scholarly journals Demonstration of in vivo mammogenic and lactogenic effects of recombinant ovine placental lactogen and mammogenic effect of recombinant ovine GH in ewes during artificial induction of lactation

1999 ◽  
Vol 160 (3) ◽  
pp. 365-377 ◽  
Author(s):  
G Kann ◽  
A Delobelle-Deroide ◽  
L Belair ◽  
A Gertler ◽  
J Djiane
Keyword(s):  
Plasma Levels ◽  
Placental Lactogen ◽  
Mammary Tissue ◽  
Control Group ◽  
Dependent Manner ◽  
Exogenous Hormone ◽  
Daily Group ◽  
Igf I ◽  
Beta Casein

The present study demonstrates that ovine placental lactogen (oPL) (ovine chorionic somatotrophin) may have an important role in the mammogenesis and/or lactogenesis of the ewe. Its effects were compared with that already described for ovine growth hormone (oGH). In the first experiment, 40 nulliparous ewes were induced to lactate by means of a 7 day (days 1-7) oestro-progestative treatment (E2+P4). The ewes from Group 1 (n=12) received no further treatment, while those of the other groups received either recombinant oGH (roGH, 28 micrograms/kg, i.m., twice daily, Group 2, n=12) or recombinant oPL (roPL, 79 micrograms/kg, i.m., twice daily, Group 3, n=12) from day 11 to 20. All ewes received 25 mg hydrocortisone acetate (HC) twice daily on days 18-20. Control Group 00 (n=2) received no steroid treatment at all, and the control Group 0 (n=2) received only the E2+P4 treatment. Thirteen ewes (three from each experimental group and the two of each control group) were slaughtered at the end of hormone treatments (day 21) before any milking stimulus. The 27 remaining ewes from Groups 1-3 were machine-milked and milk yields recorded daily from day 21 to 76. The E2+P4 treatment enhanced the plasma levels of oPRL, oGH and IGF-I between days 1 and 7 by 1.5, 2. 3 and 2.6 times respectively (P=0.002); roGH treatment induced a highly significant enhancement of IGF-I plasma levels from day 11 to 20, whereas a similar effect appeared for roPL-treated ewes only from day 17 to 20 (P<0.01). Eight weeks after the last exogenous hormone injections, milk yields of both roGH- and roPL-treated groups progressively rose to twice that of unsupplemented groups (P<0.001). The mammary DNA content on day 21 was higher for animals which received either oGH or oPL but, due to individual variations in so few samples (n=3), this difference was not significant. No beta-casein was measured in mammary tissue from control ewes, whereas steroid-treated ewes (E2+P4+HC) had higher casein concentrations regardless of subsequent hormonal treatment on days 11-20 (P<0.001). beta-Casein concentrations in mammary parenchyma of roGH-treated ewes did not differ from that of ewes which received only E2+P4+HC; roPL supplementation clearly enhanced expression of beta-casein (P<0.001). IGF-I stimulation by either roGH or roPL was more precisely examined during a second experiment, in which two twice-daily i.m. doses (58 or 116 micrograms/kg) of either roGH or roPL were administered to four groups of six ewes that were E2+P4 treated as those of Experiment 1. A control group (n=6) received no exogenous hormone from day 11 to 13. On day 13, hourly blood samples were taken from all ewes over 11 h. Both doses of roGH significantly stimulated IGF-I in a dose-dependent manner. The 58 micrograms/kg dose of roPL did not significantly stimulate IGF-I, but although being somewhat less efficient than the 58 micrograms/kg dose of roGH, the 116 micrograms/kg dose of roPL significantly stimulated IGF-I secretion (P<0. 001). These results suggest that mammogenesis and/or lactogenesis in the ewe is in part controlled by somatotrophic hormones such as oGH and oPL and that IGF-I could be one of the mediators of these hormones.

