Inhibition of thrombin generation by simvastatin and lack of additive effects of aspirin in patients with marked hypercholesterolemia

AbstractOBJECTIVESTo assess the effects of aspirin compared with simvastatin on thrombin generation in hypercholesterolemic men, and to establish whether the reduction of elevated blood cholesterol by simvastatin would affect the action of aspirin on thrombin formation.BACKGROUNDAspirin inhibits thrombin formation, but its performance is blunted in hypercholesterolemia. By virtue of altering lipid profile, statins could be expected to influence thrombin generation.METHODSThirty-three men, aged 34 to 61 years, with minimal or no clinical symptoms, serum total cholesterol >6.5 mmol/liter and serum triglycerides <4.6 mmol/liter, completed the study consisting of three treatment phases. First, they received 300 mg of aspirin daily for two weeks (phase I), which was then replaced by simvastatin at the average dose of 24 mg/d for three months (phase II). In phase III, aspirin, 300 mg/day, was added for two weeks to simvastatin, the dose of which remained unchanged. Thrombin generation was assessed: 1) in vivo, by measuring levels of fibrinopeptide A (FPA) and prothrombin fragment 1+2 (F1+2) in venous blood; and 2) ex vivo, by monitoring the rates of increase of FPA and F1+2 in blood emerging from standardized skin incisions of a forearm. A mathematical model was used to describe the kinetics of thrombin formation at the site of microvascular injury.RESULTSTwo-week treatment with aspirin had no effect on thrombin markers in vivo, while ex vivo it depressed the total amount of thrombin formed, though not the reaction rate. After simvastatin treatment, serum cholesterol decreased by 31% and LDL cholesterol by 42%, while thrombin generation became markedly depressed. In venous blood, FPA was significantly reduced. Concomitantly, the initial thrombin concentration and total amount of thrombin generated decreased significantly. Addition of aspirin to simvastatin (phase III) had no further effect on any of these parameters.CONCLUSIONSIn men with hypercholesterolemia, lowering serum cholesterol level by a three-month simvastatin treatment is accompanied by a marked reduction of thrombin generation both at basal conditions in venous blood and after activation of hemostasis by microvascular injury. Once blood cholesterol became reduced, adding aspirin to simvastatin did not enhance dampening of thrombin formation

Multiple applications of mesenchymal stem cells derived from Wharton’s jelly in the treatment of incomplete spinal cord injury – case report

Publikacja recenzowana / Peer-reviewed publicationWprowadzenie: Przerwanie ciągłości rdzenia kręgowego pozostaje chorobą nieuleczalną, prowadzącą do utraty czynności neurologicznych i mechanicznych poniżej poziomu uszkodzenia. Wciąż brakuje skutecznego sposobu leczenia tego typu urazów. Terapie komórkowe są rozwijającym się intensywnie nowym sposobem leczenia, który może prowadzić do regeneracji uszkodzonego rdzenia kręgowego. Celem niniejszej pracy jest ocena bezpieczeństwa i potencjalnej skuteczności podania macierzystych komórek mezenchymalnych z galarety Whartona (Wharton’s Jelly Mesenchymal Stem Cells – WJMSC) u pacjenta z niekompletnym przerwaniem ciągłości rdzenia kręgowego. Materiał i metody: Pacjent z niecałkowitym przerwaniem ciągłości rdzenia kręgowego na poziomie Th11–12, oceniony w skali ASIA (American Spinal Injury Association Im pairment Scale), został zakwalifikowany do eksperymentalnej terapii z wykorzystaniem komórek WJMSC. U pacjenta przeprowadzono terapię polegającą na pięciokrotnym podaniu komórek WJMSC, co trzy miesiące kolejna dawka. Wyniki: W trakcie terapii nie odnotowano skutków ubocznych bezpośrednio związanych z leczeniem eksperymentalnym. Po każdym podaniu WJMSC zaobserwowano stałą poprawę neurologiczną, a co za tym idzie – poprawę jakości życia. Wynik skali ASIA pacjenta zmienił się z A/B na C/D. Poziom czucia obniżył się istotnie, z Th12 do L3–4. Pacjent odzyskał umiejętność poruszania nogami w podporze, wykorzystując czynną ruchomość mięśni czworogłowych obustronnie z przewagą kończyny dolnej lewej. EMG, ENG i SEP (Somatosensory Evoked Potentials – SEP) obiektywnie potwierdziły poprawę. Wnioski: Wyniki leczenia WJMSC wskazują na obiektywną poprawę, uzyskaną u pacjenta z przewlekłym, niekompletnym uszkodzeniem rdzenia kręgowego.Introduction: Interruption of the spinal cord’s continuity remains an incurable disease, leading to loss of neurological and mechanical functions below the level of damage. Until now, there are no effective ways to treat patients with this type of injury. Cellular therapies are an intensively developing new method of treatment that can lead to the regeneration of a damaged spinal cord. The aim of this study was to assess the safety and potential efficacy of Wharton’s Jelly Mesenchymal Stem Cells (WJMSC) in a patient with an incomplete disruption of the spinal cord’s continuity. Material and methods: A patient with incomplete discontinuation of the spinal cord at Th11–12 level was qualified for experimental therapy using WJMSCs. The patient was rated according to American Spinal Injury Association Impairment Scale (ASIA). The patient underwent a five-time administration of WJMSCs every 3 months. Results: During the therapy there were no side effects directly related to the experimental treatment. After each administration of WJMSC, permanent neurological improvement was observed, followed by improvement in quality of life. The patient’s ASIA score changed from A/B to C/D. The level of sensation decreased significantly from Th12 to L3–4. The patient regained the ability to move his legs in the support, using the active mobility of the quadriceps muscles on both sides with the advantage of the left lower limb. EMG, ENG and SEP objectively confirmed the improvement. Conclusions: The results of WJMSCs treatment indicate an objective improvement in the patient with chronic incomplete spinal cord injury

