ABSTRACT
The central serous chorioretinopathy (CSCR) is characterized by serous retinal detachments SRD associated with one or several retinal pigment epithelium detachments/irregularities (PEDs). The choroid is thickened with dilated choroidal veins and choroidal hyperpermeability suggesting an underlying choroidopathy. CSCR belongs to the pachychoroid spectrum. CSCR affects mostly middle-aged men and the main risk factor is the corticosteroid intake. In most cases, the subretinal detachment resolves spontaneously with a good visual prognosis. However, recurrent or chronic form of the disease can lead to irreversible retinal damage and decreased visual acuity. Laser on an extra foveal leak point or half dose/half fluence photodynamic therapy are the first-line treatment options.
Subject(s)
Central Serous Chorioretinopathy , Retinal Detachment , Middle Aged , Male , Humans , Central Serous Chorioretinopathy/complications , Central Serous Chorioretinopathy/diagnosis , Central Serous Chorioretinopathy/epidemiology , Chronic Disease , Fluorescein Angiography , Retinal Detachment/diagnosis , Retinal Detachment/etiology , Retinal Detachment/therapy , Retina , Tomography, Optical Coherence , Retrospective StudiesABSTRACT
BACKGROUND: Since 2016, France is the only country in the World where continuous deep sedation until death (CDSUD) is regulated by law. CDSUD serves as a response to refractory suffering in palliative situations where the patients' death is expected to occur in the following hours or days. Little is known on the psychological adjustment surrounding a CDSUD procedure for healthcare providers (HCPs) and relatives. Our study aims to gather qualitative and quantitative data on the specific processes behind the psychological adjustment of both relatives and HCPs, after the administration of CDSUD for patients with cancer. METHODS: The APSY-SED study is a prospective, longitudinal, mixed-methods and multicenter study. Recruitment will involve any French-speaking adult cancer patient for who a CDSUD is discussed, their relatives and HCPs. We plan to include 150 patients, 150 relatives, and 50 HCPs. The evaluation criteria of this research are: 1/ Primary criterion: Psychological adjustment of relatives and HCPs 6 and 13 months after the death of the patient with cancer (psychological adjustment = intensity of anxiety, depression and grief reactions, CDSUD-related distress, job satisfaction, Professional Stress and Professional experience). Secondary criteria: a)occurrence of wish for a CDSUD in patients in palliative phase; b)occurrence of wish for hastened death in patients in palliative phase; c)potential predictors of adjustment assessed after the discussion concerning CDSUD as an option and before the setting of the CDSUD; d) Thematic analysis and narrative account of meaning-making process concerning the grief experience. DISCUSSION: The APSY-SED study will be the first to investigate the psychological adjustment of HCPs and relatives in the context of a CDSUD procedure implemented according to French law. Gathering data on the grief process for relatives can help understand bereavement after CDSUD, and participate in the elaboration of specific tailored interventions to support HCPs and relatives. Empirical findings on CDSUD among patients with cancer in France could be compared with existing data in other countries and with results related to other medical fields where CDSUD is also conducted. TRIAL REGISTRATION: This protocol received the National Registration Number: ID-RCB2021-A03042-39 on 14/12/2021.
Subject(s)
Deep Sedation , Neoplasms , Adult , Humans , Emotional Adjustment , Prospective Studies , Health Personnel , Observational Studies as Topic , Multicenter Studies as TopicABSTRACT
Objective: In this study, we examine the prevalence and demographic, academic, and psychosocial correlates of perfectionism typologies among postsecondary students. We focus on a lesser-known typology characterized by low personal standards and moderate self-critical cognitions, which we label "discordant perfectionism." Participants: Our sample of 8,689 students from 15 U.S. institutions was drawn from a larger longitudinal investigation of well-being and academic success. Methods: Students completed self-reported measures of perfectionism, demographics, and psychosocial adjustment in spring 2016. GPA was obtained from registrars in fall 2016. Results: A substantial proportion of students were classified as discordant perfectionists (26.1% of undergraduates, 18.8% of graduate students) with Asian students, men, first-generation undergraduates, and international students overrepresented. Discordant perfectionism was associated with markedly worse outcomes than the other typologies, with the lowest average GPA, subjective well-being, coping self-efficacy, and social connectedness. Conclusions: Discordant perfectionism merits further consideration as a risk factor for postsecondary students.
