormal electrical discharges in the brain. Medicinal plants may play an invaluable role to discover the new antiepileptic drugs. The aim of the present study was to investigate the anticonvulsant activity of α-terpineol isolated from Myristica fragrans Hountt. The α-terpineol showed a significant inhibition of the seizure episodes and spikes in absence seizures model of Genetic Absence Epilepsy Rats from Strasbourg (GAERS) rats by using electroencephalography records. It showed dose-dependent anticonvulsant activity that was comparable to the known antiepileptic drug of diazepam. It showed a rapid onset and relatively short duration of anticonvulsant effects. The present findings suggest that α-terpineol might possess antiepileptic activities against the partial seizures of human because it prevented seizures in well-established genetic absence seizure animal model of GAERS rats.
    Matched MeSH terms: Diazepam
  9. Fulltext An Experimental Evaluation of Adaptogenic Potential of Standardized Epipremnum Aureum Leaf Extract
    Das SK, Sengupta P, Mustapha MS, Sarker MMR
    J Pharm Bioallied Sci, 2017 Apr-Jun;9(2):88-93.
    PMID: 28717330 DOI: 10.4103/0975-7406.183227
    BACKGROUND: Stress is a normal part of everyday life but chronic stress can lead to a variety of stress-related illnesses including hypertension, anxiety, and depression. In the present investigation, standardized leaf extract of Epipremnumaureum was evaluated for its anti-stress potential.

    MATERIALS AND METHODS: For the evaluation of anti-stress activity, groups of mice (n = 6) were subjected to forced swim stress and anoxic stress tolerance test in mice 1h after daily treatment of E.aureumextract. Diazepam (5 mg/kg) was taken as a reference standard. Urinary vanillylmandelic acid (VMA) and ascorbic acid were selected as noninvasive biomarkers to assess the anti-stress activity and plasma cortisol, blood ascorbic acid, and weight of adrenal were measured. The 24 h urinary excretion of VMA and ascorbic acid were determined by spectrophotometric methods in all groups under normal and stressed conditions. The hematological parameters (neutrophils, lymphocytes, and eosinophils) were also determined.

    RESULTS: Administration of E.aureumat doses of 400 and 600 mg/kg wasfound to be effective in inhibiting the stress induced urinary biochemical changes in a dose-dependent manner. Treatment with E. aureum extract prevents the rise in blood ascorbic acid and plasma cortisol. Moreover, the extract prevented the increase in weight of adrenal gland also significantly increased the anoxia stress tolerance time. Dose-dependent significant reduction in white blood cell count was observed in anoxic stress tolerance test as compared to stressed group.

    CONCLUSION: Hence, the present study provides scientific support for the positiveadaptogenic effect of E. aureum extract.
    Matched MeSH terms: Diazepam
  10. Fulltext Analysis of the Binding of Aripiprazole to Human Serum Albumin: The Importance of a Chloro-Group in the Chemical Structure
    Sakurama K, Kawai A, Tuan Giam Chuang V, Kanamori Y, Osa M, Taguchi K, et al.
    ACS Omega, 2018 Oct 31;3(10):13790-13797.
    PMID: 30411049 DOI: 10.1021/acsomega.8b02057
    Aripiprazole (ARP), a quinolinone derivative, is an atypical antipsychotic drug that is used in the treatment of schizophrenia. ARP has an extensive distribution and more than 99% of the ARP and dehydro-ARP, the main active metabolite, is bound to plasma proteins. However, information regarding the protein binding of ARP is limited. In this study, we report on a systematic study of the protein binding of ARP. The interaction of ARP and structurally related compounds with human serum albumin (HSA) was examined using equilibrium dialysis, circular dichroism (CD) spectroscopy, fluorescent probe displacement, and an X-ray crystallographic analysis. The binding affinities (nK) for ARP and its main metabolite, dehydro-ARP with HSA were found to be significantly higher than other structurally related compounds. The results of equilibrium dialysis experiments and CD spectral data indicated that the chloro-group linked to the phenylpiperazine ring in the ARP molecule plays a major role in the binding of these ligands to HSA. Furthermore, fluorescent probe displacement results indicated that ARP appears to bind at the site II pocket in subdomain III. A detailed CD spectral analysis suggests that the chloro-group linked to the phenylpiperazine ring may control the geometry of the ARP molecule when binding in the site II binding pocket. X-ray crystallographic analysis of the ARP-HSA complex revealed that the distance between the chlorine atom at the 3-positon of dichlorophenyl-piperazine on ARP and the sulfur atom of Cys392 in HSA was 3.4-3.6 Å. A similar halogen bond interaction has also been observed in the HSA structure complexed with diazepam, which also contains a chloro-group. Thus, the mechanism responsible for the binding of ARP to a protein elucidated here should be relevant for assessing the pharmacokinetics and pharmacodynamics of ARP in various clinical situations and for designing new drugs.
