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1.
Sci Justice ; 59(2): 117-124, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30798858

RESUMO

A comparison study of the effects of environmental conditions on the development of latent fingermarks on raptor feathers using green magnetic fluorescent powder was undertaken using both sebaceous loaded and natural fingermark deposits. Sparrowhawk feathers were stored in indoor conditions for 60 days (Study 1), and buzzard feathers were left exposed to two different environmental conditions (hidden and visible) for 21 days (Study 2), with developments made at regular ageing periods. In Study 1, latent fingermarks were successfully developed (Grade 1-4) on the indoor feathers up to 60 days after deposition - 98.6% of the loaded deposits and 85.3% for natural deposits. Under outdoor conditions in Study 2, both loaded and natural deposits were affected by environmental exposure. Latent fingermarks were successfully developed up to 14 days after deposition on the outdoor feathers, with some occasional recovery after 21 days. The visible feathers recorded 34.7% (loaded) and 16.4% (natural) successful developments (Grade 1-4), whereas the hidden feathers recorded 46.7% (loaded) and 22.2% (natural) successful developments, suggesting that protection from the environment helps to preserve latent fingermarks on the surface of a feather. Environmental exposure accelerated the deterioration of ridge detail and the number of successful developments.


Assuntos
Dermatoglifia , Plumas , Corantes Fluorescentes/química , Pós/química , Aves Predatórias , Animais , Conservação dos Recursos Naturais , Crime , Meio Ambiente , Ciências Forenses , Humanos , Fenômenos Magnéticos , Fatores de Tempo
2.
Phys Rev Lett ; 120(13): 132504, 2018 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-29694208

RESUMO

A new method to tag the barium daughter in the double-beta decay of ^{136}Xe is reported. Using the technique of single molecule fluorescent imaging (SMFI), individual barium dication (Ba^{++}) resolution at a transparent scanning surface is demonstrated. A single-step photobleach confirms the single ion interpretation. Individual ions are localized with superresolution (∼2 nm), and detected with a statistical significance of 12.9σ over backgrounds. This lays the foundation for a new and potentially background-free neutrinoless double-beta decay technology, based on SMFI coupled to high pressure xenon gas time projection chambers.

3.
Epidemiol Infect ; 146(8): 970-971, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29656723

RESUMO

An emerging recombinant norovirus GII.P16/GII.4 Sydney 2012 strain caused a gastroenteritis outbreak amongst attendees at a large health function in regional New South Wales, Australia. This was the third outbreak caused by the recombinant GII.P16/GII.4 Sydney 2012 strain in this region in 2017, which appears to be emerging as a common strain in the Hunter New England region.


Assuntos
Infecções por Caliciviridae/epidemiologia , Surtos de Doenças , Gastroenterite/epidemiologia , Norovirus/isolamento & purificação , Adulto , Idoso , Infecções por Caliciviridae/virologia , Feminino , Gastroenterite/virologia , Humanos , Masculino , Pessoa de Meia-Idade , New South Wales/epidemiologia , Norovirus/classificação
4.
Eur Phys J C Part Fields ; 84(5): 518, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38784120

RESUMO

Noble element time projection chambers are a leading technology for rare event detection in physics, such as for dark matter and neutrinoless double beta decay searches. Time projection chambers typically assign event position in the drift direction using the relative timing of prompt scintillation and delayed charge collection signals, allowing for reconstruction of an absolute position in the drift direction. In this paper, alternate methods for assigning event drift distance via quantification of electron diffusion in a pure high pressure xenon gas time projection chamber are explored. Data from the NEXT-White detector demonstrate the ability to achieve good position assignment accuracy for both high- and low-energy events. Using point-like energy deposits from 83mKr calibration electron captures (E∼45 keV), the position of origin of low-energy events is determined to 2 cm precision with bias <1mm. A convolutional neural network approach is then used to quantify diffusion for longer tracks (E≥1.5 MeV), from radiogenic electrons, yielding a precision of 3 cm on the event barycenter. The precision achieved with these methods indicates the feasibility energy calibrations of better than 1% FWHM at Qßß in pure xenon, as well as the potential for event fiducialization in large future detectors using an alternate method that does not rely on primary scintillation.