ABSTRACT
New processing techniques for manipulating blood and its components at a microfluidic scale are currently implemented. As for extracorporeal circulation, the in-line evaluation and monitoring of blood properties during these microfluidic techniques is a challenging task. Here, we show that the blood hematocrit can be measured non-invasively in a sub-millimeter medical tube using the non-Newtonian behavior of blood velocity profile. This hematocrit measurement is demonstrated on human blood with a simple Doppler ultrasound system. Results show a mean measurement error of 4.6 ± 1.3%Hct for hematocrit up to 52% and for 5 s-long ultrasonic signals. The simplicity and the measurement scale of the approach make it highly valuable for measuring hematocrit in new blood separation techniques. The approach may have an impact on in-vitro blood processing in general.
Subject(s)
Blood/diagnostic imaging , Hematocrit/methods , Ultrasonography/methods , Adult , Extracorporeal Circulation/methods , Healthy Volunteers , Humans , Hydrodynamics , Microfluidics/methods , Ultrasonics/methodsSubject(s)
Choroidal Neovascularization/diagnosis , Missed Diagnosis , Tomography, Optical Coherence , Aged , Choroid/diagnostic imaging , Choroid/pathology , Choroidal Neovascularization/classification , Choroidal Neovascularization/pathology , Fluorescein Angiography , Humans , Male , Tomography, Optical Coherence/standardsABSTRACT
The goal of this study was to demonstrate the feasibility of semi-automatic evaluation of cardiac Doppler indices in a single heartbeat in human hearts by performing 4D ultrafast echocardiography with a dedicated sequence of 4D simultaneous tissue and blood flow Doppler imaging. 4D echocardiography has the potential to improve the quantification of major cardiac indices by providing more reproducible and less user dependent measurements such as the quantification of left ventricle (LV) volume. The evaluation of Doppler indices, however, did not benefit yet from 4D echocardiography because of limited volume rates achieved in conventional volumetric color Doppler imaging but also because spectral Doppler estimation is still restricted to a single location. High volume rate (5200 volume s-1) transthoracic simultaneous tissue and blood flow Doppler acquisitions of three human LV were performed using a 4D ultrafast echocardiography scanner prototype during a single heartbeat. 4D color flow, 4D tissue Doppler cineloops and spectral Doppler at each voxel were computed. LV outflow tract, mitral inflow and basal inferoseptal locations were automatically detected. Doppler indices were derived at these locations and were compared against clinical 2D echocardiography. Blood flow Doppler indices E (early filling), A (atrial filling), E/A ratio, S (systolic ejection) and cardiac output were assessed on the three volunteers. Simultaneous tissue Doppler indices e' (mitral annular velocity peak), a' (late velocity peak), e'/a' ratio, s' (systolic annular velocity peak), E/e' ratio were also estimated. Standard deviations on three independent acquisitions were averaged over the indices and was found to be inferior to 4% and 8.5% for Doppler flow and tissue Doppler indices, respectively. Comparison against clinical 2D echocardiography gave a pâ value larger than 0.05 in average indicating no significant differences. 4D ultrafast echocardiography can quantify the major cardiac Doppler indices in a single heart beat acquisition.
