Abstract 524: Influenza Vaccination Reduces The Risk Of Venous Thromboembolism

It is widely accepted that influenza vaccination reduces the risk of cardiovascular events in patients with coronary artery diseases. However, no information is available concerning the role of influenza vaccination in venous thromboembolism (VTE). Methods: A case-control study was conducted in 727 cases and 727 age and sex-matched controls from 11 centers in France (the FARIVE study). Cases were patients with a first documented episode of VTE and without any personal history of cancer within the last 5 years; controls were recruited in the same hospital and had no personal history of venous or arterial thrombosis. Results: Overall, 202 (28.2%) of cases and 233 (32.1%) of controls had influenza vaccination during the previous 12 months at the time of recruitment. Information was not available for only 12 subjects out of 1454. The crude odds ratio (OR) for VTE associated with influenza vaccination was 0.76 (95% CI 0.58–0.99). After adjustment for potential confounding variables (age, sex, inclusion date, BMI, educational levels and varicose veins), the OR for VTE associated with vaccination was 0.74 (95% CI 0.57–0.97). The protective effect of vaccination toward VTE was higher in the population below 52 years (median of age), with an OR of 0.52 (95% CI 0.32–0.85). In women below the age of 51, the crude OR for VTE associated with influenza vaccination was 0.50 (95% CI 0.24–1.05) and was significant after adjustment for confounding variables including oral contraceptives, with an OR of 0.41 (95% CI 0.19–0.92). The protective effect of vaccination was similar for different types of VTE (DVT or PE). There was no statistical differences in the protective effects when we compared provoked with unprovoked VTE events. Conclusion: This is the first study that demonstrates a protective effect of influenza vaccination in VTE. In vitro influenza induces activation of coagulation and inflammation but we cannot rule out that the protective effect of influenza vaccination was due to other unknown mechanisms, as the protective effect was similar within the different seasons of the year. Influenza vaccination may reduce the risk of VTE by 26%. This relationship between influenza vaccination and VTE and its underlying mechanism still need to be analyzed and confirmed in further studies.

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Decreased anticoagulant response to tissue factor pathway inhibitor in patients with venous thromboembolism and otherwise no evidence of hereditary or acquired thrombophilia

Thrombosis and Haemostasis ◽

10.1160/th03-05-0329 ◽

2004 ◽

Vol 91 (01) ◽

pp. 80-86 ◽

Cited By ~ 8

Author(s):

Brigitte Piccapietra ◽

Johanna Boersma ◽

Joerg Fehr ◽

Thomas Bombeli

Keyword(s):

Venous Thromboembolism ◽

Venous Thrombosis ◽

Mean Value ◽

Healthy Controls ◽

Crude Odds Ratio ◽

Sensitivity Ratio ◽

Increased Risk ◽

History Of ◽

Anticoagulant Response ◽

Acquired Thrombophilia

SummaryNo relevant deficiency of TFPI or genetic polymorphisms could thus far consistently be associated with venous thromboembolism. We hypothesized that the substrates of the TFPI protein, including FVII or FX (rather than the protein itself) could induce a hypercoagulable state. We created a novel TF-based clotting assay that evaluated the anticoagulant response to exogenously added recombinant TFPI. The response to TFPI was expressed as the ratio of the clotting time with and without TFPI. By using 118 healthy controls, we established a reference range between 1.31 and 1.93 (mean value ± 2 standard deviations (SD), 1.62 ± 0.31). We then evaluated samples from 120 patients with a history of venous thromboembolism but no evidence of hereditary and acquired thrombophilia. The range of the patients’ ratios was significantly (P < 0.001) lower, falling between 1.2 and 1.78 (mean value ± 2 SD, 1.49 ± 0.29). Of the 120 patients, 39 (32.5%) had a TFPI sensitivity ratio below the 10th percentile of the controls, compared with 11 (9.3%) of the healthy controls. The crude odds ratio for venous thrombosis for subjects with a TFPI sensitivity ratio below the 10th percentile was 13 (95% CI; range, 3.1 to 54.9) compared with those with a ratio above 1.8 (90th percentile). Patients with idiopathic thromboembolism did not have a decreased TFPI sensitivity ratio more often than patients with thrombosis with a circumstantial risk factor. Based on these results, a reduced response to TFPI may lead to an increased risk of venous thrombosis.