5.
Sci Justice ; 62(6): 691-695, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36400490

RESUMO

Flipped learning with the incorporation of certain elements of gamification aims to improve student engagement, motivation and attainment. In this study we present an analysis of two approaches used in consecutive years on two modules. A traditional flipped learning approach "standard learning" where material is released weekly online and there are supporting tutorials and an end of term assessment; and a "structured active learning" strategy where a more scaffolded approach is applied, requiring participation to progress. In this approach students' work on the virtual learning environment and in tutorials could be used to contribute towards their end of term assessment (no more than 10% of the module credit), connected to a learning outcome on the breadth or range of topics. Students received feedback in rubric form throughout the topic, to see their progression. It was found that for module 1, over 90% of the students had accessed the pre-released material by week 2 in the structured active learning approach while this level of engagement was only reached in week 5 using the standard approach. Participation in learning events was far better using the structured active learning approach when compared to the standard approach, for example rising from 40% to 78% in week 2. The second module, with a different cohort of students, followed similar trends with the active learning approach attracting higher levels of engagement and participation far earlier in the term. Following the increased engagement, the structured active learning approach was beneficial in assessment with improved grade profiles.


Assuntos
Educação a Distância , Aprendizagem Baseada em Problemas , Humanos , Retroalimentação
6.
Sci Justice ; 62(5): 644-656, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36336458

RESUMO

The surface structure of mint (as-issued) and handled polymer five pounds sterling banknotes was studied by atomic force microscopy and laser scanning confocal microscopy. A total of 1856 fingermarks on mint and handled banknotes from four different issuing banks (Bank of England, Bank of Scotland, Royal Bank of Scotland and Clydesdale Bank) were visualised with Vacuum Metal Deposition (VMD), Cyanoacrylate Fuming (CAF) and, on Clydesdale Bank notes, magnetic fluorescent powder. VMD was significantly more effective in developing fingermarks on handled banknotes, across all the banks studied, although effectiveness varied with issuing bank. For example, on handled Bank of England notes 45% of marks showed ridge detail with VMD development and 28% with CAF; for Bank of Scotland handled notes success rates were 17% with VMD and 1% with CAF. Microscopy of degraded banknotes showed the loss of intaglio printing and the formation of a cracked surface structure in the handled notes. These features can lead to the trapping of powder, or contaminants, increasing quantity of development agent in fingermark background between the ridges, decreasing contrast and decreasing performance of powder-based fingermark development techniques. These same features can restrict the migration of components of the fingermark, preventing fingermarks degrading through spread of material and thus reducing potential formation of empty prints, so that VMD development is not adversely affected.


Assuntos
Dermatoglifia , Polímeros , Humanos , Pós , Cianoacrilatos/química , Vácuo , Metais
7.
Sci Justice ; 50(3): 150-5, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20709276

RESUMO

Titanium dioxide based powders are regularly used in the development of latent fingerprints on dark surfaces. For analysis of prints on adhesive tapes, the titanium dioxide can be suspended in a surfactant and used in the form of a powder suspension. Commercially available products, whilst having nominally similar composition, show varying levels of effectiveness of print development, with some powders adhering to the background as well as the print. X-ray fluorescence (XRF), analytical transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and laser particle sizing of the fingerprint powders show TiO(2) particles with a surrounding coating, tens of nanometres thick, consisting of Al and Si rich material, with traces of sodium and sulphur. Such aluminosilicates are commonly used as anti-caking agents and to aid adhesion or functionality of some fingerprint powders; however, the morphology, thickness, coverage and composition of the aluminosilicates are the primary differences between the white powder formulations and could be related to variation in the efficacy of print development.