Subject(s)
Echocardiography, Doppler/methods , Echocardiography, Four-Dimensional/methods , Heart Rate , Laser-Doppler Flowmetry/methods , Regional Blood Flow , Blood Flow Velocity , Cardiac Output , Humans , Ventricular Function, LeftABSTRACT
We present herein 3D elastic tensor imaging (3D ETI), an ultrasound-based volumetric imaging technique to provide quantitative volumetric mapping of tissue elastic properties in weakly elastic anistropic media. The technique relies on (1) 4D ultrafast shear wave elastography (SWE) at very high volume rate (e.g. > 8000 Hz, depending only on the imaging depth), (2) a volumetric estimation of shear wave velocity using the eikonal equation and (3) a generalized 3D elastic tensor-based approach. 3D ETI was first evaluated using numerical simulations in homogeneous isotropic and transverse isotropic media. Results showed that 3D ETI can accurately assess tissue stiffness and tissue anisotropy in weakly transversely isotropic media (elastic fractional anisotropy coefficient < 0.34). Experimental feasibility was shown in vitro in a transverse isotropic phantom. Quantification of the elastic properties by 3D ETI was in good agreement with 2D SWE results performed at different orientations using a clinical ultrafast ultrasound scanner. 3D ETI has the potential to provide a volumetric quantitative map of tissue elastic properties in weakly transversely isotropic soft tissues within less than 20 ms of acquisition for the entire imaged volume.
Subject(s)
Elasticity Imaging Techniques/methods , Imaging, Three-Dimensional/methods , Phantoms, Imaging , Soft Tissue Neoplasms/diagnostic imaging , Ultrasonography/methods , Anisotropy , HumansABSTRACT
4D ultrafast ultrasound imaging was recently shown using a 2D matrix (i.e. fully populated) connected to a 1024-channel ultrafast ultrasound scanner. In this study, we investigate the row-column addressing (RCA) matrix approach, which allows a reduction of independent channels from N × N to N + N, with a dedicated beamforming strategy for ultrafast ultrasound imaging based on the coherent compounding of orthogonal plane wave (OPW). OPW is based on coherent compounding of plane wave transmissions in one direction with receive beamforming along the orthogonal direction and its orthogonal companion sequence. Such coherent recombination of complementary orthogonal sequences leads to the virtual transmit focusing in both directions which results into a final isotropic point spread function (PSF). In this study, a 32 × 32 2D matrix array probe (1024 channels), centered at 5 MHz was considered. An RCA array, of same footprint with 32 + 32 elements (64 channels), was emulated by summing the elements either along a line or a column in software prior to beamforming. This approach allowed for the direct comparison of the 32 + 32 RCA scheme to the optimal fully sampled 32 × 32 2D matrix configuration, which served as the gold standard. This approach was first studied through PSF simulations and then validated experimentally on a phantom consisting of anechoic cysts and echogenic wires. The contrast-to-noise ratio and the lateral resolution of the RCA approach were found to be approximately equal to half (in decibel) and twice the values, respectively, obtained when using the 2D matrix approach. Results in a Doppler phantom and the human humeral artery in vivo confirmed that ultrafast Doppler imaging can be achieved with reduced performances when compared against the equivalent 2D matrix. Volumetric anatomic Doppler rendering and voxel-based pulsed Doppler quantification are presented as well. OPW compound imaging using emulated RCA matrix can achieve a power Doppler with sufficient contrast to recover the vein shape and provides an accurate Doppler spectrum.
Subject(s)
Image Processing, Computer-Assisted/methods , Phantoms, Imaging , Signal Processing, Computer-Assisted , Ultrasonography/methods , HumansABSTRACT
Ultrasonic strain imaging has been applied to echocardiography and carries great potential to be used as a tool in the clinical setting. Two-dimensional (2D) strain estimation may be useful when studying the heart due to the complex, 3D deformation of the cardiac tissue. Increasing the framerate used for motion estimation, i.e. motion estimation rate (MER), has been shown to improve the precision of the strain estimation, although maintaining the spatial resolution necessary to view the entire heart structure in a single heartbeat remains challenging at high MERs. Two previously developed methods, the temporally unequispaced acquisition sequence (TUAS) and the diverging beam sequence (DBS), have been used in the past to successfully estimate in vivo axial strain at high MERs without compromising spatial resolution. In this study, a stochastic assessment of 2D strain estimation precision is performed in vivo for both sequences at varying MERs (65, 272, 544, 815 Hz for TUAS; 250, 500, 1000, 2000 Hz for DBS). 2D incremental strains were estimated during left ventricular contraction in five healthy volunteers using a normalized cross-correlation function and a least-squares strain estimator. Both sequences were shown capable of estimating 2D incremental strains in vivo. The conditional expected value of the elastographic signal-to-noise ratio (E(SNRe|ε)) was used to compare strain estimation precision of both sequences at multiple MERs over a wide range of clinical strain values. The results here indicate that axial strain estimation precision is much more dependent on MER than lateral strain estimation, while lateral estimation is more affected by strain magnitude. MER should be increased at least above 544 Hz to avoid suboptimal axial strain estimation. Radial and circumferential strain estimations were influenced by the axial and lateral strain in different ways. Furthermore, the TUAS and DBS were found to be of comparable precision at similar MERs.