    Matched MeSH terms: Diazepam
  11. Immigrant Health Study. 8. Screening for abused drugs among immigrant workers. [Abstract]
    Mustafa AM, Yap CG
    JUMMEC, 1998;3:63-64.
    Screening for drugs of abused were conducted by using Gas chromatography-Mass spectrometry (GCMS) fitted with capillary column. Urine samples supplied by Centre of Inmigrant Studies, University of Malaya were processed upon arrival and screened for the following drugs. Amphetamines, methamphetamines, aphedrine, hydroxy-amphetamines, ecstasy, benzamphetamines, codeine, morphine, heroine, cocaine and diazepam. The analysis was done using Shimadzu QP5000 Gas chromatograph-mass spectrometer by selected ion monitoring with BPX35 column, 15 m length, 0.32 ID, helium gas as carrier and quadropole mass detector at 1.60 kV electron gain. Analysis were performed using selected ion monitoring (SIM) mode and quantitations were based on area under the curve of individual standards at various concentrations. The method is sensitive to nanogram levels and are able to detect the presence of these drugs in both urine and plasma. From this study (n-100), none of the urine were found positive for the drugs screened. The major problem encountered were adulterated with water based on the clearness and the colour of the urine. Based on this suspicion we would like to suggest that the testing be done on blood samples as this would be more confirmative and quantitative.
    Matched MeSH terms: Diazepam
  12. Fulltext Orthosiphon stamineus Leaf Extract Affects TNF-α and Seizures in a Zebrafish Model
    Choo BKM, Kundap UP, Kumari Y, Hue SM, Othman I, Shaikh MF
    Front Pharmacol, 2018;9:139.
    PMID: 29527169 DOI: 10.3389/fphar.2018.00139
    Epileptic seizures result from abnormal brain activity and can affect motor, autonomic and sensory function; as well as, memory, cognition, behavior, or emotional state. Effective anti-epileptic drugs (AEDs) are available but have tolerability issues due to their side effects. The Malaysian herbOrthosiphon stamineus, is a traditional epilepsy remedy and possesses anti-inflammatory, anti-oxidant and free-radical scavenging abilities, all of which are known to protect against seizures. This experiment thus aimed to explore if an ethanolic leaf extract ofO. stamineushas the potential to be a novel symptomatic treatment for epileptic seizures in a zebrafish model; and the effects of the extract on the expression levels of several genes in the zebrafish brain which are associated with seizures. The results of this study indicate thatO. stamineushas the potential to be a novel symptomatic treatment for epileptic seizures as it is pharmacologically active against seizures in a zebrafish model. The anti-convulsive effect of this extract is also comparable to that of diazepam at higher doses and can surpass diazepam in certain cases. Treatment with the extract also counteracts the upregulation of NF-κB, NPY and TNF-α as a result of a Pentylenetetrazol (PTZ) treated seizure. The anti-convulsive action for this extract could be at least partially due to its downregulation of TNF-α. Future work could include the discovery of the active anti-convulsive compound, as well as determine if the extract does not cause cognitive impairment in zebrafish.
