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1.
J Antimicrob Chemother ; 77(2): 338-344, 2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-34791307

RESUMO

BACKGROUND: CoNS bacteraemia causes significant neonatal morbidity. Previous work has suggested that ß-lactam antibiotics vary in their binding affinity to PBP2a (produced by the mecA gene) present in most CoNS. OBJECTIVES: We evaluated cefazolin MICs for CoNS isolated in an Australian neonatal ICU (NICU) and correlated them with isolate genotype and phenotype. METHODS: Significant blood isolates from 2009 to 2017 were speciated and underwent broth microdilution testing for cefazolin, cefoxitin, oxacillin and flucloxacillin. Correlation with mecA presence and PBP2a expression was evaluated. A selection of Staphylococcus capitis isolates underwent WGS. RESULTS: The CoNS (n = 99) isolates were confirmed as S. capitis (n = 57), Staphylococcus epidermidis (n = 32), Staphylococcus haemolyticus (n = 2) and Staphylococcus warneri (n = 8). The MIC of cefazolin was ≤2 mg/L for 30% of isolates and 75% had an MIC of ≤8 mg/L (MIC90 = 16 mg/L). This contrasted with MIC90s of cefoxitin, oxacillin and flucloxacillin, which were all ≥32 mg/L. WGS found a number of S. capitis isolates closely related to the globally established NRCS-A clone. CONCLUSIONS: CoNS displayed distinctly lower MIC values of cefazolin than of other agents tested. MIC variation may be related to binding affinity of PBP2a or regulation of expression of mecA by mecR1-mecI functional genes. Further, NRCS-A S. capitis strains were present in this Australian NICU before and after the unit underwent physical relocation, which raised questions about a common environmental source. It is considered justified to conduct a randomized clinical trial that assesses cefazolin versus vancomycin for management of late-onset neonatal sepsis.


Assuntos
Bacteriemia , Cefazolina , Infecções Estafilocócicas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Austrália , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Cefazolina/farmacologia , Coagulase , Humanos , Recém-Nascido , Testes de Sensibilidade Microbiana , Oxacilina/farmacologia , Infecções Estafilocócicas/tratamento farmacológico
2.
R Soc Open Sci ; 7(2): 191994, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32257351

RESUMO

The study aimed to evaluate sensory laterality and concentration of faecal immunoglobulin A (IgA) as non-invasive measures of stress in horses by comparing them with the already established measures of motor laterality and faecal glucocorticoid metabolites (FGMs). Eleven three-year-old horses were exposed to known stressful situations (change of housing, initial training) to assess the two new parameters. Sensory laterality initially shifted significantly to the left and faecal FGMs were significantly increased on the change from group to individual housing and remained high through initial training. Motor laterality shifted significantly to the left after one week of individual stabling. Faecal IgA remained unchanged throughout the experiment. We therefore suggest that sensory laterality may be helpful in assessing acute stress in horses, especially on an individual level, as it proved to be an objective behavioural parameter that is easy to observe. Comparably, motor laterality may be helpful in assessing long-lasting stress. The results indicate that stress changes sensory laterality in horses, but further research is needed on a larger sample to evaluate elevated chronic stress, as it was not clear whether the horses of the present study experienced compromised welfare, which it has been proposed may affect faecal IgA.

3.
Intern Med J ; 42(7): 780-5, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21627743

RESUMO

BACKGROUND: Since 2007, Townsville Cancer Centre (Queensland, Australia) has provided routine and urgent medical oncology services to rural and remote communities through videoconferencing. At remote sites, patients were accompanied by doctors and other health workers. The aim of this study was to describe satisfaction of patients and rural health workers with this model of teleoncology. METHODS: Between May 2007 and June 2010, 55 videoconferencing patients were invited to participate in a questionnaire-based telephone survey after informed consent. The survey included responses to 16 satisfaction statements using a 5-point Likert scale. Perspectives of health workers involved were recorded using open-ended questions on six themes related to telehealth. RESULTS: Among the 50 participating cancer patients, median age was 56 years (range 28-83). Seventy-six per cent of patients thought specialist physical examination was important despite local doctors performing it. Seventy-six per cent of patients felt the presence of accompanying local health workers was not important. Seventy-eight per cent of patients preferred to be seen in Mt Isa for the first consultation through videoconferencing than travelling to Townsville. More than 80% of patients were in agreement with the rest of the satisfaction statements. Ninety-six per cent of patients were in agreement with the question relating to overall satisfaction. Eighteen health workers participated and their responses and attitudes were favourable towards telehealth. CONCLUSION: Satisfaction with this model of care was proven to be high among both patients and health workers. Benefits perceived included effective communication between patients and specialists, reduced travel time and money expenditure, and superior specialist support for rural health workers.


