34 results on '"Dar DE"'
Search Results
2. Neuroactive steroids: their mechanism of action and their function in the stress response
- Author
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Dar De and Zinder O
- Subjects
medicine.medical_specialty ,Neuroactive steroid ,Physiology ,medicine.drug_class ,GABAA receptor ,medicine.medical_treatment ,Pharmacology ,Anxiolytic ,Steroid ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Mechanism of action ,Internal medicine ,medicine ,Chloride channel ,medicine.symptom ,Neurotransmitter ,Receptor - Abstract
Steroids are usually identified as genomic regulators, yet recently a body of evidence has accumulated demonstrating specific plasma membrane effects, as well as coordinative effects, of some steroids on both membrane and intracellular receptors. The resulting rapid (< 1 min) modulation of cellular activity has strongly suggested a non-genomic, and possibly modulatory, role for certain steroid compounds, and dramatic effects on membranes of excitable as well as other tissues have been demonstrated. Steroid synthesis and metabolism have been shown to exist in the CNS, and the effects have been seen in both the central and peripheral nervous systems. The major groups of neuroactive steroids, and their metabolites, have been progesterone, deoxycorticosterone, and some androgens, notably dihydroxyepiandrosterone (DHEA). These compounds show increased concentrations both in blood and in the brain following stress and they have also been associated with anxiolytic effects and antiepileptic activity. In the periphery, some of these compounds show remarkable inhibitory effects on the secretion of catecholamines and other neurotransmitters. The mechanism for the majority of the effects of these steroids is via their effect on receptor-mediated binding to ligand-gated ion channels. Activation of the GABA A receptor complex, resulting in the opening of its central chloride channel, is the major target of the neuroactive steroids, resulting in re-polarization of the plasma membrane and inhibition of further neuronal firing. The anxiolytic, anticonvulsant and sedative-hypnotic actions of these neuroactive steroids have resulted in their being used as therapeutic agents for the treatment of anxiety, epilepsy, insomnia, and possibly for the alteration of pain thresholds.
- Published
- 1999
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3. Trends in clinical reproductive medicine research: 10 years of growth
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Universitat Politècnica de València. Instituto de Gestión de la Innovación y del Conocimiento - Institut de Gestió de la Innovació i del Coneixement, Euroscreen, Wyeth, Actavis, Ferring, DAR DE ALTA. YA PEDIDO, Roche, Schering España, S.A., Finox Biotech, Aleixandre-Benavent, Rafael, Simón, Carlos, Fauser, Bart C. J. M., Universitat Politècnica de València. Instituto de Gestión de la Innovación y del Conocimiento - Institut de Gestió de la Innovació i del Coneixement, Euroscreen, Wyeth, Actavis, Ferring, DAR DE ALTA. YA PEDIDO, Roche, Schering España, S.A., Finox Biotech, Aleixandre-Benavent, Rafael, Simón, Carlos, and Fauser, Bart C. J. M.
- Abstract
Objective: To study the most important metrics of publication in the field of reproductive medicine over the decade 2003 2012 to aid in discerning the clinical, social, and epidemiologic implications of this relatively new but rapidly emerging area in medical sciences. Design: Bibliometric analysis of most-cited publications from Web of Science databases. Main Outcome Measure(s): Most productive and frequently cited investigators, institutions, and countries and specific areas of research, scientific collaborations, and comparison of the growth of reproductive medicine research compared with other areas of medical investigation such as obstetrics and gynecology and related science categories. Result(s): We found that 90 investigators with more than 1,000 citations had jointly published 4,010 articles. A continued rise in the impact factor of reproductive medicine journals was seen. The number of publications in reproductive medicine grew more rapidly compared with other science categories. Presently 22% of highly cited articles in reproductive medicine research are published in journals belonging to science categories outside reproductive medicine. The most-cited study groups are situated in the Netherlands, Belgium, Spain, the United States, and the United Kingdom, and collaborative studies have been increasing. Conclusion(s): Reproductive medicine research and subsequent clinical development have attained scientific growth and maturity. High-quality research is increasingly being published in high-impact journals. The increase in (inter)national collaborations seems to be key to the field's success.
- Published
- 2015
4. British Association of Dermatologists national clinical audit on the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults.
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Tasker F, Smith SP, Mohd Mustapa MF, and de Berker DAR
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- Humans, Adult, United Kingdom, Male, Female, Middle Aged, Clinical Audit, Aged, Severity of Illness Index, Young Adult, Dermatology standards, Aged, 80 and over, Stevens-Johnson Syndrome therapy, Stevens-Johnson Syndrome diagnosis, Practice Guidelines as Topic
- Abstract
Background: UK guidelines for managing adults with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), published by the British Association of Dermatologists (BAD) in 2016, outline a set of audit standards., Objectives: To audit current management of SJS/TEN in adults against standards in the BAD guidelines., Methods: BAD members were invited to submit data on five consecutive adults with SJS/TEN per department over an 8-week period in 2022., Results: Thirty-nine dermatology centres in the UK (29%) participated, and data for 147 adults with SJS/TEN were collected. Within 24 h of the diagnosis being made or suspected, the following were documented, per 147 submitted cases: Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) for 76 (52%), list of medications for 113 (77%) and timelines for commencement/alterations of medications for 104 (71%). The initial assessment was documented of the eyes by an ophthalmologist in 71 (48%), of the mouth in 130 (88%), of the genital skin in 103 (70%) and of the urinary tract in 93 (63%). During the first 10 days after a suspected or confirmed diagnosis of SJS/TEN, daily assessments of the mouth were documented in 26 of 147 cases (18%), of the eyes in 12 (8%), and of the urinary tract and genital skin in 14 (10%). At discharge, a drug was declared to be the cause of SJS/TEN for 130 of 147 cases (88%), while 9 (6%) were thought to be secondary to infection. Eleven of 147 (8%) had no response to this question. Documentation regarding advice was present on avoidance of the culprit drug in 76 of 130 declared SJS/TEN cases (58%), and on requesting a MedicAlert® bracelet/amulet in 9 of the 147 cases (6%)., Conclusions: This audit suggests that a clinical review checklist might be needed to enable colleagues to maintain standards outlined in the guidelines, including documentation of SCORTEN, daily assessments of mucosal areas, and advice to avoid culprit drug(s) and to request a MedicAlert® bracelet/amulet., (© British Association of Dermatologists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
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5. Evaluation of kernel low-rank compressed sensing in preclinical diffusion magnetic resonance imaging.