Subject(s)
Echocardiography/methods , Elasticity Imaging Techniques/methods , Heart Ventricles/diagnostic imaging , Heart/physiopathology , Image Interpretation, Computer-Assisted/methods , Stochastic Processes , Stress, Mechanical , Adult , Heart Rate , Humans , Signal-To-Noise RatioABSTRACT
BACKGROUND: Non-small cell lung cancers (NSLC) are aggressive cancers that are insensitive to chemotherapies and accounts for nearly 33% of all cancer deaths in the United States. Two hallmarks of cancer that allow cells to invade and metastasize are sustained proliferation and enhanced motility. In this study we investigate the relationship between urokinase plasminogen activator (uPA)/uPA receptor (uPAR) signaling and Na(+)/H(+) exchanger isoform 1 (NHE1) expression and activity. METHODS AND RESULTS: The addition of 10nM uPA increased the carcinogenic potential of three NSCLC cell lines, NCI-H358, NCI-H460, and NCI-H1299. This included an increase in the rate of cell proliferation 1.6 to 1.9 fold; an increase in the percentage of cells displaying stress fibers 3.05 to 3.17 fold; and an increase in anchorage-independent growth from 1.64 to 2.0 fold. In each of these cases the increase was blocked when the experiments were performed with NHE1 inhibited by 10 µM EIPA (ethylisopropyl amiloride). To further evaluate the role of uPA/uPAR and NHE1 in tumor progression we assessed signaling events using full-length uPA compared to the uPA amino terminal fragment (ATF). Comparing uPA and ATF signaling in H460 cells, we found that both uPA and ATF increased stress fiber formation approximately 2 fold, while uPA increased matrix metalloproteinase 9 (MMP9) activity 5.44 fold compared to 2.81 fold for ATF. To expand this signaling study, two new cell lines were generated, one with reduced NHE1 expression (H460 NHE1 K/D) and one with reduced uPAR expression (H460 uPAR K/D). Using the K/D cell lines we found that neither uPA nor ATF could stimulate stress fiber formation or MMP9 activity in cells with dramatically decreased NHE1 or uPAR expression. Finally, using in vivo tumor formation studies in athymic mice we found that when mice were injected with H460 cells 80% of mice formed tumors with an average volume of 390 mm(3). This was compared to 20% of H460 uPAR K/D injected mice forming tumors with an average volume of 15 mm(3) and 10% of H460 NHE1 K/D injected mice forming tumors with an average volume of 5 mm(3). CONCLUSION: Taken together, these data demonstrate that uPA/uPAR-mediated tumor progression and metastasis requires NHE1 in NSCLC cells and suggests a potential therapeutic approach to blocking cancer progression.
ABSTRACT
The right ventricular apex (RVA) is a potential hot spot for development of cardiac rhythm anomalies. Many conditions, including arrhythmogenic right ventricular cardiomyopathy and Brugada's syndrome affect the RVA, and further, the RVA remains an incompletely characterized pacing region. Whether there are structural reasons underlying these conduction properties remains unsettled. In the current study, we characterize the mechanical strains and structural attributes of the right ventricular wall, and test the hypothesis that the right ventricular apex experiences heterogeneous strain distributions and altered fiber organization, and is thus susceptible to conduction alterations. Electromechanical wave imaging (EWI), or elastography, of hearts was used to quantify mechanical strains occurring through a cardiac cycle. Histological and immunofluorescence imaging techniques were used to examine cardiac wall structure and arrangement of junctional proteins. Right ventricular mechanical strains were elevated and sustained throughout systole, compared to the left ventricle and septum. Heterogeneous strain distributions, myocardial fiber disarray, and altered junctional protein localization occured at the RVA. Disarray and altered strain distributions suggest decreased structural strength at the right ventricular apex in particular and increased mechanical impositions in the right ventricle, respectively. Thus, these data demonstrate why the right ventricular apex may be particularly vulnerable to conduction abnormalities.