Assuntos
Adesivos , Dermatoglifia , Nanotecnologia , Corantes , Humanos , Microscopia Eletrônica de Transmissão , Pós , Espectrometria por Raios X , Titânio
8.
Ann Clin Biochem ; 46(Pt 2): 165-6, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19176644

RESUMO

BACKGROUND: The National Academy of Clinical Biochemistry (NACB) recommends that the presence of a variant or modified haemoglobin be considered when any HbA1c result is below the lower limit of the reference interval or >or=15%. In those instances where a variant haemoglobin is suspected, repeat measurement using an alternative method is the usual course of action. In the present study, we undertook to determine the impact of this guideline on our identification of variant and modified haemoglobins. METHODS: All requests for HbA1c estimation received over a 32-month period, and which gave a result of <4% or >15% were re-analysed by a different method and the results compared. RESULTS: Over the 32-month period, 94 samples with a HbA1c result of <4% or >or=15% were identified. Of these, 80 were re-analysed using a different method. No chromatographic abnormalities were seen and there were no significant differences between the results obtained using the two methods. CONCLUSIONS: No variant or modified haemoglobins were identified in this study and this observation is likely to be representative of the ethnic makeup of our patient population. On the basis of this finding, we recommend that laboratories consider local factors when deciding whether to comply with the NACB guidelines.


Assuntos
Técnicas de Laboratório Clínico/normas , Hemoglobinas Glicadas/análise , Hemoglobinopatias/diagnóstico , Cromatografia por Troca Iônica , Feminino , Hemoglobinas Anormais/análise , Humanos , Imunoensaio , Guias de Prática Clínica como Assunto
9.
Int J Clin Pract ; 63(1): 170-2, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19125999

RESUMO

AIM: Long-term lithium therapy is associated with hypercalcaemia in 10-60% of patients, but unlike creatinine and thyroid stimulating hormone (TSH), monitoring by general practitioners of serum calcium for patients on lithium is not a requirement of the Qualities and Outcomes Framework (QOF) of 2004. We aimed to assess requesting patterns for serum calcium in patients on long-term lithium therapy and subsequent diagnosis of hypercalcaemia. METHODS: We identified 100 patients on long-term lithium therapy, as indicated by regular monitoring of lithium levels in our laboratory for at least 1 year. We determined how many of these patients had had serum calcium analysed, noting the assay date, concentration, source of request and clinical details stated. RESULTS: Forty-three out of hundred patients had serum calcium analysed during the course of their treatment including 28 in the previous 15 months. Twenty-one patients had serum calcium analysed by their GP, including 12 in the previous 15 months. Hypercalcaemia was diagnosed in five patients (11.6%). CONCLUSION: A significant proportion of patients in whom calcium was checked developed hypercalcaemia on lithium therapy. However, only 12% of the patients had serum calcium requested by their GP in the previous 15 months, which compares unfavourably with TSH and creatinine, for which monitoring approaches 100%. We recommend that serum calcium be checked every 15 months along with creatinine and TSH. This might be achieved by incorporating appropriate targets into the QOF, or by reflective or reflex adding-on of calcium to lithium specimens from patients who have not had calcium analysed in the previous 15 months.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Cálcio/sangue , Hipercalcemia/induzido quimicamente , Compostos de Lítio/efeitos adversos , Humanos , Compostos de Lítio/uso terapêutico , Avaliação de Resultados em Cuidados de Saúde
10.
Sci Rep ; 9(1): 15097, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641206

RESUMO

The nature of the neutrino is one of the major open questions in experimental nuclear and particle physics. The most sensitive known method to establish the Majorana nature of the neutrino is detection of the ultra-rare process of neutrinoless double beta decay. However, identification of one or a handful of decay events within a large mass of candidate isotope, without obfuscation by backgrounds is a formidable experimental challenge. One hypothetical method for achieving ultra- low-background neutrinoless double beta decay sensitivity is the detection of single 136Ba ions produced in the decay of 136Xe ("barium tagging"). To implement such a method, a single-ion-sensitive barium detector must be developed and demonstrated in bulk liquid or dry gaseous xenon. This paper reports on the development of two families of dry-phase barium chemosensor molecules for use in high pressure xenon gas detectors, synthesized specifically for this purpose. One particularly promising candidate, an anthracene substituted aza-18-crown-6 ether, is shown to respond in the dry phase with almost no intrinsic background from the unchelated state, and to be amenable to barium sensing through fluorescence microscopy. This interdisciplinary advance, paired with earlier work demonstrating sensitivity to single barium ions in solution, opens a new path toward single ion detection in high pressure xenon gas.

