MedWorm: Diazepam

  Adaptogenic effect of

Conclusion : The results indicate that M. alba possesses significant adaptogenic activity, indicating its possible clinical utility as an antistress agent. (Source: Indian Journal of Pharmacology)

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  Experimental design for optimization of microwave-assisted extraction of benzodiazepines in human plasma.

Authors: Fernández P, Vázquez C, Lorenzo RA, Carro AM, Alvarez I, Cabarcos P A simple and fast microwave-assisted-extraction (MAE) method has been evaluated as an alternative to solid-phase extraction (SPE) for the determination of six benzodiazepines widely prescribed in European countries (alprazolam, bromazepam, diazepam, lorazepam, lormetazepam and tetrazepam) in human plasma. For MAE optimization a Doehlert experimental design was used with extraction time, temperature and solvent volume as influential parameters. A desirability function was employed in addition to the simultaneous optimization of the MAE conditions. The analysis of variance showed that the solvent volume had a positive influence on the extraction of all the analytes tested, achieving a statistically sig...

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  [Medication dependency and physician's role.]

Authors: Holzbach R, Martens M, Kalke J, Raschke P The administration of benzodiazepines in suicidal, anxious, or agitated patients with depression is common international practice. Nevertheless, the prescription of BZDs is recommended to be limited to a period of a few weeks. There are several epidemiological studies about the situation in Germany, but many questions are still unanswered. The BfArM sought a new method to track prescription of medications with the risk to induce dependency. The present article describes the methodology and the early results of the pilot study. As a new approach, data from a processing center for pharmacies were used; patient-years, a risk scale with six steps, and diazepam-equivalence dose instead of defined daily dose were used for the analysis. About...

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  Measurement of benzodiazepines in urine by liquid chromatography-tandem mass spectrometry: confirmation of samples screened by immunoassay

Conclusion The validated LC/MS/MS method developed is effective for the confirmation of immunoassay screening results for benzodiazepines. The lower limit of detection and assay specificity offers a longer window of detection and more detailed clinical information compared with immunoassay screening. (Source: Annals of Clinical Biochemistry)

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  Effects of Ginkgo biloba extracts on diazepam metabolism: a pharmacokinetic study in healthy Chinese male subjects

Conclusion  The above data suggest that GBE, when taken in normally recommended doses over a 4-week time period, may not affect the pharmacokinetics of diazepam via CYP2C19 and the excretion of N-desmethyldiazepam in healthy volunteers. No drug-drug interaction was observed between GBE and diazepam. Content Type Journal ArticleCategory Pharmacokinetics and DispositionDOI 10.1007/s00228-010-0795-4Authors Xiao-Cong Zuo, Third Xiangya Hospital, Central South University Clinical Pharmacy and Pharmacology Research Institute Changsha 410013 ChinaBi-Kui Zhang, Third Xiangya Hospital, Central South University Clinical Pharmacy and Pharmacology Research Institute Changsha 410013 ChinaSu-Jie Jia, Third Xiangya Hospital, Central South University Clinical Pharmacy and Pharmacolo...

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  Acute psychotropic effects of oral cannabis extract with a defined content of Delta9-tetrahydrocannabinol (THC) in healthy volunteers. - Kaufmann RM, Kraft B, Frey R, Winkler D, Weiszenbichler S, Bäcker C, Kasper S, Kress HG.

INTRODUCTION: The medical use of cannabinoids is limited mainly by their undesirable effects. With respect to acute psychotropic effects, the aim of this study is the comparison of an oral cannabis extract and low-dose diazepam in a cross-over experiment i... (Source: SafetyLit: All (Unduplicated))

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  Psychopharmacological Neuroprotection in Neurodegenerative Disease: Assessing the Preclinical Data [SPECIAL ARTICLES]

This manuscript reviews the preclinical in vitro, ex vivo, and nonhuman in vivo effects of psychopharmacological agents in clinical use on cell physiology with a view toward identifying agents with neuroprotective properties in neurodegenerative disease. These agents are routinely used in the symptomatic treatment of neurodegenerative disease. Each agent is reviewed in terms of its effects on pathogenic proteins, proteasomal function, mitochondrial viability, mitochondrial function and metabolism, mitochondrial permeability transition pore development, cellular viability, and apoptosis. Effects on the metabolism of the neurodegenerative disease pathogenic proteins alpha-synuclein, beta-amyloid, and tau, including tau phosphorylation, are particularly addressed, with application to Alzheime...

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  Behind the Headlines: 'Valium link to heroin is unfounded'

Source: NHS Choices Area: News The Behind the Headlines feature on NHS Choices has featured a quality assessment of press reports that anxiety medicines such as Valium® (diazepam) are addictive in the same way as heroin (Daily Mail and The Daily Telegraph; 11th Feb 2010).    The articles were based on neuroscience research conducted in mice, which found that single injections of benzodiazepines increased firing of dopamine neurons in some parts of the brain.  This process appears to be behind the addictive potential of this class of medicines.      The authors of the assessment comment that the animal study was thorough and well-conducted, and that it increases our knowledge about the neurological basis for addictive behaviour.   ...

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  Michael Jackson toxicology report released

This week, the Los Angeles medical examiner’s office released the autopsy report on Michael Jackson. Included in the release are toxicology findings, and a discussion by an anesthesiologist concerning the effects and proper administration of propofol. The cause of death was listed as “acute propofol intoxication”, with the “benzodiazepine effect” contributing.  The toxicology tests determined the following: Propofol:                   Heart blood – 3.2 mcg/ml;       Hospital blood – 4.1 mcg/ml;         Femoral blood – 2.6 mcg/ml Lidocaine:                Heart blood  - 0.68 mcg/ml;   Hospital blood – 0.5 mcg/ml;         Femoral blood – 0.34 mcg/ml Lorazepam:              Heart blood – 0....

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  Non-addictive anxiety drugs hope

Scientists have expressed hope for a new generation of non-addictive calming drugs in the form of valium-like substances. (Source: Pharmacy Europe)

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  Adaptogenic effect of <i>Morus alba</i> on chronic footshock-induced stress in rats

Conclusion&lt;/b&gt; : The results indicate that M. alba possesses significant adaptogenic activity, indicating its possible clinical utility as an antistress agent. (Source: Indian Journal of Pharmacology)

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  My Diagnosis is Killing Me!

   I used to find it somewhat odd, looking around my ex-psychiatrist's office, to see how many promotional items he had scattered around. There were Pfizer note pads, Prozac pens, Merck coffee cups, an Adderal wastebasket, and Eli Lilly toilet paper.<!--break-->I'm exaggerating, but not by much; the shelf in his foyer was stacked high with boxes of this stuff, as well as countless free samples of the actual medications. Often, before my session would start, I shared the waiting room with a well-groomed, young, salesman-type who was apparently the Fuller Brush Man of Psychiatry, anxious to unload his free wares, hoping, I supposed, that when my doctor picked up a monogrammed GlaxoSmithKline ballpoint pen to write me a prescription, he might be more inclined to go with P...

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  Evaluation of three automated enzyme immunoassays for detection of anti-cyclic citrullinated peptide antibodies in qualitative and quantitative aspects

Conclusions. The overall diagnostic performance of the automated anti-CCP assays was comparable, and it provides reliable information on antibody levels, making them useful in monitoring disease activity. (Source: Rheumatology)

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  Valium link to heroin is unfounded

Conclusion This animal study has been thorough and well conducted. The findings will be of interest to the research community and to those interested in designing drugs that have lower addictive potential. The result of this research may also lead to an improved understanding of the mechanisms behind individuals’ varying susceptibility to addiction, an area that has further research potential.  However, despite the researchers finding that BDZ works using a similar pathway to certain illegal drugs, media comparisons to heroin addiction seems to be quite alarmist. This research has concentrated on identifying neurological processes in mice and not the complex factors involved in substance abuse or drug addiction. Based on this research it seems inappropriate to compare the use of oral d...

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  Anxiety drugs like Valium are addictive in the same way as heroin, warn scientists

A popular form of anxiety drugs use the same potentially addictive 'reward pathways' in the brain as heroin and cannabis, scientists have warned. (Source: the Mail online | Health)

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  Scientists find clue to anxiety drug addiction

LONDON (Reuters) - Valium-like drugs use the same potentially addictive "reward pathways" in the brain as heroin and cannabis, scientists said on Wednesday, findings which may help in the search for non-addictive alternative anxiety drugs. (Source: Reuters: Health)

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  Scientists Find Clue to Anxiety Drug Addiction

Valium-like drugs use the same potentially addictive "reward pathways" in the brain as heroin and cannabis, scientists said on Wednesday, findings which may help in the search for non-addictive alternative anxiety drugs. Source: Reuters Health Related MedlinePlus Topics: Anxiety, Prescription Drug Abuse (Source: MedlinePlus Health News)

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  Evaluation of the anticonvulsant effect of Centella asiatica (gotu kola) in pentylenetetrazol-induced seizures with respect to cholinergic neurotransmission.

Authors: Visweswari G, Prasad KS, Chetan PS, Lokanatha V, Rajendra W The study described here was carried out to investigate the anticonvulsant effect of different extracts of Centella asiatica with respect to cholinergic activity on pentylenetetrazol (PTZ)-induced seizures. Rats were randomly divided into eight groups of six rats each: nonepileptic rats treated with saline; PTZ (60mg/kg, IP)-induced seizure rats treated with saline; PTZ-induced seizure rats pretreated with n-hexane, chloroform, ethyl acetate, n-butanol, and water extracts of C. asiatica; and PTZ-induced seizure rats pretreated with diazepam (2mg/kgbodywt). The seized rats pretreated with different extracts were administered a dose of 200mg/kgbodywt orally for 1week before induction of epilepsy. Increased acetylcholine...

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  Psychopharmacological effects of oxycodone in healthy volunteers: Roles of alcohol-drinking status and sex

Conclusions: Studies have established that moderate drinkers report a greater degree of abuse liability-related effects than do light drinkers with several different drugs, including diazepam, amphetamine, and nitrous oxide, but we were unable to establish this with the prescription opioid, oxycodone. However, we did observe sex differences in several subjective effects of oxycodone, a finding that is consistent with the extant literature showing sex differences in pharmacodynamic effects of opioids. (Source: Drug and Alcohol Dependence)

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  Child presenting to the ED with prolonged autonomic symptoms followed by generalized seizure activity

A 5-year-old girl presented to the emergency department (ED) with a parental complaint of vomiting and seizure-like activity. The patient had been in her normal state of health before the onset of this activity and had had no recent illnesses. Shortly after the child had gone to bed, she awoke complaining of feeling sick to her stomach. Over several minutes the child became less responsive to questioning, followed by rightward eye and head deviation and vomiting. Following this, the child's eyes remained fixed in a rightward gaze and she was no longer responsive to questioning despite appearing awake. On the way to the hospital the child became flaccid, which was shortly followed by further vomiting and right upper extremity jerking and finally full upper extremity convulsive activity. In ...

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  New AAN/CNS Guideline on Treatment of Spasticity in Cerebral Palsy

The new Practice Parameter endorses use of botulinum toxin A for localized and segmented spasticity and diazepam and, to a lesser degree, tizanidine for short-term treatment of generalized spasticity but finds insufficient data for other agents. Medscape Medical News (Source: Medscape Today Headlines)

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  Tolerance, Sensitization and Dependence to Diazepam in Balb/c Mice Exposed to a Novel Open Space Anxiety Test.