Assuntos
Pessoal de Saúde , Oncologia/métodos , Satisfação do Paciente , População Rural , Telemedicina/métodos , Comunicação por Videoconferência , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude do Pessoal de Saúde , Feminino , Pessoal de Saúde/psicologia , Inquéritos Epidemiológicos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Serviços de Saúde Rural
4.
Environ Pollut ; 144(3): 746-51, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16781029

RESUMO

Although the fate of organotins has been widely studied in the marine environment, fewer studies have considered their impact in terrestrial systems. The degradation and toxicity of triphenyltin in autoclaved, autoclaved-reinoculated and non-sterilised soil was studied in a 231 day incubation experiment following a single application. Degradation and toxicity of phenyltin compounds in soil was monitored using both chemical and microbial (lux-based bacterial biosensors) methods. Degradation was significantly slower in the sterile soil when compared to non-sterilised soils. In the non-sterilised treatment, the half-life of triphenyltin was 27 and 33 days at amendments of 10 and 20 mg Sn kg(-1), respectively. As initial triphenyltin degradation occurred, there was a commensurate increase in toxicity, reflecting the fact that metabolites produced may be both more bioavailable and toxic to the target receptor. Over time, the toxicity reduced as degradation proceeded. The toxicity impact on non-target receptors for these compounds may be significant.


Assuntos
Bactérias/metabolismo , Fungicidas Industriais/toxicidade , Compostos Orgânicos de Estanho/toxicidade , Poluentes do Solo/toxicidade , Biodegradação Ambiental , Monitoramento Ambiental/métodos , Fungicidas Industriais/metabolismo , Luminescência , Compostos Orgânicos de Estanho/análise , Compostos Orgânicos de Estanho/metabolismo , Microbiologia do Solo , Poluentes do Solo/metabolismo , Testes de Toxicidade
5.
J Hazard Mater ; 98(1-3): 1-13, 2003 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-12628774

RESUMO

In this study, prediction of the thermal decomposition pathway of the volatile liquid anaesthetics such as halothane, enflurane and isoflurane in contact with various metal/metal oxides at elevated temperatures has been deduced by evaluating the mass spectrometric fragmentation pattern of each anaesthetic observed in the ionisation process. In the light of the molecular structures and fragmentation components, it was believed that the thermal decomposition pathway of each anaesthetic on metal/metal oxide surface, particularly at higher temperatures, is similar to the ionisation mechanism occurring in the mass spectrometer ionisation process with minor differences for each molecule. The ionisation clusters for each anaesthetic molecule show the most likely fragment and radicals formed in the mass spectrometric ionisation process by considering the isotopic effect. From these clusters, thermal decomposition pathway of the liquid anaesthetics and formation mechanisms of the major halogenated thermal decomposition products have been predicted. It was concluded that the ionisation and thermal decomposition pathway resembles each other, but are not completely similar.


Assuntos
Anestésicos/análise , Óxido Nitroso , Oxigênio , Isoflurano , Isótopos , Espectrometria de Massas
6.
J Environ Monit ; 3(1): 133-8, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11253006

RESUMO

This study was carried out to characterise the mineralogical forms of barium and the trace heavy metal impurities in commercial barytes of different origins using electron probe microanalysis (EPMA), X-ray diffraction (XRD) and inductively coupled plasma mass spectrometry (ICP-MS). Qualitative EPMA results show the presence of typically eight different minerals in commercial barytes including barite (BaSO4), barium feldspar, galena (PbS), pyrite (FeS2), sphalerite (ZnS), quartz (SiO2), and silicates, etc. Quantitative EPMA confirms that the barite crystals in the barytes contain some strontium and a little calcium, whereas trace heavy metals occur in the associated minerals. Analysis of aqua regia extracts of barytes samples by ICP-MS has shown the presence of a large number of elements in the associated minerals. Arsenic, copper and zinc concentrations correlate closely in all 10 samples. The findings suggest that barytes is not, as traditionally thought, an inert mineral, but is a potentially toxic substance due to its associated heavy metal impurities, which can be determined by an aqua regia digest without the need for complete dissolution of the barite itself. X-ray powder diffraction was not informative as the complex barite pattern masks the very weak lines from the small amounts of associated minerals.