    Matched MeSH terms: Diazepam
  13. Biomolecular interaction mechanism of an anticancer drug, pazopanib with human serum albumin: a multi-spectroscopic and computational approach
    Kandandapani S, Kabir MZ, Ridzwan NFW, Mohamad SB, Tayyab S
    J Biomol Struct Dyn, 2022 Nov;40(18):8312-8323.
    PMID: 33870854 DOI: 10.1080/07391102.2021.1911850
    Pazopanib (PZP) is a multi-targeting tyrosine kinase inhibitor and is currently approved by FDA for the treatment of soft tissue sarcoma and renal cancer. Molecular interaction mechanism of PZP with human serum albumin (HSA) was explored under simulated physiological conditions (pH = 7.4), using fluorescence and UV absorption spectroscopy along with computational methods. Based on the inverse correlation between the Stern-Volmer constant (Ksv) and temperature, it was concluded that PZP quenched the protein fluorescence through static quenching mechanism. This was also confirmed from the UV-vis absorption spectral results. Moderate binding affinity between PZP and HSA was evident from the Ka values (5.51 - 1.05 × 105 M-1) while PZP-HSA complex formation was driven by hydrophobic and van der Waals interactions as well as hydrogen bonds, as revealed by positive entropy change (ΔS = +98.37 J mol-1 K-1) and negative enthalpy change (ΔH = -60.31 kJ mol-1). Three-dimensional fluorescence spectral results disclosed microenvironmental perturbations around Trp and Tyr residues of the protein upon PZP binding. Interestingly, the addition of PZP to HSA significantly protected the protein against thermal stress. Competitive drug displacement results obtained with warfarin, phenylbutazone and diazepam elucidated Sudlow's Site I, positioned in subdomain IIA of HSA, as the preferred binding site of PZP which was well supported by molecular docking analysis, while molecular dynamics simulation results suggested the stability of the PZP-HSA complex.Communicated by Vsevolod Makeev.
    Matched MeSH terms: Diazepam
  14. Fulltext A 3 year case study of alcohol related psychotic disorders at Hospital Seremban
    George S, Chin CN
    Med J Malaysia, 1998 Sep;53(3):223-6.
    PMID: 10968157
    This paper reports the characteristics and psychopathology of alcohol dependents with alcohol induced psychotic disorder admitted to the Seremban Hospital. The method is that of a case study of all alcohol dependents with alcohol induced psychotic disorder admitted to the Psychiatric Ward, Hospital Seremban over 3 years (1993-1995). There were 34 subjects, 30 Indians, 3 Chinese and 1 Malay with a mean age of 43 years. 32 were men and predominantly of Social Class IV and V (91%). They had a mean duration of drinking of 14.2 years and had a mean weekly consumption of 69.5 units of alcohol. There was a family history of alcohol dependence in (44%). The majority (68%) consumed samsu with beer the second choice. Auditory hallucinations (26) and delusions (16) were common while visual hallucinations (3) and depression (2) were less frequent. Speech disorder occurred in 4 subjects. 2 developed delirium tremens and 1 died. Liver function test was normal in 55%. All except the death from delirium tremens responded to treatment with a combination of anxiolytics, thiamine and antipsychotics and were rapidly discharged. The mean stay was 7 days. However, (68%) did not return for follow up and only 4 were abstinent from alcohol at the time of follow up.
    Matched MeSH terms: Diazepam/therapeutic use
  15. Anxiolytic-like effects of mitragynine in the open-field and elevated plus-maze tests in rats
    Hazim AI, Ramanathan S, Parthasarathy S, Muzaimi M, Mansor SM
    J Physiol Sci, 2014 May;64(3):161-9.
    PMID: 24464759 DOI: 10.1007/s12576-014-0304-0
    The effects of mitragynine on anxiety-related behaviours in the open-field and elevated plus-maze tests were evaluated. Male Sprague-Dawley rats were orally treated with mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) 60 min before behavioural testing. Mitragynine doses used in this study were selected on the basis of approximately human equivalent doses with reference to our previous literature reports. Acute administration of mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) increased central zone and open arms exploration in the open-field and elevated plus-maze tests respectively. These anxiolytic-like effects of mitragynine were effectively antagonized by intraperitoneal administration of naloxone (2 mg/kg), flumazenil (10 mg/kg), sulpiride (0.5 mg/kg) or SCH 23390 (0.02 mg/kg) 15 min before mitragynine treatments. These findings reveal that the acute administration of mitragynine produces anxiolytic-like effects and this could be possibly attributed to the interactions among opioidergic, GABAergic and dopaminergic systems in brain regions involved in anxiety.