Authors: Ennaceur A, Michalikova S, van Rensburg R, Chazot PL BALB/c mice were exposed to an elevated platform that is extended on two opposite sides with lowered steep slopes. They were tested for 12min per session in 6 successive days. They received i.p. administration of either saline or one dose of diazepam (DZP 0.5, 1, 3mg/kg) in sessions 1 to 3, and saline in sessions 4 and 5. All groups of mice received a single dose of DZP (1mg/kg) in session 6. DZP produced inverted U-shaped dose-responses on the number of entries into different areas of the apparatus, with a peak in mean response at 1mg/kg whereas its effect on the duration of entries was mostly comparable between the 3 doses. It increased the number of crossings on the surface of the platform and facilitated entries onto the...

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  Severe Lactic Acidosis After an Iatrogenic Propylene Glycol Overdose

We describe a 50-year-old man who experienced severe lactic acidosis after receiving an accidental overdose of lorazepam, which contains propylene glycol. The patient was acutely intoxicated, with a serum ethanol concentration of 406 mg/dl. He had choked on a large piece of meat and subsequently experienced pulseless electrical activity with ventricular fibrillation cardiac arrest. He was brought to the emergency department; within 2 hours, he was admitted to the intensive care unit for initiation of the hypothermia protocol. The patient began to experience generalized tonic-clonic seizures 12 hours later, which resolved after several boluses of lorazepam. A lorazepam infusion was started; however, it was inadvertently administered at a rate of 2 mg/minute instead of the standard rate of 2...

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  Practice Parameter: Pharmacologic treatment of spasticity in children and adolescents with cerebral palsy (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society

Objective: To evaluate published evidence of efficacy and safety of pharmacologic treatments for childhood spasticity due to cerebral palsy. Methods: A multidisciplinary panel systematically reviewed relevant literature from 1966 to July 2008. Results: For localized/segmental spasticity, botulinum toxin type A is established as an effective treatment to reduce spasticity in the upper and lower extremities. There is conflicting evidence regarding functional improvement. Botulinum toxin type A was found to be generally safe in children with cerebral palsy; however, the Food and Drug Administration is presently investigating isolated cases of generalized weakness resulting in poor outcomes. No studies that met criteria are available on the use of phenol, alcohol, or botulinum toxin type B inj...

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  Methadone toxicity in infants: a report of two fatalities

We report two cases of fatality attributed to methadone toxicity in infants aged 3½ and 15 months of age, respectively. One of the two cases was also associated with diazepam ingestion. We discuss the difficulties with the interpretation of paediatric forensic toxicology and review the current literature related to methadone and diazepam toxicity in infants and older children. Content Type Journal ArticleCategory Case ReportDOI 10.1007/s12024-009-9138-0Authors V. Mistry, University of Warwick Warwick Medical School Coventry CV4 7AL UKA. J. Jeffery, University of Leicester, Leicester Royal Infirmary East Midlands Forensic Pathology Unit Robert Kilpatrick Building Leicester LE2 7LX UKW. Madira, University Hospitals of Leicester, Leicester Royal Infirmary Forensic Toxicology Ser...

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  Premedication with clonidine is superior to benzodiazepines. A meta analysis of published studies

Premedication is considered important in pediatric anesthesia. Benzodiazepines are the most commonly used premedication agents. Clonidine, an [alpha]2 adrenoceptor agonist, is gaining popularity among anesthesiologists. The goal of the present study was to perform a meta-analysis of studies comparing premedication with clonidine to Benzodiazepines. A comprehensive literature search was conducted to identify clinical trials focusing on the comparison of clonidine and Benzodiazepines for premedication in children. Six reviewers independently assessed each study to meet the inclusion criteria and extracted data. Original data from each trial were combined to calculate the pooled odds ratio (OR) or the mean differences (MD), 95% confidence intervals [95% CI] and statistical heterogeneity were ...

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  Brain uptake of diazepam and phenytoin in a genetic animal model of absence epilepsy.

In this study, the brain uptake of diazepam (DIAZ) and phenytoin (PHT) was assessed in a genetic mouse model of absence seizures harbouring a human GABA(A) receptor gamma2 subunit gene GABRG2 mutation (R43Q), and results were compared to those obtained during acute seizures induced by subcutaneous administration (90 mg/kg) of pentylenetetrazole (PTZ). DIAZ and PHT were administered intraperitoneally at doses of 2 and 30 mg/kg, respectively, and brain and plasma concentrations determined 60 min post-dose using liquid chromatography-mass spectrometry. 3. While the brain uptake of PHT was significantly reduced following PTZ administration, no alteration to PHT disposition was observed in the genetic absence epilepsy model. Similarly, the brain uptake of DIAZ was significantly enhanced followi...

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  Benzodiazepines medazepam and midazolam are activators of pregnane X receptor and weak inducers of CYP3A4: Investigation in primary cultures of human hepatocytes and hepatocarcinoma cell lines.

In conclusion, Alprazolam, Bromazepam, Chlordiazepoxide, Clonazepam, Diazepam, Lorazepam, Nitrazepam, Oxazepam, Tetrazepam and Triazolam can be considered as safe drugs in term of their inability to induce PXR- and AhR-dependent cytochrome P450 enzymes CYP1A2 and CYP3A4. Medazepam and Midazolam slightly activated pregnane X receptor and displayed weak potency to induce CYP3A4 mRNA in human hepatocytes. PMID: 20080160 [PubMed - as supplied by publisher] (Source: Toxicology Letters)

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  Anxiolytic, hypnotic and sedative medication use in Australia

We examined the trends in the prescribing of subsidised anxiolytic, hypnotic and sedative (AHS) medication use in the Australian population from 2002 to 2007.We analysed the Medicare Australia and Drug Utilisation Sub-Committee databases for AHS script data from 2002 to 2007 by source, class of prescriber, gender and 5-year age groups. Scripts were converted to defined daily dose per 1000 population per day (DDD/1000 population/day) using Australian Bureau of Statistics population data.Overall use of AHS increased from 23.76 to 24.11 DDD/1000 population/day between 2002 and 2007. Anxiolytic medication utilisation increased as hypnotic medication utilisation decreased. Diazepam was the most widely used anxiolytic followed by alprazolam and oxazepam. Temazepam was the most widely used hypnot...

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  Retrospective chart review of vaginal diazepam suppository use in high-tone pelvic floor dysfunction

Abstract  To study intravaginal diazepam suppositories as adjunctive treatment for high-tone pelvic floor dysfunction (HTPFD) and sexual pain. A retrospective chart review was conducted on 26 patients who received diazepam suppositories as adjuvant therapy to pelvic physical therapy and intramuscular trigger point injections for bladder pain, sexual pain, and levator hypertonus. Pelvic floor muscular tone and pain were assessed by palpation and perineometry; sexual pain was objectively rated by Female Sexual Function Index (FSFI) and the Visual Analog Scale for Pain (VAS-P). Twenty-five out of 26 patients reported subjective improvement with suppository use; six out of seven sexually active patients resumed intercourse. Sexual pain as assessed on FSFI and serial VAS-P impro...

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  Buccal administration of dexmedetomidine as a preanesthetic in children

Conclusion  These results suggest that the buccal administration of dexmedetomidine (3–4 μg/kg) 1 h before the operation can be safely and effectively applied as a preanesthetic in children. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00540-009-0863-zAuthors Yoshio Sakurai, Saitama Medical Center, Saitama Medical University Department of Anesthesiology 1981, Tsujido-cho, Kamoda Kawagoe Saitama 350-8550 JapanToru Obata, Microbial Chemistry Research Foundation, Specified Research Promoting Group Tokyo JapanAkio Odaka, Saitama Medical University Department of Pediatric Surgery, Saitama Medical Center Kawagoe Saitama JapanKatsuo Terui, Saitama Medical Center, Saitama Medical University Department of Anesthesiology 1981, Tsujido-cho, Kamoda...

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  How are we doing with the treatment of essential tremor (ET)?

Conclusions: Nearly one of every three patients with ET who had been prescribed medication for tremor had discontinued pharmacotherapy. Even more revealing was that a similar proportion of cases with severe tremor had stopped medication. These data make tangibly evident that there is a sizable population of patients with ET who are untreated and disabled, and underscore the inadequacy of current pharmacotherapeutic options for this common neurological disease. (Source: European Journal of Neurology)

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  A systematic review and meta-analysis of randomized, controlled trials of moderate sedation for routine endoscopic procedures

Source: DARE Area: Evidence > Disease Focused Reviews CRD Summary: This review concluded that moderate sedation provided high levels of satisfaction and low risk of serious adverse events in patients undergoing esphagogastroduodenoscopy or colonoscopy. Midazolam-based regiments had longer sedation and recovery times than propofol. The search was limited, studies were generally poor quality and the appropriateness of the synthesis was unclear. Thus, the reliability of the conclusions was unclear. [Included studies assessed the following interventions: diazepam, midazolam, propofol or narcotic; and combinations of these agents with each other or with diphenhydramine or droperidol. ] CRD Commentary: The review question and the inclusion criteria were clear and specific. The authors sear...

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  Effects of capture stress on free-ranging, reproductively active male Weddell seals

Abstract  Physiological stress responses to capture may be an indicator of welfare challenges induced by animal handling. Simultaneously, blood chemistry changes induced by stress responses may confound experimental design by interacting with the biological parameters being measured. Cortisol elevation is a common indicator of stress responses in mammals and reproductive condition can profoundly influence endocrine response. We measured changes in blood cortisol and testosterone induced by handling reproductively active male Weddell seals (Leptonychotes weddellii) early and late in the breeding season. Weddell seals have the highest resting cortisol levels of all mammals yet showed a clear, prolonged elevation in cortisol in response to capture. Responses were similar when f...

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  Evaluation of Hemodynamic, Metabolic, and Electrolytic Changes After Graft Reperfusion in a Porcine Model of Intestinal Transplantation

Conclusion: The anesthetic protocol for donors and recipients was safe to perform the procedure, allowing control of hemodynamic and metabolic changes after reperfusion without differences regarding immunosuppression. (Source: Transplantation Proceedings)

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  Solubility of Lamotrigine and Diazepam in Propylene Glycol + Water + Carboxymethyl Cellulose at a Temperature of 298.2 K

Journal of Chemical & Engineering Data, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Chemical and Engineering Data)

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  EFNS guideline on the management of status epilepticus in adults

The objective of the current article was to review the literature and discuss the degree of evidence for various treatment strategies for status epilepticus (SE) in adults. We searched MEDLINE and EMBASE for relevant literature from 1966 to January 2005 and in the current updated version all pertinent publications from January 2005 to January 2009. Furthermore, the Cochrane Central Register of Controlled Trials (CENTRAL) was sought. Recommendations are based on this literature and on our judgement of the relevance of the references to the subject. Recommendations were reached by informative consensus approach. Where there was a lack of evidence but consensus was clear, we have stated our opinion as good practice points. The preferred treatment pathway for generalised convulsive status epil...

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  Neurosteroid biosynthetic pathways changes in prefrontal cortex in Alzheimer's disease.

Authors: Luchetti S, Bossers K, Van de Bilt S, Agrapart V, Morales RR, Frajese GV, Swaab DF Expression of the genes for enzymes involved in neurosteroid biosynthesis was studied in human prefrontal cortex (PFC) in the course of Alzheimer's disease (AD) (n=49). Quantitative RT-PCR (qPCR) revealed that mRNA levels of diazepam binding inhibitor (DBI), which is involved in the first step of steroidogenesis and in GABAergic transmission, were increased, as were mRNA levels for several neurosteroid biosynthetic enzymes. Aromatase, 17beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) and aldo-keto reductase 1C2 (AKR1C2), were all increased in the late stages of AD. Several GABA-A subunits were significantly reduced in AD. Increased expression of aromatase in the PFC was confirmed by immunohis...