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The Effect of a Fennel Extract on the STAT Signaling and Intestinal Barrier Function

10.1101/2021.07.01.450766 ◽

2021 ◽

Author(s):

John Rabalais ◽

Philip Kozan ◽

Tina Lu ◽

Nassim Durali ◽

Kevin Okamoto ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Protective Effect ◽

Bowel Disease ◽

Barrier Function ◽

Intestinal Barrier Function ◽

Protective Effects ◽

Foeniculum Vulgare ◽

Inflammatory Bowel ◽

Stat Pathway

Background: Foeniculum vulgare, F. vulgare, commonly known as fennel, is believed to be one of the worlds oldest medicinal herbs and has been exploited by people for centuries as a nutritional aid for digestive disorders. In many southeast Asian countries it is ingested as an after-meal snack, mukhvas, due to its breath-freshening and digestive aid properties. F. vulgare is used in some countries, such as Iran, as a complementary and alternative treatment for inflammatory bowel disease (IBD). Methods: This study investigated the effects of F. vulgare on the barrier function of the intestinal epithelium Signal Transducer and Activator of Transcription (STAT) pathway, which is active in inflammatory bowel disease. To study the protective effects of F. vulgare extract in vitro, monolayers derived from the T84 colonic cell line were challenged with interferon-gamma (IFN-γ) and monitored with and without F. vulgare extract. To complement our in vitro studies, the dextran sodium sulfate induced murine colitis model was employed to ascertain whether the protective effect of F. vulgare extract can be recapitulated in vivo. Results: F. vulgare extract was shown to exert a protective effect on TEER in both T84 and murine models and showed increases in tight junction-associated mRNA in T84 cell monolayers. Both models demonstrated significant decreases in phosphorylated STAT1 (pSTAT1), indicating reduced activation of the STAT pathway. Additionally, mice treated with F. vulgare showed significantly lower ulcer indices than control mice. Conclusions: We conclude barrier function of the gastrointestinal tract is improved by F. vulgare, suggesting the potential utility of this agent as an alternative or adjunctive therapy in IBD.

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Rutin prevents retinal ganglion cell death and exerts protective effects by regulating transforming growth factor-β2/Smad2/3Akt/PTEN signaling in experimental rat glaucoma

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v18i5.11 ◽

2021 ◽

Vol 18 (5) ◽

pp. 985-993

Author(s):

Ying Li ◽

Leilei Qin ◽

Liang Ying ◽

Hanguang Dong ◽

Dabo Wang

Keyword(s):

Protective Effect ◽

Rat Model ◽

Transforming Growth Factor ◽

Ganglion Cells ◽

Protective Effects ◽

Retinal Ganglion ◽

Sprague Dawley ◽

Apoptotic Pathway ◽

Ganglion Cell Death

Purpose: To investigate the protective effect of rutin against glaucoma in a rat model, and the mechanisms involved. Methods: Sprague-Dawley rats were injected hypertonic saline in the limbal vein for elevation of intraocular pressure (IOP). Rats in the treatment group were administered rutin at doses of 12.5, 25 or 50 mg/kg orally and daily for 21 days. Results: Rutin markedly (p < 0.05) reduced IOP and prevented loss of retinal ganglion cells (RGCs). The expression of apoptotic pathway proteins, i.e., Bcl-xL, Bcl-2, Bad and Bax were significantly (p < 0.05) regulated by rutin. Moreover, rutin caused a substantial decrease in TGF-β2 expression, and also down-regulated p-Smad2 and p-Smad3 dose-dependently (p < 0.05). Raised levels of collagen I, fibronectin and elastin were effectively down-regulated. Rutin substantially up-regulated the Akt pathway involved in cell survival, and markedly improved the survival of RGCs subjected to hypoxia in vitro (p < 0.05). Conclusion: These results reveal that rutin exerts protective effect against glaucoma in a rat model via a mechanism involving regulation of the TGF-β2/Smad2/3Akt/PTEN signaling pathways. Thus, rutin has potentials for use in the management of glaucoma.

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Mangiferin Prevents TBHP-Induced Apoptosis and ECM Degradation in Mouse Osteoarthritic Chondrocytes via Restoring Autophagy and Ameliorates Murine Osteoarthritis

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/8783197 ◽

2019 ◽

Vol 2019 ◽

pp. 1-17 ◽

Cited By ~ 2

Author(s):

Yao Li ◽

Yaosen Wu ◽

Kaixia Jiang ◽

Wen Han ◽

Jing Zhang ◽

...

