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1.
Phys Chem Chem Phys ; 25(15): 10367-10383, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37009842

RESUMO

A set of experimental dichroic order parameters ranging from ca. +0.66 to -0.22 was obtained by recording polarized UV-visible absorption spectra from aligned samples of fifteen different guest anthraquinone and azo dyes in the nematic host 4-cyano-4'-pentylbiphenyl (5CB). DFT-optimised structures were calculated for between 1 and 16 conformers/tautomers of each dye, and their relative energies, UV-visible absorption wavelengths, oscillator strengths, transition dipole moments, molecular surface tensors and quadrupole tensors were obtained and used in subsequent calculations. A simple approach provided calculated UV-visible absorption spectra of the dyes that gave a qualitative match with the experimental spectra, and the calculated peak positions showed a linear correlation with the experimental values across the full visible range of ca. 350-700 nm. A short-range, shape-based, mean-field orienting potential based on the calculated surface tensors was combined with the calculated transition dipole moment vectors to give calculated dichroic ratios of the dyes that showed a linear correlation across the full range of experimental values. A modification of this mean-field orienting potential to include a long-range, electrostatic component based on the calculated quadrupole tensors gave a slightly improved linear correlation but a slightly worse overall match to the experimental values. The results show that short-range, shape-based interactions dominate the orienting potential for the systems studied here, with the inclusion of long-range quadrupole interactions providing a slightly better model for only some of the dyes. Overall, the use of a mean-field approach allied with molecular properties that can be calculated with relative ease and low computational expense has provided calculated peak positions and dichroic ratios that show good matches and correlations with experimental data from a variety of dye structures without the need to input any experimental data from the dyes. Hence, this method may provide a general and rapid approach to predicting the optical properties of dyes in liquid crystal hosts, enabling candidate dye structures to be screened prior to synthesis.

2.
Chemistry ; 26(2): 428-437, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31489718

RESUMO

The synthesis and evaluation of three novel bis-1,2,4-triazine ligands containing five-membered aliphatic rings are reported. Compared to the more hydrophobic ligands 1-3 containing six-membered aliphatic rings, the distribution ratios for relevant f-block metal ions were approximately one order of magnitude lower in each case. Ligand 10 showed an efficient, selective and rapid separation of AmIII and CmIII from nitric acid. The speciation of the ligands with trivalent f-block metal ions was probed using NMR titrations and competition experiments, time-resolved laser fluorescence spectroscopy and X-ray crystallography. While the tetradentate ligands 8 and 10 formed LnIII complexes of the same stoichiometry as their more hydrophobic analogues 2 and 3, significant differences in speciation were observed between the two classes of ligand, with a lower percentage of the extracted 1:2 complexes being formed for ligands 8 and 10. The structures of the solid state 1:1 and 1:2 complexes formed by 8 and 10 with YIII , LuIII and PrIII are very similar to those formed by 2 and 3 with LnIII . Ligand 10 forms CmIII and EuIII 1:2 complexes that are thermodynamically less stable than those formed by ligand 3, suggesting that less hydrophobic ligands form less stable AnIII complexes. Thus, it has been shown for the first time how tuning the cyclic aliphatic part of these ligands leads to subtle changes in their metal ion speciation, complex stability and metal extraction affinity.

