Relationship of chronic neurogenic pain and fibrinolysis in the blood of patients with melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22085-e22085
Author(s):  
Ludmila Ya. Rozenko ◽  
Elena M. Frantsiyants ◽  
Valeria A. Bandovkina ◽  
Yulia A. Pogorelova ◽  
Natalia D. Cheryarina ◽  
...  

e22085 Background: The plasminogen regulation system is critical in triggering proteolysis to cleave the extracellular matrix and basement membrane. The “uPA-uPAR” system is involved in extravascular fibrinolysis and is responsible for the formation of plasmin associated with invasion and metastasis. The purpose of the study was to analyze levels of factors of the plasminogen regulation system in the blood of patients with cutaneous melanoma (M) and chronic neurogenic pain (CNP). Methods: Blood levels of PAP, uPA, uPAR and PAI-1 were measured by ELISA in patients with Т3-4NxM0 melanoma: 21 women with CNP (pelvic pain - 7, osteochondrosis – 14), mean age 67.2±2.7 years; 17 men with CNP (osteochondrosis), mean age 65.6±3.1 years. The control group included patients with melanoma similar in age, gender and disease stages without CNP. Results: Blood levels of PAP in women with M+CNP were twice higher than in patients with M without CNP, the levels in men with M+CNP did not change; uPA content increased in both women and men with M without CNP by 1.4 and 1.5 times, uPA activity was elevated only in women by 2.4 times, in men it was reduced by 2 times; uPAR was increased by 1.5 times in women and men compared to the values in both female and male patients with M without CNP. PAI-1 content in women and men with M+CNP was similar to control values, and its activity was increased in women by 1.5 times and decreased in men by 2.5 times. Conclusions: The study gives significant additional information on the effect of CNP on relationships in the plasminogen activation system in a combination of cutaneous melanoma and CNB showing marked gender differences. The results should be taken into account in the special treatment of patients with melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22082-e22082
Author(s):  
Valeria A. Bandovkina ◽  
Elena M. Frantsiyants ◽  
Ludmila Ya. Rozenko ◽  
Viktoria V. Pozdnyakova ◽  
Natalia D. Cheryarina ◽  
...  

e22082 Background: Clusters of tumor cells in blood vessels secrete VEGF family factors necessary for the formation of premetastatic niches. TGF-β activates the epidermal-mesenchymal transition (EMT). The purpose of the study was to analyze levels of angiogenesis and EMT factors in the blood of patients with cutaneous melanoma (M) and chronic neurogenic pain (CNP). Methods: Blood levels of VEGF-A, VEGF-C, VEGFR-1, VEGFR-3, TGF-β1 and TGF-βR2 were measured by ELISA in patients with Т3-4NxM0 melanoma: 21 women with CNP (pelvic pain - 7, osteochondrosis – 14), mean age 67.2±2.7 years; 17 men with CNP (osteochondrosis), mean age 65.6±3.1 years. The control group included patients with melanoma similar in age, gender and disease stages without CNP. Results: VEGF-A in women and men with M+CNP was higher than in controls by 2.7 and 24.9 times respectively; VEGFR-1 was decreased in women by 1.8 times and increased in men by 1.8 times. VEGF-С was unchanged in women and 1.5 times higher in men, and VEGFR-3 was increased by 2.2 times in women and unchanged in men. TGF-β1 was elevated in women and men with M+CNP by 1.4 and 1.8 times, compared to controls, TGF-βR2 – by 1.9 and 2 times respectively. Conclusions: In the blood of women with M+CNP, CNP activates the blood vascular endothelial growth factor VEGF-A and the factor of epidermal-mesenchymal transition TGF-β, while in the blood of men with M+CNP it activates the blood vascular endothelial growth factor VEGF-A, the lymphatic vascular endothelial growth factor VEGF-C and the factor of epidermal-mesenchymal transition TGF-β. VEGF mediates vascular permeability and is associated with the mobilization of endothelial progenitor cells from the bone marrow into premetastatic niches. Activation of TGF-β signaling promotes the induction of the epidermal-mesenchymal transition and supports the properties of cancer stem cells.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22097-e22097
Author(s):  
Viktoria V. Pozdnyakova ◽  
Elena M. Frantsiyants ◽  
Valeria A. Bandovkina ◽  
Ludmila Ya. Rozenko ◽  
Maria G. Ilchenko ◽  
...  