12.
Placenta ; 28(11-12): 1174-81, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17714779

RESUMO

BACKGROUND/OBJECTIVES: Mesenchymal stem cells (MSC) can be isolated from human placenta and have the potential to contribute to the immunosuppressive properties of placental tissue. The objectives of this study were to investigate the phenotype and differentiation characteristics of MSC derived from human placenta and evaluate the role of the tryptophan degrading enzyme, indoleamine 2,3 dioxygenase (IDO), in mediating their immunosuppressive affect. METHODS: MSC obtained from placental tissue (pMSC) were characterised using flow cytometry and tested for multipotency by determining differentiation into all mesenchymal lineages. The immunosuppressive properties of pMSC were tested in allogeneic mixed lymphocyte reactions and IDO expression and activity were measured by semi-quantitative real-time PCR and HPLC respectively. RESULTS: Multipotent stem cells were isolated from placenta and displayed chondrogenic, osteogenic and limited adipogenic differentiation. Cell surface antigen expression of pMSC was similar to bone marrow MSC (bMSC) with lack of the haematopoietic and common leukocyte markers (CD34, CD45), and expression of adhesion (CD29, CD166, CD44) and stem cell (CD 90, CD105, CD73) markers. Placental MSC were suppressive of allogeneic T-cell proliferation, an effect which was intensified following IDO induction by IFN-gamma. Replenishment of tryptophan or treatment with the IDO-blocker, 1-methyl-tryptophan (1-MT), attenuated the immunosuppressive action of pMSC. CONCLUSIONS: These results suggest that placental tissue contains MSC, which are phenotypically and functionally similar to bMSC, and that IDO is a key mediator of their immunosuppressive effect. Further investigation is needed to determine if pMSC function effects pregnancy outcome.


Assuntos
Tolerância Imunológica/fisiologia , Indolamina-Pirrol 2,3,-Dioxigenase/fisiologia , Células-Tronco Mesenquimais/fisiologia , Placenta/enzimologia , Diferenciação Celular/fisiologia , Células Cultivadas , Indução Enzimática/fisiologia , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Interferon gama/farmacologia , Isoantígenos/imunologia , Teste de Cultura Mista de Linfócitos , Células-Tronco Mesenquimais/efeitos dos fármacos , Placenta/citologia , Placenta/imunologia , Gravidez , RNA Mensageiro/biossíntese , Linfócitos T/imunologia
13.
Forensic Sci Int ; 275: 44-56, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28292657

RESUMO

Latent fingermark morphology was examined over a period of approximately two months. Variation in topography was observed with atomic force microscopy and the expansion of the fingermark occurred in the form of the development of an intermediate area surrounding the main fingermark ridge. On an example area of a fingermark on silicon, the intermediate region exists as a uniform 4nm thick deposit; on day 1 after deposition this region extends approximately 2µm from the edge of the main ridge deposit and expands to a maximum of ∼4µm by day 23. Simultaneously the region breaks up, the integrity is compromised by day 16, and by day 61 the area resembles a series of interconnected islands, with coverage of approximately 60%. Observation of a similar immediate area and growth with time on surfaces such as Formica was possible by monitoring the mechanical characteristics of the fingermark and surfaces though phase contrast in tapping mode AFM. The presence of this area may affect fingermark development, for example affecting the gold distribution in vacuum metal deposition. Further study of time dependence and variation with donor may enable assessment of this area to be used to evaluate the age of fingermarks.


Assuntos
Dermatoglifia , Microscopia de Força Atômica , Silício , Humanos , Processamento de Imagem Assistida por Computador , Fatores de Tempo
15.
Eur Psychiatry ; 21(4): 233-7, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16762533

RESUMO

OBJECTIVE: Current and past research strongly indicates a high prevalence of schizophrenia in the lower class in the USA and other stratified societies. To date, no study has tested for a connection between type of schizophrenia and socioeconomic status (SES). We tested for an interrelationship between schizophrenic subtype, SES and race. METHODS: Positive and negative symptom scales were used to evaluate 436 schizophrenic patients at a state hospital in the USA. All patients were also diagnosed by DSM standards. Social class of origin was assessed by the Occupational Classification Distributions of the U.S. Bureau of the Census. Multivariate analysis was conducted with the likelihood ratio chi-square. RESULTS: We uncovered a distinct propensity for deficit schizophrenia to be elevated among the poor. The finding presents as a pure SES effect since the likelihood of deficit schizophrenia does not vary by race when social class is held constant. CONCLUSION: The finding is potentially an important new insight into the epidemiology of schizophrenia. It offers a better understanding for poor outcome among lower class patients in stratified societies such as the United States. It is also consistent with longitudinal research by European investigators.