    Matched MeSH terms: Diazepam/pharmacology
  16. Fulltext Adequacy of pain relief in closed manipulative reduction of fracture and dislocation
    Wan Hazmy CH, Maizuliana SH, Mastura MT, Norazlina M
    Med J Malaysia, 2006 Feb;61 Suppl A:45-9.
    PMID: 17042229
    Adequate pain relief is a requisite for a successful closed manipulative reduction (CMR) of fractures and dislocations. This prospective study was undertaken to assess the mode and adequacy of pain relief given to patients undergoing such procedures at Seremban Hospital from the 1st April to the 31st May 2001. All patients with fractures and dislocations scheduled to undergo CMR were included in this study. The type of sedative agents and analgesia administered were recorded. Demographic data and the type of fracture or dislocation of the selected patients were documented. A visual analogue scale (VAS) for pain perception was given to both to the patients and the medical personnel who performed the procedure. All data were collected manually before entered into computerized database for analysis. Of 72 patients included in this study, 47% were Malay, 26% Indian, 21% Chinese and 6% others. There was male predominance and the patients' age ranged between 9 to 79 years (average 27.4 years). Upper limb injuries (79%) were mainly fractures of the radius and ulna (29%) and isolated fracture radius (21%). For the lower limb injuries (21%), combined tibia and fibula fractures constituted 10% of the total cases followed by isolated tibia fractures (10%) and hip dislocation (1%). The most common pain relieving agents given during the CMR were intravenous pethidine alone (43%) followed by combination of intravenous pethidine and valium (36%), intramuscular pethidine (17%) and intramuscular tramal (4%). The Visual Analogue Score (VAS) for pain perception revealed that 61% of the patients had moderate pain while 21% had severe pain during the course of the procedures. Suboptimal pain relief administered during CMR should prompt positive actions to ensure that the patient is not subjected to undue pain just for the sake of an acceptable fracture reduction.
    Matched MeSH terms: Diazepam/therapeutic use
  17. Intensive therapy in neonatal tetanus
    Ganendran A
    Anaesthesia, 1974 May;29(3):356-62.
    PMID: 4599155
    Matched MeSH terms: Diazepam/therapeutic use
  18. Fulltext Embelin Protects Against Acute Pentylenetetrazole-Induced Seizures and Positively Modulates Cognitive Function in Adult Zebrafish
    Kundap UP, Choo BKM, Kumari Y, Ahmed N, Othman IB, Shaikh MF
    Front Pharmacol, 2019;10:1249.
    PMID: 31708779 DOI: 10.3389/fphar.2019.01249
    Purpose of the research: Epilepsy is a continuous process of neurodegeneration categorized by an enduring tendency to generate uncontrolled electrical firing known as seizures causing involuntary movement all over the body. Cognitive impairment and behavioral disturbances are among the more alarming co-morbidities of epilepsy. Anti-epileptic drugs (AEDs) were found to be successful in controlling epilepsy but are reported to worsen cognitive status in patients. Embelin (EMB) is a benzoquinone derived from the plant Embelia ribes and is reported to have central nervous system (CNS) activity. This study aims to evaluate the effectiveness of EMB against pentylenetetrazole (PTZ) induced acute seizures and its associated cognitive dysfunction. This was done via docking studies as well as evaluating neurotransmitter and gene expression in the zebrafish brain. The principal results: Behavioral observations showed that EMB reduced epileptic seizures and the T-maze study revealed that EMB improved the cognitive function of the fish. The docking study of EMB showed a higher affinity toward gamma-aminobutyric acid (GABAA) receptor as compared to the standard diazepam, raising the possibility of EMB working via the alpha subunit of the GABA receptor. EMB was found to modulate several genes, neurotransmitters, and also neuronal growth, all of which play an important role in improving cognitive status after epileptic seizures. Healthy zebrafish treated with EMB alone were found to have no behavioral and biochemical interference or side effects. The immunohistochemistry data suggested that EMB also promotes neuronal protection and neuronal migration in zebrafish brains. Major Conclusions: It was perceived that EMB suppresses seizure-like behavior via GABAA receptor pathway and has a positive impact on cognitive functions. The observed effect was supported by docking study, T-maze behavior, neurotransmitter and gene expression levels, and immunohistology study. The apparatus such as the T-maze and seizure scoring behavior tank were found to be a straightforward technique to score seizure and test learning ability after acute epileptic seizures. These research findings suggest that EMB could be a promising molecule for epilepsy induced learning and memory dysfunction.