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  Developmental Neurotoxicity of Pyrethroid Insecticides in Zebrafish Embryos

In this study, we sought to investigate the developmental toxicity of six common pyrethroids, three type I compounds (permethrin, resmethrin, and bifenthrin) and three type II compounds (deltamethrin, cypermethrin, and -cyhalothrin), and to determine whether zebrafish embryos may be an appropriate model for studying the developmental neurotoxicity of pyrethroids. Exposure of zebrafish embryos to pyrethroids caused a dose-dependent increase in mortality and pericardial edema, with type II compounds being the most potent. At doses approaching the LC50, permethrin and deltamethrin caused craniofacial abnormalities. These findings are consistent with mammalian studies demonstrating that pyrethroids are mildly teratogenic at very high doses. However, at lower doses, body axis curvature and spas...

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  Cochrane review: Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children

Tonic-clonic (grand mal) convulsions and convulsive status epilepticus (currently defined as a grand mal convulsion lasting at least 30 minutes) are medical emergencies and demand urgent and appropriate anticonvulsant treatment. Benzodiazepines (midazolam, diazepam, lorazepam), phenobarbitone, phenytoin and paraldehyde may all be regarded as drugs of first choice. This is an update of a Cochrane review first published in 2002 and previously updated in 2005.To review the evidence comparing the efficacy and safety of midazolam, diazepam, lorazepam, phenobarbitone, phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status epilepticus in children treated in hospital.We searched the Cochrane Epilepsy Group's Specialized Register (1st July 2007), the Cochrane Cen...

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  Acute Psychotropic Effects of Oral Cannabis Extract with a Defined Content of Δ9-Tetrahydrocannabinol (THC) in Healthy Volunteers

PharmacopsychiatryDOI: 10.1055/s-0029-1237397Abstract The medical use of cannabinoids is limited mainly by their undesirable effects. With respect to acute psychotropic effects, the aim of this study is the comparison of an oral cannabis extract and low-dose diazepam in a cross-over experiment in drug-naïve healthy women.[...]© Georg Thieme Verlag KG Stuttgart · New YorkGet connected:Table of contents  |  Abstract  |  Full text (Source: Pharmacopsychiatry)

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  Modeling withdrawal syndrome in zebrafish.

Authors: Cachat J, Canavello P, Elegante M, Bartels B, Hart P, Bergner C, Egan R, Duncan A, Tien D, Chung A, Wong K, Goodspeed J, Grimes C, Elkhayat S, Suciu C, Rosenberg M, Chung KM, Kadri F, Roy S, Gaikwad S, Stewart A, Zapolsky I, Gilder T, Mohnot S, Beeson E, Amri H, Zukowska Z, Soignier RD, Kalueff AV The zebrafish (Danio rerio) is rapidly becoming a popular model species in behavioral neuroscience research. Zebrafish behavior is robustly affected by environmental and pharmacological manipulations, and can be examined using exploration-based paradigms, paralleled by analysis of endocrine (cortisol) stress responses. Discontinuation of various psychotropic drugs evokes withdrawal in both humans and rodents, characterized by increased anxiety. Sensitivity of zebrafish to drugs of ab...

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  The modified Geller-Seifter test in rats was insensitive to GABA(B) receptor positive modulation or blockade, or 5HT(1A) receptor activation.

Authors: Paterson NE, Hanania T Rationale: Both the GABA(B) receptor positive modulator GS39783 and the GABA(B) receptor antagonist CGP46381 exhibit anxiolytic-like properties in animal models. In the present studies, the effects of GS39783 and CGP46381 in the modified Geller-Seifter task were assessed. First, the predictive validity of the task was confirmed by assessing the effects of multiple anxiolytic and non-anxiolytic compounds on punished and unpunished responding. Methods: Rats were trained in the modified Geller-Seifter task. After successful acquisition of the task, chlordiazepoxide, diazepam, MPEP, haloperidol, GS39783, 8-OH-DPAT, alprazolam and CGP46381 were tested consecutively. For each test compound, doses were administered in a randomized, counter-balanced, within-subj...

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  Dipeptide Tyr-Leu (YL) exhibits anxiolytic-like activity after oral administration via activating serotonin 5-HT1A, dopamine D1 and GABAA receptors in mice

Abstract: We found that Tyr-Leu (YL) dose-dependently exhibits potent anxiolytic-like activity (0.1–1mg/kg, i.p.) comparable to diazepam in the elevated plus-maze test in mice. YL was orally active (0.3–3mg/kg). A retro-sequence peptide or a mixture of Tyr and Leu was inactive. The anxiolytic-like activity of YL was inhibited by antagonists for serotonin 5-HT1A, dopamine D1 and GABAA receptors; however, YL had no affinity for them. We also determined the order of their activation is 5-HT1A, D1 and GABAA receptors using selective agonists and antagonists. Taken together, YL may exhibit anxiolytic-like activity via activation of 5-HT1A, D1 and GABAA receptors. (Source: FEBS Letters)

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  Use of Propofol–Xylazine and the Anderson Sling Suspension System for Recovery of Horses from Desflurane Anesthesia

To characterize the behavior of horses recovering in the Anderson Sling Suspension System after 4 hours of desflurane anesthesia and postdesflurane intravenous (IV) administration of propofol and xylazine. Experimental study. Healthy horses (n=6), mean±SEM age 12.3±1.8 years; mean weight 556±27 kg. Each horse was anesthetized with xylazine, diazepam, and ketamine IV and anesthesia was maintained with desflurane in O2. At the end of 4 hours of desflurane, each horse was positioned in the sling suspension system and administered propofol[ndash]xylazine IV. Recovery events were quantitatively and qualitatively assessed. Venous blood was obtained before and after anesthesia for biochemical and propofol analyses. Anesthetic induction and maintenance were without incident. Apnea commonly acco...

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  Proconvulsant potential of cyproheptadine in experimental animal models

In epileptic patients cyproheptadine is frequently prescribed as an appetite stimulant for the treatment of anorexia associated with anti-epileptic drugs and for the management of 'serotonin syndrome' in depressed epileptic patients. However, the study of serotonergic and histaminergic pathway shows that the decreased neurotransmission of serotonin and histamine in the brain reduces seizures threshold. Since, cyproheptadine interferes with these pathways via antagonizing subtypes of 5-HT1/2 receptors and H1 receptor, therefore the present study was undertaken to investigate its effect on seizures threshold, so as to substantiate its use in epileptics. In the present study convulsions were induced in mice by, maximum electroshock (MES), picrotoxin, and pentylenetetrazol (PTZ). Cyproheptadin...

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  Synthesis, pharmacological studies and molecular modeling of some tetracyclic 1,3-diazepinium chlorides.

Authors: Grant JA, Bonnick T, Gossell-Williams M, Clayton T, Cook JM, Jackson YA Seven new 1,3-diazepinium chlorides exhibiting some structural similarities to the 1,4-benzodiazepines were synthesized. In a Hippocratic screen using mice, three of these salts, 3-methoxy-6-oxo-7,13-dihydro-6H-benzofuro[2,3-e]pyrido[1,2-a][1,3]diazepin-12-ium chloride (8a), 3-methoxy-9-methyl-6-oxo-7,13-dihydro-6H-benzofuro[2,3-e]pyrido[1,2-a][1,3]diazepin-12-ium chloride (8c) and 3-methoxy-11-methyl-6-oxo-7,13-dihydro-6H-benzofuro[2,3-e]pyrido[1,2-a][1,3]diazepin-12-ium chloride (8e) were examined for their effect on the central nervous system, and their activities compared to that of diazepam. On their own, salts 8a, 8c and 8e solicited no sedative effects on the behaviour of the animals. However, they ...

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  Tetanus, in childhood

Summary  110 cases of tetanus, excluding neonatal tetanus, were studied with reference to aetiology, clinical manifestations, prognosis and evaluation of an effective combination of drugs. Most of the children belonged to rural (92.8%) areas, with unhygienic environmental conditions and a poor socioeconomic status. Otogenic tetanus was the commonest followed by idiopathic tetanus (22.6%) and traumatic tetanus (14%). Lockjaw, rigidity, spasm and fever were the most common presenting symptoms. Phenobarbitone and diazepam was the best combination of drugs for the treatment of tetanus. The overall mortality rate was 17.1%. This could be due to the drugs used in the present study. The incubation period, period of onset and fever had an inverse relationship with mortality. Tetanu...

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  Postoperative opioid usage in children receiving Remifentanil vs. sufentanil

Conclusion: This study found no difference in opioid consumption between children who received remifentanil versus sufentanil infusions. Findings suggest that these short-acting potent opioids similarly affect morphine requirements following spine fusion. (Source: Acute Pain)

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  The toxicological challenges in the European research project DRUID

Abstract: Within the epidemiological studies of the integrated European research project DRUID (Driving Under the Influence of Drugs, alcohol and medicines), 13 laboratories from across Europe will analyse whole blood, oral fluid (OF) or urine from the general driving population and injured drivers. To ensure the comparability of toxicological results from the different studies, the collection of samples, analytical methods, target analytes and analytical cut-offs have been standardized for all laboratories involved.Target analytes were selected based on suspected impairing effects and prevalence. Twenty-three drugs are included in the ‘core list’ for which analysis is mandatory: ethanol, amphetamine, MDMA, MDA, MDEA, methamphetamine, cocaine, benzoylecgonine, THC, THC-COOH, 6-acetylmo...

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  Neuronal network pharmacodynamics of gABAergic modulation in the human cortex determined using pharmaco-magnetoencephalography

Neuronal network oscillations are a unifying phenomenon in neuroscience research, with comparable measurements across scales and species. Cortical oscillations are of central importance in the characterization of neuronal network function in health and disease and are influential in effective drug development. Whilst animal in vitro and in vivo electrophysiology is able to characterize pharmacologically induced modulations in neuronal activity, present human counterparts have spatial and temporal limitations. Consequently, the potential applications for a human equivalent are extensive. Here, we demonstrate a novel implementation of contemporary neuroimaging methods called pharmaco-magnetoencephalography. This approach determines the spatial profile of neuronal network oscillatory power ch...

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  Comparison of treatment modalities in burning mouth syndrome

Conclusions: A greater percentage of patients taking clonazepam reported either partial or complete relief of symptoms compared to diazepam. However, the differences were not statistically significant. There was no correlation found between underlying psychopathology and treatment success with benzodiazepines. (Source: Australian Dental Journal)

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  A Comparative Study of UV-Spectrophotometry and First-Order Derivative UV-Spectrophotometry Methods for the Estimation of Diazepam in Presence of Tween-20 and Propylene Glycol.

Authors: Dastidar DG, Sa B Nonionic surfactants like polysorbates (Tweens) and co-surfactant like propylene glycol are used in pharmaceutical dosage forms, like microemulsion of diazepam. These additives interfere significantly with the estimation of diazepam by UV spectrophotomery method. The aim of this work was to develop a first-order derivative UV-spectrophotometry method that can estimate diazepam in presence of Tween-20 and propylene glycol. The experimental results clearly suggested that, in comparison with the UV-spectrophotometry method, the first-order derivative UV-spectrophotometry is a simple method to estimate diazepam with sufficient accuracy, specificity, and precision even in the presence of 282-times Tween-20 and 2,072-times propylene glycol. PMID: 19936936 [PubM...

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  Suppressive Effect of Diazepam on IFN-gamma Production by Human T Cells.