3.
J Physiol ; 597(17): 4481-4501, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31241168

RESUMO

KEY POINTS: Acute hyperglycaemia at the time of a heart attack worsens the outcome for the patient. Acute hyperglycaemia is not limited to diabetic patients and can be due to a stress response in non-diabetics. This study suggests that the damaging cardiac effects of hyperglycaemia can be reversed by selective PKC inhibition. If PKCα/ß isoforms are inhibited, then high glucose itself becomes protective against ischaemic damage. Selective PKC inhibition may therefore be a useful therapeutic tool to limit the damage that can occur during a heart attack by stress-induced hyperglycaemia. ABSTRACT: Hyperglycaemia has a powerful association with adverse prognosis for patients with acute coronary syndromes (ACS). Previous work shows that high glucose prevents ischaemic preconditioning and causes electrical and mechanical disruption via protein kinase C α/ß (PKCα/ß) activation. The present study aimed to: (i) determine whether the adverse clinical association of hyperglycaemia in ACS can be replicated in preclinical cellular models of ACS and (ii) determine the importance of PKCα/ß activation to the deleterious effect of glucose. Freshly isolated rat, guinea pig or rabbit cardiomyocytes were exposed to simulated ischaemia after incubation in the presence of normal (5 mm) or high (20 mm) glucose in the absence or presence of small molecule or tat-peptide-linked PKCαß inhibitors. In each of the four conditions, the following hallmarks of cardioprotection were recorded using electrophysiology or fluorescence imaging: cardiomyocyte contraction and survival, action potential stability and time to failure, intracellular calcium and ATP, mitochondrial depolarization, ischaemia-sensitive leak current, and time to Kir 6.2 opening. High glucose alone resulted in decreased cardiomyocyte contraction and survival; however, it also imparted cardioprotection in the presence of PKCα/ß inhibitors. This cardioprotective phenotype displayed improvements in all of the measured parameters and decreased myocardium damage during whole heart coronary ligation experiments. High glucose is deleterious to cellular and whole-heart models of simulated ischaemia, in keeping with the clinical association of hyperglycaemia with an adverse outcome in ACS. PKCαß inhibition revealed high glucose to show a cardioprotective phenotype in this setting. The results of the present study suggest the potential for the therapeutic application of PKCαß inhibition in ACS associated with hyperglycaemia.


Assuntos
Glicólise/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Proteína Quinase C beta/antagonistas & inibidores , Proteína Quinase C-alfa/antagonistas & inibidores , Animais , Glucose/farmacologia , Glicólise/fisiologia , Cobaias , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Masculino , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Coelhos , Ratos , Ratos Wistar
4.
Soft Matter ; 15(38): 7722-7732, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31509149

RESUMO

Temperature-dependent X-ray scattering studies have been carried out on 4-undecyloxy-4'-cyanobiphenyl (11OCB) and 4-(12,12-dimethyltridecyloxy)-4'-cyanobiphenyl (t-Bu-11OCB) in the smectic A phase, from which their layer spacings and translational order parameters were obtained. Marked differences between the layer structures of the two compounds were demonstrated, showing that the addition of the t-Bu group results in a higher translational order parameter and wider layer spacing for t-Bu-11OCB than 11OCB. Fully atomistic MD simulations of both compounds run for >1000 ns demonstrated the spontaneous formation of smectic mesophases from isotropic starting geometries, and experimental trends in order parameters and absolute layer spacings were shown to be replicated well. Further analysis showed that both the aromatic head-groups and the alkyl tail-groups exhibit interdigitation in the simulated smectic phases of both compounds, and the difference in the layer structures between 11OCB and t-Bu-11OCB could be attributed mainly to a shape segregation effect arising from the addition of the bulky t-Bu end-group to the alkyl chain.

5.
Chemistry ; 23(21): 5090-5103, 2017 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-28195368

RESUMO

Photoswitches and dyes in the liquid-crystalline nematic phase have the potential for use in a wide range of applications. A large order parameter is desirable to maximize the change in properties induced by an external stimulus. A set of photochromic and nonphotochromic dyes were investigated for these applications. It was found that a bent-shaped 7-substituted dihydroazulene (DHA) photoswitch exhibited liquid-crystalline properties. Further investigation demonstrated that this material actually followed two distinct reaction pathways on heating, to a deactivated form by a 1,5-sigmatropic shift and to a linear 6-substituted DHA. In addition, elimination of hydrogen cyanide from the photoactive DHA gave both bent and linear azulene dyes. In a nematic host that has no absorbance around 350 nm, it was found that only the linear DHA derivative has nematic properties; however, both 6- and 7-substituted DHAs were found to have large order parameters. In the nematic host, ring opening of either DHA to the corresponding vinylheptafulvene resulted in a decrease in dichroic order parameter and an unusually fast back-reaction to a mixture of both DHAs. Likewise, only the linear azulene derivative showed mesomorphic properties. In the same nematic host, large order parameters were also observed for these dyes.