Keyword(s):

Protective Effect ◽

Chondrocyte Apoptosis ◽

Protective Effects ◽

Ampk Signaling ◽

Age Related ◽

Osteoarthritic Chondrocytes ◽

Ecm Degradation ◽

Induced Apoptosis ◽

Amp Activated Protein Kinase

Osteoarthritis (OA) is an age-related degenerative disease with complicated pathology involving chondrocyte apoptosis and extracellular matrix (ECM) degradation. Previous studies have shown that moderate autophagy has a protective effect against apoptosis in chondrocyte. Mangiferin is a natural polyphenol and exerts multiple pharmacological effects on different diseases in various preclinical studies. In this study, we investigated the effects of mangiferin on OA and delineated a potential molecular mechanism. In vitro, mangiferin treatment inhibited the expression of proapoptotic proteins induced by tert-butyl hydroperoxide (TBHP), increased the expression of antiapoptotic Bcl-2, and prevented ECM degradation by inhibiting the production of matrix-degrading enzyme. Mechanistically, mangiferin enhanced autophagy by activating the AMP-activated protein kinase (AMPK) signaling pathway. On the contrary, inhibition of autophagy partly abolished the protective effects of mangiferin on antiapoptosis and ECM synthesis in TBHP-treated chondrocyte. Correspondingly, the protective effect of mangiferin was also found in a mouse OA model. In conclusion, our results suggested that mangiferin serves as a potentially applicable candidate for treating OA.

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Modulation of Adenosine Receptors and Antioxidative Effect of Beer Extracts in in Vitro Models

Nutrients ◽

10.3390/nu11061258 ◽

2019 ◽

Vol 11 (6) ◽

pp. 1258

Author(s):

Patricia Alonso-Andrés ◽

Mairena Martín ◽

José Luis Albasanz

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Adenosine Receptors ◽

Receptor Gene ◽

Neuroblastoma Cells ◽

In Vitro Models ◽

Protective Effects ◽

Receptor Level ◽

A1 Receptor

The fight against neurodegenerative diseases is promoting the searching of nutrients, preferably of wide consumption, with proven effects on health. Beer is widely consumed and has potential benefits on health. In this work, three different extracts from dark beer (DB), non-alcoholic beer (NAB), and lager beer (LB) were assayed at 30 min and 24 h in rat C6 glioma and human SH-SY5Y neuroblastoma cells in order to study their possible protective effects. Cell viability and adenosine A1, A2A, A2B, and A3 receptor gene expression and protein levels were measured in control cells and in cells challenged with hydrogen peroxide as an oxidant stressor. Among the three extracts analyzed, DB showed a greater protective effect against H2O2-induced oxidative stress and cell death. Moreover, a higher A1 receptor level was also induced by this extract. Interestingly, A1 receptor level was also increased by NAB and LB extracts, but to a lower extent, and the protective effect of these extracts against H2O2 was lower. This possible correlation between protection and A1 receptor level was observed at 24 h in both C6 and SH-SY5Y cells. In summary, different beer extracts modulate, to a different degree, adenosine receptors expression and protect both glioma and neuroblastoma cells from oxidative stress.

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Amelioration of Cisplatin Toxicity in Rat Renal Cortical Slices by Dithiothreitol In vitro

Human & Experimental Toxicology ◽

10.1177/096032719401300205 ◽

1994 ◽

Vol 13 (2) ◽

pp. 89-93 ◽

Cited By ~ 17

Author(s):

J.G. Zhang ◽

L.F. Zhong ◽

M. Zhang ◽

X.L. Ma ◽

Y.X. Xia ◽

...

Keyword(s):

Lactate Dehydrogenase ◽

Protective Effect ◽

Protective Mechanism ◽

Protective Effects ◽

Metal Chelator ◽

Rat Renal Cortical Slices ◽

Antioxidative Action ◽

Cortical Slices ◽

Related Increase

1 The protective effects of dithiothreitol (DTT) on cisplatin-induced nephrotoxicity were investigated with rat renal cortical slices. 2 The nephrotoxic effects of cisplatin (2 mmol l-1) were manifested in several ways: the Na+ and water content were increased while K+ was decreased. The malondiadehyde (MDA) concentration in the slices and the lactate dehydrogenase (LDH) released into the medium were increased. The uptake of p-aminohippurate (PAH), the synthesis of glucose and the glutathione (GSH) concentration in the slices were all decreased. 3 Despite a DTT-related increase in platinum (Pt) uptake by the slices, DTT (0.5-2 mmol I-1 ) ameliorated all these toxic effects of cisplatin in a concentration related manner. 4 The results suggest that the protective mechanism of DTT is its antioxidative action, DTT is also a metal chelator, however, and so a protective effect via chelation of Pt by DTT cannot be excluded.