- Author
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de Souza DAR, Mathieu H, Deloulme JC, and Barbier EL
- Abstract
Compressed sensing (CS) is widely used to accelerate clinical diffusion MRI acquisitions, but it is not widely used in preclinical settings yet. In this study, we optimized and compared several CS reconstruction methods for diffusion imaging. Different undersampling patterns and two reconstruction approaches were evaluated: conventional CS, based on Berkeley Advanced Reconstruction Toolbox (BART-CS) toolbox, and a new kernel low-rank (KLR)-CS, based on kernel principal component analysis and low-resolution-phase (LRP) maps. 3D CS acquisitions were performed at 9.4T using a 4-element cryocoil on mice (wild type and a MAP6 knockout). Comparison metrics were error and structural similarity index measure (SSIM) on fractional anisotropy (FA) and mean diffusivity (MD), as well as reconstructions of the anterior commissure and fornix. Acceleration factors (AF) up to 6 were considered. In the case of retrospective undersampling, the proposed KLR-CS outperformed BART-CS up to AF = 6 for FA and MD maps and tractography. For instance, for AF = 4, the maximum errors were, respectively, 8.0% for BART-CS and 4.9% for KLR-CS, considering both FA and MD in the corpus callosum. Regarding undersampled acquisitions, these maximum errors became, respectively, 10.5% for BART-CS and 7.0% for KLR-CS. This difference between simulations and acquisitions arose mainly from repetition noise, but also from differences in resonance frequency drift, signal-to-noise ratio, and in reconstruction noise. Despite this increased error, fully sampled and AF = 2 yielded comparable results for FA, MD and tractography, and AF = 4 showed minor faults. Altogether, KLR-CS based on LRP maps seems a robust approach to accelerate preclinical diffusion MRI and thereby limit the effect of the frequency drift., Competing Interests: EB was a consultant at Bruker BioSpin. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 de Souza, Mathieu, Deloulme and Barbier.)
- Published
- 2023
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6. Treating early postnatal circuit defect delays Huntington's disease onset and pathology in mice.
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Braz BY, Wennagel D, Ratié L, de Souza DAR, Deloulme JC, Barbier EL, Buisson A, Lanté F, and Humbert S
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- Animals, Disease Models, Animal, Humans, Mice, Mice, Transgenic, Brain abnormalities, Huntingtin Protein genetics, Huntington Disease embryology, Huntington Disease genetics, Nerve Net abnormalities, Neurogenesis genetics, Synapses physiology
- Abstract
Recent evidence has shown that even mild mutations in the Huntingtin gene that are associated with late-onset Huntington's disease (HD) disrupt various aspects of human neurodevelopment. To determine whether these seemingly subtle early defects affect adult neural function, we investigated neural circuit physiology in newborn HD mice. During the first postnatal week, HD mice have less cortical layer 2/3 excitatory synaptic activity than wild-type mice, express fewer glutamatergic receptors, and show sensorimotor deficits. The circuit self-normalizes in the second postnatal week but the mice nonetheless develop HD. Pharmacologically enhancing glutamatergic transmission during the neonatal period, however, rescues these deficits and preserves sensorimotor function, cognition, and spine and synapse density as well as brain region volume in HD adult mice.
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- 2022
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7. Simulation of Organic Liquid Product Deoxygenation through Multistage Countercurrent Absorber/Stripping Using CO 2 as Solvent with Aspen-HYSYS: Process Modeling and Simulation.
- Author
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Junior MRDS, Costa EC, Ferreira CC, Bernar LP, da Silva MP, de Andrade Mâncio A, Santos MC, da Mota SAP, de Castro DAR, Junior SD, Borges LEP, Araújo ME, and Machado NT
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- Computer Simulation, Palm Oil, Solvents, Carbon Dioxide, Hydrocarbons
- Abstract
In this work, the deoxygenation of organic liquid products (OLP) obtained through the thermal catalytic cracking of palm oil at 450 °C, 1.0 atmosphere, with 10% (wt.) Na
2 CO3 as a catalyst, in multistage countercurrent absorber columns using supercritical carbon dioxide (SC-CO2 ) as a solvent, with an Aspen-HYSYS process simulator, was systematically investigated. In a previous study, the thermodynamic data basis and EOS modeling necessary to simulate the deoxygenation of OLP was presented. This work addresses a new flowsheet, consisting of 03 absorber columns, 10 expansions valves, 10 flash drums, 08 heat exchanges, 01 pressure pump, and 02 make-ups of CO2 , aiming to improve the deacidification of OLP. The simulation was performed at 333 K, 140 bar, and (S/F) = 17; 350 K, 140 bar, and (S/F) = 38; 333 K, 140 bar, and (S/F) = 25. The simulation shows that 81.49% of OLP could be recovered and that the concentrations of hydrocarbons in the extracts of absorber-01 and absorber-02 were 96.95 and 92.78% (wt.) on a solvent-free basis, while the bottom stream of absorber-03 was enriched in oxygenated compounds with concentrations of up to 32.66% (wt.) on a solvent-free basis, showing that the organic liquid products (OLP) were deacidified and SC-CO2 was able to deacidify the OLP and obtain fractions with lower olefin contents. The best deacidifying condition was obtained at 333 K, 140 bar, and (S/F) = 17.- Published
- 2022
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8. British Association of Dermatologists National Clinical Audit on the Management of Hidradenitis Suppurativa in the UK.
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Hasan SB, Smith SP, Brain A, Mohd Mustapa MF, Cheung ST, Ingram JR, and de Berker DAR
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- Adalimumab therapeutic use, Anti-Infective Agents, Local therapeutic use, Anti-Inflammatory Agents therapeutic use, Body Mass Index, Dermatologic Agents therapeutic use, Guideline Adherence, Hidradenitis Suppurativa complications, Humans, Practice Guidelines as Topic, Quality of Life, Risk Factors, Severity of Illness Index, Smoking adverse effects, Tetracyclines therapeutic use, United Kingdom, Clinical Audit, Hidradenitis Suppurativa diagnosis, Hidradenitis Suppurativa drug therapy
- Abstract
Background: The first UK guidelines for the management of hidradenitis suppurativa (HS) were published by the British Association of Dermatologists (BAD) in 2018. The guidelines contained a set of audit criteria., Aim: To evaluate current HS management against the audit standards in the BAD guidelines., Methods: BAD members were invited to complete audit questionnaires between January and May 2020 for five consecutive patients with HS per department., Results: In total, 88 centres participated, providing data for 406 patients. Disease staging using the Hurley system and disease severity using a validated tool during follow-ups was documented in 75% and 56% of cases, respectively, while quality of life and pain were documented in 49% and 50% of cases, respectively. Screening for cardiovascular disease risk factors was as follows: smoking 75%, body mass index 27% and others such as lipids and diabetes 57%. Screening for depression and anxiety was performed in 40% and 25% of cases, respectively. Support for smokers or obese patients was documented in 35% and 23% of cases. In total, 182 patients were on adalimumab, of whom 68% had documentation of baseline disease severity, and 76% were reported as having inadequate response or contraindications to systemic treatments; 44% of patients continued on adalimumab despite having < 25% improvement in lesion count., Conclusion: UK dermatologists performed well against several audit standards, including documenting disease staging at baseline and smoking status. However, improvements are needed, particularly with regard to screening and management of comorbidities that could reduce the long-term complications associated with HS. A re-audit is required to evaluate changes in practice in the future., (© 2021 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)
- Published
- 2021
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9. Inflammatory nail conditions. Part 1: nail changes in psoriasis.