6.
Phys Chem Chem Phys ; 18(30): 20651-63, 2016 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-27411959

RESUMO

Five anthraquinone dyes with bis(4-propylphenyl) substituents, connected via sulfide or amine linking groups at the 1,5-positions or directly at the 2,6-positions, have been studied as guests in the nematic liquid crystal host, E7. Polarized UV-visible absorption spectra of aligned samples were used to obtain experimental dichroic order parameters, which exhibit values in the range 0.51-0.74. Fully atomistic MD simulations of these guest-host systems were carried out, generally using default parameters but using new force constants derived here for the dyes containing flexible phenyl-sulfide and phenyl-amine linking groups. An analysis of the alignment of the dye molecules in these simulations provides calculated molecular order parameters, which are combined with calculated order parameters for the alignment of the transition dipole moments within the dyes, reported previously, to give calculated dichroic order parameters. The trend in the calculated dichroic order parameters between the dyes shows a good match with the trend in the experimental values, enabling the observed variation to be rationalised primarily by changes in the alignment of the calculated transition dipole moments within the dyes; the calculated molecular order parameters show a relatively small variation between the dyes. The results indicate that this computational approach may be used generally to rationalise trends in the alignment of guest molecules in liquid crystal hosts, suggesting that it may also be able to provide a predictive aid in the design of guest dyes.

7.
Phys Chem Chem Phys ; 19(1): 813-827, 2016 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-27929151

RESUMO

An assessment of five different definitions of the principal molecular axis along which molecules align in a nematic liquid crystal system has been made by analysing fully atomistic molecular dynamics (MD) simulations of a set of anthraquinone dyes in the cyanobiphenyl-based nematic host mixture E7. Principal molecular axes of the dyes defined by minimum moment of inertia, minimum circumference, minimum area, maximum aspect ratio, and surface tensor models were tested, and the surface tensor model was found to give the best description. Analyses of MD simulations of E7 alone showed that the surface tensor model also gave a good description of the principal molecular axes of the host molecules, suggesting that this model may be applicable more generally. Calculated dichroic order parameters of the guest-host systems were obtained by combining the surface tensor analysis with fixed transition dipole moment (TDM) orientations from time-dependent density functional theory (TD-DFT) calculations on optimised structures of the dyes, and the trend between the dyes generally matched the trend in the experimental values. Additional analyses of the guest-host simulations identified the range of conformers explored by the flexible chromophores within the dyes, and TD-DFT calculations on corresponding model structures showed that this flexibility has a significant effect on the TDM orientations within the molecular frames. Calculated dichroic order parameters that included the effects of this flexibility gave a significantly improved match with the experimental values for the more flexible dyes. Overall, the surface tensor model has been shown to provide a rationale for the experimental alignment trends that is based on molecular shape, and molecular flexibility within the chromophores has been shown to be significant for the guest-host systems: the computational approaches reported here may be used as a general aid in the predictive design of dyes with appropriate molecular shapes and flexibilities for guest-host applications.

8.
J Mol Cell Cardiol ; 79: 42-53, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25450614

RESUMO

ATP-sensitive potassium (KATP) channels are abundantly expressed in the myocardium. Although a definitive role for the channel remains elusive they have been implicated in the phenomenon of cardioprotection, but the precise mechanism is unclear. We set out to test the hypothesis that the channel protects by opening early during ischemia to shorten action potential duration and reduce electrical excitability thus sparing intracellular ATP. This could reduce reperfusion injury by improving calcium homeostasis. Using a combination of contractile function analysis, calcium fluorescence imaging and patch clamp electrophysiology in cardiomyocytes isolated from adult male Wistar rats, we demonstrated that the opening of sarcolemmal KATP channels was markedly delayed after cardioprotective treatments: ischemic preconditioning, adenosine and PMA. This was due to the preservation of intracellular ATP for longer during simulated ischemia therefore maintaining sarcolemmal KATP channels in the closed state for longer. As the simulated ischemia progressed, KATP channels opened to cause contractile, calcium transient and action potential failure; however there was no indication of any channel activity early during simulated ischemia to impart an energy sparing hyperpolarization or action potential shortening. We present compelling evidence to demonstrate that an early opening of sarcolemmal KATP channels during simulated ischemia is not part of the protective mechanism imparted by ischemic preconditioning or other PKC-dependent cardioprotective stimuli. On the contrary, channel opening was actually delayed. We conclude that sarcolemmal KATP channel opening is a consequence of ATP depletion, not a primary mechanism of ATP preservation in these cells.