Authors: Wei M, Li L, Meng R, Fan Y, Liu Y, Tao L, Liu X, Wu C Many studies showed that benzodiazepines could modulate immune responses through interaction with peripheral benzodiazepine receptors (PBRs) in immune cells but most of the studies were focused on monocytes and macrophages. In the present study, we revealed that diazepama mixed-type benzodiazepine, inhibited IFN-gamma production by human peripheral blood mononuclear cells (PBMCs) induced by anti-CD3 in dose-dependent manner. Flow cytometry analysis demonstrated that diazepam could inhibit the frequency of IFN-gamma-producing CD4(+) and CD8(+) T cells. The inhibitory effect of diazepam on IFN-gamma production is similar to that of R(0)5-4864, a selective PBRs ligand. However, D8555, a selective ligand for PBRs in microglia i...

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  Diazepam/lormetazepam abuse: Dependence, sedative withdrawal and depressive disorder unspecified: case report

(Source: Reactions)

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  Effects of organic solvents on the time-dependent inhibition of CYP3A4 by diazepam.

In conclusion, the time-dependent inhibition of CYP3A4 by diazepam was attenuated by DMSO, while acetonitrile and methanol had no effect. The metabolite formation profile under the conditions tested suggested that DMSO competitively inhibit the formation of the reactive metabolites of diazepam by CYP3A4. The effect of organic solvents should be taken into consideration when evaluating the in vitro time-dependent inhibition of new chemical entities. PMID: 19905875 [PubMed - as supplied by publisher] (Source: Xenobiotica)

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  Anxiolytic-like effect of Carvacrol (5-isopropyl-2-methylphenol) in mice: involvement with GABAergic transmission

Carvacrol (5-isopropyl-2-methylphenol) is a monoterpenic phenol present in the essencial oil of many plants. It is the major component of the essential oil fraction of oregano and thyme. This work presents the behavioral effects of carvacrol in animal models of elevated plus maze (EPM), open field, Rotarod and barbiturate-induced sleeping time tests in mice. Carvacrol (CVC) was administered orally, in male mice, at single doses of 12.5; 25 and 50 mg/kg while diazepam 1 or 2 mg/kg was used as standard drug and flumazenil (2.5 mg/kg) was used to elucidate the possible anxiolytic mechanism of CVC on the plus maze test. The results showed that CVC, at three doses, had no effect on the spontaneous motor activity in the Rotarod test nor in the number of squares crossed in the open-field test. Ho...

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  Development of a method to measure methadone enantiomers and its metabolites without enantiomer standard compounds for the plasma of methadone maintenance patients.

Authors: Wang SC, Ho IK, Wu SL, Liu SC, Kuo HW, Lin KM, Liu YL A liquid chromatography-photodiode array (LC-PDA) method using a chiral analytical column was developed to determine the plasma levels of enantiomers of methadone and its chiral metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), without the standard compounds of R-form or S-form enantiomers. This method was established by the characteristics of recombinant cytochrome P-450 (CYP) isozymes, where CYP2C19 prefers to metabolize R-methadone and CYP2B6 prefers to metabolize S-methadone. We incubated the racemic methadone standard with either enzyme for 24 h. We identified the retention times of R- and S-methadone to be around 10.72 and 14.46 min, respectively. Furthermore, we determined the retention times of R...

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  Will nano-fibers permit to turn liver cell transplantation into a curative tool against liver failure?

The article by Navarro-Alvarez and colleagues, entitled “Intramuscular transplantation of engineered hepatic tissue constructs corrects acute and chronic liver failure in mice” and published in the current issue of Journal of Hepatology, offers an interesting approach towards the future of cell transplantation and tissue engineering. These authors investigated whether a non-immnunogenic self-assembling peptide nano-fiber (SAPNF), used in combination with conditioned media (CM) derived from an immortalized human hepatocyte cell line, was capable of providing a three dimensional scaffold that allowed hepatocytes to maintain their function. The experiments were performed in culture and in vivo after transplantation of engineered tissue within the skeletal muscle of mice, and the results c...

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  Identification of a CYP3A form (CYP3A126) in fathead minnow (Pimephales promelas) and characterisation of putative CYP3A enzyme activity.

In this study we report on the cloning of a CYP3A family gene from fathead minnows (Pimephales promelas), which has been designated as CYP3A126 by the P450 nomenclature committee (GenBank no. EU332792). The cDNA was isolated, identified and characterised by extended inverse polymerase chain reaction (PCR), an alternative to the commonly used method of rapid amplification of cDNA ends. In a fathead minnow cell line we identified a full-length cDNA sequence (1,863 base pairs (bp)) consisting of a 1,536 bp open reading frame encoding a 512 amino acid protein. Genomic analysis of the identified CYP3A isoenzyme revealed a DNA sequence consisting of 13 exons and 12 introns. CYP3A126 is also expressed in fathead minnow liver as demonstrated by reverse transcription PCR. Exposure of fathead minnow...

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  Man Sentenced For Sale And Supply Of Controlled And Counterfeit Drugs

A 41-year-old man, Mr Harish Gami, received an eight month prison sentence suspended for two years at Aylesbury Crown Court today for the illicit sale and supply of controlled drugs as well as counterfeit and unlicensed medicines. The Medicines and Healthcare products Regulatory Agency (MHRA) discovered more than 86,000 Valium tablets and a further 11,500 medicinal products in an undercover investigation into Gami's illegal online dealing. (Source: Pharma Industry News From Medical News Today)

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  Man Sentenced For Sale And Supply Of Controlled And Counterfeit Drugs

The Medicines and Healthcare products Regulatory Agency (MHRA) discovered more than 86,000 Valium tablets and a further 11,500 medicinal products in an undercover investigation into Gami's illegal online dealing. (Source: Pharmaceutical Online News)

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  Prof Nutt's dangerous drug list

How harmful are the drugs on the list drawn up by the ousted government drugs adviser and his colleagues?Professor David Nutt was last week forced to resign from his role as chairman of the Advisory Council on the Misuse of Drugs. Research by Nutt and his colleagues, published in the medical journal the Lancet in 2007, rates the following as the most dangerous drugs (They are listed in descending order from the most harmful and all figures are for England and Wales in 2008 unless stated otherwise):1. HeroinClass A drug. Originally used as a painkiller and derived from the opium poppy. There were 897 deaths recorded from heroin and morphine use in 2008 in England and Wales, according to the Office of National Statistics (ONS). There were around 13,000 seizures amounting to 1.6m tonnes of he...

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  Use of fluoxetine, diazepam, and behavior modification as therapy for treatment of anxiety-related disorders in dogs

The objective of this study was to evaluate the use of fluoxetine, diazepam, and behavior modification for the treatment of a variety of anxiety disorders in dogs of different breeds, ages, and sexes that presented to a university veterinary behavior clinic. Forty dogs were enrolled in the study, and 34 completed it. The dogs were grouped into 2 major diagnostic categories, aggressive and anxious, according to the presenting signs. Moreover, the dogs further subdivided into 4 groups: neutered, intact, juveniles, and adults. Diazepam was administered orally, at a dosage of 0.3mg/kg once a day for 4 weeks; fluoxetine was administered orally at a dosage of 1mg/kg once a day for 10 weeks. The drugs were started simultaneously. The owners were given a behavior modification plan for their dogs t...

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  Office Endometrial Ablation with Local Anesthesia Using the HydroThermAblator System: Comparison of Outcomes in Patients with Submucous Myomas with Those with Normal Cavities in 246 Cases Performed Over 5½ Years

Conclusions: Hydrothermablation performed in the medical office using local anesthesia seems to be a safe, effective, and cost-saving procedure for treatment of abnormal uterine bleeding in women with both normal and myomatous uteri. Although the success rate in patients with normal cavities was higher than that achieved in patients with submucous myomas, hysterectomy because of abnormal bleeding related to myomas was avoided in 88.4% of the group with myomas. (Source: The Journal of Minimally Invasive Gynecology)

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  Theophylline-associated status epilepticus in an infant: pharmacokinetics and the risk of suppository use.

CONCLUSION: The parents of children and also physicians should be educated to ensure the proper use of the suppository formula. PMID: 19911151 [PubMed - in process] (Source: World Journal of Pediatrics : WJP)

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  m-Trifluoromethyl-diphenyl diselenide attenuates pentylenetetrazole-induced seizures in mice by inhibiting GABA uptake in cerebral cortex slices.

Authors: Prigol M, Brüning CA, Godoi B, Nogueira CW, Zeni G The present study investigated the anticonvulsive effect of the disubstituted diaryl diselenides diphenyl diselenide (PhSe)(2), m-trifluoromethyl-diphenyl diselenide (m-CF(3)-C(6)H(4)Se)(2), p-chloro-diphenyl diselenide (p-Cl-C(6)H(4)Se)(2) and p-methoxyl-diphenyl diselenide (p-CH(3)O-C(6)H(4)Se)(2) on a chemical model of seizure induced by pentylenetetrazole (PTZ) in mice. (PhSe)(2), (p-Cl-C(6)H(4)Se)(2) and (p-CH(3)O-C(6)H(4)Se)(2) did not abolish seizures induced by PTZ in mice. (m-CF(3)-C(6)H(4)Se)(2) at the dose of 100 mg/kg significantly prolonged the latency of the onset of the first convulsive episode and reduced the number of animals that presented seizures. To investigate the possible mechanisms involved in the ...

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  Gestational manganese intoxication and anxiolytic-like effects of diazepam and the 5-HT1A receptor agonist 8-OH-DPAT in male Wistar rats.

In conclusion, findings indicate that gestational Mn exposure attenuated benzodiazepine-mediated anxiolytic-like effects but not those of the 5-HT(1A) receptor agonist 8-OH-DPAT. PMID: 20081241 [PubMed - in process] (Source: Pharmacological Reports)

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  Just how safe are herbal medicines?

While many of us believe that "herbal" is synonymous with "safe" herbal remedies can in fact be deadly says Tammy Cohen. (Source: Telegraph Health)

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  Relative positioning of diazepam in the benzodiazepine-binding-pocket of GABAA receptors

We describe here such proximity-accelerated chemical coupling reactions of [alpha]1S205C and [alpha]1T206C with a diazepam derivative modified at the C-3 position with a reactive isothiocyanate group ([ndash]NCS). We also provide new data that identify [alpha]1H101C and [alpha]1N102C as exclusive sites of the reaction of a diazepam derivative where the [ndash]Cl atom is replaced by a [ndash]NCS group. Based on these observations we propose a relative positioning of diazepam within the benzodiazepine-binding site of [alpha]1[beta]2[gamma]2 receptors. (Source: Journal of Neurochemistry)

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  Antiepileptic drugs combined with high-frequency electrical stimulation in the ventral hippocampus modify pilocarpine-induced status epilepticus in rats

Discussion: Subeffective doses of antiepileptic drugs that increase the [gamma]-aminobutyric acid (GABA)ergic neurotransmission may represent a therapeutic tool to augment the HFS-induced anticonvulsant effects. (Source: Epilepsia)

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  Treatment of febrile seizures: Historical perspective, current opinions, and potential future directions

Abstract: Although most febrile seizures do no harm and two-thirds of initial cases have no witnessed recurrence, the seizures cause much family anxiety, and are sometimes prolonged. In rare cases they are the first evidence of important epilepsy syndromes or are implicated in the development of epilepsy with mesial temporal sclerosis in later life. There have been trials of prophylactic treatment with antiepileptic drugs including carbamazepine, diazepam, phenobarbital, phenytoin, and sodium valproate. Several strategies have been employed with these drugs, including continuous secondary prophylaxis, intermittent secondary prophylaxis in response to later episodes of fever, and rescue medication early in the course of further seizures. Another treatment strategy has been using one or more...