ABSTRACT
Measurement of the Henry factor over large optical bandwidth is carried out in a single step without any filtering, using a technique based on the sinusoidal phase modulation method. This fast technique was successfully applied to a directly modulated Fabry Perot laser to obtain simultaneously the linewidth enhancement factor (LEF) of 14 longitudinal modes. It is also well suited for electro-absorption modulators (EAM) for which the α-factor is determined over 15 nm optical bandwidth. A very good agreement is found with the well established fiber transfer function method.
ABSTRACT
The role of phospholipase D (PLD) in cytoskeletal reorganization, ERK activation, and migration is well established. Both isoforms of PLD (PLD1 and PLD2) can independently activate stress fiber formation and increase ERK phosphorylation. However, the isoform's specificity, upstream activators, and downstream targets of PLD that coordinate this process are less well understood. This study explores the role of α(1) -adrenergic receptor stimulation and its effect on PLD activity. We demonstrate that PLD1 activators, RhoA, and PKCα are critical for stress fiber formation and ERK activation, and enhance the production of phosphatidic acid (PA) upon phenylephrine addition. Ectopic expression of dominant negative PLD1 and not PLD2 blocks ERK activation, inhibits stress fiber formation, and reduces cell motility in CCL39 fibroblasts. Furthermore, we demonstrate the mechanism for PLD1 activation of ERK involves Ras. This work indicates that PLD1 plays a novel role mediating growth factor and cell motility events in α(1) -adrenergic receptor-activated cells.
Subject(s)
Cytoskeleton/metabolism , Fibroblasts/metabolism , Phospholipase D/metabolism , Receptors, Adrenergic, alpha-1/metabolism , Animals , Cell Movement/drug effects , Cricetinae , Cricetulus , Cytoskeleton/drug effects , Fibroblasts/drug effects , Phenylephrine/pharmacology , Phosphatidic Acids/metabolism , Protein Kinase C-alpha/metabolism , Signal Transduction/drug effects , ras Proteins/metabolism , rhoA GTP-Binding Protein/metabolismABSTRACT
Four gas-permeable wrapping films exhibiting different degrees of water permeability (ranging from 1.6 to 500 g/m(2) per d) were tested to study their effect on soft-mold (Camembert-type) cheese-ripening dynamics compared with unwrapped cheeses. Twenty-three-day trials were performed in 2 laboratory-size (18L) respiratory-ripening cells under controlled temperature (6 ± 0.5°C), relative humidity (75 ± 2%), and carbon dioxide content (0.5 to 1%). The films allowed for a high degree of respiratory activity; no limitation in gas permeability was observed. The wide range of water permeability of the films led to considerable differences in cheese water loss (from 0.5 to 12% on d 23, compared with 15% for unwrapped cheeses), which appeared to be a key factor in controlling cheese-ripening progress. A new relationship between 2 important cheese-ripening descriptors (increase of the cheese core pH and increase of the cheese's creamy underrind thickness) was shown in relation to the water permeability of the wrapping film. High water losses (more than 10 to 12% on d 23) also were observed for unwrapped cheeses, leading to Camembert cheeses that were too dry and poorly ripened. On the other hand, low water losses (from 0.5 to 1% on d 23) led to over-ripening in the cheese underrind, which became runny as a result. Finally, water losses from around 3 to 6% on d 23 led to good ripening dynamics and the best cheese quality. This level of water loss appeared to be ideal in terms of cheese-wrapping film design.
