The volume of healthy red blood cells is optimal for advective oxygen transport in arterioles.

Red blood cells (RBCs) are vital for transporting oxygen from the lungs to the body's tissues through the intricate circulatory system. They achieve this by binding and releasing oxygen molecules to the abundant hemoglobin within their cytosol. The volume of RBCs affects the amount of oxygen they can carry, yet whether this volume is optimal for transporting oxygen through the circulatory system remains an open question. This study explores, through high-fidelity numerical simulations, the impact of RBC volume on advective oxygen transport efficiency through arterioles, which form the area of greatest flow resistance in the circulatory system. The results show that, strikingly, RBCs with volumes similar to those found in vivo are most efficient to transport oxygen through arterioles. The flow resistance is related to the cell-free layer thickness, which is influenced by the shape and the motion of the RBCs: at low volumes, RBCs deform and fold, while at high volumes, RBCs collide and follow more diffuse trajectories. In contrast, RBCs with a healthy volume maximize the cell-free layer thickness, resulting in a more efficient advective transport of oxygen.

The stress-free state of human erythrocytes: Data-driven inference of a transferable RBC model.

The stress-free state (SFS) of red blood cells (RBCs) is a fundamental reference configuration for the calibration of computational models, yet it remains unknown. Current experimental methods cannot measure the SFS of cells without affecting their mechanical properties, whereas computational postulates are the subject of controversial discussions. Here, we introduce data-driven estimates of the SFS shape and the visco-elastic properties of RBCs. We employ data from single-cell experiments that include measurements of the equilibrium shape of stretched cells and relaxation times of initially stretched RBCs. A hierarchical Bayesian model accounts for these experimental and data heterogeneities. We quantify, for the first time, the SFS of RBCs and use it to introduce a transferable RBC (t-RBC) model. The effectiveness of the proposed model is shown on predictions of unseen experimental conditions during the inference, including the critical stress of transitions between tumbling and tank-treading cells in shear flow. Our findings demonstrate that the proposed t-RBC model provides predictions of blood flows with unprecedented accuracy and quantified uncertainties.

Validation of inducible basophil biomarkers: Time, temperature and transportation.

BACKGROUND: The short stability window of several hours from blood collection to measuring basophil activation has limited the use of flow cytometry-based basophil activation assays in clinical settings. We examine if it is possible to extend this window to 1 day allowing for shipment of samples between laboratories. Several options exist for reporting the results including reporting all the measured values directly, calculating ratios and reporting a single value covering all measured results. Each of these options have different stability and value to the physician. METHODS: Whole blood samples from peanut allergic patients were stimulated with four different peanut concentrations at Day 0, Day 1, and Day 2. Samples were stored under temperature-controlled conditions. Flow cytometry was used to analyze the samples. The basophil activation and degranulation were measured as percentage of positive CD63 basophils and CD203c MFI fold change. Shipped samples were transported under ambient conditions. RESULTS: The results show that CD63 is a stable marker at Day 1. The CD203c ratio decreases significantly at Day 1. Calculating the CD63/IgE ratio proves to be more stable than CD63 alone. The most stable readouts are the semi-quantitative results and the trajectory of the dose response curve. Finally, we confirmed that the stability can be extended to samples shipped overnight to the laboratory. CONCLUSIONS: It is possible to extend the stability of the basophil activation assay to 1 day for samples stored at 18-25°C as well as samples shipped under ambient conditions as long as the temperature is within the 2-37°C range.

Effects of long-term inhaled corticosteroids on adrenal function in patients with asthma.

BACKGROUND: Inhaled corticosteroids (ICSs) are effective asthma controllers, but long-term use could lead to adverse effects. OBJECTIVE: To examine adrenal responsiveness of patients with persistent asthma treated with long-term ICSs. METHODS: Morning plasma cortisol levels before and 30 minutes after adrenocorticotropic hormone (ACTH) (1 microg intravenously) stimulation were compared. Primary end points included mean prestimulation and poststimulation cortisol levels; secondary end points included morning cortisol level of 5 microg/dL or less, post-ACTH stimulation cortisol level of 18 microg/dL or less, and/or a net change of 7 microg/dL or less from baseline. RESULTS: A total of 103 asthmatic patients (29 in the triamcinolone acetonide group, 18 in the flunisolide group, 45 in the fluticasone propionate group, and 11 in the oral corticosteroids group [positive controls]) completed the study. Mean daily ICS doses and durations were as follows: triamcinolone acetonide: 448 microg for 36 months; flunisolide: 1,181 microg for 41 months; and fluticasone propionate: 745 microg for 19 months. Eleven of 30 patients taking high-dose ICSs (10 of 28 taking fluticasone propionate and 1 of 2 taking flunisolide) had both low morning cortisol levels and abnormal post-ACTH stimulation cortisol levels. Few patients taking lower doses of any ICS had abnormal results. CONCLUSIONS: Patients who require long-term treatment with high-dose ICSs may have abnormal morning plasma cortisol levels and reduced responsiveness to ACTH stimulation. Careful monitoring of adrenal function should be considered in such patients.

Rhinitis and rhinologic headaches.

Rhinologic headache, a headache of nasal origin, generally has been attributed to past facial trauma causing nasal mucosa-septal contact points. Patients who have not knowingly experienced nasal trauma may have contact points caused by mucosal inflammation or anatomic abnormalities (septal spurs, septal deviation, and enlarged turbinates) and can develop rhinologic headaches. A population of 66 such patients was studied to classify the type of patient susceptible to such headaches and to examine the type of underlying inflammation or anatomic abnormality responsible for creating their mucosal contact points. Most patients were women with a mean age at the time of initial presentation of 40 years. VMR was the most frequent cause of nasal inflammation, either alone or in combination with allergic rhinitis. Generally, headache symptoms improved with treatment of the underlying nasal inflammation in the majority of patients.

Relative potency of fexofenadine HCl 180 mg, loratadine 10 mg, and placebo using a skin test model of wheal-and-flare suppression.

BACKGROUND: H1-receptor antagonists differ in their ability to produce peripheral H1-blockade. Suppression of histamine-induced flares and wheals is a useful objective test for measuring these differences. OBJECTIVE: To evaluate the relative potency of fexofenadine HCI 180 mg, loratadine 10 mg, and placebo (PBO) in suppressing histamine-induced flares and wheals and compare the onset, duration, and maximum suppression of histamine achieved with each agent. METHODS: Thirty healthy volunteers were enrolled in this randomized, double-blind, single-dose, crossover study. Flares and wheals induced by skin-prick testing with histamine 1.8 mg/mL were measured before treatment, every 20 minutes during the first hour after dosing, and thereafter hourly between 2 and 12 hours and between 23 and 25 hours postdose. RESULTS: Fexofenadine was significantly more effective than loratadine in suppressing the histamine-induced flare response at hours 2 through 7 and 10 through 12 and produced greater flare suppression than did PBO at hours 2 through 25. Onset of flare suppression occurred 2 hours after dosing with fexofenadine and 4 hours after dosing with loratadine. Likewise, fexofenadine was superior to loratadine in suppressing the wheal response from hours 1 through 12 and was more effective than PBO at hours 1 through 12, 24, and 25. Throughout the 25-hour measurement interval, the magnitude of difference in both wheal and flare suppression consistently favored fexofenadine over loratadine. CONCLUSIONS: In a skin test model of wheal-and-flare suppression, fexofenadine showed rapid distribution into the skin compartment with faster onset of action and greater potency vs loratadine.