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  Dementia: 'My mother has pleaded to die for 10 years'

A searingly honest and moving account by a writer who has witnessed her mother's slide into Dementia (Source: Telegraph Health)

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  Current management of febrile seizures in Japan: An overview

Abstract: Febrile seizures (FS) require both acute and chronic management. Acute management includes the treatment and differential diagnosis of FS and depend on the presence of seizures and a patient’s level of consciousness upon arrival at hospital: a patient may be discharged after physical examination if there are no seizures and no alteration of consciousness; close observation and laboratory examinations may be indicated in cases when there are no seizures but the patient exhibits altered consciousness; and intravenous diazepam (DZP) is indicated if seizures persist. Central nervous system infections should be ruled out: if the patient has signs of meningeal irritation or increased intracranial pressure, disturbed consciousness for >1h, atypical seizures (partial seizures, seizures...

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  Effects of xylazine–ketamine–diazepam anesthesia on blood cell counts and plasma biochemical values in sheep and goats

Abstract  To examine the effects of xylazine, ketamine, diazepam anesthesia on clinical pathology parameters in sheep and goats, seven adult, healthy, non-pregnant Awassi sheep weighing 40–60 kg and seven adult, healthy non-pregnant Damascus breed goats weighing 35 to 55 kg were used. Anesthesia was induced using 0.1 mg/kg xylazine, 5 mg/kg ketamine, and 0.25 mg/kg diazepam as a single intravenous injection. Blood cell counts and plasma biochemical analysis were performed before anesthesia (T0), 2 h after recovery, 24 h after recovery, and 5 days later. Hematological analysis indicated that there was a significant increase in neutrophil percentages (P ≤ 0.05) in sheep and goats at 2 h and 24 h after recovery. There wa...

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  Discriminative stimulus effects of L-838,417 (7-tert-Butyl-3-(2,5-difluoro-phenyl)-6-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine): Role of GABA(A) receptor subtypes.

Authors: Licata SC, Platt DM, Rüedi-Bettschen D, Atack JR, Dawson GR, Van Linn ML, Cook JM, Rowlett JK Previous reports suggest that gamma-aminobutyric acid type A (GABA(A)) receptors containing alpha1 subunits may play a pivotal role in mediating the discriminative stimulus effects of benzodiazepines (BZs). L-838,417 (7-tert-Butyl-3-(2,5-difluoro-phenyl)-6-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine) is a GABA(A) receptor modulator with intrinsic efficacy in vitro at alpha2, alpha3, and alpha5 subunit-containing GABA(A) receptors, and little demonstrable intrinsic efficacy in vitro at alpha1 subunit-containing GABA(A) receptors. The present study evaluated the discriminative stimulus effects of L-838,417 in order to determine the extent to which the ...

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  DIAZEPAMsolution DIAZEPAM INTENSOLsolution, Concentrate [Roxane Laboratories, Inc]

Updated Date: Oct 20, 2009 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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  Sequential intrarectal diazepam and intravenous levetiracetam in treating acute repetitive and prolonged seizures

In this retrospective study of institutionalized patients with mental retardation, we present the efficacy and safety of sequential treatment with intrarectal diazepam (IRD) gel (Diastat) and intravenous levetiracetam (IVL) in comparison with either treatment alone for acute repetitive or prolonged seizures (ARPS). We defined ARPS as [ge]3 seizures of any type within 1 h or a single seizure of any type lasting [ge]3 min. Eighty-eight ARPS episodes were treated in 25 patients (14 female, age 21[ndash]72 years), with mainly symptomatic generalized epilepsy. There were no adverse events directly attributable to the administration of IRD or IVL. Seizure recurrence within 4 h of treatment, the primary outcome measure, was significantly lower after combined sequential IRD + IVL treatment (3 of 3...

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  Inhibitory Transmission in Locus Coeruleus Neurons Expressing GABAA Receptor Epsilon Subunit Has a Number of Unique Properties

Fast inhibitory synaptic transmission in the brain relies on ionotropic GABAA receptors (GABAAR). Eighteen genes code for GABAAR subunits, but little is known about the subunit. Our aim was to identify the synaptic transmission properties displayed by native receptors incorporating . Immunogold localization detected at synaptic sites on locus coeruleus (LC) neurons. In situ hybridization revealed prominent signals from , and mRNAs, some low β1 and β3 signals, and no signal. Using in vivo extracellular and in vitro patch-clamp recordings in LC, we established that neuron firing rates, GABA-activated currents, and mIPSC charge were insensitive to the benzodiazepine flunitrazepam (FLU), in agreement with the characteristics of recombinant receptors including an subunit. Surprisingly...

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  Diazepam/flurazepam overdose: Persistent toxic metabolite concentrations leading to prolonged coma and treated with rifampicin: case report

(Source: Reactions)

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  Relaxing With God

When Thoreau was on his deathbed, his aunt asked him if he had made his peace with God, and he responded, "I was not aware that we had quarreled." Someone else once said—I don't recall the source—that "The most salient characteristic of an enlightened being is not what one might think—having great wisdom, emanating love, and so forth—but rather, that they are completely relaxed."I have certainly had my share of restful times in hot tubs over the years, and have received countless wonderful and deeply soothing massages, but truthfully, I don't think I have been completely relaxed since I was, oh, say, two hours old.<!--break-->Actually, come to think of it, those first two hours weren't so great either. On the contrary, I was the youngest person ever to suffer from Post-Trauma...

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  Epilepsia partialis continua responsive to intravenous levetiracetam

We report on a case of epilepsia partialis continua with rapid response to intravenous bolus administration of levetiracetam. A 60-year-old woman presented with continuous jerking of the right foot and hallux persisting for more than two days. She had a 9-year history of epilepsy due to a left temporoparietal oligodendroglioma with occasional focal seizures clinically presenting as speech arrest, which was treated with levetiracetam and oxcarbazepine administered orally. After hospital admission, the twitching of the foot and toe was refractory to add-on treatment with lorazepam and diazepam but stopped within 15min after intravenous bolus administration of 2000mg levetiracetam. This observation suggests that intravenous bolus administration of levetiracetam may be an effective therapeutic...

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  Management of Terminal Hemorrhage in Patients With Advanced Cancer: A Systematic Literature Review

Abstract: Although terminal hemorrhage is an infrequent occurrence in advanced cancer patients, it is extremely distressing for patients, their families, and health care professionals when it does occur. By definition, there is a very short time period to support and comfort the patient, and it is vital that the management approach follows the best available evidence base. A systematic literature search was carried out to retrieve relevant publications relating to the management of terminal hemorrhage in patients with advanced cancer in whom invasive or interventional procedures are no longer appropriate. From 3,564 initial citations, 18 were appropriate to include in the final review, many of which focused on patients with head and neck tumors. The reported incidence of significant bleedi...

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  Effect of repeated administration of Annona diversifolia Saff. (ilama) extracts and palmitone on rat amygdala kindling.

Authors: González-Trujano ME, López-Meraz L, Reyes-Ramírez A, Aguillón M, Martínez A Annonas are consumed as fresh fruits, but, because of their effects on the central nervous system, are also used in folk medicine. The effect on rat amygdala kindling of repeated administration of Annona diversifolia hexane (100mg/kg IP or PO) and ethanol (100mg/kg, PO) leaf extracts and palmitone (10mg/kg, IP) was determined. Electrographic and/or behavioral changes were monitored during kindling-induced seizures 60minutes after treatments. Antiepileptic efficacy was evaluated with respect to afterdischarge (AD) duration, spike frequency, and/or behavioral seizure activity. Oral administration of both extracts significantly decreased spike frequency, whereas intraperitoneally ...

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  MHRA warns about unlicensed `herbal valium'

(Source: Reactions)

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  Diazepam/promethazine abuse: Intoxication: case report

(Source: Reactions)

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  ANTICONVULSANT EFFECT OF SEED EXTRACT OF Caesalpinia bonducella (Roxb.)

Conclusion: The present investigation revealed that, the PECB possessed anticonvulsant activity. This activity profile of PECB may be contributed to the presence of phytoconstituents such as saponins, proteins, homoisoflavone (bonducillin), carbohydrates and sterols present in the drug, as these are already reported for their anxiolytic and anti-convulsant activities.Keywords: C. bonducella, seed kernel, petroleum ether extract, anti-convulsant activity. (Source: Iranian Journal of Pharmacology & Therapeutics (IJPT))

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  Outpatient utilization of drugs acting on nervous system: a study from the Republic of Srpska, Bosnia & Herzegovina

Conclusions  The observed tendency toward increased total drug utilization observed in our study is comparable to worldwide trends. Implementation of new clinical guidelines for nervous diseases and updating of the list of reimbursable drugs with the addition of new ones contributed to the observed improvement in prescribing patterns in primary healthcare during the study period. The DU90% is shown to be a simple rough method for assessing prescribing quality. More stratified analyses should be performed on a routine basis to ensure a rational use of medicines and a cost-efficient use of limited healthcare resources. Content Type Journal ArticleCategory Pharmacoepidemiology and PrescriptionDOI 10.1007/s00228-009-0732-6Authors Vanda Marković-Peković, Health Insuranc...

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  Domestic Abuse Victims Struggle With Another Blow: Difficulty Getting Health Insurance

Kaiser Health News reporter Jenny Gold details the difficulties faced by domestic abuse victims in getting health insurance. "In 2006, attorney Jody Neal-Post tried to get health insurance but was rejected because of treatment -- counseling and Valium -- she received following a domestic-abuse incident. (Source: Health News from Medical News Today)

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  A comparison of midazolam nasal spray and diazepam rectal solution for the residential treatment of seizure exacerbations

Rectal diazepam is established as a standard rescue or emergency treatment for seizure or status epilepticus; however, the rectal route of administration has not been universally accepted. To determine if an alternative route of administration of a benzodiazepine was equally effective, we compared a novel midazolam HCl concentrated nasal spray (MDZ-n) with diazepam rectal solution (DZP-r) in the treatment of prolonged seizures in a residential epilepsy center. In 21 adult patients with medically refractory epilepsy, 124 seizure-exacerbations were treated by their caregivers, alternatively with 10 mg DZP-r and 10 mg concentrated MDZ-n, two or three treatments with each medication for each patient. No difference was demonstrated in efficacy or time to effect between the two drugs. Common tre...

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  Genoproteomic Mining of Urothelial Cancer Suggests {gamma}-Glutamyl Hydrolase and Diazepam-Binding Inhibitor as Putative Urinary Markers of Outcome after Chemotherapy.

Authors: Pollard C, Nitz M, Baras A, Williams P, Moskaluk C, Theodorescu D Urinary biomarkers for the detection of bladder cancer have been developed, but no similar markers exist for prediction of clinical outcomes after receiving chemotherapy. Here we evaluate an approach that combines genomic, proteomic, and therapeutic outcome datasets to identify novel putative urinary biomarkers of clinical outcome after neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). Using this method, we identified gamma-glutamyl hydrolase (GGH), emmprin, survivin, and diazepam-binding inhibitor (DBI). Interestingly, GGH is a protein associated with methotrexate resistance, whereas emmprin, survivin, and DBI had been previously identified as predictors of outcome after platinum-contain...

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  Early-Life Blockade of 5-HT1A Receptors Alters Adult Anxiety Behavior and Benzodiazepine Sensitivity

Conclusions: Absence of 5-HT1AR signaling during early stages of brain maturation predisposes an organism to affective dysfunction later in life. Because early-life treatment with WAY-100,635 in Swiss-Webster mice reduced diazepam sensitivity and increased GABAAR α subunit levels in the prefrontal cortex and hippocampus, our data suggest a putative link between early-life disruption of the serotonergic system and the emergence of increased anxiety and decreased benzodiazepine responsivity at adult age. Moreover, early-life 5-HT1A receptor functionality appears to be essential for the development of normal GABAAR functionality. This study may have clinical implications for psychoactive drug use during pregnancy and for the pharmacogenetic background of benzodiazepine sensitivity. (Source: ...