Assuntos
Bário/análise , Monitoramento Ambiental/métodos , Metais Pesados/análise , Bário/química , Microanálise por Sonda Eletrônica , Indústrias , Lubrificação , Espectrometria de Massas , Metais Pesados/química , Difração de Raios X
7.
Analyst ; 125(12): 2206-15, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11219054

RESUMO

N-Acylthioureas are excellent ligands for a variety of heavy metals, but their metal selectivity is highly dependent on the precise nature of the substituents present. In this paper we show how combinatorial chemistry techniques can be used to establish relative affinities for copper within a mixture of 100 such thioureas. Following a straightforward synthesis, and copper extraction using standard liquid-liquid extraction techniques, LC-MS was used to identify the ligands which bind most strongly to the copper ions. Among the 100 ligands XC(O)N(Z)C(S)NHY, the most important substituent is the Y group bound to the NH: only aromatic Y substituents give strong binding to copper. The acyl X substituents are invariably aromatic, and an electron-rich X group is best; the affinity for copper seems to be less dependent on the Z substituent, although a large group such as benzyl disfavours copper binding. The five ligands from the library which bind copper most strongly have been clearly identified by a series of experiments: they all have aromatic groups in the Y position, but the X and Z substituents can be more varied. This is a very convincing demonstration of the power of combinatorial methods: to have found the same information by conventional methods would have required a lengthy and repetitive series of syntheses and investigations. In addition, our results give some preliminary evidence for synergistic binding of two different ligands, but this requires further investigation.

8.
Sci Total Environ ; 231(2-3): 145-58, 1999 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-10472131

RESUMO

Dissolved oxygen cycling patterns in a tropical lake (Weija Lake) were shown to be useful as a potential indicator of biodegradable organic pollution, by dosing with liquid malt to give an additional organic burden of 2.5 and 5.0 mg l-1 TOC, and monitoring the DO values continuously for 140 h. These loadings were added to water columns (in tubes) suspended from a raft in a lake in south-east Ghana. The addition of organic pollution burden to the lake water produced two main effects: the mean DO value was lowered, and the amplitude of the DO cycle decreased as organic loading increased from 2.5 to 5.0 mg l-1 TOC. There was also an indication of heterotrophic respiration associated with organic inputs for the 5.0 mg l-1 added TOC suggesting a P/R ratio of well below 1.0. Taking the results of a DO cycling computer model together with those from the lake raft experiments, it can be concluded that dissolved oxygen cycles can be a good indicator of biodegradable organic pollution load.


Assuntos
Oxigênio/análise , Poluição Química da Água/análise , Biodegradação Ambiental , Monitoramento Ambiental , Água Doce/análise , Gana , Modelos Teóricos , Clima Tropical
9.
J Chromatogr B Biomed Sci Appl ; 709(2): 217-23, 1998 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-9657218

RESUMO

Thermal stability of pressurised ready-to-use volatile liquid anaesthetic mixtures (halothane, isoflurane and enflurane) in Entonox (commercially available premixed 50% N2O, 50% O2 mixture) were investigated at temperatures of 20, 258, 400, 503 and 602 degrees C on glass, stainless steel, copper and aluminium by gas chromatography and GC-MS. It was found that most of the decomposition products formed were halogenated compounds and the observed thermal stabilities in glass, stainless steel and copper allowed a thermal treatment up to 250 degrees C without any decomposition problem. Aluminium was found to be the most effective metal at causing decomposition of the anaesthetic mixtures even at lower temperatures.