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Yesudian PD and de Berker DAR
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- Administration, Topical, Dermoscopy, Humans, Injections, Intralesional, Methotrexate therapeutic use, Nail Diseases diagnosis, Nail Diseases drug therapy, Psoriasis pathology, Steroids administration & dosage, Triamcinolone administration & dosage, Dermatologic Agents administration & dosage, Glucocorticoids administration & dosage, Nail Diseases etiology, Nails pathology, Psoriasis complications
- Abstract
Nail changes are visible in a variety of inflammatory dermatoses. The commonest dermatological condition with nail manifestations is chronic plaque psoriasis. This two-part article reviews the nail signs in psoriasis in Part 1, and the nail changes in cutaneous lichen planus and alopecia areata in Part 2. It provides a brief summary of the salient points in the clinical features, management and prognosis of these entities, with practical recommendations that may be beneficial to all dermatologists., (© 2020 British Association of Dermatologists.)
- Published
- 2021
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10. Inflammatory nail conditions. Part 2: nail changes in lichen planus and alopecia areata.
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Yesudian PD and de Berker DAR
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- Administration, Intravesical, Administration, Topical, Humans, Nail Diseases drug therapy, Prognosis, Steroids administration & dosage, Alopecia Areata complications, Lichen Planus complications, Nail Diseases etiology, Nails pathology
- Abstract
Nail changes are frequently seen in patients with cutaneous lichen planus and alopecia areata. This manuscript provides an updated overview on the clinical features, management and prognosis of both conditions. Searches of electronic databases PubMed and EMBASE were conducted and eligible articles were accessed. Practical management principles relevant to these two conditions are also included., (© 2020 British Association of Dermatologists.)
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- 2021
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11. A service evaluation between 2-week wait (2WW) skin cancer referrals via teledermatology and the standard face-to-face pathway at a teaching hospital.
- Author
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Hunt WTN, Ali L, Marder H, Sansom JE, and de Berker DAR
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- Adult, Biopsy statistics & numerical data, Dermatology trends, General Practitioners standards, Hospitals, Teaching standards, Humans, Photography methods, Reference Standards, Skin Neoplasms diagnosis, Skin Neoplasms epidemiology, Surveys and Questionnaires, Time Factors, Dermatology statistics & numerical data, Referral and Consultation statistics & numerical data, Remote Consultation instrumentation, Skin Neoplasms pathology
- Published
- 2020
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12. National audit on the management of bullous pemphigoid.
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Smith H, Mohd Mustapa MF, Cheung ST, and de Berker DAR
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- Clinical Audit, Comorbidity, Documentation statistics & numerical data, Fluorescent Antibody Technique, Humans, Patient Satisfaction, Practice Guidelines as Topic, United Kingdom, Adrenal Cortex Hormones therapeutic use, Guideline Adherence statistics & numerical data, Pemphigoid, Bullous diagnosis, Pemphigoid, Bullous drug therapy
- Abstract
Background: Bullous pemphigoid (BP) is an autoimmune, subepidermal, blistering condition that typically affects elderly people., Aim: To undertake a national clinical audit based on standards derived from the British Association of Dermatologists (BAD) clinical guidelines on the management of BP., Methods: In 2018, BAD members were invited to submit data for five consecutive adults with BP per centre, who had been under hospital supervision for at least 12 months, in a national audit over an 11-week period., Results: In total, 123 responders from 120 hospitals provided data for 524 cases. Diagnosis was made either clinically (10.7%; 56 of 524) or through histology with direct immunofluorescence (41.6%; 218 of 524), indirect immunofluorescence (10.3%; 54 of 524) or both (37.4%; 196 of 524). Most patients had very mild baseline disease (63.9%; 225 of 352) with 21.9% (77 of 352) considered mild, 9.8% (31 of 352) moderate and 5.4% (19 of 352) severe. Documentation of diabetes, glycated haemoglobin (HbA1c), blood pressure and hypertension was available for 54.1% (283 of 523), 51% (267 of 524), 44.2% (231 of 522) and 61.5% (321 of 522) of cases, respectively. Oral corticosteroids were commenced in 85.5% (448 of 524) of patients, with 38.4% (172 of 448) of these having documented risk of osteoporosis; data regarding prescription of bone-protection therapies were available for 99.7% (447 of 448) of cases, with 75.6% (338 of 447) of these having a bone-protection prescription. Patient satisfaction was documented in 59.3% (310 of 523) of cases. Systemic treatment was commenced in 95.9% (502 of 524) of cases during the 12-month assessment period, with baseline blood test and follow-up data available for 96.6% (485 of 502) and 95.6% (480 of 502), respectively. Documentation of baseline blood tests was available for 87.4% (424 of 485) of cases, with follow-up tests recorded in 69.8% (335 of 480)., Conclusion: Overall, compliance with elements of documentation was moderate or low, whereas standards pertaining to direct care were high., (© 2019 British Association of Dermatologists.)
- Published
- 2020
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13. British Association of Dermatologists (BAD) National Audit on Non-Melanoma Skin Cancer Excision 2016 in collaboration with the Royal College of Pathologists.
- Author
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Keith DJ, Bray AP, Brain A, Mohd Mustapa MF, Barrett HE, Lane S, Emmerich M, Jakes A, Barrett PD, and de Berker DAR
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- Carcinoma, Basal Cell surgery, Carcinoma, Squamous Cell surgery, Clinical Audit, Dermatologic Surgical Procedures statistics & numerical data, Margins of Excision, Skin Neoplasms diagnosis, Skin Neoplasms pathology, Societies, Medical, United Kingdom, Dermatologists, Pathologists, Practice Patterns, Physicians' statistics & numerical data, Skin Neoplasms surgery
- Abstract
Background: We conducted a re-audit of the surgical practice of UK dermatologists for the treatment of nonmelanoma skin cancer and examined changes with reference to our previous audit in 2014. The audit was supplemented by a detailed assessment of completeness of the histopathology reports for each tumour., Methods: UK dermatologists collected data on 10 consecutive nonmicrographic excisions for basal cell carcinoma (BCC) and 5 for squamous cell carcinoma (SCC). Data were collected on site, preoperative diagnosis, histological diagnosis, proximity to previous scars, and histological deep and peripheral margins., Results: In total, 222 responses were received from 135 centres, reporting on 3290 excisions. Excisions from the head and neck accounted for 56.7% of cases. Tumour diameter (mean ± SD) was 11.4 ± SD 7.1 mm (maximum size 100 mm) and 97% of cases were primary excisions. BCCs and SCCs respectively accounted for 65.7% and 26.8% of total cases. Of the suspected BCCs and SCCs, 95.8% and 80.4%, respectively, were confirmed histologically. All margins for any tumour were clear in 97.0% of cases, and complication rate in the audit was < 1%. Of the 2864 histology reports evaluated, only 706 (24.6%) contained all core data items; 95% of these were structure (synoptic) reports. Commonly omitted items were level of invasion, risk and T stage, which were absent from 35.7%, 64.2% and 44.1% of reports, respectively., Conclusions: Diagnostic accuracy and complete excision rates remain high. Complication rates may be under-reported owing to lack of follow-up. Histopathology reporting has a greater chance of being complete if reports are generated on a field-based platform (synoptic reporting)., (© 2019 British Association of Dermatologists.)