Assuntos
Cardiotônicos/metabolismo , Ativação do Canal Iônico , Canais KATP/metabolismo , Proteína Quinase C-épsilon/metabolismo , Sarcolema/metabolismo , Potenciais de Ação/efeitos dos fármacos , Adenosina/farmacologia , Animais , Separação Celular , Diazóxido/farmacologia , Ativação Enzimática/efeitos dos fármacos , Insuficiência Cardíaca/enzimologia , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Ativação do Canal Iônico/efeitos dos fármacos , Precondicionamento Isquêmico Miocárdico , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Masculino , Contração Miocárdica/efeitos dos fármacos , Reperfusão Miocárdica , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fenótipo , Pinacidil/farmacologia , Proteína Quinase C-épsilon/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Ratos Wistar , Acetato de Tetradecanoilforbol/farmacologia , Fatores de Tempo
9.
Chemistry ; 21(28): 10123-30, 2015 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-26031244

RESUMO

Practical applications of guest-host liquid crystal systems are critically dependent on the alignment of the guest species within the liquid crystal host. UV/Vis absorption spectroscopy shows that the 1,5-dihydroxy-2,6-bis-(4-propylphenyl)-9,10-anthraquinone dye aligns within the E7 nematic host, giving an experimental dichroic ratio of 9.40 and dye order parameter of 0.74. This alignment was modelled by using a combination of density functional theory (DFT) and molecular dynamics (MD) computational approaches that do not require the input of experimental data. Time-dependent DFT calculations show that the electronic transition dipole moment is highly aligned with the long molecular axis of the dye. Fully atomistic MD simulations show that the long axis of the dye is less highly aligned within the E7 host, indicating that this contribution limits the overall dye alignment and, thereby, the potential practical applications of this particular system. Importantly, this study demonstrates an experimental and combined DFT and MD computational approach that may be applied generally to guest-host systems, providing a potential route to their rational design.

10.
Am J Physiol Heart Circ Physiol ; 307(4): H587-97, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-24951755

RESUMO

While it is well established that mortality risk after myocardial infarction (MI) increases in proportion to blood glucose concentration at the time of admission, it is unclear whether there is a direct, causal relationship. We investigated potential mechanisms by which increased blood glucose may exert cardiotoxicity. Using a Wistar rat or guinea-pig isolated cardiomyocyte model, we investigated the effects on cardiomyocyte function and electrical stability of alterations in extracellular glucose concentration. Contractile function studies using electric field stimulation (EFS), patch-clamp recording, and Ca2+ imaging were used to determine the effects of increased extracellular glucose concentration on cardiomyocyte function. Increasing glucose from 5 to 20 mM caused prolongation of the action potential and increased both basal Ca2+ and variability of the Ca2+ transient amplitude. Elevated extracellular glucose concentration also attenuated the protection afforded by ischemic preconditioning (IPC), as assessed using a simulated ischemia and reperfusion model. Inhibition of PKCα and ß, using Gö6976 or specific inhibitor peptides, attenuated the detrimental effects of glucose and restored the cardioprotected phenotype to IPC cells. Increased glucose concentration did not attenuate the cardioprotective role of PKCε, but rather activation of PKCα and ß masked its beneficial effect. Elevated extracellular glucose concentration exerts acute cardiotoxicity mediated via PKCα and ß. Inhibition of these PKC isoenzymes abolishes the cardiotoxic effects and restores IPC-mediated cardioprotection. These data support a direct link between hyperglycemia and adverse outcome after MI. Cardiac-specific PKCα and ß inhibition may be of clinical benefit in this setting.


Assuntos
Glucose/toxicidade , Miócitos Cardíacos/metabolismo , Proteína Quinase C/metabolismo , Potenciais de Ação , Animais , Sinalização do Cálcio , Células Cultivadas , Ventrículos do Coração/citologia , Ventrículos do Coração/metabolismo , Precondicionamento Isquêmico Miocárdico , Isoenzimas/metabolismo , Masculino , Contração Miocárdica , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/terapia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/fisiologia , Ratos , Ratos Wistar
11.
Br J Pharmacol ; 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38763521