e22097 Background: Chronic neurogenic pain (CNP) as a comorbid disease is quite frequent, but its effect on malignant diseases is poorly studied. The risk of cutaneous melanoma in women is higher, but the disease course in men is more severe. The purpose of the study was to reveal the effect of CNP on the levels of sex hormones in the blood of patients with melanoma depending on their gender. Methods: Blood levels of estradiol (E2), estrone (E1), progesterone (P4), testosterone (T) and prolactin (PRL) were measured by ELISA in patients with Т3-4NxM0 melanoma (M): 21 women with CNP (pelvic pain - 7, osteochondrosis – 14), mean age 67.2±2.7 years; 17 men with CNP (osteochondrosis), mean age 65.6±3.1 years. The control group included patients with melanoma similar in age, gender and disease stages without CNP. Results: In women with M+CNP, E2 and P4 were decreased by 1.8 times, while E1 was 1.4 times, T – 2 times, PRL – 1.5 times higher, compared to controls. In men with M+CNP, blood levels of estrogens were unchanged, PRL was 2.5 times lower and P4 and T – 1.3 times higher, compared to the corresponding control levels. Conclusions: CNP upregulated blood levels of androgens in both male and female melanoma patients, and caused the inversion of estrogens only in women with the prevalence of E1 over E2. Gender differences in the CNP influence included the elevation of progesterone and a decrease of prolactin in the blood of men, and P4 deficiency with increased prolactin in women with M+CNP. The specific effect of CNP on the hormonal profile in patients with cutaneous melanoma should be considered in choosing antitumor treatment.


Author(s):  
И.Г. Попова ◽  
С.Б. Назаров ◽  
О.Г. Ситникова ◽  
Г.Н. Кузьменко ◽  
М.М. Клычева ◽  
...  

Введение. Новорожденные, родившиеся у матерей с патологией во время беременности, составляют группу высокого риска тромботических и геморрагических осложнений, которые повышаются при наличии у новорожденных перинатальной патологии. Цель исследования: оценить показатели, характеризующие состояние системы фибринолиза и сосудистой стенки в крови новорожденных, родившихся у матерей с преэклампсией (ПЭ), для прогнозирования риска тромботических и геморрагических осложнений у таких детей. Материалы и методы. Обследовано 60 новорожденных, родившихся у матерей с ПЭ. Контрольную группу составили 30 новорожденных от матерей без ПЭ. Исследовали венозную кровь, взятую у новорожденных на 3–5-е сутки жизни. В крови определяли уровень тканевого активатора плазминогена (t-РА), ингибитора тканевого активатора плазминогена (PAI-1) и тромбомодулина. Результаты. Выявлено, что у новорожденных от матерей с ПЭ на 3–5-е сутки жизни отмечаются признаки повреждения эндотелия и повышение фибринолитической активности крови, на что указывает повышение содержания t-РА, PAI-1 и тромбомодулина в крови. Заключение. Полученные данные свидетельствуют о риске развития геморрагических осложнений у таких детей. Background. Neonates born to mothers with pathology during pregnancy are at high risk of thrombotic and hemorrhagic complications that are increased if neonates have perinatal pathology. Objectives: to assess blood parameters characterizing fibrinolysis and vascular wall of neonates born to mothers with preeclampsia (РЕ), to predict the risk of hemorrhagic complications in these children. Patients/Methods. 60 neonates born to mothers with РЕ were examined. The control group consisted of 30 neonates born to mothers without РЕ. We studied levels of tissue plasminogen activator (t-PA), inhibitor of tissue plasminogen activator (PAI-1) and thrombomodulin (TM) in venous blood taken from neonates on the 3–5th days of life. Results. In neonates born to mothers with PE we revealed on the 3–5th days of life increased blood levels of t-PA, PAI-1 and TM that characterized endothelial damage and increased blood fibrinolytic activity. Conclusions. The data obtained indicate the risk of hemorrhagic complications development in these children.