- Published
- 2020
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14. Case 2: A 2-month-old Girl with Liver Failure and a Brother with Tyrosinemia Type I.
- Author
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Tal G, Dar DE, Almashanu S, Korman SH, and Dumin E
- Subjects
- Amino Acids blood, Calcium-Binding Proteins metabolism, Citrullinemia complications, Citrullinemia diet therapy, Diagnosis, Differential, Female, Humans, Infant, Liver Failure genetics, Male, Organic Anion Transporters metabolism, Siblings, Tyrosinemias diagnosis, Citrullinemia diagnosis, Liver Failure etiology
- Published
- 2019
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15. Argininemia, Hyperornithinemia, and 3-Hydroxyisovaleric Aciduria.
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Tal G, Dar DE, Idin A, Korman SH, and Dumin E
- Subjects
- Amino Acid Metabolism, Inborn Errors complications, Crohn Disease complications, Humans, Hyperargininemia complications, Male, Middle Aged, Amino Acid Metabolism, Inborn Errors diagnosis, Hyperargininemia diagnosis, Ornithine blood, Valerates urine
- Published
- 2018
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16. Atherogenicity of amino acids in the lipid-laden macrophage model system in vitro and in atherosclerotic mice: a key role for triglyceride metabolism.
- Author
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Rom O, Grajeda-Iglesias C, Najjar M, Abu-Saleh N, Volkova N, Dar DE, Hayek T, and Aviram M
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- Amino Acids blood, Amino Acids pharmacology, Animals, Atherosclerosis drug therapy, CD36 Antigens metabolism, Cholesterol metabolism, Diacylglycerol O-Acyltransferase metabolism, Lipid Metabolism drug effects, Lipid Peroxidation drug effects, Lipoproteins, VLDL metabolism, Macrophages drug effects, Macrophages metabolism, Male, Mice, Knockout, ApoE, Receptors, LDL metabolism, Scavenger Receptors, Class B metabolism, Sterol Regulatory Element Binding Protein 1 metabolism, Amino Acids metabolism, Atherosclerosis metabolism, Macrophages pathology, Triglycerides metabolism
- Abstract
Atherosclerosis-related research has focused mainly on the effects of lipids on macrophage foam cell formation and atherogenesis, whereas the role of amino acids (AAs) was understudied. The current study aimed to identify anti- or pro-atherogenic AA in the macrophage model system and to elucidate the underlying metabolic and molecular mechanisms. J774A.1 cultured macrophages were treated with increasing concentrations of each 1 of the 20 AAs. Macrophage atherogenicity was assessed in terms of cellular toxicity, generation of reactive oxygen species (ROS) and cellular cholesterol or triglyceride content. At nontoxic concentrations (up to 1 mM), modest effects on ROS generation or cholesterol content were noted, but six specific AAs significantly affected macrophage triglyceride content. Glycine, cysteine, alanine and leucine significantly decreased macrophage triglyceride content (by 24%-38%), through attenuated uptake of triglyceride-rich very low-density lipoprotein (VLDL) by macrophages. In contrast, glutamate and glutamine caused a marked triglyceride accumulation in macrophages (by 107% and 129%, respectively), via a diacylglycerol acyltransferase-1 (DGAT1)-dependent increase in triglyceride biosynthesis rate with a concurrent maturation of the sterol regulatory element-binding protein-1 (SREBP1). Supplementation of apolipoprotein E-deficient (apoE
-/- ) mice with glycine for 40 days significantly decreased the triglyceride levels in serum and in peritoneal macrophages (MPMs) isolated from the mice (by 19%). In contrast, glutamine supplementation significantly increased MPM ROS generation and the accumulation of cholesterol and that of triglycerides (by 48%), via enhanced uptake of LDL and VLDL. Altogether, the present findings reveal some novel roles for specific AA in macrophage atherogenicity, mainly through modulation of cellular triglyceride metabolism., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2017
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17. Compliance with national guidelines on isotretinoin: where are we 2 years since the last audit? Results of the National Isotretinoin Re-Audit 2014.
- Author
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Exton LS, Cheung ST, Brain AG, Mohd Mustapa MF, and de Berker DAR
- Abstract
Background: In 2010, the British Association of Dermatologists (BAD) published clinical guidelines for the safe introduction and continued use of isotretinoin in patients with acne in the UK. The BAD provides UK dermatologists with a facility for national audit, and it undertook an audit on compliance with these guidelines in 2012., Aim: To determine current clinical practices relating to use of isotretinoin among dermatologists in the UK (including geographical variations) as measured against BAD standards, and to ascertain any improvement since the 2012 audit., Methods: The 2012 isotretinoin audit proforma was used, with additional questions on clinical setting, complaints and litigation. A web-based survey tool was used for data entry and submission, with email invitation to working, UK-based BAD members (n = 1226) in December 2013 and weekly reminders during the 8.5-week data collection period. Responders were requested to enter data for the three most recent consecutive patients (including one male and one female patient) who had completed treatment within the previous 6 months., Results: In total, 338 (27.6%) respondents provided data on 1013 patients. Serum lipids were checked in 93.4% of patients and documentation of mental health and/or mood state was recorded in 82.1%. Regarding the Pregnancy Prevention Programme (PPP), 91.6% of female patients of childbearing potential had signed the PPP information form, while 93.3% who had followed the PPP had taken pregnancy tests both before and during treatment, and 54.7% had taken a pregnancy test 5 weeks post-treatment., Conclusion: Overall, there is currently good compliance with standards. Certain aspects of care that are less frequently preformed, such as pregnancy testing post-treatment, are highlighted., (© 2017 British Association of Dermatologists.)
- Published
- 2017
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18. Severe traumatic brain injury and controlled hemorrhage in rats: quest for the optimal mean arterial blood pressure after whole fresh donor blood resuscitation.