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Evidence of Increased Plasma Coagulative Capacity by CloFAL Assay among Pediatric Factor V Leiden and Prothrombin G20210A Heterozygotes with, Versus without, a First-or Second-Degree Family History of Venous Thromboembolism

Blood ◽

10.1182/blood.v112.11.5345.5345 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5345-5345

Author(s):

Chris Bombardier ◽

Linda J. Jacobson ◽

Marilyn J. Manco-Johnson ◽

Neil A Goldenberg

Keyword(s):

Venous Thromboembolism ◽

Family History ◽

Positive Family History ◽

Personal History ◽

Clot Formation ◽

Factor V ◽

History Of ◽

Study Population ◽

Fv Leiden ◽

Thrombophilia Testing

Abstract BACKGROUND: The factor V (FV) Leiden and prothrombin (PT) G20210A polymorphisms in heterozygous state are present in 5% and 1–2% of Caucasians, respectively, and confer approximately 5-fold and 2-fold increases in the risk of incident venous thromboembolism (VTE). While some families who carry these genetic thrombophilia traits exhibit a prothrombotic phenotype, others have no (or only a limited) history of VTE. The ability to discern which individuals with personal and familial carriage of these genetic thrombophilias possess a clinically meaningful increase in VTE risk remains elusive, and (particularly among children) is perhaps best informed presently by family history of VTE. OBJECTIVE AND HYPOTHESES: We sought to evaluate overall plasma coagulative capacity in FV Leiden and PT G20210A heterozygotes using the Clot Formation and Lysis (CloFAL) assay, a global turbidimetric plasma assay of tissue-factor induced fibrin clot formation and tissue-type plasminogen activator enhanced fibrinolysis. We hypothesized that children heterozygous for either thrombophilia would not uniformly demonstrate hypercoagulability, but that coagulative capacity would be increased among heterozygotes who have a family history of VTE. PATIENTS AND METHODS: Children aged birth to 18 years (inclusive) enrolled in prospective inceptional cohort study of thrombosis/thrombophilia/stroke were included in the analysis if they were found to be heterozygous for FV Leiden or PT G20210A upon comprehensive thrombophilia testing and had undergone CloFAL assay testing on a research basis. Data on personal and family history of thrombotic events, thrombophilia testing, and CloFAL assay findings were analyzed. Intergroup comparisons of continuous data were performed by Mann-Whitney U test and proportions were compared between groups using chi-square or Fisher’s exact test, as appropriate. RESULTS: Characteristics of the study population are shown in Table 1. Approximately 70% of patients were evaluated for a family history of VTE (with/without known thrombophilia) and nearly 50% had personal histories of VTE or arterial ischemic stroke (AIS)/recurrent transient ischemic attack (TIA); those evaluated for events were significantly older than those without events, and this difference was statistically significant among those with a positive family history fo VTE. Hypercoagulability was shown in 50% of patients and hypofibrinolysis in 13% using the CloFAL assay. Plasma coagulative capacity and maximal amplitude (MA) of the CloFAL waveform were significantly increased in patients with, versus without, family history of VTE (coagulation index, CI: 102% vs. 72% of the adult normal pooled plasma standard, respectively, p=0.04; MA: 0.415 vs. 0.322, p=0.02), and were not explained by age differences between groups. However, in this relatively small study population, the proportion of CloFAL CI results that exceeded the upper limit of normal values did not significantly differ between those with, versus without, family history of VTE. Pediatric FV Leiden or PT G20210A heterozygotes with positive family history of VTE were more likely to have multi-trait (>1) thrombophilia, in which case a trend toward increased plasma coagulability was demonstrated (CI: 139% [multi-trait] vs. 86% [isolated trait]; p=0.07); superimposed thrombophilias in this group most often consisted of elevated factor VIII activity and Lp(a) concentration. CONCLUSIONS: The present findings using the CloFAL global assay indicate that, while pediatric FV Leiden or PT G20210A heterozygotes do not uniformly exhibit hypercoagulability, plasma coagulative capacity is nevertheless significantly increased among heterozgyotes who have a family history of VTE, which may relate to the presence of superimposed thrombophilias. Table 1. Summary characteristics of the study population. *VTE, AIS, or recurrent TIA **Two patients were dual heterozygotes. N 32 Median age at evaluation (range) 9.5 y (1–18 y) Personal history of events* 14 y (1–18 y) No personal history of events* 8 y (2–18 y) FV Leiden heterozygote (n) 26** PT G20210A heterozygote (n) 8** Personal history of VTE (n) 11 Personal history of AIS/recurrent TIA 4 Family history (1st/2nd degree) of VTE 71% Multi-trait (>1) thrombophilia 45% Acquired thrombophilia 24% Hypercoagulability by CloFAL assay 50% Hypofibrinolysis by CloFAL assay 13%

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Zishenwan Decreases Kidney Damage in Recurrent Urinary Tract Infection through the Inhibition of Toll-Like Receptor 4 Signal

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/5968657 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Guoqiang Liang ◽

Hua Tang ◽

Daolei Ni ◽

Yan Ren ◽

Chenxi Zhang ◽

...