Subject(s)
Cheese/analysis , Food Handling/methods , Animals , Food Technology , Gases , Permeability , WaterABSTRACT
In the visual system, neurons with similar functional properties such as orientation and direction selectivity are clustered together to form modules. Optical imaging recordings in combination with episodic paradigms have been previously used to estimate direction selectivity, a fundamental property of visual neurons. The major drawback of the episodic approach is that the extraction of the signal from various forms of physiological noise is difficult, leading to a poor estimation of direction. Recent work, based on periodic stimulation and Fourier decomposition improved the extraction of periodic stimulus responses from noise and thus, reduced the recording time considerably. Given the success of this new paradigm in mapping orientation, the present study evaluated its reliability to measure direction selectivity in the visual cortex of anesthetized cats. Here, a model that exploits the harmonics of the Fourier decomposition is proposed where the first harmonic is related to direction responses, and the second to orientation. As expected, the first harmonic was absent when a static stimulus was presented. Contrarily, the first harmonic was present when moving stimuli were presented and the amplitude was greater with random dots kinematograms than with drifting gratings. The phase of the first harmonic showed a good agreement with direction preference measured by episodic paradigm. The ratio of the first/the second harmonic amplitude, related to a direction index, was weaker in fracture. It was also weaker in areas of the ventral pathway (areas 17 and 21a) where direction selectivity is known to be reduced. These results indicate that a periodic paradigm can be easily used to measure specific parameters in optical signals, particularly in situations when short acquisition periods are needed.
Subject(s)
Brain Mapping/methods , Motion Perception/physiology , Optics and Photonics/methods , Visual Cortex/physiology , Visual Perception/physiology , Algorithms , Animals , Cats , Fourier Analysis , Mice , Models, Theoretical , Photic Stimulation , Rats , Vision, Binocular/physiology , Vision, Monocular/physiology , Visual Cortex/blood supplyABSTRACT
Prevention of cardiovascular disease should target high-risk subjects based on genetic/familial factors, blood chemistry, blood pressure, body mass index (BMI), and a history of/or current cigarette smoking. We selected active adults (n=76) aged 30-60 and investigated these risk factors, in order to recommend preventive measures. Another interesting variable is the preclinical status or atheroma of the arterial (carotid) wall or lumen. We also investigated the presence of oxidative stress in, and the anti-oxidant status of these subjects. We studied the anti-oxidative efficacy of superoxide dismutase (SOD) and variations of malondialdehyde (MDA). Supplementation with GliSODin, a vegetal SOD associated with gliadin, was effective in controlling the thickness of the carotid artery intima and media layers as measured by ultrasonography-B. We could demonstrate the preventive efficacy of GliSODin at a preclinical stage in subjects with risk factors of cardiovascular disease.
Subject(s)
Carotid Artery Diseases/prevention & control , Gliadin/administration & dosage , Superoxide Dismutase/administration & dosage , Adult , Carotid Arteries/diagnostic imaging , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/metabolism , Dietary Supplements , Female , Humans , Male , Malondialdehyde/metabolism , Middle Aged , Ultrasonography/methodsABSTRACT
The aim of the current study was to establish the quantitative relationship between plasma potassium concentrations and the QT interval of the electrocardiogram in dogs. Furosemide, a potent diuretic, was given at increasing doses (5-60 mg/kg) to five male and five female beagle dogs. Electrocardiogram (ECG) was recorded three times each day, simultaneous to blood sampling for measurement of plasma potassium. Furosemide treatment produced a clear hypokalaemia, which was associated with an increase in QT and corrected QT intervals (QTc) duration. On average, the slopes of the negative linear correlation between potassium plasma levels and QT or QTc were steeper in females than in males. These results show that a decrease in potassium plasma level may explain a concomitant increase in QT duration in a toxicity study in dogs, in particular if potassium values are decreased below 3.3 mmol/L. Correction of QT interval for K+ plasma level has, therefore, been established separately for males and females. A global formula correcting QT for K+ and heart rate simultaneously was established. Hypokalaemia was also associated with changes in the morphology of the T wave recorded in CV5RL, in particular, with a flattening and/or a notching of the wave (appearance of a second peak), biphasic aspect or inversion of polarity. These changes are probably related to an increased heterogeneity of repolarization between different populations of cardiomyocytes. In conclusion, hypokalaemia is quantitatively associated with an increase in QT and QTc duration in dogs. The relationship is apparently stronger for females than for males. A formula may be used to correct QT for potassium plasma level.
