Our data indicate a high prevalence of comorbidities in patients with PA. The hypokalemic variant is defined by a higher morbidity than the normokalemic variant regarding some cardiovascular but not cerebrovascular events. Thus, PA should be sought not only in hypokalemic but also in normokalemic hypertensives because high-excess morbidity occurs in both subgroups.
In this study photophysical characteristics of LOV-based fluorescent proteins which are essential for analytic methods as well as imaging approaches have been comparatively analyzed in detail.
In a large cohort of patients with PA, markers of disease activity such as plasma aldosterone and serum potassium are independent predictors of a lower GFR. Specific interventions, such as adrenalectomy or spironolactone treatment, are associated with a further decline in GFR.
Abstract-In comparison with essential hypertension, primary aldosteronism (PA) is associated with an increased risk of cardiovascular morbidity. To date, no data on mortality have been published. We assessed mortality of patients treated for PA within the German Conn's registry and identified risk factors for adverse outcome in a case-control study.Patients with confirmed PA treated in 3 university centers in Germany since 1994 were included in the analysis. All of the patients were contacted in 2009 and 2010 to verify life status. Subjects from the population-based F3 survey of the Cooperative Health Research in the Region of Augsburg served as controls. Final analyses were based on 600 normotensive controls, 600 hypertensive controls, and 300 patients with PA. Kaplan-Meyer survival curves were calculated for both cohorts. Ten-year overall survival was 95% in normotensive controls, 90% in hypertensive controls, and 90% in patients with PA (P value not significant). In multivariate analysis, age (hazard ratio, 1.09 per year [95% CI, 1.03-1.14]), angina pectoris (hazard ratio, 3.6 [95% CI, 1.04 -12.04]), and diabetes mellitus (hazard ratio, 2.55 [95% CI, 1.07-6.09]) were associated with an increase in all-cause mortality, whereas hypokalemia (hazard ratio, 0.41 per mmol/L [95% CI, 0.17-0.99]) was associated with reduced mortality. Cardiovascular mortality was the main cause of death in PA (50% versus 34% in hypertensive controls; PϽ0.05). These data indicate that cardiovascular mortality is increased in patients treated for PA, whereas all-cause mortality is not different from matched hypertensive controls. (Hypertension. 2012;60:618-624.) • Online Data Supplement Key Words: Conn syndrome Ⅲ aldosterone Ⅲ renin Ⅲ cardiovascular Ⅲ morbidity Ⅲ mortality A ldosterone is a key regulator of fluid and electrolyte balance in human physiology. Aldosterone excess in the presence of a high-sodium diet raises blood pressure. High blood pressure, together with direct proinflammatory and profibrotic effects of aldosterone on the vessel wall, causes and sustains cardiovascular atherosclerosis. 1,2 In keeping with these findings, high aldosterone levels are associated with mortality in heart failure cohorts, 3 and blockade of the renin-angiotensin-aldosterone system by mineralocorticoid antagonists improves outcome in heart failure and after myocardial infarction. 4,5 The contribution of aldosterone to the development of arterial hypertension in the general population has been suggested by the Framingham Offspring Study, in which plasma aldosterone levels in normotensive subjects predicted subsequent increases in blood pressure and the development of hypertension. 6 Recent evidence suggests that primary aldosteronism (PA) is more common than previously thought. 7 Several studies have provided evidence that patients with PA are especially prone to cardiovascular and renal complications. In a recent study by Catena et al, 8 aldosterone excess caused left ventricular hypertrophy and diastolic dysfunction independent of blood pressu...
