Wpływ oligomerów procyanidolowych na aktywność antykoagulacyjną osocza

Background. Procyanidolic oligomers (PO) inhibit the degradation of subendothelial connective tissue by collagenase and elastase neutralization. Their efficacy in postphlebitic syndrome and venous insufficiency may suggest an additional systemic action mediated by endothelium. Therefore, the plasma anticoagulant response and the tissue plasma pathway inhibitor (TFPI) release induced by PO was assessed. Material and methods. Twenty-six patients, both surgical and medical, aged 29–86 years, who required antithrombotic prophylaxis for at least 5 days, were included in the study. The patients with higher thrombotic risk received either unfractionated heparin (UFH; 5000 IU bid, s.c., n = 8) or low molecular weight heparin (LMWH; 2850 IU AXa/0.3 mL o.d, s.c., n = 8). The patients with lower thrombotic risk received PO (150 mg bid, p.o., n = 10). In the control group there were age- and sex-matched healthy volunteers, to whom a placebo was administered. Blood samples were drawn before, on the 1, 4, 8 h, as well as on the days 2, 5 after administration of the study medication. Results. The TFPI concentration did not change significantly from the baseline value at any time, either in patients or in controls. Anti-Xa activity increased at 1 h until day 5 after administration of each study medication. Anti-IIa activity increased at 1 hour and remained elevated until day 5 under UFH and LMWH treatment, but only until day 2 in the PO group. The area under the curve of both anti-Xa and anti-IIa activity was similar in all three study groups but significantly larger as compared to the controls. Conclusions. Procyanidolic oligomers, like heparin and LMWH, induce anticoagulant response in plasma, but do not release TFPI into the blood.Wstęp. Oligomery procyanidolowe (PO) hamują degradację podśródbłonkowej tkanki łącznej poprzez neutralizację kolagenazy i elastazy. Skuteczność PO w zespole pozakrzepowym i niewydolności żylnej może sugerować ich dodatkowe działanie układowe, w którym pośredniczy śródbłonek. Było to przesłanką do oceny odpowiedzi antykoagulacyjnej osocza wywoływanej przez PO i uwalniania inhibitora drogi zewnątrzpochodnej (TFPI). Materiał i metody. Do badania włączono 26 chorych z oddziałów chirurgicznego i internistycznego w wieku 29–86 lat, u których konieczne było zastosowanie profilaktycznej terapii przeciwzakrzepowej przez co najmniej 5 dni. Chorzy z dużym ryzykiem zakrzepowym otrzymywali albo heparynę niefrakcjonowaną (UFH; 5000 jm. dwa razy dziennie podskórnie, n = 8), albo heparynę drobnocząsteczkową (LMWH; 2850 jm. AXa/0,3 ml raz dziennie podskórnie, n = 8). Pacjenci, u których ryzyko zakrzepowe było małe, otrzymywali PO (150 mg dwa razy dziennie doustnie, n = 10). Grupę kontrolną stanowili zdrowi ochotnicy zaklasyfikowani według wieku i płci, otrzymujący placebo. Krew do badań pobierano przed podaniem leku oraz w 1., 4. i 8. godzinie oraz w 2. i 5. dniu od podania leku. Wyniki. Stężenie TFPI nie zmieniało się w porównaniu z wartością wyjściową zarówno w grupach badanych, jak i kontrolnej. Aktywność anty-Xa zwiększała się od 1. godziny do 5. dnia po podaniu każdego leku. Aktywność anty-IIa była zwiększona od 1. godziny do 5. dnia po podaniu UFH i LMWH, ale tylko do 2. dnia po PO. Całkowita aktywność anty-Xa i anty-IIa, oceniana jako wielkość pola pod krzywą w badanym czasie, była podobna we wszystkich grupach badanych, ale znacząco wyższa w porównaniu z grupą kontrolną. Wnioski. Oligomery procyanidolowe, podobnie jak heparyna niefrakcjonowana i drobnocząsteczkowa, wywołują odpowiedź antykoagulacyjną w osoczu, ale nie powodują uwalniania TFPI do krwi

A Quantitative and Qualitative Report of Psilocybin Induced Mystical-Type Experiences and Their Relation to Lasting Positive Effects

Psychedelic drugs such as psilocybin are under investigation for the treatment of several psychiatric conditions. They also have the remarkable property of producing persisting positive psychological changes in healthy volunteers for at least several months. In this study, 35 medium-high doses of psilocybin were administered to 28 healthy volunteers (12 females). By the end of the dosing day, participants reported the intensity of their acute experience using the 30-item Mystical Experience Questionnaire (MEQ) and an open-form qualitative report from home. Persisting psychological effects attributed to the psilocybin experience were measured using the Persisting Effects Questionnaire (PEQ) three-months after administration. Using a linear latent-variable model we show that the MEQ total score is positively associated with the later emergence of positive PEQ effects (p = 3x10-5). Moreover, the MEQ subscales “Positive Mood” (pcorr = 4.1x10-4) and “Mysticality” (pcorr = 2.0x10-4) are associated with positive PEQ whereas the subscales “Transcendence of Time and Space” (pcorr = 0.38) and “Ineffability” (pcorr = 0.45) are not. Using natural language pre-processing, we provide the first qualitative descriptions of the “Complete Mystical Experience” induced by orally administered psilocybin in healthy volunteers, revealing themes such as a sense of connection with the universe, familial love, and the experience of profound beauty. Combining qualitative and quantitative methods, this paper expands understanding of the acute psilocybin induced experience in healthy volunteers and suggests an importance of the type of experience in predicting lasting positive effects

Psilocybin-Induced Mystical-Type Experiences are Related to Persisting Positive Effects:A Quantitative and Qualitative Report

Psychedelic drugs such as psilocybin have shown substantial promise for the treatment of several psychiatric conditions including mood and addictive disorders. They also have the remarkable property of producing persisting positive psychological changes in healthy volunteers for at least several months. In this study (NCT03289949), 35 medium-high doses of psilocybin were administered to 28 healthy volunteers (12 females). By the end of the dosing day, participants reported the intensity of their acute experience using the 30-item Mystical Experience Questionnaire (MEQ) and an open-form qualitative report from home. Persisting psychological effects attributed to the psilocybin experience were measured using the Persisting Effects Questionnaire (PEQ) 3-months after administration. Using a linear latent-variable model we show that the MEQ total score is positively associated with the later emergence of positive PEQ effects (p = 3 × 10(−5)). Moreover, the MEQ subscales “Positive Mood” (p (corr) = 4.1 × 10(−4)) and “Mysticality” (p (corr) = 2.0 × 10(−4)) are associated with positive PEQ whereas the subscales “Transcendence of Time and Space” (p (corr) = 0.38) and “Ineffability” (p (corr) = 0.45) are not. Using natural language pre-processing, we provide the first qualitative descriptions of the “Complete Mystical Experience” induced by orally administered psilocybin in healthy volunteers, revealing themes such as a sense of connection with the Universe, familial love, and the experience of profound beauty. Combining qualitative and quantitative methods, this paper expands understanding of the acute psilocybin induced experience in healthy volunteers and suggests an importance of the type of experience in predicting lasting positive effects