1989 ◽  
Vol 4 (6) ◽  
pp. 369-373
Author(s):  
I.R. de Oliveira ◽  
B. Diquet ◽  
V. Van der Meersch ◽  
J. Gonidec ◽  
P.A. do Prado-Lima

SummaryWe studied the relationship of blood and brain levels of imipramine (IMI) and/or its active metabolite desipramine (DMI) to behavioural response, in the tail suspension test (TST). Compared to the control group, doses of 3.75, 7.5, 15, 30 and 60 mg/kg of IMI given intraperitoneally reduced immobility scores significantly. There were significant negative correlations between doses, brain levels of IMI, DMI, IMI + DMI, blood levels of IMI, DMI, IMI + DMI and the animal behaviour. Higher level of IMI and its metabolite in brain and in blood did not impair anti-immobility effect. These findings agree with most results found in men treated with IMI, and suggest a linear or sigmoid relationship between the antidepressant concentrations and its biological response.


1999 ◽  
Vol 82 (07) ◽  
pp. 104-108 ◽  
Author(s):  
Franck Paganelli ◽  
Marie Christine Alessi ◽  
Pierre Morange ◽  
Jean Michel Maixent ◽  
Samuel Lévy ◽  
...  

Summary Background: Type 1 plasminogen activator inhibitor (PAI-1) is considered to be risk factor for acute myocardial infarction (AMI). A rebound of circulating PAI-1 has been reported after rt-PA administration. We investigated the relationships between PAI-1 levels before and after thrombolytic therapy with streptokinase (SK) as compared to rt-PA and the patency of infarct-related arteries. Methods and Results: Fifty five consecutive patients with acute MI were randomized to strep-tokinase or rt-PA. The plasma PAI-1 levels were studied before and serially within 24 h after thrombolytic administration. Vessel patency was assessed by an angiogram at 5 ± 1days. The PAI-1 levels increased significantly with both rt-PA and SK as shown by the levels obtained from a control group of 10 patients treated with coronary angioplasty alone. However, the area under the PAI-1 curve was significantly higher with SK than with rt-PA (p <0.01) and the plasma PAI-1 levels peaked later with SK than with rt-PA (18 h versus 3 h respectively). Conversely to PAI-1 levels on admission, the PAI-1 levels after thrombolysis were related to vessel patency. Plasma PAI-1 levels 6 and 18 h after SK therapy and the area under the PAI-1 curve were significantly higher in patients with occluded arteries (p <0.002, p <0.04 and p <0.05 respectively).The same tendency was observed in the t-PA group without reaching significance. Conclusions: This study showed that the PAI-1 level increase is more pronounced after SK treatment than after t-PA treatment. There is a relationship between increased PAI-1 levels after thrombolytic therapy and poor patency. Therapeutic approaches aimed at quenching PAI-1 activity after thrombolysis might be of interest to improve the efficacy of thrombolytic therapy for acute myocardial infarction.


1994 ◽  
Vol 71 (04) ◽  
pp. 424-427 ◽  
Author(s):  
Masahide Yamazaki ◽  
Hidesaku Asakura ◽  
Hiroshi Jokaji ◽  
Masanori Saito ◽  
Chika Uotani ◽  
...  

SummaryThe mechanisms underlying clinical abnormalities associated with the antiphospholipid antibody syndrome (APAS) have not been elucidated. We measured plasma levels of lipoprotein(a) [Lp(a)], the active form of plasminogen activator inhibitor (active PAI), thrombin-antithrombin III complex (TAT) and soluble thrombomodulin (TM), to investigate the relationship of these factors to thrombotic events in APAS. Mean plasma levels of Lp(a), TAT, active PAI and TM were all significantly higher in patients with aPL than in a control group of subjects. Plasma levels of Lp(a) and active PAI were significantly higher in patients with aPL and arterial thromboses than in patients with aPL but only venous thromboses. There was a significant correlation between plasma levels of Lp(a) and active PAI in patients with aPL. These findings suggest that patients with aPL are in hypercoagulable state. High levels of Lp(a) in plasma may impair the fibrinolytic system resulting in thromboses, especially in the arterial system.


