Red blood cells (RBC) may act as selective carriers of drugs to macrophages, an important reservoir of viruses such as human immunodeficiency virus (HIV) and herpes simplex virus type 1 (HSV-1). We ...therefore assessed the incorporation of 9-(2-phosphonylmethoxyethyl)adenine (PMEA, a potent inhibitor of HIV and HSV-1) into RBC, its delivery to macrophages and its activity against HIV or HSV-1. Loading of PMEA in artificially aged opsonized RBC affords significant levels of intracellular PMEA. RBC metabolize PMEA to its active congener PMEA-diphosphate, although with low efficiency. Exposure of macrophages to RBC-encapsulated PMEA inhibits the replication of both HIV and HSV-1 (about 90% inhibition at the highest RBC:macrophages ratios) even if RBC were removed before virus challenge. By contrast, the antiviral activity of free PMEA removed before virus challenge was irrelevant at concentrations up to 150-fold higher than the 50% effective concentration (EC
50). Finally, the antiviral effect of RBC-encapsulated PMEA correlates with PMEA levels in macrophages about 500-fold higher than those achieved by free PMEA (at concentrations 10-fold higher than the EC
50). The efficacy of RBC-mediated delivery to macrophages of PMEA (and perhaps of compounds with shorter intracellular half-lives) warrants further studies in infectious diseases involving phagocytizing cells as main targets of the pathogen.
The importance of establishing correlations between cardiac function (cardiac output and stroke volume) and total body water (TBW) content in normal and hypertensive pregnancy focuses primarily on ...their potential relevance in treatment. Total body water content and cardiac function were evaluated in 25 normotensive (N) and 22 gestational hypertensive (GH) pregnant women matched for age, gestational age, and pre-pregnancy body mass index (BMI) during the third trimester of gestation.
Patients underwent maternal echocardiography, bioelectrical impedance analysis (BIA), and hematocrit (Hct) evaluation, and the water balance index (WBI), i.e. the ratio of total body water to hematocrit, was computed. Hematocrit showed significantly lower values in normal than in GH women (31.9+/-2.2% vs. 36.2+/-2.5%; p<0.001).
There was no difference in TBW between the two groups. The WBI was higher in normal than in GH women (1.35+/-0.20 l.kg-1.m-2 vs. 1.19+/-0.18 l.kg-1.m-2; p<0.001). Normal subjects showed a higher stroke volume than GH patients (78.0+/-9.7 ml vs 67.9+/-10.2 ml; p=0.001). Atrial function was also higher in normal than in GH women (left atrial fractional area change: 57.4+/-5.1% vs. 42.5+/-7.5%; p<0.001). Correlation was found between stroke volume and WBI (r=0.93, p<0.0001).
Maternal cardiac function and the water balance index are strongly related and might help in comprehending the mechanisms of adaptation in physiologic and hypertensive pregnancy.
DARTWARS (Detector Array Readout with Traveling Wave AmplifieRS) is a three years project that aims to develop high-performing innovative Traveling Wave Parametric Amplifiers (TWPAs) for low ...temperature detectors and qubit readout (C-band). The practical development follows two different promising approaches, one based on the Josephson junctions (TWJPA) and the other one based on the kinetic inductance of a high-resistivity superconductor (KITWPA). This paper presents the advancements made by the DARTWARS collaboration to produce a first working prototype of a KITWPA.
The DARTWARS project has the goal of developing high-performing innovative travelling wave parametric amplifiers with high gain, large bandwidth, high saturation power, and nearly quantum-limited ...noise. The target frequency region for its applications is 5 - 10 GHz, with an expected noise temperature of about 600 mK. The development follows two different approaches, one based on Josephson junctions and one based on kinetic inductance of superconductors. This contribution mainly focuses on the Josephson travelling wave parametric amplifier, presenting its design, preliminary measurements and the test of homogeneity of arrays of Josephson junctions.