- Author
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Brotfain E, Leibowitz A, Dar DE, Krausz MM, Shapira Y, Koyfman L, Klein M, Hess S, and Zlotnik A
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- Animals, Blood Transfusion, Brain Injuries complications, Disease Models, Animal, Male, Nervous System Diseases etiology, Nervous System Diseases physiopathology, Nervous System Diseases therapy, Rats, Rats, Inbred Lew, Shock complications, Shock physiopathology, Shock therapy, Trauma Severity Indices, Arterial Pressure, Brain Injuries physiopathology, Brain Injuries therapy, Resuscitation
- Abstract
Treatment of combined traumatic brain injury and hypovolemic shock poses a particular challenge due to the possible conflicting consequences. While restoring diminished volume is the treatment goal for hypovolemia, maintaining and adequate cerebral perfusion pressure and avoidance of secondary damage remain a treatment goal for the injured brain. Various treatment modalities have been proposed, but the optimal resuscitation fluid and goals have not yet been clearly defined. In this study, we investigate the physiological and neurological outcomes in a rat model of combined traumatic brain injury and hypovolemic shock, submitted to treatment with varying amounts of fresh blood. Forty-eight male Lewis rats were divided into control and treatment groups. Traumatic brain injury was inflicted by a free-falling rod on the exposed cranium. Hypovolemia was induced by controlled hemorrhage of 30% blood volume. Treatment groups were treated by fresh whole blood with varying volumes, reaching resuscitation goals of a mean arterial blood pressure (MAP) of 80, 100, and 120 mmHg at 15 min. Mean arterial blood pressure was assessed at 60 min and neurological outcomes and mortality in the subsequent 48 h. At 60 min, MAP was highest for the group resuscitated most aggressively. Neurological outcomes and mortality inversely correlated with the aggressiveness of resuscitation. In this study, we find that mild resuscitation with goals of restoring MAP to 80 mmHg (which is lower than baseline) provided best results when considering hemodynamic stability, survival, and neurological outcomes. An aggressive resuscitation may be detrimental, inducing processes that eventually cause a significant decrease in survival.
- Published
- 2012
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19. Moderate Ringer's lactate solution resuscitation yields best neurological outcome in controlled hemorrhagic shock combined with brain injury in rats.
- Author
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Dar DE, Soustiel JF, Zaaroor M, Brotfain EM, Leibowitz A, Shapira Y, Semenikhina L, Solopov A, and Krausz MM
- Subjects
- Animals, Brain metabolism, Brain physiopathology, Brain Injuries blood, Brain Injuries physiopathology, Lactic Acid blood, Male, Rats, Rats, Inbred Lew, Ringer's Lactate, Shock, Hemorrhagic blood, Shock, Hemorrhagic physiopathology, Brain Injuries therapy, Isotonic Solutions therapeutic use, Shock, Hemorrhagic therapy
- Abstract
Anesthetized rats were assigned to sham; brain injury (BI); controlled hemorrhagic shock (CHS); BI combined with CHS (combined injury [CI]); and CI groups resuscitated with 2.5 mL/kg Ringer's lactate solution (RL-2.5), 10 mL/kg RL (RL-10), or 40 mL/kg RL (RL-40). Brain injury was induced by applying 400 millibar negative pressure for 10 s through a hollow screw inserted into a 4.5-mm burr hole drilled into the left parietal region of the skull. Five minutes after BI, 30% of circulating blood volume was withdrawn for 10 min to induce CHS. One hour of fluid resuscitation commenced 20 min posthemorrhage. MAP, lactate, and base excess levels were significantly improved in the RL-40 group compared with all other hemorrhaged groups. The hematocrit level 1 h after resuscitation began was significantly lower in the RL-40 group (27.6% +/- 0.57%) than in all other groups. The RL-40 group had the worst neurological severity score 24 h postsurgery. MAP, lactate, and base excess levels were not significantly improved in the RL-2.5 group, however, the number of surviving neuronal cells in the perilesional brain region was significantly higher than in the CI or RL-40 groups. MAP, lactate, and base excess levels were significantly improved in the RL-10 group (P < 0.05). Mobility and the number of surviving neurons in the perilesional region of the brain were significantly better in the RL-10 group than in the CI or RL-40 groups (P < 0.05). Although massive fluid resuscitation yields preferable hemodynamic and metabolic outcomes, neurological outcomes are better after moderate fluid resuscitation for BI combined with controlled hemorrhagic shock.
- Published
- 2010
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20. Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis.
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Taliaz D, Stall N, Dar DE, and Zangen A
- Subjects
- Animals, Brain drug effects, Brain-Derived Neurotrophic Factor genetics, Brain-Derived Neurotrophic Factor metabolism, Bromodeoxyuridine metabolism, Cell Line, Depression physiopathology, Disease Models, Animal, Doublecortin Domain Proteins, Exploratory Behavior drug effects, Food Preferences drug effects, Glioma pathology, Humans, Locomotion drug effects, Locomotion physiology, Male, Maze Learning drug effects, Microinjections methods, Microtubule-Associated Proteins metabolism, Neurogenesis drug effects, Neuropeptides metabolism, RNA, Small Interfering pharmacology, Rats, Rats, Sprague-Dawley, Statistics, Nonparametric, Sucrose administration & dosage, Sweetening Agents administration & dosage, Swimming psychology, Transfection methods, Brain metabolism, Brain-Derived Neurotrophic Factor antagonists & inhibitors, Depression pathology, Depression therapy, Neurogenesis physiology, RNA, Small Interfering therapeutic use
- Abstract
Depression has been associated with reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. In addition, animal studies suggest an association between reduced hippocampal neurogenesis and depressive-like behavior. These associations were predominantly established based on responses to antidepressant drugs and alterations in BDNF levels and neurogenesis in depressive patients or animal models for depressive behavior. Nevertheless, there is no direct evidence that the actual reduction of the BDNF protein in specific brain sites can induce depressive-like behaviors or affect neurogenesis in vivo. Using BDNF knockdown by RNA interference and lentiviral vectors injected into specific subregions of the hippocampus we show that a reduction in BDNF expression in the dentate gyrus, but not the CA3, reduces neurogenesis and affects behaviors associated with depression. Moreover, we show that BDNF has a critical function in neuronal differentiation, but not proliferation in vivo. Finally, we found that a specific BDNF knockdown in the ventral subiculum induces anhedonic-like behavior. These findings provide substantial support for the neurotrophic hypothesis of depression and specify anatomical and neurochemical targets for potential antidepressant interventions. Moreover, the specific effect of BDNF reduction on neuronal differentiation has broader implications for the study of neurodevelopment and neurodegenerative diseases.