Assuntos
Esquizofrenia/classificação , Esquizofrenia/epidemiologia , Classe Social , Humanos , Pennsylvania/epidemiologia , Prevalência , Grupos Raciais/psicologia , Grupos Raciais/estatística & dados numéricos , Psicologia do Esquizofrênico
16.
J Thromb Haemost ; 14(6): 1121-34, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27061380

RESUMO

The development of inhibitors, i.e. neutralizing alloantibodies against factor (F) VIII or FIX, is the most significant complication of protein replacement therapy for patients with hemophilia, and is associated with both increased mortality and substantial physical, psychosocial and financial morbidity. Current management, including bypassing agents to treat and prevent bleeding, and immune tolerance induction for inhibitor eradication, is suboptimal for many patients. Fortunately, there are several emerging gene therapy approaches aimed at addressing these unmet clinical needs of patients with hemophilia and inhibitors. Herein, we review the mounting evidence from preclinical hemophilia models that the continuous uninterrupted expression of FVIII or FIX delivered as gene therapy can bias the immune system towards tolerance induction, and even promote the eradication of pre-existing inhibitors. We also discuss several gene transfer approaches that directly target immune cells in order to promote immune tolerance. These preclinical findings also shed light on the immunologic mechanisms that underlie tolerance induction.


Assuntos
Terapia Genética/métodos , Hemofilia A/imunologia , Tolerância Imunológica , Animais , Linfócitos T CD4-Positivos/citologia , Cães , Fator IX/química , Fator VIII/química , Feminino , Técnicas de Transferência de Genes , Células-Tronco Hematopoéticas/citologia , Hemofilia A/genética , Hemorragia/tratamento farmacológico , Humanos , Isoanticorpos/química , Masculino , Camundongos
17.
Clin Microbiol Infect ; 22(1): 87-93, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26432192

RESUMO

Bloodstream infections caused by Candida species remain a significant cause of morbidity and mortality in hospitalized patients. Biofilm formation by Candida species is an important virulence factor for disease pathogenesis. A prospective analysis of patients with Candida bloodstream infection (n = 217) in Scotland (2012-2013) was performed to assess the risk factors associated with patient mortality, in particular the impact of biofilm formation. Candida bloodstream isolates (n = 280) and clinical records for 157 patients were collected through 11 different health boards across Scotland. Biofilm formation by clinical isolates was assessed in vitro with standard biomass assays. The role of biofilm phenotype on treatment efficacy was also evaluated in vitro by treating preformed biofilms with fixed concentrations of different classes of antifungal. Available mortality data for 134 patients showed that the 30-day candidaemia case mortality rate was 41%, with predisposing factors including patient age and catheter removal. Multivariate Cox regression survival analysis for 42 patients showed a significantly higher mortality rate for Candida albicans infection than for Candida glabrata infection. Biofilm-forming ability was significantly associated with C. albicans mortality (34 patients). Finally, in vitro antifungal sensitivity testing showed that low biofilm formers and high biofilm formers were differentially affected by azoles and echinocandins, but not by polyenes. This study provides further evidence that the biofilm phenotype represents a significant clinical entity, and that isolates with this phenotype differentially respond to antifungal therapy in vitro. Collectively, these findings show that greater clinical understanding is required with respect to Candida biofilm infections, and the implications of isolate heterogeneity.