Assuntos
Anestésicos Combinados/química , Anestésicos Inalatórios/química , Temperatura Alta , Óxido Nitroso/química , Oxigênio/química , Alumínio , Cobre , Estabilidade de Medicamentos , Enflurano/química , Cromatografia Gasosa-Espectrometria de Massas , Vidro , Halotano/química , Isoflurano/química , Aço
10.
Naunyn Schmiedebergs Arch Pharmacol ; 357(3): 232-9, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9550293

RESUMO

The effect of histamine and related drugs on the tritium overflow evoked electrically (0.3 Hz) or by introduction of Ca2+ ions into Ca2+-free K+-rich (25 mmol/l) medium containing tetrodotoxin was studied in superfused guinea-pig brain cortex, cerebellum, hippocampus or hypothalamus slices and in mouse brain cortex slices preincubated with 3H-noradrenaline. The electrically evoked tritium overflow in guinea-pig cortex slices was inhibited by histamine; the H3 receptor antagonist clobenpropit reversed the effect of histamine to a slight facilitation. The facilitatory effect of histamine (obtained in the presence of clobenpropit) was not affected by the H1 receptor antagonist mepyramine but abolished by the H2 receptor antagonist ranitidine. In the absence of clobenpropit, ranitidine augmented the inhibitory effect of histamine. In slices superfused in the presence of ranitidine, the evoked overflow was inhibited by histamine and, more potently, by the H3 receptor agonist R-alpha-methylhistamine in a concentration-dependent manner (maximum inhibitory effect obtained for both agonists 30-35%). The concentration-response curve of histamine was shifted to the right by the H3 receptor antagonist thioperamide. R-alpha-methylhistamine inhibited the electrically evoked tritium overflow also in guinea-pig cerebellar, hippocampal and hypothalamic slices. In cortex slices superfused in the presence of clobenpropit, the H2 receptor agonists impromidine and, less potently, R-sopromidine facilitated the evoked overflow in a concentration-dependent manner. S-Sopromidine only tended to increase the evoked overflow. The effect of impromidine was counteracted by the H2 receptor antagonists ranitidine and cimetidine. The extent of the maximum facilitatory effect of impromidine (by 15-20%) was about the same when (i) the Ca2+ concentration in the medium was reduced from 1.3 to 0.98 mmol/l, (ii) the time of exposure to impromidine was reduced from 28 to 8 min or (iii) cerebellar, hippocampal or hypothalamic slices were used instead of cortical slices. The Ca2+-induced tritium overflow in guinea-pig cortex slices was inhibited by histamine (in the presence of ranitidine); this effect was abolished by clobenpropit. In slices superfused in the presence of clobenpropit, impromidine failed to facilitate the Ca2+-evoked tritium overflow. The electrically evoked tritium overflow in mouse brain cortex slices was inhibited by histamine by about 60% (both in the absence or presence of ranitidine). The inhibitory effect of histamine was abolished (but not reversed) by clobenpropit. In conclusion, noradrenaline release in the guinea-pig brain cortex is inhibited via presynaptic H3 receptors and facilitated via H2 receptors not located presynaptically. In the mouse brain cortex, only inhibitory H3 receptors occur. The extent of the H3 receptor-mediated effect is more marked in the mouse than in the guinea-pig brain cortex.


Assuntos
Encéfalo/metabolismo , Histamina/farmacologia , Norepinefrina/metabolismo , Receptores Histamínicos H2/metabolismo , Receptores Histamínicos H3/efeitos dos fármacos , Animais , Cálcio/farmacologia , Córtex Cerebelar/efeitos dos fármacos , Córtex Cerebelar/metabolismo , Estimulação Elétrica , Cobaias , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Receptores Histamínicos H3/metabolismo , Trítio/metabolismo
11.
Naunyn Schmiedebergs Arch Pharmacol ; 358(6): 623-7, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9879720