Subject(s)
Heart/physiology , Potassium/blood , Animals , Calcium/blood , Dogs , Dose-Response Relationship, Drug , Electrocardiography/drug effects , Female , Furosemide/pharmacology , Heart Rate , Male , Sodium/blood , Sodium Potassium Chloride Symporter Inhibitors/pharmacologyABSTRACT
This study directly demonstrates that cardiac troponin I (cTnI) is a sensitive, specific, and persistent biomarker in laboratory animals. Histopathological and pathophysiological cardiac changes in dogs, rats and mice correlated with increased serum cTnI with various cardiac inotropic agents, and cardiotoxic drugs and with cardiac arrhythmias, tachycardia, cardiac effusion with dyspnoea, and ageing. A comparison of six immunoassays for cTnI and cardiac troponin T (cTnT) to detect and monitor cardiac injury in a rodent model indicated that enzyme-linked immunosorbent (Life Diagnostics Inc and TriChem Resources Inc, West Chester, Philadelphia, USA) and Immulite (Diagnostic Products Corporation, Llanberis, UK) assays had low sensitivity and less than 1% of the dynamic range of Centaur (Bayer Healthcare Diagnostics, Newbury, UK) cTnI and Elecsys (Roche Diagnostics, Basel, Switzerland) and M8 (Bioveris Europe, Whitney, UK) cTnT assays. In dogs, however, the Immulite assay was effective and correlated with the Centaur. Serum concentrations were highly correlated but 10-fold lower for cTnT compared with cTnI with cardiac injury. Centaur assay also detected cTnI in myocardium from marmosets, swine, cattle, and guinea pigs, indicating it to be candidate cardiac biomarker for these species as well. Purified rat cTnI was 50% more reactive than purified human cTnI in the Centaur assay. In the rat, an age- and gender-dependent variation in serum cTnI was found. Male rats aged six and eight months had a 10-fold greater serum cTnI than age-matched females and three-month-old rats. These increases correlated with minimal histopathological change. Isoproterenol-induced serum cTnI increased up to 760-fold the minimal detectable concentration of 0.07 microg/L, within 4-6 h and decreased with a half-life of 6 h, with an expected return to baseline of 60 h. Severity of histopathological change correlated with serum cTnI during the ongoing injury.
Subject(s)
Animal Diseases/blood , Animals, Laboratory/blood , Heart Diseases/veterinary , Luminescent Measurements/veterinary , Troponin I/blood , Animal Diseases/diagnosis , Animals , Biomarkers/blood , Dogs , Female , Heart Diseases/blood , Luminescent Measurements/standards , Male , Mice , Myocardium/chemistry , Rats , Sensitivity and Specificity , Troponin T/bloodABSTRACT
The activation of the Na+-H+ exchanger 1 (NHE1) and extracellular-signal regulated kinase (ERK) phosphorylation in Chinese hamster lung fibroblasts (CCL39) was characterized in response to the specific alpha1-adrenergic agonist, phenylephrine (PE). Addition of 100 micromol PE/L increased the steady-state intracellular pH (pHi) by 0.16 +/- 0.03 pH units, as well as increasing the phosphorylation of ERK. The response of NHE1 to PE in CCL39 cells was determined by the use of specific antagonists. Use of 2 specific chemical inhibitors of phosphoinositide-specific phospholipase C (PLC) reduced the ability of PE to activate either the exchanger or ERK. Studies were conducted in PLCbeta-deficient cell lines derived from parental CCL39 cells. NHE1 activity in both mutant cell lines was increased in response to phorbal esters or lysophosphatidic acid, whereas the addition of PE only caused a minimal change in either pHi or ERK phosphorylation. These results, combined with reconstitution experiments with exogenously expressed PLCbeta1, PLCbeta2, or PLCbeta3, revealed that stimulation of NHE1 activity by PE in CCL39 cells is a PLCbeta1-coupled event. Furthermore, the data indicate that alpha1-adrenergic signaling of PLCbeta is upstream of ERK activation. These data demonstrate that PLCbeta1 is primarily involved in the activation of NHE1 in CCL39 fibroblasts.