Prognostic value of static and dynamic biomarkers in COVID-19 patients: a prospective cohort study.

OBJECTIVE: The aim of this study was to analyze in a prospective cohort of hospitalized COVID-19 patients the relationship between biomarkers levels and their variation within the first 4 days since admission, and prognosis. METHODS: Prospective cohort study. Individuals with confirmed diagnosis of covid-19 admitted in our hospital were included. Blood samples were obtained systematically on days 1 and 4 of hospitalization. Levels of RCP, LDH, Ferritin and D-dimer, together with platelets, lymphocytes and neutrophils counts were measured. A combined outcome that included ICU admission and death was considered the primary outcome. Logistic regression analysis was performed. RESULTS: We included 335 patients with confirmed COVID-19. During their hospitalization, 23 (6.8%) needed ICU admission, and 10 (2.9%) died. In the multivariate analysis, a value of RCP greater than 10 mg/dl (OR 8.69, CI95% 1.45-52), an increase in RCP greater than 20% (OR 26.08, CI 95% 3.21-211.3), an increase in LDH greater than 20% (OR 6.29, CI 95% 1.84-21.44), a count of lymphocytes lower than 1500/mm3 (OR 2.74, CI 95% 1.04-7.23), a D-dimer value greater than 550 ng/ml (OR 9.8, CI 95% 1.78-53.9) and a neutrophil/lymphocyte index greater than 3(OR 4.5, CI 95% 1.43-14.19) were all associated with the primary outcome. CONCLUSIONS: Our study shows that the utilization of static and dynamic biomarkers may represent an important tool to assess prognosis of COVID-19 patients.

Cytotoxic activity of Amaryllidaceae alkaloids.

25 Amaryllidaceae alkaloids belonging to different skeletal types were evaluated for their cytotoxic activity against one murine non-tumoral cell line (LMTK) and two human tumoral cell lines (Molt4 and HepG2) according to established protocols. Significant differences of activity related with the type of skeleton of the tested alkaloids could be observed. Pretazettine (22) was among the most active compound among the 25 tested alkaloids on the Molt4 lymphoid cells, but was inactive against HepG2 hepatoma. On the other hand, lycorenine (11) was found to be the most cytotoxic compound against HepG2 hepatoma, even though it appears to be active against Molt4 cells. Almost all of the tested alkaloids showed cytotoxic activity against fibroblastic LMTK cells. Only mesembrenone (25) showed some specificity against Molt4 cells in comparison to LMTK cells.

Comparative evolution of endocytosis levels and of the cell surface area during the L929 cell cycle: a fluorescence study with TMA-DPH.

1-[4-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene (TMA-DPH), a membrane fluorescence probe, interacts with living cells by instantaneous partition between the external medium and the plasma membrane, where it becomes fluorescent. The corresponding fluorescence intensity is then proportional to the cell surface. On the other hand, once incorporated into the plasma membrane, TMA-DPH follows this membrane in the constitutive intracellular traffic and behaves as a monitor for endocytosis. Using this tool on L929 synchronized cells, we showed that the endocytosis levels after 30 min uptake of the probe increased from G1 to mitosis, when they abruptly decreased. The cell surface remained constant throughout the cell cycle, except at the beginning of mitosis when it almost doubled.

Studies on the immunosuppressive properties of 7,25-dihydroxycholesterol--I. Reduction of interleukin production by treated lymphocytes.

Several oxysterols are powerful immunosuppressors. Among them 7,25-dihydroxycholesterol (7,25-OHC) seems to be particularly interesting. The effect of this synthetic sterol on murine lymphocytes, stimulated by Con A, or by allogeneic or TNP-modified syngeneic lymphocytes, was investigated. The results showed that the induction of cytotoxic T-lymphocytes (CTL) was strongly inhibited by a treatment with non-toxic concentrations of this sterol. A marked reduction of interleukin 2 (IL-2) production by alloantigen stimulated lymphocytes occurred at the same concentrations. We also showed that receptors to IL-2 did not appear on lymphocytes stimulated by Con A, when 7,25-OHC was added at the beginning of the culture. The addition of exogenous IL-2 to the culture was found to only slightly reverse the inhibition caused by 7,25-OHC. Taken together, these results indicate that an impairment at the early steps of lymphocyte activation, involving IL-2 secretion, could be responsible, at least in part for the various immunosuppressive effects of 7,25-OHC.