- Published
- 2010
- Full Text
- View/download PDF
21. Age-dependent effects of chronic stress on brain plasticity and depressive behavior.
- Author
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Toth E, Gersner R, Wilf-Yarkoni A, Raizel H, Dar DE, Richter-Levin G, Levit O, and Zangen A
- Subjects
- Aging, Analysis of Variance, Animals, Animals, Newborn, Behavior, Animal physiology, Brain-Derived Neurotrophic Factor metabolism, Bromodeoxyuridine metabolism, Disease Models, Animal, Exploratory Behavior physiology, Food Preferences physiology, Locomotion physiology, Male, Rats, Rats, Sprague-Dawley, Receptors, AMPA metabolism, Sucrose administration & dosage, Swimming, Brain pathology, Depression etiology, Neurogenesis physiology, Neuronal Plasticity physiology, Stress, Psychological complications, Stress, Psychological pathology
- Abstract
Exposure to chronic mild stress (CMS) is known to induce anhedonia in adult animals, and is associated with induction of depression in humans. However, the behavioral effects of CMS in young animals have not yet been characterized, and little is known about the long-term neurochemical effects of CMS in either young or adult animals. Here, we found that CMS induces anhedonia in adult but not in young animals, as measured by a set of behavioral paradigms. Furthermore, while CMS decreased neurogenesis and levels of brain-derived neurotrophic factor (BDNF) in the hippocampus of adult animals, it increased these parameters in young animals. We also found that CMS altered alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor GluR1 subunit levels in the hippocampus and the nucleus accumbens of adult, but not young animals. Finally, no significant differences were observed between the effects of CMS on circadian corticosterone levels in the different age groups. The substantially different neurochemical effects chronic stress exerts in young and adult animals may explain the behavioral resilience to such stress young animals possess.
- Published
- 2008
- Full Text
- View/download PDF
22. Dopamine uptake and cocaine binding mechanisms: the involvement of charged amino acids from the transmembrane domains of the human dopamine transporter.
- Author
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Dar DE, Metzger TG, Vandenbergh DJ, and Uhl GR
- Subjects
- Alanine genetics, Alanine metabolism, Amino Acid Substitution genetics, Animals, Arginine genetics, Arginine metabolism, Binding Sites genetics, Binding, Competitive, COS Cells, Chlorocebus aethiops, Cocaine analogs & derivatives, Dopamine Plasma Membrane Transport Proteins genetics, Glutamic Acid genetics, Glutamic Acid metabolism, Humans, Kinetics, Lysine genetics, Lysine metabolism, Mutation, Transfection, Tritium, Cocaine metabolism, Dopamine pharmacokinetics, Dopamine Plasma Membrane Transport Proteins metabolism
- Abstract
The wild type human dopamine transporter (DAT) and five DAT mutants were transfected into COS-7 cells and their ability to uptake dopamine or to bind cocaine was examine three days later. In each mutant, a single charged amino acid, located in areas that initial hydrophobic analysis had indicated were DAT transmembrane domains was substituted by alanine. Mutants used in this study were lysines 257 and 525 (termed K257A and K525A), arginines 283 and 521 (termed R283A and R521A), and glutamate 491 (termed E491A). Dopamine affinity was significantly enhanced in the K257A and R283A mutants, and the IC(50) for displacement of the radioactive cocaine analog 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (CFT) by cocaine was significantly elevated in the E491A mutant. All mutants displayed a reduction or complete loss of the maximal velocity (V(m)) of dopamine transport.
- Published
- 2006
- Full Text
- View/download PDF
23. Structure-activity relationship of trihexyphenidyl analogs with respect to the dopamine transporter in the on going search for a cocaine inhibitor.
- Author
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Dar DE, Thiruvazhi M, Abraham P, Kitayama S, Kopajtic TA, Gamliel A, Slusher BS, Carroll FI, and Uhl GR
- Subjects
- Carbonic Anhydrase Inhibitors chemistry, Carbonic Anhydrase Inhibitors pharmacology, Carbonic Anhydrases metabolism, Molecular Structure, Structure-Activity Relationship, Trihexyphenidyl chemistry, Cocaine antagonists & inhibitors, Dopamine Plasma Membrane Transport Proteins metabolism, Trihexyphenidyl analogs & derivatives, Trihexyphenidyl pharmacology
- Abstract
A series of trihexyphenidyl (THP) analogs were used to search for a derivative that could serve as a cocaine inhibitor. A compound that blocks binding of the cocaine analog carboxyfluorotropane (CFT), allows dopamine uptake and exhibits low side effects could serve as a good candidate for that purpose. All analogs were tested for the extent to which they inhibit CFT binding, dopamine uptake and n-methyl scopolamine (NMS) binding. Several structure-function relationships emerged. Methylation/halogenation of THP's benzene ring enhanced the compound's ability to block CFT binding in comparison to its ability to block dopamine uptake (5a-e). Replacement of the cyclohexyl ring with a benzene ring tended to create compounds that had lower affinities to the dopamine transporter (7b compared to THP, 7d compared to 5h, 7c compared to 8c) and modification of THP's piperidine ring tended to enhance affinity to the dopamine transporter (5f-h, 8a, 8c). One analog (5f) that showed little muscarinic activity indicating that it would probably have few side effects was investigated for its effects as an in vivo cocaine inhibitor. However, it showed few antagonistic effects in vivo. Nevertheless, this work greatly elucidates the structure-function relationships required for potential cocaine inhibitors and so lays out promising directions for future research.
- Published
- 2005
- Full Text
- View/download PDF
24. The interaction of methylphenidate and benztropine with the dopamine transporter is different than other substrates and ligands.
- Author
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Dar DE, Mayo C, and Uhl GR
- Subjects
- Amino Acid Sequence, Animals, Benztropine chemistry, Benztropine pharmacology, Binding Sites drug effects, Binding Sites physiology, COS Cells, Chlorocebus aethiops, Dopamine Plasma Membrane Transport Proteins, Dose-Response Relationship, Drug, Fishes, Ligands, Male, Membrane Glycoproteins chemistry, Membrane Glycoproteins genetics, Membrane Transport Proteins chemistry, Membrane Transport Proteins genetics, Methylphenidate chemistry, Methylphenidate pharmacology, Molecular Sequence Data, Nerve Tissue Proteins chemistry, Nerve Tissue Proteins genetics, Rats, Substrate Specificity drug effects, Substrate Specificity physiology, Benztropine metabolism, Membrane Glycoproteins metabolism, Membrane Transport Proteins metabolism, Methylphenidate metabolism, Nerve Tissue Proteins metabolism
- Abstract
A substantial body of evidence suggests that the dopamine transporter (DAT) is the principal site for cocaine-induced reward and euphoria. Interactions between the DAT and its substrates and ligands may therefore be of clinical relevance. The pharmacological characteristics of DAT compounds were compared in wild type (WT) and mutant DATs. The DAT mutants chosen for study were those with reduced binding and uptake activities (aspartic acid 79 mutated to alanine, termed D79A), reduced binding but normal uptake (tyrosine 251 mutated to alanine, termed Y251A; tyrosine 273 mutated to alanine, termed, Y273A), and normal binding but reduced uptake (a double mutation: serines 356 and 359 mutated to alanine, termed S356,359A). The WT and mutant DATs were transfected into COS-7 cells, and their pharmacological activities were examined 3 days later. Different patterns of pharmacological activity emerged. GBR 12909, cocaine, and mazindol each showed reduced affinity for the Y251A and the Y273A mutants, but their affinity for the S356,359A mutant was similar to that of the WT DAT. d-Amphetamine, MPP+, and dopamine each showed reduced affinity for the S356,359A mutant. Benztropine and methylphenidate had a different effect. Relative to the WT DAT, they both showed reduced affinity for the S356,359A mutant when displacing radioactive carboxyfluorotropane (CFT) binding, but similar affinity when inhibiting radioactive dopamine uptake. These results indicate that methylphenidate and benztropine may interact with the DAT in a different fashion then other substrates and ligands.
