Immunological response to nitroglycerin-loaded shear-responsive liposomes in vitro and in vivo

Liposomes formulated from the 1,3-diamidophospholipid Pad-PC-Pad are shear- responsive and thus promising nano-containers to specifically release a vasodilator at stenotic arteries. The recommended preclinical safety tests for therapeutic liposomes of nanometer size include the in vitro assessment of complement activation and the evaluation of the associated risk of complement activation-related pseudo-allergy (CARPA) in vivo. For this reason, we measured complement activation by Pad-PC- Pad formulations in human and porcine sera, along with the nanopharmaceutical- mediated cardiopulmonary responses in pigs. The evaluated formulations comprised of Pad-PC-Pad liposomes, with and without polyethylene glycol on the surface of the liposomes, and nitroglycerin as a model vasodilator. The nitroglycerin incorporation efficiency ranged from 25% to 50%. In human sera, liposome formulations with 20 mg/mL phospholipid gave rise to complement activation, mainly via the alternative pathway, as reflected by the rises in SC5b-9 and Bb protein complex concentrations. Formulations having a factor of ten lower phospholipid content did not result in measurable complement activation. The weak complement activation induced by Pad- PC-Pad liposomal formulations was confirmed by the results obtained by performing an in vivo study in a porcine model, where hemodynamic parameters were monitored continuously. Our study suggests that, compared to FDA-approved liposomal drugs, Pad-PC-Pad exhibits less or similar risks of CARPA

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Phosphate Test 2.0

The accurate measurement of the phosphate content of a liposomal suspension is important when working with differential scanning calorimetry. Standard phosphate tests date back several decades and require extended hands-on time. Here, we present a rapid version of a phosphate test taking advantage of microwave-assisted chemical digestion and multiwell plate reading technology allowing for the fast and accurate testing of many samples in parallel

The synthesis of an amine-bearing polymerizable phospholipid

Exchange of the natural glycerol phospholipid backbone with an artificial 1,3-diaminopropanol backbone led to the first synthetic 1,3-diaminophospholipid. The amines in the polar head group region were reacted to acrylamides giving a UV polymerizable phospholipid. Preliminary experiments demonstrate that formulated vesicles can be polymerized into large aggregates of vesicles

Association between Current and Cumulative Cannabis use and Heart Rate. The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND Resting heart rate can predict cardiovascular disease. Heart rate increases with tobacco smoking but its association with cannabis use is unclear. We studied the association between current and cumulative cannabis use and heart rate. METHODS We used data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a large prospective cohort of 5,115 Black and white women and men followed over 30 years. We explored the association between cannabis exposure and heart rate, adjusted for demographic factors, cardiovascular risk factors, alcohol and other illicit drug use, physical activity, and beta-blockers, in mixed longitudinal models censoring participants with cardiovascular disease. RESULTS CARDIA participants contributed to 35,654 individual exams over 30 years. At the Year 30 exam, 471/3,269 (14%) currently used cannabis. In multivariable adjusted models, compared to no current use, using cannabis five times per month was associated with lower heart rate of -0.7 bpm (95% CI: -1.0 to -0.3), and daily use with lower heart rate of -2.1 bpm (95% CI: -3.0 to -1.3, overall p<0.001). Cumulative exposure to cannabis use was not associated with heart rate. CONCLUSION Recent current cannabis use was associated with lower resting heart rate. The findings appeared to be transient, as past cumulative exposure to cannabis was not associated with heart rate. This adds to the growing body of evidence suggesting a lack of deleterious association of cannabis use at a level typical of the general population on surrogate outcomes of cardiovascular disease