Anti-Spike SARS-CoV-2 IgG Assessment with a Commercial Assay during a 4-Month Course after COVID-19 Vaccination

We intended to assess the humoral response induced by the Pfizer/BioNTech Comirnaty COVID-19 vaccine with commercially available immunoassays: anti-spike (S) IgG and IgM, and anti-nucleocapsid (N) IgG antibodies, over a 4-month course. One hundred subjects, including 15 COVID-19 convalescents, comprised the study cohort. The SARS-CoV-2 antibodies concentrations were measured on day 0′ and 10′, 20′, 30′, 60′, 90′, and 120′ after the first dose administration. Over the course of the study, 100% of the participants developed and sustained anti-SARS-CoV-2 S IgG antibodies. The highest concentration, exceeding the quantification range of the test (2080 BAU/mL), was reached by 67% of the subjects on day 30′. The concentration of the antibodies remained stable between days 30′ and 90′ but was followed by a significant decrease between days 90′ and 120′. The stronger and more persistent humoral response was noted for women. The COVID-19 convalescents developed higher antibody levels, particularly 10 days after the first Comirnaty dose. Twenty-three out of the eighty-five naïve vaccinees failed to develop a detectable IgM response. LIAISON® SARS-CoV-2 TrimericS IgG (DiaSorin S.p.A, Saluggia, Italy) may be useful in the assessment of the humoral response to the Comirnaty vaccine. In contrast, Abbott’s anti-S SARS-CoV-2 IgM has a limited utility in this context

Head-to-Head Comparison of 5 Anti-SARS-CoV-2 Assays Performance in One Hundred COVID-19 Vaccinees, over an 8-Month Course

The immunoassays used to measure anti-spike SARS-CoV-2 antibodies are widely available on the market. However, their performance in COVID-19 vaccinees is not yet adequately assessed. Our study provides a head-to-head comparison of five methods: Abbott&rsquo;s S1-RBD IgG, Roche&rsquo;s S1-RBD total antibody, Euroimmun&rsquo;s S1 IgG, and DiaSorin&rsquo;s TrimericS IgG and S1/S2 IgG assays. Testing was performed in one hundred vaccinated subjects, at eight timepoints over eight months after vaccination. The results differed substantially between methods; however, they correlated strongly and demonstrated the individuals&rsquo; responses to both doses of vaccination and the waning of humoral immunity after eight months. Importantly, we encountered a high percentage of results above the assay-specific upper quantitation limit (UQL) for undiluted samples. This was the most pronounced for the Roche&rsquo;s and Euroimmun&rsquo;s assays. The Abbott&rsquo;s assay showed the lowest percentage of results above the UQL. We also attempted to find a common way to establish antibody concentrations that might be classified as high. However, this resulted in between 10% and 100% of such results for different methods on day 240&prime;. This highlights the need for an assay-specific approach for adjusting the cut-offs that may indicate COVID-19 immunity

The Influence of Booster Shot and SARS-CoV-2 Infection on the Anti-Spike Antibody Concentration One Year after the First COVID-19 Vaccine Dose Administration

This study pictures the humoral response of 100 vaccinees to Pfizer/BioNTech COVID-19 vaccine over a year, with particular focus on the influence of a booster shot administered around 10 months after the primary immunization. The response to the vaccination was assessed with Diasorin’s SARS-CoV-2 TrimericSpike IgG. Abbott’s SARS-CoV-2 Nucleocapsid IgG immunoassay was used to identify SARS-CoV-2 contact, even asymptomatic. In contrast to the gradual decline of the anti-spike IgG between 30 and 240 days after the first dose, an increase was noted between days 240 and 360 in the whole cohort. However, a statistically significant rise was seen only in boosted individuals, and this effect of the booster decreased over time. An increase was also observed in non-boosted but recently infected participants and a decrease was reported in non-boosted, non-infected subjects. These changes were not statistically significant. On day 360, a percentage of new SARS-CoV-2 infections was statistically lower in the boosted vs. non-boosted subgroups. The booster immunization is the most efficient way of stimulating production of anti-spike, potentially neutralizing antibodies. The response is additionally enhanced by the natural contact with the virus. Individuals with a low level of anti-spike antibodies may benefit the most from the booster dose administration