1994 ◽  
Vol 71 (05) ◽  
pp. 684-691 ◽  
Author(s):  
László Damjanovich ◽  
Csaba Turzó ◽  
Róza Ádány

SummaryThe plasminogen activation system is a delicately balanced assembly of enzymes which seems to have primary influence on tumour progression. The conversion of plasminogen into serine protease plasmin with fibrinolytic activity depends on the actual balance between plasminogen activators (urokinase type; u-PA and tissue type; t-PA) and their inhibitors (type 1 and 2 plasminogen activator inhibitors; PAI-1 and PAI-2). The purpose of this study was to determine the exact histological localization of all the major factors involved in plasminogen activation, and activation inhibition (plasmin system) in benign and malignant breast tumour samples. Our results show that factors of the plasmin system are present both in benign and malignant tumours. Cancer cells strongly labelled for both u-PA and t-PA, but epithelial cells of fibroadenoma samples were also stained for plasminogen activators at least as intensively as tumour cells in cancerous tissues. In fibroadenomas, all the epithelial cells were labelled for PAM. Staining became sporadic in malignant tumours, cells located at the periphery of tumour cell clusters regularly did not show reaction for PAI-1. In the benign tumour samples the perialveolar connective tissue stroma contained a lot of PAI-1 positive cells, showing characteristics of fibroblasts; but their number was strongly decreased in the stroma of malignant tumours. These findings indicate that the higher level of u-PA antigen, detected in malignant breast tumour samples by biochemical techniques, does not necessarily indicate increased u-PA production by tumour cells but it might be owing to the increased number of cells producing u-PA as well. In malignant tumours PAI-1 seems to be decreased in the frontage of malignant cell invasion; i.e. malignant cells at the host/tumour interface do not express PAI-1 in morphologically detectable quantity and in the peritumoural connective tissue the number of fibroblasts containing PAI-1 is also decreased.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bernd Wegener ◽  
Maik Behnke ◽  
Stefan Milz ◽  
Volkmar Jansson ◽  
Christian Redlich ◽  
...  

AbstractDespite the high potential of healthy bone to regenerate, the reconstruction of large bone defects remains a challenge. Due to the lack of mechanical stability of existing bone substitutes, recently developed degradable metallic alloys are an interesting alternative providing higher load-bearing capabilities. Degradable iron-based alloys therefore might be an attractive innovation. To test the suitability of a newly-designed iron-based alloy for such applications, an animal experiment was performed. Porous iron-based degradable implants with two different densities and a control group were tested. The implants were positioned in the proximal tibia of Merino sheep. Over a period of 6 and 12 months, blood and histological parameters were monitored for signs of inflammation and degradation. In the histological evaluation of the implants` environment we found degraded alloy particles, but no inflammatory reaction. Iron particles were also found within the popliteal lymph nodes on both sides. The serum blood levels of phosphorus, iron and ferritin in the long term groups were elevated. Other parameters did not show any changes. Iron-based degradable porous bone replacement implants showed a good biocompatibility in this experiment. For a clinical application, however, the rate of degradation would have to be significantly increased. Biocompatibility would then have to be re-evaluated.


2015 ◽  
Vol 22 (4) ◽  
pp. 177-180 ◽  
Author(s):  
Huseyin Bayazit ◽  
Erdinc Cicek ◽  
Salih Selek ◽  
Nurten Aksoy ◽  
I. Fatih Karababa ◽  
...  

Background: It has been determined that cannabis has adverse effects on brain tissue, and that increased S100 calcium binding protein B (S100B) blood levels are markers of neuronal damage. Therefore, the aim of this study was to evaluate the S100B levels in cannabis use disorder. Method: Thirty-two patients with cannabis use disorder and 31 matched healthy controls were enrolled in this study. Appropriate blood samples were taken from the enrolled subjects, and the serum S100B protein levels were measured with an electrochemiluminescence immunoassay for the quantification of the protein. Findings: We found significantly increased S100B protein levels in patients with cannabis use disorder. The mean serum concentration of S100B was 0.081 ± 0.018 μg/l in patients with cannabis use disorder, and 0.069 ± 0.018 μg/l in the control group (p = 0.008). Interpretation: Our data suggest that elevated S100B protein levels might indicate neuronal damage in the brains of people with cannabis use disorder.


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