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1.
Br J Hosp Med (Lond) ; 81(10): 1-12, 2020 Oct 02.
Article in English | MEDLINE | ID: mdl-33135923

ABSTRACT

The major component of non-traumatic thoracic aortic emergencies is the acute aortic syndromes. These include acute aortic dissection, intramural haematoma and penetrating atherosclerotic ulcer, grouped together because they are indistinguishable clinically and highly fatal. All three entities involve disruption to the tunica intima and media and may be complicated by rupture, end-organ ischaemia or aneurysmal transformation. Early diagnosis is vital to allow timely and appropriate management. Paired unenhanced and electrocardiogram-gated computed tomography angiography of the chest, extending more distally if required, is recommended for diagnosis. Specific computed tomography features of all three entities are reviewed, with a focus on morphological features associated with complications. Those with type A pathology are usually managed with open surgery because this has a high risk of complication. Patients with uncomplicated type B pathology are usually managed with best medical therapy whereas those with complicated type B pathology are usually offered either surgery or thoracic endovascular aortic repair. The limited evidence regarding the use of thoracic endovascular aortic repair in patients with subacute uncomplicated type B pathology is briefly discussed.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Diseases , Aortic Dissection , Endovascular Procedures , Aortic Dissection/diagnostic imaging , Aortic Dissection/therapy , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/therapy , Aortic Diseases/diagnostic imaging , Aortic Diseases/therapy , Emergencies , Hematoma/diagnostic imaging , Hematoma/therapy , Humans , Treatment Outcome
2.
FASEB J ; 32(4): 1969-1981, 2018 04.
Article in English | MEDLINE | ID: mdl-29183963

ABSTRACT

Most mammalian cells can intercommunicate via connexin-assembled, gap-junctional channels. To regulate signal transmission, connexin (Cx) channel permeability must respond dynamically to physiological and pathophysiological stimuli. One key stimulus is intracellular pH (pHi), which is modulated by a tissue's metabolic and perfusion status. Our understanding of the molecular mechanism of H+ gating of Cx43 channels-the major isoform in the heart and brain-is incomplete. To interrogate the effects of acidic and alkaline pHi on Cx43 channels, we combined voltage-clamp electrophysiology with pHi imaging and photolytic H+ uncaging, performed over a range of pHi values. We demonstrate that Cx43 channels expressed in HeLa or N2a cell pairs are gated biphasically by pHi via a process that consists of activation by H+ ions at alkaline pHi and inhibition at more acidic pHi. For Cx43 channel-mediated solute/ion transmission, the ensemble of these effects produces a pHi optimum, near resting pHi. By using Cx43 mutants, we demonstrate that alkaline gating involves cysteine residues of the C terminus and is independent of motifs previously implicated in acidic gating. Thus, we present a molecular mechanism by which cytoplasmic acid-base chemistry fine tunes intercellular communication and establishes conditions for the optimal transmission of solutes and signals in tissues, such as the heart and brain.-Garciarena, C. D., Malik, A., Swietach, P., Moreno, A. P., Vaughan-Jones, R. D. Distinct moieties underlie biphasic H+ gating of connexin43 channels, producing a pH optimum for intercellular communication.


Subject(s)
Connexin 43/metabolism , Ion Channel Gating , Protons , Animals , Cell Communication , Connexin 43/chemistry , HeLa Cells , Humans , Hydrogen-Ion Concentration , Mice
3.
AIDS Rev ; 19(4): 190-197, 2017.
Article in English | MEDLINE | ID: mdl-29271970

ABSTRACT

With the advent and subsequent success of antiretroviral therapy, HIV infection has largely become a chronic condition and is increasingly seen alongside metabolic disorders such as dyslipidemia and insulin resistance. Furthermore, the administration of antiretroviral therapy itself is associated with an increase in the incidence of metabolic risk factors, namely insulin resistance, lipoatrophy, dyslipidemia, and abnormalities of fat distribution, in HIV patients. Thus, further challenges in the management of HIV patients include the management of diabetes and the metabolic syndrome, non-alcoholic fatty liver disease. Importantly, HIV and non-alcoholic fatty liver disease are both associated with increased risk of cardiovascular disease. Overall, the management of non-alcoholic fatty liver disease and cardiovascular risks associated with HIV is complex and requires specialist management. Further research is needed to address the best strategies in the management of cardiovascular disease in patients with HIV. This narrative review aims to discuss non-alcoholic fatty liver disease and HIV infection, HIV and cardiovascular disease, as well as how fatty liver modulates cardiovascular disease in HIV patients.


Subject(s)
Cardiovascular Diseases/etiology , HIV Infections/complications , Non-alcoholic Fatty Liver Disease/complications , Cardiovascular Diseases/therapy , Humans , Risk Factors
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