RESUMO

We determined the affinities of five newly synthesized histamine H3-receptor antagonists in an H3-receptor binding assay and their potencies in a functional H3-receptor model. Furthermore, we determined their potencies in a histamine H2- and H1-receptor model. The compounds differ from histamine in that the ethylamine side chain is replaced by an aryl-substituted propyloxy chain and they differ from one another by varying substituents of the aryl rest. Iodoproxyfan, a highly potent and selective antagonist at H3 receptors, is structurally related to these five compounds. The specific binding of [3H]-Nalpha-methylhistamine to rat brain cortex membranes was monophasically displaced by each of the five compounds at pKi values ranging from 8.24 to 9.27. Inhibition by histamine of the electrically evoked tritium overflow from mouse brain cortex slices preincubated with [3H]noradrenaline was antagonized by all compounds and the concentration-response curve was shifted to the right with apparent pA2 values ranging from 7.78 to 9.39. The five compounds under study possess negligible potencies at histamine H2 and H1 receptors studied in the guinea-pig right atrium and ileum, respectively (pD'2 or pKp values < or = 5.2). The present paper shows that the five compounds under study possess high affinities and potencies at histamine H3 receptors, four out of the five compounds in this respect being equipotent with iodoproxyfan. Like iodoproxyfan, the five compounds show an at least 1000-fold selectivity for H3 as compared to H2 and H1 receptors.


Assuntos
Antagonistas dos Receptores Histamínicos/farmacologia , Imidazóis/farmacologia , Norepinefrina/metabolismo , Receptores Histamínicos H3/efeitos dos fármacos , Animais , Córtex Cerebral/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Átrios do Coração/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores H2 da Histamina/farmacologia , Íleo/efeitos dos fármacos , Técnicas In Vitro , Masculino , Camundongos , Modelos Biológicos , Estrutura Molecular , Ratos , Trítio/farmacocinética
12.
Neuroscience ; 79(1): 247-54, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9178880

RESUMO

We studied whether interactions between the presynaptic histamine H3 and prostaglandin EP3 receptors on the noradrenergic neurons of the mouse brain cortex occur. Cerebral cortex slices from the mouse (and, in few experiments, from the rat) were preincubated with [3H]noradrenaline and then superfused with a physiological salt solution. Tritium overflow was evoked electrically, either at 0.3 or 3 Hz (2 min) (standard stimulation protocol) or at 100 Hz (eight pulses) (stimulation protocol under which almost no activation of the presynaptic alpha2-adrenoceptors by endogenous noradrenaline occurs). In another set of experiments, Ca2+ ions were introduced into Ca2+-free K+-rich medium containing tetrodotoxin to evoke tritium overflow. The electrically-evoked tritium overflow (0.3 Hz) was inhibited by histamine or the H3 receptor agonist imetit, acting via H3 receptors. and by prostaglandin E2 or the EP3 receptor agonist sulprostone, acting via EP3 receptors. When histamine or imetit was given first (at concentrations causing the maximum effect at H3 receptors), the effect of prostaglandin E2 on the evoked tritium overflow was attenuated by 5-10%. When prostaglandin E2 or sulprostone was given first (at concentrations causing the maximum effect at EP3 receptors), the effect of histamine or imetit on the evoked overflow was attenuated by almost 50%. The previous administration of prostaglandin E2 also blunted the effect of histamine on the evoked tritium overflow evoked at 3 Hz; the degree of attenuation was identical when the current strength was 25 mA or was increased to 100 or 200 mA in order to partially compensate for the inhibitory effect of prostaglandin E2 on the evoked overflow. In addition, prostaglandin E2 attenuated the effect of histamine when tritium overflow was evoked (i) by 100 Hz, eight pulses or (ii) by Ca2+ ions or (iii) when rat (instead of mouse) brain cortex slices were used. An interaction of prostaglandin E2 or sulprostone with the H3 receptor recognition site could be excluded since both prostanoids did not affect the specific binding of the H3 agonist radioligand [3H]N(alpha)-methylhistamine to rat brain cortex membranes. In conclusion, mutual interactions occur between the presynaptic H3 and EP3 receptors involved in the inhibition of noradrenaline release in the mouse brain cortex. Pre-activation of the H3 receptor slightly attenuates the EP3 receptor-mediated effect whereas pre-activation of the EP3 receptor more markedly attenuates the H3 receptor-mediated effect. The interactions may occur between the receptors themselves or at a step behind the receptors (e.g., at the level of G proteins). The physiological significance of these interactions may be to limit the total extent of inhibition of noradrenaline release in a scenario under which both receptors are activated simultaneously.