RESUMO

BACKGROUND AND PURPOSE: The canonical Kir6.2/SUR2A ventricular KATP channel is highly ATP-sensitive and remains closed under normal physiological conditions. These channels activate only when prolonged metabolic compromise causes significant ATP depletion and then shortens the action potential to reduce contractile activity. Pharmacological activation of KATP channels is cardioprotective, but physiologically, it is difficult to understand how these channels protect the heart if they only open under extreme metabolic stress. The presence of a second KATP channel population could help explain this. Here, we characterise the biophysical and pharmacological behaviours of a constitutively active Kir6.1-containing KATP channel in ventricular cardiomyocytes. EXPERIMENTAL APPROACH: Patch-clamp recordings from rat ventricular myocytes in combination with well-defined pharmacological modulators was used to characterise these newly identified K+ channels. Action potential recording, calcium (Fluo-4) fluorescence measurements and video edge detection of contractile function were used to assess functional consequences of channel modulation. KEY RESULTS: Our data show a ventricular K+ conductance whose biophysical characteristics and response to pharmacological modulation were consistent with Kir6.1-containing channels. These Kir6.1-containing channels lack the ATP-sensitivity of the canonical channels and are constitutively active. CONCLUSION AND IMPLICATIONS: We conclude there are two functionally distinct populations of ventricular KATP channels: constitutively active Kir6.1-containing channels that play an important role in fine-tuning the action potential and Kir6.2/SUR2A channels that activate with prolonged ischaemia to impart late-stage protection against catastrophic ATP depletion. Further research is required to determine whether Kir6.1 is an overlooked target in Comprehensive in vitro Proarrhythmia Assay (CiPA) cardiac safety screens.

12.
Dalton Trans ; 52(31): 10927-10932, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37489645

RESUMO

Inverse electron demand Diels Alder (IEDDA) reactions of 1,2,4-triazines are of interest to biorthogonal chemistry but suffer from slow kinetics. It is shown here that coordination of Re(I) to a 1,2,4-triazine ring speeds up the IEDDA reaction with bicyclooctyne (BCN) by a factor of 55. Comparative analysis with corresponding 1,2,4,5-tetrazine analogues reveals that the origin of the increased reactivity is markedly different and more profound than in tetrazine analogues. DFT calculations and subsequent analysis indicated the greater increase for the triazine than the tetrazines on coordination could be attributed to the triazine's lower distortion energy and more favourable interaction energy for the triazine, the latter attributable to lower Pauli repulsion than the tetrazines rather than to favourable frontier orbital energies.

13.
Chem Sci ; 14(25): 6992-6996, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37389260

RESUMO

General methodologies enabling the two-carbon homologation of pyrrolidine and piperidine systems have yet to be developed. Herein we report that palladium-catalysed allylic amine rearrangements enable efficient two-carbon ring expansion of 2-alkenyl pyrrolidine and piperidines to their azepane and azocane counterparts. Conditions are mild, tolerant of a range of functional groups and the process can occur with high enantioretention. The products formed undergo a range of orthogonal transformations, making them ideal scaffolds for the creation of compound libraries.

14.
Front Cardiovasc Med ; 9: 997013, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36158799

RESUMO

Hyperglycaemia at the time of myocardial infarction has an adverse effect on prognosis irrespective of a prior diagnosis of diabetes, suggesting glucose is the damaging factor. In ex vivo models of ischaemia, we demonstrated that deleterious effects of acutely elevated glucose are PKCα/ß-dependent, and providing PKCα/ß are inhibited, elevated glucose confers cardioprotection. Short pre-treatments with high glucose were used to investigate time-dependent glucose cardiotoxicity, with PKCα/ß inhibition investigated as a potential mechanism to reverse the toxicity. Freshly isolated non-diabetic rat cardiomyocytes were exposed to elevated glucose to investigate the time-dependence toxic effects. High glucose challenge for >7.5 min was cardiotoxic, proarrhythmic and lead to contractile failure, whilst cardiomyocytes exposed to metabolic inhibition following 5-min high glucose, displayed a time-dependent protection lasting ∼15 min. This protection was further enhanced with PKCα/ß inhibition. Cardioprotection was measured as a delay in contractile failure and KATP channel activation, improved contractile and Ca2+ transient recovery and increased cell survival. Finally, the effects of pre-ischaemic treatment with high glucose in a whole-heart coronary ligation protocol, where protection was evident with PKCα/ß inhibition. Selective PKCα/ß inhibition enhances protection suggesting glycaemic control with PKC inhibition as a potential cardioprotective therapeutics in myocardial infarction and elective cardiac surgery.