Dilepton invariant-mass spectra for heavy-ion collisions at SIS 18 and BEVALAC energies are calculated using a coarse-grained time evolution from the Ultra-relativistic Quantum Molecular Dynamics (UrQMD) model. The coarse-graining of the microscopic simulations enables to calculate thermal dilepton emission rates by application of in-medium spectral functions from equilibrium quantum-field theoretical calculations. The results show that extremely high baryon chemical potentials dominate the evolution of the created hot and dense fireball. Consequently, a significant modification of the ρ spectral shape becomes visible in the dilepton invariant-mass spectrum, resulting in an enhancement in the low-mass region Mee = 200 to 600 MeV/c 2 . This enhancement, mainly caused by baryonic effects on the ρ spectral shape, can fully describe the experimentally observed excess above the hadronic cocktail contributions in Ar+KCl (E lab = 1.76 AGeV) reactions as measured by the HADES collaboration and also gives a good explanation of the older DLS Ca+Ca (E lab = 1.04 AGeV) data. For the larger Au+Au (E lab = 1.23 AGeV) system, we predict an even stronger excess from our calculations. A systematic comparison of the results for different system sizes from C+C to Au+Au shows that the thermal dilepton yield increases stronger (∝ A 4/3 ) than the hadronic background contributions, which scale with A, due to its sensitivity on the time evolution of the reaction. We stress that the findings of the present work are consistent with our previous coarse-graining results for the NA60 measurements at top SPS energy. We argue that it is possible to describe the dilepton results from SIS 18 up to SPS energies by considering the modifications of the ρ spectral function inside a hot and dense medium within the same model.However, this also means that lepton pairs from all stages of the reaction will reach the detector. Especially for a theoretical description this is a big challenge, as it demands a realistic description of the whole space-time evolution of the heavy-ion reaction and taking the various dilepton sources into account.On the experimental side several groups have undertaken the challenging task to measure dilepton spectra in heavy-ion collisions and thereby constrain the theoretical predictions. At SPS energies the NA60 Collaboration was able to measure the ρ in-medium spectral function for the first time, thanks to the high precision of the measurement [11]. The results were in line with previous CERES results [12] and found an excess in the invariant mass range from 0.2 to 0.6 GeV/c 2 . This excess can be explained by a broadening of the ρ meson inside the hot and dense medium with small mass shifts [13][14][15][16]. At RHIC, these investigations were extended to even higher collision energies with basically the same results except for less dominant baryonic effects and a larger fraction of dileptons stemming from the QGP [17,18].Still more challenging is the interpretation of the dilepton measurements, which were performed in the...
BackgroundLight, oxygen, voltage (LOV) domains are widely distributed in plants, algae, fungi, bacteria, and represent the photo-responsive domains of various blue-light photoreceptor proteins. Their photocycle involves the blue-light triggered adduct formation between the C(4a) atom of a non-covalently bound flavin chromophore and the sulfur atom of a conserved cysteine in the LOV sensor domain. LOV proteins show considerable variation in the structure of N- and C-terminal elements which flank the LOV core domain, as well as in the lifetime of the adduct state.ResultsHere, we report the photochemical, structural and functional characterization of DsLOV, a LOV protein from the photoheterotrophic marine α-proteobacterium Dinoroseobacter shibae which exhibits an average adduct state lifetime of 9.6 s at 20°C, and thus represents the fastest reverting bacterial LOV protein reported so far. Mutational analysis in D. shibae revealed a unique role of DsLOV in controlling the induction of photopigment synthesis in the absence of blue-light. The dark state crystal structure of DsLOV determined at 1.5 Å resolution reveals a conserved core domain with an extended N-terminal cap. The dimer interface in the crystal structure forms a unique network of hydrogen bonds involving residues of the N-terminus and the β-scaffold of the core domain. The structure of photoexcited DsLOV suggests increased flexibility in the N-cap region and a significant shift in the Cα backbone of β strands in the N- and C-terminal ends of the LOV core domain.ConclusionsThe results presented here cover the characterization of the unusual short LOV protein DsLOV from Dinoroseobacter shibae including its regulatory function, extremely fast dark recovery and an N-terminus mediated dimer interface. Due to its unique photophysical, structural and regulatory properties, DsLOV might thus serve as an alternative model system for studying light perception by LOV proteins and physiological responses in bacteria.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-015-0365-0) contains supplementary material, which is available to authorized users.
Aldosterone excess in the context of primary aldosteronism (PA) has been associated with impaired glucose tolerance and diabetes mellitus. We retrospectively assessed the prevalence of diabetes mellitus in patients from the German Conn's Register and compared the data with those from hypertensive subjects of a population-based survey. In a case-control study, we have compared 638 patients with PA from the German Conn's registry who were treated in 6 German centers with 897 hypertensive control subjects from the population-based F3 survey of the Cooperative Health Research in the Region of Augsburg (KORA). The samples were matched for age, sex, and blood pressure in a 1:1 ratio. Risk factors associated with the presence of diabetes mellitus were calculated in 638 patients with PA and 897 hypertensive controls. In the case control study, the diabetes prevalence was calculated in 338 cases and controls. In patients with primary aldosteronism, age, BMI, and a higher number of antihypertensive drugs (lowest tertile vs. highest tertile) were variables associated with diabetes mellitus. In contrast, serum potassium and plasma aldosterone concentrations were not associated with higher diabetes prevalence, whereas diastolic blood pressure was inversely associated with diabetes mellitus. Diabetes mellitus was more prevalent in patients with PA than in 338 matched controls (23 vs. 10% in controls). Our data for the German population show that diabetes mellitus is more prevalent in patients with primary aldosteronism than in hypertensive controls.
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