Assuntos
Encéfalo/fisiologia , Córtex Cerebral/fisiologia , Terminações Nervosas/fisiologia , Norepinefrina/metabolismo , Receptores Histamínicos H3/fisiologia , Receptores de Prostaglandina E/fisiologia , Animais , Cálcio/farmacologia , Dinoprostona/análogos & derivados , Dinoprostona/farmacologia , Estimulação Elétrica , Histamina/farmacologia , Agonistas dos Receptores Histamínicos/farmacologia , Imidazóis/farmacologia , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos , Terminações Nervosas/efeitos dos fármacos , Técnica de Diluição de Radioisótopos , Ratos , Receptores Adrenérgicos alfa 2/efeitos dos fármacos , Receptores Adrenérgicos alfa 2/fisiologia , Receptores de Prostaglandina E Subtipo EP3 , Tioureia/análogos & derivados , Tioureia/farmacologia , Trítio
13.
Naunyn Schmiedebergs Arch Pharmacol ; 353(5): 482-8, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8740140

RESUMO

We determined the affinities of 16 newly synthesized H3 receptor antagonists in an H3 receptor binding assay and the potencies of 12 of these compounds at functional H3 receptors in the mouse brain cortex and guinea-pig ileum. The compounds differ from histamine in that the C-C-N side chain is replaced by a chain of the structure C-C-C-O. The two major aims of the study were (1) to investigate whether the two functional H3 receptors are pharmacologically different and (2) to derive structure-activity relationships. The specific binding of 3H-Na-methylhistamine to rat brain cortex membranes was monophasically displaced by each of the 16 compounds at pKi values ranging from 7.30 to 9.48. In superfused mouse brain cortex slices preincubated with 3H-noradrenaline, the electrically evoked tritium overflow was slightly decreased by iodoproxyfan and its deiodo analogue; this effect was counteracted by the H3 receptor antagonist clobenpropit. The other compounds did not affect the evoked tritium overflow by themselves. The concentration-response curve of histamine for its inhibitory effect on the electrically evoked tritium overflow was shifted to the right by the 12 compounds with apparent pA2 values ranging from 7.02 to 9.00. The 12 compounds also shifted to the right the concentration-response curve of R-a-methylhistamine for its inhibitory effect on the electrically induced contraction in guinea-pig ileum strips; the apparent pA2 values ranged from 5.97 to 9.00. Iodoproxyfan decreased the electrically induced contraction by itself and this effect was counteracted by the H3 receptor antagonist thioperamide. The apparent pA2 values in the two functional H3 receptor models showed a highly significant correlation (r = 0.882; P < 0.001). Highly significant correlations were also obtained when the pKi values of the compounds in the binding assay were compared to their apparent pA2 values in the mouse brain (r = 0.799; P < 0.004) and in the guinea-pig ileum (r = 0.851; P < 0.001). In each of the three experimental models, iodoproxyfan was the most potent compound; its deiodo analogue was less potent by more than 1.1 log units. The present results show that the compounds under study possess moderate to high affinity and/or (partial) H3 receptor antagonist potency. The two functional H3 receptors in the mouse brain cortex and the guinea-pig ileum may be slightly different; further studies are necessary to clarify whether this difference is due to H3 receptor heterogeneity, species variants or differences in the efficiency of receptor coupling. The marked difference in the affinity/potency between iodoproxyfan and its deiodo analogue may suggest that a highly lipophilic residue in that part of the molecule favours a high affinity/antagonistic potency at H3 receptors.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos , Antagonistas dos Receptores H2 da Histamina/farmacologia , Imidazóis/farmacologia , Intestino Delgado/efeitos dos fármacos , Animais , Ligação Competitiva , Córtex Cerebral/metabolismo , Relação Dose-Resposta a Droga , Feminino , Cobaias , Antagonistas dos Receptores Histamínicos/metabolismo , Antagonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores H2 da Histamina/metabolismo , Imidazóis/química , Imidazóis/metabolismo , Técnicas In Vitro , Intestino Delgado/metabolismo , Radioisótopos do Iodo , Masculino , Metilistaminas/metabolismo , Camundongos , Piperidinas/metabolismo , Piperidinas/farmacologia , Ratos , Ratos Wistar , Relação Estrutura-Atividade
14.
Naunyn Schmiedebergs Arch Pharmacol ; 353(3): 290-4, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8692283