15.
PLoS One ; 15(11): e0241843, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33237918

RESUMO

BACKGROUND: The measurement of body temperature has become commonplace in the current COVID-19 pandemic. Body temperature can be measured using thermal infrared imaging, a safe, non-contact method that relies on the emissivity of the skin being known to provide accurate readings. Skin pigmentation affects the absorption of visible light and enables us to see variations in skin colour. Pigmentation may also affect the absorption of infrared radiation and thus affect thermal imaging. Human skin has an accepted emissivity of 0.98 but the effect of different skin pigmentation on this value is not known. In this study, we investigated the influence of different skin pigmentation on thermal emissivity in 65 adult volunteers. METHODS: A reference object of known emissivity (electrical tape) was applied to participant's skin on the inner upper arm. Tape and arm were imaged simultaneously using a thermal infrared camera. The emissivity was set on the camera to the known value for electrical tape. The emissivity was altered manually until the skin temperature using thermal imaging software was equal to the initial tape temperature. This provided the calculated emissivity value of the skin. Participants were grouped according to skin pigmentation, quantified using the Fitzpatrick skin phototyping scale and reflectance spectrophotometry. Differences in emissivity values between skin pigmentation groups were assessed by one-way ANOVA. RESULTS: The mean calculated emissivity for the 65 participants was 0.972 (range 0.96-0.99). No significant differences in emissivity were observed between participants when grouped by skin pigmentation according to the Fitzpatrick scale (p = 0.859) or reflectance spectrophotometry (p = 0.346). CONCLUSION: These data suggest that skin pigmentation does not affect thermal emissivity measurement of skin temperature using thermal infrared imaging. This study will aid further research into the application of thermal infrared imaging as a screening or bedside diagnostic tool in clinical practice.


Assuntos
Raios Infravermelhos , Pigmentação da Pele , Temperatura Cutânea , Termografia/métodos , Adulto , Idoso , COVID-19/diagnóstico , COVID-19/virologia , Etnicidade , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2 , Espectrofotometria/métodos , Adulto Jovem
16.
Chem Commun (Camb) ; 55(95): 14283-14286, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31709444

RESUMO

In this paper we describe unprecedented Ir(iii) complexes of 5-(2-pyridyl)-1,2,4-triazine and their reactivity towards the strained cyclooctyne BCN. The coordination of a 1,2,4-triazine ring to an iridium(iii) ion drastically increases the speed of the reaction, showing the second order rate constant of 8 M-1 s-1, the record value to date for a triazine-BCN reaction.

17.
PLoS One ; 13(7): e0201562, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30063766

RESUMO

BACKGROUND: Medical Infrared Imaging (MII) is an investigative method that can be potentially used in emergency care to non-invasively detect thermal signatures associated with change in blood flow. We have developed a protocol for the use of MII in the Emergency Department (ED) and shown that it is feasible. To derive initial data for sample size calculations, we performed an exploratory study in patients with fever and sepsis. METHODS: The Leicester MII protocol was used to image the temperature patterns along the arm among three patient groups (control, fever and sepsis) of a total 56 patients. Anatomical markers were used to divide this gradient into upper arm, forearm, hand and finger regions. Variations in measurements within and between these regions were described. RESULTS: The thermal gradient down the arm was successfully extracted in all patients. The distribution of values in each region of the arm was described in control, fever and sepsis patients. There was a significant gradient between upper arm and finger in controls (2.75, p < 0.0001), but no gradient in fever (p = 0.944) or sepsis (p = 0.710). This was reflected in the finger/arm difference, which was of -2.74°C (±3.50) in controls, -0.39C (±2.48) in fever, and -1.80°C (±3.09) in sepsis. CONCLUSIONS: This study found different thermal gradients along the arm in control and febrile groups, and defined the degree of individual variation. It is likely that the difference between upper arm temperature and finger temperature (representing the temperature gradient down the arm) may be more useful than absolute measurements in future studies.