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  The anti-epileptic drug lacosamide (Vimpat((R))) has anxiolytic property in rodents.

Authors: Higgins GA, Breysse N, Undzys E, Quo C, Joharchi N, Derksen DR, Xin T, Isaac M, Slassi M Lacosamide ((R)-2-acetamido-N-benzyl-3-methoxypropionamide; formerly harkoseride, SPM 927; Vimpat((R))), has been recently approved by US and European regulatory authorities for use as add-on therapy for partial-onset seizures in adults. Because a number of anti-epileptic drugs are used to treat conditions beyond epilepsy, including anxiety, in the present study we investigated the anxiolytic potential of lacosamide in a conditioned emotional response (CER) model in rat, and the mouse marble burying assay. In each test lacosamide produced a significant effect consistent with anxiolysis, i.e. lacosamide increased suppression ratio in the CER test, and reduced the number of marbles buried in...

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  Watchdog warns over "herbal valium"

The medicines watchdog has warned people to be on their guard after it was revealed that a plant used in some "herbal valium" drugs could prove deadly (Source: Nursing in Practice)

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  Etoricoxib/diazepam overdose: Heartburn: case report

(Source: Reactions)

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  MHRA issues warning over 'extremely poisonous' herbal valium

Using so-called ‘herbal valium’ drugs, which contain the plant aconite, could prove deadly, according to the MHRA. (Source: Nursing Times Breaking News)

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  Herbal valium could prove deadly, medicines watchdog warns

An extremely toxic plant is in some 'herbal valium' drugs and should be avoided, a medicines watchdog has warned today. (Source: the Mail online | Health)

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  MHRA issues warning over unlicensed 'herbal valium'

Source: MHRA Area: News The Medicines and Healthcare products Regulatory Agency (MHRA) has issued a warning highlighting the dangers of taking unlicensed herbal medicines containing aconite.   According to the press release, aconite has recently been portrayed in the media as 'herbal valium'; however, it is an extremely poisonous plant that is toxic to the heart. It is also known as monkshood and herbal products containing this ingredient could be fatal or cause serious illness if consumed.   It appears that the warning has been issued following two reports of suspected adverse reactions to aconite, one where a patient suffered kidney problems and another where the patient was hospitalised after suffering dizziness and paresthesia.   (Source: NeLM - News)

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  Warning Over Unlicensed 'Herbal Valium'

The Medicines and Healthcare products Regulatory Agency (MHRA) is warning people of the dangers of taking unlicensed herbal medicines containing aconite. Aconite has recently been portrayed in the media as 'herbal valium', however, it is actually an extremely poisonous plant that is toxic to the heart. (Source: Health News from Medical News Today)

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  Effect of Brewer's Yeast-Induced Pyrexia on Aminophylline-Elicited Convulsions in Mice.

In this study, we investigated the basic mechanism of aminophylline [theophylline-2-ethylenediamine]-induced convulsions and the effects of Brewer's yeast-induced pyrexia in mice. Diazepam (5-10mg/kg, i.p.), a benzodiazepine receptor agonist, significantly prolonged the onset and significantly decreased the incidence of convulsions induced by aminophylline (350mg/kg, i.p.). However, the gamma aminobutyric acid (GABA)A receptor agonist muscimol (1-4mg/kg, i.p.), the GABAB receptor agonist baclofen (2-4mg/kg, i.p.) and the N-methyl-D-aspartic acid receptor antagonist dizocilpine (0.1-0.3mg/kg, i.p.) failed to protect against the convulsions. 20% Brewer's yeast (0.02ml/g, s.c.) increased body temperature by 1.03, and also significantly shortened the onset and significantly increased the incid...

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  Simultaneous analysis of diazepam and its metabolites in rat plasma and brain tissue by HPLC-UV and SPE.

Authors: Mercolini L, Mandrioli R, Iannello C, Matrisciano F, Nicoletti F, Raggi MA Diazepam is frequently used as an adjuvant during antidepressant therapy. Recently, some studies have suggested that the treatment with benzodiazepines could have different efficacy in depressed patients as opposed to non-depressed ones. To clarify the matter, a study is currently underway, regarding the drug metabolism in rats. In order to obtain a more complete and significant set of data, the main diazepam metabolites have also been considered, namely: nordiazepam, temazepam and oxazepam. A feasible and reliable HPLC method has been developed for the simultaneous determination of these compounds in plasma and brain tissue of rats. The method has been applied to "normal" rats and to genetic rat models...

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  Loop 2 Structure in Glycine and GABAA Receptors Plays a Key Role in Determining Ethanol Sensitivity [Mechanisms Of Signal Transduction]

The present study tests the hypothesis that the structure of extracellular domain Loop 2 can markedly affect ethanol sensitivity in glycine receptors (GlyRs) and -aminobutyric acid type A receptors (GABAARs). To test this, we mutated Loop 2 in the 1 subunit of GlyRs and in the subunit of 1β22GABAARs and measured the sensitivity of wild type and mutant receptors expressed in Xenopus oocytes to agonist, ethanol, and other agents using two-electrode voltage clamp. Replacing Loop 2 of 1GlyR subunits with Loop 2 from the GABAAR (L2), but not the GABAAR subunit, reduced ethanol threshold and increased the degree of ethanol potentiation without altering general receptor function. Similarly, replacing Loop 2 of the subunit of GABAARs with L2 shifted the ethanol threshold from 50 mm in WT to 1...

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  Tanshinone I enhances learning and memory, and ameliorates memory impairment in mice via the extracellular signal-regulated kinase signalling pathway

Conclusions and implications: Tanshinone I ameliorates the learning and memory impairments induced by diazepam and MK-801 through activation of ERK signalling. (Source: British Journal of Pharmacology)

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  Translocator protein (18 kDa) mediates the pro-growth effects of diazepam on Ehrlich tumor cells in vivo.

Authors: Sakai M, Ferraz de Paula V, Pinheiro ML, Ribeiro A, Quinteiro-Filho WM, Rone MB, Martinez-Arguelles DB, Dagli ML, Papadopoulos V, Palermo-Neto J The Translocator Protein (TSPO), previously known as the peripheral-type benzodiazepine receptor, is a ubiquitous drug- and cholesterol- binding protein that is upregulated in several types of cancer cells. TSPO drug ligands (e.g., diazepam) induce or inhibit tumor cell proliferation, depending on the dose and tissue origin. We have previously shown that TSPO is expressed in Ehrlich tumor cells and that diazepam increases proliferation of these cells in vitro. Here, we investigated the in vivo effects of diazepam on Ehrlich tumor growth and the role of TSPO in mediating this process. Oral administration of diazepam to mice (3.0mg/kg/d...

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  A clinical, radiological and outcome study of status epilepticus from India

The objective of this study is to evaluate the clinical and radiological characteristics and the outcome of status epilepticus (SE). 117 consecutive patients with SE were evaluated including their demographics, history of epilepsy, antiepileptic drug (AED) default, comorbidities, SE type and duration. The study included 22 children, 77 adults and 18 elderly patients with SE. Blood counts, serum chemistry, ECG, cranial MRI, cerebrospinal fluid and EEG were done. Patients were treated with IV phenytoin, valproate, lorazepam or diazepam as per a fixed protocol and responses to first and second drugs were noted. Death during hospital was recorded. The etiology of SE was infection in 53.8%, drug default in 7.9%, metabolic in 14.5%, stroke in 12.8% and miscellaneous in 11% of patients. 92....

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  Scopolamine Induced Amnesia is Reversed by Bacopa monniera Through Participation of Kinase-CREB Pathway.

Authors: Saraf MK, Anand A, Prabhakar S Scopolamine, an anticholinergic drug, is reported to produce amnesia by interference of long term potentiation and has been used for discerning the efficacy of various antiamnesic drugs. The intoxication with anticholinergics and benzodiazepines tend to produce neurodegeneration which cause memory deficits. Our earlier reports have shown the antiamnesic drug, B. monniera to be capable of alleviating diazepam induced memory deficits. We have now tested how scopolamine affects downstream signaling molecules of long term potentiation and if B. monniera can also modulate the scopolamine induced amnesia. We used Morris water maze scale to test the amnesic effect of scopolamine and its reversal by B. monniera. Rota-rod test was used to screen muscle co...

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  Finch (Taeneopygia guttata) sedation with intranasal administration of diazepam, midazolam or xylazine

(Source: Journal of Veterinary Pharmacology and Therapeutics)

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  Changes in hippocampal arc protein expression and synaptic plasticity by the presentation of contextual cues linked to drug experience

In this study, we investigated if the environmental context associated with withdrawal experience was able to evoke the same behavioral alteration observed after chronic benzodiazepine administration. Furthermore, we studied the hippocampal synaptic plasticity and anatomical expression of Arc protein during withdrawal and the re-exposure to the context associated with anxiety expression (characteristic sign of benzodiazepines withdrawal). It was demonstrated that re-exposure evoked on days 15 and 25 after the first exposure the same behavior. An increased hippocampal synaptic plasticity, expressed as a lower threshold to induce long-term potentiation on dentate gyrus, was observed in animals dependent on diazepam and during retrieval, in the same group, until day 15. This plastic change di...

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  Radiolabelled Molecules for Imaging the Translocator Protein (18 kDa) Using Positron Emission Tomography.

Authors: Dollé F, Luus C, Reynolds A, Kassiou M The translocator protein (18 kDa) (TSPO), formerly known as the peripheral benzodiazepine receptor (PBR), was originally identified as an alternate binding site for the central benzodiazepine receptor (CBR) ligand, diazepam, in the periphery, but has now been distinguished as a novel site. The TSPO is ubiquitously expressed in peripheral tissues but only minimally in the healthy brain and increased levels of TSPO expression have been noted in neuroinflammatory conditions such as Alzheimer's disease, Parkinson's disease and stroke. This increase in TSPO expression has been reported to coincide with the process of microglial activation, whereby the brain's intrinsic immune system becomes active. Therefore, by using recently developed h...

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  Statistical evaluation of influence of polymers concentration on disintegration time and diazepam release from quick disintegrating rapid release tablet.

This study describes the formulation of rapidly disintegrating, fast dissolving diazepam tablets intended for use in the oral cavity. The tablets were prepared by the conventional wet granulation method using solid dispersion of the drug with PEG-4000 and/or PEG-6000. A 3(2) factorial design was used to reduce the number of experimental runs and to obtain several formulations by which tablets disintegrated within 3 min and released 85% of the drug in less than 30 min. Several tablet formulations prepared with different amounts of PEGs in solid dispersion met the above two criteria. However, tablets which were prepared with PEG-4000 alone at the lowest concentration disintegrated in the shortest time (32.12 sec) and released 85% of the drug most rapidly (11.03 min). PMID: 19721383 [PubM...

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  Intranasal Midazolam Versus Rectal Diazepam for Acute Management of Prolonged Seizures Without Intravenous Access: A Synthesis of the Evidence-based Research

Problem: The National Institute of Neurological Disorders and Stroke estimates that more than 2 million people in the United States—1 in 10—will have an unprovoked seizure, and 1 in 100 will be diagnosed with epilepsy. (Source: Journal of Pediatric Health Care)

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  Population Patch-Clamp Electrophysiology Analysis of Recombinant GABAA {alpha}1{beta}3{gamma}2 Channels Expressed in HEK-293 Cells

-Amino butyric acid (GABA)—activated Cl— channels are critical mediators of inhibitory postsynaptic potentials in the CNS. To date, rational design efforts to identify potent and selective GABAA subtype ligands have been hampered by the absence of suitable high-throughput screening approaches. The authors describe 384-well population patch-clamp (PPC) planar array electrophysiology methods for the study of GABAA receptor pharmacology. In HEK293 cells stably expressing human 1β32 GABAA channels, GABA evoked outward currents at 0 mV of 1.05 ± 0.08 nA, measured 8 s post GABA addition. The IGABA was linear and reversed close to the theoretical ECl (—56 mV). Concentration-response curve analysis yielded a mean pEC50 value of 5.4 and Hill slope of 1.5, and for a ser...