RESUMO

We determined the affinity and/or potency of two metabolites of clozapine (clozapine-N-oxide and N-desmethylclozapine) and of five atypical neuroleptics, chemically related (olanzapine) or unrelated to clozapine (remoxipride, risperidone, thioridazine, zotepine), at H3 receptors. The specific binding of 3H-N alpha-methylhistamine to rat brain cortex homogenates was inhibited by the seven compounds; the pKi values were: N-desmethylclozapine (5.33); clozapine-N-oxide (4.18); olanzapine (5.45); thioridazine (4.91); zotepine (4.75); remoxipride (4.51) and risperidone (4.43). Three compounds were examined in a functional H3 receptor model as well. The electrically evoked tritium overflow from superfused mouse brain cortex slices, which represents quasi-physiological noradrenaline release, was not affected by N-desmethylclozapine (3.2 and 10 microM), clozapine-N-oxide (3.2-100 microM) and olanzapine (3.2-32 microM). On the other hand, the three compounds shifted to the right the concentration-response curve of histamine for its inhibitory effect on the evoked overflow; the apparent pA2 values were 5.84, 4.21 and 5.80, respectively. The present study shows that five atypical neuroleptics of different chemical classes and the two major metabolites of clozapine possess a lower affinity and/or antagonistic potency at H3 receptors than clozapine itself (pKi 6.15, pA2 6.33; Kathmann M, Schlicker E, Göthert M (1994). Psychopharmacology 116: 464-468).


Assuntos
Antipsicóticos/farmacologia , Clozapina/farmacologia , Antagonistas dos Receptores Histamínicos/metabolismo , Metilistaminas/metabolismo , Receptores Histamínicos H3/metabolismo , Animais , Antipsicóticos/metabolismo , Benzodiazepinas , Ligação Competitiva/efeitos dos fármacos , Clozapina/metabolismo , Dibenzotiepinas/metabolismo , Dibenzotiepinas/farmacologia , Relação Dose-Resposta a Droga , Marcação por Isótopo , Masculino , Camundongos , Olanzapina , Pirenzepina/análogos & derivados , Pirenzepina/metabolismo , Pirenzepina/farmacologia , Ratos , Ratos Wistar , Receptores Histamínicos H3/efeitos dos fármacos , Remoxiprida/metabolismo , Remoxiprida/farmacologia , Risperidona/metabolismo , Risperidona/farmacologia , Relação Estrutura-Atividade , Tioridazina/metabolismo , Tioridazina/farmacologia , Trítio
15.
Talanta ; 42(10): 1533-44, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18966386

RESUMO

A new method for determining (34)S:(32)S ratios using Fourier transform infrared spectroscopy has been developed. The four sulphur-containing gases SCO, H(2)S, SF(6) and SO(2) are assessed as possible compounds for the spectroscopic measurements, from which, after a consideration of available lines showing a clear isotopic shift and also of possible synthetic routes to the gas starting from a range of natural sample types, SO(2) was selected for further development of the instrumental method for the isotopic ratio determination. Sulphur in the samples present as the element, as metal sulphides or as organosulphur compounds, is converted by heating with V(2)O(5) into gaseous SO(2), and a part of the 518 cm(-1) band is recorded in the absorbance mode. The optimisation of instrumental parameters and of the chemical reaction conditions is described, and the results from the application of the method to the measurement of the level of enrichment of (34)S in a soil fungus are presented. The agreement between results at the natural abundances of 4.2% was better than 0.04% absolute for a sample size of 1.5 mg of sulphur.