Assuntos
Biofilmes/crescimento & desenvolvimento , Candida albicans/isolamento & purificação , Candida albicans/fisiologia , Candidemia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/farmacologia , Candida glabrata/isolamento & purificação , Candida glabrata/fisiologia , Candidemia/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mortalidade , Estudos Retrospectivos , Medição de Risco , Escócia/epidemiologia
18.
Aliment Pharmacol Ther ; 22(6): 565-70, 2005 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-16167973

RESUMO

BACKGROUND: The use of antibiotic prophylaxis prior to percutaneous endoscopic gastrostomy insertion has been encouraged following development of guidelines by a number of professional societies within the past few years. However, not all evidence supports routine prophylaxis, particularly in patients with 'benign' disease indications for percutaneous endoscopic gastrostomy insertion. AIM: To identify whether prophylactic antibiotic usage is beneficial in patients undergoing percutaneous endoscopic gastrostomy insertion without malignant disease. METHODS: Adult patients without malignant disease who were referred for percutaneous endoscopic gastrostomy insertion at our unit were assessed for participation in this prospective, double-blind, randomized controlled study. Patients were randomized to receive either placebo or 2.2 g co-amoxiclav (or 2 g cefotaxime if penicillin-allergic) at time of percutaneous endoscopic gastrostomy insertion. Clinical endpoints studies were percutaneous endoscopic gastrostomy site or systemic infection and death within 7 days of percutaneous endoscopic gastrostomy insertion. Results : Ninety-nine patients completed the study (51 antibiotics, 48 placebo). Outcomes in the antibiotic and placebo groups respectively were: percutaneous endoscopic gastrostomy site infection, 11% vs. 47% (P < 0.01); systemic infection, 16% vs. 38% (P < 0.05); and death, 8% vs. 15% (P = 0.5). CONCLUSIONS: Antibiotic prophylaxis prior to percutaneous endoscopic gastrostomy insertion reduces both percutaneous endoscopic gastrostomy site and systemic infections in patients without malignant disease.


Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Cefotaxima/uso terapêutico , Gastroscopia/efeitos adversos , Gastrostomia/efeitos adversos , Infecção da Ferida Cirúrgica/prevenção & controle , Idoso , Método Duplo-Cego , Feminino , Gastroscopia/métodos , Gastrostomia/métodos , Humanos , Intubação Gastrointestinal/efeitos adversos , Masculino , Estudos Prospectivos
19.
Neuropharmacology ; 21(6): 587-9, 1982 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-6896745

RESUMO

The effects of the methyl, ethyl and propyl esters of beta-carboline-3-carboxylic acid have been studied in vitro and in vivo. All three esters were found to be potent inhibitors of 3H-flunitrazepam binding in the rat cerebellum and cerebral cortex in vitro. In vivo, the methyl and ethyl esters were potent proconvulsant agents, whereas the propyl ester was not. Furthermore, the methyl ester produced convulsions which were blocked by the ethyl and propyl esters as well as by diazepam. These in vivo differences may be due to the beta-carboline esters having different proportions of agonistic and antagonistic actions at their recognition sites.


Assuntos
Carbolinas/farmacologia , Indóis/farmacologia , Convulsões/induzido quimicamente , Animais , Cerebelo/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Eletrochoque , Masculino , Muridae
20.
Neuropharmacology ; 23(7A): 797-802, 1984 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-6147788

RESUMO

The triazolopyridazine, CL218,872, inhibited the binding of [3H]flunitrazepam in the cerebellum more potently than in cortex, both in vitro and in vivo. The relationship between this phenomenon and the selectivity of benzodiazepine receptor subtypes is considered. In a range of behavioural tests the overall profile of CL218,872 was similar to that of diazepam in the rat and mouse, although CL218,872 was half as potent as diazepam in the rat and some 20-fold weaker in the mouse. In particular contrast to published observations, CL218,872 reduced locomotor activity in rats and mice at doses only slightly larger than those required to inhibit conflict in rats and footshock-induced fighting in mice. The only qualitative difference between the compounds that could be detected was in the mouse where large doses of CL218,872 did not produce the marked degree of motor incoordination seen after diazepam. However, no such difference was observed in the rat. The presently held view that CL 218,872 is a non-sedative anxiolytic agent needs to be revised in the light of these observations.


Assuntos
Ansiolíticos/farmacologia , Nível de Alerta/efeitos dos fármacos , Piridazinas/farmacologia , Receptores de Superfície Celular/efeitos dos fármacos , Agressão/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Diazepam/farmacologia , Relação Dose-Resposta a Droga , Flunitrazepam/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos , Atividade Motora/efeitos dos fármacos , Destreza Motora/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Receptores de Superfície Celular/metabolismo , Receptores de GABA-A
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