- Published
- 2005
- Full Text
- View/download PDF
25. Behavioral analysis during the forced swimming test using a joystick device.
- Author
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Gersner R, Dar DE, Shabat-Simon M, and Zangen A
- Subjects
- Animals, Behavior, Animal drug effects, Drug Evaluation, Preclinical methods, Exercise Test instrumentation, Exercise Test methods, Extremities physiology, Male, Rats, Rats, Sprague-Dawley, Reproducibility of Results, Sensitivity and Specificity, Video Recording instrumentation, Video Recording methods, Antidepressive Agents administration & dosage, Behavior, Animal physiology, Computer Peripherals, Drug Evaluation, Preclinical instrumentation, Image Interpretation, Computer-Assisted instrumentation, Image Interpretation, Computer-Assisted methods, Swimming physiology, User-Computer Interface
- Abstract
The behavioral test described by Porsolt in 1977 for screening potential antidepressant drugs is extensively used both in basic research and in the pharmaceutical industry. The measured behavior is the immobility time during the swimming test (preformed in rodents), which decreases upon acute antidepressant treatment. Several research groups have suggested some modifications on the original Porsolt paradigm and its analysis. Nevertheless, there are still inaccuracies resulting from either undefined intermediate behaviors or from considering the movement of the whole body as one unit without analyzing the motion of the limbs. Herein, we propose a novel and simple scoring method, based on continuous measurement of the limbs motion, using a joystick, a computer screen and simple software. We validated the method, using antidepressant drugs and studied examples of false positives and false negatives of the traditional Porsolt paradigm. The proposed method is easy to use, it accounts for all range of movements and the analysis is relatively fast. Moreover, the results obtained using this analysis method show a normal Gaussian distribution in a population of rats (while the traditional Porsolt analysis does not) which allows selective breeding of 'motivated' and 'depressed' lines of animals.
- Published
- 2005
- Full Text
- View/download PDF
26. Catecholamine secretion from bovine adrenal chromaffin cells induced by the dextrorotatory isomer of anatoxin-a.
- Author
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Dar DE and Zinder O
- Subjects
- Adrenal Medulla cytology, Animals, Bacterial Toxins chemistry, Calcium metabolism, Calcium Channel Blockers pharmacology, Cattle, Chelating Agents pharmacology, Cyanobacteria Toxins, Dose-Response Relationship, Drug, Egtazic Acid pharmacology, In Vitro Techniques, Marine Toxins chemistry, Microcystins, Muscarinic Antagonists pharmacology, Neurotoxins chemistry, Nicotinic Agonists chemistry, Nicotinic Antagonists pharmacology, Stereoisomerism, Time Factors, Tropanes, Verapamil pharmacology, Adrenal Medulla metabolism, Bacterial Toxins pharmacology, Catecholamines metabolism, Chromaffin Cells metabolism, Marine Toxins pharmacology, Neurotoxins pharmacology, Nicotinic Agonists pharmacology
- Abstract
1. The nicotinic agonist (+)anatoxin-a was studied in acute preparations of adrenal chromaffin cells and was compared with other known stimulants in this system. 2. (+)Anatoxin-a was found to be a potent stimulant of catecholamine secretion with EC50=545.7 nM, which was 5.8 times as strong as nicotine (EC50=3,165 nM). (+)Anatoxin-a action was time dependent and saturable. 3. The pharmacological characteristics of (+)anatoxin-a were tested by using nicotinic and muscarinic antagonists (mecamylamine and atropine, respectively). Mecamylamine (1 microM) and atropine (100 microM) inhibited the secretion induced by (+)anatoxin-a (1 microM), as well as that induced by nicotine (10 microM), acetylcholine (10 microM and 100 microM) and oxotremorine-M (100 microM). 4. The calcium requirement for (+)anatoxin-a action was tested in comparison with the aforementioned stimulants. Addition of the calcium antagonist verapamil (10 microM) or the calcium chelator EGTA (3 mM) reduced all stimulants' action. 5. These results show that the (+)enantiomer of anatoxin-a is both dose and time dependent. Its action is mediated through the classical operation of the nicotinic acetylcholine receptor, by using calcium influx.
- Published
- 1998
- Full Text
- View/download PDF
27. Dopamine transporter mutants, small molecules, and approaches to cocaine antagonist/dopamine transporter disinhibitor development.
- Author
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Uhl G, Lin Z, Metzger T, and Dar DE
- Subjects
- Animals, Carrier Proteins metabolism, Cocaine chemistry, Dopamine metabolism, Dopamine Plasma Membrane Transport Proteins, Drug Design, Models, Molecular, Molecular Conformation, Mutagenesis, Site-Directed, Protein Conformation, Protein Structure, Secondary, Recombinant Proteins chemistry, Recombinant Proteins metabolism, Structure-Activity Relationship, Transfection, Carrier Proteins chemistry, Carrier Proteins genetics, Cocaine antagonists & inhibitors, Cocaine pharmacokinetics, Membrane Glycoproteins, Membrane Transport Proteins, Nerve Tissue Proteins
- Published
- 1998
- Full Text
- View/download PDF
28. Short term effect of steroids on catecholamine secretion from bovine adrenal medulla chromaffin cells.
- Author
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Dar DE and Zinder O
- Subjects
- Adrenal Medulla cytology, Adrenal Medulla drug effects, Animals, Cattle, Cell Separation, Chromaffin Cells drug effects, Ion Channels drug effects, Ion Channels metabolism, Kinetics, Nerve Tissue Proteins metabolism, Progesterone pharmacology, Adrenal Medulla metabolism, Catecholamines metabolism, Chromaffin Cells metabolism, Steroids pharmacology
- Abstract
Bovine chromaffin cells were used to examine neuronal modulation, as their function is similar to sympathetic post-ganglionic neurons. The effect of steroids on evoked catecholamine secretion from primary culture of bovine adrenal medullary cells was investigated. A wide range of progestins, androgens and estrogens was found to have a significant effect on catecholamine secretion induced by the natural neurotransmitter acetylcholine (ACh). The androgens (especially androstandione and androsterone), as a class were the most effective in inhibition of stimulated secretion, while the estrogens had little, to no, effect. Among all steroids tested, progesterone had the most significant effect, other progestins were less potent. Progesterone inhibited catecholamine secretion evoked by ACh, nicotine and oxotremorine-M in a dose-dependent manner with similar IC50 values in the microM range. It also blocked the secretion evoked by high potassium concentration (59 nM) or veratradine (100 microM), but no effect was seen on the secretion evoked by the calcium ionophore A-23187 (10 microM). Progesterone inhibition of ACh or oxotremorine-M stimulation was immediate and sustained. These results suggest that progesterone and other steroids might have a membrane effect probably acting through blockade of calcium influx necessary for the secretory response.