16.
Thorax ; 49(4): 352-6, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8202906

RESUMO

BACKGROUND: There is widespread concern that the cultivation of oilseed rape leads to seasonal epidemics of respiratory symptoms in populations living in the neighbourhood, and it has been suggested that the plant is a potent allergen. A study was therefore undertaken to determine the prevalence of seasonal symptoms in rural populations close to and far from areas of oilseed rape cultivation, and to measure the levels of allergen and other potentially harmful substances released by the crop. METHODS: Random samples of 1000 adults from the general practice populations of two villages surrounded by oilseed rape fields, and 1000 adults from one village far from such cultivation, were taken. The subjects completed a previously validated questionnaire on respiratory and other symptoms, including questions on symptom seasonality, occupation, and smoking habits. Pollen and fungal spore counts were made around fields of oilseed rape and in the villages. The chemicals released by oilseed rape were measured in the field. RESULTS: Overall, 86.8% of the subjects completed the questionnaires and the populations of the two samples were generally comparable. Spring and summer exacerbations of symptoms occurred equally in the two areas in approximately 25% of the population. There were small but significant excesses of cough, wheeze, and headaches in spring in the oilseed rape area (2.3% v 1.1%, 6.8% v 4.6%, and 4.8% v 2.8%, respectively), and cough, wheeze, and itchy skin were more prevalent in smokers. Counts of oilseed rape pollen were generally low except adjacent to fields, and counts of fungal spores were mostly higher in the rape than the non-rape areas. Oilseed rape was shown to give off terpenes and these were detected close to fields. CONCLUSIONS: While it is likely that a proportion of the spring symptoms occurring in people living in close proximity to oilseed rape is caused by the plant, the excess of such symptoms is small. This, together with the low levels of pollen in the area, suggests that allergy to oilseed rape pollen is uncommon. The general prevalence of seasonal symptoms in rural areas is of interest, and a proportion of these cases is likely to be caused by factors other than allergy. Release of chemicals by plants and natural rises in summer ozone levels may be contributors.


Assuntos
Alérgenos , Brassica/efeitos adversos , Exposição Ambiental/efeitos adversos , Hipersensibilidade/epidemiologia , Estações do Ano , Adolescente , Adulto , Aldeídos/metabolismo , Brassica/metabolismo , Estudos Transversais , Monitoramento Ambiental , Monitoramento Epidemiológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólen , Prevalência , Distribuição Aleatória , Terpenos/metabolismo , Reino Unido/epidemiologia
17.
Talanta ; 29(10): 869-70, 1982 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18963251

RESUMO

A simple procedure is described for the determination of tin in PVC by atomic-absorption spectroscopy with an air-hydrogen flame, after wet digestion of the sample with sulphuric acid and hydrogen peroxide.

18.
Talanta ; 22(7): 597-600, 1975 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18961693

RESUMO

The most important terms in information theory (information, character, code, message and signal) are defined and interpreted with reference to automation in analytical chemistry. The aim of this communication and the earlier one dealing with systems theory, is to facilitate communication and understanding between all specialists working on or with automated systems for analysis.

19.
Talanta ; 22(4-5): 387-94, 1975.
Artigo em Inglês | MEDLINE | ID: mdl-18961654

RESUMO

Existing procedures for the determination of tin in organotin compounds are reviewed, and a new procedure is described which can be used for the rapid microanalysis of most organotin compounds. Wet oxidation with sulphuric acid and 30% hydrogen peroxide is followed by spectrophotometric determination of the extracted ternary tin(IV)-chloride-oxine complex in chloroform. Time for a single determination is 20 min, and the relative standard deviation is 0.7% for 1-5 mg of tin. On account of their volatility, methyltin compounds must be subjected to a sealed-tube wet oxidation in sulphuric-nitric acid mixture. Addition of sulphamic acid after boiling to remove most of the nitric acid makes this compatible with the solvent extraction step. Tin present as organotin stabilizer in PVC samples can also be determined by this method, after destruction of the organic matter with sulphuric acid and 50% hydrogen peroxide.

20.
Talanta ; 20(9): 811-27, 1973 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18961351

RESUMO

The twelve basic terms of systems theory-system, element, relation, function, structure, organization, feedback, Black Box, model, input-output analysis, trial-and-error method, simulation-are given general definitions and are also interpreted in terms of chemical analysis. The distinction between a generally acceptable brief and precise definition and an interpretation peculiar to one particular specialized field avoids, in the case of universally used terms, a biased view and conception. Simple systems are deliberately chosen and the terms used are clarified by means of diagrams. A system-oriented approach is outlined, with feedback-coupled stages (defining the problems, setting the limits, designing the model, simulation) which has proved useful in practical systems analysis and in systems design. The working group will report, in subsequent publications, on specific analytical systems which are of considerable importance in automation. Those with special interests in these fields are warmly invited to communicate their critical opinions, suggestions, and examples of interpretations based on these definitions.

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