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  Interaction of polyphenolic metabolites with human serum albumin: a circular dichroism study.

Authors: Nozaki A, Kimura T, Ito H, Hatano T Binding sites of polyphenolic compounds on human serum albumin (HSA) were investigated using induced Cotton effects on the circular dichroism (CD) spectra. Polyphenolic compounds used in this study are known to be metabolites from tannins and their related polyphenols in food and medicinal plants. The present investigation revealed that the structural differences markedly affected the binding of the compounds to HSA. Protocatechuic acid, together with its methylated compounds vanillic and isovanillic acids, were assigned to be bound to sites I and II of HSA, based on the competitive relationships with site-I-binding phenylbutazone (PB) and site-II-binding diazepam (DP). 4-O-Methylgallic acid, which is the metabolite from gallic acid, was bou...

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  Inadequate Dose of Opioid-agonist Medication is Related to Misuse of Benzodiazepines

Conclusions: The inadequate dose of OAM in opioid substitution treatment for opioid-dependent patients seems to be related to the misuse of benzodiazepines. (C) 2009 Lippincott Williams & Wilkins, Inc. (Source: Addictive Disorders & Their Treatment)

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  Diazepam and cocaine potentiate brain stimulation reward in C57BL/6J mice.

In this study we examined the effects of cocaine and diazepam on reward-facilitation and response rate in C57BL/6J mice, the most frequently used mouse line to study genetic modifications. Both cocaine and diazepam potentiated the rewarding effects of lateral hypothalamic brain stimulation in a dose-dependent manner and increased the rate of responding. Interestingly, the maximum decrease in ICSS thresholds was comparable for both drugs, suggesting a similar ability to affect reward and motivation despite different effects on brain reward systems. PMID: 19716385 [PubMed - as supplied by publisher] (Source: Behavioural Brain Research)

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  Jackson pleaded with doctor for powerful anesthetic, records show

The mixture of the sedatives Valium, lorazepam and midazolam, combined with propofol, was enough to kill the singer, a warrant affidavit unsealed Monday in Houston shows. A sleepless Michael Jackson spent his last hours pleading for a dose of a powerful anesthetic, his doctor told police, according to court records unsealed Monday. (Source: Los Angeles Times - Science)

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  Behavioral and histological assessment of the effect of intermittent feeding in the pilocarpine model of temporal lobe epilepsy

Summary: Temporal lobe epilepsy (TLE) is the most resistant type of epilepsy. Currently available drugs for epilepsy are not antiepileptogenic. A novel treatment for epilepsy would be to block or reverse the process of epileptogenesis. We used intermittent feeding (IF) regimen of the dietary restriction (DR) to study its effect on epileptogenesis and neuroprotection in the pilocarpine model of TLE in rats. The effect of IF regimen on the induction of status epilepticus (SE), the duration of latent period, and the frequency, duration, severity and the time of occurrence of Spontaneous Recurrent Seizures (SRS) were investigated. We also studied the effect of IF regimen on hippocampal neurons against the excitotoxic damage of prolonged SE (about 4h) induced by pilocarpine. The animals (Wistar...

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  A Drosophila Resource of Transgenic RNAi Lines for Neurogenetics [Developmental and behavioral genetics]

Conditional expression of hairpin constructs in Drosophila is a powerful method to disrupt the activity of single genes with a spatial and temporal resolution that is impossible, or exceedingly difficult, using classical genetic methods. We previously described a method (Ni et al. 2008) whereby RNAi constructs are targeted into the genome by the phiC31-mediated integration approach using Vermilion-AttB-Loxp-Intron-UAS-MCS (VALIUM), a vector that contains vermilion as a selectable marker, an attB sequence to allow for phiC31-targeted integration at genomic attP landing sites, two pentamers of UAS, the hsp70 core promoter, a multiple cloning site, and two introns. As the level of gene activity knockdown associated with transgenic RNAi depends on the level of expression of the hairpin constru...

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  A study of cardiovascular function under controlled and spontaneous ventilation in isoflurane–medetomidine anaesthetized horses

Conclusions There was no difference in cardiovascular function in horses undergoing elective surgery during isoflurane[ndash]medetomidine anaesthesia with SV in comparison with IPPV, provided the horses are maintained slightly hypercapnic.Clinical relevance In horses with health status ASA I and II, cardiovascular function under general anaesthesia is equal with or without IPPV if the PaCO2 is maintained at 50[ndash]60 mmHg. (Source: Veterinary Anaesthesia and Analgesia)

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  Assessment of cardiac troponin I and C-reactive protein concentrations associated with anesthetic protocols using sevoflurane or a combination of fentanyl, midazolam, and sevoflurane in dogs

Conclusions and clinical relevance There was no significant difference in serum cTnI and CRP concentrations between anesthetic protocols. Further investigation in a larger number of dogs is necessary to confirm the current findings. (Source: Veterinary Anaesthesia and Analgesia)

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  Alfaxalone in cyclodextrin for induction and maintenance of anaesthesia in ponies undergoing field castration

Conclusions and clinical relevance Alfaxalone provided smooth induction and recovery characteristics and was considered suitable for maintenance of anaesthesia for castration in ponies. (Source: Veterinary Anaesthesia and Analgesia)

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  Ayurvedic processed seeds of nux-vomica: Neuropharmacological & chemical evaluation.

Ayurvedic processed seeds of nux-vomica: Neuropharmacological & chemical evaluation. Fitoterapia. 2009 Aug 20; Authors: Katiyar C, Kumar A, Bhattacharya LS, Singh LR The effect of detoxification on Strychnos nux-vomica seeds by traditional processing with aloe and ginger juices (B), by frying in cow ghee (C), and by boiling in cow milk (D) was investigated. The ethanolic extract was analyzed for spontaneous motor activity (SMA), pentobarbitone-induced hypnosis, PTZ induced convulsions, diazepam-assisted protection, and morphine induced catalepsy. All samples could reduce SMA and inhibited catalepsy. The seeds processed in milk (D) showed the lowest strychnine content in the cotyledons, exhibited marked inhibition of PTZ induced convulsions and maximal potentiation of hypnos...

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  Impact of rat P450 genetic polymorphism on diazepam metabolism

Expert Opinion on Drug Metabolism & Toxicology , Early Online. (Source: Expert Opinion: Expert Opinion on Drug Metabolism & Toxicology: Table of Contents)

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  Effect of xylazine–ketamine–diazepam anesthesia on certain clinical and arterial blood gas parameters in sheep and goats

This study was conducted to evaluate the effect of xylazine–ketamine–diazepam anesthesia on heart rate, respiration rate, rectal temperature, rumen motility, peripheral blood pH, PaO2, and PaCO2 in adult female nonpregnant Awassi sheep and adult female nonpregnant Damascus goats. Anesthesia was induced using 0.1 mg/kg, 5 mg/kg, and 0.25 mg/kg xylazine, ketamine, and diazepam respectively as a single intravenous injection. The heart rate, respiration rate, rectal temperature, rumen motility, peripheral arterial blood pH, PaO2, and PaCO2 were evaluated 15 min before and at 15, 30, and 60 min during anesthesia. In sheep, the heart rate, rumen motility, and PaO2 were decreased significantly (P < 0.05) at 15, 30, and 60 min following anesthesia. The...

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  Poisoning in goats by Aspidosperma pyrifolium Mart.: Biological and cytotoxic effects.

Authors: de Souza Lima MC, Soto-Blanco B Spontaneous cases of poisoning by Aspidosperma pyrifolium, the toxicity to rats and in vitro cytotoxicity were evaluated. On all spontaneous cases studied, ingestion of the plant and cases of abortion occurred exclusively in goats. The majority of the cases of abortion occurred during the early dry season and the early rainy season, and experienced goats were less likely to be affected than naïve goats. Pregnant Wistar rats dosed with A. pyrifolium extract on the 15(th) gestational day or from the 15(th) to the 17(th) gestational day presented reduction of fetal weight and strong evidence of maternal toxicity was found. Female rats injected A. pyrifolium extract intraperitoneally presented motor disturbances and death; male rats were more r...

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  Pharmacological evaluation of a phytotherapeutic product - CPV (dry extract of Crataegus oxyacantha L., Passiflora incarnata L. and Valeriana officinalis L.) in laboratory animals

O presente estudo teve por objetivo avaliar em modelos animais, os possíveis efeitos do produto fitoterápico CPV (extrato seco de Crataegus oxyacantha, Passiflora incarnata e Valeriana officinalis) quanto à sua ação ansiolítica avaliada no modelo do labirinto em cruz elevado (LCE). Outros efeitos como neuroléptico (bloqueio da estereotipia por apomorfina), analgésico (testes: placa quente; retirada da cauda e contorções abdominais), bem como sobre a memória (esquiva passiva) também foram considerados. O extrato CPV (430 e 860 mg/kg) apresentou um efeito ansiolítico (aumento do número de entradas nos braços abertos do LCE) em ratos e uma tendência de efeito amnésico para ambas as doses (430 e 860 mg/kg), embora menos intenso quando comparado com o diazepam (1,5 mg/kg). O ex...

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  New to forum, 3rd day on suboxone...

Author: jamez70 Posted: Thu Aug 13, 2009 12:22 am Diary, I have had SEVERE SEVERE anxiety in my life. Let me try to describe it. Suddenly, out of nowhere, I have a severe panic attack without any real reason (no phobia). I try to go on.. That night, I have another one. I then become afraid to sleep in my bed, because I associate it with the panic attack. Then about 8 hours later, I have another one. Then I wonder "whats wrong with me? Do I have a tumor? Did I have a stroke?".. Then they keep coming and coming. Eventually, I enter a constant state of severe anxiety.. I sleep very little, and I stop eating. I get afraid to leave the house. Usually by that time, I seek out a psychiatrist, and I'm on the waiting list. TH...

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  Effects of rolipram and diazepam on the adaptive changes induced by morphine withdrawal in the hypothalamic paraventricular nucleus.

In this study we investigated whether morphine dependence was inhibited by phosphodiesterase (PDE) 4 inhibitors rolipram and diazepam. Dependence on morphine was induced by a 7-day s.c. implantation of morphine pellets. On day 8, morphine withdrawal was precipitated by an injection of naloxone. In order to determine the effect of rolipram and diazepam rats were injected with these drugs once daily for seven days as well as 30 min before of naloxone injection. When opioid withdrawal was precipitated, an enhanced noradrenaline turnover and increased level of cyclic AMP and cyclic GMP in the hypothalamic paraventricular nucleus (PVN) were observed 30 min after naloxone administration. Moreover, c-Fos expression was induced in the PVN after naloxone-precipitated morphine withdrawal. Co-adminis...

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  Alprazolam/diazepam: Dependence: case report

(Source: Reactions)

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  Intraneuronal β-Amyloid Accumulation in the Amygdala Enhances Fear and Anxiety in Alzheimer's Disease Transgenic Mice

Conclusions: We propose a deleterious role of intraneuronal Aβ on amygdala-dependent emotional responses by affecting the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway. (Source: Biological Psychiatry)

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  The impact of diazepam's discovery on the treatment and understanding of status epilepticus

The fortuitous discovery of the benzodiazepines and the subsequent application of these agents to the treatment of status epilepticus (SE) heralds in the modern age of treating this neurologic emergency. More than 50 years after their discovery, the benzodiazepines remain the drugs of first choice in the treatment of SE. However, the benzodiazepines can be ineffective, especially in those patients whose seizures are the most prolonged. The benzodiazepines act by increasing the affinity of [gamma]-aminobutyric acid (GABA) for GABAA receptors. A receptor's subunit composition affects its functional and pharmacologic properties, trafficking, and cellular localization. The GABAA receptors that mediate synaptic inhibition typically contain a [gamma]2 subunit and are diazepam-sensitive. Among th...