GRF treatment of late pregnant ewes alters maternal and fetal somatotropic axis activity

1991 ◽  
Vol 260 (4) ◽  
pp. E575-E580 ◽  
Author(s):  
M. M. Blanchard ◽  
C. G. Goodyer ◽  
J. Charrier ◽  
G. Kann ◽  
R. Garcia-Villar ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Late Gestation ◽  
Placental Lactogen ◽  
Maximal Response ◽  
Pituitary Cells ◽  
In Vitro Test ◽  
Fetal Sheep ◽  
Igf I

To examine the effects of anabolic agents given during late gestation on the maternal and fetal somatotropic axes, we injected pregnant ewes twice daily with 0.15 mg somatocrinin (GRF)-(1-29) for 10 days beginning on day 130 of gestation. Maternal and fetal endocrine changes were compared with control animals using both in vivo and in vitro approaches. Treatment with GRF increased maternal plasma levels of growth hormone (GH) and insulin-like growth factor I (IGF-I;P less than 0.05) but not IGF-II. Under in vitro test conditions, maternal pituitary cells showed a greater maximal response (P less than 0.001) to GRF. In the fetuses of treated ewes, cord plasma GH levels were not significantly increased compared with controls. These animals had similar IGF-I but higher IGF-II (P less than 0.05) plasma levels. The maximal response of fetal pituitary cells to GRF was increased (P less than 0.001). GRF treatment had no influence on maternal and fetal pituitary cell responses to somatostatin under either basal or GRF-stimulated conditions. In addition, these treatments did not affect plasma levels of placental lactogen, glucose, or free fatty acids in the maternal and fetal sheep. These data are compatible with the hypothesis that treatment of pregnant ewes in the last days of gestation with GRF could support accelerated fetal growth.

Ethanol Extract of Achillea fragrantissima Enhances Angiogenesis through Stimulation of VEGF Production

2020 ◽  
Vol 21 ◽  
Author(s):  
Hana M. Hammad ◽  
Amer Imraish ◽  
Maysa Al-Hussaini ◽  
Malek Zihlif ◽  
Amani A. Harb ◽  
...  
Keyword(s):  
Wound Healing ◽  
Rural Communities ◽  
Ex Vivo ◽  
Ethanol Extract ◽  
Aortic Ring ◽  
Treated Group ◽  
Control Group ◽  
Dependent Manner ◽  
Achillea Fragrantissima

Objective: Achillea fragrantissima L. (Asteraceae) is a traditionally used medicinal herb in the rural communities of Jordan. Methods: The present study evaluated the efficacy of the ethanol extract of this species on angiogenesis in both, ex vivo using rat aortic ring assay and in vivo using rat excision wound model. Results: In concentrations of 50 and 100 µg/ml, the ethanol extract showed angiogenic stimulatory effect and significantly increased length of capillary protrusions around aorta rings of about 60% in comparison to those of untreated aorta rings. In MCF-7 cells, the ethanol extract of A. fragrantissima stimulates the production of VEGF in a dose-dependent manner. 1% and 5% of ethanol extract of A. fragrantissima containing vaseline based ointment was applied on rat excision wounds for six days and was found to be effective in wound healing and maturation of the scar. Both preparations resulted in better wound healing when compared to the untreated control group and vaseline-treated group. This effect was comparable to that induced by MEBO, the positive control. Conclusion: The results indicate that A. fragrantissima has a pro-angiogenic effect, which may act through the VEGF signaling pathway.

scholarly journals Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 386
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh
Keyword(s):  
Stereotactic Body Radiation Therapy ◽  
In Vivo Studies ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Hep G2 ◽  
Time Curve ◽  
Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

In Vivo Anti-Anemic Effect of an Aqueous Root Extract of Phyllanthus Muellerianus (Kuntze) Exell in Model Rats.

2021 ◽  
Author(s):  
James Nyirenda ◽  
Gershom B. Lwanga ◽  
Kaampwe M. Muzandu ◽  
David K. Chuba ◽  
Gibson M. Sijumbila
Keyword(s):  
Plant Extract ◽  
Hematological Parameters ◽  
Negative Control ◽  
Control Group ◽  
Albino Rats ◽  
Root Extract ◽  
Dependent Manner ◽  
Phytochemical Screening ◽  
Aqueous Root Extract