Assuntos
Diagnóstico por Imagem/métodos , Febre/diagnóstico , Raios Infravermelhos , Sepse/diagnóstico , Adolescente , Adulto , Idoso , Braço , Temperatura Corporal/fisiologia , Criança , Pré-Escolar , Protocolos Clínicos , Serviço Hospitalar de Emergência , Estudos de Viabilidade , Feminino , Dedos , Antebraço , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto Jovem
18.
Astrobiology ; 7(4): 578-604, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17723091

RESUMO

The European Space Agency's ExoMars mission will seek evidence of organic compounds of biological and non-biological origin at the martian surface. One of the instruments in the Pasteur payload may be a Life Marker Chip that utilizes an immunoassay approach to detect specific organic molecules or classes of molecules. Therefore, it is necessary to define and prioritize specific molecular targets for antibody development. Target compounds have been selected to represent meteoritic input, fossil organic matter, extant (living, recently dead) organic matter, and contamination. Once organic molecules are detected on Mars, further information is likely to derive from the detailed distribution of compounds rather than from single molecular identification. This will include concentration gradients beneath the surface and gradients from generic to specific compounds. The choice of biomarkers is informed by terrestrial biology but is wide ranging, and nonterrestrial biology may be evident from unexpected molecular distributions. One of the most important requirements is to sample where irradiation and oxidation are minimized, either by drilling or by using naturally excavated exposures. Analyzing regolith samples will allow for the search of both extant and fossil biomarkers, but sequential extraction would be required to optimize the analysis of each of these in turn.


Assuntos
Exobiologia/métodos , Meio Ambiente Extraterreno , Marte , Voo Espacial , Voo Espacial/tendências , Estados Unidos , United States National Aeronautics and Space Administration
19.
J Intensive Care Soc ; 18(3): 221-227, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29118834

RESUMO

The microcirculation describes the smallest elements of the cardiovascular conducting system and is pivotal in the maintenance of homeostasis. Microcirculatory dysfunction is present early in the pathophysiology of sepsis, with the extent of microcirculatory derangement relating to disease severity and prognosis in ICU patients. However, at present microcirculatory function is not routinely monitored at the bedside. This article describes the pathophysiology of microcirculatory derangements in sepsis, methods of its measurement and evidence to support their clinical use.

20.
J Hand Surg Asian Pac Vol ; 22(4): 472-478, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29117844

RESUMO

BACKGROUND: Thumb carpometacarpal joint arthroplasty for osteoarthritis may hold advantages over trapeziectomy by preserving range of motion, whilst providing stability and preventing thumb shortening. METHODS: We compare functional and satisfaction outcomes scores, radiological shortening and complication rates between patients treated with trapeziectomy and those receiving the ARPE thumb CMCJ arthroplasty. RESULTS: Seventy-five trapeziectomies and one hundred and ten ARPE arthroplasties were performed over the study period. Both treatments resulted in significant improvements in functional scores. When matching patients according to pre-operative function, patients receiving the ARPE arthroplasty had better post-operative function (Quick DASH: trapeziectomy = 25.1, ARPE = 16.8). More patients receiving the ARPE arthroplasty were satisfied with their treatment (trapeziectomy = 7.8/10, ARPE = 8.7/10) and would have the same treatment again (trapeziectomy = 76%, ARPE = 89%). The ARPE also resulted in less thumb shortening. However the ARPE arthroplasty is associated with a higher complication rate, with 14% of patients requiring further surgery at a mean of 2 years follow up (95% implant survival). CONCLUSIONS: Both trapeziectomy and the ARPE CMCJ arthroplasty are effective treatment options for thumb CMCJ osteoarthritis. Arthroplasty may offer potential advantages in terms of post-operative function and patient satisfaction. However the risk of complications and requirement for further surgery is greater and must be carefully considered during patient selection and pre-operative counselling.


Assuntos
Artroplastia/métodos , Articulações Carpometacarpais/cirurgia , Osteoartrite/cirurgia , Osteotomia/métodos , Trapézio/cirurgia , Idoso , Articulações Carpometacarpais/diagnóstico por imagem , Articulações Carpometacarpais/fisiopatologia , Feminino , Humanos , Masculino , Osteoartrite/diagnóstico , Osteoartrite/fisiopatologia , Satisfação do Paciente , Período Pós-Operatório , Radiografia , Amplitude de Movimento Articular , Polegar/cirurgia , Trapézio/diagnóstico por imagem , Resultado do Tratamento
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