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  Successful treatment for refractory convulsive status epilepticus by parenteral lacosamide

We report a case of refractory convulsive status epilepticus (CSE) that was successfully controlled with lacosamide. The 38-year-old male patient was admitted for a series of complex partial seizures with secondary generalization leading to refractory CSE. During the transport to the hospital the patient was given 22.5 mg diazepam, 12.5 mg etomidate, and 5 mg midazolam without success. An additional dose of 4 mg lorazepam and a dose of 1,500 mg levetiracetam after admission were yet without clinical effect. A further treatment with lacosamide (300 mg via percutaneous gastric fistula) resulted in complete clinical remission of the epileptic activity within 30 min. The application of lacosamide resulted in cessation of CSE and was well tolerated. To our knowledge, this is the first case of s...

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  Effect of administration of propofol and xylazine hydrochloride on recovery of horses after four hours of anesthesia with desflurane.

Conclusions and Clinical Relevance-Propofol and xylazine administered IV to horses after 4 hours of desflurane anesthesia improved the quality of transition from lateral recumbency to standing but added potential for harmful respiratory depression during the postanesthetic period. PMID: 19645576 [PubMed - in process] (Source: American Journal of Veterinary Research)

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  Major issue, plz help!

Author: MACKENZY3376 Posted: Fri Jul 31, 2009 1:18 am DUDE!!! u cant do this alone all by urself. from my experience if i had been alone i would have killed myself. pleeease if nothing else-cant you go to a hospital or something? im not familiar with where you are or how in general the healthcare is and this might sound childish but if nothing else i would go to a hospital and tell them if they dont help you that you think you might commit suicide. you need help and i always try to put myself in the others shoes and if i didnt have the help from my parents or anyone else, i think i would have to go to that extreme. i can hardly imagine being in a foreign country and feeling that desperate, helpless and alone but i have no idea what ...

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  Medical treatment of acute poisoning with organophosphorus and carbamate pesticides.

Authors: Jokanović M Organophosphorus compounds (OP) are used as pesticides and developed as warfare nerve agents such as tabun, soman, sarin, VX and others. Exposure to even small amounts of an OP can be fatal and death is usually caused by respiratory failure. The mechanism of OP poisoning involves inhibition of acetylcholinesterase (AChE) leading to inactivation of the enzyme which has an important role in neurotransmission. AChE inhibition results in the accumulation of acetylcholine at cholinergic receptor sites, producing continuous stimulation of cholinergic fibers throughout the nervous systems. During more than five decades, pyridinium oximes have been developed as therapeutic agents used in the medical treatment of poisoning with OP. They act by reactivation of AChE inh...

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  Comparison of efficacy of oral drotaverine plus mefenamic acid with paracervical block and with intravenous sedation for pain relief during hysteroscopy and endometrial biopsy

Conclusions :&lt;/b&gt; Oral drotaverine with mefenamic acid is effective in women undergoing hysteroscopy and endometrial biopsy. (Source: Indian Journal of Medical Sciences)

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  Effects of Different Concentrations of Poly(vinyl pyrrolidone) on the Solubility of Lamotrigine and Diazepam in Ethanol + Water Mixtures at 298.2 K

Journal of Chemical & Engineering Data, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Chemical and Engineering Data)

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  Magnitude of potentially inappropriate prescribing in Germany among older patients with generalized anxiety disorder

Conclusions: GPs in Germany often prescribe medications that have been designated as potentially inappropriate to their elderly patients with GAD--especially those with comorbid depressive disorders. Further research is needed to ascertain whether there are specific subgoups of elderly patients with GAD for whom the benefits of these medications outweigh their risks. (Source: BMC Geriatrics)

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  [Off-label use of psychotropic medications in paediatric wards: A prospective study.]

CONCLUSION: The high rates of off-label prescription documented here and elsewhere highlight the need for further controlled clinical trials to evaluate the risks and benefits of psychotropic medication in children and adolescents. PMID: 19640689 [PubMed - as supplied by publisher] (Source: Archives de Pediatrie)

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  Quantitative determination of dipyridamole in human plasma by high-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

Authors: Qin T, Qin F, Li N, Lu S, Liu W, Li F Dipyridamole is a classic platelet inhibitor which has been a key medicine in clinical therapy of thrombosis and cerebrovascular disease. A rapid, selective and convenient method using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed for determination of dipyridamole in human plasma. After protein precipitation of 200 muL plasma with methanol, dipyridamole and diazepam (internal standard) were chromatographed on an Ultimate XB-C(18) (50 x 2.1 mm i.d, 3 mu) column with the mobile phase consisting of methanol-ammonium acetate (5 mM; 80 : 20, v/v) at a flow rate of 0.25 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode via positive...

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  Different phases of afterdischarge during rapid kindling procedure in mice

Summary: The basic mechanisms of hippocampal networks in epileptogenesis are not entirely understood. To help achieve a better understanding of these mechanisms, we studied the extra-cellular electrically evoked responses in the hippocampi of mice during rapid kindling. Kindling protocol was achieved by stimulating the dorsal right hippocampus six times daily for four days using bipolar electrodes to produce sub-convulsive electrical discharges. Motor responses and analyzed electroencephalographic recordings showed progression from partial complex seizures to generalized seizures associated with different consecutive patterns within the afterdischarges. A spike-wave pattern appeared immediately after stimulation in combination with a poly-spike complex superimposed over the wave (AD1). AD1...

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  Emergency management of paediatric status epilepticus in Australia and New Zealand: Practice patterns in the context of clinical practice guidelines

Conclusions: Initial seizure management by CPG recommendations and reported physician practice was broadly similar across PREDICT sites and consistent with APLS guidelines. Practice was variable for second/third line SE management. Areas of controversy would benefit from multi-centred trials. (Source: Journal of Paediatrics and Child Health)

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  Treatment of early and late kainic–acid induced status epilepticus with the noncompetitive AMPA receptor antagonist GYKI 52466

Discussion: Noncompetitive AMPA receptor antagonists represent a promising approach for early treatment of status epilepticus; they may also be effective at later times when there is refractoriness to benzodiazepines. (Source: Epilepsia)

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  [Epileptic seizures in critically ill patients]

Authors: Stasiukyniene V, Pilvinis V, Reingardiene D, Janauskaite L THE AIM OF THIS ARTICLE: To review the causes, clinical signs, pathophysiology, consequences, and treatment of seizures and status epilepticus in critically ill patients. Only 25% of people, who have seizures and status epilepticus, have epilepsy as well. In the intensive care settings, seizures and status epilepticus are a common neurologic complication, which is attributable to primary neurologic pathology (stroke, hemorrhage, tumor, central nervous system infection, head trauma) or secondary to critical illness (anoxic brain damage, intoxications, metabolic abnormalities) and clinical management. There are three main subtypes of status epilepticus in intensive care units: generalized convulsive status epilepticus, f...

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  The Mothers Act Disease Mongering Campaign - Part I

(NaturalNews) The Mothers Act represents the ultimate example of disease mongering at its worst because the eight-year attempt to pass this federal legislation has evolved into profiteering never before exhibited so conspicuously.Disease mongering "is the selling of sickness that widens the boundaries of illness and grows the markets for those who sell and deliver treatments," according to Ray Moyniahan and David Henry in the April 11, 2006 paper in PLoS Med, titled, "The Fight against Disease Mongering." "It is exemplified most explicitly by many pharmaceutical industry -- funded disease-awareness campaigns -- more often designed to sell drugs than to illuminate or to inform or educate about the prevention of illness or the maintenance of health," the authors explain. "Drug companies are ...

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  Comparison of efficacy of oral drotaverine plus mefenamic acid with paracervical block and with intravenous sedation for pain relief during hysteroscopy and endometrial biopsy

Conclusions :&lt;/b&gt; Oral drotaverine with mefenamic acid is effective in women undergoing hysteroscopy and endometrial biopsy. (Source: Indian Journal of Medical Sciences)

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  Purple glove syndrome: a case report. Hand surgeons and physicians be aware

A 26-year-old lady was seen at the Emergency department with sudden onset of pain and discolouration of her right forearm and hand following intra-venous (IV) infusion of Phenytoin (PHT). She had been seen the night before at a peripheral clinic with history of generalized tonic-clonic seizures for which IV Diazepam was given and she was started on PHT infusion. Four hours later she complained of pain at the infusion site on the dorsum of right wrist associated with swelling of the entire hand and distal-third of forearm. Within a few hours she started developing blisters on the entire hand and distal forearm – the hand appearing like a distended glove (). The Radial and Ulnar artery pulse were not palpable at presentation. There was absence of sensation in the entire hand. The forearm w...

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  A Family With Paroxysmal Nonkinesigenic Dyskinesia: Genetic and Treatment Issues

Paroxysmal nonkinesigenic dyskinesia is a condition characterized by attacks of sudden involuntary movements triggered by caffeine or alcohol intake, stress, or fatigue. The paroxysms are usually of the generalized type and may last up to an hour. Described here is a Polish family with this disorder seen in two children and their father. Variable expressivity as well as reduced penetrance of the causative mutation were noteworthy in this kindred. Treatment options included abortive diazepam and prophylactic levetiracetam, with the latter having a more pronounced effect in this family. Favorable response to levetiracetam is probably linked to action of the drug on calcium channels in neurons, muscle cells, or both. (Source: Pediatric Neurology)

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  The interaction of sildenafil with the anticonvulsant effect of diazepam.

Authors: Gholipour T, Rasouli A, Jabbarzadeh A, Nezami BG, Riazi K, Sharifzadeh M, Dehpour AR In order to assess the role of nitric oxide/cyclicGMP signaling pathway in the anticonvulsant effect of benzodiazepines, we studied the potential interaction of a phosphodiesterase type 5 inhibitor, sildenafil with the effect of diazepam on a mouse model of clonic seizures induced by intravenous infusion of GABA antagonist, pentylenetetrazole (PTZ). Administration of sildenafil (10 mg/kg; per se effective on seizure threshold) could abolish the anticonvulsive effect of diazepam, and a subeffective dose (5 mg/kg), when added to NO precursor L-arginine (50 mg/kg) could cause the same effect. Conversely, subeffective doses of diazepam (0.02 mg/kg) and NO synthase inhibitor N(omega)-nitro- L-argin...

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  Altered responses of dopamine D3 receptor null mice to excitotoxic or anxiogenic stimuli: possible involvement of the endocannabinoid and endovanilloid systems.

Authors: Micale V, Cristino L, Tamburella A, Petrosino S, Leggio GM, Drago F, Di Marzo V Dopamine and the endocannabinoids, anandamide and 2-arachidonoylglycerol, interact at several levels in the brain, with the involvement of both cannabinoid CB(1) receptors and transient receptor potential vanilloid type-1 (TRPV1) channels (which are alternative anandamide receptors). Using pharmacological, immunohistochemical and analytical approaches, we investigated the response of dopamine D(3) receptor null (D3R((-/-))) mice in models of epilepsy and anxiety, in relation to their brain endocannabinoid and endovanilloid tone. Compared to wild type mice, D3R((-/-)) mice exhibited a delayed onset of clonic seizures, enhanced survival time, reduced mortality rate and more sensitivity to anticonvuls...

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