Abstract Ethnopharmacological relevanceAnemia is a very serious condition in Zambia. One of the plants that has been used traditionally is Phyllanthus muellerianus where different parts of shrub are used to treat a number of diseases in Zambian folklore medicine. Earlier studies have investigated medicinal properties of its aqueous root extracts. This study evaluated the effect of P. muellerianus roots on the hematological indices of albino rats and determined its phytochemical profile. Aim of the studyTo carry out phytochemical screening of the root extract and assess the ant-anemic effect of the aqueous extract on laboratory rats with tail-bled induced anemia Materials and MethodsThirty-six male albino rats placed in six groups were used for the study. The groups comprised the 100, 200, and 400 mg/kg plant extract, Ranferon (200 mg/kg) positive control, anemic non treated control and a normal (non-anemic) control. Anemia, induced through bleeding of the rats, was defined as hemoglobin (Hb) levels less than 12 g/dL. The anti-anemic potential of the plant was determined by comparing its effect on the hematological parameters of rats on treatment to that of the control group.ResultsAfter treatment, rats on the 400 mg/kg plant extract dose showed the greatest increase in the mean values for Hb, Packed cell volume (PCV) and RBC count were 43.3±1.2%, 15.4±0.3 g/dL and 6.3±0.3 x106 /mL respectively, when compared to the negative control group (P < 0.05). Phytochemical screening revealed positive results for alkaloids, flavonoids, saponins, glycosides, steroids, triterpenoids and tannins with varying amounts.Conclusions. The aqueous root extract of P. muellerianus was efficacious against anemia in a dose-dependent manner. The phytochemical compositions seem to be responsible for its hematopoietic properties. Thus, the root decoction of P. muellerianus is useful in alleviating anemia and the results lend credence to its use in traditional medicine in the management of anemia.

scholarly journals Sequestration of erythrocytes infected with Plasmodium berghei ANKA in BALB/c mice treated with goat bile

2020 ◽  
Vol 4 (2) ◽  
pp. 179
Author(s):  
Kartika Arum Wardani ◽  
Kholida Nur Aini ◽  
Heny Arwati ◽  
Willy Sandhika
Keyword(s):  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Negative Control ◽  
Control Group ◽  
Dependent Manner ◽  
Plasmodium Berghei Anka ◽  
Concentration Dependent Manner ◽  
Control Group Design ◽  
Bile Concentration

Abstract Sequestration of Plasmodium berghei ANKA-infected erythrocytes occurs in BALB/c mice as characteristic of  Plasmodium falciparum infection in humans. Animals’ bile has been widely used for centuries in Traditional Chinese Medicine. Goat bile has been used in healing infectious and non-infectious diseases; however, no report on the use of goat bile against malaria infection and sequestration. The purpose of this study was to analyze the correlation between parasitemia and sequestration in the liver of P.berghei ANKA-infected BALB/c mice treated with goat bile. This research was an in vivo experimental study using the post-test control group design. The male BALB/c mice aged ± 6 weeks, body weight 20-25 g were used. The mice were divided into five groups where Group 1-3 were mice treated with goat bile 25%, 50%, and 100%, respectively. Group 4-5 were negative (sterile water) and positive controls (DHP). Parasitemia was observed daily from each mouse and the number of sequestered infected erythrocytes on the endothelium of sinusoids. The data were analyzed using t independent test. Antimalarial activity of goat bile was shown by the lower parasitemia in goat bile-treated mice compared with the negative control. The average number of sequestration was goat bile concentration-dependent manner. The higher the concentration, the lower the number of sequestration. Sequestration was correlated with parasitemia (p=0,0001). Sequestration of P.berghei ANKA-infected erythrocytes correlated with parasitemia, and was goat bile concentration-dependent manner. Keywords: Malaria, parasitemia, sequestration, goat bileCorrespondence: [email protected]

Effects of IGF-I infusion on growth and muscle Na(+)-K+ pump concentration in K(+)-deficient rats

1993 ◽  
Vol 264 (5) ◽  
pp. E810-E815 ◽  
Author(s):  
I. Dorup ◽  
A. Flyvbjerg
Keyword(s):  
Binding Site ◽  
Control Group ◽  
Recombinant Human Insulin ◽  
Ouabain Binding ◽  
Muscle Weight ◽  
Igf I ◽  
Organ Specific ◽  
K Deficiency ◽  
Edl Muscle