- Published
- 1997
- Full Text
- View/download PDF
29. Electroconvulsive therapy down-regulates platelet peripheral-type benzodiazepine receptors in medication-resistant major depressed patients.
- Author
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Weizman R, Karp L, Dar DE, Butin B, Hermesh H, Munitz H, and Gavish M
- Subjects
- Adult, Benzodiazepines administration & dosage, Benzodiazepines therapeutic use, Depressive Disorder drug therapy, Female, Humans, Male, Middle Aged, Blood Platelets physiology, Depressive Disorder therapy, Electroconvulsive Therapy, Receptors, GABA-A blood
- Published
- 1996
- Full Text
- View/download PDF
30. Strychnine affects catecholamine secretion from bovine adrenal medulla chromaffin cells.
- Author
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Dar DE and Zinder O
- Subjects
- Acetylcholine pharmacology, Animals, Calcium pharmacology, Cattle, Dose-Response Relationship, Drug, Nicotine pharmacology, Potassium pharmacology, Time Factors, Adrenal Medulla drug effects, Catecholamines metabolism, Chromaffin System drug effects, Strychnine pharmacology
- Abstract
The effect of strychnine on evoked release of catecholamines from a primary culture of bovine adrenal medullary cells was investigated. Strychnine at > 1 microM inhibited catecholamine release stimulated by 10 microM acetylcholine, or 10 microM nicotine, but not by excess K+ (59 mM), the sodium ionophore veratridine (100 microM) or the calcium ionophore A-23187 (10 microM). The inhibitory response elicited by exposure of the cells to strychnine was rapid (< 3 min) and competitive with acetylcholine. High concentrations of acetylcholine (1 mM) completely overcame this inhibition. Strychnine might be acting on a regulatory site of the nicotinic-cholinergic receptor, which is genetically similar to the strychnine-binding 48 KD subunit of the glycine receptor.
- Published
- 1995
- Full Text
- View/download PDF
31. Alteration of platelet benzodiazepine receptors by stress of war.
- Author
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Weizman R, Laor N, Karp L, Dagan E, Reiss A, Dar DE, Wolmer L, and Gavish M
- Subjects
- Anxiety Disorders blood, Depressive Disorder blood, Down-Regulation, Female, Humans, Hydrocortisone blood, Israel, Life Change Events, Male, Middle Aged, Stress, Psychological diagnosis, Up-Regulation, Blood Platelets chemistry, Receptors, GABA-A analysis, Stress, Psychological blood, Warfare
- Abstract
Mitochondrial benzodiazepine receptors play a major role in steroidogenesis. The authors determined plasma cortisol levels, platelet levels of mitochondrial benzodiazepine receptors, and anxiety and depression scores in 11 civilians exposed to the Persian Gulf war. The density of mitochondrial benzodiazepine receptors was 22% and 15% lower before and during the war, respectively, than 4 weeks after the end of the war. Relief of stress led to an increase in receptors, which correlated with the improvement in anxiety but not mood.
- Published
- 1994
- Full Text
- View/download PDF
32. "Peripheral" benzodiazepine receptor density is not altered by methylphenidate treatment in children with attention-deficit hyperactivity disorder.
- Author
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Weizman R, Dar DE, Landa S, Apter A, and Gavish M
- Abstract
ABSTRACT "Peripheral" benzodiazepine receptors (PBRs) are located in the central nervous system and the periphery, are involved in the release of dopamine, and are sensitive to agents active at the dopaminergic system. Because attention-deficit hyperactivity disorder (ADHD) is related to dysregulation of dopaminergic neurotransmission, and because benzodiazepines can potentially aggravate the symptoms of ADHD, we have assessed the possible involvement of PBRs in the pathophysiology and pharmacotherapy of ADHD. [(3)H]PK 11195 was used to label platelet PBRs. Platelet PBRs were measured in eight ADHD boys (aged 9-15 years) before and after 4 weeks of treatment with methylphenidate 10-20 mg/day. ADHD patients before treatment did not differ from age-matched healthy controls in [(3)H]PK 11195 binding values. Four weeks of methylphenidate treatment did not significantly affect platelet PBR density in children with ADHD, despite the beneficial clinical effects. These results do not support the involvement of the PBRs in the pathophysiology of ADHD or in the therapeutic effects of methylphenidate.
- Published
- 1993
- Full Text
- View/download PDF
33. The platelet benzodiazepine receptor is unaltered in obsessive-compulsive disorder.
- Author
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Weizman R, Hermesh H, Karp L, Dar DE, Munitz H, and Gavish M
- Subjects
- Adult, Blood Platelets drug effects, Clomipramine pharmacology, Female, Humans, Isoquinolines metabolism, Male, Middle Aged, Mitochondria drug effects, Mitochondria metabolism, Radioligand Assay, Receptors, GABA-A drug effects, Blood Platelets metabolism, Obsessive-Compulsive Disorder blood, Receptors, GABA-A metabolism
- Abstract
Mitochondrial benzodiazepine receptors (MBR) are sensitive to anxiety and stress. The aim of the present study was to investigate whether platelet MBR are altered in untreated obsessive-compulsive disorder (OCD) patients and whether chronic treatment with clomipramine (CMI) regulates these receptors. MBR were assessed in 13 drug-free OCD patients as compared with 15 healthy controls. Seven of the 13 patients were treated with CMI (200-300 mg/day). The density and affinity of the receptors to their ligand [3H]PK 11195 in OCD patients and controls were not affected by the CMI treatment despite the clinical improvement. It seems that, in contrast to generalized anxiety disorder, OCD is not associated with alterations in platelet benzodiazepine receptors.
- Published
- 1993
- Full Text
- View/download PDF
34. Platelet peripheral benzodiazepine receptors in repeated stress.
- Author
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Dar DE, Weizman A, Karp L, Grinshpoon A, Bidder M, Kotler M, Tyano S, Bleich A, and Gavish M
- Subjects
- Adolescent, Adult, Cell Membrane metabolism, Humans, Hydrocortisone blood, Isoquinolines metabolism, Male, Prolactin blood, Radioimmunoassay, Reference Values, Blood Platelets metabolism, Receptors, GABA-A metabolism, Stress, Physiological blood
- Abstract
[3H]PK 11195 binding to platelet membranes and plasma stress hormones were studied in soldiers at the beginning of a parachute training course, following 6 days of preparatory exercises, and after the fourth actual parachute jump. A slight reduction (15%; NS) in the number of peripheral benzodiazepine receptors (PBR) was detected at the end of the exercise period, prior to the first jump. Reduced (26%; P less than 0.05) density of PBR was observed immediately after the repeated actual jumps. Equilibrium dissociation constants were not affected by the stressful situation. Plasma cortisol and prolactin levels remained unaltered during the entire study period.
- Published
- 1991
- Full Text
- View/download PDF
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