Modulation of Temoporfin Distribution in Blood by β-Cyclodextrin Nanoshuttles

Photodynamic therapy represents a more targeted and less invasive alternative cancer treatment to traditional modalities. Temoporfin, as with many photosensitizers, is given by injection into a vein, and its subsequent fate is largely determined by the binding to plasma proteins and interaction with endothelial and blood cells. Thus, it is essential to be able to control and to alter the biodistribution of temoporfin in blood. In the present study, we evaluated the effect of co-administration of temoporfin with randomly methylated β-CD (Me-β-CD) on the distribution of temoporfin in the main subpopulations of blood cells of healthy donors using absorbance spectrophotometry and flow cytometry. We showed that cell-bound temoporfin fraction in blood strongly depends on the concentration of Me-β-CD. In fact, the accumulation of temoporfin in white blood cells was more sensitive than that in red blood cells, due to the higher volume of membranous organelles in white blood cells. Finally, we demonstrated that Me-β-CD significantly increases cellular uptake of temoporfin cancer human Burkitt′s lymphoma Raji cells. The presence of Me-β-CD resulted in a spotted pattern of temoporfin distribution in the plasma membrane compartment. Our results clearly demonstrated that β-CDs derivatives provide new options to modulate temoporfin biodistribution in blood.

Analysis of the Mercury Distribution in Blood as a Potential Tool for Exposure Assessment — Results from Two Artisanal and Small-Scale Gold Mining Areas in Zimbabwe

People in artisanal and small-scale gold mining (ASGM) areas are frequently exposed to high levels of mercury (Hg). Hg analyses in urine and whole blood are the gold standard of biomonitoring, although this may not provide sufficient information about the source of exposure, e.g., due to the use of Hg for gold extraction or due to nutrition. To evaluate, whether the pharmacokinetic properties of individual Hg species may be useful for exposure assessment, we determined the Hg levels in different blood components from 199 participants. Therefore, whole blood was centrifuged on-site to yield erythrocytes and plasma. Globin was isolated from the erythrocytes by precipitation with ethyl acetate. Albumin was isolated from plasma by gradual precipitation with saturated ammonium sulfate solution. Hg levels in all samples were determined by using a direct Hg analyzer. Median Hg levels for whole blood, erythrocytes, and plasma were 2.7, 3.7, and 1.3 μg/l, respectively. In globin and albumin, median Hg levels were 10.3 and 7.9 μg/kg, respectively. The distribution of Hg was strongly correlated with whole blood Hg levels (p < 0.01) and the time between the last use of Hg and the date of the participation (p < 0.01). The results suggest that the distribution of Hg in blood is substantially affected by the extent and the frequency of the exposure to elemental Hg. Therefore, the analysis of Hg in erythrocytes and plasma may be a valuable tool for Hg exposure assessment in ASGM areas.

Potential Role of the Galectin-9/TIM-3 Axis in the Disparate Progression of SARS-CoV-2 in a Married Couple: A Case Report

We report the disparate clinical progression of a couple infected by SARS-CoV-2 based on their immune checkpoint (IC) levels and immune cell distribution in blood from admission to exitus in patient 1 and from admission to discharge and recovery in patient 2. A detailed clinical follow-up accompanied by a longitudinal analysis of immune phenotypes and IC levels is shown. The continuous increase in the soluble IC ligand galectin-9 (Gal-9) and the increment in T-cell immunoglobulin and mucin domain-containing 3 (TIM-3) protein in T cells in patient 1 suggests an activation of the Gal-9/TIM-3 axis and, subsequently, a potential cell exhaustion in this patient that did not occur in patient 2. Our data indicate that the Gal-9/TIM-3 axis could be a potential target in this clinical setting, along with a patent effector memory T-cell reduction.

Study of the new 4-phenylpyrrolidinone-2 derivative pharmacokinetics and neuroprotective effect in the ischemic stroke animal model

The development of methods of drug therapy and rehabilitation in different periods of ischemic cerebral lesion is currently an urgent problem. Our study was aimed to investigate the pharmacokinetics and anti-ischemic effect of the new 4-phenylpyrrolidone-2 derivative in rats. To study the drug pharmacokinetics, the Wistar rats were once administered with the substance at a dose of 250 mg/kg, then, the substance distribution in blood and cerebral cortex was evaluated. Elimination half-life value was determined, which was 83.2 min. The substance remained in the brain tissue for 24 hours. To assess the anti-ischemic effect, the stroke was modeled by endovascular middle brain artery transition occlusion, and the drug was administered intravenously for 5 days at two doses, 250 and 125 mg/kg. After that the lesion focus volume was evaluated by MRI, as well as the neurological deficit severity, locomotor and explorative behavior. The studied drug significantly decreased the neurological deficit in model animals compared to control group (1.72 vs 4.4, p < 0.05). According to the MRI data, the effect on the ischemic focus was negligible, while the explorative behavior significantly increased under the influence of the 4-phenylpyrrolidone-2 derivative (hole board test, horizontal activity 12.1 ± 6.8, 22.5 ±10.5, p < 0.05). The data obtained allow us to conclude that the studied substance penetrates the blood-brain barrier (BBB), and accumulates in the brain tissue promoting the neurological deficit correction and increasing the explorative behavior in the ischemic stroke model animals.