K(+)-deficient rats and control rats were infused for 14 days with vehicle: acetic acid (AcA) or recombinant human insulin-like growth factor-I (IGF-I, 240 micrograms/day) by osmotic minipumps. IGF-I treatment of K(+)-deficient rats did not result in overall growth of carcass or muscles but in marked selective growth of adrenals (+42%) and spleen (+66%). In control rats, IGF-I induced increased body and muscle weight, tibia length, and thymus weight. K+ deficiency was associated with reduced serum IGF-I but unchanged thyroid status. IGF-I treatment of the K(+)-deficient rats restored serum IGF-I and decreased total 3,5,3'-triiodothyronine. In AcA-treated K(+)-deficient rats [3H]ouabain binding site concentration decreased by 63 and 43% in soleus and extensor digitorum longus (EDL) muscle, respectively, compared with the AcA-treated controls. IGF-I had no effect on the [3H]ouabain binding site concentration in the control group, but in K(+)-deficient rats a significant lowering of 26% was observed in EDL. K+ deficiency causes relative organ-specific resistance to the growth-promoting effects of IGF-I, comparable to the effects seen in protein-restricted rats. Reduced circulating IGF-I is not the only cause of the downregulation of Na(+)-K+ pumps in K+ deficiency, and IGF-I treatment of control animals in vivo has no stimulatory effect on the synthesis of Na(+)-K+ pumps.

scholarly journals In Vivo and In Vitro Evaluation of the Protective Effects of Hesperidin in Lipopolysaccharide-Induced Inflammation and Cytotoxicity of Cell

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 478 ◽  
Author(s):  
Rasha Al-Rikabi ◽  
Hanady Al-Shmgani ◽  
Yaser Hassan Dewir ◽  
Salah El-Hendawy
Keyword(s):  
Breast Cancer ◽  
Chromatin Condensation ◽  
Control Group ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Protective Effects ◽  
Mcf7 Cells ◽  
Tnf Α

(1) Background: Plant flavonoids are efficient in preventing and treating various diseases. This study aimed to evaluate the ability of hesperidin, a flavonoid found in citrus fruits, in inhibiting lipopolysaccharide (LPS) induced inflammation, which induced lethal toxicity in vivo, and to evaluate its importance as an antitumor agent in breast cancer. The in vivo experiments revealed the protective effects of hesperidin against the negative LPS effects on the liver and spleen of male mice. (2) Methods: In the liver, the antioxidant activity was measured by estimating the concentration of glutathione (GSH) and catalase (CAT), whereas in spleen, the concentration of cytokines including IL-33 and TNF-α was measured. The in vitro experiments including MTT assay, clonogenity test, and sulforhodamine 101 stain with DAPI (4′, 6-diamidino-2-phenylindole) were used to assess the morphological apoptosis in breast cancer cells. (3) Results: The results of this study revealed a significant increase in the IL-33 and TNF-α cytokine levels in LPS challenged mice along with a considerable elevation in glutathione (GSH); moreover, the catalase (CAT) level was higher compared to that of the control group. Cytotoxicity of the MCF-7 cell line revealed significant differences among the groups treated with different concentrations when compared to the control groups, in a concentration-dependent manner. Hesperidin significantly inhibited the colony formation of MCF7 cells when compared to that of control. Clear changes were observed in the cell shape, including cell shrinkage and chromatin condensation, which were associated with a later apoptotic stage. (4) Conclusion: The results indicate that hesperidin might be a potential candidate in preventing diseases.