    Matched MeSH terms: Diazepam
  19. Fulltext The α6 subunit-containing GABAA receptor: A novel drug target for inhibition of trigeminal activation
    Fan PC, Lai TH, Hor CC, Lee MT, Huang P, Sieghart W, et al.
    Neuropharmacology, 2018 09 15;140:1-13.
    PMID: 30016665 DOI: 10.1016/j.neuropharm.2018.07.017
    Novel treatments against migraine are an urgent medical requirement. The α6 subunit-containing GABAA receptors (α6GABAARs) are expressed in trigeminal ganglia (TG), the hub of the trigeminal vascular system (TGVS) that is involved in the pathogenesis of migraine. Here we reveal an unprecedented role of α6GABAARs in ameliorating TGVS activation using several pharmacological approaches in an animal model mimicking pathological changes in migraine. TGVS activation was induced by intra-cisternal (i.c.) instillation of capsaicin in Wistar rats. Centrally, i.c. capsaicin activated the trigeminal cervical complex (TCC) measured by the increased number of c-Fos-immunoreactive (c-Fos-ir) TCC neurons. Peripherally, it elevated calcitonin gene-related peptide immunoreactivity (CGRP-ir) in TG and depleted CGRP-ir in the dura mater. Pharmacological approaches included a recently identified α6GABAAR-selective positive allosteric modulator (PAM), the pyrazoloquinolinone Compound 6, two α6GABAAR-active PAMs (Ro15-4513 and loreclezole), an α6GABAAR-inactive benzodiazepine (diazepam), an α6GABAAR-selective antagonist (furosemide), and a clinically effective antimigraine agent (topiramate). We examined effects of these compounds on both central and peripheral TGVS responses induced by i.c. capsaicin. Compound 6 (3-10 mg/kg, i.p.) significantly attenuated the TCC neuronal activation and TG CGRP-ir elevation, and dural CGRP depletion induced by capsaicin. All these effects of Compound 6 were mimicked by topiramate, Ro15-4513 and loreclezole, but not by diazepam. The brain-impermeable furosemide antagonized the peripheral, but not central, effects of Compound 6. These results suggest that the α6GABAAR in TG is a novel drug target for TGVS activation and that α6GABAAR-selective PAMs have the potential to be developed as a novel pharmacotherapy for migraine.
    Matched MeSH terms: Diazepam/pharmacology
  20. Reversal of memory deficits by Coriandrum sativum leaves in mice
    Mani V, Parle M, Ramasamy K, Abdul Majeed AB
    J Sci Food Agric, 2011 Jan 15;91(1):186-92.
    PMID: 20848667 DOI: 10.1002/jsfa.4171
    Coriandrum sativum L., commonly known as coriander and belonging to the family Apiaceae (Umbelliferae), is cultivated throughout the world for its nutritional value. The present study was undertaken to investigate the effects of fresh Coriandrum sativum leaves (CSL) on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. In this study, CSL (5, 10 and 15% w/w of diet) was fed orally with a specially prepared diet for 45 days consecutively to experimental animals. Elevated plus-maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam, scopolamine and ageing-induced amnesia served as the interoceptive behavioral models.
    Matched MeSH terms: Diazepam
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