Keyword(s):

Urinary Tract Infection ◽

Urinary Tract ◽

Tract Infection ◽

Protective Effect ◽

Tissue Damage ◽

Immunoglobulin A ◽

Protective Effects ◽

Toll Like Receptor 4 ◽

Secretory Immunoglobulin

Objectives. To investigate the mechanism of the protective effect of Zishenwan on pyelonephritis rats. Methods. In the rat model of pyelonephritis, protective effects of Zishenwan, the content of secretory immunoglobulin A (SIg A), and interleukins were detected by ELISA. The expressions of TLR4-NFκB pathway were detected by Western blot in renal and urinary tract mucosa. The protective effect and influence on TLR4-NFκB pathway of Zishenwan were studied. Results. Zishenwan protected rats from pyelonephritis which related to the increase of SIgA, the regulation of interleukins, and the inhibition of TLR4-NFκB pathway. Serum containing Zishenwan can significantly decrease LPS-induced expression of TLR4, MyD88, and NFκB in vitro. And the inhibition of TLR4 signal by Zishenwan related to the degradation of TRAF3 and TRAF6. Conclusions. Zishenwan protected rats from urinary tract infection by clearance of bacteria and decrease of tissue damage. 20S proteasomes mediated the degradation of TRAF3 which is important to the decrease of tissue damage from Zishenwan.

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Carbon Monoxide Protects against Liver Failure through Nitric Oxide–induced Heme Oxygenase 1

Journal of Experimental Medicine ◽

10.1084/jem.20031003 ◽

2003 ◽

Vol 198 (11) ◽

pp. 1707-1716 ◽

Cited By ~ 157

Author(s):

Brian S. Zuckerbraun ◽

Timothy R. Billiar ◽

Sherrie L. Otterbein ◽

Peter K.M. Kim ◽

Fang Liu ◽

...

Keyword(s):

Nitric Oxide ◽

Carbon Monoxide ◽

Cell Death ◽

Protective Effect ◽

Heme Oxygenase ◽

Heme Oxygenase 1 ◽

No Production ◽

Protective Effects ◽

In Vivo Models

Carbon monoxide (CO) and nitric oxide (NO) each have mechanistically unique roles in various inflammatory disorders. Although it is known that CO can induce production of NO and that NO can induce expression of the cytoprotective enzyme heme oxygenase 1 (HO-1), there is no information whether the protective effect of CO ever requires NO production or whether either gas must induce expression of HO-1 to exert its functional effects. Using in vitro and in vivo models of tumor necrosis factor α–induced hepatocyte cell death in mice, we find that activation of nuclear factor κB and increased expression of inducible NO are required for the protective effects of CO, whereas the protective effects of NO require up-regulation of HO-1 expression. When protection from cell death is initiated by CO, NO production and HO-1 activity are each required for the protective effect showing for the first time an essential synergy between these two molecules in tandem providing potent cytoprotection.

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Protective Effects of Total Saponins of Panax Notoginseng on Steroid-Induced Avascular Necrosis of the Femoral Head In Vivo and In Vitro

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/165679 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Heng-feng Yuan ◽

Jian-feng Pan ◽

Shuo Li ◽

Chang-an Guo ◽

Shu-hao Liu ◽

...

Keyword(s):

Femoral Head ◽

Protective Effect ◽

Avascular Necrosis ◽

Caspase 3 ◽

In Vitro Study ◽

Panax Notoginseng ◽

Protective Effects ◽

Model Group

This research was designed to investigate the protective effects of TSPN on steroid-induced avascular necrosis of the femoral head (ANFH) and the likely mechanisms of those effects. As an in vivo study, TSPN was shown to be protective against steroid-induced ANFH due to the upregulation of VEGF-A. Furthermore, TSPN attenuated the apoptosis of osteocytes and reduced the expression of Caspase-3 relative to the model group. As an in vitro study, TSPN exerted a concentration-dependent protective effect against apoptosis in MC3T3-E1 cells. Moreover, TSPN (at a dose of 100 μg/mL) significantly reversed the dexamethasone-induced augmentation of Caspase-3 expression and activity. Therefore, our study demonstrated that TSPN had a protective effect against steroid-induced ANFH that was related to the upregulation of VEGF-A and the inhibition of apoptosis and Caspase-3 activation.

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