Selective chronic regulation of GLUT1 and GLUT4 content by insulin, glucose, and lipid in rat cardiac muscle in vivo

1997 ◽  
Vol 273 (3) ◽  
pp. H1309-H1316 ◽  
Author(s):  
D. R. Laybutt ◽  
A. L. Thompson ◽  
G. J. Cooney ◽  
E. W. Kraegen
Keyword(s):  
Cardiac Muscle ◽  
Plasma Glucose ◽  
Glucose Transporter ◽  
Close Association ◽  
Nonesterified Fatty Acid ◽  
Control Group ◽  
Dependent Manner ◽  
Energy Status ◽  
Glut1 Expression

The glucose transporter GLUT1 may play a more important role in cardiac than in skeletal muscle, but its regulation is unclear. During fasting, cardiac GLUT1 declines in the presence of low plasma insulin and glucose and high nonesterified fatty acid (NEFA) levels, whereas GLUT4 is unchanged. We investigated insulin, glucose, and NEFA levels as regulatory factors of cardiac GLUT content in chronically cannulated rats. Fasting rats were infused for 24 h with saline or insulin (2 rates) while plasma glucose was equalized by a glucose clamp; final transporter content was compared with a fed control group. There was a close association of GLUT1 content with insulin (r2 = 0.83, P < 0.001), with GLUT1 varying over a threefold range, under equivalent fasting glycemic conditions (plasma glucose, 5.1 +/- 0.1 mM). Maintenance of fed insulin levels during fasting prevented the GLUT1 fall (P < 0.01), whereas hyperinsulinemia (117 +/- 10 mU/l) led to significant overexpression of GLUT1 (155 +/- 12% of control, P < 0.01). When high glucose (7.6 +/- 0.1 mM) or high NEFA (0.76 +/- 0.05 mM) levels accompanied the hyperinsulinemia, upregulation of GLUT1 was blocked. GLUT1 content correlated with an estimate of cardiac glucose clearance across the groups. Cardiac GLUT4 content, hexokinase, and acyl-CoA synthase activities were unaffected by fasting, insulin, or substrate manipulation. In conclusion, insulin preferentially upregulates GLUT1 (but not GLUT4) in a dose-dependent manner in cardiac muscle in vivo, and substrate supply modulates this response, since upregulation can be effectively blocked by increased glucose or lipid availability. Therefore, both insulin exposure and energy status of cardiac muscle may be important determinants of cardiac GLUT1 expression.

Inhibition Effects of baicalin on Lymphoma Cell Line CA46 in Vitro and in Vivo

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5053-5053
Author(s):  
Jian Da Hu ◽  
Yi Huang ◽  
Yingyu Chen ◽  
Tiannan Wei ◽  
Tingbo Liu ◽  
...  
Keyword(s):  
Cell Line ◽  
Biological Effects ◽  
Annexin V ◽  
Lymphoma Cell ◽  
Control Group ◽  
Dependent Manner ◽  
Lymphoma Cell Line ◽  
Proliferation Inhibition

Abstract Baicalin is a traditional Chinese medicine with multiple biological effects. Some researches showed baicalin has anti-tumor effects in solid tumor, such as prostate cancer. In order to investigate its effects on proliferation inhibition and apoptosis induction in human lymphoma cell, we treated Burkitt lymphoma cell line CA46 with baicalin in vitro and in vivo of CA46 xenograft. Baicalin remarkably inhibited the cell proliferation, with an IC50 value of 10μM. Apoptosis was remarkably induced by baicalin in a dose-dependent manner, which was detected by Annexin V FITC/PI double staining analysis, TUNEL labeling method and DNA fragmentation respectively. Furthermore, RT-PCR showed that the mRNA expressions of c-myc and bcl-2 in treated CA46 cell decreased in a time-dependent manner. Western-Blot showed that the protein expressions of c-myc, bcl-2, procaspase-3 and PARP(116KD) in baicalin treated CA46 cell were down-regulated, while the expression of PARP(85KD) increased. Based on the results in vitro, we investigated in vivo efficacy of baicalin, alone or in combination with cytotoxic drug VP16, for treatment in CA46 nude mice xenograft. Baicalin with the dosage of 40mg/kg/d and 80kg/mg/d could remarkably inhibit the growth of the tumor compared with control group. Combination of baicalin and VP16 had better anti-tumor effects. Histological examination of tumor samples showed more necrotic cells in treated groups. And obvious apoptosis could be observed by electron microscope. No adverse events were found in treated groups. From above we could conclude that baicalin could efficiently induce proliferation inhibition and apoptosis of CA46 cells in vitro and in vivo, which may be related with the down-regulation of c-myc and bcl-2 expressions, as well as the up-regulation of caspase-3 activity.

Circulating Microparticles and Risk of Venous Thromboembolism.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3987-3987
Author(s):  
Paolo Bucciarelli ◽  
Emanuele Previtali ◽  
Ida Martinelli ◽  
Andrea Artoni ◽  
Serena M Passamonti ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Venous Thromboembolism ◽  
Body Mass ◽  
Plasma Levels ◽  
Conflicts Of Interest ◽  
Factor V Leiden ◽  
Control Group ◽  
Dependent Manner ◽  
Healthy Controls ◽  
Increased Risk

Abstract Abstract 3987 Poster Board III-923 Background Microparticles (MPs) are circulating, submicroscopic fragments (<1 μm of diameter) of membrane-bound cytoplasm that shed from the surface of an activated or apoptotic cell and play a role in coagulation, inflammation, cell remodelling and proliferation. There is increasing evidence that MPs are involved in thrombosis, but whether or not they are an independent risk factor for venous thromboembolism (VTE) is not established. Aim of the study To investigate the association between high plasma levels of MPs and risk of VTE Patients and Methods In a case-control study, 186 patients with a first episode of VTE (deep venous thrombosis and/or pulmonary embolism) and 418 healthy controls were included. MPs were analyzed by flow cytometry with a gate defined by a 1 μm beads and using APC-Annexin V together with FITC anti-CD41 or FITC anti-CD142 antibodies in order to identify platelet MPs (MP-Plts) and MPs exposing tissue factor (MP-TF), respectively. MPs levels were expressed as number/μL. Results Patients had significantly higher median plasma levels of both MPs-Plts and MPs-TF than controls [1942 vs 1519 (p<0.0001) and 579 vs 454 (p<0.0001)]. Higher median levels of MP-Plts and MP-TF were found in 41 patients who underwent blood sampling within 6 months from VTE than in those sampled later [2114 vs 1694 (p=0.086) and 652 vs 543 (p=0.120)]. Sex, age, body mass index and factor VIII plasma levels had no influence on MPs levels, as well as the use of oral contraceptives (this latter evaluated only in controls). In the whole study population, carriership of thrombophilia (antithrombin, protein C or protein S deficiency, factor V Leiden, prothrombin G20210A, antiphospholipid antibodies, hyperhomocysteinemia or combined abnormalities) had higher levels of MP-Plts and MP-TF than non-carriers [1907 vs 1565 (p=0.002) and 532 vs 468 (p=0.011)]. The odds ratio (OR) for VTE, adjusted for sex, age, body mass index and thrombophilia was 2.5-fold higher in individuals with MPs plasma levels >95th percentile of the control group (3633/μL for MPs-Plts and 1113/μL for MPs-TF) than in those with MPs levels ≤95th percentile [for MPs-Plts: OR=2.59 (95%CI 1.23 – 5.45); for MPs-TF: OR=2.38 (1.15 – 4.92)]. The risk increased in a dose-dependent manner for both MPs-Plts and MPs-TF, particularly above the 75th percentile of the distribution in controls. The exclusion of patients whose MPs levels were measured within 6 months from VTE (in order to avoid the possible effect of the acute phase on MPs measurements), did not change the results [adjusted OR: 2.63 (1.18 – 5.89) for MPs-Plts and 2.36 (1.10 – 5.19) for MPs-TF]. The Table shows the relative risks of VTE associated with the presence or absence of high MPs levels and thrombophilia. Individuals with MPs >95th percentile or thrombophilia alone had a 2 to 3-fold increased risk of VTE, whereas those with both MPs-Plts >95th percentile and thrombophilia had a 9-fold increased risk of VTE. This synergistic effect was confirmed also for MPs-TF and remained after the exclusion of patients whose blood sample was collected within 6 months from VTE [OR 7.72 (1.68-35.4) for MP-Plts and 8.14 (2.08-31.8) for MP-TF]. Conclusions Plasma levels of MPs are significantly higher in patients with VTE than in healthy controls. MPs levels >95th percentile are associated with a 2.5-fold increased risk of VTE. There is a synergistic interaction between high levels of MPs and thrombophilia on VTE risk. Disclosures: No relevant conflicts of interest to declare.

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